FDA, EMA Parallel Scientific Advice is Effective: Study

Four FDA and European Medicines Agency staffers who work in the joint parallel scientific advice (PSA) program say their evaluation of program activity from 2017 through 2021 demonstrated its value to product sponsors and the two agencies. Writing in Therapeutic Innovation and Regulatory Science, the four say the program “provides a mechanism for experts to concurrently engage in scientific discussions with sponsors on key issues during the development phase of new drugs, biologicals, vaccines, and advanced therapies.”

As part of the process, the report says, both agencies engage with each other to compare perspectives in advance of and during the actual interaction with the sponsor. The program was launched in 2005 to:

• increase dialog between the two agencies and sponsors from the beginning of the lifecycle of a new product;
• provide a deeper understanding of the bases of regulatory decisions;
• optimize product development; and
• avoid unnecessary testing.

While the agencies don’t commit to harmonizing advice, in bilateral meetings they can discuss the sponsor’s questions and focus on sharing information and their perspectives to identify areas of convergence and divergence, the staffers write. In sharing their respective preliminary feedback with the sponsor in writing, they add, including requests for further clarification and discussion, the sponsor has an opportunity to plan for more in-depth discussion during a subsequent trilateral meeting.

“It is common for PSA trilateral discussions to result in a convergence in advice on approaches to a product’s development even though full harmonization is not always possible,” the report says. “And in cases of divergence, the trilateral meeting is an opportunity for the sponsor to offer proposals for how to meet both regulators’ requirements without having to explain each regulator’s perspective to the other. Even when agencies maintain differing perspectives, an important benefit of PSA is that all parties in the process understand the reason(s) for the divergence.”

The five-year review found that uptake of the PSA pathway has been limited, with four to seven procedures annually. “Although not easy to quantify,” the authors conclude, “our experience has been that once underway the outcome of the process is remarkably productive and positive for all parties. The interactions between the two regulators are critical and serve as a form of peer discussion, an opportunity to expand thinking and explore ways to address common challenges in drug development together, especially in areas where there is little experience or thorny scientific issues at hand.”

The FDA and EMA staffers suggest these strategies for sponsors who are considering PSAs:

• consider the timing of the request as it is strongly recommended to have begun the pre-IND or IND process at FDA before requesting PSA so there is a baseline for reference;
• research existing guidance on the topic to see potential alignment or divergence between the two agencies;
• consider the public health benefit of the product since additional agency resources are needed for PSAs and thus the program focuses on products that address unmet needs, rare diseases, pediatric populations, or other areas of importance to patients and public health; and
• make the best use of the trilateral meeting by focusing on the most critical scientific questions and preparing proposals and rationales that address the issues noted in the preliminary feedback from each agency.

Given the success of PSA so far, FDA and EMA launched in 2021 a pilot PSA program for complex generic products in hopes that it will be a tool for optimizing the global development of products for which traditional bioequivalence methods are challenging.