EAS Intern Publishes in FDLI Update Magazine

Neha Mookuparambil, a recent EAS intern focusing on pharmaceutical studies at Georgetown University published an article of FDA’s perspective on continuous manufacturing in FDLI Update, the bi-monthly magazine of the Food Drug Law Institute. EAS has partnered with Georgetown for a number of years hosting masters level interns with a focus on biotechnology.

Equipment and Utility Change Control for GMP Production Facilities

By Greg Weilersbacher

Despite FDA’s guidance documents on change control, “…managing change to prevent unintended consequences,” many companies limit change control to documentation such as batch records, SOPs, protocols, and specifications and only sporadically evaluate that of equipment and facilities, if it is done at all. A lack of knowledge and even conceptualization of the use of change control for equipment and facilities severely limits GMP compliance, particularly when new equipment is installed and connected.

Equipment change control (ECC) applies to equipment from all departments (GMP and non-GMP) that connect to the facility’s GMP utilities, including electrical, water systems, drainage, clean gases, venting /exhausting of heat and fumes, equipment cooling, clean steam, GMP servers and networks, HVAC and any system that has direct or indirect impact on cleanroom operations. Why include non-GMP equipment in ECC? The answer is simple: shared utilities. Any time a piece of equipment (R&D or GMP) is connected to a shared utility it has the potential to affect the performance of other equipment connected to the utility. It also has the potential to damage the utility. This is why ECC is so important and where it shows its value. One of the biggest errors a company can make is assuming that a utility is dedicated to R&D.

Equipment change control can be grouped into six primary stages:

Stage 1: Understanding the Utility and IT Requirements for new Equipment

This is the starting point for ECC and is one of the most important steps. Before the equipment is purchased you must detail the equipment’s utility requirements when operating at full capacity.

An often-overlooked need is the connections to GMP servers and networks. Equipment configured with outputs that can be connected to GMP servers is now the norm for new instruments. This represents one of several elements in ensuring data integrity of electronic records and can be a particular challenge when purchasing used or refurbished equipment.

Stage 2: Comparison of Equipment Requirements to the Capabilities of Utilities

Electrical – For facilities personnel to determine if an electric utility has the capability of meeting the needs of your new equipment, first they will need to know where it will be installed. Seems obvious right? Wrong. Too often those who purchase equipment don’t know exactly where the new equipment will be installed or assume it will be put in one of the cleanrooms. If the equipment requires a significant power draw the circuit panel will need to be evaluated to ensure that not only is the panel fed by the right power supply, but the panel must also be balanced. Enlist subject matter experts to make a technical assessment on a critical parameter.

Capacity of Emergency Generators – The most ignored utility. Emergency generators are typically installed during facility construction and their size is reflective of only the equipment that was on-site or projected to be on-site at that time. If it is critical that the new piece of equipment is connected to an e-power circuit and the power requirements are evaluated in comparison to the current load.

Exhausting of Solvents – In pharmaceutical and biopharmaceutical cleanrooms, it is essential that every trace of any hazardous vapor be removed from a room or piece of equipment to protect against fire or explosion. Exhausting of solvents through non-corrosive and non-flammable ducting is key. Refer to National Fire Protection Association’s Standard 318, NFPA Standard, and local requirements for materials of construction for ducting in your area.

Heat Dissipation – Heat generated by production equipment, including drying ovens and pan coaters, can impact temperature control in GMP production suites. Keep this in mind as it can be difficult for the HVAC to maintain temperature set points and operate within validated ranges.

Cooling – Installation of process piping wrapped with non-shedding insulation is often required to deliver chilled water to its point of use in cleanrooms.

Water Quality – A variety of grades of water are used for pharmaceutical purposes. It is important to confirm the quality of water required for new equipment as well as the pressure, flow rate, and temperature requirements (as applicable). When contemplating installing an additional autoclave or replacing an existing autoclave with one with larger capacity, its important to sum the consumption rates of all equipment using clean steam and those that use only reverse osmosis/de-ionizing water (RO/DI).

Clean Gases – Nitrogen, oxygen, argon, carbon dioxide, clean compressed air and other specialty high purity gases are often used in pharmaceutical production settings to operate production equipment, The introduction of new equipment requiring one or more clean gas requires an assessment of the capacity of the utility to meet the requirements of all equipment it connects to.

Not only is it important to assess the capabilities of gas generating equipment and storage tanks capacity but also the length and internal diameter of distribution piping. Flow rate, pressure, and volume requirements of each piece of equipment currently installed must be evaluated in comparison with the ability of the system to keep up with demand. The last thing you want is to install a $2,000,000 spray dryer and find out that the nitrogen system and piping is too small to satisfy its consumption.

Drainage – The Most Difficult Utility to Retrofit – All drains are not created equal. Some are designed to transfer liquids to normal waste streams, others require special treatment before going to city waste, and still other effluents must be captured and taken away for processing. Equally problematic is the location where the new equipment will reside. Does the room currently have the proper drain system with floor connections next to the intended equipment location?

Explosion Proofing – Pharmaceutical production equipment and cleanrooms, including those than employ solvent handling and processing such as spray drying, are categorized in terms of their potential for explosivity. In North America, hazardous location electrical codes and standards uses a “class, division” system as the basis for area classification of hazardous locations.

Cleanrooms can be protected to mitigate against the potential for explosions by ensuring that electrical outlets, lighting, sources of heat and spark are separated from their surrounding environments protecting them from dust, moisture, vapors or other contaminants. This isolation can also protect the surrounding environment from outgassing, heat, arching, air pressure leakage, electromagnetic interference and other conditions that could negatively affect process integrity and personal safety. In cases where cleanrooms can pose an explosion risk, it’s prudent to seek the advice of a qualified industrial electrician or other expert to assess the controls that are currently in place and those that need strengthening.

Connecting Equipment to GMP Networks and Servers – Critical to Quality Attributes (CQA) must be defined by the organization and followed by equipment owners and IT to ensure that data from equipment is automatically sent from equipment to servers, is backed up per schedule, and periodically tested for retrieval of data and meta data to ensure that data integrity and the principles of ALCOA are met when connecting to GMP networks.

The network architecture must be able to identify the equipment that is connected to specific data port IDs located in cleanrooms and map the equipment’s data to secured and compliant server locations. FDA warning letters for computer networks site the failure of validation documentation to include complete updated design documentation, and complete wiring/network diagrams to identify all computers and devices connected to the system. Given that networks change frequently, maintaining accurate diagrams that reflect the current configuration of the network requires revision control (i.e., formal change control).

Stage 3: Assessing the impact of New Equipment on Utility Validations

If the installation and functionality of new equipment requires adding new utility points of use (POU, i.e., valves that connect the equipment to the utility) the drawings, schematics, and materials of construction detailed in the utility’s Installation Qualification (IQ) will need to be updated. Tied to this change, the Operational Qualification will likely require revision to test the functionality of the new POU and for gas system a pressure-hold challenge.

Performance qualification (PQ) – This validation phase tests the ability of the utility to perform consistently over long periods of time within tolerances deemed acceptable by the manufacturing process as a whole. This is the most important element to test when tying in new equipment to an existing utility. It asks the question: Will the utility keep up with the demand while all POU are in operation serving equipment?

Stage 4: Calibration/Validation of New Equipment

When calibrating equipment, it is important that the calibration match or exceed the intended operational range of the equipment that will be used during actual production activities. Too often, equipment is operated at RPMs, flow rates, compression forces, etc., at settings that exceed the lower or high-end calibrated range of the equipment. This is a common audit observation made in sponsor and regulatory inspections of production facilities.

Requirements for validating equipment should be detailed in a validation master plan (VMP) that outlines the quality requirements for the types of equipment already in-house.

Equipment change control should reference both the manufacturer’s validation package and the gap validations, IQ, OQ, PQ, performed. Note that in all cases, the manufacturer’s validation protocols and your internal gap validation protocols must be approved by the equipment owner, validation, and quality prior to executions. These deliverables should be documented in the equipment change control.

Stage 5: Review of Turn-Over Packages, Executed Validations/Data/Reports, Release of equipment for GMP use

This stage in the change control process is often treated as a rubber-stamp. It is however, is an extremely critical phase where issues, gaps, deviations, deficiencies etc are identified and remedied with input from quality, engineering, validation and the department owning the equipment.

A common mistake made by companies is forgetting to complete a written statement, approved by all parties including quality, that the equipment is now released for GMP use. Although all of the associated validation and calibration documentation may be approved, inspectors from regulatory agency around the world look for this designation that the equipment is now suitable and released for GMP activities.

Stage 6: Change Control Effectiveness Check (i.e., what did we miss)

An effectiveness check is a valuable way to identify where equipment commissioning gaps and problems were found and also for formulating a plan to prevent the same issues from happening during future activities A robust change control effectiveness check, which is often neglected due to competing demands, should be built-in to the company’s equipment commissioning process as a required step.

The Take Away

New production equipment can be exciting to the end user. The challenge is that it is often viewed as plug-and-play: connect the equipment and we’re off and running. There is an impact on the utilities that provide electrical, gases, water, drainage, heating and cooling that serve a wide array of equipment in the GMP setting. These six stages of equipment change control provide a detailed roadmap for evaluating a facility’s current capabilities and comparison to requirements of new equipment. With careful evaluation, planning, and direct input from engineers, validations, and quality departments the common pitfalls associated with installing new equipment can be avoided. Consult a qualified consultant for assistance in marrying the expertise of your various departments to ensure a seamless assessment of equipment and facility requirements, installation, validation of conformance and use.

Meet Issue of the Month Author Greg Weilersbacher

Greg Weilersbacher

Greg Weilersbacher, has 25 years of industry experience successfully managing Quality Assurance, Quality Control, Analytical Development, Materials Management, GMP Manufacturing, GMP Facilities and Utilities Validation, and Facility Design and Construction Management in CMOs, biotechs and pharmaceutical companies. He has hosted FDA Pre-Approval Inspections and has led numerous European QP inspections of GMP facilities. As an independent consultant for EAS, Mr. Weilersbacher brings practical application of root causes analysis to deviations and CAPAs and adds significant value to the execution of Supplier Qualifications, Regulatory Audit Preparation, Internal Audits, Training Systems and the evolution of a company’s Quality Systems.

Crane Return to CHPA OTC 101 Academy

Susan Crane, Independent Advisor for OTC Drugs and Listings is an invited speaker at the CHPA OTC Academy and Workshop taking place in Wilmington, DE October 28-29, 2019. OTC Academy is a great learning opportunity for those new to the industry and those wishing to better understand how the industry works. Susan is a popular return speaker at this event and shares her career expertise in the OTC industry.

Navigating CBP and Prior Notice of FDA’s Imported Products – October 29, 2019

As the pace of FDA regulated products increases, companies importing food, dietary supplements, food additives, food and dietary ingredients to the United States must keep pace with changing regulations intended to ensure the safety of the U.S. consumer and integrity of the food-based products being imported. FDA has historically seen an import rate increase of 5-10% in the last decade and in 2018, 31% of those were food products requiring prior notice.

Join EAS Consulting Group’s Independent Consultants William Scopa and Angel Suarez for a deep dive into the regulatory challenges of importing FDA regulated products into the US and streamlining opportunities for companies able to demonstrate a record of safety and compliance. Register Today!

Menu Labeling

By Cathryn Sacra

Each month EAS selects one question sent in by readers to be answered in EASeNews. This month’s answer is provided by Cathryn Sacra, Director of Labeling and Cosmetic Services. Cathryn oversees EAS’ labeling team, assisting clients with food and dietary supplement product labeling as well as menu labeling for restaurants. To learn more about EAS labeling services for restaurants and how we may assist in development and verification of accuracy, contact Cathryn today.

Question: How should I prepare in the event of an FDA audit for accuracy of my restaurant’s menu labeling?

Sacra: On May 7, 2018, the US Food and Drug Administration implemented a landmark menu labeling law that requires chain restaurants and similar retail food establishments with 20 or more locations to provide nutrition information for their standard menu items. There is no doubt that requiring restaurants to disclose their nutrition information empowers customers to make healthier dietary choices. This empowerment is especially relevant for the increasingly health-conscious public and those with medical issues. Thus, it is critically important that the information provided by foodservice establishments is solidly substantiated either through nutrient databases, cookbooks, or laboratory analysis and that the information is conveyed accurately to the consumer. Industry misunderstanding and confusion of the requirements is evidenced by the Agency’s many updates including Key Facts on declaring calories, answers to common questions, and a Constituent Update Fact Sheet and Menu Labeling Requirements released August 13, 2019 which clarified some concerns.

Some foodservice establishments lack understanding of the critical importance of providing accurate information and in many cases view this important task as merely a technicality required by law, a hassle, as well as a waste of restaurant resources. Further, and problematically, the absence of a technical person on the restaurant establishment staff who is capable of guiding proper sampling to obtain accurate nutrition analysis, means results can be inconsistent and inaccurate.

As part of the FDA’s continued efforts to provide support to stakeholders through education and outreach, it is expected that the Agency will establish a random systematic labeling auditing process to verify the accuracy of the information provided to customers by establishments covered by the FDA Menu Labeling Law. Stakeholders must ensure completeness and accuracy to stay in compliance. Menu labeling requires continued monitoring, even after initial laboratory testing of data is verified and published. It is important to identify a laboratory that is competent in this type of assessment and one that can provide validated and verified results. Additionally, supplier labels need to be verified so their information is in line with that your organization is projecting to customers. Any changes to the restaurant menu or ingredient sourcing must be assessed to ensure continued accuracy. There are many components to the development and execution of an evergreen plan to ensure menu labeling success. Choose EAS and our experts in menu labeling to ensure your restaurant’s compliance with FDA’s Final Rule.

EAS Offers OTC Labeling Review and Design in Compliance with FDA Monograph Regulations

Did you know that the current regulations for labeling of Over-the-Counter (OTC) drug products were initiated in 1972 as part of the OTC Drug Review? That’s over 50 years ago and the monograph system that arose from that process has not yet come to completion in terms of finalizing regulations for all OTC products.

The monographs establish conditions (for each therapeutic category) under which OTC drug products are generally recognized as safe and effective. These conditions include labeling requirements such as indications, warnings, directions as well as any required testing.

Some monographs are final and codified in the regulations while others are “tentative” in that the monograph was proposed but has not yet been finalized. Marketing a product under a tentative monograph is allowed through FDA’s enforcement discretion as long as it meets the conditions in that monograph. OTC drug products that do not meet the requirements under the monograph system are considered new drugs and must be submitted to FDA through the application process for approval to market.

In addition to the requirements of the monographs, numerous other laws have passed over time and new regulations issued further complicate your labeling.

These myriad requirements can make compliance confusing, not to mention that the industry is still awaiting Senate passage of the Over-the-Counter Monograph Safety, Innovation, and Reform Act which may address some of these issues.

EAS offers review of OTC product ingredients and claims to ensure they are in compliance with Federal regulations. Our experts are also able to assist with the required drug listings and registrations for OTC products. To learn more about our services visit our webpage. You may also wish to view our On-Demand webinars on OTC regulations, also found on our webpage under the Resources tab.

September 2019 Drug and Device Corner

The FDA has announced the Reorganization of the Office of New Drugs with Corresponding Changes to the Office of Translational Sciences and the Office of Pharmaceutical Quality. This move is one critical component of the agency’s initiative to modernize the New Drugs Regulatory Program. The FDA expects these changes to not only enable greater efficiency, but to also better understand the diseases intended to be treated by the drugs being evaluated for approval. The OND will also create cross-functional support offices of New Drug Policy, Drug Evaluation Sciences, Regulatory Operations, Operations, and Administrative Operations.

On 9 September 2019, the FDA published the Acceptance Review for De Novo Classification Requests

Final Guidance Document. The purpose of this document is to explain the procedures and criteria FDA intends to use in assessing whether a request for an evaluation of automatic class III designation (De Novo classification request or De Novo request) meets a minimum threshold of acceptability and should be accepted for substantive review. The guidance includes 2 appendices similar in form to a ‘check list’. Appendix A includes information regarding the acceptance criteria which will ensure the DeNovo classification request includes sufficient information for substantive review. This checklist will determine whether the request is accepted or whether an RTA will be issued. Appendix B is a recommended content checklist. The FDA is observing a 60-day transition period between 8 September – 7 November, 2019 during which applications will be accepted per existing process. RTA reviews will begin on 8 November 2019. Please see the guidance document for further information.

The FDA committed to developing “electronic submission templates that will serve as guided submission preparation tools for industry to improve submission consistency and enhance efficiency in the review process” and “[by] FY [fiscal year] 2020, the Agency will issue a draft guidance document on the use of the electronic submission templates.” Providing Regulatory Submissions for Medical Devices in Electronic Format — Submissions Under Section 745A(b) of the Federal Food, Drug, and Cosmetic Act

Draft Guidance Document, is intended to satisfy the draft guidance documents referenced in section 745A(b)(3) and the MDUFA IV Commitment Letter. This draft guidance is not final nor is it in effect at this time. The agency has concluded that it is not feasible to provide and implement an electronic format that would apply to all submissions covered by section 745A(b) of the FD&C Act in one guidance document. Therefore, the published draft document describes the FDA’s plan to develop individual guidances specific to submission type with corresponding timetables for implementation, as well as criteria for waivers of and exemptions from the requirements.

With FDA’s commitment to facilitate generic drug product availability and to assist the generic pharmaceutical industry with development, 53 Product-Specific Guidances for Generic Drug Development have recently been published. Of these guidances – 34 are new and 19 are revised. Five of the new draft guidances and 11 of the revised draft guidances are for complex drug products. Nearly half of these 53 PSGs (8 complex and 18 non-complex) are for products with no approved Abbreviated New Drug Application (ANDA).

On 20 September 2019, the FDA announced limits on packaging for the anti-diarrhea medicine loperamide (Imodium) to encourage safe use. This link will bring you to the agency’s webpage where you may find more information on the FDA’s approved changes to the packaging.

Guidance Document updates on the FDA website

ALL DIVISIONS

Clinical Decision Support Software

The Food and Drug Administration (FDA) has long regulated software that meets the definition of a device in section 201(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), including software that is intended to provide decision support for the diagnosis, treatment, prevention, cure, or mitigation of diseases or other conditions (often referred to as clinical decision support software). This guidance provides clarity on the scope of FDA’s oversight of clinical decision support software intended for health care professionals, patients, or caregivers.

CDER

Citizen Petitions and Petitions for Stay of Action Subject to Section 505(q) of the Federal Food, Drug, and Cosmetic Act

This draft guidance updates the November 2014 guidance to account for recent regulatory changes and describes a change in FDA’s current thinking on what constitutes a 505(q) petition. In addition, FDA is revising this guidance to describe some of the considerations FDA will take into account in determining whether a petition is submitted with the primary purpose of delaying the approval of an application.

Drugs for Treatment of Partial Onset Seizures: Full Extrapolation of Efficacy from Adults to Pediatric Patients 2 Years of Age and Older

This guidance provides recommendations to sponsors on the clinical development of drugs for the treatment of partial onset seizures (POS) in pediatric patients.

Evaluation of Internal Standard Responses During Chromatographic Bioanalysis: Q & A

This guidance provides recommendations to sponsors, applicants, and contract research organizations regarding internal standard (IS) response variability in chromatographic analytical data submitted in investigational new drug applications, new drug applications, abbreviated new drug applications, biologics license applications, and supplements.

CDER & CBER

Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment

The purpose of this guidance is to assist sponsors in the clinical development of drugs and biological products for the treatment of amyotrophic lateral sclerosis (ALS).

Wholesale Distributor Verification Requirement for Saleable Returned Drug Product—Compliance Policy

This guidance is intended for wholesale distributors who must verify the product identifier upon receipt of a returned product that the wholesale distributor intends to further distribute as required under section 582(c)(4)(D) of the Federal Food, Drug, and Cosmetic Act.

Interacting with the FDA on Complex Innovative Trial Designs for Drugs and Biological Products

This document provides guidance to sponsors and applicants on interacting with the FDA on complex innovative trial design (CID) proposals for drugs or biological products. FDA is issuing this guidance to satisfy, in part, a mandate under section 3021 of the 21st Century Cures Act (Cures Act).

Placebos and Blinding in Randomized Controlled Cancer Clinical Trials for Drug and Biological Products

This guidance provides recommendations to industry about the use of placebos and blinding in randomized controlled clinical trials in development programs for drug or biological products to treat hematologic malignancies and oncologic diseases.

CDRH & CBER

Changes to Existing Medical Software Policies Resulting from Section 3060 of the 21st Century Cures Act

Section 3060(a) of the 21st Century Cures Act (Cures Act) amended section 520 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) on December 13, 2016, removing certain software functions from the definition of device in section 201(h) of the FD&C Act. This guidance provides FDA’s current thinking regarding the amended device definition and the resulting effect the amended definition has on FDA’s guidances related to medical device software.

Medical Device Data Systems, Medical Image Storage Devices, and Medical Image Communications Devices

FDA’s current thinking on the definition of MDDS is reflected in this guidance.

Policy for Device Software Functions and Mobile Medical Applications

The FDA is issuing this guidance document to inform manufacturers, distributors, and other entities about how the FDA intends to apply its regulatory authorities to select software applications intended for use on mobile platforms (mobile applications or “mobile apps”) or on general-purpose computing platforms.

The Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program

In accordance with amendments made to section 514 by the FDA Reauthorization Act of 2017 (FDARA), and as part of the enactment of the Medical Device User Fee Amendments of 2017 (MDUFA IV), FDA was directed to issue a draft guidance regarding the goals and implementation of the ASCA Pilot. This draft guidance refers to voluntary consensus standards.

Safety and Performance Based Pathway

This guidance provides FDA’s current thinking on expanding the concept of the Abbreviated 510(k) Program for demonstrating substantial equivalence for premarket notification (510(k)) submissions.

Safer Technologies Program for Medical Devices

The FDA is introducing a new, voluntary program for certain medical devices and device-led combination products that are reasonably expected to significantly improve the safety of currently available treatments or diagnostics that target an underlying disease or condition associated with morbidities and mortalities less serious than those eligible for the Breakthrough Devices Program. Devices and device-led combination products are eligible for this program if they are subject to review under a premarket approval application (PMA), De Novo classification request (“De Novo request”), or premarket notification (510(k)).

Format for Traditional and Abbreviated 510(k)s

The main focus of this document is to provide guidance on how to format an original submission for a Traditional or Abbreviated premarket notification (510(k)) submission.

The Abbreviated 510(k) Program

This guidance provides recommendations on an optional approach that may be used to demonstrate substantial equivalence in premarket notifications (510(k)s).

The Special 510(k) Program

This guidance provides the Food and Drug Administration’s (FDA) current thinking on premarket notifications (510(k)s) appropriate for review as a Special 510(k).

Refuse to Accept Policy for 510(k)s

The purpose of this document is to explain the procedures and criteria FDA intends to use in assessing whether a premarket notification (510(k)) submission meets a minimum threshold of acceptability and should be accepted for substantive review.

FDA and Industry Actions on De Novo Classification Requests: Effect on FDA Review Clock and Goals

Performance goals were negotiated and agreed to under MDUFA IV for De Novo requests received in FY 2018-2022. These performance goals and process improvements are outlined in the MDUFA IV Commitment Letter from the Secretary of Health and Human Services (the Secretary) to Congress and are further described in the document.

User Fees and Refunds for De Novo Classification Requests

The purpose of this guidance document is to identify: 1) the types of De Novo requests subject to user fees; 2) exceptions to user fees; and 3) the actions that may result in refunds of user fees that have been paid. This document incorporates the impact of process improvements from MDUFA IV.

Humanitarian Device Exemption (HDE) Program

FDA developed this guidance document to provide clarity to industry and FDA staff about the current review practices for the Humanitarian Device Exemption (HDE) Program.

Humanitarian Use Device (HUD) Designations

This guidance document is intended to assist applicants in the preparation and submission of Humanitarian Use Device (HUD) designation requests to the U.S. Food and Drug Administration’s (FDA or Agency) Office of Orphan Products Development (OOPD).

Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications

FDA has developed this guidance document to provide greater clarity for FDA reviewers and industry regarding the principal factors FDA considers when making benefit-risk determinations during the premarket review process for certain medical devices.

Patient Engagement in the Design and Conduct of Medical Device Clinical Investigations

This draft guidance is intended to: 1) help sponsors understand how they can use patient engagement to elicit experience, perspectives, and other relevant information from patient advisors (see definition in Section IV) to improve the design and conduct of medical device clinical investigations; 2) highlight the benefits of engaging with patient advisors early in the medical device development process; 3) illustrate which patient engagement activities are generally not considered by FDA to constitute research or an activity subject to FDA’s regulations, including regulations regarding institutional review boards (IRBs); and 4) address common questions and misconceptions about collecting and submitting to FDA patient engagement information regarding the design and conduct of a medical device clinical investigation.

CDRH

General Wellness: Policy for Low Risk Devices

The Food and Drug Administration (FDA) is issuing this guidance document to provide clarity to industry and FDA staff on the Center for Devices and Radiological Health’s (CDRH’s) compliance policy for low risk products that promote a healthy lifestyle (general wellness products). This guidance does not apply to products (e.g., drugs, biologics, dietary supplements, foods, or cosmetics) regulated by other FDA Centers or to combination products.

Off-The-Shelf Software Use in Medical Devices

This guidance document was developed to address the many questions asked by medical device manufacturers regarding what they need to provide in a premarket submission to the FDA when they use OTS Software.

Conventional Foley Catheters – Performance Criteria for Safety and Performance Based Pathway

This draft guidance provides performance criteria for conventional Foley catheters in support of the Safety and Performance Based Pathway.

Cutaneous Electrodes for Recording Purposes – Performance Criteria for Safety and Performance Based Pathway

This draft guidance provides performance criteria for cutaneous electrodes in support of the Safety and Performance Based Pathway.

Orthopedic Non-Spinal Metallic Bone Screws and Washers – Performance Criteria for Safety and Performance Based Pathway

This draft guidance provides performance criteria for non-spinal metallic bone screws and their associated washers in support of the Safety and Performance Based Pathway.

Spinal Plating Systems – Performance Criteria for Safety and Performance Based Pathway

This draft guidance provides performance criteria for spinal plating systems in support of the Safety and Performance Based Pathway.

Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemptions

This guidance document describes the Food and Drug Administration’s (FDA or Agency) current approach to considering uncertainty in making benefit-risk determinations to support FDA premarket decisions for medical device premarket approval applications (PMAs), De Novo requests, and humanitarian device exemption (HDE) applications.

CVM

#171 Demonstrating Bioequivalence for Soluble Powder Oral Dosage Form Products or Type A Medicated Articles Manufactured from Active Pharmaceutical Ingredients Considered to be Soluble in Aqueous Media

This document describes how the Center for Veterinary Medicine (CVM) intends to evaluate requests for waiving the requirement for performing in vivo bioequivalence studies (biowaivers) for animal drugs administered orally as soluble powders or as Type A medicated articles manufactured from active pharmaceutical ingredients (APIs) considered to be soluble in aqueous media (water soluble APIs).

#261 Eligibility Criteria for Expanded Conditional Approval of New Animal Drugs

This guidance is intended for sponsors and potential sponsors interested in pursuing conditional approval of new animal drugs for certain major uses in major species.

#263 Recommendations for Sponsors of Medically Important Antimicrobial Drugs Approved for Use in Animals to Voluntarily Bring Under Veterinary Oversight All Products That Continue to be Available Over-the-Counter

This guidance is intended for sponsors of approved applications and abbreviated applications for new animal drugs containing medically important antimicrobials for use in non-food (companion), food-producing animals, or both, that are currently approved with over-the-counter marketing status.

EAS to Exhibit at Food Safety Consortium

Join EAS at booth #321 at the Food Safety Consortium in Schaumburg, IL October 1-3, 2019 where Cathryn Sacra, Director of Labeling and Cosmetics Programs as well as GRAS submissions will be joined by Charlotte Peyton, an expert on cannabis GMPs and state regulations. EAS offers a wealth of services in food safety, food defense and protection again intentional adulteration under FSMA. Additionally, our expertise extends to Good Manufacturing Practices of cannabis products. Learn more about our services by stopping by our booth or make an appointment to ensure dedicated time by contacting Cathryn Sacra.

Dietary Supplement GMP Enforcement – a Look at Recent FDA Observations and Warning Letters – November 7, 2019

Though FDA’s 21 CFR 111 Good Manufacturing Practices (GMPs) for Dietary Supplements has been in place for over a decade, the industry continues to be plagued by the complexities of compliance. The establishment of specifications for components, in-process materials, and finished products; and then testing to those specifications has continuously been among the top observations issued by FDA.

EAS Consulting Group’s Robert Fish, Independent Advisor for Quality and Compliance, will review recent FDA observations and Warning Letters to help you gain insight to FDA’s enforcement focus as well as trends in problem areas that your firm can proactively address. When FDA shows up for a surprise inspection, you’ll be ready. Register Today!

Protection Against Intention Adulteration is High Priority for FDA

Dear Readers,

Edward A. Steele

Welcome to the October issue of EASeNews, the free newsletter for industries regulated by FDA.

