FDA to propose revamps to guidance development and communication process in coming weeks

The FDA is in the late stages of preparing a report and plan, required by Congress, which aim to set the stage for modernizing the FDA’s approach to developing and communicating guidance. While the documents aren’t expected for a few more weeks, AgencyIQ has a preview of what we expect the agency might do – as well as some additional ideas they may not yet be considering.

Regulatory background on guidance documents

• FDA guidance documents are used to fill in the gaps of regulation. While the documents are technically non-binding (unless otherwise specified in statute), they are most often used by the FDA to describe how the agency interprets certain statutory and regulatory provisions and how companies can best comply with those provisions. For example, while federal law might require a company to submit substantial evidence of effectiveness to the FDA in order to obtain approval, the FDA could then issue a guidance document on how it interprets the phrase “substantial” in terms of the number of trials, the types of enrollees, and the design of the studies for a specific disease.
• For the FDA, guidance documents come in a variety of different forms and formats. Essentially all guidance documents are published as PDFs with lengths ranging from the single-digits to the upper double-digits, depending on the subject matter. Guidance documents will either be “Level 1” guidance documents (which set forth interpretations of statutory or regulatory requirements, set forth a change in policy, include complex scientific issues or cover highly controversial issues) or “Level 2” guidance documents (which set forth existing practices or minor changes in interpretation or policy”).
• The FDA does maintain a Good Guidance Practices (GGP) regulation as well, which clarifies what the documents are and are not intended for (e.g., guidance documents are not internal FDA policy and procedure documents). It also clarifies that guidance documents are typically not legally binding for either sponsors or the FDA.
• The GGP describes how the agency solicits or collects feedback on guidance documents, including in advance of publication. Documents are generally issued in draft form, and the FDA will then collect comments on the document for a set period of time before working to finalize it. Some guidance documents are eventually finalized; others are revised in draft form or never finalized.

Last year, the FDA was asked to draft a report related to its guidance development and communication process

• The December 2022 passage of the Food and Drug Omnibus Reform Act (FDORA) included Section 2505, Improving FDA Guidance and Communication. The section called on the FDA to develop and publish a report “identifying best practices for the efficient prioritization, development, issuance, and use of guidance documents, within centers, across the Food and Drug Administration, and across other applicable agencies,” and a plan to streamline development of guidance documents and implement “innovative guidance development processes and practices,” among other things.
• This section also calls for a report on “Best Practices for Communicating With External Stakeholders,” which will review the FDA’s methods to broadly communicate with external stakeholders other than through guidance documents. This report also asks for the identification of best practices for the development and issuance of those communications and a plan to implement those best practices. The plan is specifically instructed to include ways to “advance the use of innovative forms of communications,” including novel document types and formats, new tools like product submission templates and FAQ documents, streamlined processes for regulatory submissions, and more. The legislation specifically calls out improvements that the FDA made during the Covid-19 pandemic and asks that the agency consider wider application.
• Notably, the legislation calls on the FDA to consult with “stakeholders,” including researchers, academic organizations, clinical laboratories, healthcare providers, the life sciences industry, patient groups, and “other appropriate stakeholders,” to develop and publish the report.
• The report and plan are due by December 29, 2023. They will first be published in draft form and must then be finalized within 180 days of their publication, at which point the FDA must begin implementing the best practices part of the plan.
• To date, we haven’t heard anything from the FDA regarding a public input process for this report. Congress didn’t require the FDA to engage with all stakeholders through a public input process, so the lack of a formalized opportunity for input does not necessarily imply that the FDA is breaking the letter of the law, so long as they are actually working behind the scenes to solicit input. That said, the FDA could come under criticism for not following the spirit of the law with respect to stakeholder input by not issuing a public call for feedback.

But the big question remains: What improvements might the FDA suggest? AgencyIQ has a few ideas regarding what the FDA may propose.

