Following a public meeting at the United States Food and Drug Administration (FDA) in November 2019, a handful of drug makers sent comments and suggestions to the agency on how to reorganize and improve the Office of New Drugs (OND). Some of the companies to submit suggestions include: Pfizer, Amgen, Sanofi, Regeneron, and Janssen.
The comments include a variety of suggestions, with some focused on applying guidance consistently, others on novel clinical trial designs, and still others on better communications and guidance from the Agency about expectations.
Guidance Inconsistencies
For example, in its comments, Pfizer noted that the 1995 ICH E1A guideline specifies that “100 patients exposed for a minimum of one year is considered to be acceptable to include as part of the safety database,” but that there is “wide variation in actual expectations across divisions.” Pfizer also noted that it has seen/experienced inconsistencies around waiving the “collection/submission of non-serious adverse events for drugs that have a well characterized safety profile,” as outlined in the 2012 Agency guidance, Safety Reporting Requirements for INDs and BA/BE Studies.
Sanofi also touched upon inconsistencies in its comment, noting, “Often, due to lack of a broader line of sight into FDA decisional points or feedback, or other comparator data, companies rely on anecdotal experience to gauge and anticipate differences between review divisions. This approach can be susceptible to bias and misinterpretation. Broader, more holistic analysis of performance metrics and regulatory decisions can provide a more objective assessment of consistencies and differences in regulatory review.”
Novel Clinical Trial Designs
In its comments, Amgen discussed how the Complex Innovative Trial Designs pilot is a “good opportunity to address issues related to novel designs. However, more timely and iterative FDA advice is needed. Approaches taken for various aspects of innovative trials may be untried and require rapid feedback from FDA to reduce sponsor risk.” Amgen also noted that advice from different regulators around the world on innovative trial designs can be different, or even conflict, and that difference can increase uncertainty of a company around pursuing an innovative approach.
Guidance from the Agency
In its comments, Janssen called on the FDA and OND to facilitate more quick and informal communications with sponsors. The comments cited back to a specific instance where during a review of a combination product using a supplier’s 510(k)-cleared needle safety device, Janssen received an information request to justify not conducting simulated use testing. However, as simulated use testing had already been submitted in the supplier’s 510(k) and referenced in the biologics license application (BLA), Janssen was unclear what additional information the agency was requesting. Eventually, the ambiguity was resolved in a Type C meeting, but an informal meeting could have quickly provided the necessary guidance.
Amgen commented that accumulated FDA experience could provide helpful insights to sponsors and should be shared “more quickly and broadly.” Amgen made the recommendation that the FDA “share current case examples and information from its implementation experience by publishing FAQs or a Q&A section on FDA’s webpage associated with specific guidance.” Such a change would “allow for more timely updates with current information for sponsors to consider as FDA’s knowledge and experience develops.”
Conclusion
PhRMA also submitted comments and asked FDA to provide additional guidance on a handful of topics, including novel data sources, simulation and analysis, novel clinical trial designs, and novel statistical methods.
There were other comments made focused on different parts of the OND reorganization. If you are interested in reading more about the comments, they can be found here.