If you missed it FDA has released an online Food Defense Plan tool which will help companies think through the important requirements and action steps of developing this important protection against Intentional Adulteration. If you missed our webinar on Food Defense in September, our Independent Advisor for FSMA, Charles Breen and Independent Consultant, Kathy Knutson, Ph.D. did a fantastic job laying out FDA’s expectations, who is expected to comply and how to begin developing a food defense plan. I invite you to watch it free On-Demand.

Additionally, on the food front, a reminder to firms exporting seafood products from the U.S. to the EU that FDA updated three Export Listing Module (ELM) requirements. Effective September FDA has fully transitioned to the ELM for the EU dairy export list and all export lists maintained for Chile and China.

U.S. establishments that are currently included on the EU collagen, gelatin, or seafood export lists should submit applications in the ELM if they wish to remain on these lists and effective immediately, any U.S. establishment that wishes to be included on any FDA-maintained export list for food products should apply in the ELM. Contact EAS with any questions.

FDA also published final Guidance for medical device companies seeking to file a 510(k) based on Safety and Performance Criteria and draft guidance on a pilot program assessing consistency and predictability of premarket reviews for medical devices through a voluntary conformity assessment initiative, called the Accreditation Scheme for Conformity Assessment (ASCA) Pilot. More information on both, as well as other FDA initiatives, can be found in the Drug Device Corner.

We have a very interesting issue of the month article written by Greg Weilersbacher that discusses the importance of equipment change control. How often do we purchase a new piece of equipment without fully vetting the additional or different requirements on utilities. Planning for these upgrades before they are installed can save countless hours, additional cost and frustration later.

Our Ask the Expert is answered by Cathryn Sacra and discusses the importance of restaurant menu labeling compliance. As you know EAS has a labeling team that helps clients with food and dietary supplement labeling issues. Our labeling team also includes experts in restaurant menu labeling, and services run the gamut of identification of qualified labs to reviewing product specs for label development and accuracy verification.

EAS is exhibiting and speaking at numerous trade shows and conferences this month, the details of which you’ll find in the EAS in Action section. I would also like to remind you of our complimentary webinars coming up on navigating Customs and Border Patrol for imported FDA products; a look at FDA observations related to dietary supplement compliance; a continuation of our food fraud webinar with a closer look at analytical tools; and an in-depth overview of what it takes to be a expert witness in legal proceedings. All of this information can be found in EAS in Action as well.

Lastly, if you have not already registered for our November food labeling, dietary supplement labeling and dietary supplement GMP seminars taking place in Irvine, CA I encourage you to do so. Seats are still available. We also have a one-day dietary supplement GMP refresher training in November in Long Island. You may find registration information on the EAS website.

Thank you as always for your interest in EAS and please reach out to me with any questions.

Sincerely,

Edward A. Steele Signature

Ed

EAS to Exhibit at ISPE Annual Conference Focusing on Pharmaceuticals

Bryan Coleman, Senior Director for Drugs and Medical Devices, and Robert Fish, Independent Advisor for Quality and Compliance will be at the EAS booth, #524, at the International Society of Pharmaceutical Engineers Annual Meeting and Expo October 27-29, 2019 in Las Vegas. We invite you to stop by to discuss your regulatory challenges, or feel free to make an appointment to ensure your dedicated time for questions by emailing Bryan directly.

Tajkarimi Discusses Food Fraud Detection Methods in MeatingPlace

Independent Consultant Mehrdad Tajkarimi, Ph.D. wrote about next-generation sequencing technology as it applies to detect plant and animal species in food adulteration cases for MeatingPlace magazine. NGS produces more variable and more in-depth genome sequencing datasets to find food-related genes for verification of the actual food’s content, ingredients, sourcing and labels for the prevention of Food Fraud. Learn more at MeatingPlace (Complimentary login required).

EAS Exhibits, Presents Educational Sessions at SupplySide West

If you’ll be in Las Vegas October 15-18, 2019 attending the SupplySide West, stop by EAS booth #5409 and say hello to Tara Lin Couch, Ph.D., Senior Director for Dietary Supplements and Tobacco Products and Independent Consultant Heather Fairman. Both Tara and Heather will present educational sessions at the event. Tara will speak on contract laboratories and Heather is a keynote speaker on a panel concerning contract manufacturing. If you’d like to make an appointment to meet with the EAS team at SupplySide West, contact Tara Couch.

Register for Upcoming EAS Webinars on Food Defense, Effective Expert Witness Techniques and QMS

Register now for the EAS complimentary webinar Food Defense – Untangling Challenges and Strengthening Opportunities, presented by Independent Advisor for FSMA, Charles Breen and Independent Consultant, Kathy Knutson, Ph.D. which will be held September 12, 2019, at 1 pm eastern. Food Defense is increasingly a worry for firms as our global business climate opens opportunities for intentional harm both domestically and overseas. Charles and Kathy will help food manufacturers understand how to identify and mitigate the impact of intentional attacks that compromise food safety.

On September 25 George Yanulis D.Eng. will present a webinar focusing on the medical device Quality Management System transition from CFR 820 to the ISO 13485:2016. Dr. Yanulis will discuss reasons behind the change as well as some of the more technically challenging areas of ISO compliance. Join George by registering here.

Ronald Levine, EAS Independent Consultant and General Counsel with Herrick Feinstein LLP will present a webinar on considerations for becoming an expert witness on November 6, 2019, at 1 pm​. Ron’s has decades of experience preparing expert witnesses in a variety of legal cases focusing on compliance with FDA regulations. Ron’s complimentary webinar will help those interested in exploring a career as an expert witness understand expectations and those already acting in an expert witness capacity to strengthen their skills. Register here.

GRAS Determination: Lessons and Pitfalls

By Tom Jonaitis

Over the 14 years of working as a scientific and regulatory consultant in the food industry, I have had the opportunity to work with many companies that were bringing a wide range of exciting and innovative food ingredients to the marketplace in the United States and abroad.

Beyond the extensive resources put into the R&D phase to identify and produce the right ingredient and ensure it does what it needs to, companies also need to address the regulatory requirements for these ingredients. Whether in the US (through the GRAS process[1]) or elsewhere, the ingredients must have substantial and robust evidence of safety under intended conditions of use. I will focus on the food additive regulations here and put aside the multitude of other regulations companies need to address.

The safety of food additives is supported by 2 main areas of data: a) chemistry and manufacturing and b) toxicology data that corroborates the safety of the estimated intake of the ingredient. Companies familiar with the GRAS process will plan for the requirements of the regulatory stretch of the journey (or get the help they will need) well in advance of being “market ready”. This ensures that any data gaps or hiccups are dealt with quickly and efficiently to avoid costly delays. There’s nothing worse than needing your ingredient approved to meet customer demands, to find out more data is required, which means more time and resources.

Many times, I’ve worked with companies that may have had a great product yet were unclear of the depth of data required to satisfy the regulatory requirements. Fortunately, in most cases, I was able to work with them to help them obtain the necessary data and compile a robust dossier.

Looking back at the obstacles some companies faced, as well as reviewing the publicly available outcomes of FDA’s review of GRAS notifications (both successful and unsuccessful submissions), I will highlight just a few of the key areas that have cause some issues:

  1. Identification/Characterization:

    • The ingredient should be characterized both qualitatively and quantitatively and defined to 100% purity with validated methods. This is easier to do with a single ingredient compared to more complex ones, i.e., certain botanical extracts, waxes, starches. A company must know exactly what is in their ingredient so as to show that the ingredient, and any impurities, are safe.

  2. Processing Aids used in manufacturing:

    • In the US, anything used in the manufacturing of a food ingredient is technically considered a “food additive” – so every substance used must be permitted for use in food production. It will need to be either a permitted food additive (and permitted for your particular application, as described in the CFR) or a GRAS substance. Otherwise, the safety of the processing aid will need to be assessed and supported either in a separate GRAS determination or within the existing determination. Generally, the best course of action is to ensure only permitted substances are used to avoid the need for additional safety assessments.

  3. Toxicology/Safety Studies:

    The GRAS status of an ingredient can be based either on scientific procedures (safety studies and expert consensus) or a history of use in food prior to 1958. Essentially all new ingredients (>95%) will fall into the former category due to the particular requirements needed to meet the history of use in foods definition.

    • Generally, a 90-day rodent toxicity study, in conjunction with a battery of genotoxicity tests (all conducted to GLP/OECD requirements), on the specific ingredient, will be the minimum testing requirements to support the safety of a novel food ingredient.

    • Many times, companies have identified a plethora of published studies and consider that the safety of their ingredient is supported by existing data. In most cases the data will not meet the minimum safety requirements, due to quality of the safety studies and comparability to actual ingredient and intended uses (i.e., duration of study too short, dose too low compared to intended food uses, issues with study populations used, or purity profile of test article is too different from the novel ingredient).

Obtaining GRAS status for an ingredient is no small feat and preparing for it in advance will create ample opportunity to get all your ducks in a row for a smooth and predictable path to market. If your company has not gone through the process a few times, it could be invaluable to discuss your strategy and data requirements with an experienced food regulatory consulting firm to ensure there are no critical gaps that could cause unnecessary delays and wasted resources.

EAS Consulting Group offers world-class food regulatory consulting services with an extensive team of experts, including ex-US FDA agency officials, board-certified toxicologists, and other regulatory professionals. It has an excellent record of successfully helping companies obtain GRAS status for its ingredients, with and without FDA notification.


[1] https://www.fda.gov/food/food-ingredients-packaging/generally-recognized-safe-gras

August 2019 Drug and Device Corner

The FDA has announced FY2020 User fees, please scroll down for further information.

EAS recently sent an email update regarding FDA’s intention to begin inactivating drug listing records, effective 13 Sept 2019. The FDA has found that tens of thousands of drug listing records contain errors. The agency announced their intentions in the Federal Register on 14 August 2019. The main concern with these non-compliant listings is their lack of certification as being active and up-to-date, or the listings are associated with a drug establishment no longer duly registered with the FDA. The notification also points out that some companies have simply opted to not renew registrations / certify listings and have considered this sufficient notification to the FDA. However, this practice is not compliant with the regulations. To appropriately close files, a de-registration SPL file must be submitted to the FDA for an establishment registration and a ‘Marketing Complete’ file (which includes the expiration date of the last batch of product introduced into U.S. commerce) must be submitted for a drug listing.

If the FDA does inactivate a listing, the listing record will note this and it will be removed from all public drug listing databases maintained by FDA. This includes the NDC Directory and the NDC SPL Data Elements (NSDE) file. Any such drug that is still marketed will be deemed misbranded and the company involved will be subject to FDA enforcement action. This would be particularly problematic for foreign companies when importing products into the U.S.

The agency also notes in their announcement that manufacturers and repackagers of products subject to the new product identification requirement, must submit the updated labeling to their product listings. This update will satisfy the annual certification requirement and therefore such products will not need the “blanket no changes” submission to maintain the listings’ active status.

While on the topic, labeler codes should also be current and reflect accurate contact information for the labeler. If you have any questions or concerns regarding your company’s status, EAS is here to assist.

A message was communicated recently from the FDA re approved (A)NADA labeling. By 30 September 2023 the following statements (as applicable) must be included on approved (A)NADA labeling: Approved by FDA under NADA# xxx-xxx OR Approved by FDA under ANADA# xxx-xxx. This requirement applies to all approved animal drugs currently on the market. If you need further information on this topic, please contact EAS.

The FDA, in their ongoing effort to update the IID Database, has announced their most recent changes. Information about FDA’s plans for upcoming changes to the IID can be found on the IID web page. The web page will be continually updated as FDA makes changes to the IID over the coming year.

The FDA has published the following user fee rates for their FY2020, which runs from 1 Oct 2019 – 30 Sept 2020:

Annual Establishment facility fee rates effective 1 October 2019 are as follows:

  • Medical Device: $5,236

GDUFA

  • Domestic API facility: $44,400
  • Foreign API facility: $59,400
  • Domestic FDF facility: $195,662
  • Foreign FDF facility: $210,662
  • Domestic CMO facility: $65,221
  • Foreign CMO facility: $80,221

Guidance Document updates on the FDA website:

ALL DIVISIONS

CDER

CDER & CBER

  • Male Breast Cancer: Developing Drugs for Treatment This guidance provides recommendations to sponsors regarding the development and labeling of cancer drugs, including biological products, regulated by the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) for the treatment of male patients with breast cancer.
  • Child-Resistant Packaging Statements in Drug Product Labeling The guidance discusses what information should be included to support CRP statements in labeling for new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), and supplements to these applications.
  • Fabry Disease: Developing Drugs for Treatment The purpose of this guidance is to provide recommendations to sponsors regarding clinical trial design features that can support approval of drugs and biological products intended for the treatment of Fabry disease (FD).
  • Bacterial Vaginosis: Developing Drugs for Treatment The purpose of this guidance is to assist sponsors in the overall development program and clinical trial designs to support development of topical and systemic drugs and biological products for the treatment of bacterial vaginosis (BV).
  • General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products This draft guidance is intended to assist sponsors of new drug applications (NDAs), biologics license applications (BLAs), and supplements who are planning to conduct clinical studies in neonatal populations.
  • Rare Pediatric Disease Priority Review Vouchers This guidance provides information on the implementation of section 908 of the Food and Drug Administration Safety and Innovation Act (FDASIA), which added section 529 to the Federal Food, Drug, and Cosmetic Act (the FD&C Act). Under section 529, FDA will award priority review vouchers to sponsors of certain rare pediatric disease product applications that meet the criteria specified in that section.
  • Delayed Graft Function in Kidney Transplantation: Developing Drugs for Prevention This guidance addresses the FDA’s current thinking regarding the overall development program and clinical trial designs for systemic drugs administered to the kidney transplant recipient to support an indication of prevention of DGF.

CDRH

CVM

  • CVM GFI #257 (VICH GL57) The objective of this guidance is to provide study design recommendations that will facilitate the universal acceptance of the generated residue depletion data to fulfill the national/regional requirements for drugs intended for using in aquatic food-producing species.

Meet New Consultant Penny Vyskocil

Penny Vyskocil

Penny Vyskocil is a food safety, regulatory, and quality professional with extensive experience in both manufacturing and retail, inclusive of corporate and plant leadership positions. She has a proven track record of strategic planning, organizational effectiveness, staff development and project execution. Her expertise includes cereal, snacks, dry meals, IQF vegetables, Low Acid Canned Foods (LACF) and milling.

Meet September 2019 Issue of the Month Author

Tom Jonaitis

Tom Jonaitis

Canadian-based Tom Jonaitis works with clients in the food, dietary supplement, consumer product and related industries, providing comprehensive toxicology and regulatory consulting guidance and support. He is an expert in regulatory evaluations including scientific literature hazard reviews and summaries, as well as creating pre-market quality and safety dossiers for novel food and dietary supplement ingredient applications to government agencies – FDA, Health Canada and Australia’s TGA, FSANZ. Tom reviews and evaluates the results of in vitro and in vivo toxicological studies and has additional expertise in pesticide/agricultural chemical regulations, workplace hazard classifications, and spray foam human health risk assessments.

FDA Begins Enforcement of FSVP

Dear Readers,

Edward A. Steele

Welcome to the September 2019 edition of EASeNews, the free news publication dedicated to FDA regulated industries.

FDA issued its first warning letter related to FSVP Final Rule enforcement of FSMA. The industry has long been anticipating FDA’s enforcement vs educational-based approach to FSVP. After two years of working to ensure importers of foreign foods and foreign food ingredients understand their requirements to verify supplier safety policies and track records, the Agency will now begin cracking down on those firms still not in compliance. EAS’ Team FSMA offers comprehensive services in the area of FSMA and FSVP. From desk audits of current policies to mock-FDA inspections of facilities, our experts help you to identify gaps and develop actions plans to mitigate risks. Learn more about our services by viewing our short promotional videos and reviewing our industry services sheets.

Additionally, FDA has indicated that drug firms that do not certify updated information or that no changes have taken place since the last renewal cycle can expect FDA to begin delisting products which can lead to misbranding. FDA has been taking an educational-based​ approach to the enforcement of product and facility renewals, however in a constituent update dated August 13, 2019, the Agency confirmed firms can expect greater hardships for not complying. EAS offers assistance with registrations and listings of both facilities and products as well as proactive annual updates and renewals. We invite you to contact us to learn more about our services and how we may assist you.

I am pleased that EAS has been invited to participate in educational sessions at a number of industry events this month. From FDLI to CHPA to NCBFAA to a keynote speaker at an international dairy event in Turkey, our experts will be traveling the globe in September ensuring FDA compliance is at the top of everyone’s agenda.

Additionally, we are offering a number of complimentary regulatory webinars with topics ranging from Food Defense, (September 12); to Quality Management Systems for medical devices (September 25) and a reintroduction to our expert witness training via webinar on November 6. There is always something new happening at EAS and we look forward to your participation in any of our regulatory events.

Our issue of the month is written by Tom Jonaitis and discusses common pitfalls with GRAS submissions. If you missed our recent webinar on GRAS submissions, presented by Robin Guy and Robert Kapp, you may now view it on demand. EAS has a dedicated team of toxicologists and regulatory scientists who regularly assist EAS clients with both GRAS and independent GRAS submissions.

Finally, we welcome new consultant, Penny Vyskocil, an expert in food safety in a variety of product types, from cereal, snacks, dry meals, IQF vegetables, Low Acid Canned Food (LACF) and milling.

Thank you for your interest in EAS and as always please feel free to contact me if you have any questions or if EAS can be of assistance.

Sincerely,

Edward A. Steele Signature

Ed

EAS Instructs at FDLI Educational Events

EAS Senior Director for Food Consulting Services, Allen Sayler will present a lunch-time seminar for FDLI’s Law Over Lunch program on September 17 at DLA Piper in Washington D.C.. Allen’s topic, Recent FDA and CDC Human Illness Investigations, Recalls & Enforcement Actions – Trends and Lessons Learned is open to FDLI members only.

Additionally, two of our experts in food and dietary supplement labeling are speaking at FDLI’s Intro to Food Law and Regulation on September 24-25, 2019 at Crowell Moring in Washington, D.C.. Gisela Leon will present an Introduction to Food Law and Regulation and Andrea Yablunosky will instruct Food Labeling, Nutrient Content and Other Claims.

Finally, James Hoadley, Ph.D., will teach a session on FDA Food Labeling for an FDLI seminar presented at CFSAN, on September 12, 2019. EAS is pleased to be a frequent contributor to numerous FDLI educational programs on a variety of product areas.

What Should We Consider When Exporting Our FDA Regulated Products to the US?

By Victoria Pankovich

Each month EAS experts answer one question sent in by readers of EASeNews. This month’s question, on considerations for a reliable US Agent, is answered by Victoria Pankovich, Regulatory Specialist, who assists EAS clients with US Agent requirements. If you would like to ask a question of our experts contact us here.

Question: As a firm operating outside of the US, what criteria should we consider when choosing a reliable US Agent for exporting our FDA regulated products to the US?

Pankovich: While most foreign companies engaged in exporting products to the United States understand their regulatory obligation to appoint a US Agent to liaise with the US FDA, what many may not understand is the business benefits that can be gained by working with a professional and reliable US Agent. You should look for a US Agent, who is a proactive partner that can provide guidance on FDA regulations, assist in electronic and paper submission actions and who understands the organization, structure and authorities of the US FDA.

US Agents can be single individuals, or they may be named individuals as part of a larger organization such as the case of consulting firms, like EAS, that provide not only a US Agent service but other regulatory support services as well. The latter provides a depth of capability that allows a firm to be prepared for any eventuality when dealing with the FDA.

Simply put, a US Agent acts as a liaison between the FDA and the foreign company for purposes of communication. This is important in many instances, for example, the case of submitting a food ingredient, medical device or pharmaceutical product application. It is critical for the FDA to have a US-based contact to which they can address any questions or requirements needing clarification prior to the product going to market.

In addition to this basic function, it is not only prudent but extremely beneficial to choose a U.S. Agent with regulatory strength that can assist with any importing issues should they arise. FDA inspects products as they arrive at the US border. Products may be detained for any number of reasons – from lack of prior notice, to product labeling that does not meet US specifications, to products shipped from facilities without an active foreign facility registration or low-acid canned food registration. In the case of detained products, expediting the receipt of required information from the Agency and responding with the missing documentation in a timely manner is critical. Keep in mind, the FDA only allows a certain, generally small, window of time within which to respond to their inquiry. Products waiting for US entry cost manufacturers time and money and a proactive US Agent who understands how to navigate the many bureaucratic layers in order to quickly provide answers to the FDA or US Customs Border Patrol is imperative for business flow.

The FDA copies US Agents on notifications of facility and FSVP inspections. US Agents such as EAS, that possess a broad understanding and capability in all areas of FDA regulatory compliance, can often assist with preparing for these inspections by reviewing documentation and / or conducting a mock-inspection so that plant managers and staff will know what to expect when the Agency arrives. In some cases, a firm may wish to have a consultant familiar with the Agency and their inspection process on site during the inspection itself. After the inspection, should the Agency find violations that need to be addressed, a US Agent knowledgeable in FDA regulations should be able to help the firm makethe needed corrections to bring themselves into full compliance with FDA requirements.

When considering a US Agent, ask important questions to help determine the level of service and competence they will be able to provide. You should also consider how comfortable you are with the clarity of their communications and their ability to represent your firm and its objectives to the FDA, they are after all going to be seen as an extension of your organization. Are they able to meet the most basic requirement of having a named US-based point of contact for US FDA communications? Does the US Agent have the technical know-how to assist with gathering important information in the event of a detained product or a question posed by the Agency? Do they have direct experience in helping firms prepare for a US FDA inspection? Should you wish, are they able to be present and provide support during the US FDA inspection? In the event of a detained product, does that US Agent understand how to interpret the Agency’s requests for documentation so that correct responses can be quickly provided?

EAS provides US Agent assistance with our vast network of independent consultants who specialize in various product areas. We invite you to learn more about our US Agent services on our webpage. Regardless of whether you choose EAS to act as your US Agent, we do recommend that you watch our free on-demand video which discusses the roles that US Agents play. If EAS can answer any questions please feel free to contact us. It is an easy matter to officially change your appointed US Agent.

Crane to Instruct CHPA OTC Academy Courses

Independent Advisor for OTC Drugs and Labeling, Susan Crane, will be an instructor at the October 28-29, 2019 Consumer Healthcare Products Association (CHPA) OTC 101 Seminar followed by an October 30 Monograph Workshop in Wilmington, DE. EAS has been a proud participant in OTC Academy educational events for a number of years. Registrations are being taken directly through CHPA.

Meet New Consultant Rebecca Harter

Rebecca Harter

Rebecca Harter assists EAS clients with a variety of food safety, labeling and sensory product development challenges in both human and animal food industries. She is well versed in both FDA and USDA regulations including shelf life analysis, product matching, flavor development, thickeners (Hydrocolloids and Starches), managing ingredient density variation in dry blending, freeze-thaw stability, colorants, and spice-extractive conversions. Prior to consulting, Rebecca was the Director of Regulatory, New Products, and Quality at PetAg, Inc.

Avoiding Delays of Your Import Cargo Shipments through US Customs and Border Protection (CBP)

By William (Bill) Scopa

The US Customs and Border Protection (CBP) has varied enforcement responsibilities, including detecting drug smuggling, weapons of mass destruction, and Immigration. Typically, these concerns are not what will cause the importer delays in their cargo shipments. The more common delays, ones where consultants such as EAS with expertise in CBP operations can assist, are due to CBP’s other mission, assigned to it from its inception in 1789 – trade and revenue. Under this mission, CBP has programs such as Antidumping and Countervailing Duties; Import Safety, Intellectual Property Rights; Revenue; Textiles; Trade Agreements; and country of origin marking. All of these have risk to them, and any inconsistencies in paperwork, descriptions, value; and tariff classification are likely to cause delays. It is up to you and/or your Customs broker to be knowledgeable of all requirements.

As an importer, it is your personal responsibility to take “reasonable care” to ensure that you are compliant. As a consultant, we can review or even generate documents based on your data that keeps your company in compliance with the many varied and complex entities that oversee the legality and safety of product entry into the U.S. Generally, “reasonable care” means that you have put in place the proper compliance procedures. CBP has put out excellent informed compliance documents, even one on taking “reasonable care”. Click for CBP Compliance Documents.

Before you import, a few fundamental questions need to be answered. Did you consult these documents? CBP also has a system, Customs Rulings Online Search System (CROSS), where importers request rulings on classification and other matters, and CBP publicizes its response. Click for CROSS. If your facts and circumstance are the same, the ruling can assist you to make the proper entry, or help should your shipment be detained at the border. Understanding how to assess the similarity of products within CROSS is key to compliance.

One important point is to ensure that your broker is knowledgeable about your products, understands program codes associated and has verified that data. Many products can be regulated by other federal agencies, and you and your broker need to know those requirements. Generally, the importer remains liable, even for a broker error. Are you sure that your broker knows which FDA program code to submit? Mistakes will likely cause delays. CBP’s Automated Commercial Environment (ACE) verifies data as well as provides FDA and other agencies visibility into your entries. Are you sure that your broker is provided all the necessary information by you or the manufacturer to submit a proper entry?

CBP also provides programs to help importers increase the level of trust with CBP. Being trusted means benefits such as fewer exams and expedited releases. Did you know that at the land border the delay could be with the trucking company or driver? CBP offers a program for low risk commodities named The Free and Secure Trade (FAST) program Click for FAST This program allows expedited processing for commercial carriers who have completed background checks and fulfill certain eligibility requirements. To be eligible, you must also be a part of CBPs Customs-Trade Partnership Against Terrorism (C-TPAT) program. C-TPAT is available to all qualified importers, and other entities. The issues with both concern supply chain security. The CTPAT benefits are:

  • Reduced number of CBP examinations,
  • Moving your imported product entries to the front of the inspection line,
  • Possible exemption from Stratified Exams,
  • Shorter wait times at the border,
  • Assignment of a Supply Chain Security Specialist to the company, and
  • Access to the Free and Secure Trade (FAST) Lanes at the land borders.

Besides securing the supply chain, CBP offers programs to assist with trade compliance. One is account management through CBP’s Centers of Excellence and Expertise (CEE). CBP has 10 CEES, and each focuses on certain parts of the tariff. For example, there is the Agriculture and Prepared Products CEE in Miami. There is also the Pharmaceutical, Health and Chemicals CEE in New York. Consultants such as EAS can help address any questions or confusion with these CBP CEEs.

Finally, CBP has an Importer and Self-assessment (ISA) Program CBP ISA Program. Show CBP that you can monitor your own compliance with proper controls, and you can be removed from CBP’s regulatory audit pool, and should CBP find noncompliance, there is an opportunity to avoid penalties by filing a [Prior Disclosure](https://www.cbp.gov/sites/default/files/assets/documents/2017-Oct/Prior Disclosure FINAL.pdf). Generally, an importer can file a prior disclosure and avoid penalties when it finds its own mistakes and informs CBP. One way to proactively keep your business on top of irregularities is to have a qualified consultant perform a desk audit of documentation and filings to ensure data is in order. A more in-depth audit of SOPs and facilities could be warranted in instances where significant discrepancies are found.
Let’s discuss a little bit about the different programs that can cause delays.

Antidumping and Countervailing Duties (ADCVD). There are 483 different ADCVD orders issued, these orders affect a wide range of products from grocery plastic bags; to pencils, and seafood products. The orders are assessed, not only against specific countries, but against different exporters and manufactures, and each exporter or manufacturer can be assessed different rates of duty. In the agricultural arena, duty rates can be high 2 or 3 hundred percent. CBP enforces these orders. Did you check the ITC and Commerce websites or have your consultant check to see if your product is covered? ITC ADCVD Orders Did you or your consultant check CBP web site for ADCVD messages which describe the products covered? CBP ADCVD messages Submitting a tariff classification covered by one of these ADCVD orders without the proper entry type will likely have your cargo stopped.

Import safety. Did you know there are 47 government agencies that have access to all or parts of the import entry data? Fifteen of them actually require that importers provide import data attached to the CBP entry. Products can overlap different agency regulation; especially with FDA; for example, drugs with DEA, food products with APHIS, wildlife with FWS, seafood with NMFS, and tobacco and alcohol with TTB. CBP is the border agency and CBP officers and import specialist will assist the other agencies in enforcement.

Revenue (value, classification, description) All of your imports require proper Harmonized Tariff classification, valued correctly and described accurately. An ambiguous or too general description on the entry or manifest cargo description increase the risk for further review

Trade Agreements There are trade agreements with 20 countries that CBP enforces. Free-trade-agreements all have their own document requirements. Delays can occur, for instance, by not having the proper country of origin certificates.

Country of Origin No matter what type of examination CBP does, if a product is found not to be properly marked with the country of origin, the importer can be forced to mark the goods before release. Please see the Marking Requirements for more information.

