Temporary Marketing Permits – Opportunity and Pitfalls of the Specialized FDA Application

Food Standards are an important component of FDA’s oversight, ensuring honesty and fairness to the consumer through requirements that provide for the basic nature of a standardized food to be uniform in terms of its characteristics as well as the ingredients that it must or may contain, (i.e., mandatory and optional ingredients. But what happens when a newly developed food or production method warrants consideration of a product category outside of the standard? Petitioning to amend a food standard or to create a new one, is a lengthy and complicated process; however, a temporary solution may be available through a specialized category called a Temporary Marketing Permit(TMP’s). With TMP’s companies with novel standardized food innovations may apply to market test a food product that deviates from the standard of identity for that particular food, providing FDA with data needed to consider a future petition to amend the standard.

About the Presenter

April Kates was most recently a supervisory consumer safety officer at FDA. Prior to that position, she served with USDA’s Food Safety and Inspection Service Federal-State Audit Branch, also as a supervisory consumer safety officer. Previously, she served as manager of regulatory compliance at McCormick Spice Company, as a food regulatory specialist at American Ingredients Company (now Corbion), as a program analyst at FSIS, and as a food technologist at FDA.

Preparing for Foreign FDA Inspections

Have you ever wondered why your foreign suppliers: API, intermediates, food ingredients, etc. are suddenly in trouble with regulatory authorities? Did they just go astray or is your auditing program not performing as designed? Actually, there are several things at play. EAS Independent Consultant, Peter Saxon, will shed some light on reasons FDA inspections can “go south” as well as provide insight on how disappointing results can be managed. Saxon has personally attended 90 FDA inspections of foreign facilities and another 15 inspections by other regulatory agencies (TGA, WHO, EDQM). His insights will provide an opportunity for companies to consider improvements to their internal audit structure to help minimize regulatory risks.

About the Presenter

Peter Saxon has extensive experience in assisting pharmaceutical companies to prepare for FDA inspections of API and finished dosage plants for the U.S. market. He brings 45 years of experience in technical operations, materials management, and business development background in the pharmaceutical industry. His expertise includes pre-inspection audits, Drug Master File (DMF) preparation, equipment, cleaning, computer and process validations as well as QA training. A consultant since 1993, he has assisted major US pharmaceutical companies through FDA consent decrees and guided foreign API and finished dosage manufacturers through FDA inspections. Prior to consulting Saxon served in management roles with Ciba-Geigy Corporation, including stints in Cairo, Egypt, and Basel, Switzerland. Mr. Saxon holds an MBA from Rutgers University, and a BS in chemical engineering from Manhattan College, Riverdale, NY. He is fluent in German and has a working knowledge of Spanish, French, Arabic, and Chinese

Sean T. Wall

Just wanted to say thank you for the information shared at the Dietary Supplement GMP training last week. I’ve been to many trainings/seminars over the years, many of which I left thinking “WOW…I’m never going to use what I just learned.” I’m pleased to say that after leaving this training, I felt confident that I’d be immediately using at least 90% of the information that I learned. There are several follow-ups that I have planned here, some of which were points that I’m not sure we were aware of, and others that will only strengthen some of our current programs. The training was informative and very well delivered. The Q&A allowed throughout was also informative, yet never veered too far off course. As a previous trainer, I understand how important good interaction can be, but I also understand how quickly a conversation can go off on a tangent. You had a great mix of letting things happen, yet kept it corralled. Great job!

Hanna S.

Thanks for delivering a jam-packed learning experience. It was so well done and very important work. I’m feeling ready to roll up my sleeves!

Cheryl Ensign

I consider myself a seasoned professional in regulatory compliance for the food/supplement industry. The instructors were very personal and information was presented with lots of practical experiences and details. Powerful take aways! Never too experienced to learn a whole lot more!

Jessica Wurtz

I wanted to write a quick note and say that I thoroughly enjoyed the training class. It was extremely thorough, packed with useful information, and was presented very well. Thank you very much for sharing both of your experiences as well; they definitely added significant value because of the real-world applications for the information. I was really excited to share it with my management team!

Kimberly Vance

You [Bob Fish] and the other instructors did a great job with the course! I learned a lot. I feel like a new person, and am now more equipped to audit my contract manufacturers against the standard. Thanks for answering all of my questions and giving your insight on industry findings.

