Revamping OND: Drugmakers Offer Suggestions
Pfizer, Amgen, Sanofi, Regeneron, Janssen and others sent comments earlier this week to the US Food and Drug Administration (FDA) on ways to improve the Office of New Drugs (OND).The comments follow the ongoing reorganization of OND and a public meeting at FDA in November, where OND division leadership received input on areas that may need additional guidance or scientific discussion.
Drugmakers offered OND several suggestions, some of which focused on applying guidance consistently, novel clinical trial designs and the use of more case studies from the agency to better set expectations.
On the inconsistencies of applying guidance, Pfizer pointed to ICH’s E1A guideline, which 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 Pfizer said it sees “wide variation in actual expectations across divisions.” Pfizer also pointed to inconsistencies around “‘waiving’ collection/submission of non-serious adverse events for drugs that have a well characterized safety profile” described in a 2012 guidance.
Sanofi added: “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.”
Janssen, meanwhile, called on OND to facilitate more “quick and informal” communications with sponsors. The company noted that 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. But simulated use testing had already been submitted in the supplier’s 510(k), which was referenced in the biologics license application (BLA), so Janssen said it was unclear what additional information the agency was requesting. Eventually, Janssen said the ambiguity was resolved with a simple clarifying question in a Type C meeting, but an informal meeting could have quickly provided the necessary guidance.
Sanofi also called for more FDA analyses of data underlying regulatory decision-making and review division activities that can help inform similar development strategies.
Similarly, Amgen called for accumulated FDA experience to be shared “more quickly and broadly. We recommend that 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.”
On novel trial designs, Amgen explained how the Complex Innovative Trial Designs (CID) pilot “provides 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.”
Advice provided by different regulators around the world on innovative trial designs can sometimes be different or conflicting, increasing the uncertainty of pursuing an innovative approach, Amgen added.
Regeneron focused its comments on the broader use of genomic data, noting that FDA “should strongly consider the utilization of genomic information as a component of the efficacy and safety evaluation of new drugs, and fundamentally, as a valued source of substantial evidence in regulatory decision-making.”
In addition to the companies, industry group PhRMA also weighed in, specifically calling for additional guidance on the development and use of natural history study data as an external control group or the use of synthetic control arms.
Comments