Preparing and maintaining the required documentation, applications and oversight of suppliers and transporters of your imported FDA regulated products can be a challenging and confusing process if you try to “go it alone”. It is crucial for the smooth flow of your products through US Customs, that all requirements are addresses properly. One way to do so is to work with a consultant such as EAS Consulting Group to conduct an assessment of your current CBP program for imports, review documentation prior to filing with CBP or to just have a periodic consultant with your import team and that of EAS’ import team. Doing so increases the confidence that your shipments will arrive on-time and in a salable condition. EAS’ CBP Team is managed by Senior Director Allen Sayler. For more information on services or to discuss you specific CBP questions send Allen an email here.

EAS Assistance Simplifies FDA Registrations, Listings and Renewals

The FDA requires firms that manufacture foods, pharmaceuticals and medical devices to register their facilities on an annual or biennial basis, depending on the product category. Keep in mind, FDA assesses a Medical Device establishment registration user fee annually. Drug products and medical device products must also be listed with the FDA.

Any changes or updates to a facility’s information, such as address, contact information, or designated U.S. Agent, should the location be based outside of the U.S., must be reported in a timely manner. Changes to a drug listing must also be updated as soon as possible. The agency dictates these changes be reported, at the very least, the June or December following such a change.

FDA uses facility registration and product listing information as part of their compliance reviews for cross referencing product listings and forms at U.S. ports of entry. Discrepancies can cause products to be considered misbranded and / or potentially lead to the detaining of goods. Additionally, FDA may at any time make announced or unannounced inspections at registered facilities, so it is imperative that all information uploaded into the FDA system is done with care and accuracy.

EAS offers registration and listing services to our clients, as well as appointment as the U.S. Agent for foreign clients. Our comprehensive services enable your firm to outsource these important, yet cumbersome, administrative tasks to our experts. EAS helps you to keep track of compliance deadlines, applicable user fees and acts as a conduit of information between your firm and the FDA.

For more information, we invite you to view our website and Video Shorts which offer quick snapshots of many of EAS’s services. For more information on our registration and listing services specifically, you may wish to view the “Registrations and Listing Services” video found in the third row. For a more detailed look at many FDA compliance requirements we invite you to view our On-Demand regulatory webinars which offer regulatory information on a variety of topics. More information on U.S. Agent requirements can be found here.

Contact EAS with any questions on registration and listings or to engage EAS as your U.S. Agent. The process is simple, and the benefits can be endless.

EAS Offers Internationally Recognized Training Programs to Ensure Compliance Success

Training is an important component for all levels of employees – from managers who must understand the overarching requirements and FDA expectations, down to the line employees and facilities staff who must also execute them. There is no level of responsibility that is exempt from training, no matter the industry.

EAS offers publicly available trainings held around the country and at industry trade events. Recent examples include the GMP workshop held at the AHPA Cannabis-Hemp Congress and the seminar on sanitary equipment held at this summer’s Snaxpo Conference. Upcoming events include Dairy Processing which will be held at the Process Expo in Chicago and a training on OTC monographs at the upcoming CHPA OTC Academy in Wilmington, DE, not to mention the many technical sessions our experts present around the world. Additionally, our public Food and Dietary Supplement Labeling and Dietary Supplement GMP seminars are being held in Irvine, CA in November, and our Dietary Supplement GMP one-day refresher will take place on Long Island.

EAS also offers custom-tailored programs to meet your in-house training needs. Whether we build that program around one of our already designed and internationally recognized events or create a training based on your specific requirements, EAS and our over 150 expert independent consultants offer in-depth and personalized educational events to ensure your company’s compliance with FDA training requirements as well as your staff’s understanding of their unique responsibilities. Contact us for more information and to discuss bringing our in-house experts to you.

EAS to Present Webinar on Prior Notice of Imported Foods for NCBFAA

EAS Independent Consultant Angel Suarez will present a webinar on October 8, 2019 for the National Customs Brokers and Forwarders Association of America (NCBFAA). Discussing the Roles of Import Divisions Review and Compliance, Angel will share insights from his many years of experience as a Supervisor Consumer Safety Officer with FDA where he had responsibility of import enforcement in areas of seafood and Low-Acid Canned Food (LACF) as well as foreign inspections, warning letters, detentions, import alerts, import bulletins, and sample collections. Registrations are being taken by NCBFAA directly. Please visit their website to learn more.

Expert Witness Training Set for November 6 in Alexandria, VA

EAS Independent Consultant and General Counsel with Herrick Feinstein LLP, Ronald J. Levine, will present a one-day intensive seminar on understanding the requirements and expectations of becoming a strong expert witness and will be joined by EAS Independent Advisor for Label and Claims, Betty Campbell. With more and more matters finding their way to the courts, in many cases the expert witness reports and testimony can provide the key pieces of information to make or break a case. Ron will share his expertise and help participants hone their skills on developing reports and testimony as well as how to build their resume. Join Ron and Betty in Alexandria, VA on November 6 (register early as seating is limited) or attend the training remotely. More information can be found here.

EAS Webinar on Food Defense – Untangling the Challenges and Strengthening Opportunities

EAS Independent Advisor for FSMA, Charles Breen and Consultant Kathy Knutson, Ph.D. will co-present a webinar on Food Defense on September 12, 2019 at 1pm eastern. Food Defense is increasingly a worry for firms as our global business climate opens opportunities for intentional harm both domestically and overseas. The ability of food manufacturers to identify and mitigate the impact of intentional attacks that compromise food safety is not only required as part of the Food Safety Modernization Act (FSMA) it makes good business sense to protect consumer health and brand reputation. Join Charles and Kathy for this complimentary webinar by registering here.

July 2019 Drug and Device Corner

The FDA recently issued a warning letter to a company for inaccurate information in one of their drug listings. Section 510(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act and 21 CFR Part 207) outlines the requirements for registration and listing of drug products. EAS would like to remind our clients of the importance of ensuring not only that your drug listings are current, but also correct with regard to both product and label information. Failure to fulfill your listing obligations renders your product misbranded. If you have questions or would like further information, please contact EAS.

The Office of Global Policy and Strategy (OGPS) has launched its own Twitter account, https://twitter.com/FDA_Global. The FDA invites all to follow their new Twitter handle for day-to-day information on FDA’s global regulatory work, foreign offices and international arrangements. Have questions? Contact: FDA_Global@fda.hhs.gov.

Guidance Document updates on the FDA website

All Divisions

Postmarketing Safety Reporting for Combination Products

This guidance addresses how to comply with the final rule on postmarketing safety reporting (PMSR) requirements for combination products that FDA issued on December 20, 2016 (81 FR 92603, hereafter the “combination product PMSR final rule,” “final rule,” or “rule”).

CDER

Federal Register Generic Drug User Fee Rates for Fiscal Year 2020
The FDA has published the FY2020 GDUFA fee rates.

07-22-2019 FDA is announcing the withdrawal of the draft guidance for industry Providing Regulatory Submissions in Electronic Format—Submission of Manufacturing Establishment Information, issued in December 2016.

Establishing Effectiveness and Safety for Hormonal Drug Products Intended to Prevent Pregnancy

This guidance provides recommendations for clinical trials designed to establish clinical effectiveness and safety for hormonal drug products intended to prevent pregnancy.

Harmonizing Compendial Standards With Drug Application Approval Using the USP Pending Monograph Process

This guidance describes the process that allows for the revision of compendial standards that are harmonized with the approved quality and labeling requirements for a drug product application.

Using the Inactive Ingredient Database

This guidance describes the Food and Drug Administration’s (FDA’s) Inactive Ingredient Database (IID) and provides recommendations for how to use the IID in the development of drug products.

Compliance Policy for Certain Compounding of Oral Oxitriptan (5-HTP) Drug Products for Patients With Tetrahydrobiopterin (BH4) Deficiency Immediately in Effect

This guidance describes the Food and Drug Administration’s policy concerning the conditions under which the Agency does not generally intend to take regulatory action against a licensed pharmacist in a State-licensed pharmacy or Federal facility or a licensed physician using the bulk drug substance oxitriptan to compound oral drug products for patients with tetrahydrobiopterin (BH4) deficiency.

E19 Optimisation of Safety Data Collection

This Guideline is intended to provide internationally harmonised guidance on when it would be appropriate to use a selective approach to safety data collection in some late-stage pre-marketing or post-marketing studies, and how such an approach would be implemented.

Advanced Prostate Cancer: Developing Gonadotropin-Releasing Hormone Analogues

This guidance describes the Food and Drug Administration’s (FDA’s) current recommendations regarding the overall development program to establish the effectiveness and safety of gonadotropin-releasing hormone (GnRH) analogues for treating advanced prostate cancer.

Submitting Next Generation Sequencing Data to the Division of Antiviral Products Guidance for Industry Technical Specifications Document

The purpose of this technical specifications document is to provide the current thinking of FDA’s Division of Antiviral Products (the Division) in regard to the submission of next generation nucleotide sequence analysis procedures and data in support of resistance assessments for the development of antiviral drug products.

CDER & CBER

Population Pharmacokinetics

This guidance is intended to assist sponsors of new drug applications (NDAs) and biologics license applications (BLAs) in the application of population pharmacokinetic (population PK) analysis.

Risk Evaluation and Mitigation Strategies: Modifications and Revisions

This guidance provides information on how the FDA defines the types of changes to approved risk evaluation and mitigation strategies (REMS), how application holders should submit changes to an approved REMS, and how the FDA will process submissions from application holders for changes to REMS.

Drug Abuse and Dependence Section of Labeling for Human Prescription Drug and Biological Products — Content and Format

This guidance is intended to assist applicants in writing the DRUG ABUSE AND DEPENDENCE section of labeling, as described in the regulations for the content and format of labeling for human prescription drug and biological products.

Instructions for Use — Patient Labeling for Human Prescription Drug and Biological Products and Drug-Device and Biologic-Device Combination Products — Content and Format 

This guidance provides recommendations for developing the content and format of an Instructions for Use (IFU) document for human prescription drug and biological products and drug-device or biologic-device combination products submitted under a new drug application (NDA) or a biologics license application (BLA).

Epidermolysis Bullosa: Developing Drugs for Treatment of Cutaneous Manifestations

The purpose of this guidance is to assist sponsors with the development of drugs for treatment or prevention of the serious cutaneous manifestations of the heterogeneous group of disorders collectively known as epidermolysis bullosa (EB).

Treatment for Heart Failure: Endpoints for Drug Development

This guidance has two purposes: 1) to make it clear that an effect on symptoms or physical function, without a favorable effect on survival or risk of hospitalization, can be a basis for approving drugs to treat heart failure; and 2) to provide recommendations to sponsors on the need to assess mortality effects of drugs under development to treat heart failure.

M10 Bioanalytical Method Validation 

This guideline is intended to provide recommendations for the validation of bioanalytical assays for chemical and biological drug quantification and their application in the analysis of study samples.

Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications

This guidance describes how sponsors and applicants must organize the content that they submit to the Agency electronically for all submission types under section 745A(a) of the FD&C Act.

CDRH

Live Case Presentations During Investigational Device Exemption (IDE) Clinical Trials

This document provides guidance on important information about a live case presentation that should be provided as part of an original IDE application or a supplement to an IDE application when requesting inclusion of a live case presentation during a clinical investigation.

Center for Devices and Radiological Health (CDRH) Appeals Processes

This guidance document describes the processes available to outside stakeholders to request additional review of decisions or actions by Center for Devices and Radiological Health (CDRH or the Center) employees.

Center for Devices and Radiological Health (CDRH) Appeals Processes: Questions and Answers About 517A

This guidance document provides the Center for Devices and Radiological Health of key provisions set forth in section 517A of the Federal Food, Drug, and Cosmetic Act, as those provisions pertain to requests for appeals of significant decisions under 21 CFR 10.75, as well as for the timeframes and procedures of regulatory decisions and actions taken by CDRH under 21 CFR 800.75.

Marketing Clearance of Diagnostic Ultrasound Systems and Transducers

In addition to outlining regulatory approaches for certain diagnostic ultrasound devices, this guidance document describes the types of modifications to a diagnostic ultrasound device for which FDA does not intend to enforce the requirement for a new premarket notification (510(k)).

Clinical Investigations for Prostate Tissue Ablation Devices

This draft guidance document, when finalized, will provide recommendations for (1) complying with the clinical testing special control under 21 CFR 876.4340(b)(8) for premarket notifications (510(k)s) for high intensity ultrasound systems for prostate tissue ablation, and (2) collecting clinical data to support marketing submissions for new types of prostatic tissue ablation devices.

Metal Expandable Biliary Stents – Premarket Notification (510(k)) Submissions

This guidance document provides recommendations for 510(k) submissions for metal expandable biliary stents and their associated delivery systems.

CVM

CVM GFI #181 Blue Bird Medicated Feed Labels

The purpose of this guidance is to provide NADA sponsors of Type A medicated articles with FDA’s current thinking on the recommended content and format of Blue Bird labels.

Determining the Risk-Base of High-Risk Foods

Each month EAS answers one question sent in by readers of EASeNews. This month’s question on the risk-base of high-risk foods is answered by EAS Independent Advisor for FSMA, Charles Breen.

Question: How do you determine the Risk-Base of High-Risk Foods?

Breen: With the passage of the Food Safety and Modernization Act in 2011, Congress told FDA to identify high risk foods. FDA had (and continues) to understand the term “high risk” to mean foods that may present hazards, which, if not controlled, are likely to cause illnesses or injury when consumed.

FDA has given high risk food firms priority for inspectional purposes but has never clearly defined what is or is not “high risk.” Many high-risk food facilities are covered by specific rules, such as juice and seafood HACCP, or special programs, such as Domestic and Imported Cheese and Cheese Products, and agency support to States for the Pasteurized Milk Ordinance and Interstate Milk Shippers list.

So, what are High-risk foods? As defined in the Food Safety Modernization Act (FSMA) section 204(d)(2)(A), these include:

  • Those in which there is a known safety risks of a particular food, including the history and severity of foodborne illness outbreaks attributed to such food, while taking into consideration foodborne illness data collected by the Centers for Disease Control and Prevention (CDC);
  • Food with a high likelihood of potential risk for microbiological or chemical contamination or that would support the growth of pathogenic microorganisms due to the nature of the food or the processes used to produce such food;
  • The point in the manufacturing process of the food where contamination is most likely to occur;
  • The likelihood of contamination and steps taken during the manufacturing process to reduce the possibility of contamination;
  • Foods that result in a likelihood of foodborne illness should it be contaminated, and
  • The likely or known severity, including health and economic impacts, of a foodborne illness attributed to a particular food.

In the absence of defined formulas, each of these criteria could be applied qualitatively and to varying degrees to assign high risk or not high risk to facilities. In FDA’s view, this was useful to efficiently respond to new risk-based information. Likewise, it allows for less FDA attention to known high risk foods such as fluid milk that have long history of safe production. But it does not comply with the mandate in section 204(d)(2)(A) of FSMA.

Prior to the Court order to finally publish a list of high-risk firms, inspections could be tailored to meet goals within appropriated and often unpredictable resources. For example, if the goal is to inspect X % of the high-risk inventory in one fiscal year, and resources are cut, the number of facilities classed as high risk could be tweaked to still allow FDA to meet the goal. (Management cliché: Never set a milestone you don’t know you can reach.)

There are negatives to this approach. A few that come to mind include the fact that a facility can never be certain whether or not it is on the high-risk list. The lack of flexibility is frustrating for agency critics and oversight committees due to an inability to hold FDA accountable on a clearly defined, fixed level of accomplishment. Lastly and importantly, it does not comply with FSMA.

FDA recently was mandated to take specific and determined action in creating designation criteria for these high-risk categories and submitting documentation to the Office of the Federal Register for publication. Deadlines include:

  • Designation of the list of high-risk foods required by FSMA Section 204(d)(2)(A) by September 8, 2020
  • Publication of Proposed Rule for recordkeeping requirements for the designated high-risk foods as required by FSMA Section 204(d)(1) by September 8, 2020, with final rule publication no later than November 7, 2022
  • Publication of the list of high-risk foods on the FDA website is required by FSMA Section 204(d)(2)(B) Upon publication of the Final rule in the Federal Register.

Agency critics hope that having a defined list will mean FDA’s attention to high risk foods will drive down the number of illnesses and deaths caused by pathogens. I am less sure there will be a cause and effect relationship between a list and declining harm to consumers.

While there is considerable overlap between factors in the old way FDA used, and the new way FSMA prescribes, the basic assumption has changed. It’s no longer “as many high-risk foods as the budget allows” and is now “every high-risk food no less than every three years.” It will make it more difficult to obfuscate budget shortfalls as easily as was the case before FSMA.

GRAS Submissions of Food Safety Webinar Announced

EAS Independent Consultants and Toxicologists, Robin Guy and Robert Kapp will present a discussion on the challenges and pitfalls of successful GRAS submissions. GRAS, or Generally Recognized as Safe, is a designation granted by FDA for food ingredients. It can take years of safety studies and thorough documentation before a GRAS designation is warranted so understanding the requirements is essential for streamlining the process.

Join Robin and Bob on August 22 at 1 pm eastern for an informative discussion on GRAS and how you can increase your chances for a successful submission the first time. Register today!

Meet Issue of the Month Author William Scopa

William Scopa

William (Bill) Scopa has over 30 years at Customs and Border Protection (CBP) at both ports of entry and Headquarters. During his 15 years at the ports, he processed import and export clearance of cargo and passengers. At Headquarters, as a Branch Chief, he led the development of policies and procedures addressing such areas as, intellectual property rights, anti-dumping and countervailing duties, and revenue collections. He spent several years leading CBP’s trade enforcement efforts in targeting evasion such as misclassification and undervaluation. His last position was CBP’s liaison to other government agencies to develop CBP import processing of imports for EPA, FDA, and DEA.

Expediting Imports at U.S. Ports of Entry

Dear Readers,

Edward A. Steele

Welcome to the August issue of EASeNews, the free newsletter for industries regulated by FDA. We had numerous questions after the brief mention of FDA’s new requirements for identifying and communicating information on high-risk foods. Our Independent Advisor for FSMA, Charles Breen is shedding light on the subject in this month’s Ask the Expert when he answers our most frequently received question – How is the risk-base of a high-risk food determined?

Bill Scopa, who was formerly with Customs and Border Patrol, has provided a very interesting article on CPB and steps firms importing products into the U.S. marketplace should take to ensure expeditious entry. As you know, EAS Consulting Group is frequently called upon to assist firms which have detained products for any number of reasons. EAS acts as a U.S. Agent for foreign firms and can assist you with import requirements per FDA and USDA regulations. Contact us to learn more about these services.

Registration for our November 6 Expert Witness seminar is underway. Expert Witnesses are relied upon for their opinion reports and testimony as cases are adjudicated through arbitration, mediation and trials. Our Independent Consultant, Ron Levine, who is also General Counsel at Herrick Feinstein will conduct a one-day seminar to help those interested or already acting as an Expert Witness to improve their skills and positioning as an expert when called upon to act in this capacity. Learn more and register here.

We also invite you to join us August 22 for a complimentary webinar on GRAS submissions. This will cover pertinent information that must be included in a GRAS submission, as well as pitfalls firms face when preparing the dossier. Additionally, there will be a discussion on the process once submitted and expectations for working with FDA’s OFAS during their review. For more information, and to register click here.

Lastly, we welcome Rebecca Harter to the EAS team of independent consultants. Rebecca has a unique skillset with her background in sensory experience including blending for optimal texture development and quality, flavor development and product stability.

Thank you for your interest in EAS and as always please feel free to contact me with any questions and to share this newsletter with your colleagues.

Sincerely,

EAS Signature Ed

Ed

Ron Levine Expands EAS Services Offering with Creation of Expert Witness Training and Consulting on Complex Commercial Matters

Ron Levine

Ron Levine, EAS Independent Consultant and General Counsel of Herrick, Feinstein LLP will lead EAS’ newest training initiative with a comprehensive look at how to be an effective and sought-after Expert Witness.

Ron Levine has over 40 years of experience advising consumer products companies in complex commercial matters. He offers a wealth of services to EAS clients including

  • Litigation research including relevant records and subpoena requests
  • Research on outcomes of litigations involving similar claims
  • Due diligence assessments including claim history of a target company, risk management policies and procedures
  • Preparing for FDA inspections from the perspective of record production and management
  • Preparing and editing reports to federal agencies and other entities

Ron’s latest projects include helping Expert Witnesses strengthen their understanding of the role, expectations and skills required for being an effective expert witness. With topics including 

  • Understanding the discovery process and the role of the expert
  • The engagement process of becoming an expert
  • How experts are utilized in investigations, trials, and arbitrations
  • Projecting expertise as part of written reports and oral testimony 
  • The business of being an expert witness 

Ron is a pragmatic advisor who helps clients anticipate, minimize and resolve the financial and reputational damage arising from claims and potential claims, Ron specializes in crisis management, for food and beverage manufacturers, where he advises on class action litigations and investigations, including labeling, FSMA, advertising claims, product recalls, FDA regulations, new technologies such as 3-D printing and block chain and many others.

Additionally, Ron has developed EAS’s newest seminar on how to become and strengthen skills as an expert witness. This seminar, in Alexandria, VA and offered remotely will be November 6m 2019. For more details see EAS in Action.

Risks to OLDs Discussed in Natural Products Insider

Natural Products Insider

Independent Consultant Bruce Elsner discussed considerations of Own Label Distributors for the assurance of GMP compliance and certificates of analysis in Natural Products Insider. Dietary supplement companies that contract out some or all their operations often fail to consider how little they know about the operations of those providing the contracted services and thus may be taking significant risks, he says.

Warehousing Compliance and FSMA Reviewed in Food Safety Strategies

Food Safety Strategies

The requirement to comply with FSMA is well understood for food manufacturers, and there are no exceptions for warehousing facilities. FDA inspections of facilities that receive, store and distribute human or animal food can occur at any time and firms must be prepared for such an inspection 24 hours a day. Jerry Heaps discusses ways warehousing facilities can and should stay on top of FSMA requirements in Food Safety Strategies.

Register for EAS Webinar on FDA Inspections in India

Independent Consultant, Sophia Lily, is expert of pharmaceuticals who is based in India will present a webinar on how to prepare for FDA facility inspections, including a look at recent FDA observations and trends. Understanding how gaps may be addressed before FDA knocks on your door will lead to a safer consumer product as well as a smoother inspection process. Join Sophia Lily on July 24 at — eastern and — Indian Standard Time. This webinar is conveniently timed for our overseas audiences. Register today!

EAS Offers Dairy 101 at Process Expo

Process Expo

EAS will bring its popular Dairy Processing 101 seminar to the Process Expo in Chicago, October 8-11, 2019. This full day event covering an overview of the US dairy industry will include the impact of dairy farm practices on the quality and composition of raw milk; how raw milk and dairy product prices are established; an appreciation of government requirements for dairy plants including FSMA’S PCHF regulation; exposure to milk chemistry and microbiology (including dairy cultures); an in-depth overview of dairy processing technologies related to milk beverages, cheese, yogurt, ice cream, as well as hands-on practical knowledge of dairy laboratory testing systems and capabilities. Registrations are being taken by Process Expo.

EAS to Offer Training on Expert Witness Preparations

As highly regulated industries are subject to more claims and litigations, and with growing agency challenges to ingredients, processes and branding, the target company’s regulatory compliance is often a key issue in presenting a successful defense. An expert witness’ opinion, report and testimony will play an essential role in mounting the response. Join EAS Consulting Group’s Independent Consultant and General Counsel at Herrick Feinstein LLP, Ronald J. Levine, for a one-day seminar on the role, expectations and skills for being an effective expert witness. Serving as an expert can be a part-time or full-time career. Whether you are just starting as an expert, or are looking to improve your skills, this seminar is meant to help to arm you for the important role you will be playing. We will also be discussing how to craft your resume and promote yourself with an aim of increasing opportunities to serve as an expert. [Add hyperlink when ready]

Next Dietary Supplement GMP Refresher Training in Andover, MA

EAS’ next Dietary Supplement GMP Refresher Training takes place August 13, 2019 in Andover, MA. Taught by Independent Consultant Tamika Cathey, this one-day intensive training is designed and priced so that firms can outsource their GMP training requirements to EAS. Conveniently located around the country, following the August training in Massachusetts, the fall GMP Refresher training will take place in Long Island November 12, 2019. Visit the EAS website for more information on the August 13 GMP Refresher training in Andover and the November 12 GMP Refresher training in Long Island.

EAS Presents cGMP Workshop at AHPA Hemp-CBD Supplement Congress

AHPA Logo

EAS Senior Director for Dietary Supplements and Tobacco Services, Tara Lin Couch, Ph.D. will present a workshop on cGMPs for dietary supplements along with attorney Marc Ullman of Rivken Radler, LLP at the upcoming American Herbal Products Association Hemp-CBD Supplement Congress in Denver, August 14-15, 2019. This event, focused on the challenges and opportunities of marketing hemp and CBD in dietary supplement products, will provide critical information for companies navigating the rapidly evolving legal, regulatory and financial landscapes to manufacture and market dietary supplement products with hemp or hemp-derived ingredients like CBD. For more information and to register visit the AHPA webpage.

How Does USDA Labeling Differ From FDA Food Labeling?

By Susan Glenn

Each month EAS experts answer one question sent in by readers. This month’s answer regarding USDA labeling is provided by Susan Glenn. Susan is an expert in matters pertaining to USDA and FDA regulations of the food industry with a particular focus on labeling, product standards and requirements. To ask your question of our experts, contact us.

Question: How does USDA labeling differ from FDA food labeling?

Glenn: Though both food products, USDA labeling is uniquely different from FDA labeling. While covering the full scope of regulations would require more time than can be answered simply here, (EAS does offer an in-house one-day USDA labeling compliance seminar), here are some brief facts to help you understand the differences.

USDA does not require an allergen statement at the end of the ingredient statement.

USDA requires all ingredients be listed by their common and usual name. Adding the allergen statement is voluntary but, if used, must follow all of the requirements of the Food Allergen Labeling and Consumer Protection Act (FALCPA).

USDA does not require the type size of the ingredient statement and address line to be 1/16”. 9 CFR 317.2(b) states “Any word, statement, or other information required by this part to appear on the label must be prominently placed thereon with such conspicuousness (as compared with other words, statements, designs, or devices, in the labeling) and in such terms as to render it likely to be read and understood by the ordinary individual under customary conditions of purchase and use.” For poultry, the reference is 9 CFR 318.116.

The New Nutrition Facts Panel formats for FDA are not required for USDA. On January 19, 2017 USDA published a proposed rule to revise the nutrition facts panel format and certain reference amounts customarily consumed (RACC) to be consistent with FDA nutrition facts panel formats and certain RACC changes. By the end of July 2017, USDA announced the purposed rule was placed on the inactive list of rules and could be re-introduced “at a later time.” Meat and Poultry companies have the option to use the new FDA formats but must adhere to all of the FDA regulations pertaining to the formats and RACCS.

There are many additional differences between USDA and FDA regulated products, with labeling a big concern and one which can be confusing if the nuances between USDA and FDA labeling and not well understood. For more information on USDA labeling contact EAS.

June 2019 Drug and Device Corner

As part of the FDA’s ongoing efforts in their goal of more ANDA approvals in order to increase access to high-quality lower cost generic drugs, the agency began on 18 June 2019 to publish additional data in the existing Paragraph IV Patent Certifications list. The FDA hopes to assist ANDA applicants in their business decisions to pursue generic drug development. The list will now include, on a prospective basis, the following information:

  • Number of potential first applicants
  • 180-day decision status
  • Date of first “first applicant” approval
  • Date of first commercial marketing
  • Expiration date of last qualifying patent

For further information, please see the FDA’s Patent Certifications and Suitability Petitions website.

The FDA has posted a website regarding products containing cannabis or cannabis-derived compounds, and particularly cannabidiol (CBD), articulating their current position and 4 specific points they are working to learn more about. The webpage includes a link to a public docket the FDA is using to gather information and data. The docket is available for comment until 16 July 2019. The agency has consistently stated, however, that it believes that CBD is not a legal ingredient in a food or a dietary supplement because it has been investigated as a Investigational New Drug (IND) and has been approved for use in the drug Epidiolex.

Effective 17 June 2019, the FDA is making pre-assigned ANDA number requests available via the CDER NextGen Portal.

Guidance Document updates on the FDA website

CDER

CDER & CBER

CDRH

CDRH & CBER

  • Testing for Biotin Interference in In Vitro Diagnostic Devices
    This guidance is intended to help device developers and clinicians understand how FDA recommends biotin interference testing be performed, and how the results of the testing should be communicated to end-users, including clinical laboratories and clinicians.

CVM

Did you know? EAS Consulting Group Offers Preparatory Assessments Against VQIP Requirements for Firms

The Voluntary Qualified Import Program (VQIP) enables qualified importers of food and food products into the U.S. an expedited review and entry. However, meeting the stringent requirements of the VQIP program requires a thorough demonstration of documented safety of foreign suppliers of human and animal foods as well as an unblemished history of imports.

FDA uses its Predictive Risk-based Evaluation for Dynamic Import Compliance Targeting (PREDICT) import screening tool to recognize shipments of food that are part of an approved VQIP application. The technical application requirements to achieve VQIP status can be time-consuming and complicated, but the end result is a smoother facilitation of imports. Many firms find VQIP to be of benefit to their operations and that of their customers in the US. In some cases, firms wishing to apply for VQIP seek an independent third-party certification of assurance of compliant practices.