Brittini Gehring, MH, Chief Botanical Officer

The program was extremely comprehensive. The course materials were structured and detailed. It broke down 21 CFR Part 111 into very easy to comprehend sections that allowed me to simultaneously create a list of immediate actions to apply at our facility to help us become even more GMP compliant! The course helped me to understand how to tie up a lot of previously confusing loose ends. Thank you to all the instructors and to EAS for providing the course!

Sydnie Boral

I am very impressed with the quality of this presentation and the presenters. I am new to cGMP and this has been a most valuable overview.

Quality Systems for the Cannabis Industry – Preparing for State GMP Regulations

Presented by:
Tara Lin Couch, Ph.D.
Senior Director, Dietary Supplement and Tobacco Services

As states begin to regulate legalized cannabis, the concern of how Good Manufacturing Practices (GMPs) apply to this unique industry cannot be understated. While regulations vary from state to state the quality systems under which cannabis products are grown and manufactured have similarities that can begin to pave the way for putting practices and procedures in place to meet compliance expectations, including those of testing and quality control of in-process materials, finished batches and packaged/labeled products. The time is right for the Cannabis industry to begin assessing your manufacturing processes and implementing sound and effective quality systems in order to help you begin to prepare for GMP regulations. Stay ahead of the curve, standardize your product quality and be a leader in your industry.

About the instructor

Tara Lin Couch, PhD
Senior Director, Dietary Supplement and Tobacco Services

Dr. Tara Lin Couch is a Ph.D. Analytical / Organic Chemist with exceptional analytical abilities and over 25 years of diverse laboratory and regulatory experience in academic, field, contract, and manufacturing environments. She is a sought-after expert on issues pertaining to Quality Control in pharmaceutical, dietary supplement and tobacco manufacturing facilities including the establishment of specifications and the development of well-organized, sophisticated laboratories. As a Senior Director for EAS Consulting Group, Dr. Couch has assisted numerous companies with the development, improvement, and implementation of strong Quality Systems that are scientifically sound, efficient, practical, and compliant with all FDA regulations. She also performs mock FDA inspections, gap-analyses, and contractor facility audits. In addition, Dr. Couch provides GMP and laboratory training via seminar, webinar, and on-site presentations.

FDA 483 Responses – Missing the Mark?

By Cindy Beehner, Independent Consultant

In recent months, it appears more companies are having difficulties meeting the requirements of FDA Form 483, List of Observations, response. The inspection situation is very stressful and if it ends with the dreaded “483”, it can be positively overwhelming. However, when the initial reaction is over, it’s time to rally the staff and prepare the corrective and preventative action strategy that will be presented in the response within the allotted time frame. It is also critical to understand what is expected of the response letter.

The 483 is a list of inspectional observations that is the result of what the inspectors viewed while in your facility. It is a legal document from federal agents performing a law enforcement function where the evidence is the collection of documents and data that the agents evaluated at the company. All of the observations should first be reviewed for accuracy. Hopefully, any discrepancies or misunderstandings were discussed during the closing meeting and resolved, but if they were not found until after the inspectors left the facility, they will need to be addressed in the response. The 483 response is also a legal document so the tenor and exact wording used are critical. It must demonstrate that the company understands the issues, has made the necessary corrective and preventative actions, and that there is documented evidence to verify the latter.

Each observation requires a response and that response must describe the associated corrective and preventative actions are taken. It should be thorough and detailed and written to present steps in the order taken. Procedures and related documents prepared and implemented during these actions must also be included. It is not enough to only describe actions, there must be documented evidence of the correction such as photographs, procedures, training records, specific forms, and other types of documentation. Many Warning Letters are issued by the FDA because a company’s response letter did not include evidence of the corrective and preventative actions taken for the FDA to evaluate to determine if the situation was appropriately addressed.

Consider three potential categories of actions to be taken for each observation; immediate, short-term and long-term. Think of this from a medical emergency perspective where initial triage occurs to keep the patient’s condition from getting worse, additional short-term actions are needed to stabilize the patient, and then long-term actions may be needed to deal with any underlying problems. A systematic issue will have to be addressed with preventative measures. It is also important to review the observations collectively, in addition to individual, to determine if other underlying systemic issues exist. These too will have to be addressed with corrective and preventative actions.

