October 2019 Drug and Device Corner

REMINDER: we are currently in the renewal period (1 Oct – 31 Dec) for medical device & drug establishment registrations, as well as drug listing certifications.

The FDA, in their commitment to assisting industry in the development of affordable, available, generic drugs, and as part of the Drug Competition Action Plan, is working toward addressing and improving transparency with regard to potential generic applicants obtaining brand RLD samples for generic drug development. The significant issue of industry’s inability to obtain certain RLDs for generic drug development, those that are in limited distribution, is being addressed by the agency in part by posting a list identifying all drug products for which the FDA has received an RLD access inquiry related to limited distribution. Further information is available on the website.

In the October 25, 2019 issue of the Federal Register, FDA announced that it was withdrawing Compliance Policy Guide Sec. 400.400 “Conditions under Which Homeopathic Drug Products May be Marketed”, effective immediately. This CPG was issued in 1988 and has served as the mechanism by which the regulation of homeopathic drug products was enforced.

However, due to ongoing concerns about the safety of homeopathic drug products, the FDA determined that the CPG did not prevent unsafe products from reaching the market nor did it reflect the agency’s current thinking with regard to its risk-based approach to regulatory and enforcement action.

In addition to withdrawing the CPG, the FDA also revised the draft guidance Drug Products Labeled as Homeopathic Guidance for FDA Staff and Industry that had been issued in 2017. The revised draft adds a definition for “homeopathic drug product”, incorporates additional information regarding safety issues that contributed to the development of the guidance and clarifies the agency’s intent to use risk-based factors to prioritize enforcement and regulatory actions involving homeopathic drug products.

In an effort to assist Applicants with supplying correct and complete facility information to the FDA for NDAs, ANDAs, BLAs and submissions associated to these applications, the FDA has published the Guidance Document Identification of Manufacturing Establishments in Applications Submitted to CBER and CDER Q & A. This guidance is intended to clarify Agency expectations regarding facility information that should be included in original NDAs; ANDAs; original BLAs; amendments; supplements; CMC supplements; and resubmissions to these submission types. It is the FDAs hope that this guidance document will reduce the frequency of IRs, RTFs and RTRs as well as increase the efficiency of the application assessment process. The document addresses form 356h, Module 3 and referenced DMF details.

Federal Register Vol 84, No 207, Medical Devices; Exemptions from Premarket Notification: Class II Devices; Request for Comments. FDA is announcing a publication containing modifications the Agency is making to the list of standards FDA recognizes for use in premarket reviews (FDA Recognized Consensus Standards). FR Vol 84, No 206, entitled “Modifications to the List of Recognized Standards, Recognition List Number: 052” (Recognition List Number: 052), will assist manufacturers who elect to declare conformity with consensus standards to meet certain requirements for medical devices.

Quarterly Inactive Ingredient Database (IID) Change Log

Guidance Document updates on the FDA website:







Equipment Sanitation May be Co-packer Liability

Natural Products Insider

Gabe Miller, independent consultant and expert in equipment sanitation, published an article in Natural Products Insider on equipment sanitation and the need for co-packers to be aware of how this can impact their business – and liability. “Food processing equipment requires proper design, operation and sanitary maintenance to minimize the risk of contamination from microbial, chemical and physical hazards,” he says.

Couch Interviewed for Insider Podcast

Senior Director for Dietary Supplement and Tobacco Services, Tara Lin Couch, Ph.D., was interviewed for a Natural Products Insider podcast on how important paper audits are to a contract lab qualification. Couch spoke at the SupplySide West show on this subject in a session titled: Trust in Testing: Contract Labs for Safe, Compliant Supplements.

FDA Releases Plans for Draft Guidance on the Human Hazard Analysis and Risk-Based Preventive Control (HARPC) Rule – Chapter 14: Recall

FDA Logo

FDA announced the release of the next chapter, in draft, of the Guidance for Industry “Hazard Analysis and Risk-Based Preventive Controls for Human Food” on recall plans. This newest chapter will assist the food industry establish and implement a written recall plan as required by 21 CFR 117.139.

