EBE Position Paper: “A Risk-Based Approach to Identity Sampling of Biological Drug Substances”
Good Manufacturing Practices require that the identity of materials received for use in the manufacturing of drug products is confirmed. However, the direct sampling of primary containers of biological drug (active) substances at the biological drug product manufacturing site, after thaw can expose the biological drug substance to risks. The use of a representative sample taken at the biological drug substance manufacturing site to confirm identity avoids these risks.
There are basically two major international guidance documents for identity sampling of “starting materials” or “components”:
- Annex 8 of EudraLex Vol 4 GMP Guidelines – Sampling of Starting and Packaging Materials
- 21 CFR 211.84- Control of Components and Drug Product Containers and Closures: Testing and approval or rejection of components, drug product containers, and closures; with the explanatory Questions and Answers (Q&A) on Current Good Manufacturing Practices, Good Guidance Practices, Level 2 Guidance – Control of Components and Drug Product Containers and Closures.
Due to imprecise terminology, Annex 8 is subject to variable interpretation. Since “starting materials” are not defined in Annex 8, it is questionable whether Annex 8 is applicable to biological drug substance. However, with a literal interpretation of Annex 8, this guidance requires identity verification of ALL containers in a batch as soon as a parenteral application of the end product is intended.
The purpose of this position paper is to provide a framework for the Identity testing of biological drug substance without thawing, sampling and testing of each incoming main Biological Drug Substance container, because the risk of degradation and microbial contamination in case of 100% container-wise sampling may jeopardize the quality of the final biological drug product.
The position paper also provides recommendations for the adaptation of the current main international guidelines, to take account of the specificities of biological substances.
Read here the position paper.