The Role of Your US Agent

Foreign entities who operate in US FDA regulated industries must have an appointed US Agent before doing business and importing products into the US. US Agents act as an intermediary between the foreign company and FDA, assisting with two-way communication on requirements and questions such as establishment and facility registrations, product listings as well as submissions such as Foreign Color Manufacturers Testing and Approval through FDA, drug submissions such as IND, DMF, ANDA and their amendments and annual updates, and medical device applications such as 510(k), 513(g), PMA and IDE.

In addition to these basic requirements, regulatory US Agents have expertise in providing additional services to foreign clients such as technical reviews of submissions prior to FDA submission, preparation for FDA facility inspections (both through mock-inspections and desk-reviews of documentation), any Corrective Action Plans required by FDA and by providing answers to various questions surrounding the complex FDA regulatory requirements.

This webinar is presented by EAS Senior Director for Pharmaceutical and Medical Device Consulting Services, Bryan J. Coleman and Regulatory Specialist, Victoria Pankovich have covered important basic requirements of the US Agent role as well as opportunities to enhance your understanding of FDA oversight of foreign facilities.

Ask the Expert February 2018

By Tara Couch

EAS is pleased to introduce a new column in our EAS-e-News called Ask the Expert. Each month our expert consultants and Senior Directors will answer one question sent in by readers (edited if applicable to remove identifying information). If you’d like to submit a question, please use the “contact us” link on our website.

Tara Lin Couch Ph.D.

This month’s question answered by Tara Lin Couch, Ph.D., Senior Director for Dietary Supplement and Tobacco Services and the topic is whether there is a crossover between ISO certifications and GMPs in the laboratory.

QuestionIf a contract Laboratory is ISO certified, can we bypass an onsite audit if we incorporate this statement in our SOPs?

Couch: Absolutely not, ISO certification does not equal GMP compliance. I have seen many labs that are ISO certified and have terrible GMP compliance. Remember, ISO 17025 is not looking at the whole lab, it is looking at a specific test method or operation. It will dictate that the lab can run a particular test, Vitamin C for example, or operate a balance, but does not look at the entire laboratory quality systems. There are certain things that are covered in GMPs that are not covered in ISO, OOS (Out of Specifications) investigations would be one of those. OOS investigations should be conducted in accordance with the FDA, Center for Drug Evaluation and Research (CDER), Guidance for Industry: Out of Specification (OOS) Test Results for Pharmaceutical Production, issued in October of 2006. In this guidance, the FDA states that an investigation must be thorough, timely, unbiased, well-documented, and scientifically sound to be meaningful. There is a quality manual requirement in ISO 17025 that touches on investigations, but it is not near the level of detail that you would find in a GMP environment.

January 2018 FDA Drug / Medical Device Activity

EAS would like to remind all DMF holders that the FDA DEADLINE for eCTD submissions is fast approaching. As of 5 May 2018, the FDA will only accept eCTD submissions to ALL DMF files. If you have not already made plans for conversion, you should do so immediately. If you have any questions, feel free to contact EAS. While on the topic of DMFs Albert Yehaskel, EAS Independent Advisor for Pharmaceutical Submissions, has written a very informative white paper, “An Overview of Drug Master Files”. This has been slightly updated and added to our website, please use this link to access this valuable resource.

The Food and Drug Administration is reopening the comment period for the document published in the Federal Register on September 26, 2017, announcing a public hearing on a potential approach for device sponsors who seek to obtain marketing authorization for their products that are intended for a new use with an approved, marketed drug when the sponsor for the approved, marketed drug does not wish to pursue or collaborate on the new use. Submit either electronic or written comment by February 21, 2018.

In the event you missed the FDA announcement, the agency has created a new platform to request pre-ANDA meetings. This platform, CDER Direct NextGen Collaboration Portal, was designed to help the FDA minimize manual data entry and support the agency’s GDUFA II performance goals. The new technology platform, which will allow the industry to request pre-ANDA meetings for complex generic drug products with the FDA. In just a few steps, potential applicants of abbreviated new drug applications (ANDAs) will be able to initiate requests by uploading a meeting request package. The portal also allows the industry to submit supporting documents, such as meeting presentation materials, requests for additional information made by the FDA, and post-meeting comments. For additional information about the portal, please visit the FDA Pre-ANDA Program webpage.