The Preventive Control Human Food (PCHF) requirements specify that processors must establish a written recall plan for food that requires a preventive control (21 CFR 117.139(a)). The PCHF requirements also specify that the written recall plan must include procedures that describe the steps to be taken, and assign responsibility for taking those steps, to perform the following actions as appropriate to the facility (21 CFR 117.139(b)).
Written comments on the draft guidance are due by February 4, 2020.

FDA Publishes Required Records for FSVP

FDA has published a list of required records for foreign firms exporting food products for both animal and human consumption into the U.S. The Foreign Supplier Verification Program (FSVP), which is part of the Food Safety Modernization Act (FSMA), includes a number of additional requirements placed on food importers to ensure the safety and traceability of food sourcing down the supply chain. Stay informed of the latest roll-outs for provisions of FSMA and all other FDA updates through the EAS webpage listserv by clicking here.

Last Chance to Register for November Compliance Seminars and Webinars

If you haven’t made plans to join EAS in Irvine California in mid-November there are a few days left to register for our Food Labeling, Dietary Supplement Labeling and Dietary Supplement GMP seminars. We hope to see you there! If these seminars don’t fit your schedule, you can always bring EAS in-house for a customized program. Contact Cathryn Sacra, Director of Labeling Services, for more information on in-house labeling programs and Tara Couch, Senior Director for Dietary Supplement Services, for information on GMPs.

Additionally, Ron Levine will provide fantastic insight on becoming an expert witness in legal matters. Ron has decades of experience as a partner at Herrick, Feinstein LLP and EAS is honored that he has also chosen to act as a consultant, assisting clients with 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 and preparing and editing reports to federal agencies and other entities. Ron’s webinar will be on November 6, 2019 at 1pm.

EAS Independent Advisor for Quality and Compliance, Robert Fish, is conducting webinar overview of GMP observations for dietary supplement firms and how those observations provide insight into FDA’s thinking and compliance focus for the coming year. Bob Fish is a former FDA Director, Division of Field Investigations where he was responsible for general policy and guidance for the Agency’s domestic and international investigation activities. Bob’s webinar is on November 6, 2019 at 1pm.

EAS Exhibiting, Speaking at CannaPharma West

EAS independent consultant and cannabis expert, Charlotte Peyton, will be at the CannaPharma West conference, along with EAS Independent Advisor for Dietary Supplements, Timothy Stewart, Ph.D., in San Diego, November 13-14, 2019. Charlotte will be speaking at the EAS sponsored breakfast on Thursday covering Practical Implementation of Cannabis Regulations Through FDA Good Manufacturing Practices (GMPs), and both Charlotte and Tim will be at the EAS exhibit table. We invite you to come by and say hello to discuss your regulatory questions about this unique but thriving industry!

EAS Discusses Medical Device 510(k) Safety and Performance Measures in ISPE iSpeak Blog


Medical device manufacturers have a new tool available to demonstrate substantial equivalence through FDA’s 510(k) Safety and Performance measures. In a recently released Final Guidance, the Agency, as part of their effort towards stimulating innovation and reducing administrative burdens, all while keeping a keen eye on safety, is adding to their arsenal of abbreviated device submissions available for products based on previously approved predicates. Read more about FDA’s latest initiative in an EAS authored blog published by ISPE and contact Bryan Coleman, Senior Director for Pharmaceuticals and Medical Devices, to learn more about EAS services to support Medical Device manufacturers and their development of innovative new products.

Safe Foods for Canadians Act (SFCA) Discussed in Food Safety Magazine

EAS Independent Consultant, Ramakrishnan “Rama” Narasimhan published an article in Food Safety Magazine on the Safe Food for Canadians Act, including areas where it is similar to FDA’s FSMA. Did you know EAS offers food safety services for Canadian firms and has a number of Canadian independent consultants who assist? Contact Allen Sayler, Senior Director for Food Consulting Services, for more information.