• First, shifting away from the use of PDFs. The FDA is hardly alone in its use of Adobe’s Portable Document Format (PDF) to publish its guidance documents – many other regulators, such as the European Medicines Agency (EMA) and International Council on Harmonization (ICH), also use this format. However, the format does not lend itself to linking to specific parts within the documents, is not web-friendly (and especially not on mobile devices), is time-consuming for the FDA to put together and is difficult to update. It wouldn’t surprise us if the FDA proposes an eventual shift to a web-text based guidance document format, similar to what the U.K.’s Medicines and Health care Regulatory Agency (MHRA) now does. This would also add a searchability component to guidance documents that is currently missing.
• Faster publication: During the Covid-19 pandemic, the FDA prided itself on publishing guidance documents quickly and updating those same documents more promptly. While some of those documents were arguably not the agency’s finest work (as measured by the durability of the recommendations), they did manage to help minimize industry uncertainty and promote the development of important products. The use of more Q&A-style documents, in particular, might be preferable to both the FDA and industry, as they can be more easily updated based on new or emerging questions and information.
• Improving the commenting process: Earlier this year, FDA’s Center for Devices and Radiological Health (CDRH) unveiled a new webpage offering practical tips on structuring and submitting comments on guidance documents so as to ensure that industry comments are best able to be ingested by the FDA. If we had to guess, an efficient, modern commenting process would best be served by the FDA developing guidance comment “templates” – a guidance document on commenting on guidance documents, if you will.
• Soliciting regular input on guidance documents to develop: The FDA’s major product centers all publish guidance agendas on a semi-annual basis. However, the agency currently doesn’t offer a uniform process for soliciting public input on the guidance documents that stakeholders think it should develop. That’s curious since the FDA’s Product-Specific Guidances (PSGs) do have such a public comment period. Under the Generic Drug User Fee Act (GDUFA) III Commitment Letter, FDA is instructed to “seek public input on prioritization of PSGs annually” during a public meeting on research prioritization. It could make sense for the FDA to expand this process further to apply to all guidance documents.
• Expanding FDA’s approach to “guiding” industry: During the Covid-19 pandemic, the FDA made frequent use of “ Town Hall”-style webinars, at which it offered FAQ-style advice on emerging topics. While the initial meetings were focused on diagnostics, the agency has since adopted the Town Hall approach for cell and gene therapies as well. While there are downsides to this approach – most notably that stakeholders may feel compelled to attend every single meeting lest they miss out on important advice, as transcripts may not be available for weeks or months – it does allow a glimpse into FDA’s real-time thinking about complex issues. We could foresee the FDA conducting more of these Town Hall events in fast-moving areas of important policy.
• Guidance prioritization: The FDA maintains a database of more than 2,700 guidance documents. Of those, 399 remain in draft form. Of these draft documents, 114 were published prior to 2018. The FDA would do well to prioritize either the finalization of draft guidance documents within a certain time period or the withdrawal of such documents if it feels they no longer represent the agency’s current thinking on the topic.

Beyond what the FDA might suggest, AgencyIQ has nine additional ideas for potential improvements:

• Creating a guidance dashboard: The FDA already has a guidance document database. Unfortunately, it only contains basic information on documents that have already been published (Issue date, issuing center, basic topics, draft/final status, and whether it’s open for comment). It doesn’t include guidance documents that are under development, documents that may no longer have the confidence of regulators (such as ones still in draft form after several years), or information on whether a guidance is expected to be revised or refreshed. That sort of information is extremely important for some stakeholders. For example, a pharmaceutical company planning to develop a drug using a clinical development approach recommended in a years-old guidance document might want to know if the FDA is no longer confident in that approach before embarking on an expensive, multi-year trial.
• Guidance summaries: Guidance agendas published by FDA Centers generally only provide the title of the proposed guidance. That differs significantly from the FDA’s Unified Agenda for regulations, for which the FDA will provide both the title of the proposed rule and a summary statement of what it hopes to accomplish. Absent a similar summary statement for guidance documents, stakeholders are left to guess as to the FDA’s intent. Summaries would allow stakeholders to assess what the agency is thinking about doing.
• Getting FDA Centers on board with the same Guidance Agenda philosophies: As AgencyIQ has previously explained in greater depth, each FDA center uses slightly different criteria and philosophies for its guidance agendas. CBER publishes a relatively short list of guidance documents it proposes to publish in draft or final form during the calendar year. CDER publishes an expansive list of proposed draft, but not final, guidance documents that are under development each calendar year, and typically does not publish the significant majority of those documents. CDRH, meanwhile, publishes a fiscal-year based list of guidance documents that are expected to be published in draft or final form, with a further breakdown into prioritized “A” and “B” lists. CFSAN publishes a relatively modest list of draft and final guidance documents it plans to publish in the calendar year. This divergent set of processes doesn’t make much sense. It would be better for centers to adopt a single set of best practices: A fiscal year calendar (corresponding to FDA’s fiscal year) with both draft and final guidance documents under development, prioritized into a list of high-priority, moderate-priority and low-priority, of which the latter would reflect documents under development, but not actively so.
• Create an agency-wide list of guidance documents under development: An agency-wide Guidance Agenda would be beneficial since there are other sources of guidance (such as the Oncology Center of Excellence) which do not currently release guidance agendas. Guidance documents developed in partnership between various centers also do not typically appear on guidance agendas.
• Use control numbers: Like a new regulation, the development of a new guidance document can take years – even decades. But unlike federal regulations, for which regulators assign unique tracking numbers known as a Regulatory Identifier Number (RIN) that allows tracking across time, the FDA assigns no such tracking numbers to its guidance documents. That makes it difficult to determine where guidance documents are within the development process, or even if documents have changed names since initial inception. A Guidance Information Number (GIN) could be assigned at the time a guidance document is first added to a guidance agenda, be tracked on a centralized dashboard by the FDA, carry through to the White House’s Office of Information and Regulatory Affairs (OIRA) in the case of certain high-profile guidance documents requiring review and clearance, and be listed in the document upon publication. Critically, it would also help to determine which guidance documents that were under development have since been published, making it easier to assess what the agency might be working on next.
• Change documentation: When the FDA publishes a final guidance document, one of the biggest questions that stakeholders have is: What changed in this guidance relative to the prior version? That’s a question that AgencyIQ helps our subscribers solve through our guidance comparison tool, but it’s also a question that the FDA really ought to be answering on its own – and in greater detail. There are a few changes that FDA could consider, including publishing a track-changes version of the guidance listing every single change that was made and also explaining why specific changes were made. This would help to provide clarity as to the intent of the changes rather than leaving stakeholders guessing.
• Rethinking the comment process: The FDA doesn’t control all aspects of its guidance document process. If someone wants to comment on a guidance document, they need to submit that comment through Regulations.gov, which is managed through the General Services Administration (GSA). While that isn’t unusual from a regulatory agency perspective, it does subject the FDA to at least one significant problem: The submission of form letters. On some federal dockets, the FDA receives literally thousands of pre-written letters to which advocates sign their name, but generally change little (or nothing) else. That makes it profoundly difficult to identify unique comments raising novel issues or offering support for a proposal. The FDA may wish to work with the GSA to develop tools to either discourage form letters or to better organize or filter them.
• Rethinking the comment period: Typically, when a guidance is drafted and published, the FDA opens either a 30-day or 60-day comment period. However, some documents are inherently more complex, resulting in requests for extensions. In general, any guidance that either proposes major, sweeping changes or is intricately connected to other documents (such as a series of guidance documents which must all be understood collectively) typically receives a request for additional time to comment. The FDA may wish to consider a default extension of comment deadlines for these types of major guidance documents (for example, to 90 days) to improve the quality of the comments it receives and reduce the number of petitions and extension requests from industry.
• Eliminate the distinction between Level 1 and Level 2 guidance: As noted above, there are two types of guidance documents, with Level 1 guidance being considered significant and Level 2 being considered non-significant. In practice, however, the only difference we have seen over the last decade is that the FDA publishes Level 1 guidance documents in the Federal Register, whereas Level 2 guidance documents are published with no fanfare, leaving stakeholders to stumble upon them and guess why they weren’t announced. Our advice: Announce them both equally and explain the reasoning for the classification.

To contact the author of this item, please email Alec Gaffney ( [email protected]).
To contact the editor of this item, please email Chelsey McIntyre ( [email protected]).

Key Documents and Dates

• Food and Drug Omnibus Reform Act (FDORA), Section 2505
• December 29, 2023 – The date by which the report and plan must be published
• 21 CFR 10.115 Good guidance practices