EAS Instructs at FDLI Educational Events

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

Additionally, two of our experts in food and dietary supplement labeling are speaking at FDLI’s Intro to Food Law and Regulation on September 24-25, 2019 at Crowell Moring in Washington, D.C.. Gisela Leon will present an Introduction to Food Law and Regulation and Andrea Yablunosky will instruct Food Labeling, Nutrient Content and Other Claims. EAS is pleased to be a frequent contributor to numerous FDLI educational programs on a variety of product areas.

Finally, James Hoadley, Ph.D., will teach a session on FDA Food Labeling for an FDLI seminar presented at CFSAN, on September 12, 2019.

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

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

Crane to Instruct CHPA OTC Academy Courses

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

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

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

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

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

September 2019 Ask the Expert

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

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

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

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

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

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

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

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

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

Meet New Consultant Penny Vyskocil

Penny Vyskocil

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

Meet September 2019 Issue of the Month Author

Tom Jonaitis

Tom Jonaitis

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

GRAS Determination: Lessons and Pitfalls

By Tom Jonaitis

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

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

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

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

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

  1. Identification/Characterization:

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

  2. Processing Aids used in manufacturing:

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

  3. Toxicology/Safety Studies:

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

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

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

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

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

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

September 2019 From the Desk of the Chairman

Dear Readers,

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

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

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

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

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

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

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

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



Meet New Consultant Rebecca Harter

Rebecca Harter

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

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

By William (Bill) Scopa

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

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

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

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

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

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

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

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

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

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

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

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

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

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

EAS Assistance Simplifies FDA Registrations, Listings and Renewals

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

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

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

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

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

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

Expert Witness Training Set for November 6 in Alexandria, VA

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

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

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

July 2019 Drug and Device Corner

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

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

Guidance Document updates on the FDA website

All Divisions

Postmarketing Safety Reporting for Combination Products

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


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

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

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

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

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

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

Using the Inactive Ingredient Database

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

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

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

E19 Optimisation of Safety Data Collection

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

Advanced Prostate Cancer: Developing Gonadotropin-Releasing Hormone Analogues

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

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

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


Population Pharmacokinetics

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

Risk Evaluation and Mitigation Strategies: Modifications and Revisions

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

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

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

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

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

Epidermolysis Bullosa: Developing Drugs for Treatment of Cutaneous Manifestations

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

Treatment for Heart Failure: Endpoints for Drug Development

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

M10 Bioanalytical Method Validation 

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

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

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


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

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

Center for Devices and Radiological Health (CDRH) Appeals Processes

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

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

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

Marketing Clearance of Diagnostic Ultrasound Systems and Transducers

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

Clinical Investigations for Prostate Tissue Ablation Devices

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

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

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


CVM GFI #181 Blue Bird Medicated Feed Labels

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

Determining the Risk-Base of High-Risk Foods

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

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

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

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

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

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

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

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

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

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

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

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

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

GRAS Submissions of Food Safety Webinar Announced

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

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

Meet Issue of the Month Author William Scopa

William Scopa

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

Expediting Imports at U.S. Ports of Entry

Dear Readers,

Edward A. Steele

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

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

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

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

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

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


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