By Mark Land, AAHP President

It can take several years for manufacturers to implement new guidelines from the Food and Drug Administration (FDA)—and that means they could be at risk in the meantime. However, manufacturers can “get ahead of the game” by monitoring FDA’s guidance development agenda.

FDA’s authority to regulate stems from the Federal Food, Drug, and Cosmetic Act (FD&C Act), and the Public Health Service Act (PHS Act). The FD&C Act, first enacted in 1906, covers drugs and devices; whereas, the PHS Act, first enacted in 1944, covers biologics. The FD&C and PHS Acts are written at a high level. More specific detail can be found in the Code of Federal Regulations (CFR). Even these extensive regulations will not address every situation so the agency produces guidance documents with still more detail.

The law is the law and the expectations of the FD&C and PHS Acts are non-negotiable. Regulations represent requirements of the law in greater detail. Guidance documents, however, represent “the current thinking of FDA on a particular topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.”

FDA is required to publish a guidance agenda in the Federal Register once per year with the goal of soliciting comment on its intentions to develop guidance. FDA’s Center for Drug Evaluation and Research (CDER) also maintains a guidance agenda on its website, listing the guidances it intends to issue in the current year. This enables the public to see what the Center is working on. The development of guidance documents follows the rules codified at 21 CFR 10.115.

CDER’s guidance agenda for 2019 included 98 projects in 15 categories. Categories include: Biosimilars, Clinical/Medical, Pharmacology, Safety, Quality, Labeling, Generics, Procedures, Submissions, Rare Diseases and others. Thus far in 2019, CDER has published 79 final or draft guidance documents. Of the guidance documents published this year, 25 were for guidance projects referenced on the 2019 guidance agenda. It has also withdrawn 15 previously published guidance documents.

Readers are encouraged to review the full list of published guidance documents for applicability to individual companies or products. Below are recently published guidance documents of general interest to homeopathic manufacturers:

 

CategoryTitle
Clinical Pharmacology; Over the CounterMaximal Usage Trials for Topically Applied Active Ingredients Being Considered for Inclusion in an Over-The -Counter Monograph: Study Elements and Considerations  
LabelingChild-Resistant Packaging Statements in Drug Product Labeling Guidance for Industry
Pharmaceutical Quality/CMCUsing the Inactive Ingredient Database Guidance for Industry
ProceduralCDER’s Program for the Recognition of Voluntary Consensus Standards Related to Pharmaceutical Quality

 

CDER’s guidance agenda is an interesting insight into what FDA is working on. Readers are encouraged to stay in touch with FDA’s agenda and its progress towards publication. Below is a list of guidance objectives potentially of interest to homeopathic manufacturers:

 

CategoryProject
Drug Safety

 

Best Practices in Developing Proprietary Names for Non-Prescription Drug Products
Restricted Delivery Systems: Flow Restrictors and Oral Liquid Drug Products
Electronic SubmissionsEstablishment Registration and Drug Listing
LabelingQuantification of Sodium, Potassium, and Phosphate in Human Over-the-Counter and Prescription Drug Labeling
Pharmaceutical Quality/MicrobiologyMicrobiological Considerations for Non-Sterile Drug Products
Risk Management Plans for Drug Manufacturers
Quality Considerations for Topical Ophthalmic Drug Products

 

FDA and CDER participate in the International Council for Harmonization (ICH). FDA adopts ICH guidance documents in the course of their publication. In general, FDA simply publishes ICH guidance with an FDA cover page using both the ICH title and numbering system. Thus far in 2019, FDA published four ICH guidance documents for public comment. Readers are encouraged to remain in touch with the ICH guidance agenda for potential implications for your products and processes.

As many readers know, FDA published a draft guidance entitled Drug Products Labeled as Homeopathic in December 2017. AAHP filed comments detailing shortcomings of the guidance. AAHP’s comments can be found under FDA’s docket FDA-2015-N-0540. In addition to information missing from the guidance, the draft guidance raises new compliance questions. AAHP’s Quality and Safety Summit in June offered solutions on those topics. For comparison reading on the subject of marketing of drugs without an approved NDA, see FDA’s Compliance Policy Guide Marketed Unapproved Drugs.

FDA’s guidance documents represent the agency’s current thinking on a given topic. Manufacturers are expected to comply or be able to justify alternative approaches. Because a plan to comply with guidance expectations may take several years to implement, readers are encouraged to maintain surveillance on FDA’s guidance development agenda. Take advantage of the web links below to familiarize yourself with the location of guidance development pages and think critically about the proposed or published guidance for potential impact on your firm.

References

United States Food and Drug Administration Center for Drug Evaluation and Research. Guidance Agenda New & Revised, Draft Guidances CDER Plans to Publish During Calendar Year 2019. https://www.fda.gov/media/124386/download

United States Food and Drug Administration Center for Drug Evaluation and Research. Manual of Policies and Procedures 4000.2 Developing and Issuing Guidance. https://www.fda.gov/media/71702/download

Seevers, R. What is an FDA guidance document? Pearl Pathways, Jan. 18, 2018. https://www.pearlpathways.com/what-is-an-fda-guidance-document/

United States Food and Druga Administration. Drug Products Labeled as Homeopathic Guidance for FDA Staff and Industry. December 2017. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/drug-products-labeled-homeopathic-guidance-fda-staff-and-industry

United States Food and Drug Administration. Homeopathic Product Regulation: Evaluating FDA’s Regulatory Framework After a Quarter-Century. https://www.regulations.gov/docket?D=FDA-2015-N-0540

International Council for Harmonization, Work Plans and Reports. https://www.ich.org/about/work-plans-reports.html

United States Food and Drug Administration. Marketed Unapproved Drugs – Compliance Policy Guide Section 440.100. Sept. 19, 2011. https://www.fda.gov/media/71004/download