Gene therapy products allow administration of nucleic acids to modify the genetic material of cells. Gene therapy products
can be broadly classified based on the approach to delivery and include the following: 1) viral vectors [viruses that harbor the
gene(s) of interest but usually without the mechanism to self-replicate in vivo]; 2) nucleic acids in a simple formulation (naked
DNA); and 3) nucleic acids formulated with agents such as liposomes that enhance their ability to penetrate the cell. Where
introduction of nucleic acid to cells takes place ex vivo, the cell population that is administered becomes the gene therapy
product. Guidance specific to the manufacturing, processing, characterization, and administration of cell-based products is
provided in ▲Cell-based Advanced Therapies and Tissue-based Products\
The FDA Guidance for Industry: Human Somatic Cell Therapy and Gene Therapy (March 1998) provides specific
recommendations for qualifying MCBs. Additional guidance is provided in ICH Q5D. A description and history of the cell line
is required, along with a description of the freezing process, storage conditions, and the number of vials prepared. The identity
of the cells should be analyzed by genotypic and/or phenotypic markers. For MCB containing vector sequences, the presence
and integrity of the vector should be demonstrated using molecular assays (restriction endonuclease mapping and/or nucleic
acid sequencing) and/or measurement of vector gene expression. Purity must be analyzed to exclude bacterial, mycoplasma,
fungal, and viral contamination (other than vector sequences). Freedom from adventitious viruses should be demonstrated
using both in vitro and in vivo virus tests and appropriate species-specific tests such as the mouse antibody production (MAP)
test. Special attention should be given to the detection of replication-competent virus (RCV) arising from recombination of the
vector and viral sequences. The MCB is further qualified by tests conducted on cells (from the MCB or WCB) expanded to the
limit of in vitro cell age for production
