By: Sarah Ibrahim, PhD, Associate Director of Stakeholder and Global Engagement, Office of Generic Drugs, CDER

CDER’s Office of Generic Drugs (OGD) and the European Medicines Agency (EMA) launched a voluntary pilot program to facilitate concurrent discussions between generic drug applicants and the two regulatory bodies, our ultimate goal was improving patient access to harder to develop generic drugs. This pilot program is an expansion of FDA and EMA’s existing Parallel Scientific Advice (PSA) program and focuses on complex generics/“hybrid medicines” (an EMA term for medications that loosely corresponds to complex generics).

Advancing complex generic drug development is a critical part of FDA’s goal to help patients access safe, effective and high-quality generic medicines. The generic drug industry faces several challenges such as increased competition, price erosion, and decreasing profit margins that may make it less attractive for companies to continue their generic drug operations. Complex generic drugs can offer significant market opportunities with potentially higher profit margins, but manufacturers may be challenged in developing these drugs because of a lack of expertise, methodologies, or supportive evidence.

Because of the extensive investments in research and development that may be needed, generic drug manufacturers and the regulatory agencies overseeing them are increasingly looking for proactive engagement opportunities during the early phases of drug development. Early engagement with regulatory agencies can enhance the scientific quality and validity of a generic drug applicant’s development plan and reduce the risk of regulatory hurdles or surprises later on.

The PSA Pilot Program

The PSA pilot program focuses on sharing information and regulatory perspectives and allows prospective generic drug applicants to engage in concurrent scientific conversation on key issues with both agencies during the development phase. Under the pilot program, applicants can request a joint meeting with FDA and EMA to address specific scientific inquiries pertaining to the development of complex generic drugs or hybrid medicines.

This joint meeting helps the applicant receive feedback from both regulatory bodies simultaneously, and work toward drug approval in both areas of the globe. It can also help align FDA and EMA’s scientific thinking on a particular drug application because there are potential differences in how the agencies assess these products under their jurisdictions.

Following a PSA meeting, an applicant should have a clearer understanding of the agencies’ regulatory requirements, scientific recommendations, and areas where the agencies may diverge. By streamlining the regulatory process, the pilot program can help applicants avoid redundancy in testing and ultimately accelerate the market access of the drug.

Prospective generic drug applicants may use the PSA pilot program to determine whether a study design, or designs, might be acceptable to both regulatory agencies. These include recommendations on comparative non-clinical and comparative clinical studies involving innovative bioequivalence (BE) study designs and methodologies such as modeling and simulation.

Examples of good candidates for the PSA program include:

1. Proposals for a single BE study that may satisfy both agencies, especially when FDA and EMA have different recommendations in their respective product-specific guidances.
2. Proposals for scientific approaches with data/information to support the use of a common comparator in BE studies that are acceptable to both agencies.
3. Proposals to use modeling and simulation to improve efficiency of the development program.

What We Have Learned So Far

To date, two applicants were granted PSA meetings and completed the PSA process. Based on preliminary assessment of the program, applicants have recommended the agencies provide procedural clarifications, clarify program timelines and expectations, and share best practices for meeting package preparation and participation. FDA and EMA intend to implement these key recommendations to further improve the PSA process.

We have also heard potential applicants may hesitate to join the PSA pilot program due to misperceptions that conflicting advice from both agencies could require additional testing, a lack of binding or enforceable commitments from the agencies could limit the value and impact of the PSA advice, and sharing confidential information may potentially compromise competitive advantages. However, this has not been the experience of the pilot applicants and these concerns may be unfounded. For example, safeguards for applicants are in place to protect confidential or proprietary information through confidentiality agreements and the redaction of sensitive data from the public documents.

Overall, the implemented pilot program provides a unique forum for increased global collaboration that is demonstrating long-term potential for both regulators and applicants. Pilot applicants have gained a greater understanding of the differences in processes and meeting expectations between the two agencies. The process has already helped regulators converge on scientific data needed to address specific challenges, reducing the need for an applicant to conduct additional testing. As more applicants take advantage of this pilot program, we believe it can be an opportunity to expand the number of generic drug applicants that submit applications to both agencies.

Moving Forward

FDA and EMA will continue to receive meeting requests until the agencies determine the number of completed PSA meetings is sufficient to assess the pilot program. During and after the pilot, each agency will continue to evaluate the benefits and challenges of the program and determine next steps. The PSA pilot program is an important opportunity for the generic drug industry to leverage the expertise and experience of both agencies to optimize their global generic drug development.

Generic drug applicants are encouraged to participate in the pilot program. Industry can request PSA meetings for complex generic drug products or hybrid medicines by sending a single “Request for PSA” justification letter to both EMA at emainternational@ema.europa.eu and FDA at preANDAHelp@fda.hhs.gov.