Quality standards are often difficult to properly anticipate across today's global regulatory environments. In recent years, quality expectations have increased due to public demand and to government regulation. In addition, agencies such as the Food and Drug Administration (FDA) frequently change regulatory requirements without giving an absolute set of rules to follow. The regulations pertaining to parental cell lines (i.e., cells that are engineered to become production cell lines) leave room for interpretation. In this publication we explore some important considerations when determining quality standards for parental cell lines.
The regulatory standards for the characterization of master and working cell banks prepared from engineered cells that express a desired biotherapeutic product are provided in the following documents:
- FDA, 21 Code of Federal Regulations Part 610
- FDA Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals (1993)
- International Conference on Harmonization (ICH),
- Guidance for Industry: Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients
- Guidance for Industry: Q5D Quality of Biotechno logical/Biological Products: Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products
A crucial step is the choice of a suitable parental cell line. For recombinant products, a parental cell line is typically the untransfected recipient cell line. The use of characterized parental cell banks is suggested, but is not considered essential. A characterized parental cell bank may be of benefit, especially when multiple cell substrates are generated from the same parental cell type, by providing a set of information on which the quality assessment of the Master Cell Bank (MCB) can be based.