Please note that, unlike an FDA Warning Letter, a response to a 483 is not legally required. However, it is strongly recommended that a 483 response be provided to the FDA within 15 business days. Some observations can be appropriately addressed and the actions concluded within this time frame, but others, particularly systematic issues, may require more time. When that is the case, all of the planned corrective and preventative actions should be described in the initial response, immediate and short-term actions should be taken, and completion dates for long-term items provided. It is important that these proposed dates be aggressive, yet reasonable and obtainable. Monthly updates to the FDA stating the progress made on these long-term items, with supportive documented evidence included, should then follow. This strategy may prevent the FDA from escalating enforcement actions and issue a Warning Letter.

Confirmation that the FDA is satisfied with the 483 response will be provided by the issuance of an Establishment Inspection Report (EIR) which states that all of the corrective and preventative actions will be evaluated upon “the next inspection.” The EIR is also a more detailed summary of the inspectional findings and it is wise to use this as an opportunity to further review operations, controlled processes, and the overall quality system. Look at these findings from a systems approach; facilities and equipment, materials, production, packaging and labeling, laboratory controls and, of course, the most important and critical one – the quality incident system. The entirety of the inspection and the inspectional review should also be another piece to the internal audit program, make the experience work to improve compliance and not just an exercise in writing letters to the FDA.

For assistance in understanding FDA 483 findings as well as developing an appropriate response and corrective actions contact EAS.

Are Plant-Based Proteins Milking Dairy?

By Allen Sayler, Senior Director for Food Consulting Services

When FDA announced recently that the agency is seeking public comment for standards of identity overhaul that will focus in part on plant-based products that are marketed as “milk” substitutes, manufacturers of those products as well as the consumers who enjoy them were left wondering how this review and any future changes would affect them. Consumers of soy, almond, rice, coconut and other plant-based “milk” enjoy these dairy alternative products for any number of reasons, but in some cases, their consumption decisions are based on incomplete or inaccurate information and may result in a diet deficient in certain nutrients found in dairy milk but not the substitute protein. This issue is of interest to others outside of the US as Canada, the European Union and Codex all have laws, regulations and beverage standards that limit the use of the term “milk” to only beverages where dairy “milk” is the major or characterizing ingredient.

There are nearly 300 standards of identity on the books at FDA, and these plant-based proteins which use qualified terms as part of their “milk”, “yogurt” and “cheese” product names aren’t in-fact “milk” as we have come to know it. Based on this technical violation of the standard of identity for “milk” and a concern regarding consumer misunderstanding of the nutritional value of plant-based beverages, FDA has decided to look at the term milk as part of its overall effort of modernizing standards of identity and improving information provided to consumers and their physicians so that the nutritional composition and benefits of products is clear.

FDA is currently seeking information on how consumers understand the term “milk” and whether the nutritional differences between dairy-based and plant-based “milk” products is understood. FDA is also trying to understand if the use of the term “milk” in non-dairy products is misleading and if that lack of understanding plays a role in less informed dietary choices. Stakeholder feedback is actively recruited by the agency and, based on initial comments gathered, FDA will provide an additional request for information in late summer or fall targeted more directly towards consumer awareness and understanding of the use of milk and other dairy terms on plant-based alternatives, including a focus on nutritional impact. The agency will use this feedback to refine its policy for these standards of identity and will issue new guidance for industry as well as their compliance and enforcement approach (no timeline is currently established). 

In addition to gaining an understanding of milk products, the agency is additionally seeking feedback on how the agency should consider food technology, nutritional science, fortification practices and marketing trends for not only dairy but all foods as part of their standards of identity review to gain an understanding of how each may enhance or stymie innovation or nutritional improvements.

As manufacturers of foods, standards of identity can at times protect the consumer and food industry from misleading or fraudulent foods, food ingredients, and labels, but they can also hinder efforts at product innovation, use of new ingredients and processing technologies and restriction on modification of the standard to improve nutritional content. Understanding food labels, content, nutritional value and product claims are all critical for consumers to make informed choices today. It is equally important for food manufacturers, who are committed to providing cleaner food labels while trying to deliver more nutritionally sound food into the US marketplace.