EAS Consulting Group offers preparatory assessments against VQIP requirements for firms seeking approval into the program directly or through third-party certifications. EAS ensures that all processes and procedures are compliant with the rigorous safety requirements and identifies any gaps which must be addressed, ultimately better positioning firms when seeking FDA recognition into the VQIP program.

Contact EAS today for a desk assessment of SOPs and review of safety documentation, including that of suppliers, or bring EAS consultants in-house for a mock third-party certification audit prior to undergoing the official inspection. Thorough preparation for VQIP recognition will make for a smoother inspection process and ultimate certification, saving your business time and money by getting your products to the consumer in an expedited manner. For more information contact EAS today. You may also wish to view our recent on-demand webinar on VQIP requirements or search VQIP in the search bar of the EAS website to learn more about the program and our services.

Meet New Consultants for July 2019

Rama Narasimhan

Ramakrishnan Narasimhan (aka ‘Rama’) is a versatile, knowledgeable and competent professional with over 35 years of management experience in the manufacturing sectors pertaining to food, pharmaceutical and dietary supplement industries. He has wide ranging experience in designing, developing, guiding and auditing customized and standard product safety and quality system standards. His ‘think outside the box’ approach to solving complicated technical issues and problems enables novel solutions for clients. He is a frequent invited speaker in the area of product safety (food, pharmaceutical and dietary supplements) in international and domestic conferences.

Rama Narasimhan

Angel Suarez

Angel Suarez is a former Supervisor Consumer Safety Officer with the Food & Drug Administration. In this role he had responsibility of import enforcement in areas of seafood and Low-Acid Canned Food (LACF) as well as foreign inspections, warning letters, detentions, import alerts, import bulletins, and sample collections. He is the co-author of numerous publications including portions of the National Shellfish Sanitation Program’s Shellfish Equipment Construction Guide and the National Shellfish Sanitation Program’s Guide for the Control of Molluscan Shellfish Annotated Manual. In addition, he has developed training courses including FDA Certified Better Process Control School, Inspection and Sampling of Abnormal Food Metal Containers and the FDA Shellfish Officer Standardization Course. Angel has a B.S. with a major in Biology and minor in Chemistry and Physics from the Inter American University.

Angel Suarez

Meet July 2019 Issue of the Month Author

Robert Kapp, Ph.D. has over 30 years’ experience as a toxicologist involved with the management, development, and safety of new and existing products in a broad spectrum of industries including preclinical program study design, study reports, occupational and industrial toxicology and evaluating clinical and product safety data. Dr. Kapp assists EAS clients with writing critical position papers, GRAS notifications, 510(k) submissions, US EPA Premarketing Notifications, toxicology profiles, Safety Data Sheets and labels in the US and in global markets. Prior to consulting Dr. Kapp worked as Director, Toxicology Laboratory at Exxon Biomedical Sciences, Inc. He has a Ph.D. in toxicology from George Washington University.

Robert Kapp Ph.D.

What are SDSs?

By Robert Kapp, Ph.D.

Safety Data Sheets (SDSs) (formerly known as Material Data Sheets (MSDSs) contain basic information about a chemical or product needed to insure the safety and health of the user at all stages of its manufacture, storage, use, and disposal.

Interestingly, SDSs have a long and involved history, extending back into time – ultimately resulting in the present-day format. There are records indicating that MSDS-like documents were used 4000 years ago to describe pharmaceutical use in Egypt. A thousand year later, the Greeks recorded not only their own observations, but also some of their early experimental work on similar documents. Skipping ahead another millennium, chemical data sheets were continuously being developed by chemists at avante garde chemical companies as a way of transmitting various data to fellow chemists: melting/freezing/flash points, viscosity, density. As the industry became more enlightened in the last 100 years or so, the chemists began adding additional items, such as reactions and fire hazards. While health/safety and toxicological data had been developing over the past few 1000 years, it was only recently included on these data sheets as the next logical step in an all-inclusive document.

The US Federal Government got involved in the mid-1960s and developed its original Form LSB-00S-4 to meet the needs of maritime workers, added safety and hazard information for the first time to a chemical safety sheet. It was published and became law on August 23, 1968 in 33 FR 12008 as amendments to 29 CFR parts 1501, 1502 and 1503. Over the ensuing few years, there was pressure on Congress to extend benefits of the Longshoreman’s Act, plus additional safety and health coverages, to all of the nation’s industrial workers. With the passage of Public Law 91-596, on December 29, 1970, OSHA was established within the Department of Labor.

Initially, the formatting for these MSDS’s was fluid and varied considerably from company to company and from country to country. The EU standardized the format into what is now the 16-section document. Nevertheless, the quality, type of information and specifics of the MSDSs remained chaotic and in the minds of regulators, need some consistency. There was an effort to coordinate these vastly different documents by the US Government: The Hazard Communication Standard (HCS) (29 CFR 1910.1200(g)), was revised in 2012, requiring that the chemical manufacturer, distributor, or importer provide Safety Data Sheets (SDSs) (formerly MSDSs or Material Safety Data Sheets) for each hazardous chemical to downstream users to communicate information on these hazards.

The information contained in the SDS is largely the same as the familiar MSDS, except now the SDSs are required to be presented in a consistent user-friendly, 16-section format. When one creates an SDS, he/she must be aware that the proper labeling and warnings are included for the area (country) the product will be sold – the place that regulates the product.

Sections 1 through 8 contain general information about the chemical, identification, hazards, composition, safe handling practices, and emergency control measures (e.g., firefighting). This information should be helpful to those that need to get the information quickly. Sections 9 through 11 and 16 contain other technical and scientific information, such as physical and chemical properties, stability and reactivity information, toxicological information, exposure control information, and other information including the date of preparation or last revision. The SDS must also state that no applicable information was found when the preparer does not find relevant information for any required element.

The basic toxicological information is placed methodically in Section 11. While the specific format is not set, the acute data is a generally good place to start. Toxicological data such as the oral and dermal LD50s (Dose at which 50% of the animals exposed would be expected to succumb – this is a calculated formulaic number from a limited number of animals) as well as the inhalation LC50s (Concentration of a chemical at which 50% of the animals exposed would be expected to succumb). Basic information on skin, mucous membrane, respiratory and eye irritation as well as any repeated dose information would also be inserted in this section. Any cancer listings from IARC, EPA, NTP, ACGIH, NIOSH or OSHA would be included here. Any repeated dose studies that generate the no observed adverse effect level (NOAEL) should be briefly included here. Some companies insist on a toxicological profile of the chemical in this section, while others put minimal information.

There are other sections which will depend upon the toxicology section. For instance, Section 3 is the Hazard Identification and usually deals with the safe handling of the material by the user. This also includes things other than toxicity (e.g. flammability, vapor, etc.) but it is the application of the toxicological data to direct how the user must handle the product. If there are serious issues in handling the product, this has to be pointed out here. Sometimes potential health effects are detailed in this section. If this is global/EU, then those warning pictograms go in this section.

Section 4 is first aid. There are stock phrases that go in here based upon the toxicological profile of the material. Section 5 is Fire Fighting measures and can also relate back to the toxicology section if there’s some serious chemical reactions with the product.

Section 12 is ecological information. This is very important for EU. They put more emphasis on this than we have historically here in the US. The EU regulators want to know the potential ecotoxicity to fish, daphnia, algae and if the product biodegrades and/or bio-accumulates which can produce long-term harm to the environment.

The relevant regulatory information including exemptions, what agency takes precedence, rules to follow in the country that product is in, Toxic Substances Control Act (TSCA) – 1976 Public Law 94-469) listing, etc., should be in Section 15.

To summarize, many companies put a considerable amount of information on their SDSs while others – not so much. As a rule of thumb, the data should be as complete as possible with what is at hand with toxicological statements evaluated by a certified toxicologist. One should never speculate or overstate the effect of the product. As in all things scientific – be truthful and accurate.

FDA Strengthens Commitment to Defining High-Risk Foods, FSMA Enforcement

Dear readers,

Welcome to the July edition of EAS-e-News, the free newsletter for industries regulated by FDA. FDA took an important step this month when it agreed to settle a lawsuit filed by the Center for Science and commit to defining a designated list of “high-risk” foods as well as a proposed rule for high-risk food record keeping requirements by September 8, 2020. Additionally, the final rule will be established no later than November 7, 2022. Originally, Congress mandated that FDA designate high-risk foods by January 2012 and propose recordkeeping requirements for facilities that handle those foods by January 2013, so this renewed effort is welcomed as an important protection against food-borne illnesses which sickens countless annually.

I am pleased to say that EAS is an invited training partner for two upcoming events. First, Tara Lin Couch, Ph.D., Senior Director for Dietary Supplements and Tobacco Services will present a workshop on dietary supplement GMPs along with long-time training partner Marc Ullman, Of Counsel at Rivkin Radler, at the upcoming AHPA Hemp-CBD Congress taking place in Denver, August 14-15, 2019. Additionally, EAS will bring its popular Dairy Processing 101 seminar to the Process Expo in Chicago, October 8-11, 2019. More information on both of these seminars can be found in the EAS in Action section of this issue.

Additionally, EAS is announcing a new training seminar that we are very excited about. Coming on November 6, 2019, EAS Independent Consultant and General Counsel at Herrick Feinstein, Ronald Levine, will instruct a full-day event in Alexandria, VA on how to become, and strengthen skills, in the important service of providing Expert Witness services for FDA litigation, arbitration and mediation matters. EAS has over 30 consultants who serve in the capacity of Expert Witness. This important and critical component, as part of a comprehensive legal team, has become a critical factor in the demonstration of compliance expectations.

We invite you to join EAS at the International Association of Food Protection Annual Meeting, July 21-24, 2019 in Louisville, KY. EAS will be exhibiting at booth #319 and additionally independent consultant PC Vasavada will be speaking as part of an esteemed panel, along with Senior Director Allen Sayler, on FSMA compliance and FDA enforcement. You may wish to also view our recent webinar, Understanding the Food Fraud Puzzle, available on-demand on the EAS website.

I am pleased to welcome two new independent consultants, Rama Narasimhan and Angel Suarez. I am always impressed with the caliber of independent consultants who choose to work with EAS for the benefit of our clients. I invite you to learn more about both in the Who’s Who section of this issue.

I hope you enjoy this issue and please feel free to share with friends and colleagues who may also have interest.

Sincerely,

EAS Signature Ed

Ed

Join EAS for Complimentary Webinars

EAS will host two complimentary webinars in June. First, on the 18th, EAS Independent Consultant Mehrdad Tajkarimi, Ph.D. teams up with Leann Chuboff from SQFI for a webinar on understanding the food fraud puzzle. This webinar is co-sponsored by Food Safety News magazine and will be held at 1pm eastern. Register here.

On June 20, also at 1pm eastern, Senior Director for Pharmaceuticals and Devices, Bryan J. Coleman, will present on GMPs for OTCs with suggestions for how to improve compliance as FDA ramps up enforcement and inspections. With more than 80 therapeutic categories, OTC drug products play an ever-increasing role in health care and manufacturers must recognize that the FDA applies the same, stringent 21 CFR 210 and 211 drug GMP standards to OTC products. Register for the GMPs for OTCs webinar here.

Challenges with Implementing Cleaning Validation

By Miguel Montalvo

Though published well over 25 years ago, FDA’s guidance surrounding cleaning validation continues to cause industry confusion. While everyone agrees that cleaning validation is critical, the application of incorrect or ineffective approaches whether by misunderstanding the purpose of validating cleaning procedures or taking an extremely conservative approach create impractical demands on resources.

Planning is the root of all successful and compliant cleaning validation programs to ensure the assessment will accurately test the desired points. These plans will include a process flow to determine the activities to be conducted starting with the development of matrices for equipment/cleaning procedure combinations for all manufactured products. The next step is to select a worst-case product for each equipment/cleaning procedure combination. It is acceptable to use product family grouping if applicable. Once the worst-case product(s) is(are) chosen, analytical methods that quantify residue levels of target components of these product must be established, including acceptable limits for the residues (also called Maximum Carryover or MACO). The CV protocol can also be prepared at this point. Also, as part of the planning stage, a review of all training programs and process for the cleaning procedures will help to ensure adequate levels of challenges and qualifications are incorporated.

Prerequisites within each protocol execution must be established before initiating cleaning validations. This includes equipment design, analytical methods, adequate cleaning procedures, employee training and calibration of equipment. Cleaning procedures appropriate to each piece of equipment must be documented in appropriate detail. It is not always necessary for the analytical methods to be specific to the chemical entity under examination. If a non-specific method that appropriately measures and quantifies residues of interest under the sampling conditions applied, it’s use may be appropriate. Non-specific analytical methods save time by a considerable factor.

It should be noted that cleaning and sanitizing are often incorrectly combined into one step. The reason these should not be combined is the differences in the purposes. Cleaning is concerned with removing the residues from the previous product (and the cleaning agent if applicable) using a worst-case dirty hold time. Sanitization is concerned with the condition of the equipment before it is used next, particularly from a microbial consideration. As a good option, many companies are establishing a sanitization process/step before using the equipment again and this step is validated separately from the cleaning validation. Or, separately they may test for the microbial bioburden in the equipment surface after the worst-case clean hold time has elapsed to see whether a sanitization step is necessary. If the test fails, the option will be to apply a sanitization step which could be as simple as a high purity water rinse or other more sophisticated processes such as a hydrogen peroxide rinse/application. Of course, these considerations will be affected by the type of product/process being manufactured – from a topical drug, oral solid dosage to the more critical sterile products, specifically those aseptically filled.

There are many considerations when designing and implementing a cleaning validation approach. Ensuring due diligence is paid to assessing and determining which factors best suit each situation will pay dividends in the long run with a thorough and well documented program.

For more information on cleaning validation, including critical missteps, you may wish to view Miguel’s full length article recently published by the International Society of Pharmaceutical Engineers blog (ISPE iSpeak). EAS offers assessment and development of cleaning validation protocols. Contact us to learn more.

EAS Offers Pre-Clinical Safety/Tox Study Services for GRAS and NDI Submissions.

EAS offers holistic and cohesive services for clients looking to submit GRAS and NDI submissions to FDA. From the assessments to design of early feasibility studies, ongoing study oversight with the Contract Research Organization, strategy meetings with FDA and the preparation and dossier submissions, EAS’ expert toxicologists, microbiologists and chemists work closely to ensure prioritization of your study needs and execution. 

Choose EAS for:

  • Determination of required performance outcomes and appropriate studies 
  • Development of study design and protocols
  • Identification of an appropriate Contract Research Organization (CRO)
  • Coordination of the study initiation and management oversight with the CRO
  • On-going monitoring of study protocols and outcomes
  • Input of appropriate data for inclusion in study reports
  • Support the writing of the dossier for FDA submission

What are the Steps to Reporting an Adverse Event to FDA?

By Robert Fish

Each month EAS independent consultants answer one question sent in by readers of EASeNews. This month’s question on adverse events reporting for both OTCs and dietary supplements is answered by Independent Advisor for Quality and Compliance, Robert Fish. Mr. Fish spent 33 years with FDA, including time as the Director, Division of Field Investigations where was responsible for general policy and guidance for the Agency’s domestic and international investigation activities. He has expertise in compliance matters and cGMPs as they relate to pharmaceutical, device, and biologics manufacture. Further, Mr. Fish is ISO 9000 Lead Assessor Trained and is an AFDO Certified HACCP Instructor. He is a sought-after expert, speaking at international events on FDA inspections and GMPs.

Question: What are the steps to reporting an Adverse Event to FDA? 

Fish: In December 2007 the Dietary Supplement and Non-prescription Drug Consumer Protection Act (The Act) became effective. That law required that all over the counter drug and dietary supplement manufacturers and distributors investigate and report to FDA any serious adverse event reports concerning any of their marketed products.

The Act defines an adverse event as any undesirable experience associated with the use of a medical product in a patient. The event is considered serious when the patent outcome is:

  • Death
  • Life-threatening
  • Hospitalization (initial or prolonged)
  • Disability or Permanent Damage
  • Congenital anomaly/birth defect

Other serious (example-required medical or surgical intervention, allergic bronchospasm)

The Act requires that reports of serious adverse events be reported to FDA within 15 business days of receiving the information. The reports are required to submitted using Med Watch Form 3500A.

FDA issued Guidance for Industry concerning this adverse event reporting as well as guidance for completion of the Med Watch 3500A form.

Companies must have procedures in place to screen all complaints for any possible indications of adverse events with the marketed products. Those that meet the definition of serious must be investigated and reported on the Med Watch Form 3500A within 15 business days. Screening of the complaints may require the assistance of medically trained staff.

Once a 3500A has been submitted, update reports can and should be submitted as more information becomes available. 

EAS offers assistance with the completion of 3500A reports as well as assessments of consumer comments and complaints for applicability to this regulation. Contact EAS for more information.

Couch to Speak at the ACI – CRN Legal, Regulatory and Compliance Forum

Tara Couch will also speak at the ACI – CRN Dietary Supplement Legal, Regulatory and Compliance Forum taking place June 18-20, 2019 in New York City. Tara will present as part of a panel called Coattails, Master Files, and NDIs which will be held on June 18 and will be analyzing the latest statements and activities from FDA with regard to NDI systems and guidance that would help protect the manufacturers’ significant investment in developing new dietary ingredients; comparing similarities with FDA’s proposals for NDIs to similar proprietary systems enforced by FDA; and exploring mechanisms for FDA enforcement.

Final Guidance for Food Contact Notifications – Infant Formula and / or Human Milk

FDA’s Final Guidance for preparation of Food Contact Notifications for substances that come into contact with infant formula and human milk is intended to help industry understand FDA’s process for evaluating the safety of food contact substances. It incorporates the latest scientific thinking about the effects chemical substances may have on infant health. If you missed the recent EAS webinar on infant formula submissions, you may find it On-Demand. If you have specific questions about this Guidance, development of infant formula products, including GRAS submissions, or submission of a Food Contact Notification contact EAS.

EAS Exhibiting at Future Food Tech

EAS Senior Director for Food Consulting Services, Allen Sayler and Independent Consultant, Ron Levine, will represent EAS at Future Food Tech – NYC taking place June 18-19, 2019 in New York City. Stop by the EAS booth to learn more about our services for food innovators such as product development and labeling, food additive submissions for new ingredients, claims substantiation and more.

Challenges with Implementing Pharma Cleaning Validation

Edward A. Steele

Dear Reader,

Welcome to the June 2019 issue of EASeNews, the free newsletter for FDA regulated industries. FDA has been busy with initiatives this month. As you’ll see in our What’s New at FDA section, two of these include FDA’s finalized Guidance for abbreviated drug submissions as well as food contact notifications products that come into contact with infant formula and human milk. Additionally, FDA announced the decision to extend the registration period for the Voluntary Qualified Importer Program (VQIP) for fiscal year 2020 until July 31, 2019. Annual benefits will then take effect beginning October 1. VQIP is a voluntary fee-based program established by the FDA FSMA that provides for expedited review and importation of human and animal foods into the US for approved applicants who achieve and maintain a high level of control over the safety and security of their supply chains. If you feel your company qualifies for VQIP or would like an assessment or assistance completing the application process, please feel free to contact me.

I am happy to say EAS has announced our fall line-up of compliance seminars taking place in Irvine, CA. We are offering Dietary Supplement Labeling November 12-13, 2019 Food Labeling November 14-15 and Dietary Supplement GMPs November 14-15. We invite you to register now for early-bird pricing.

We welcome two new consultants this month, Tom Jonaitis and Veronica Ortiz de Montellano, both of whom will be of invaluable assistance particularly to clients working with both USFDA and Health Canada as well as firms operating in Mexico who export products to the US.

Our issue of the month is written by Miguel Montalvo and discusses some of the many challenges with pharmaceutical Cleaning Validation. This article is a condensed version of a full-length feature published by the International Society of Pharmaceutical Engineering’s website, ISPE iSpeak. EAS consultants are pleased to provide monthly articles for ISPE iSpeak readers on a variety of topics pertaining to the pharmaceutical and OTC-drug industry. Our Ask the Expert is written by Robert Fish, Independent Advisor for Quality and Compliance and discusses Adverse Events Reporting requirements; and our Did you Know covers EAS capabilities with Contract Research Organizations (CROs) which are heavily utilized and a lifeblood for companies conducting safety studies in the preparation of food additive submissions.

We have two complimentary webinars coming up in June – on June 18 independent consultant Mehrdad Tajkarimi, PH.D. and Leann Chuboff of SQFI will discuss the food fraud puzzle. This webinar is co-sponsored by Food Safety News magazine. On June 20 Bryan J. Coleman, Senior Director for Drugs and Devices will present on GMPs for OTCs and how to improve compliance. We hope that you join us for these and watch any of our previous webinars available on-demand on the EAS website, including May’s webinars on cosmetics claims and how FDA views certain terms when considering whether a product to be a cosmetic or unapproved new drug; and compliance with 21 CFR Part 11.

Thank you as always for your interest in EAS and please feel free to share this newsletter with your colleagues.

Sincerely,

Edward A. Steele Signature

Edward A. Steele

Fairman Authors Supply Chain Transparency and Quality Assurance Articles for Natural Products Insider

EAS Independent Consultant Heather Fairman authored two recent articles for Natural Products Insider. First, Supply Chain Transparency on the demand by consumers and regulators for supply chain transparency from farm to fork. Next, Quality Assurance for manufacturers of nutrition bars. In addition to consulting for EAS, Heather is a technical advisor for the Small Island Developing States (SIDS) DOCK Island Women Open Network (IWON, sidsdock.org), an intergovernmental organization.

Cathey on Creating Dietary Supplement Specifications

Tamika Cathey was a guest columnist for Ask the Expert in Tablets and Capsules Solid Dose Digest where she responded to the question of creating a dietary supplement specification program that meets FDA expectations. In June 2007, the FDA published 21 CFR Part 111, which established cGMP requirements for dietary supplements. Since then, manufacturers have struggled to understand and comply with these requirements regarding specifications development.

Meet June 2019 Issue of the Month Author Miguel Montalvo

EAS Consulting Group independent consultant, Miguel Montalvo, is an expert in GMP and GAP assessments for pharmaceuticals, including injectables, solid dosage, OTC topicals and biologics, as well as medical devices and dietary supplements. He has developed, implemented, reviewed, managed and audited quality and GMP compliance functional procedures including those related to laboratory operations, Quality Systems, CAPA, Non-Conformance documentation, Change Control management, calibrations, procedural and documentation controls and internal audit programs. Prior to consulting Miguel worked in industry holding positions at Baxter Healthcare and Bristol Myers Squibb.

Meet New Consultants for June 2019

Tom Jonaitis

Tom Jonaitis

Canadian-based Tom Jonaitis works with clients in the food, dietary supplement, consumer product and related industries, providing comprehensive toxicology and regulatory consulting guidance and support. He is an expert in regulatory evaluations including scientific literature hazard reviews and summaries, as well as creating pre-market quality and safety dossiers for novel food and dietary supplement ingredients applications to government agencies – FDA, Health Canada and Australia’s TGA, FSANZ. Tom reviews and evaluates the results of in vitro and in vivo toxicological studies and has additional expertise in pesticide/agricultural chemical regulations, workplace hazard classifications, and spray foam human health risk assessments.

Veronica Ortiz de Montellano

Veronica Montellano

Veronica Ortiz de Montellano is based in Mexico and offers assistance in foods, packaging and preservation. She is an expert in food design and process developments including structure, formulation and additives including Thermal Process controls and records for Aseptic Processing and Packaging Systems including microbiological testing for Aseptic Production and CIP programs for Aseptic Systems. In addition, she conducts analyses of packaging materials and utensils to analyze stability, migration, contamination, flavor degradation and more.

EAS Blogs on Proposed Efficiencies in Pharma Manufacturing

EAS regulatory intern Neha Mookuparambil authored a blog for ISPE iSpeak on FDA’s Proposed Approach to Improve Efficiencies for the Advancement of Pharma Manufacturing through Continuous Manufacturing. The FDA has been pushing for advanced manufacturing processes in the pharmaceutical industry. The efficiency, consistency, reliability and ease with adoption of CM could provide for cost benefits and timely supply of drugs.

FDA Strengthens Process of Initiating Voluntary Recalls

Voluntary recalls are a vital means to protect public health and typically are the quickest way to remove defective or potentially harmful food, medical, and consumer products from the market. FDA’s new Draft Guidance includes steps companies may take to plan, prepare and initiate a voluntary recall in the event of a problem. The Guidance includes information on employee training, record keeping and written procedures for executing a recall. Companies in need of assistance in developing these tools or who feel a voluntary recall is warranted may contact EAS for assistance. 

Final Guidance for Abbreviated Drug Application Submissions

FDA has issued Final Guidance related to drug marketing application submissions for human drugs and recommendations for considerations of whether to submit a 501(b)(2) New Drug Application, commonly referred to as an NDA, or a 505(j) Abbreviated New Drug Application, commonly referred to as an ANDA. These are two of the four available pathways for drug submissions for FDA approval, with ANDA known as an abbreviated pathway.

While an NDA is required for all new drug products, administration routes, etc, an ANDA may be an appropriate submission for products which duplicate a previously reference listed drug (RLD) that FDA has already determined is safe and effective. In such cases where the active ingredient(s), dosage form, route of administration, strength, previously approved conditions of use, and labeling (with certain exceptions) mimic that of a RLD, an ANDA may be appropriate. ANDAs must still include full investigative reports of safety and effectiveness, and may also rely on FDA’s previous finding of such to the extent that the proposed drug shares the same characteristics as the RLD.

It is important to note that in cases where an ANDA is the appropriate submission choice, FDA will reject a 501(b)(2) application as a duplicate of an RLD. Therefore, a thorough consideration of the drug under submission compared to RLDs already approved by FDA is warranted. Firms wishing to outsource this review and seek recommendations on the appropriate FDA filing are invited to contact Bryan Coleman, Senior Director of Drugs and Medical Devices.

Couch to Present at World Tea Expo

Tara Lin Couch, Ph.D., Senior Director of Dietary Supplement and Tobacco Services will present a session on “Dietary Supplements or Food – What is Tea?” at the World Tea Expo which is being held June 10-13, 2019 in Las Vegas. With the enforcement of provisions under FSMA and FDA’s dedicated review of ingredients it considers to be DSHEA, understanding how to market teas, powders and botanicals has never been more critical. Join Tara on June 12, 2019 for her presentation.

EAS to Exhibit at IFT Annual Meeting

Join EAS Chairman and CEO, Ed Steele, President and COO, Dean Cirotta and Director of Labeling and Cosmetics, Cathryn Sacra at the EAS booth #424 on June 3-5, 2019 at the IFT Annual Meeting in New Orleans. Discuss regulatory needs pertaining to foods and dietary supplements and learn how EAS can assist your firm. Interested in registering for our fall food and dietary supplement compliance seminars? Stop by the EAS booth to pick up our special IFT registration discount code.

May 2019 Drug and Device Corner

Guidance Document updates on the FDA website

CDER

CDER & CBER

CBER

CDRH

Sayler Interviewed for Food Processing Magazine Article on Trump’s Effect on Food Industry

EAS Senior Director for Food Consulting Services, Allen Sayler, was interviewed for an article published in Food Processing Magazine on the regulatory state of the food industry under the Trump administration. Published during Scott Gottlieb’s tenure as FDA commissioner, Sayler discussed how Gottleib appeared to have the full confidence of the Trump administration. EAS continues to monitor Agency updates under the acting commissioner, Norman Sharpless.

Big Data, Real World Evidence and The Digital Revolution – Hang On!

By: John Brennan

Executives from AbbVie, AstraZeneca, Bristol-Myers Squibb, Merck and Co., Johnson and Johnson, Pfizer and Sanofi were grilled on Capital Hill in February on topics ranging from drug pricing, reimbursement, rebates and patent extensions to executive compensation. Senators called for new actions to address the high cost of prescription drugs in America.

Costs to the consumer and healthcare systems are immense. The US spent 345 billion USD on prescription drugs in 2018 and growth estimates could reach 500 billion by 2025. Although not discussed at the hearing, a significant portion (15% to 20%) of the pharma revenue stream is used for pharmaceutical R and D. This investment is the lifeblood of the global pharmaceutical industry. However, discovery, development and commercialization of a NCE or biologic could cost as much as 2.0 billion USD when failures and opportunity costs are taken into consideration. Adding to the cost and risk is the complexity of modern drug development. Establishing drug safety, determining efficacy and ensuring product quality are expensive tasks that must be monitored by sponsors and regulatory agencies. Then, there is the issue of reimbursement: market access, value proposition and pricing are the domain of the commercial payers, the new stakeholder with requirements that must be addressed in all development and commercialization scenarios.

Designing and aligning the appropriate regulatory strategy for each development asset is a critical component of program success. Here are a few of the emerging topics in drug development that should be contemplated when constructing the regulatory pathway for a NCE or biologic.

