EMA/FDA joint Q&As on Quality and GMP aspects of Breakthrough Therapy Applications

Recommendation

7/8 May 2024

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The FDA and the European Medicines Agency (EMA) published "EMA–FDA joint Q&As on Quality and GMP aspects" supporting quality development for FDA’s Breakthrough Therapy (BT) and EMA's Priority Medicines (PRIME) programs.

The Q&As are a result of a 2018 workshop held by both FDA and EMA where regulators and industry discussed quality challenges and scientific and regulatory approaches for facilitating development and preparation of pharmaceutical quality data packages. The conversations focused on enabling timely access to medicines for patients while keeping in mind the importance of drug safety, efficacy, and quality and maintaining current regulatory standards of approval. FDA and EMA have engaged in further discussions on these topics, sharing their experiences and regulatory expectations in the context of PRIME/BT applications, and the Q&A document is the result of these discussions.

For  the EMA, these Q&As are applicable to chemical and biological medicinal products for human use, including complex biologicals (such as ATMPs). However, for the FDA, the Q&As are only applicable to CDER-regulated products. Therefore, CBER -regulated products, such as advanced therapy medicinal products (ATMPs), are not in the scope of the document.

The document contains the following four Q&A sections: 

• Q&A on Control Strategy 
• Q&A on Process Validation 
• Q&A on Alternatives for determination of re-test period or shelf-life
• Q&A on GMP 

Post-Approval Change Management Protocol (PACMP)

While a proposed control strategy may be acceptable for initial approval, there may be a need to revise specifications post-approval when additional information becomes available. For example:

• Revising acceptance criteria using information gained from additional manufactured batches
• Re-evaluating acceptance criteria based on additional clinical experience
• Adding an orthogonal or replacement method that was under development at the time of approval

In this context, the use of a post approval change management protocol (PACMP), as described in the ICH Q12 guideline, is a possible tool that could be used.

GMP Considerations

An investigational medicinal product (IMP) manufacturing process and facility should meet at least the following conditions to be acceptable to start commercial manufacturing from:

• The facility should be GMP compliant
• The manufacturing process should be fully validated using robust Quality Risk Management (QRM)

Any differences in the GMP approach at the IMP facility (for initial commercial manufacturing) compared to a commercial production, should be fully assessed and the potential impact on product quality should be identified, controlled, and mitigated utilizing QRM. The applicant and manufacturing facility should justify these approaches to the regulator. In addition, the applicant, should provide a detailed plan for the development and transition to a full commercial manufacturing process at the intended commercial manufacturing facility, including demonstration of comparability between the process used for launching and the intended commercial process (e.g. as a PACMP). Moreover, there should be a post-marketing CMC commitment specifying when the commercial manufacturing will be fully established.

For more information please see the document "EMA–FDA joint Q&As on Quality and GMP aspects of PRIME/Breakthrough therapy applications".