Regulatory Open Forum

Hi.

For master cell banks (MCBs) and working cell banks (WCB) I have always registered the facilities for MCB and WCB manufacturing and testing (qualification) in Section 3.2.S.2.1 of a US biologics license application (gene therapy products, CBER). However, a recent question got me thinking...

If you only want to add the activities of cell bank production and testing and the site is already listed in S.2.1 - what is your opinion as to how this should be registered? Tell and do (CBE)? Do and tell (annual report)? Something else?!

I'd value any experiences RAPS members can share. Also for master virus seed/working virus seed.

Is this approved product? isn't the activities of cell bank described under manufacturing process already in your application?

Dear Anon,

The original question was referring to BLAs. Thus, all commercial regulations regarding manufacturing changes should apply. However, the important thing to know is how you define your MCB and WCB. Is it a starting material for a drug substance or drug substance intermediate, or a final drug product cell bank (e.g., an allogeneic cell therapy). Without understanding the definition and context of the cell banks used in the manufacturing process, it will be difficult to answer. The definition of a cell bank in CGT manufacturing process needs to be clarified and risk assessed before adequate regulation is applied to answer this question.

Dear Anon,

The original question was referring to BLAs. Thus, all commercial regulations regarding manufacturing changes should apply. However, the important thing to know is how you define your MCB and WCB. Is it a starting material for a drug substance or drug substance intermediate, or a final drug product cell bank (e.g., an allogeneic cell therapy). You stated that you have always registered the cell banking facility in 3.2.S.2.1, implying it is not a drug product cell bank. If it is a starting material for DS or DS intermediate, you should describe it in 3.2.S.2.3. Without understanding the definition and context of the cell banks used in your manufacturing process, it will be difficult to answer. The definition of a cell bank in the context of your CGT manufacturing process needs to be clarified and risk assessed before adequate regulation is applied to answer this question.