Methodological aspects of the development of product files for biomedical cell products

Preparation of a product file (PF) for a biomedical cell product (BCP) is an important stage in the preparation of documents for marketing authorisation. The PF is the main document of a regulatory submission and is used as the basis for BCP quality control. The requirements for the content of a PF, including appropriate specifications, are laid out in the relevant laws and regulations that support Federal Law No. 180-FZ “On Biomedical Cell Products” of 23.06.2016. However, given the novelty of the Russian legislative framework for innovative products for human use represented by BCPs, the specificity of their composition (i.e., components based on viable human cells) which differs significantly from conventional medicines, and lack of marketing authorisation experience— there is a need to examine specific aspects of a BCP PF. The aim of the study was to formulate methodological approaches to the development and preparation of a BCP PF in accordance with the national legislation and taking into account the experience of foreign regulatory authorities in evaluation of regulatory submissions for BCP analogues. The paper summarises the national regulatory requirements for the description of quality characteristics of cell lines used as components in BCPs, as well as test methods and test procedures used for cell line quality control. These data are required both for quality control of BCP samples, and for preparation of the Expert Commission Conclusion. The paper looks into the content of cellular and process-related impurities in a cell line and a finished BCP, and presents considerations on the description of the viral safety strategy for the finished product and for the cells from the master and working cell banks. The approaches to the presentation of quality characteristics and quality control methods for a finished BCP and for the cell line used in its production could be used by BCP developers for preparation of a PF.