“Big Data” is a term used to describe large complex historical data sets that can be extracted and analyzed using methods that are different from traditional data management procedures. One application of “big data” gaining some traction in clinical trial design is the use of historical information to create a “synthetic” control arm instead of a traditional placebo treatment. The use of synthetic controls will never replace the randomized controlled study design but the new analysis tools for complex “big data” sets could cut control groups in half or replace them altogether, especially when traditional designs become prohibitive or historical data is complete and well-characterized.

Real World Evidence (RWE) and Patient Centricity. RWE is information collected outside of a formal clinical trial. It includes electronic medical records, claims and billing data, patient and disease registries and data gathered through wearable digital devices. In a recent address to the National Academy of Sciences and in a subsequent publication, CDER’s Janet Woodcock advocated for the use of RWE as a way of collecting and using patient data in clinical trials. Woodcock noted there has been little use of RWE in drug regulatory decisions regarding drug effectiveness. A draft guidance on RWE and a framework for its use is in the works at FDA and scheduled for release in 2020. Further, regulatory agencies have been asking for information on how clinical trials can be “fit for purpose” “with the patient population. Sponsors are now checking protocol design and interventions with patients, not just investigators, KOLs and internal experts. Patient centricity will be very relevant in future regulatory dossier reviews and approvals.

The Digital Health Revolution. Ten years ago it was hard to envision that connectable biosensors, wearables, implantables, smartphone applications, artificial intelligence, remote patient monitoring and machine learning would impact data collection and enable the emergence of personalized medicine. Now, many study protocols use digital and mobile technology as an integral part of study execution.

Value Proposition and Reimbursement. The “fee for care” model used in healthcare is shifting to value-based reimbursement. While regulatory approval requires demonstration of patient safety and efficacy, payer access requires a clear demonstration of a value proposition to qualify for reimbursement. Pipeline commercial development centered on pricing, market access and payer acceptance are now built into development programs long before final investment decisions are made at the governance level. Elements of the value proposition could include differentiation over standard-of-care, price, ease of use and innovative packaging.

These are just a few of the issues that impact strategic regulatory drug development right now. There are others: biosimilars, regulatory guidance for cell and gene therapy and precision medicine applications to minimize patient variability and improve response rate. On top of all this, regulators and sponsors will have to guide new product promotion to be consistent with product labeling as drug development and regulatory approval become more complex.

EAS offers a wealth of knowledge, enabling the development of regulatory strategies that best position your products in today’s environment. For more information or to discuss your product’s challenges contact Bryan J. Coleman, Senior Director for Pharmaceuticals and Medical Devices at bcoleman@easconsultinggroup.com. We also invite you to view our industry services sheet or the pharmaceutical tab on the EAS website.

Coleman to Present at CHPA Regulatory and Scientific Affairs Committee Meeting

Senior Director for Pharmaceutical and Device Consulting Services, Bryan Coleman, will speak on recent inspection trends for cosmetic to OTC crossover products at the upcoming CHPA Regulatory and Scientific Affairs Committee Meeting on May 20 in Bethesda, MD. In addition, EAS is a proud sponsor of the Regulatory and Scientific Quality conference which takes place May 21-22, also in Bethesda.

EAS to Sponsor, Exhibit and Participate on Panel at Upcoming FDLI Annual Meeting

EAS is a proud sponsor of the FDLI Annual Conference, taking place in Washington, D.C. May 2-3. In addition, Senior Director Tara Couch will be participating in a breakout session on day one covering a status update on Modified Risk Tobacco Applications. Also in attendance at the conference, Allen Sayler, Senior Director for Food Consulting Services and Cathryn Sacra, Director of Labeling and Cosmetics Cosmetic Consulting Services. Stop by the EAS table to learn more about our services.

Meet May 2019 Issue of the Month Author

John J Brennan Ph.D.

John J. Brennan, Ph.D. is a former Senior Project Leader in Global Pharmaceutical Research and Development at AbbVie in North Chicago, Illinois. At Abbvie he served as the Enterprise Leader for 3 Global Asset Development teams accountable for creating and executing development strategies in several therapeutic disciplines including exocrine pancreatic insufficiency, cystic fibrosis and diabetic nephropathy. His areas of interest include First-in-Man, Proof-of-Concept, Proof-of-Principle, and late-stage registration studies and lifecycle management. Prior to joining AbbVie, he worked at Solvay Pharmaceuticals, Inc. in Global Project Management and as a Therapeutic Area Leader in Women’s Health, Men’s Health and Clinical Pharmacology. Dr. Brennan is a graduate of Temple University and received the Ph.D. degree in Pharmaceutical Sciences from the Philadelphia College of Pharmacy and Science (now University of the Sciences).

Pharma’s Big Data, Real World Evidence and The Digital Revolution

Dear Reader,

Edward A. Steele

Welcome to the May 2019 edition of EAS-e-News, the free newsletter dedicated to FDA regulated industries. It has been a busy month at EAS, with the release of new complimentary On-Demand webinars, announcements of new training seminars, publication of numerous articles on a wide-variety of subjects as well as a fantastic attendance at the EAS booth during the recent Supplyside East. For those of you who had an opportunity to meet with Tara Couch, our senior director for dietary supplements and Heather Fairman, one of our expert independent consultants I am sure you came away with a lot of great information on EAS and how we can begin to assist your company with any number of FDA requirements. For those who were unable to attend, I invite you to take a look at our quick reference information sheets to learn more about EAS. We are always glad to speak with you about your GMP questions or concerns.

If you will be in Geneva for Vitafoods Europe, May 7-9 we invite you to come by the EAS booth, B149, to meet Tara Couch and Charles Breen, our Independent Advisor for FSMA. In addition to exhibiting at Vitafoods, EAS is a proud training partner for the show, offering a one-day comprehensive look at GMPs for the dietary supplement industry. Registration for this seminar, taking place May 6, the day before the official start of Vitafoods, is being handled through Vitafoods directly. In addition, Charles Breen will be speaking as part of the technical sessions on hygienic commitments for food safety.

FDA has OMB approval to initiate a short voluntary survey of the cosmetics industry, which will assess a variety of GMP aspects. This survey is important to help FDA gain a better understanding of the current state of industry GMPs, and the results provided to FDA will have no identifying information, nor will responses be used by the agency to initiate enforcement actions. A Federal Register notice regarding the survey can be found here and we encourage cosmetics firms to participate in this effort.

In other FDA news, a new effort to bolster the collaboration between FDA and the Customs and U.S. Border Patrol (CBP) is underway to better protect against illegal and harmful products from gaining entry into the U.S. through the mail system, or other ports of entry. More information on this effort can be found in the What’s New at FDA section of this edition.

As mentioned earlier, we are pleased that numerous compliance seminars are both approaching and new on the horizon. Our next GMP One-day Refresher training will take place in Denton, TX on May 7, and then Andover, MA on August 13, just outside of Boston. This one-day session is designed as an opportunity to outsource your department’s GMP refresher training. At just $300 per registration it is a great and cost-effective opportunity for your entire team to learn from our experts. More information can be found on the EAS website.

Additionally, we have two complimentary webinars coming up in May. On May 7 join Norma Skolnik for a look at how FDA eyes certain cosmetics claims and on May 14 join Jeff Roberts for a look at compliance with 21 CFR Part 11. Also, on June 13 we invite you to join EAS Senior Director for Pharmaceuticals and Devices, Bryan Coleman for a look at GMPs for OTCs.

Our issue of the month is written by John Brennan and looks at pharma big data, real world evidence and the Digital Revolution and our Ask the Expert on FDA’s plans to revamp the 510(k) process is answered by George Yanulis. Finally, I am pleased to welcome a new independent consultant, Dennis Gaalswyck and a new office manager, Kate Gibson. Learn more in our Who’s Who section of this edition.

As always, thank you for your interest in EAS and we invite you to share this newsletter with your colleagues.

Sincerely,

Edward A. Steele Signature

Ed Steele
Chairman and CEO

510(k) Guidance and Substantial Equivalence Discussed in MedTech Intelligence

Independent Consultant, Jay Mansour, discussed the movement away from substantial equivalence in favor of performance testing for the 510(k) application process in a recent MedTech Intelligence. “Expanding on the Abbreviated 510(k) Program for demonstrating substantial equivalence for 510(k) premarket submissions, FDA is identifying certain “well understood” medical devices that may be cleared based on performance criteria,” he says.

April 2019 Drug and Device Corner

It has come to EAS’s attention that there is significant confusion regarding the exemption of Class 1 Medical Device products to comply with the 21 CFR 801.20 requirement for the label of a medical device to bear a unique device identifier. Per 21 CFR 801.30 A class I device that FDA has by regulation exempted from the good manufacturing practice requirements found at 21 CFR 801.20 is not required to comply with the UDI label requirement. You can check the FDA’s Medical Device Exemptions 510(k) and GMP Requirements webpage for more specific information to determine if your product is indeed exempt. All other Class I devices will be required to bear the UDI number on the packaging/device beginning no later than September 24, 2020. If you have questions on UDI requirements, please contact EAS.

Guidance Document updates on the FDA website

Immediately in effect Guidance Document

Compliance Policy for Combination Product Postmarketing Safety Reporting: This guidance document is intended to assist Combination Product Applicants who are subject to the Combination Product Postmarketing Safety Reporting Final Rule issued on December 20, 2016, and codified in 21 CFR Part 4, Subpart B. This guidance document discusses FDA’s compliance policy for the rule. The Federal Registernotification can be found at this link.

CDER & CBER

Bispecific Antibody Development Programs: This guidance provides recommendations to assist industry and other parties involved in the development of bispecific antibodies. This guidance does not discuss development considerations for other multitarget therapies that are combinations of monoclonal antibodies or are antibody cocktails or polyclonal antibodies. Although this guidance is specific to bispecific antibodies, the principles discussed in this guidance may also be applicable to the development of other types of bispecific protein products. 

This guidance focuses on general regulatory and scientific considerations for bispecific antibodies, not on development of a particular bispecific antibody. Industry and other stakeholders are encouraged to engage FDA to discuss their individual bispecific antibody development program.

REMS: FDA’s Application of Statutory Factors in Determining When a REMS Is Necessary: This guidance is intended to clarify how the FDA applies the factors set forth in section 505-1 of the FD&C Act (21 U.S.C. 355-1) in determining whether a risk evaluation and mitigation strategy (REMS) is necessary to ensure that the benefits of a drug outweigh its risks.

CDER, CDRH & CBER

Guidance for Industry Pharmacogenomic Data Submissions: This guidance is intended to facilitate scientific progress in the field of pharmacogenomics and to facilitate the use of pharmacogenomic data in drug development.

CDRH

Technical Considerations for Non-Clinical Assessment of Medical Devices containing Nitinol: The 25 purpose of this draft guidance is to outline technical considerations associated with medical devices that have at least one patient contacting component comprised of nitinol. Due to the unique properties of nitinol, the Agency has developed this draft guidance to provide FDA’s current thinking on technical considerations specific to devices using nitinol. These recommendations are intended to be general and not product-specific and should be evaluated in conjunction with the intended use and technological characteristics of your device and any relevant device-specific guidances.

Technical Performance Assessment of Quantitative Imaging in Device Premarket Submissions: This draft guidance document is applicable to all devices that generate quantitative imaging values across the information, a wide range of imaging modalities, intended uses, levels of automation, and complexity of algorithms. This guidance document provides FDA’s recommendations on technical performance assessment, and user information that should be included in a premarket submission for devices that include quantitative imaging functions. 

Class II Special Controls Guideline: In Vitro Diagnostic Devices for Bacillus spp. Detection: Guideline for Industry and FDA staff. This special controls guideline was developed to establish special controls for in vitro diagnostic devices for Bacillus species (spp.) detection. This guideline identifies measures that FDA believes are necessary to mitigate the risks to health associated with devices of this type and provide a reasonable assurance of safety and effectiveness. Following the effective date of the final rule classifying the device,1 manufacturers of in vitro diagnostic devices for Bacillusspp. detection2 will need either to (1) comply with the particular mitigation measures set forth in the special controls guideline or (2) use alternative mitigation measures, which demonstrate to the Agency’s satisfaction that those alternative measures identified by the firm will provide at least an equivalent assurance of safety and effectiveness.

Surgical Staplers and Staples for Internal Use – Labeling Recommendations: The Food and Drug Administration (FDA) is issuing this guidance to provide labeling recommendations for surgical staplers and staples for internal use. These labeling recommendations are being issued because malfunctions and misuse associated with these devices have resulted in serious adverse events, including deaths.

DCRH & CBER

Review and Update of Device Establishment Inspection Processes and Standards: FDA is issuing this draft guidance to comply with section 702(b)(1) of the FDA Reauthorization 77 Act of 2017 (FDARA) (Public Law 115-52), which directs FDA to issue draft guidance that specifies how the Agency will implement uniform processes and standards that are applicable to inspections (other than for-cause) of foreign and domestic medical device establishments. FDA updated processes and standards as needed, to address the new provisions in section 704(h)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) that were added by FDARA section 702(a), and to establish a standard timeframe for inspections. This draft guidance also describes standardized methods of communication during the inspection process, and identifies practices for investigators and device establishments to facilitate the continuity of inspections of such establishments.

CVM

#120 Veterinary Feed Directive Regulation Questions and Answers (Revised)

FDA to Begin Inspections for Intentional Adulteration in March 2020

FDA recently announced that verification of compliance with the Intentional Adulteration (IA) rule will begin in March 2020. Addressing hazards that may be intentionally introduced to foods, including by acts of terrorism, with the intent to cause wide-spread harm to public health, the IA rule requires the food industry to implement risk-reducing strategies for processes in food facilities that are significantly vulnerable to intentional adulteration. Those food facilities covered by the rule will be required to develop and implement a food defense plan, (which is part of the Food Safety Modernization Act (FSMA) requirements), identifying vulnerabilities and mitigation strategies for those vulnerabilities. Additionally, facilities will be required to ensure that the mitigation strategies are working. The first compliance date arrives in July 2019. EAS Consulting Group’s FSMA team can help assess current food defense strategies and strengthen those that do not meet FDA’s stringent requirements.

Insider Podcast on 25 Years of DSHEA Features Senior Director, Tara Lin Couch, Ph.D.

Tara Lin Couch was interviewed for a Natural Products Insider podcast on her reflections of 25 years of DSHEA. Recorded at SupplySide East, she discusses how the dietary supplement industry, pre-DSHEA, was the “wild, wild west” and that 21 CFR 111, Current Good Manufacturing Practices, completely changed the way the dietary supplement industry operates, with “current” processes adapting as technology advances.

FDA Proposing to Change the 510(k) Submission Process for Medical Devices

By George Yanulis

Each month, EAS selects one question sent in by readers to be answered by one of our experts. This month’s question is answered by George Yanulis D.Eng., an expert in medical device safety and the 510(k) process.

Question: Why is FDA proposing to change the 510(k) submission process for medical devices?

Yanulis: The rapid technological advances in the medical device arena have been dramatic. A 510(k), otherwise known as a Premarket Notification, is the mechanism by which device manufacturers notify FDA of their intent to market a medical device at least 90 days in advance of doing so. By reviewing the data in a 510(k), FDA is able to determine whether the device is equivalent to a device already placed into one of the three classification categories, Class I (General Controls requiring the least amount of regulatory control because they present minimal harm to users), Class II, (General Controls with Special Controls that must comply with specific labeling requirements, mandatory performance standards and postmarket surveillance) or Class III, (those devices requiring a PMA due to insufficient information to assure the safety and effectiveness solely through general or special controls. As a consultant, Class III medical devices have been my primary focus, particularly in the ICD and cardiac pacemaker device areas.

On November 26, 2018, then FDA Commissioner Scott Gottlieb announced changes to the process for approving medical devices for the U.S. market aimed at dramatically revamping the popular 510(k) clearance pathway which enables approvals based on predicates. FDA recognizes its current approach has the potential to limit advancing technological innovation and FDA is now looking to limit the age of predicates to ten years in order to avoid using outdated technologies as older predicates are less relevant to today’s requirements of interconnectivity and complexity.

FDA is proposing an approval outside of the 510(k) process if the comparable device being used is older than a decade, a change that would significantly disrupt the current process through which the vast majority, (80%) of devices are approved. FDA proposes creating a new alternative 510(k) pathway that will focus on objective safety and performance criteria. While devices more than 10 years old are not believed to be unsafe, nor would those devices need to be removed from the market, the change will encourage use of more modern predicates and as such encourage competition to adopt modern technologies and features while improving overall standards and improving outcomes.

As an expert who has collaborated directly with the FDA and particularly with CDRH, I welcome these changes. My expectation is that all devices will continue to be safe and effective, and substantially equivalent as dictated in the 510(k).

You may find some of the below FDA resources to be helpful, and please contact EAS with specific questions regarding your 510(k) filing.

https://www.fda.gov/medicaldevices/productsandmedicalprocedures/deviceapprovalsandclearances/510kclearances/

https://www.fda.gov/downloads/Training/CDRHLearn/UCM421766.pdf

New EAS Complimentary On-Demand Webinars Available

EAS recently presented three complimentary webinars that are now available for on-demand viewing. The first, on the challenges of preparing infant formula notifications presented by EAS Independent Advisor Robert Martin, Ph.D., Independent Consultants Timothy Morck and Robbie Burns and Senior Director for Food Consulting Services Allen Sayler, covered an overview of filing and safety study requirements. It can now be viewed on-demand on the EAS website.

Next, The FSMA Foreign Supplier Verification Program requires a Qualified Individual, who has the pertinent education and on the job experience enabling him or her to perform their duties, overseeing FSVP. EAS Independent Advisors, Charles Breen and Domenic Veneziano presented an overview of the program as well as addressed common questions asked by the exporters of food products into the U.S. marketplace. Find this on-demand webinar here.

Finally, in late March, Susan Crane, EAS Independent Advisor for OTC Drugs and Labeling discussed cosmetics labeling and claims requirements. Those wishing for a deeper dive into Cosmetics Claims regulations are invited to join Norma Skolnik on May 7 for a look at how words do matter when it comes to marketing a product.

Final Rule on OTC Hand Sanitizers Issued

FDA issued a Final Rule, effective April 13, 2019, which aims to ensure the safety and effectiveness of OTC hand sanitizers, formally known as topical consumer antiseptic rub products. These products are intended for use without water and marketed under the FDA’s OTC Drug Review.

Active ingredients of ethanol, isopropyl alcohol, benzalkonium chloride, which the majority of hand sanitizer rubs on the market contain, have deferred action to allow for the ongoing study and submission of additional safety and effectiveness data to enable FDA’s safety determination for use in OTC consumer antiseptic rub products.  At this time, FDA states that it does not intend to take action to remove hand sanitizers containing these three active ingredients from the market and their status will be addressed either after completion and analysis of the studies or at another time, if these studies are not completed.

However, 28 other active ingredients, identified in the 2016 Consumer Antiseptic Rub proposed rule, including triclosan and benzethonium chloride, are no longer eligible for inclusion in any future OTC monograph.

This long awaited rule finalizes a June 30, 2016 proposed rule on consumer antiseptic rubs, where FDA requested additional scientific data to support the safety and effectiveness of active ingredients used in OTC consumer antiseptic rubs. FDA has determined that less than 3% of the marketplace will be affected by the issuance of this final rule, as most OTC consumer antiseptic rubs use ethyl alcohol as the active ingredient.

Concerned companies may contact EAS to learn more about how this Final Rule impacts product formulations and compliance with the OTC monograph.

Did You Know? EAS Offers Verification and Validation Services of Electronic Signatures Under 21 CFR Part 11

Increasing usage of electronic methods to capture and produce critical data, which are subject to regulatory scrutiny led to the effect of Title 21 CFR Part 11. This part of the Code of Federal Regulations establishes the United States Food and Drug Administration (FDA) regulations on electronic records and electronic signatures.

The aim of this regulation is to define the criteria under which the agency will consider electronic records, electronic signatures, and handwritten signatures executed to electronic records to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper.

The FDA released a guidance document in 2003 to clarify how part 11 should be implemented and enforced. This has been updated many times, partly due to the fast-emerging changes in technology. In June 2017, the FDA also issued a draft guidance on the use of Electronic Records and Electronic Signatures in Clinical Investigations.

The FDA takes accountability of electronic signatures very seriously and upon inspection of these records deficiencies may result in a warning letter.

These constantly evolving rules can be daunting to understand and implement. EAS’ team of experts is available to assist your firm in understanding your requirements under 21 CFR Part 11 as well as assess your compliance.  Areas in need of strengthening will be addressed giving your firm a detailed action plan for maintaining compliance for both signatures and storage of electronic data.

Meet New Office Manager, Kate Gibson

Kate Gibson is a graduate of UNC Chapel Hill with a degree in Psychology and Peace, War and, Defense. While at university, Kate was involved in the Triangle Institute for Security Scholars and UNC Neural Connections and has a passion for inclusive STEM Education. Prior to EAS she held a position at the UNC Gillings School of Global Public Health, specializing in tobacco marketing regulation research. Kate is originally from Denver, North Carolina.

The Future of Homeopathy Discussed in ISPE iSpeak blog

ISPE Logo

EAS Independent Advisor for OTC Drugs and Labeling, Susan Crane, published a blog discussing the future of Homeopathy on the International Society of Pharmaceutical Engineering (ISPE) blog page iSpeak. FDA and FTC are taking a more proactive approach to homeopathic drugs indicating that they will be held to the same standard as other products with regard to claims.

Jeffrey Roberts to Discuss 21 CFR Part 11 Compliance with Electronic Signatures

Regardless of the type of industry, if you are regulated by the FDA you are bound by the rules around electronic data integrity. Whether preparing to release a finished batch of material, making decisions on data and information that was created and generated electronically or preparing to file a technical dossier with the FDA; your electronic recordkeeping and other electronic data forms require more than just being available for review and inspection. The FDA requires these sources of evidence to be generated, processed and maintained in a manner that provides complete traceability, prevents unauthorized alteration and requires a verified electronic signature that ensures identity and authenticity. Learn the specifics of Part 11 requirements for electronic signatures with Jeffrey Roberts on May 14, 2019. This complimentary webinar will discuss how record keeping is inclusive of a larger focus on GMPs for electronic records that are created, modified, maintained, archived, retrieved, or transmitted as well the specifics of content that must be included in these records for verification and validation.

Crossing T’s and Dotting I’s – Preparing for a FDA Preventive Controls Inspection

Dear Reader,

Welcome to the April 2019 edition of EASeNews, the free newsletter for industries regulated by FDA.

Edward A. Steele

We are pleased to announce our latest short video describing the many services that EAS provides. This month our regulatory specialist, Victoria Pankovich, shares the various FDA requirements for company registrations and product listings. As you may know, the complexities of registrations differ by product category, and not all commodities are required to list their products. EAS helps you to sort through what is required and what information is needed to comply with FDA regulations in this regard. Should you wish to outsource this annual or biannual requirement, EAS is available to help.

If we missed you at our recent food and dietary supplement labeling compliance seminars in Philadelphia, it is not too late to purchase the companion handbook for the seminar. The Food Labeling Handbook and the Dietary Supplement Labeling Handbook were written by instructor Gisela Leon and share points on how to ensure label accuracy, from what and how information must be covered to more detailed specifics of FDA compliance. To purchase your copy please visit the EAS store.

If you haven’t registered for our one-day seminar Ensuring Regulatory Compliance of GMP Laboratories seminar which will be taught by Senior Director Tara Lin Couch, Ph.D. in Denver on April 23, there is still time. This one-day intensive program will discuss FDA’s current GMP requirements for Research and Development and Quality Control Laboratories and will highlight FDA issues of concern with emphasis placed on recent FDA regulatory or administrative actions. All of this will allow participants to gain an understanding of the importance of laboratory GMPs and how to meet FDA’s requirements. Please join us in Denver!

Our issue of the month author is Joe Famiglietti who discusses preparing for a FDA Preventive Controls inspection. Our Ask the Expert is answered by Tim Hansen and discusses how seafood importers can protect themselves from unscrupulous suppliers. Lastly our new section, Did you Know? covers EAS expert witness considerations, an area in which EAS is proud to have deep roots with our over 50 independent consultants who can act in an expert witness capacity.

We welcome a number of new consultants this month: Robert Post, Heidi Stuttz, Jan Janson, William Scopa and Joel Martinez. I invite you to learn more about their backgrounds in Who’s Who.

Thank you as always for your interest in EAS and please feel free to forward this newsletter onto a colleague or link with us on LinkedIn.

Sincerely,

Edward A. Steele Signature

Ed Steele
Chairman and CEO

Peyton Discusses Continued Confusion Over Hemp Products in Cannabis Industry Journal

Cannabis Industry Journal Logo

Charlotte Peyton, a noted expert in cannabis, has published an article in a recent Cannabis Industry Journal. She discusses FDA’s stance with Hemp, CBD versus Isolates, and good manufacturing practice considerations. You may also wish to view the recent 2018 Farm Bill and the Cannabis Industry webinar presented by Attorney Marc Ullman, Of Counsel with Rivkin Radler and Tara Lin Couch, PhD, Senior Director of Dietary Supplement and Tobacco Services. This webinar is available on-demand on the EAS website.

Preparing For a FDA Preventive Controls Inspection

By Joe Famiglietti

The new rule on Preventative Controls for Human Food is mandated by the 2011 FDA Food Safety Modernization Act. Preventive Controls (PC) are steps that a food facility must take to reduce or eliminate food safety hazards. The rule also includes updates to the Current Good Manufacturing Practice (CGMP) requirements such as mandatory training and procedures to control allergen cross-contact. In general, the new rule applies to you if you are required to register with FDA and if you manufacture, process, pack or hold foods. By now, all firms meeting the activities in the prior sentence have to be in compliance with the PC rule unless they are exempt or subject to modified requirements. 

Firms covered by the new rule must have and implement a written food safety plan (FSP) and are further required to conduct a hazard analysis in order to identify food safety hazards requiring controls including preventive controls. The new rule requires an appropriate control be developed and implemented that could include process, allergen, sanitation or other controls. When preventive controls are required, the FSP must also include written procedures for monitoring, corrective actions, verification (including validation as deemed necessary) and supporting records, as well as a written recall plan and a supply chain program. The FSP must be prepared or its preparation overseen by a preventive controls qualified individual (PCQI).           

If your company is using an existing HACCP program, changes are required in developing a FSP because control need not always be at a CCP (critical control point), but can be handled by a prerequisite program or a preventative control program. For example, allergen cross-contact can be controlled by a written sanitation preventative control program that requires proper cleaning methods be implemented rather than establishing critical limits at a CCP.

The preparation of a proper FSP is crucial, since this is one of the first documents FDA will likely request to see during a PC inspection. There is no standardized or required format for the FSP, but all of the elements as required in 21 CFR 117.126(b) must be in the written document. FDA has published guidance regarding the preparation of a FSP and hazard analysis. See https://www.fda.gov/downloads/Food/GuidanceRegulation/FSMA/UC517391.pdf.

You can expect FDA to arrive unannounced to conduct a PC inspection unless you are located outside of the US, in which case FDA will provide written notice prior to arriving. During the inspection you can expect FDA to carefully review your company’s written food safety programs and to review all required records, such as monitoring and verification records. If deemed necessary, FDA may collect extensive environmental monitoring microbiological samples throughout your facility to determine if pathogens are in the plant environment. If there are positive sample results for pathogens, FDA can require products to be recalled. FDA can also compare the DNA fingerprints of any pathogens found to isolates in the CDC’s database and then require recalls if any matches are identified. If FDA deems your facility as not being compliant, you can expect the agency to take regulatory actions against your firm if voluntary compliance is not taken

You can properly prepare for an FDA PC inspection by considering the following:

Have a written plan covering how your company will handle an FDA inspection that includes a working area for the FDA and that assigns responsibilities for your employees who will be involved in the inspection. You need to have a policy on how to handle any objectionable conditions FDA may bring to your attention and make an attempt to correct any of these conditions while FDA is on-site.

Be sure your FSP is in final form and is signed by your firm’s owner, operator or agent in charge and be sure there is at least one person who is familiar with the overall food safety program who can explain it to the FDA.

Have training records readily available including PCQI training / qualifications, employee sanitation training and records documenting the qualifications all employees including supervisors.

Be sure record keeping is in order and is easily accessible including monitoring and verification records. 

If operational or FSP deviations have occurred, be sure appropriate corrective actions have been taken supported by records that must be made available for FDA review.

Be sure your allergen control procedures are in order. All ingredient labels should be reviewed to assure they are accurate and contain all required allergen labeling. Be sure all cGMPs are being followed to prevent unintentional allergen cross-contact issues during ingredient receipt, storage, process, packaging and labeling operations.

Conduct your own environmental monitoring. FDA will likely swab for microbes if you are producing ready-to-eat (RTE) foods that are exposed to the environment prior to packaging. You need to be sure you are conducting an appropriate monitoring program before FDA arrives. If problem areas are identified, corrective actions need to be implemented.

If product testing is used to verify a control, be sure the test is scientifically valid and have corrective action procedures in the event of positive results.

You must conduct reanalysis of the FSP at least once every three years or whenever there is a significant change that effects food safety.

Be sure you have information and records regarding where raw materials are sourced and documentation that the materials are being purchased from approved vendors. It is no longer an option to purchase raw materials from just any source. The new rule requires there must be a supply chain program which includes documentation demonstrating that either suppliers provide safe raw materials, or that another party will apply controls for the hazard.

