Moving the site of manufacture for commercial cell banks, microbial or mammalian, the renewal of working cell banks for commercial products, or making minor changes to cell banking processes is becoming more onerous from a regulatory perspective and does not have a consistent harmonized approach even within a single regulatory body such as the FDA.
In the past analytical comparability of cell banks was acceptable and this changed to requiring some drug substance comparability data that could be satisfied with small/pilot scale models. The current expectation of the FDA is that drug substance comparability is performed at the commercial scale as well as a comparability demonstration at the commercial scale for drug product. However there seems to be little or no consistency as these requests can vary from just a single to three batches.
As a result it is becoming increasingly onerous to make or move the manufacturing location of an operational cell bank. Leading to significant additional work before product approval and adding a huge cost to the industry, especially for multi-valent vaccines.
The intention of BioPhorum Drug Substance is to form a collaboration team of subject matter experts to develop a white paper to initiate the establishment of an industry wide harmonised, science-based approach to the safe management of making and moving operational cell banks for commercial products. This paper for will enable the group to align with regulatory authorities and propose minimum filing requirements that will:-
- Adopt one clear and consistent approach to this issue
- Apply scientific-based criteria to the characterization and comparability approach for changes to cell banks. The relative risk for a product should determine the amount of data that is reasonable for comparability
- If the FDA is unwilling to modify requirements, adopt a staged way to gain approval for a product and provide commercial batch data for drug substance and drug product when it is available post- approval