Dietary Supplements and FSMA Compliance – Fallacy or Fact? – A Complimentary EAS Webinar

Do you know which of the seven major FSMA regulations were designed to support the Food Safety Modernization Act (FSMA)? Join EAS Consulting Group’s FSMA and Dietary Supplement experts Tara Lin Couch, Ph.D., Senior Director for Dietary Supplement and Tobacco Services and Allen Sayler, Senior Director for Food Consulting Services for an overview of the FSMA regulation and a deeper dive into those aspects which specifically apply to dietary supplements. Learn the crucial steps to compliance, including what must be included in a food safety plan, required qualifications the Preventive Controls Qualified Individual and what is needed to develop an FSVP. This complimentary EAS webinar will take place on December 4, 2019, at 1 pm eastern. Register here.

FDA’s Approach to Intentional Adulteration

Joe Famiglietti

Each month EAS selects one question sent in by readers of EASeNews to answer as part of our Ask the Expert column. This month’s question on how FDA is enforcing Adulterated Foods is answered by Independent Consultant, Joe Famiglietti, who works closely with EAS clients in developing and enhancing food safety programs as well as facilitating recalls in cases where a product is adulterated. If you would like to ask a question of one of our experts, contact us.

Question: What kinds of enforcement actions does FDA take with regards to adulterated foods?

Joe Famiglietti

Famiglietti: FDA considers foods to be adulterated if such foods are impure, unsafe, or unwholesome. 21 CFR 117.1(a)(1) identifies two types of food adulteration as described in the Federal Food, Drug and Cosmetic Act (FD&C ACT) as follows:

  • Section 402(a)(3) – The food has been manufactured under such conditions that it is unfit for food, in which it is considered to be contaminated.
  • Section 402(a)(4) – The food has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or may be rendered injurious to health.

Enforcement actions FDA can take on domestic adulterated foods include seizing/condemning the product or enjoining persons from manufacturing or distributing such goods. If adulterated foods are in domestic commerce, FDA can require adulterated foods to be recalled. A food processor can sometimes reprocess an adulterated food if FDA agrees to the firm’s reprocessing plan.

FDA does not always require laboratory tests to show that a food is adulterated. Under the FD&C Act, a food can be deemed as adulterated based on insanitary conditions in a facility such as lack of cleanliness, equipment issues, poor maintenance of the facility, improper storage of foods, pest issues, etc.

Examples of recent recalls include an ice cream product because of the potential that the product may be contaminated with foreign objects; mineral spring water recalled due to the presence of arsenic and a spice powder recalled due to contamination with lead. In each case FDA considered the products to be adulterated and had the responsible firms not initiated a recall, FDA could have considered using enforcement actions.

There have been cases whereby FDA documented widespread rodent infestations in food warehouses resulting in mass seizure actions which means that every food item in the facility was placed under seizure. In these cases, where FDA testing documented the presence of rodent filth in the foods (such as fecal matter, urine and rodent hair), these products were seized under Section 402(a)(3). The remainder of the products that were not tested at the affected facilities were seized under 402(a)(4) because they were being held under insanitary conditions with a high probability of becoming contaminated.

It should be noted, FDA regulations authorize the agency to issue Defect Action Levels (DALs) for natural unavoidable defects that at low levels do not pose a human health hazard. Examples are rodent hairs and insect fragments found in foods at minimal levels which are permitted because it is economically impractical to grow, harvest or process products that are totally free of all non-hazardous defects. 21CFR117.110 covers the DAL regulations.