For food with a hazard requiring a PC, there is now a requirement to have a written recall procedure that includes descriptions of the steps to be taken as well as assigning responsibility for taking those steps.

Conduct or hire an experienced consultant to perform a mock FDA inspection that includes a thorough sanitation audit and review of your programs and records. Conducting a gap analysis audit of your operation will assist in identifying areas that require improvement before FDA finds them.

Be sure all labels being used have been reviewed and approved by a food label expert. In summary, FDA is in full enforcement mode related to the FSMA Preventive Controls regulation. The food manufacturing industry needs to have its food safety program updated to incorporate the Preventive Control provisions. Your PCQI and entire QA staff as well as plant supervisors should be prepared to answer FDA’s questions and demonstrate that you conduct your business in a preventive mode of operation. With proper planning you can have a positive experience from an FDA PC-based inspection and continue to provide consumers with safe foods.

Join EAS at SupplySide East Booth F152

SupplySideEast logo 2018


Tara Lin Couch, Ph.D. and Independent Consultant Heather Fairman will represent EAS at the upcoming SupplySide East in Secaucus, NJ April 9-10, 2019. This is a great opportunity to meet the EAS team to discuss your questions regarding dietary supplement regulations and how to prepare for cannabis GMPs. If you would like to schedule a meeting at SupplySide East please contact us.

Armstrong Publishes Article on the Delaney Clause in FDLI Update

FDLI Logo

Steve Armstrong, EAS Independent Advisor for Food Law and Regulation, is co-author of an article published in the March 2019 Food Drug Law Institute Update Magazine covering FDA’s recent decision to delist six synthetic ingredients as required by the Delaney Clause, a 60-year-old provision of the Food, Drug, and Cosmetic Act (FDCA) which states, in plain language that FDA may not approve any food additive—even one that is safe—if it is “found to induce cancer” in laboratory animals. Steve hypothesizes as to whether it is time to repeal the Delaney Clause.

2019 April Ask the Expert

By Timothy Hansen

Each month, EAS answers one question sent in by our readers. This month’s Ask the Expert is answered by Independent Consultant and former head of the NOAA Seafood Inspection Program and Division Director in FDA’s Office of Seafood, Timothy Hansen. Tim has extensive experience in seafood regulatory affairs, certification, and advises the seafood industry on science and technological matters. If you would like to ask a question of one of our experts, click here.

Question: As a seafood importer how can I protect myself from fraudulent suppliers?

Hansen: The seafood industry is mostly comprised of smart, hardworking, honest professionals that take regulatory compliance seriously, and a few unscrupulous operators who aim to misrepresent their products for financial gain or enhanced competitive advantage. It would be wise for all firms and particularly importers of seafood to be aware of some of the more common fraudulent practices so that you can protect your firm, your customers and ward off FDA enforcement action by perpetuating fraud to your customers. Some types of fraudulent activities to be aware of:

Species substitution, usually representing a lower cost but similar species as a higher cost or higher quality species such as Chum Salmon for Coho Salmon. When this occurs, not only is the fish fraudulent but so too is the labeling including PDP, weight declaration and nutritional information.

In other cases, suppliers may provide a fraudulent shipment weight due to overglazing of ice, overbreading that exceeds USDC, NIST or AOAC standards, or even what is called “rat packing” where the superior product is on top, hiding the inferior product underneath.

According to the NOAA Fisheries Seafood Inspection Program, as of 2014 around 30% of seafood in the U.S. is considered fraudulent. This can be attributed to intentional fraud where the seafood operator is looking to gain an unearned profit, “best” the competition, or they commit fraud due to pressures stemming from the inability to fill customer orders. In other cases, unintentional fraud may also be committed, attributed to honest mistakes such as the misinterpretation of regulations or miscommunications and messaging errors due to poor process controls which lead to unknowingly receiving and accepting a fraudulent product from a supplier.

There are a number of ways the seafood industry can protect themselves, the most obvious of which is to develop relationships with reputable suppliers and to regularly inspect incoming shipments. In addition, if your firm does not already have fully developed product specifications guidelines consider creating these as part of your business operations plan. You will also want to have a Quality plan in addition to your HACCP plan and enhance your labeling controls beyond the minimum HACCP requirements. Consider also utilizing process control techniques such as statistical weight control charts and Quality Assurance software.

Protocols for all Quality, HACCP and other SOPs must be developed by a competent person, either within your organization or created by an outside entity, such as EAS, with expertise specific to the seafood industry. Ensuring compliant process control techniques can significantly increase your company’s integrity, leading to a satisfied customer, and reduce your risk of regulatory action.

EAS has a team of experts with career histories in FDA inspections and the seafood industry. If we can help your company to create or improve your compliance programs, please give us a call. We invite you to view our many industry services facts sheets on the EAS website, or more specifically that which pertains to our seafood services.

Meet Issue of the Month Author, Joe Famiglietti

Joe Famiglietti

Independent Consultant, Joe Famiglietti, provides guidance to clients regarding FDA compliance matters. He has performed onsite audits at food manufacturing facilities and evaluated production and quality control operations for compliance with FDA regulations. Joe has experience in inspections of food manufacturing areas including low acid canned foods, acidified foods, infant formula and seafood HACCP. He assists in facility sanitation issues, provides in-house training to employees on food GMP issues and procedures for handling FDA inspections. Prior to consulting, Joe was a Compliance Officer at the FDA New York District, Import Operations Branch in Buffalo.

Norma Skolnik Presents Webinar on Cosmetic Claims

In the competitive cosmetics world, discerning consumers are carefully considering product purchases to determine which offer the results they are hoping to achieve. In response, the pressure on marketing and labeling teams may entice to push the envelope with regards to product claims. However, words do matter, particularly in the eyes of FDA. Learn how the words used on a cosmetic label can alter the intended meaning of a claim and FDA views on them. Ensure your cosmetic products are labeled and marketed in a compliant manner, offering consumers an accurate understanding of what they can expect and protecting your products from FDA concerns. Join Norma Skolnik on May 7, 2019 for a complimentary webinar and ensure your cosmetic product labeling and claims are compliant with FDA regulations.

EAS Sponsors CHPA Regulatory Scientific and Quality Conference, Coleman to Present

CHPA May 21-21, 2019

EAS is a proud event sponsor for the upcoming CHPA Regulatory Scientific and Quality Conference taking place in Bethesda, MD May 21-22, 2019. In addition, Bryan J. Coleman, Senior Director for Pharmaceuticals and Medical Devices will be speaking on Recent FDA inspection trends in Cosmetic to OTC cross-over products at a special Regulatory & Scientific Affairs Committee meeting which is being held May 20, before the kick-off of RSQ.

EAS to Present on Pharma Data Integrity at CPhI North America

CPHI North America 2018 logo

EAS Independent Consultant, Brian Nadel, is an invited speaker on the subject of Pharma Data Integrity at the upcoming CPhI North America which will be held in Chicago April 30-May 2, 2019. Join Brian for a discussion on the reasons why once FDA considers some of a company’s data to be inaccurate it considers all of their data to be inaccurate. Brian will also discuss methods for ensuring data integrity both now and in the future.

Meet New Consultants for April 2019

Robert Post, Ph.D., MEd., MSc.

Robert Post

Dr. Robert Post is a former food industry executive, White House and regulatory agency executive, and university instructor with expertise in food science and nutrition. His roles in the food industry have included leading nutrition and regulatory affairs; corporate health and wellness programs; and food and health communications to support marketing and customers/sales. He has also directed legislative affairs, food ingredient specifications and approvals, food product design and innovation, food labeling and nutrition labeling strategies, design, and compliance; and brand communications strategies for customers, consumers, and health professionals. In the Federal sector, Rob directed the agencies that set the Dietary Guidelines for Americans, created MyPlate(.gov), and the national nutrition evidence library, supporting the White House as a key nutrition advisor. All roles involved expert mining of food and nutrition research and setting research pipelines for product design and product and process claims substantiation. Prior to consulting Rob was the Senior Director for Chobani Health and Wellness and Regulatory Affairs. He also served as the Executive Director for Center for Nutrition Policy and Promotion in the U.S. Department of Agriculture.

Heidi Stuttz

Heidi Stuttz

Heidi Stuttz is an expert in biotech and medical device oversight. She assists clients with a variety of projects including R&D programs, FDA submissions, EMEA dossiers, compliance enhancements and quality improvement initiatives. Assisting with product development processes from clinical trials to commercialization, Heidi demonstrates proven success with facilitating product development and moving regulatory programs forward. Heidi is experienced with auditing cGMPs for continuous process improvements, FDA ISO9000, records management as well as laboratory compliance/controls and validation and facilities and utility validation and remediation. She has worked as a Senior Project/Program Manager with Solution Systems and as a Quality Assurance Specialist at Wyeth Vaccines Division. Heidi has a M.S. from Johns Hopkins University, with degree in Biotechnology, Enterprise and Entrepreneurship, and concentration in Legal/Regulatory.

William Scopa

William Scopa

Mr. Scopa has over 30 years at Customs and Border Protection (CBP) at both ports of entry and Headquarters. During 15 years at the ports, he processed both the import and export clearance of cargo and passengers. At Headquarters, as a Branch Chief, he led the development of policies and procedures. These policies and procedures addressed such areas as, Intellectual Property Rights, Anti-Dumping and Countervailing Duties, and revenue collections. He spent several years leading CBP’s trade enforcement efforts in targeting evasion such as misclassification and undervaluation. His last position was CBP’s liaison to other government agencies and he worked with the other agencies to develop CBP import processing of the other agency imports for such agencies as EPA, FDA, and DEA. These processes included clearing other agency cargo under the Automated Commercial Environment (ACE).

Jan Janson

Jan Janson

Jan Janson is a quality consultant who provides assessments and recommendations on QMS development, Quality and Supplier Management. He conducts internal and supplier audits, develops product quality initiatives, supports CAPA and complaint analysis and more. In addition, Jan has extensive experience with audits against GMPs, Process Validation Reviews including process, software and methods and helps firms develop protocols for FDA 820, ISO 3485 compliance. Prior to consulting Jan was a Quality Manager at Biomet and Senior Quality Supplier Engineer at Medtronic.

Joel Martinez

Joel Martinez

As a former certified ORA BIMO FDA Investigator, Joel Martinez has completed 20-25 BIMO inspections in all therapeutic areas, interacting with CDER’s Office of Scientific Investigations (OSI) medical reviewers and BIMO Office of Compliance personnel for CBER, CDRH and CVM. He has significant experience in recognizing and understanding significant inspectional observations which would warrant further regulatory action and assists clients with understanding critical areas for a Sponsor/CRO in terms of being compliance with applicable 21 CFR regulations. Joel also conducts GLP audits domestically and internationally gaining inspectional experience of non-clinical laboratories.

A Successful Expert Witness is One Who can Demonstrate Expertise While Connecting with a Jury

An effective Expert Witness is more than one who can write expert opinions, be deposed or provide testimony in court. Experts must represent your company accurately, independently and objectively in matters of legal proceedings and do so in a manner that enables them to communicate to, connect with, and convince the decision maker, whether that decision will be made by a jury or mediator. Agencies, judges and juries want to hear from well-respected and knowledgeable expert witnesses. Whether the issue is recalls, labeling claims, safety audits, or almost any other challenge to a facility or a product, having a competent expert by your side can make all the difference.

EAS independent advisors and consultants are routinely called to serve as an expert witness in a variety of cases. Our team of over 50 former high-level FDA officials and industry executives who act in an expert witness capacity average over 25 years of regulatory experience and include some of the most well-known and highly respected names in the industry. These experts have the knowledge, qualifications, and experience necessary to explain and clarify issues to our clients and the courts while establishing credibility and persuasiveness as witnesses.

If EAS can be of assistance as you prepare for your next litigation or mediation challenge, please reach out to Dean Cirotta, President and COO directly. EAS will assure that the specific needs and requirements of your case will be matched with an expert whose knowledge and experience enhances your client’s legal standing.

March 2019 Drug and Device Corner

Implementation of reorganization to begin for CDRH

In order to create a smart and quick-moving infrastructure that can adapt to the needs of future organizational, regulatory and scientific requirements, the Center for Devices and Radiological Health (CDRH) is beginning the implementation of a reorganization. 

The reorganization will integrate CDRH’s premarket and post-market program functions along product lines, allowing their experts to leverage their knowledge to optimize decision-making across the product life cycle. This type of approach blends many of the current aspects of product review, quality, surveillance and enforcement into a new, team-based approach. With the implementation of reorganization, the FDA aims to enhance information-sharing across the Center, increase collective decision-making, improve work-life balance and increase professional opportunities for employees.

The implementation is set to begin March 2019 and is expected to be completed by September 2019. FDA says the implementation will take place in a phased approach, and timelines for implementation will vary by office. Each office within the current CDRH structure is undergoing some change in order to better support and advance CDRH’s public health mission and vision.

More information can be found here.

CDER:

Human Immunodeficiency Virus-1 Infection: Developing Systemic Drug Products for Pre-Exposure Prophylaxis

Severely Debilitating or Life- Threatening Hematologic Disorders: Nonclinical Development of Pharmaceuticals

Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act

Quality Considerations for Continuous Manufacturing

Bioavailability Studies Submitted in NDAs or INDs — General Considerations

Assessing the Effects of Food on Drugs in INDs and NDAs — Clinical Pharmacology Considerations

Smoking Cessation and Related Indications: Developing Nicotine Replacement Therapy Drug Products

CDER & CBER:

Pediatric Information Incorporated Into Human Prescription Drug and Biological Product Labeling

Rare Diseases: Natural History Studies for Drug Development

Pediatric HIV Infection: Drug Product Development for Treatment

Enrichment Strategies for Clinical Trials to Support Determination of Effectiveness of Human Drugs and Biological Products

Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials

Cancer Clinical Trial Eligibility Criteria: Patients with Organ Dysfunction or Prior or Concurrent Malignancies

Cancer Clinical Trial Eligibility Criteria: Minimum Age for Pediatric Patients

Cancer Clinical Trial Eligibility Criteria: Brain Metastases

Nonproprietary Naming of Biological Products: Update

CDRH & CBER:

Acceptance and Filing Reviews for Premarket Approval Applications (PMAs)

Refuse to Accept Policy for 510(k)s

CDRH:

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices)

Implanted Brain-Computer Interface (BCI) Devices for Patients with Paralysis or Amputation – Non-clinical Testing and Clinical Considerations

CBER:

Standards Development and the Use of Standards in Regulatory Submissions Reviewed in the Center for Biologics Evaluation and Research

Providing Lot Release Protocol Submissions to the Center for Biologics Evaluation and Research (CBER) in Electronic Format

All Centers:

A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers

Will Pathogens Cause FDA to Suspend Your Food Facility Registrations?

Dear Reader,

Welcome to the March 2019 issue of EASeNews, the free newsletter for industries regulated by FDA. It is hard to believe it is already March and with spring right around the corner, if you haven’t already signed up for your “spring training” I invite you to join EAS at one of our upcoming regulatory compliance seminars. Food and Dietary Supplement Labeling will be held in Philadelphia beginning March 12, 2019; the Dietary Supplement GMP two-day seminar will be held April 2-3, 2019 also in Philly; the Compliance with GMP Requirements for Dietary Supplement Laboratories seminar will take place April 23, 2019 in Denver and May 7 begins our four Dietary Supplement GMP One-day Refresher Series. The first Refresher takes place in Denton, TX, just outside of Dallas on May 7th, and the second takes place in Riverside, CA on May 14th. We invite you to join us!

In addition to seminars, we have a number of complimentary webinars this spring, with two new topics recently added. What Does the 2018 Farm Bill Mean for the Cannabis Industry? will take place on March 13, 2019, and Dietary Supplements and FSMA Compliance – Fallacy or Fact? will take place April 16, 2019. As you know, we take great pride in bringing you important regulatory information which can help you develop and improve practices to meet FDA requirements. To learn more about these two newest webinars or to see our entire line up of spring EAS webinars, please visit the webinars page of the EAS website. From OTCs, to Cosmetics, to Cannabis to Dietary Supplements, we have something for you.

I am very pleased to welcome a number of esteemed colleagues who are new EAS Independent Consultants. This month we welcome Janet Collins, Sophia Lily, Jay Mansour, Jeffrey Roberts, and George Yanulis. You may read more in the Who’s Who section of this issue. 

Our issue of the month is written by Kathy Knutson, Ph.D. and concerns a very real problem for the industry – that of the identification and storage of pathogen genomic information in database trackers which can years later reemerge as a problem for a facility, even when the pathogen is not isolated in a finished product. Dr. Knutson raises interesting questions and I encourage everyone to use this article as a starting point to renew your commitment to sanitary facilities and hypervigilance against contaminations.

Our Ask the Expert is answered by Ronald J. Levine, who is both an EAS Independent Consultant and General Counsel at the firm Herrick, Feinstein LLP and discusses the importance of finding an expert witness that will well represent your firm in litigation, mediation matters, the preparation of expert opinion papers and more. EAS has nearly 70 consultants who we recognize as experts who can act as an extension of legal teams. To learn more about our services, please view our industry services sheet which explains some of our capabilities in more detail. You may have also seen our recent press release discussing EAS capabilities acting in the capacity of an expert witness. If you missed it, I invite you to view it on our LinkedIn Page.

Lastly, I am very pleased to announce the release of our new short video discussing FSVP and Qualified Individual Requirementsplaced on the Food industry by FDA. We had a lot of fun putting this together and hope that you find it enjoyable as well as informative. Please, as always let me know if you have any questions on this service or any other that EAS provides.

Thank you,

Ed Steele, Chairman and CEO

Steve Armstrong to Present at Two Upcoming FDLI Events

Join EAS Independent Advisor for Food Law and Regulation, Steve Armstrong, at the upcoming FDLI Intro to Food Law and Regulation taking place in Washington, D.C., March 19-20, 2019. Steve will be part of an esteemed group of presenters and will discuss Food Safety and Unintended Components and Contaminants of Food. Click here to hear more. In addition, Steve will be speaking again at the FDLI Food Enforcement conference on March 21, 2019. He will be part of a panel discussion on FDA’s FSMA enforcement.

How Do Legal Teams Find and Identify Good Expert Witnesses?

By Ronald J. Levine

Each month EAS answers one question sent in by a reader. This month’s question on how to choose an expert witness for FDA legal proceedings is answered by Independent Consultant, Ronald J. Levine. Ron has had a successful career history as a litigator at one of the top New York law firms and is available to EAS clients for assistance with compliance questions and risk assessments. We were interested in hearing Ron’s thoughts since EAS provides consultants who can become a part of a legal team, by writing expert opinions, participating in depositions or being called to the stand as an expert witness. You can view EAS’ Expert Witness Services Sheet to learn more. If you would like to ask a question of our independent consultants, please contact us.

How Do Legal Teams Find and Identify Good Expert Witnesses?

Thank you for an excellent question. As a litigator who has retained many expert witnesses during my 40- year career as a lawyer, I have found that finding the right expert for a case can make all the difference in the world.

In almost any investigation or litigation involving regulated products, an expert can help explain your position to the fact-finder and render opinions which an average person would not have the knowledge or experience to offer. The FDA expert’s ability to offer a deep understanding of complex regulations and production protocols, such as Good Manufacturing Practices (GMP); and assistance with developing strategy in responding to the FDA; can make the expert a valuable extension of the legal team.

Where are the Legal Teams Looking?

Once the legal team has identified the subject area and credentials of the expert required for the task, they will begin the search.

The team may well begin with publications, articles and websites in the practice area and will be most interested in the positions the expert has taken in the past on the topic at issue – to see whether the opinion aligns with the legal team’s stance.

Experts who have testified previously, with names appearing in published court opinions, may be found by attorneys who are researching the legal authority in the area. Also, legal teams may send out queries via bar groups and industry associations.

How can I find a “Good” Expert?

There are at least three qualities of a “good” expert witness.

First and foremost, experts should be able to articulate what makes them an expert. Expertise could be based upon academic and professional credentials​ and on the job experience. In some cases, experience as an academic provides extra credibility, particularly those who have published in peer-reviewed journals.

Secondly, a “good” expert is one who is able to articulate his or her opinions in a manner which lay people will understand and accept. The expert will not be addressing peers who talk the same language. They will be trying to convince a jury, who may have limited educational credentials​ and no experience in the field. Legal teams will also be looking for experts who are poised and make others feel comfortable. They are going to avoid those who arrogant or not willing to listen.

Finally, legal teams are looking for experts who are able to handle themselves under intense cross-examination. They need to be able to listen to questions. The expert must be on the alert for trick questions, and know how to answer questions posed by experienced trial lawyers. Legal teams want to work with a seasoned expert who are familiar with the courtroom.

February 2019 Drug and Device Corner

Sunscreen Innovation Act to Enhance Product Safety Requirements

On February 21, 2019 FDA issued a proposed rule that would update regulatory requirements for most sunscreen products in the United States. Aimed at bringing nonprescription, over-the-counter (OTC) sunscreens that are marketed without FDA-approved applications up to date with the latest science, the provisions address sunscreen active ingredient safety, dosage forms, and sun protection factor (SPF) and broad-spectrum requirements. It also proposes updates to how products are labeled to make it easier for consumers to identify key product information.

Per FDA, the agency is issuing this proposed rule to put into effect final monograph regulations for OTC sunscreen drug products as required by the Sunscreen Innovation Act. OTC monographs establish conditions under which the FDA permits certain OTC drugs to be marketed without approved new drug applications because they are generally recognized as safe and effective (GRASE) and not misbranded. Over the last twenty years, new scientific evidence has helped to shape the FDA’s perspective on the conditions, including active ingredients and dosage forms, under which sunscreens could be considered GRASE. For more information, please visit: Sunscreen Proposed Rule

You may also be interested in EAS complimentary webinar series on OTCs which includes a discussion of monograph reform expectations, labeling, registrations and lists and more. For more information please visit the upcoming webinars page on the EAS website or view our many on-demand webinars on a variety of topics pertinent to the industry.

Federal court enters consent decree against compound manufacturer

The FDA is continuing to see concerning activity when it comes to some compounded drugs, including problems related to the conditions under which compounded sterile medicines are made. As a result, the FDA continues intense focus in this area. The FDA will take enforcement actions against compounders who fail to produce sterile drugs in compliance with FDA regulations.

A consent decree of permanent injunction was filed against a company and its owner. The consent decree prohibits the company and its owner from, among other things, manufacturing, holding, or distributing human or animal sterile drugs compounded at their facility until they comply with the Federal FD&C Act and FDA regulations.

The complaint was filed by the U.S. Department of Justice on behalf of the FDA. Further information can be found on the FDA website.

Medical Device Classification Procedures

The FDA issued a final rule on the classification procedures for medical devices on 17th December, 2018 entitled “Medical Device Classification Procedures: Incorporating Food and Drug Administration Safety and Innovation Act Procedures”. The rule will be effective from March 18th, 2019.

The purpose of this final rule is to incorporate the amendments by Food and Drug Administration Safety and Innovation Act (FDASIA) to the FD&C Act which governs the classification and reclassification of medical devices. Also, additional changes have been made by the FDA independent of the FDASIA in efforts to update its regulations governing classification and reclassification of medical devices. The rule will enhance consistency and uniformity across reclassification processes and will also help to reduce regulatory and economic burden.

Summary of the major provisions of the final rule include the provisions for reclassification of devices and for requiring PMA applications for preamendments class III devices to change from a rulemaking proceeding to an administrative order process. Prior to publication of a final order reclassifying a device or requiring a PMA application for a preamendments class III device, FDA must publish a proposed order in the Federal Register, consider any comments submitted on the proposed order, and hold a device classification panel meeting. This final rule also clarifies the process where reclassification of a postamendments device or a transitional device is initiated by FDA, rather than in response to a petition. The final rule also removes the requirement for a hearing under part 16 (21 CFR part 16) for reclassifying transitional devices.

More information can be found at regulations.gov

Guidance Document updates on the FDA website

Guidance Document highlight

In order to improve communications regarding corrective actions in response to inspectional observations with medical device companies, the FDA issued a draft guidance titled “Nonbinding Feedback After Certain FDA Inspections of Device Establishments”, a requirement under the FDA Reauthorization Act of 2017 (FDARA). The document was issued on February 19th, 2019.

Earlier, companies could ask for a feedback on proposed corrective actions but there was no standardized process in place for provision of nonbinding feedback. The draft guidance proposes to standardize the process of communicating and submitting nonbinding feedback for companies on certain kinds of documented inspectional observations that are issued on a Form 483, during either premarket or postmarket inspections of device establishments. It also describes how the FDA evaluates and responds to such requests.

The proposed guidance has outlined steps on the process of requesting a nonbinding feedback.

These include timely submission of request, eligibility criteria, justification of request, proposed responsive actions and how the FDA will respond with a nonbinding feedback. More detailed description can be found here.

CDER

Eosinophilic Esophagitis: Developing Drugs for Treatment Guidance for Industry Draft guidance document for sponsors who are developing drugs and therapeutic biologics for Eosinophilic Esophagitis (EoE) stating FDA’s current recommendations regarding clinical trials for EoE drugs.

Opioid Use Disorder: Developing Depot Buprenorphine Products for Treatment Guidance on FDA’s current thinking about drug product development and designing of trials relevant to study of depot buprenorphine products for Opioid Use Disorder treatment through 505(b)2 pathway for a new drug application (NDA) submission

Marketing Status Notifications Under Section 506I of the Federal Food, Drug, and Cosmetic Act; Content and Format Guidance for Industry Draft guidance document intended to assist holders of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) approved under section 505(c) and 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(c) and (j)), respectively with identifying required contents for marketing status notification and format to submit these notifications required under section 506I of the FD&C Act (21 U.S.C. 356i)

Planning for the Effects of High Absenteeism to Ensure Availability of Medically Necessary Drug Product This guidance is intended to encourage manufacturers of medically necessary drug products (MNPs) and any components of those products to develop contingency production plans to use during emergencies that result in high absenteeism at production facilities.

CDER’s Program for the Recognition of Voluntary Consensus Standards Related to Pharmaceutical Quality This guidance describes a proposed program at FDA’s Center for Drug Evaluation and Research (CDER) to make public a comprehensive listing of informally recognized voluntary consensus standards related to pharmaceutical quality. CDER is issuing this draft guidance to obtain public comments on the proposed program.

Competitive Generic Therapies This guidance provides a description of the process that applicants should follow to request designation of a drug as a CGT and the criteria for designating a drug as a CGT. This guidance also includes information on the actions FDA may take to expedite the development and review of ANDAs for drugs designated as CGTs. This guidance also provides information on how FDA implements the statutory provision for a 180-day exclusivity period for certain first approved applicants that submit ANDAs for CGTs.

Smoking Cessation and Related Indications: Developing Nicotine Replacement Therapy Drug Products The purpose of this guidance is to assist sponsors in the clinical development of nicotine replacement therapy (NRT) drug products, including but not limited to those intended to help cigarette smokers stop smoking. This guidance reflects the FDA’s current recommendations regarding overall development programs to support NRT drug products for smoking cessation and related chronic indications.

CDER & CBER

Safety and Performance Based Pathway – Guidance for Industry and Food and Drug Administration This guidance provides FDA’s current thinking on expanding the concept of the Abbreviated 510(k) Program for demonstrating substantial equivalence for premarket notification (510(k)) submissions

The Least Burdensome Provisions: Concept and Principles – Guidance for Industry and FDA Staff

Rare Diseases: Common Issues in Drug Development Guidance for Industry Rev. 1 Draft guidance is to assist sponsors of drug and biological products for the treatment or prevention of rare diseases in conducting more efficient and successful drug development programs.

Providing Regulatory Submissions in Electronic Format – Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications The purpose of this document is to explain the procedures and criteria FDA intends to use in assessing whether a 510(k) submission meets a minimum threshold of acceptability and should be accepted for substantive review.

Acceptance and Filing Reviews for Premarket Approval Applications (PMAs) The PMA regulation (21 CFR 814.42(e)) identifies the criteria that, if not met, may serve as a basis for refusing to file a PMA. This guidance is intended to be used by FDA staff and the device industry to help elucidate the broad preclinical and clinical issues that need to be addressed in a PMA and the key decisions to be made during the filing process.

CDRH & CBER

Evaluation of Devices Used with Regenerative Medicine Advanced Therapies This guidance provides manufacturers, applicants, and sponsors engaged in the development of regenerative medicine therapies, with FDA’s current thinking regarding evaluation of devices used in the recovery, isolation, or delivery of regenerative medicine advanced therapies.

Refuse to Accept Policy for 510(k)s The purpose of this document is to explain the procedures and criteria FDA intends to use in assessing whether a 510(k) submission meets a minimum threshold of acceptability and should be accepted for substantive review.

CDRH & CDER

Coordinated Development of Antimicrobial Drugs and Antimicrobial Susceptibility Test Devices – Guidance for Industry and Food and Drug Administration Staff This guidance is intended to assist drug sponsors and device manufacturers who are planning to develop new antimicrobial drugs and antimicrobial susceptibility test (AST).

