ATMP The crux of penicillin

The group of Advanced Therapy Medicinal Products (ATMPs) enclose gene therapy medicinal products, somatic cell therapy medicinal products and biotechnological treated tissue products. Manufacturing of these medicinal products to the compliance of legal requirements of Good Manufacturing Practice (GMP) guidelines is a major challenge. Patient individual manufacturing, with marginal batch sizes and not completely standardized or rather not standardizable processes originated from university research, need a higher flexibly in the interpretation of GMP compared to the manufacturing of classic medicinal products. The new GMP guideline for ATMPs, valid since May 2018, incorporates the complexity of the manufacturing process. However, some questions concerning ATMP manufacturing, for example application of antibiotics, remain open.

Patient individual manufacturing requires autologous cells or tissues, whereas extraction in clinical institutes represents a concrete risk for contamination. To reduce bacterial contamination, antibiotic cocktails of penicillin/streptomycin are often added at an early stage of ex vivo culturing of cells or tissues.

This is in contradiction to the GMP guidelines comprising strict demands on the application of highly active substances like penicillin during pharmaceutical manufacturing. The application of penicillin is prohibited through manufacturing process of medicinal products and, to exclude a possible cross-contamination with penicillin or other substances of the beta-lactamases, the final product has to be analyzed for the absence of rather those compounds. The real challenge here is the establishment of an adequate detection system with equivalent validation.

Cultivation without antibiotics is also an alternative strategy, but in some cases, application of penicillin in ATMP manufacturing process cannot be avoided. The impact of contamination of the starting material used for production of the valuable ATMP and the risk for it’s unusability, must be considered. Finally , the loss of the medical product for patient´s therapy justifies the application of antibiotics preventing contamination.

But which options exist for ATMP manufacturer and how can the guidelines concerning the application of antibiotics be handled?

This is where Valicare can advise you and offer risk-based solutions. If you have further questions on this or other ATMP-related topics, please do not hesitate to contact us. Call us (0049 (0)69 7909 350) or send your question by email (info@valicare.com). We will forward you or your question to our ATMP specialists Dr. Claudia Papewalis and Dr. Hans-Georg Eckert.

Find out also about our services on the subject of GMP for ATMPs