[Stability Testing related News – vol.55]

◆  EMA and FDA update Principles for Parallel Scientific Advice in the Marketing Authorization Process (1-Sep-21 ECA)

The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) each offer applicants for marketing authorization of a drug or investigational medicinal product the opportunity to seek scientific advice on specific issues related to the development of a drug product. For pharmaceutical companies seeking approval in both the EU and the U.S., consultation with one or the other agency can often result in additional work due to duplicate testing and divergent testing methods because of differing standards and guidelines in the respective approval process. The possibility of a Parallel Scientific Advice (PSA) procedure, in which both regulatory authorities are involved at the same time, provides a remedy for this and has already existed for several years. The basic principles for this procedure have now been renegotiated between the EMA and the FDA and published in the document “General Principles EMA-FDA Parallel Scientific Advice (Human Medicinal Products)” on the websites of both authorities in July 2021.

The core contents of the updated Parallel Scientific Advice procedure are summarized below.

Target group of the PSA procedure
Sponsors or applicants seeking approval for an investigational new drug (IND) in the U.S. or a new drug or biologic drug (New Drug Application, NDA, or Biologic License Application, BLA) and simultaneously seeking marketing authorisation in the EU are eligible for this process.

Preferred drug categories for the PSA procedure
Medicinal products for which the procedure will bring the greatest benefit are, for example, oncological preparations, anti-infectives, medicinal products for rare diseases, pediatric medicinal products, medicinal products for the therapy of cardiovascular diseases, and medicinal products with indications for the development of which no or divergent guidelines exist.

Purpose and framework of the PSA procedure

• The purpose of this procedure is to clarify and, to the extent possible, harmonize the different regulatory requirements and approval-related standards, with the goal of avoiding duplicate or divergent testing at the sponsor/applicant site. Harmonized scientific advice is intended to advance the development process of the drug in question, with the goal of accelerating or at least not delaying the approval process for the European and U.S. markets.
• The basis of the procedure is the full exchange of information – including information that is subject to confidentiality – between the two authorities and the applicant. The authorities are obliged by their respective regulations to keep this information confidential from third parties.
• The request to the authorities for approval of a PSA should be limited to a specific problem in the development of the drug.
• Only one PSA will be approved per drug product.
• A request for a PSA may also be denied. In this case, the sponsor/applicant is free to initiate the respective individual consultation with the EU and FDA. Alternatively, a so-called consultative advice procedure is possible. In this case, a consultative procedure is initiated with one authority and at the same time the other authority is informed. The other authority is then only involved in the discussions on the most important problems.

The result of the consultation, the written recommendation, is then only sent by the authority where the consultative procedure was initiated.

Procedure and duration of the PSA process
Requests for a PSA should be sent to both authorities at the email addresses provided in the “General Principles…” document. The request should include the following information:

• The drug product under development
• A rationale as to why concurrent consultation between assessors from EMA and reviewers from FDA would be beneficial
• Specific issues that should be clarified
• Goal statement for the joint meeting
• An explicit authorization for full information sharing between the two agencies

No later than 70 days after approval of the PSA, the sponsor/applicant receives a confirmation letter via email from each authority, indicating the contact person who coordinates the procedure. In the PSA Joint Meeting (tele- or videoconference), representatives of both authorities and the sponsor/applicant participate to discuss the issues and seek clarification. If necessary, a pre-sponsor meeting can be held before or a post-sponsor meeting after the joint meeting, in which only the representatives of the two authorities participate.

The individual phases with the respective time windows and the total duration of the procedure are clearly presented on two charts on the EMA website.

A detailed description of all aspects of the EMA’s advisory procedure can be found on its website under the heading “Scientific advice and protocol assistance“.

◆ USP with new Chapter on Supplier Qualification and Guidance for associated Risk Assessments (15-Sep-21 ECA)

As indicated earlier this year, the U.S. Pharmacopeia USP intends to publish a new informational chapter on Supplier Qualification. It was proposed by the General Chapters-Packaging and Distribution Expert Committee. The chapter will get the number <1083>, the former number of the proposed chapter on Good Distribution Practice GDP, which was dismissed.

The aim is to “discuss the importance of supplier qualification and the application of a quality risk-based approach to select, assess, approve, and monitor suppliers of materials and services“. Core of the proposal is a six-step process:

• Preparation
• Identification and selection
• Evaluation and acceptance
• Performance monitoring
• Disqualification
• Conditional approval of an existing supplier

For each of these steps, expectations and the rationale of tasks are provided. It is also pointed out that quality risk-based approaches should be used and implemented throughout the process steps. A separate table lists examples of various items that can be considered as part of such a risk assessment. Even though the USP has no direct force of law, certainly not in Europe, interesting pointers for use in risk-based supplier qualification programmes can be found here.

The draft can be viewed in the Pharmacopeial Forum. (Please note: a one-time registration is required to access the Pharmacopeial Forum.)