CDRH

Intent to Exempt Certain Unclassified, Class II, and Class I Reserved Medical Devices from Premarket Notification Requirements † This guidance describes the Food and Drug Administration’s (FDA) intent to exempt certain unclassified medical devices, certain Class II medical devices, and certain Class I medical devices that are subject to the reserved criteria of section 510(l) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 360(l), from premarket notification requirements.

CBER

Expedited Programs for Regenerative Medicine Therapies for Serious Conditions This guidance addresses regenerative medicine therapies which are defined in section 506(g)(8) of the FD&C Act as including cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products, except for those regulated solely under section 361 of the Public Health Service Act (PHS Act) (42 U.S.C. 264) and Title 21 of the Code of Federal Regulations Part 1271 (21 CFR Part 1271).

The 21st Century Cures Act (Cures), signed into law on December 13, 2016, amended several sections of the Federal Food, Drug, and Cosmetic Act. This guidance was developed and issued prior to the enactment of Cures, and certain sections of this guidance may no longer be current as a result. FDA is assessing how to revise this guidance to represent our current thinking on this topic. For more information please contact DICE@fda.hhs.gov.

Will FDA Suspend Your Food Facility Registration Based on Environmental Results?

By Kathy Knutson, Ph.D.

In October 2018 FDA suspended the registration of Working Cow Homemade, Inc., of Florida. Working Cow is an ice cream manufacturer, ceased operations, and has cooperated with FDA. As part of its decision to suspend their registration FDA determined: 

  • Insanitary conditions were observed during inspections in both 2017 and 2018.
  • Following a 2017 inspection, an environmental sample tested positive for Listeria monocytogenes. Per FDA protocol, the whole genome sequencing data for the pathogen was uploaded to the Genome Trakr database.
  • In 2017, Working Cow conducted a recall. According to FDA, Working Cow did not implement corrective actions after the 2017 findings and recall.
  • In September 2018, the CDC informed the Florida Department of Health of a genetic match between the 2017 environmental Listeriaand a 2018 patient plus two patients in 2013.
  • Working Cow has a Florida customer base that includes potentially immunocompromised adult consumers at nursing homes and assisted living facilities.
  • A 2018 Listeria monocytogenes environmental isolate matched the 2017 environmental isolate, making the pathogen a potential resident strain.

The pathogen was not isolated from the finished product.

If Listeria monocytogenes is found in the environment from an area after a kill step and before the packaging is sealed, there is the potential for the pathogen to be transferred from the environmental site to a food contact surface and then to the product. This concept is recognized in the scientific community and is the justification for environmental monitoring programs which verify the effectiveness of equipment and facility sanitation programs, employee hygiene, and employee training programs. A pathogen in zone 4 can go to zone 3, in zone 3 can go to zone 2, and in zone 2 can go to zone 1. While every facility is different and there is no single citation of what constitutes each zone, here is one description:

  • Zone 1 – Direct product contact & indirect product contact (surfaces from which contaminants can drip, drain or be drawn onto product contact surfaces), includes pressurized air
  • Zone 2 – Equipment non-product contact areas immediately adjacent to processing equipment
  • Zone 3 – Facility non-product contact areas within processing, packaging & ingredient/finished product cooler areas, i.e. floors; walls; ceilings; overhead piping, conduit & structural supports; drains; forklifts & pallet jacks that enter processing & packaging areas
  • Zone 4 – Facility and equipment non-product contact areas located outside of the processing, packaging & ingredient/finished product cooler areas, i.e. warehouses, dock areas, break rooms, hallways

I understand the thinking that the pathogen from the environment could get into the ice cream and as a consultant I have seen the certainty of a problem break down when the details and specifics are thoroughly evaluated. Questions to ask as sites evaluate their pathogen control programs are: What is the proximity of the finding to the finished product? Is there a history of environmental sample results related to detection of pathogens? What is the laboratory’s positive control culture to ensure the reported results are correct?

PulseNet was formed in 1996 enabling laboratories to use the genetic matching method of pulsed-field gel electrophoresis (PFGE). FDA started to transition from PFGE to whole genome sequencing (WGS) after investigating a 2012 Salmonella outbreak. Isolates have been added to the Genome Trakr database at an exponential rate, and laboratories have converted or are in the process of converting from PFGE to WGS.

WGS use and values are evolving in risk assessment and investigations. There are several different WGS equipment manufacturers. The laboratory method for WGS at FDA is not the same method used by CDC. One uses SNPs, and the other uses alleles. A “match” is not always a perfect match, and there is debate among FDA, CDC, academic, and commercial laboratories as to how close the specific genetic data must be for a “match.”

The analogy I use is calling twin babies “identical” where there may still be a few physical differences; identical twins are genetically identical and a “match.” Fraternal twins are not genetically identical and clearly not a match. When WGS is conducted on an environmental isolate and a patient isolate of a pathogen to see if they match, the data may show genetic differences. The scientific community has not agreed on how much of a difference can be measured and the isolates be labeled as genetically identical.

WGS data lives forever in Genome Trakr, so it is conceivable and perhaps likely that environmental samples taken in your facility this week could be matched to a pathogen from six years ago, but without an isolate from your finished product! Even though the concept is mind-boggling, this is where enforcement currently lies in and CDC today.

So to answer my question, Will FDA Suspend Your Food Facility Registration Based on Environmental Results?, based on recent history with FDA using the tool of WGS as the “Holy Grail” for proving microbiological contamination, the answer could be is “Yes.” When there is a match between an environmental pathogen with a finished product isolate or a patient isolate, FDA will be on your doorstep. Your work is to train employees, re-emphasize and enhance current Good Manufacturing Practices, build a strong and positive food safety culture, re-evaluate your current FDA-compliant food safety plan to ensure effectiveness, and keep records that prove your food safety and corrective action efforts are occurring daily.

In conclusion, the food manufacturing and retail food industry need to prepare themselves for the increased use of all types of genetic screening of environmental and finished product isolates by not only FDA or CDC, but by state food safety regulators, third-party auditors and their customers. One way to prepare is to learn as much as possible about whole genome sequencing (WGS), identify private laboratories that conduct WGS and learn about their methodology and equipment. This will allow you to get out ahead of this new regulatory tool that has the potential of improving the safety of the US food supply but with potential damaging consequences in cases where matches are found.

EAS Welcomes New Consultants in March 2019

Janet Collins, Ph.D.

Dr. Janet Collins assists EAS clients with all matters of food regulatory compliance issues. Her expertise includes product development with an eye towards global agricultural advocacy, appreciation for diversity, and strong expertise in human health science, nutrition and food regulation, and systems for global food acceptance. Janet demonstrates strong global communications/advocacy and leadership with measurable and collaborative results. She recently retired from the position of Executive and Senior Vice President, Science and Regulatory Affairs at CropLife America and was the President of the Institute of Food Technologists from 2008-2015.

Janet Collins PhD

Sophia Lily

Sophia Lily has over 25 years of experience in the regulated pharmaceutical, nutraceutical and food industry Quality Control, Quality Assurance. She is based in India and is experienced in handling inspections, validations, vendor audits and training. She routinely works with, including training, personnel in a range of GMP topics including Data Integrity. With expertise including GMP compliance, gap analysis and remediation and development of roadmaps to compliance, she has successfully implemented effective quality management systems for many companies both small and large.

Sophia Lily

Jay Mansour

Jay Mansour is a seasoned Medical Device regulatory consultant with 20+ years of experience. He has successfully filed more than 100 510(k) clearances across many technologies and assists clients with QMS turnkey projects, including personnel training, and CE marking products as well as responding to FDA’s 483 and warning letters. He is an expert in Process Validations (software, sterilization and more).

Jay Mansour

Jeffrey Roberts

Jeffrey Roberts is an expert in software and systems auditing/validation including compliance with 21 CFR Part 11, 21 CFR Part 820 and ISO-13485. He writes Software Development Life Cycle (SDLC) documents including Validation Compliance Plan (VCP), Functional Requirements Specification (FRS), System Design Specification (SDS), Installation Qualification (IQ), Operational Qualification (OQ), Performance Qualification (PQ), Requirements Traceability Matrix (RTM) and Validation Summary Report (VSR).

Jeffrey Roberts

George Yanulis, Ph.D.

Dr. George Yanulis has consulted in Medical Device Product Development and Research for 20 years and has a Doctorate and Master’s Degree in Biomedical Engineering. He has conducted cardiovascular device research at the Cleveland Clinic Foundation on cardiac pacing paradigms used in heart failure patients. In addition, Dr. Yanulis has been involved in the R&D Medical Device Consulting & Litigation Support as an Expert Witness for over 10 years and has been involved in numerous medical device liability and patent infringement cases. He provides expertise to attorneys, medical device companies, health care systems and insurance carriers related to FDA medical device controls, PMAs, post-market surveillance issues, medical device/product failures and IP medical device issues. In addition, he has reviewed MDR(s) and other adverse events related to implant device failure. Dr. Yanulis is highly motivated in maintaining and providing the highest level of quality in the design, development and safe and effective use of all types of cardiac device implants.

George Yanulis PhD

EAS Webinar: Dietary Supplements and FSMA, Fallacy or Fact?

Since the passage of the Food Safety Modernization Act (FSMA) in 2011, dietary supplements are now subject to many aspects of the seven major regulations that were issued by FDA to support enforcement of FSMA. One of the most important of these regulations being 21 CFR 117, Current Good Manufacturing Practice (cGMP) and Hazard Analysis and Risk-Based Preventative Controls for Human Food (PCHF). Which aspects of FSMA’s Preventive Controls for Human Foods, 21 CFR 117, apply to dietary supplements? What about other FSMA responsibilities like FSVP? How does the dietary supplement industry including raw material manufacturers and suppliers, dietary supplement manufacturers, and dietary supplement brand owners avoid enforcement actions?

Join EAS Consulting Group’s FSMA and Dietary Supplement experts Heather Fairman and Maury Bandurraga for an overview of the FSMA regulation and a deeper dive into those aspects which specifically apply to dietary supplements. Register now for our April 16, 2019 webinar at 1:00 pm Eastern.

Strategic Product Development a Key Component of Regulatory Compliance

Did You Know?

Product development is more than just labeling, it is a holistic approach from ideation through commercialization that strategically looks at the category in which the product is intended to be marketed and those regulatory requirements surrounding it. Are there claims being made which have legal definitions? Is the product competing against similar products but with a unique competitive advantage? Does the product contain a new ingredient for which a GRAS submission must be filed?

Once the product idea is born, the strategic and often difficult decisions begin. EAS Consulting Group’s product development team works with companies to best position new and relaunched products in the marketplace. We can review your labels, claims and marketing materials for regulatory compliance, and assure the study design, results and dossiers demonstrate safety of the ingredients and packaging. In addition, we can also assist GMP and Food Safety Modernization Act compliance during production.

If your company is thinking of a new product, product line extension or even repositioning an already existing product, contact EAS Consulting Group for a consultation about your project and how our product development capabilities can help you meet your business goals. EAS’ product development team consists of former attorneys, microbiologists and toxicologists, labeling and claims specialists and experts in packaging and food safety. For more information, contact Allen Sayler, Senior Director of Food Consulting Services at 571-447-5509 or asayler@easconsultinggroup.com.

Meet March 2019 Issue of the Month Author

Kathy Knutson, Ph.D.

Kathy Knutson, Ph.D. is a microbiologist and certified lead instructor for Preventive Controls for Qualified Individuals through the Food Safety Preventive Controls Alliance. She consults with companies in meeting FSMA requirements, including manufacturers in the cannabis industry as she educates on issues surrounding cannabis infused food products for sale in states with medical and recreational use legislation. Kathy has a Ph.D. in Food Science from the University of Minnesota and prior to consulting worked as a Food Safety Educator and Proficiency Program Coordinator with the Northland Laboratories.

Kathy Knutson PhD

EAS Webinar – Qualified Individuals – FDA’s Final Link in the Chain of Food Safety and Food Imports

EAS Independent Advisor for Import Operations, Domenic Veneziano and EAS Independent Advisor for FSMA, Charles Breen are collaborating for a complimentary EAS webinar discussing the requirements of a Qualified Individual per FDA requirements. Join us on April 3, 2019, at 1 pm Eastern to learn about this important provision for food importers under the Foreign Supplier Verification Program (FSVP) Final Rule. Part 1 Subpart L, Section §1.503 requires that importers of human and animal food enlist a QI who has responsibility for developing a program and performing each activity to ensure the products they are importing are not adulterated or misbranded and have been produced in accordance with the preventive control regulations for human or animal food or the Produce Safety Rule. FDA has specific expectations of the QI. Does your company meet the mark? Join us for our webinar and learn more about FSVP and EAS services as a QI through this explainer video.

EAS Offers Hygienic “Best” Sanitation Practices for Delivering Safe Snack Foods at SNAXPO

EAS Independent Consultants David Blomquist and Jenifer Kane will present a one-day seminar at the upcoming SNAC International Annual Conference, SNAXPO, March 31-April 2, 2019 in Orlando, FL. The training which takes place on March 31 will provide practical information, “real-world” examples and tips on how to enhance daily operational practices related to improving existing food safety and quality programs for the snack food industry. Focusing on criteria for selecting, installing and maintaining processing equipment and utensils, how to effectively clean processing equipment and more. Participants will gain an appreciation of compliance requirements of the applicable FSMA regulations.

EAS Offers Webinar on Developing New Infant Formula Notification

The submission stage of a New Infant Formula Notification may seem like the beginning of the end of a years-long process of research and strategic development. But, without all the right documentation in place, this last step prior to product launch can be unnecessarily delayed for those companies not well-prepared for the rigors of FDA review and assessment.

Learn the steps to NIFNs as well as the pitfalls and challenges companies face in leading up to the assembling of an Infant Formula dossier. EAS Consulting Group’s experts will walk you through challenges and pitfalls which delay or prevent final FDA approval of this most important nutrient for growing infants. Join Robert Martin, Ph.D., Robert Burns, Ph.D., and Timothy Morck, Ph.D. on April 2, 2019, at 1 pm Eastern for a technical overview of one of FDA’s most challenging applications. Register today and learn more about EAS services in infant formulas in this explainer video.

New EAS Webinar Announced – What Does the Farm Bill Mean for the Cannabis Industry?

The 2018 Farm Bill answered many questions for the cannabis industry, but its message has also been largely misunderstood. Misinterpretations as to the legality of including cannabis as an ingredient in foods, herbal products, and dietary supplements have erroneously lead firms to begin planning and production of illegal products, and, in the case of those which legally include (by state) CBD ingredients there is often little regard or understanding of how to manage the quality, including product specifications for the production of a consistent and safe product.

Join EAS Senior Tara Lin Couch, Ph.D., and special guest, Marc Ullman with Rivkin Radler, LLP on March 13, 2019, at 1 pm Eastern for a dynamic discussion on what the Farm Bill really means for the cannabis industry. What is FDA’s position on cannabis and how are the states managing the patchwork of federal regulations that make this burgeoning industry so confusing? In those cases where companies are legally producing cannabis products, what steps should be taken to implement and improve upon sound quality systems? Register here and learn more about EAS quality systems services for the cannabis industry here. You may also wish to view our CBD and Hemp Regulatory Fact Sheet here.

Last Chance to Register – EAS Food and Dietary Supplement Labeling Seminars

EAS is offering our popular Food and Dietary Supplement Labeling Seminars in Philadelphia March 12-13 and March 14-15, 2019 respectively. Join independent consultants and labeling experts Gisela Leon and Jim Hoadley, Ph.D. for an in-depth look at the various requirements surrounding the development of Nutrition and Supplement Facts Panels, including FDA’s latest requirements. Join EAS for either the Food Labeling Seminar or Dietary Supplement Labeling Seminar, or both! Group discounts for two or more employees are available.

OTC Drug Safety, Innovation, and Reform Act Discussed in Solid Dose Digest

EAS Independent Consultant, Norma Skolnik and Advisor for OTC Drugs and Labeling, Susan Crane, has​ co-written an article on the OTC Drug Safety, Innovation, and Reform Act. Recently published in Solid Dose Digest, the article includes a proposed review and overhaul of the OTC Monograph process, eliminating inefficiencies and allows for better response times to safety concerns. Learn more in Solid Dose Digest and join Susan in Part 2 of her Five-part webinar series on OTC Monographs. Part 1 – an Overview of the OTC Monograph system, is available On-Demand now. Part 2 on OTC Labeling and Listing Requirements takes place on February 27, 2019.

EAS Webinar on Regulatory Challenges of Submitting New Infant Formula Notifications

The submission stage of a New Infant Formula Notification may seem like the beginning of the end of a years-long process of research and strategic development. But, without all the right documentation in place, this last step prior to product launch can be unnecessarily delayed for those companies not well-prepared for the rigors of FDA review and assessment. Learn the steps to NIFNs as well as the pitfalls and challenges companies face in leading up to the assembling of an Infant Formula dossier. EAS Consulting Group’s experts, scientists, and leaders in their fields at FDA and industry will walk you through challenges and pitfalls which delay or prevent final FDA approval of this most important nutrient for growing infants. Join Robert Martin, Ph.D., Robert Burns, Ph.D. and Timothy Morck, Ph.D. for an informative and technical overview of one of FDA’s most challenging applications on April 2, 2019, at 1:00 pm eastern. Reserve your seat today!

What Does the 2018 Farm Bill Say About Sugar, Honey, and Agave?

By James Hoadley, Ph.D.

Each month EAS Independent Consultants answer one question sent in by our readers. This month’s question is answered by James Hoadley, Ph.D., an expert in food and supplement labeling and content claims and long-time instructor for our popular Food and Dietary Supplement Labeling Compliance Seminar. Prior to consulting Jim was the Senior Regulatory Scientist, Nutrition at FDA’s CFSAN Office of Nutritional Products, Labeling and Dietary Supplements.

If you’d like to ask a question of our experts, contact us here. To learn more information on our Food and Dietary Supplement Labeling Seminars please visit our webpage.

Question: I am a smaller company that produces maple syrup and honey sold in jars. Does the 2018 Farm Bill mean I no longer have to comply with the 2016 FDA Nutrition Facts requirements for these two single-source products?

Hoadley: One of the NUTRITION FACTS changes introduced in the FDA’s 2016 revisions to nutrition labeling regulations was a new line in the Nutrition Facts for Includes __ g added sugar. When a food contains sugars, but not added sugars, then the “Includes X g added sugars” line may be omitted from the Nutrition Facts and replaced by a “Not a significant source of added sugars” footnote. The term added sugar includes both sugars that are added during the processing of foods, and sugars packaged as such; e.g., a bag of sugar or a bottle of honey would need to declare its entire sugar content as added sugar. Including the single ingredient sources of sugar as added sugar was unpopular and confusing. FDA’s rationale was that when you purchase a bag of sugar, you are going to use it to add to food, so its use is as added sugar. In the past year FDA attempted to make the added sugar declaration more palatable for producers of products like honey and maple syrup by allowing for an enforcement discretion option of footnoting the added sugars declaration with a statement such as “†All these sugars are naturally occurring in honey.” The footnote option was not enough to sugar-coat the “Includes X g added sugars” requirement in some segments of the food industry. Though your product no longer has to declare added sugar, it still needs to comply with all other requirements for Nutrition Facts. 

2018 Farm Bill. SEC. 12516. LABELING EXEMPTION FOR SINGLE INGREDIENT FOODS AND PRODUCTS.
The food labeling requirements under section 403(q) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 343(q)) shall not require that the nutrition facts label of any single-ingredient sugar, honey, agave, or syrup, including maple syrup, that is packaged and offered for sale as a single-ingredient food bear the declaration “Includes X g Added Sugars.”.

Congress joined in the party by placing an ‘added sugars’ section in the miscellaneous provisions of the 2018 Farm Bill. The 2018 Farm Bill has decreed that FDA shall not require any single-ingredient sugar, honey, agave, or syrup product to bear the “Includes X g added sugars” declaration in its Nutrition Facts. The Farm Bill is an omnibus bill that directs agriculture and nutrition policies; it gets renewed at 5-year intervals. The 2018 Farm Bill covers the years 2019-2023. Provisions of the 2018 Farm Bill go into effect January 1, 2019.

Developing VMS Products for Commercial and Compliance Success

EAS independent consultant, Steve Cammarn, is presenting a webinar on considerations for Developing Vitamin, Mineral and Supplement Products for Commercial and Compliance Success. Join EAS February 7, 2019, at 1 pm Eastern where Dr. Cammarn will share principles and techniques for a phased-approach of the development of vitamin, mineral, and supplements products incorporating product design, process development, supply chain establishment, and qualification. Dr. Cammarn weaves together the scientific principles as well as the overarching regulatory requirements that must be met for commercial and compliance success. Join us!

2019 February From the Desk of the Chairman

Dear Reader,

Welcome to the February 2019 edition of EAS-e-News, the free news publication dedicated to FDA regulated industries. I’d like to begin by bringing your attention to our many new educational opportunities. From our many complimentary webinars to regulatory compliance seminars EAS brings the best in regulatory education to you through our extensive network of independent experts. In this issue, you’ll find numerous opportunities to learn in real time in addition to our wealth of on-demand webinars available for viewing at your convenience.

On that note, two recent additions to our complimentary webinar offerings include one on the requirements for Qualified Individuals, hosted by Independent Advisors Domenic Veneziano and Charles Breen, and regulatory challenges and opportunities for companies preparing New Infant Formula Notifications, presented by EAS Independent Advisor Robert Martin, Ph.D., and Independent Consultants Robert Burns, Ph.D. and Timothy Morck, Ph.D.. More information can be found in the EAS in Action section of this issue.

Our Issue of the Month is written by Independent Advisor for FSMA, Charles Breen, and discusses two very similar sounding terms, Qualified Individual and Preventive Controls Qualified Individual, which have two very different meanings. Our Ask the Expert is written by James Hoadley, Ph.D. and discusses the provision in the recently signed Farm Bill which covers “added sugars” and when the “includes X g added sugars” can be omitted from a label.

Also in this issue, we introduce a new section called “Did you Know?” which will provide a brief spotlight of concern to FDA regulatory industries. This month we discuss Slack Fill. Did you know this is a growing area of litigation for food manufacturers? The many regulations surrounding slack fill are confusing at best and EAS is here to help if this issue is one that your firm faces.

Further, EAS has just released our newest Video Short, on cannabis quality issues and how EAS Consulting Group can help companies navigate as the industry pushes for for developing sound Good Manufacturing Practices.

Lastly, we are so pleased that there is at least a temporary solution to reopen the federal government after the longest shutdown in our nation’s history and we hope for a lasting resolution that enables both sides of the aisle to find common ground. The shut down has had numerous negative impacts, including severely curtailing operations at FDA and USDA, are we are thankful, at least for the moment, that our federal employees are able to get back to the business at hand by serving the public.

Thank you as always for your interest in EAS and EASeNews. You are one of the 16,000 who receive our newsletter and we take great pride in bringing you relevant content and compliance solutions. Please let me know if you have any questions on this issue or other areas of FDA compliance.

Sincerely,

EAS Signature Ed

Ed Steele
Chairman and CEO

EAS Announces Next GMP Compliance for Laboratories Seminar in Denver

EAS Senior Director for Dietary Supplement Consulting Services, Tara Lin Couch, Ph.D. will instruct the next EAS seminar on Good Manufacturing Practices for Dietary Supplement Laboratories April 23, 2019 in Denver, CO. This one-day intensive program will discuss FDA’s current GMP requirements for Research and Development and Quality Control of Laboratories including physical, analytical, and microbiological laboratories. Topics include analyst training and qualification; the labs’ physical facility and environment; instrument qualification, calibration and maintenance programs and more.

Meet New Consultant for February 2019

Ronald J. Levine

Ron Levine has 40 years of experience advising consumer products companies in complex commercial matters. In addition to providing consulting services for EAS, he serves as the General Counsel of Herrick, Feinstein LLP, a law firm with offices in New York and Newark, NJ. He has practiced with Herrick since 1984, where he was a partner from 1985-2018. He served as Chair of the firm’s Litigation Department for 15 years.

A pragmatic advisor who helps clients anticipate, minimize and resolve the financial and reputational damage arising from claims and potential claims, Ron specializes in crisis management, for food and beverage manufacturers, and advises on class action litigations and investigations, including serving as an expert witness, related to labeling, the Food Safety Modernization Act (FSMA), advertising claims, product recalls, FDA regulations and other concerns.

The EAS Expert Witness team is greatly enhanced with the addition of Ron. By strategically matching the regulatory purview of the case at hand with our former high-level FDA and industry executives, EAS offers in-depth analysis of FDA and other Federal and state laws as well as standard industry best practices. Ron, along with Steve Armstrong, EAS Independent Advisor for Food Law and Regulation and former Chief Counsel for Campbell Soup Company and Bruce Silverglade, an EAS Independent Consultant and a Principal with the law firm Olsson Frank and Weeda Terman Matz, PC, lead the EAS Expert Witness team of consultants providing detailed and critical services to firms in all FDA commodity areas.

Ron Levine

Slack Fill – EAS Experts are Here to Help

There has been an increasingly growing volume of litigation in the slack fill area. This is a daunting issue for food manufacturers and is complicated by a dearth of clear guidance which ultimately leads to a lack of understanding of the many competing requirements and increases a company’s risk for legal challenges. In fact, there are at least five levels of law where one should look for guidance with slack fill, including international, federal, state, local and common law. Answers on how to interpret and piece the various laws and rulings together is not found on the FDA website, and moreover, it is very difficult to predict how a consumer attorney will interpret them as they attempt to bring suits against the industry.

If you are one of the many who have questions concerning how to find, understand, interpret and implement policies and practices regarding slack fill, call EAS’ team of experts who can assist in navigating this very complicated and confusing issue. 

Own Label Distributor Responsibilities Discussed in Natural Products Insider

Senior Director for Dietary Supplement and Tobacco Services, Tara Lin Couch, Ph.D. was interviewed for an article in Natural Products Insider on Own Label Distributors and challenges of industry to establish product specifications. According to FDA data, in fiscal year 2018, about 24 percent of the FDA Form 483 inspection reports cited firms for failing to establish specifications of finished dietary supplements. This issue is clearly a challenge for the industry and one in which OLDs should be well-versed and ensure compliance.

Food Safety Magazine Part II of Series on FSMA Training

Independent Consultant Mehrdad Tajkarimi has published part two of his three-part series in Food Safety Magazine on designing food safety training programs to meet FSMA compliance expectations. Food safety training is critical, not only in meeting FDA requirements, but in protecting consumers and the safety of our food supply. Whether training is designed and hosted in-house or delivered through expert training sources such as EAS, it is important that the content and delivery meet the audience where they are and deliver the information in an easily digestible format.

GMPs Refresher Training – New Dates Announced

EAS has announced a new date for our Riverside, CA GMP One-Day Refresher Training. This California training, now hosted on May 14, 2019, and its sister one-day Refresher trainings in Texas, Massachusetts and New York, are designed to meet the annual requirements many companies have that enable employees to stay current in GMP requirements. EAS is hosting four GMP Refresher trainings around the country in 2019. Please join us and consider outsourcing your company’s Refresher compliance trainings to EAS!

January 2019 Drug and Device Corner

With the Federal Register (FR) publication unavailable, the FDA has published Safety and Performance-Based Pathway on the Guidance Document webpage. Full details will be available in the Federal Register once that site is again functioning. The existing Docket Number for this document is 

FDA-2018-D-1387. For questions about this document regarding CDRH-regulated devices, contact the 510(k) Staff at 301-796-5640. For questions about this document regarding CBER-regulated devices, contact the Office of Communication, Outreach, and Development (OCOD) at 1-800-835-4709 or 240-402-8010.

Guidance Document updates on the FDA website

CDER

ANDA Submissions – Amendments and Requests for Final Approval to Tentatively Approved ANDAs

CDER & CBER

Rare Diseases: Common Issues in Drug Development

Labeling for Human Prescription Drug and Biological Products Approved Under the Accelerated Approval Regulatory Pathway

Immunogenicity Testing of Therapeutic Protein Products —Developing and Validating Assays for Anti-Drug Antibody Detection

REMS Assessment: Planning and Reporting

CDRH

Coordinated Development of Antimicrobial Drugs and Antimicrobial Susceptibility Test Devices

FDA’s CDRH recently released a Safety and Performance-Based Pathway Guidance Document describing a new abbreviated submission process for 510(k)s which aims to simplify submissions for devices which meet performance standards developed by FDA rather than showing outright equivalence in safety/efficacy to the predicate device. This new pathway has the potential for reducing the administrative burden of building a lengthy clearance dossier as well as be a slightly faster way to gain review and clearance. More information will be forthcoming as FDA issues future guidance on the application of this Safety and Performance-Based Pathway to certain types of devices with corresponding FDA-identified performance criteria. Industry may suggest device types for which FDA should consider identifying performance criteria.

Pharmaceutical GMPs for Safer Products and Swifter Approvals

EAS published a blog on the International Society of Pharmaceutical Engineers’ iSpeak blog on how GMPs and data integrity align for safer products and swifter approvals. FDA has noted that in recent years, findings from pharma facility inspections show increasing challenges with meeting data integrity requirements, which has led to regulatory actions including warning letters, import alerts, and consent decrees.