FDA (or Agency) is announcing the timetable for updates to the FDA Data Standards Catalog for study data submitted electronically in NDAs, ANDAs, BLAs, and certain INDs to CBER and CDER. The initial implementation timetable for submitting standardized study data in electronic format was 24 months for NDAs, ANDAs, and applications, and 36 months for certain INDs after the publication of the final guidance “Providing Regulatory Submissions in Electronic Format–Standardized Study” in December 2014. When future updates to study data standards listed in the FDA Data Standards Catalog (Catalog) occur, these updated standards will be required in studies with a start date no earlier than 12 months after a Federal Register notice announcing such updates is published. When future new study data standards are listed in the Catalog, these new standards will be required in studies with a start date no earlier than 24 months after a Federal Register notice announcing such new standards is published. Please see the FDA Study Data Standards Resources webpage for further information.

Guidance Document updates on the FDA website: CDER:



Meet Issue of the Month Author Elizabeth Campbell

Elizabeth CampbellIndependent Advisor for Labeling and Claims, Elizabeth “Betty” Campbell, is a former Acting Director in the FDA’s Office of Food Labeling who played a leading role in writing the regulations implementing the Nutrition Labeling and Education Act (NLEA) in the 1990s. She joined EAS as a vice president in October 2006 after a 35-year career with FDA. In the role of independent advisor, she provides expert consulting advice and guidance to clients on complex labeling and claims issues including foods, medical foods, and infant formula. Betty has also served as an expert witness in numerous high profile labeling cases.

FDA Responds to GAO’s Report on Insufficient Agency Oversight of Recalls

By Charles Breen, Independent Advisor for FSMA

The December 2017 Department of the Inspector General report on FDA’s food recall process included some particularly harsh criticisms of the agency including inadequate authority, oversight and follow-up on voluntary food recalls. These criticisms came as little surprise as a number of issues surrounding agency oversight of recalls has been identified in recent years. A 2012 GAO report indicated that both FDA’s food advisory and recall processes need strengthening and a 2015 report again showed FDA is not keeping pace with foreign inspections.

The 2012 report findings prompted the agency to undertake significant steps in an effort to strengthen recall processes, including a revision of recall procedures published in the Regulatory Procedures Manual to better define recall categories in FDA’s database and to improve information sharing between federal and state agencies that also have oversight of food safety. Other improvement areas identified by GAO remain open, such as final guidance based on public comments on mandatory food recalls, and others that the agency said were impractical to implement.

Based on preliminary findings of the 2017 GAO report, which had been provided to FDA in 2016, the agency responded with the creation of a new management unit, the Strategic Coordinated Oversight of Recall Execution, (SCORE). It is intended to help the agency better investigate those reports of food illness that could pose a significant health hazard to consumers. Though a good start, the GAO recommends taking SCORE a step further to establish measurable performance expectations, such as timeframes, expedited decision-making, and improved electronic recall data. In other words, GAO wants to see scoring for SCORE.

One area of debate is the GAO’s review of 30 of the 1,557 voluntary FDA recalls between the years 2012 and 2015 where GAO determined in many cases FDA did not assess the hazards in a timely manner, nor did it communicate recall and safety concerns effectively. GAO cited, for instance, an extreme example where an affected product was not removed from commerce until 303 days after receipt of FDA’s warning letter prompting a recall. On average, says GAO, companies took 57 days to remove their recalled products. As well, GAO found the recall information captured and maintained in FDA’s electronic recall data system, the Recall Enterprise System (RES) to be deficient. The report noted “Our review found that FDA does not have adequate policies and procedures to ensure that firms take prompt and effective action in initiating voluntary food recalls. This means that dangerous food products may have remained in our nation’s food supply for weeks after FDA was aware of the contamination.”

