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


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.


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.


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.


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.


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.


#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.


Edward A. Steele Signature


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.