Qualified Individual and Preventive Controls Qualified Individual – What’s the Difference?

By Charles Breen

The Food Safety Modernization Act (FSMA) Preventive Control for Human Foods (PCHF) regulation (21 CFR 117) signed into law in 2011 offers a wealth of opportunity (and a requirement) for companies to improve their food safety procedures and protocols through the implementation of a preventive strategy against foodborne risks. As part of this regulation, food manufacturers must require that employees are qualified to perform their assigned tasks in a manner that protects food safety and prevents against adulteration. In addition, each company must have at least one employee, preferably located at the food manufacturing facility, who functions as a Preventive Controls Qualified Individual (PCQI). The PCQI functions as the responsible party overseeing the development and execution of all food safety programs and must have the knowledge, skills and abilities to perform these tasks based on their education, on the job experience or a combination.

Also, as part of FSMA, the Foreign Supplier Verification Program (FSVP) Final Rule for importers of human and animal food requires in Part 1 Subpart L that food manufacturers enlist a “Qualified Individual” who has responsibility for ensuring that all foreign suppliers of foods or food ingredients imported for consumption or further manufacturing in the U.S. produce their products in a manner consistent with FSMA requirements. This FSVP Qualified Individual (QI) must also have the knowledge, skills and abilities (KSAs) appropriate to evaluate foreign supplier compliance through their education OTJ experience or a combination of both. 

The FSMA PCHF regulation calls for a PCQI while the FSVP regulation calls for a QI. Though the terms are nearly the same and the regulations are related, they have different meanings. What exactly is the difference, in FDA’s view, of a PCQI and a QI, and how can companies determine that they are meeting FDA’s intent?

PCHF’s PCQI

PCHF’s big focus is on preventive controls for all food manufacturing facilities producing foods or food ingredients that will be consumed in the US. FDA requires that risk be assessed and mitigated so the risk no longer has public health significance, and that specific controls or mitigations steps be evaluated for effectiveness by a PCQI. A new term in the PCHF Final Rule, the requirement for a PCQI applies to covered domestic and foreign facilities producing human and animal food, generally those that need to register under section 415 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), (though there are, as expected, some exemptions). Though one PCQI can develop food safety plans for multiple facilities, it is important to note that each plan must be specific to the facility and address the unique processes and hazards within.

As a PCQI, considerations for biological, chemical and physical hazards must be thoroughly understood and assessed. Biological hazards include parasites and disease-causing bacteria; chemical hazards include radiological exposure, pesticides, drug residues, natural toxins, food decomposition, unapproved additives and food allergens; and physical hazards include items such as glass, rocks, metal parts or other foreign objects. FSMA requires that a food safety plan that specifically controls each of them must be developed by the PCQI. 

FDA accepts that either training or education (or a combination thereof) can provide the knowledge and skills required to perform PCQI duties as long as they equal a standardized curriculum recognized as adequate by FDA, such as that designed by the Food Safety and Preventive Controls Alliance (FSPCA) and instructed by FSPCA “Lead Instructors”. EAS offers the FDA-recognized FSPCA PCQI training curriculum, taught by Lead Instructors, as part of our comprehensive suite of in-house seminars and workshops.

Many who have already received training in HACCP, SQF, , BRC, IFS or FSSC22000 may still need additional training due to additional requirements for Good Manufacturing Practices requirements and Preventive Controls specified under PCHF in Part 117. FDA does not require, but it does recognize a formal FSPCA certificate verifying competency in Preventive Controls, for participants who successfully complete FSPCA PCQI workshop. 

FSVP’s QI

Companies importing finished food and food ingredients for further processing into the U.S. must have an FSVP QI to develop their FSVP food safety assessment program. An FSVP QI may be employed by the FSVP “Importer” or the Importer can contract with a private individual or consulting company like EAS Consulting Group to perform the FSVP QI responsibilities. A FSVP QI must evaluate the overall food safety risk of a food or food ingredient provided by a foreign supplier utilizing various documents originating from the foreign supplier and determine whether the foods or food ingredients meet FDA’s strict food safety requirements found in the PCHF and FSVP regulations. Much like PCHF’s PCQI, the FSVP QI will use the foreign supplier’s documents and the nature of the imported food or food ingredient to assess whether adequate controls are in place for potential biological, chemical and physical hazards. In addition, the FSVP QI will assess food safety risk by looking at whether their foreign supplier has been the subject of an FDA warning letter or import alert, their food safety performance history, results from testing, private or government audit results, and the supplier’s record of correcting problems. 

Once the QI has determined that a foreign supplier’s risks have appropriate controls, they will continue to monitor their performance by conducting appropriate supplier verification activities including some combination of onsite audits, reviewing supplier relevant food safety activities and sampling and testing of a food.  By regulation, these evaluation activities must be performed no less than every three years, or sooner if the FSVP importer becomes aware of new information concerning food safety or the foreign supplier’s performance.  It is our recommendation that these evaluation activities be updated annually as the food manufacturing environment is constantly changing and performing food safety risk assessments of a foreign manufacturer once every three (3) years may result in a significant food safety issue being allowed to continue for too long.

In addition to a QI’s assessment duties for a food importer, the FSVP Importer must also make sure their US Customs Broker identifies them for each incoming food or food ingredient shipment on the US Customs and Border Protection “ACE” electronic database as the FSVP Importer. The information must include the FSVP importer’s name, mailing address, and a unique facility identifier (UFI) recognized as acceptable to FDA. At present, FDA recognizes only DUNS numbers as an acceptable UFI.

Everyone with a role in importing foreign sourced foods should be familiar with applicable FSVP requirements including US Customs Brokers,foreign exporters, foreign food manufacturers, and US importers. This comprehensive approach is required under FSMA’s PCHF and FSVP regulations, intended to improve the nation’s level of protect food safety protection. FSPCA has developed an FDA-recognized FSVP training curriculum and EAS offers this in a workshop format in addition that of FSPCA’s Preventive Controls training curriculum. 

The microscope under which food safety assessments are evaluated has never been as detailed and is being scrutinized by FDA as now. With the possibility for potentially damaging regulatory enforcement consequences, many firms need to review, upgrade and have an outside, objective assessment of their food safety plans, whether they are domestic food manufacturers that have to comply with FSMA’s PCHF regulation or foreign food manufacturers that have to comply with both FSMA’s PCHF and FSVP regulations. An objective outside compliance assessment of a food manufacturer’s food safety plan needs to evaluate both the written plan and the effectiveness of its implementation. Third parties, such as EAS, can perform this objective outside assessment using a team approach to bring the correct level of expertise for development of an in-depth understanding of food manufacturer’s existing food safety system. The use of outside objective and qualified third-party private organizations such as EAS to evaluate and test the food manufacturer’s food safety program is part of any food manufacturer’s due diligence effort and can also offer a greater peace of mind to senior management of the facility and company owning the food manufacturing facility. Murphy’s Law says that if something can go wrong, it will. With a detailed food safety strategy in place, those risks can be identified and minimized before they become a problem.

More Like This?

EAS offers a wealth of additional learning opportunities on FSMA and FSVP. Check out the On-Demand Webinars page under Resources of our website for more topics like this including:

  • FSVP – What Does it Mean for your Business? – Presented by Charles Breen and Susan Moyers, Ph.D.
  • FSVP – What Does it Mean for your Business? – Presented in Spanish, Gustavo Gonzales, Ph.D.

Also, look for EAS in the News for articles such as:

FDLI Update: “FSMA After One Year: Advancing and Building Food Safety Systems for the 21st Century”, Steve Armstrong, EAS Independent Advisor, Food Law and Regulation


Steps to Develop Compliant SOPs Discussed in AHPA Report

The December American Herbal Products Association (AHPA) Report (subscription required) included an EAS authored article on steps to develop fully compliant Standard Operating Procedures. Though the development and detail of each SOP is at the discretion of individual companies, they should provide a thorough manual that enables each employee to understand their roles and responsibilities and how to perform and document them with regard to the cGMPs. As current practices evolve, so too should SOPs as they are designed to be living documents, representing best practices and required procedures.

FDA Encourages Innovation and Safety as Part of Medical Device Regulatory Overhaul

EAS authored an article in MedTech Intelligence on FDA’s efforts at encouraging innovation while keeping a close eye on safety as part of a medical device regulatory overhaul. FDA is working to retire outdated predicates for 510(k) submissions as well as improve their post-market surveillance system through a multi-collaborative effort called National Evaluation System for Health Technology (NEST).

Couch Shares Thoughts on Contract Laboratory Best Practices as Part of Insider Q&A

Senior Director for Dietary Supplement and Tobacco Services, Tara Lin Couch, Ph.D. participated in a discussion with other industry leaders on best practices for contract laboratories in a recent Natural Products Insider. Contract labs are often enlisted to certify that products are fully and validly tested, and the relationship with these labs can sometimes be complicated by a lack of provided material and product matrix information to ensure that appropriate, scientifically valid test methodologies are used. Couch and her industry colleagues share thoughts on how to convey expectations and develop agreements.

Join EAS for Complimentary Webinar Series on OTC Monograph Reforms

Join EAS Independent Advisor for OTC Drugs and Labeling, Susan Crane, as she explores the history of OTC Monographs and how OTC drug companies can expect updates to the Monograph system to impact their labels in a webinar series starting January 16, 2019. Part one will discuss the history of OTC monographs and why reforms are necessary. Part two is February 27, 2019 and will discuss understanding the FDA and FTC Labeling and Claim Requirements for Cosmetic and Homeopathic products in the OTC market. The final sessions, with dates to be announced will discuss what makes a drug an OTC and the Monographs Compliance System; and GMP obligations – understanding how the GMPs are Applied and how to prepare for FDA Inspection. Reserve your seat today!

Drug and Device January 2019

Guidance Document updates on the FDA website

All centers:

Developing and Labeling In vitro Companion Diagnostic Devices for a Specific Group or Class of Oncology Therapeutic Products

CDER:

Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis:  Developing Drugs for Treatment

Post-Complete Response Letter Meetings Between FDA and ANDA Applicants

Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act

CDER & CBER:

New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 2)

Questions and Answers on Biosimilar Development and the BPCI Act

The “Deemed to be a License” Provision of the BPCI Act Questions and Answers Guidance for Industry

Interpretation of the “Deemed to be a License” Provision of the Biologics Price Competition and Innovation Act of 2009

Biomarker Qualification: Evidentiary Framework

Data Integrity and Compliance With Drug CGMP Questions and Answers

Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics

Developing and Submitting Proposed Draft Guidance Relating to Patient Experience Data

CDRH & CBER:

User Fees and Refunds for Premarket Approval Applications and Device Biologics License Applications

CDRH:

Recommendations for Dual 510(k) and CLIA Waiver by Application Studies

Select Updates for Recommendations Select Updates for Recommendations Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices

Self-Monitoring Blood Glucose Test Systems for Over-the-Counter Use

Blood Glucose Monitoring Test Systems for Prescription Point-of-Care Use

Clarification of Radiation Control Regulations For Manufacturers of Diagnostic X-Ray Equipment

Breakthrough Devices Program

CBER:

Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion

Labeling of Red Blood Cell Units with Historical Antigen Typing Results

CVM:

Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food-Producing Species: Study Design Recommendations for Residue Studies in Honey for Establishing MRLs and Withdrawal Periods

2019 Produce Compliance Dates for FSMA

By Charles Breen, EAS Independent Advisor for FSMA Consulting Services

January 28, 2019, marks the compliance date for four categories of produce growers:

  • Sprouts from Very Small Farms (with certain exemptions), 
  • Sprouts from Very Small Farms eligible for a qualified exemption to comply with other requirements in 112.6 and 112.7, 
  • Other small farms, (except those with certain water requirements), and 
  • Small Farms eligible for a qualified exemption to comply with other requirements in 112.6 and 112.7

must come into compliance.

FSMA’s Final Rule on Produce Safety, Standards for the Growing, Harvesting, Packing, and Holding of Produce for Human Consumption, and FDA’s helpful Small Entity Compliance Guide concerning determination of business size (based on annual monetary value of the food farms sell directly to qualified end users) are two important resources for farms growing and harvesting produce for consumption without further processing.

Recent foodborne illness outbreaks from romaine lettuce illustrate why it is prudent to take a fresh look at some specific areas where the introduction and harboring of pathogens can wreak havoc and cause devastating public health and economic consequences.

FDA’s recently announced that the list of possible growing areas identified as the source of the E. coli outbreak in romaine lettuce has been narrowed to three California counties, and one farm in particular. However, FDA concedes that this does not explain all of the illnesses. As of December 13, 2018, traceback information from five restaurants in four states have identified 11 different distributors, nine different growers, and eight different farms as potential sources of the contaminated lettuce, so it is likely that the outbreak cannot be explained by a single farm, grower, harvester, or distributor. FDA continues to investigate.

It’s also not only E. coli causing produce industry woes. Listeria monocytogenes prompted recent recalls of pre-packaged salad products and asparagus, as did a summer outbreak of Cyclospora in melons and lettuce. 

Why are these events continuing to happen? FSMA’s many requirements were designed to prevent just such occurrences. Are growers not complying with the regulations because they are too difficult to understand, or too difficult to follow? Or are these outbreaks examples of Murphy’s law, that no matter the risk mitigation strategy, if something can go wrong, it will?

The answer, in my view, is yes to all three – and I’ll add that sometimes downstream consequences are not fully understood until it is too late. 

Take for instance, this past summer’s E. coli outbreak in romaine lettuce. The fact that after so many months FDA still cannot pinpoint the exact source of the outbreak suggests these companies and areas under investigation appear (at least on the surface) to be largely in compliance. As of this writing, Whole Genome Sequencing testing has identified only one result where an agricultural water reservoir sediment contains the same E. coli O157:H7 strand implicated in the outbreak. However, the agency says it isn’t clear how the water became contaminated and that additional illnesses demonstrate that this reservoir cannot be the only cause of such a widespread outbreak. 

As compliance dates for various sized produce and sprout farms arrive, FDA will continue to transition from an educational to a regulatory approach for FSMA and supplier enforcement. Prudent companies will take a step back and review their supplier, manufacturing, agricultural and transportation protocols to ensure that all conceivable entry points for microbiological, chemical and physical hazards are controlled, and, when problems do occur, quickly testing entry points to identify and reduce impacts.

Just because something hasn’t yet happened at your facility doesn’t mean it won’t, and don’t assume that just because something happens at one of your suppliers or distributors, that your company won’t see negative repercussions. Food safety is everyone’s business.

EAS stands ready to help you with all aspects of FSMA compliance. Contact us or more information end-users and we invite you to view our many industry information sheets to learn more about our services with regards to foods, FSMA and other FDA requirements for all product areas.

Dietary Supplement Specifications Development – Still Challenging the Industry Ten Years Later

By Tamika Cathey

Specifications Development, as defined in FDA’s Good Manufacturing Practices for dietary supplements (21 CFR §111) have posed one of the biggest challenges to industry since the inception of the requirements in June 2007. Specifically, 21 CFR §111.70 requires manufacturers to develop specifications for each component used in the manufacturing process and the finish product, including raw material components, in-process controls, packaging/labeling materials, and finished products. To be compliant with 21 CFR §111, each specification must ensure the quality of the material or product by addressing its identity, purity, strength or concentration, physical composition and lack of potential contaminants or ensuring that potential contaminants are present at acceptably safe levels. However, manufacturers continue to struggle with understanding specifications development and compliance. This is evidenced by the many Warning Letters and Form 483s issued by the FDA in the past ten years.

Certainly, the intent of specification requirements is well understood, at least conceptually by industry. The main purpose for requiring adequate specifications is to prevent product(s) adulteration and ensure that the finish product meets at least 100% of all nutrient claims declared on the Supplement Fact Panel (SFP) throughout its best by date or expiration date per 21 CFR §101.9 under the Nutritional Labeling and Education Act (NLEA). Once a specification is set, the specification must be verified using scientifically sound and justified testing analysis and/or visual examination analysis such as organoleptic, macroscopic, microscopic, chemical, or microbial. Recognized test methods can be obtained from compendial sources like USP monographs, AOAC, FCC, or NF and used a starting point in determining an appropriate method. Multiple tests and examinations are usually deployed to ensure specifications are met per 21 CFR §111.75 and 21 CFR §111.320. All of this ensures consistent reproducibility and reliability of a finished product that is either being manufactured or packaged.

A look at recent warning letters illustrates this lack of understanding with findings such as: 

  • A lack of or incomplete identity component specifications (e.g. dietary ingredients, excipients or process aids, coating materials etc.) for each component per 21 CFR §111.70(b)(1) and 21 CFR §111.70(b)(2).
  • Lack of or incomplete specification(s) for in-process controls in manufacturing process per 21 CFR §111.70(a).
  • Lack of or incomplete product specifications for finish products per 21 CFR §111.70(e) to include package/labeled products (e.g. 21 CFR §111.70 (d) & (f) & (g)).

Briefly, specifications are a set of defined parameters benchmarked against associated acceptance criteria providing characteristics and quality of a finish dietary supplement. The expectation is that when specifications are established, they will be written, managed in a controlled system with revision histories that are tracked, monitored, reviewed and approved by the Quality Department. This means materials and products being used from other sources will be unequivocally identified, the microbiological purity and other purity requirements will be assessed to determine strength and concentration of a dietary ingredient. The physical composition will be evaluated, and any potential contaminants will be identified.

When developing specifications, it is a good idea to begin as early as possible by identifying critical quality attributes of finish product(s) and the manufacturing process as a whole. These quality attributes are to be identified with acceptable ranges determined in order to assess the attribute. Scientifically sound/valid test methods and examinations are tools used to conduct the assessment. Each specification developed should address sections of identity, purity, strength, composition, and contaminants to meet regulatory requirements outlined in 21 CFR §111.

Dietary supplement manufacturers must consider component specifications, including dietary ingredients, as defined in 201(ff) of the FD&C Act and label claimed on SFP, and non-dietary ingredients such as excipients, capsules, and coating materials.

In addition, in-process specifications must be established for any point, step, or stage of manufacturing and packaging processes. Simply put, these specifications focus on verifying material composition thorough a series of physical tests and examinations such as in-process checks and metal detection. These specification requirements can be met by developing a comprehensive Master Manufacturing Record (MMR) as required in 21 CFR 111.210.

Packaging and labeling specifications for components including container closure systems and materials that may come in contact with finish product including desiccants, cotton, pouches, lids, outer cartons, labels, and inserts should include approved/qualified supplier information, name and description of item, and physical attributes such as material type, size, dimensions, and color. Physical attributes and item descriptions can be obtained from a reliable C of A. Keep in mind that packing specifications must be developed for every packing configuration used for finish products. Set process and control specifications within the MMR and set a requirement that visual examination for each batch will be performed.

Finally, finished product specifications (FP) establish the identity, purity, strength, composition, and limits of contaminates for each finished batch of dietary supplement. In short, the finish product specification details testing requirements for a finished batch. All dietary ingredients listed on the SFP must be identified on the FP specification and additional requirements of minimum and maximum acceptance criteria.

It is expected that the claimed SFP ingredients meet at least 100 percent of the label claim in order to meet the requirements NLEA detailed in 21 CFR 101.9. Release specifications may be set at a higher percentage to account for any needed overage amounts formulated into the product to ensure the 100-percent requirement is met throughout the product expiration date or best buy date.

In closing, specifications development can be established based upon acceptable ranges and values set forth by industry, academia, and scientific data/results from published journals, and/or product history in manufacturing. Refer to NLEA mandatory and voluntary labeling disclosure set forth by FDA 21 CFR 109 (j). Accredited laboratories and American Herbal Product Association can provide guidance for building the appropriate specification to include test method. Reference any sources used to determine appropriate specification. If further assistance is needed, manufacturers can also work closely with the qualified supplier(s), an accredited 3rd party laboratory, and/or qualified consultants to help with specification development.

FDA De-Listing of Synthetic Flavors

By Steve Armstrong

Question: FDA’s recent announcement delisting seven synthetic flavors caused a flurry of conversation and some confusion within the flavor and extract world. Would you clarify?

Armstrong: Thank you for the question and the opportunity to clear up confusion on FDA’s October 8, 2018 Constituent Update on the removal or delisting of seven synthetic flavors from the list of approved food additives. FDA was clearly reluctant to take this action, but it did so because several activist groups had petitioned for the delisting and then went to court to force FDA to take the action.

FDA made clear in its announcement in the Federal Register that it was only de-listing the synthetic form of these substances, which are labeled as “artificial flavors.” This means that a flavor manufacturer need only remove these synthetic substances from its flavor portfolio. These include synthetically-derived benzophenone, ethyl acrylate, eugenyl methyl ether (methyl eugenol), myrcene, pulegone, and pyridine. In addition, the FDA also is amending the food additive regulations to no longer provide for benzophenone’s use as a plasticizer in rubber articles intended for repeated use in contact with food.

In the Federal Register notice published on October 9, 2018 the agency said its revocation of the approvals “does not affect the legal status of foods containing natural counterparts or non-synthetic flavoring substances extracted from food.” FDA noted that each of the seven synthetic substances has a natural counterpart in food or in natural substances used to flavor foods. For example, they say, “benzophenone is present in grapes, ethyl acrylate is present in pineapple, eugenyl methyl ether (methyl eugenol) is present in basil, myrcene is present in citrus fruit, pulegone is present in peppermint, and pyridine is present in coffee.”

According to the Federal Register notice and the communication on FDA’s website, companies may continue to use the seven flavors provided they are only made from the natural extracts and are labeled as “natural flavors.” Companies using these synthetic flavors have 24 months from the publication of the rule in the Federal Register to identify suitable replacement ingredients and reformulate their food products.

This is an unusual situation and one precipitated by the Delaney Clause, an antiquated section of the Food, Drug, and Cosmetic Act. That section of the law prohibits FDA from approving a food additive if, after appropriate testing, it is found that the additive induces cancer in humans or animals. The clause is absolute. It does not provide FDA any leeway for applying a scientific risk assessment, even in situations where, as in the present case, the usage levels of an additive are low and inherently self-limiting, meaning exposures well below any area where they could possibly present any cancer risk. However, the petitioners had submitted data showing high levels of these synthetic substances did induce cancer in lab animals.

So, even though FDA had no concerns about either the synthetic or natural versions of these seven flavors, which had been used for decades, with no concerns about their safety as presently used in foods, the Delaney Clause required that the agency, as a legal matter, take the action requested by the petitioners. Six of the seven were delisted in response to these citizen petitions; the seventh (Styrene) was delisted because it is no longer in use. The agency clearly did not like having to take his step, but the Delaney Clause gave it no choice. The decision to de-list, it said, was required as a legal matter, not a scientific one. It’s possible that this action may signal an effort by the flavor and extract industry to modify the Delaney Clause.

Meet New Consultants

Timothy Morck, Ph.D.

Timothy Morck provides expertise in nutrition-related research, product development, regulatory and public policy and global scientific affairs. Dr. Morck’s career includes clinical nutrition practice, research, and medical school faculty appointments, scientific association management, entrepreneurial personalized nutrition start-ups, and executive and senior management positions at several global food, nutrition and pharmaceutical companies including The Dannon Company, Mead Johnson Nutritionals, Abbott Nutrition, Nestle Health Science and Nestle Corporate Affairs. The interplay between the legal, scientific, and regulatory framework surrounding medical foods has been a particularly sharp focus for him. He received a B.S. in animal science from Penn State University, followed by MS and Ph.D. degrees in nutrition (biochemistry & physiology minors) from Cornell University.

Paula Trumbo, Ph.D.

Paula Trumbo works with clients on food and dietary supplement labeling, claims, and other nutrition related issues for compliance with FDA regulations. Prior to consulting, she led FDA’s Nutrition Science Review Team responsible for the pre-market review of the scientific evidence for food labeling, including health claims, meeting the definition of dietary fiber, and amendments to the Nutrition and Supplement Fact label. She was the US delegate to the Codex Committee on Nutrition and Foods for Special Dietary Uses. Prior to joining the FDA, Dr. Trumbo served as Study Director for a number of study panels at the Institute of Medicine’s Food and Nutrition Board and was Associate Professor of nutrition at Purdue University. Dr. Trumbo has a PhD in biochemistry with minor in nutrition.

Farm Bill Solves “Added Sugar” Problem for Single Ingredient Products

The recently signed Farm Bill answers a number of questions, particularly for those manufacturers of single ingredient foods, jars of honey and maple syrup specifically, who objected to the requirement in FDA’s 2016 Final Rule of adding a declaration of daily value (DV) for added sugars as misleading.  Single ingredient products no longer require an added sugar declaration on the label.

FDA Technical Amendments for Nutrition and Supplement Facts Panels Released

FDA released a technical amendment correcting or further explaining minor errors and omissions in the May 27, 2016, Final Rules for Food Labeling: Revisions of the Nutrition and Supplement Facts Labels and Food Labeling: Serving Sizes of Foods that Can Reasonably be Consumed at One-Eating Occasion. These latest technical corrections are considered administerial in nature. Should you have any questions on these or other labeling issues please contact us for assistance.

Issue of the Month – Tamika Cathey

Tamika Cathey consults with an international client base on regulations pertaining to safety and quality of pharmaceuticals and dietary supplements. She evaluates client compliance readiness by conducting audits, risk assessments and mock FDA/GMP investigations and works to design improvement programs based on findings. Tamika has a B.S. in Biology from Greensboro College in North Carolina. Prior to consulting she held positions such as Associate Director, Regulatory Affairs for Charles River Laboratories, and Consumer Safety Officer at FDA’s Atlanta District. She is a certified auditor with the Natural Products Association and holdsFDA Level II certifications for the Clinical Bioresearch Monitoring Auditor and Drug Auditor Program.

Government Shut Down Impacts FDA and Industry Operations

Dear Readers,

Edward A. Steele

Welcome to the January 2019 edition of EASeNews! We hope this year, as with each year, brings a renewed commitment to safety and innovation in the advancement of your product lines and business.

As the Government Shut Down continues, FDA recently announced that agency operations will continue to the extent permitted by law, maintaining core functions that address imminent threats to the safety of human life as well as activities funded by carryover user fee funds. FDA will continue to respond to emergencies – such as monitoring for and quickly responding to outbreaks related to foodborne illness and the flu; support high-risk food and medical product recalls when products endanger consumers and patients and pursue civil and criminal investigations as appropriate and continue screening food and medical products that are imported to the U.S.. Mission critical surveillance for significant safety concerns with medical devices and other medical products will also continue.  During this period of lapsed funding, however, FDA does not have legal authority to accept user fees assessed for FY 2019 until an FY 2019 appropriation or Continuing Resolution for the FDA is enacted. This includes regulatory submissions for FY 2019 that require a fee payment and that are submitted during the lapse period.

At EAS we are also committed to ensuring our message of compliance reaches the industry. Most recently, our initiative to create video shorts discussing industry challenges and EAS capabilities is well underway! I am pleased to announce the release of Senior Director of Pharmaceuticals and Medical Devices, Bryan Coleman’s discussion of the importance of good preparation for FDA’s GxP audits as well as our auditing services; and Senior Director of Food Consulting Services, Allen Sayler’s discussion of challenges for the dairy industry, particularly in light of the many oversight organizations, as well as EAS’ dairy capabilities. In December we also released our first Hot Topic Report, a short video with Bryan Coleman discussing CDRH increased numbers of medical device inspections and what that means for the industry. We plan to release new hot topic videos to coincide with important FDA announcements. Watch your inbox for these pertinent updates impacting to your industry.

For those who work in Dietary Supplements I am pleased to announce a new training effort aimed at employees and management who are looking to complete their annual GMP compliance refresher training. EAS will host a series of four one-day GMP Refreshers around the country and we invite you to consider outsourcing your quality department’s training to our experts! Join us at one of our upcoming events taught by our internationally recognized compliance experts and gain a greater understanding of your requirements under FDA’s 21 CFR 111.

For those looking for a deeper dive into GMPs we remind you of our two-day full GMP Compliance seminar, which will take place April 2-3, 2019 in Philadelphia, PA. Earlybird rates will expire on February 2, 2019.

In addition, our Food Labeling and Dietary Supplement Labeling Compliance seminars will also take place in Philadelphia, March 12-13 and March 14-15 respectively. More information is found on our EAS website.

Our Issue of the Month article, written by Independent Consultant Tamika Cathey who works in dietary supplement GMP compliance (and who is our trainer for the August 13 Refresher training in Andover, MA), discusses specifications development – which continues to challenge the manufacturing industry. Our Ask the Expert is written by Steve Armstrong, Independent Advisor for Food Law and Regulation, and discusses FDA’s decision to delist seven synthetic flavors and how that decision impacts those firms still using them. Finally, our FSMA perspective, written by Independent Advisor for FSMA, Charles Breen, reminds all firms, (and specifically those working in produce and sprouts as new compliance dates for these industries arrive at the end of January), that food safety is a diligent and on-going process of review, redevelopment (as needed) and execution of pertinent practices to keep consumers safe.

As always, thank for reading our updates and for your interest in EAS. Feel free to share this newsletter with your colleagues and let me know if you have questions.

Sincerely,

Ed