FDA takes some exception with how the 30 voluntary recalls reviewed were chosen, as GAO self-describes them as “judgementally selected.” In FDA’s view, these companies represent “extreme outliers” and says their own data show that during this 2012-2015 period when FDA “found out about a product problem that eventually resulted in a recall, the recall initiation took place, on average, in less than four days. In the highest risk recalls, when there was a reasonable probability that the use of or exposure to a product would cause serious adverse health consequences or death, recall initiation took place, on average, in less than three days.”

That being said, the agency stresses that it understands the urgency of getting recalls right and is reviewing selected recalls to identify gaps and improve procedures. FDA Commissioner, Scott Gottlieb said in a statement responding to the report, “Making sure the FDA has effective recall practices in place, and that we take immediate action to address unsafe foods, are high priorities of mine. Our recall authorities — and how we deploy them — are a cornerstone of our vital, consumer protection mission.”

HHS Office of the Inspector General rejects the agency’s claim that the 30 selected recalls were “extreme outliers” and says that FDA lacks a reliable tracking system. The current system makes it difficult to capture the recall initiation date and the date FDA became aware of potentially hazardous food products.

Regardless of the back and forth, the importance and urgency of identifying a food safety issue and its subsequent follow-throughs cannot be overstated. Recalls are a unique challenge as a consumer may have already purchased the recalled product.

It is imperative that companies have a robust and well-documented recall plan as part of their standard operating procedures (SOP) and that those plans are routinely practiced, drilling through the process with various scenarios – from a product in the warehouse, in-transit, already on consumer shelves and the type of threat identified.

  • How will your company respond?
  • Who is the internal point of contact/liaison with FDA?
  • How will parties who may be in possession of the product be identified and contacted?
  • How will the return and destruction of a product be identified and tracked?
  • How and by whom will the media be addressed?

There are many aspects to consider, many contingencies to plan for, and only one opportunity to get this right the first time. The safety of the public and the long-term viability of your company may depend on it.

The Food Safety Modernization Act (FSMA) granted FDA the authority to initiate mandatory food recalls. While the agency is working through their requirements to do so and simultaneously monitor voluntary recalls effectively, so should you. EAS offers assistance in preparing recall strategies as part of our holistic regulatory compliance planning services under FSMA. Take steps now and be prepared.

FDA’S Policy on Medical Foods

By Elizabeth Campbell, EAS Independent Advisor for Labeling and Claims

“Medical food” is a commonly misunderstood term as it is used on FDA regulated products. Many manufacturers want to market their products as medical foods because medical foods are exempt from the disease statement limitations for health and structure/function claims and are allowed to name the diseased population for whom they are designed. The following paragraphs provide details on FDA’s approach to medical foods, but the policy can be summarized as: a medical food is intended for people who have a disease or condition that results in a distinctive nutritional need which cannot be met by a diet of regular food but is met by the medical food. The disease or condition must be identified, the distinctive nutritional need must be substantiated by data, and it must be demonstrated that the product would meet the identified nutritional need.

Prior to 1972, medical foods were primarily formulas for managing patients with inherited metabolic diseases. They were mainly orphan products for limited populations. They were considered drugs to ensure their use under medical supervision. However, in 1972 the FDA reclassified these products from drugs to foods for special dietary use to enhance their development and availability. In the intervening years, a wide variety of products categorized as medical foods have been developed. Currently, marketed medical foods with a wide variety of claims are used extensively as a life support modality in the management of the critically ill and elderly. They are required to conform only to those regulations dealing with general food safety and labeling to be distributed in the United States.

The 1988 Orphan Drug Act (21 U.S.C. 360ee(b)(3)) provides financial incentives (such as drug application fee exemptions, and market exclusivity) to promote the development of “orphan drugs” for treating rare diseases and conditions. Medical foods were included in the Orphan Drug Act to include dietary therapies, along with pharmaceuticals, as eligible for financial incentives for developing orphan drugs. Medical food was defined within the context of new drug development, not for regulating the use of such products. The Orphan Drug Act did not amend the FD&C Act to add medical foods as a regulatory category.

