Special GMP for Cell Therapy Products: European Draft Guidance Gets Mixed Reviews
​[Posted on: Thursday, March 23, 2017]

Manufacturers of cell therapy products deal with several practical, logistical and scientific limitations much different from other biologic and drug products. Taking that into consideration, last year European Commission’s Directorate-General for Health and Food Safety (DGFHS), the governing body for the European Medicines Agency (EMA), released a draft guidance aiming to create special standalone rules for cell therapy products also known as Advanced Therapeutic Medicinal Products (ATMPs) at EMA. The proposed rules have been lauded by ATMP manufacturers for the effort to create an easier nuanced approach to GMP; and denounced by other organizations who felt that two rules, one for ATMPs and another for non-ATMPs (the existing rules) will create confusion and allow ATMP manufacturers to follow riskier practices. A careful review of the draft document shows that DGFHS reviewed the existing GMP rules in the context of cellular therapies and proposed ways where taking a risk-based approach (RBA) could reduce the burden on ATMP manufacturers while providing specific feedback on what would or would not be acceptable both for investigational stages and the commercial release. The document seems to be based on common questions and concerns raised by ATMP manufacturers when trying to follow the conventional GMP rules that could be very stringent particularly for cellular therapies. The primary concern raised by most critiques was the standalone nature of the rules, thereby creating two sets of rules; one for ATMPs and another for non-ATMPs. Most critiques wanted the relaxed rules to be added on to the existing GMP rules as an addendum. On the other hand, the DGFHS/EMA seems to firmly believe that the GMP for ATMP must be separate from conventional GMP rules. Key areas of concern are the facility design, the handling of the raw material such as donor cells, the QC release methods, the role of the Qualified Person, and stability testing for the ATMPs. It is impractical for ATMP manufacturers to follow the conventional GMP requirements in these areas. The flexible approaches recommended by DGFHS seem to establish the minimum standards required to maintain acceptable quality and risk, while increasing the feasibility of reasonable production of cellular therapy products. Sponsors can go above the minimum standards if feasible but having a regulatory blessing to meet the minimum conditions will certainly be welcome. The concerns raised about two independent sets of rules are valid for large organizations that want to manufacture both kinds of products, but the draft rules do not prohibit the higher standards, just give the smaller manufactures a practical approach to minimize the risk to produce a cell therapy product. Do we need special GMP rules for cell therapy products? The short answer is yes, and this seems to be a pragmatic approach to get there.