EAS helps firms identify and protect against the introduction of adulteration. Our mock-audit service, one of the most comprehensive in the industry, brings our former FDA investigators onsite to conduct a thorough review of your processes and procedures, just as FDA would in an inspection. We then prepare a documented and detailed report of findings and opportunities for improvement. Additionally, firms needing to conduct a voluntary recall may contact EAS for our rapid-response team that offers step by step assistance in communicating product concerns with FDA, retailers, consumers and media as well as tracking shipments of products both in-transit and in the marketplace.

EAS offers the most comprehensive suite of services compared to any other FDA-regulatory consulting firm. Contact us today to discuss your questions and how we may help you. For more information on intentional adulteration, type “adulteration” into the search bar on the EAS website.

EAS offers QMS Services for Medical Devices

Quality Management Systems (QMS) for medical devices are cumbersome as layers upon layers of critical checks ensure the safety and effectiveness required for the consumer. However, in an effort to reduce overly burdensome recordkeeping processes FDA has announced a voluntary QMS switch from 21 CFR 820 to ISO 13485:2016. CFR 820 is and will remain the law, but this move to ISO 13485:2016 would harmonize the FDA Quality Systems and supplant the existing requirements with the specifications of an international consensus standard for medical device manufactures. ISO uses an improved risk management and risk-based decision-making approach in all processes of the quality management system. FDA expects to fully transition to standard ISO 13485:2016 for medical devices sometime in 2019.

It’s important for medical device firms to get this QMS transition right. EAS offers expertise and assistance in moving from CFR 820 to ISO 13485, facilitating a smooth transition and ensuring compliance. If you missed our recent webinar on the new QMS system, we invite you to view it on-demand here. For more information on our services or to discuss your regulatory challenges please contact Bryan Coleman, Senior Director for Pharmaceuticals and Medical Devices.

Meet This Month’s Ask the Expert

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.

Meet November 2019 Issue of the Month Author

Tamika Cathey

Tamika Cathey

Tamika Cathey provides regulatory compliance services pertaining to safety and quality of pharmaceuticals and dietary supplements. She evaluates client compliance readiness, executes mock GMP/FDA audits, performs risk assessments and gap analyses per FDA regulations and creates improvement programs based on findings. Cathey consulted with EAS from 2012-2016 and we are very pleased that she is again able to offer her expertise to our clients.

Basic Steps to Establish an Effective Environmental Monitoring Program

By Tamika Cathey

Tamika Cathey

Contamination prevention is a requirement across many regulated industries such as foods, cosmetics, dietary supplements, biologics, medical devices and pharmaceuticals. These requirements are established to ensure product safety and reduce the likelihood of an adverse event(s) for the consumer. Regulated industries can meet specified requirements by setting and maintaining environmental controls as part of their Good Manufacturing Practice (GMP) quality system to prevent product contamination.

An Environmental Monitoring Program (EMP) is a critical tool to understanding the types of contamination sources and levels of microbiological activity within a GMP facility. Monitoring trends within the environment using an EMP can assist in the evaluation of the effectiveness of cleaning programs, personnel practices, and production operations to limit or prevent contamination.

A systematic scientific approach is needed in order to establish an effective EMP considering the risk of contamination within the manufacturing process. If implemented appropriately, it acts as an early warning sign for the prevention of contamination in product. A few basic concepts should be considered when establishing an effective EMP:

  1. Gather an EM team– This should be a committee with subject matter experts experienced in performing risk assessments. The team should include, at a minimum, representatives from Quality, Microbiology, Facilities and Production.
  2. Regulations and Guidance– Identify all applicable statutes, compendia, regulatory, and/or guidelines based upon product classification, route of administration, and the types of GMP activities performed. Guidance documents like “FDA Guidance for Industry “Sterile Drug Products Produced by Aseptic Processing —Current Good Manufacturing Practice” can be a useful tool clarifying existing rules and outlining regulatory expectations. Risk assessment analysis tools can be used to adapt portions of the sterile guidelines where regulations for non-sterile manufacturing are not as clear.
  3. Identify Contaminants- Identify common types of contaminants that can be introduced to the GMP facility and/or product. Microorganisms such as bacteria, yeasts, and molds, and coliforms as well as pathogens like E. Coli, Salmonella, Listeria, and S. Aureus are potential microbiological contaminants; chemical contaminants may include a variety of entities including heavy metals, pesticides, and residual solvents but allergens are certainly a high priority; and physical contaminants such as metal can all be identified from both incoming raw materials and the production process. Compendia sources such as the United States Pharmacopeia (USP), Chapter <2023>, Microbiological Attributes of Nonsterile Nutritional and Dietary Supplements, can provide a framework for microbial attributes for non-sterile nutritional and dietary supplements.
  4. Route of Entry– Routes of entry should also be identified; personnel, equipment, utilities (HVAC systems, for example) and production processes are a few common sources for contamination. A firm’s supply chain can also introduce material and component contamination due to poor GMP practices. Knowing these common sources is the first step in developing a strategy on what to sample for and where to sample throughout a facility.
  5. Risk Assessment– A risk analysis is performed to determine all areas of possible contamination. Areas close to critical process, high traffic areas, difficult-to-clean facility locations and equipment, personnel and material flow, and storage areas are all places that can easily be identified by utilizing risk assessment tools like failure mode effects analysis [FMEA], hazard analysis critical control points [HACCP], or Ishikawa [aka fishbone analysis] tables. A documented thorough risk assessment will include cross-contamination​ concerns, a rationale for sampling locations, frequencies for each monitored environment, and alert and action levels for each type of potential contaminant.
  6. Sampling Plan and Mapping– When selecting sites to be sampled, it is recommended to utilize established guidelines. For example, ISO 14464-1:2015 contains tables to establish the number of nonviable particulate samples based on the size of the room. A common approach in determining where to monitor includes obtaining a map of the area and using the risk assessment results to plot out where the sample(s) should be taken. According to EU GMP Annex 1, “Environmental monitoring sampling plans should be flexible with respect to the monitoring frequencies, and sample plan locations should be adjusted based on the observed rate of contamination and ongoing risk analysis.”
  7. Setting Limits- EMP action limits may be implemented and modified from the sterile regulatory guidelines provided in ISO 14464-1, Annex 1, and others such as USP <1116>. Alert limits should be based on historical data and should be used as an alert tool for processes that drift from their state of control. Statistical analysis can be performed on trend data to establish these alert limits as they pertain to the process capabilities of the facility. The decision and rationale for the established limits, sampling frequency, and sample sites should then be documented with instructions in a written procedure or standard operating procedure (SOP).

The Human Factor of Product Safety Innovation

Dear Readers,

Edward A. Steele

Welcome to the November 2019 edition of EASeNews. You’ll see a new format to our newsletter this month, our effort to help you more quickly access the information of greatest interest to you. All the same great regulatory content is here, and with just a click of a button, you’ll be taken directly to it. We hope you enjoy the update and as always please feel free to provide any feedback on this or any other area of interest.

As we assembled the content for the November issue, the theme of product safety resonated throughout. Contamination prevention is a requirement across FDA regulated industries, ensuring product safety and reducing the likelihood of contamination and adverse events. In this issue you will find our Issue of the Month on establishing environmental monitoring programs; an Ask the Expert on Adulterated Foods; an EAS in the News section full of links to articles and webinars on strategies to identify and protect against allergens and pathogens all authored and presented by EAS’s team of very talented regulatory consultants. I am sure this issue will be one of our most pertinent, no matter the product area in which you work. 

But, while we work to automate solutions, let’s not forget the human factor of our industry. It is the people, from management to line workers who are the real machines behind innovation and who, through their actions, will always have the strongest impact on product safety. Ensure, no matter the job function that training and messaging of the human factor’s importance stays constant and relevant. EAS is always here to assist and is just a phone call or email away.


EAS Signature Ed