The Orphan Drug Act definition of medical food is:

A food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.

There are presently no FDA regulations specific to medical foods other than the exemption provisions in the nutrition labeling regulation. The following criteria that clarify the statutory definition of a medical food can be found in FDA’s regulations at 21 CFR 101.9(j)(8). A medical food is exempt from the nutrition labeling requirements of 21 CFR 101.9 only if:

  1. It is a specially formulated and processed product (as opposed to a naturally occurring foodstuff used in its natural state) for the partial or exclusive feeding of a patient by means of oral intake or enteral feeding by tube, meaning a tube or catheter that delivers nutrients beyond the oral cavity directly into the stomach or small intestine;
  2. It is intended for the dietary management of a patient who, because of therapeutic or chronic medical needs, has limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who has other special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone;
  3. It provides nutritional support specifically modified for the management of the unique nutrient needs that result from the specific disease or condition, as determined by medical evaluation;
  4. It is intended to be used under medical supervision; and
  5. It is intended only for a patient receiving active and ongoing medical supervision wherein the patient requires medical care on a recurring basis for, among other things, instructions on the use of the medical food.

FDA published in 1996 an Advanced Notice of Proposed Rulemaking (ANPR) in which the agency discussed its interpretation of the Orphan Drug Act definition of medical food. ( While FDA later withdrew this ANPR due to lack of resources to devote to the subject of medical foods, the agency stated that it still retained the positions described in the document. A subsequent guidance document on medical foods provided advice consistent with positions in the ANPR. (

FDA considers the statutory definition of medical foods to narrowly constrain the types of products that fit within the category. Outside of medical foods that have been developed for dietary management of rare diseases, FDA has considered most products marketed as medical foods, not to meet the definition of a medical food. The types of products that have been the target of FDA medical food Warning Letters include products intended for the dietary management of allergies and asthma, lactose intolerance, psoriasis, constipation, Irritable Bowel Syndrome, Crohn’s disease, colitis, arthritis, failure-to-thrive, injury/trauma, pre/post surgery, and prenatal vitamins. The FDA guidance document specifically states that pregnancy and diabetes are not diseases or conditions for which there is a distinctive nutritional need that could only be met by a medical food.

Product Development and Labeling Service

Product development is a competitive challenge whereby companies attempt to best posture themselves as an attractive option to consumers, an effective competitor against similar products on retail shelves and do so in a manner that meets FDA, USDA and FTC requirements. EAS’ strategic product development and labeling service help companies with all of these challenges and more, providing a comprehensive and holistic approach to product development from ideation to commercialization. A successful product is about more than designing the right label, it must take into account marketing objectives as well as the current regulatory, compliance, and enforcement environments. EAS is proud of this service and the many companies for which we have provided proactive solutions.

We invite you to view a short video on this Strategic Product Development and Labeling service as well as our Industry Service Sheets detailing some of the many challenges within product development and how a partnership with EAS experts would be of benefit.

Much Movement on FSMA

Dear Reader,

Edward A. SteeleWelcome to EAS-e-News, the free news update for FDA regulated industries.

There has been quite a bit of movement from the agency on FSMA, including the creation of FDA’s new FSMA landing page on the FDA website. Those companies which fall under the FSMA compliance rules should make a note and save this new bookmark.

The agency also released draft guidance #245 in the area of Hazard Analysis and Risk-Based Preventive Controls for Animal Foods. This particular draft guidance includes food safety plan requirements; recommendations for conducting a hazard analysis; hazards associated with the manufacturing, processing, packing, and holding of animal food; examples of preventive controls that may be used to significantly minimize or prevent animal food hazards; and preventive control management components. Public comment is due to the agency no later than July 23, 2018.