Regulatory opportunities, headwinds, and challenges will be facing the Agency as it begins to review and potentially revise the current food standards of identity. As the agency seeks comment, now is the time for food firms to provide their input and begin the conversation as to how technology, fortification, and sound science need to be considered in the review and revision process, to the benefit of the consumer, food industry and FDA. As an innovation for a healthier food supply continues to evolve, the ability to clearly communicate an improved and clear message of food content and nutritional value will enhance consumer understanding and allow for more informed choices. Formulating agency feedback can help to effectively lead awareness of those opportunities and challenges. Incorporating sound scientific assessments, food processing technologies and market research on consumer perceptions and trends incorporated into well-written comments can enhance a firm’s position. EAS independent consultants, toxicologists, microbiologists who are experts in dairy, plant-based beverages and FDA food standards of identity and labeling can help you to formulate your position and develop agency comment.

Drug and Device Corner 2018 July

EAS would like to bring to your attention the Draft Guidance released by the FDA for ANDA Submissions – Amendments to Abbreviated New Drug Applications Under GDUFA. This guidance describes the significant difference between GDUFA I and GDUFA II Amendments and the timelines associated with their review. The FDA considers all submissions to an ANDA to be an amendment, they will be classified based on the content and issued a goal date consistent with that classification. Please review the guidance for further details.

In the FDA’s ongoing effort to make generic affordable drugs available to the public, they have published product-specific guidances describing the Agency’s current thinking and expectations on how to develop generic drug products therapeutically equivalent to specific reference listed drugs. These guidances are hoped to assist the generic pharmaceutical industry with identifying the most appropriate methodology for developing drugs and generating the evidence needed to support ANDA approval. Please see the FDA’s Product-Specific Guidances for Generic Drug Development webpage for more details.

The FDA issued a press release regarding its recent actions on bulk drug substances used for compounding. Their Bulk Drug Substances Nominated for Use in Compounding lists for 503A Category drugs and 503B Category drugs have been updated as of 23 July 2018. Included in the update are the changes to the lists and when the changes became effective. Please see the press release for full details. 

The Food and Drug Administration (FDA) announced a public hearing to solicit input from the public on how to facilitate greater availability of biosimilar and interchangeable products while retaining the balance between competition and innovation. The hearing will be held on Tuesday 4 September 2018, from 9 a.m. to 5 p.m. at the Food and Drug Administration’s White Oak Conference Center. If you would like to participate and weigh in on this hearing, more information on how to register for the meeting or the live webcast can be found in the Federal Register Notice.

Guidance Document updates on the FDA website

All centers

Use of Electronic Health Record Data in Clinical Investigations

CDER

Oncology Therapeutic Radiopharmaceuticals: Nonclinical Studies and Labeling Recommendations

Smallpox (Variola Virus) Infection: Developing Drugs for Treatment or Prevention

Q3D(R1) Elemental Impurities

Hypertension: Conducting Studies of Drugs to Treat Patients on a Background of Multiple Antihypertensive Drugs

Innovative Approaches for Nonprescription Drug Products

Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products – Quality Considerations

Use of Liquids and / or Soft Foods as Vehicles for Drug Administration: General Considerations for Selection and In Vitro Methods for Product Quality Assessments

Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products – Quality Considerations

CDER & CBER

Assessing User Fees Under the Biosimilar User Fee Amendments of 2017

Indications and Usage Section of Labeling for Human Prescription Drug and Biological Products – Content and Format

E17 General Principles for Planning and Design of Multiregional Clinical Trials

Field Alert Report Submission Q & A

Labeling for Biosimilar Products

Inborn Errors of Metabolism That use Dietary Management: Considerations for Optimizing and Standardizing Diet in Clinical Trials for Drug Product Development

Slowly Progressive, Low-Prevalence Rare Diseases with Substrate Deposition That Results from Single Enzyme Defects: Providing Evidence of Effectiveness for Replacement or Corrective Therapies

E17 General Principles for Planning and Design of Multiregional Clinical Trials

CDRH

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

CBER

Human Gene Therapy for Retinal Disorders

Long-Term Follow-Up After Administration of Human Gene Therapy Products

Human Gene Therapy for Rare Diseases

Chemistry, Manufacturing and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)

Human Gene Therapy for Hemophilia

Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up

Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)

CVM

Antimicrobial Animal Drug Sales and Distribution Reporting

#257 Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food-Producing Species: Marker Residue Depletion Studies to Establish Product Withdrawal Periods in Aquatic Species