FDA also released new guidance in January indicating the agency is extending the enforcement for a few very specific parts of FSMA. Specifics include:

  • a two-year extension to complete required documentation for any food manufacturer that relies on their customer to control “reasonably foreseeable hazards”
  • a two-year extension for importers of food contact substances to comply with the Preventive Controls rule
  • September 17, 2018, for all Grade “A” dairy plant’s to be in compliance with the Preventive Controls rule
  • a number of extensions for certain farm-based activities including holding, packing or coloring of raw agricultural commodities as well as cotton ginning and farm water sampling.

One area that the agency will work to improve is addressed in the GAO report indicating the agency’s inadequate oversight and follow-up on voluntary food recalls and is the subject of this month’s FSMA Perspective. FDA’s oversight continues to be a challenging issue for all commodity areas as GAO has also identified challenges in the medical device industry.

Our Issue of the Month article, on how FDA defines Medical Foods is written by our Independent Advisor for Labeling and Claims, Betty Campbell. Medical foods are a very narrow category of foods prescribed by physicians, intended for patients who cannot otherwise meet their nutritional needs and is a commonly misunderstood and misused terms.

I have shared previously in EAS-e-News a new strategic service that we provide to our clients – Product Development and Labeling which combines the resources of some of our most experienced independent consultants to collectively assist companies in determining best paths forward when considering claims such as GMO and other trending claims as well as competitive challenges. There are many second and third order effects to the use of these claims and we at EAS feel that the most successful companies look at these challenges holistically and develop complimentary approaches that consider multiple aspects. I’ll bring to your attention a short video, hosted by EAS Independent Advisor for Food Law and Regulation, and former Chief Food Law Counsel at Campbell Soup, Steve Armstrong which discusses this service. More details can also be found in this issue.

EAS has a number of seminars coming up that we invite you to attend – Dietary Supplement Labeling Compliance, March 5-6 in Logan, UT, and Dairy Processing 101, March 7-9 in Logan, UT, Dietary Supplement GMP Compliance April 4-5, in Denver, CO and Food Labeling Compliance May 29-30 in Alexandria, VA. We are also offering a new GMP Online Short Course based on 21 CFR 111. This two-part online training begins February 22. In addition, through our partnership with HACCP Consulting Group, you’ll find a Developing and Implementing SQF Systems seminar February 26-27 in Dayton, OH.

EAS welcomesour new regulatory intern, Georgetown University student Youthika Gokaraju, who is pursuing a masters degree in Biotechnology with an emphasis in BioBusiness. It has been EAS’ good fortune to have hosted a series of students from this prestigious program over the years and we are pleased to provide a window into the important world of regulatory affairs in the early days of their career.

I’d also like to congratulate EAS Independent Consultant Madhu Soni who was named one of the top five most prolific GRAS experts based on an independent group analysis cited in the prestigious journal Food Chemical Toxicology. The process of submitting a GRAS dossier to FDA can be a daunting process with numerous safety studies and required background documentation. Dr. Soni has been one part of the EAS GRAS team who has facilitated “no objections” for over 18 ingredients and many other self-determinations submitted directly by companies. For a listing of our successful GRAS submissions click here. If your company is considering submitting a GRAS dossier, please consider EAS to help in this process. We would be happy to discuss your project needs and help you to determine the best path forward for your specific situation.

Thank you as always for your interest in EAS and please feel free to reach out to me if you have any comments or questions.

Dietary Supplement Good Manufacturing Practices On-line Short Course

For those seeking a broader overview of GMPs, EAS is offering a new two-part online short course which will cover the basics of working in a GMP environment including personal hygiene, sanitation, the use of Standard Operating Procedures (SOPs), and Good Documentation Practices (GDPs). It will also address the top 5 observations cited in FDA Warning Letters since 2010.

This Short Course, based on the 21 CFR 111, Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, provides a great initial training for personnel unfamiliar with GMPs and can serve as a refresher and annual GMP training requirement.

Each session runs 2.5 hours in length and the dates are February 22nd and March 1st from 1:00-3:30 pm ET and is FREE to EAS clients. Registration is $99 for both sessions for non-clients. Click here for more information and to register.