1. INTRODUCTION
This general chapter is intended to provide users with practical guidelines regarding the derivation, production, storage, characterization, and qualification of bacterial and mammalian cell banks used in the manufacture of biological drug products. The chapter is primarily focused on the characterization of cell banks used to produce biological products that are subject to approval by the US FDA. Cell banking characterization and qualification should be based on sound scientific principles and current regulatory guidance. The relevant requirements and guidances for generating cell banks for biotherapeutics seeking FDA approval include the US Code of Federal Regulations (21 CFR Part 610.18) (1), FDA Points to Consider documents (2–4), FDA Guidance for Industry documents, and International Council for Harmonisation (ICH) guidelines (5–8). These guidances state that the final biological product and production should be consistent, uniform, and free from cellular and adventitious contaminants. [Note—It is recognized that there are also relevant guidances from other international organizations such as the World Health Organization (WHO) and European Medicines Agency (EMA); however, this chapter focuses on US FDA, USP, and ICH regulations and guidances.]
Therefore, the intent of this chapter is to elaborate on principles noted in FDA and ICH guidances and in USP general chapters for the establishment and characterization of mammalian and bacterial cell banks used in the manufacture of biological products. This chapter represents current best practices for the production, characterization, and maintenance of controlled and consistent cell sources using risk-based and product-phase-appropriate quality considerations.
The evaluation of the risk to quality (9) should be based on scientific knowledge and ultimately link to the protection of the patient; the level of effort, formality, and documentation of the quality risk management process should be commensurate with the level of risk. Regarding good cell line banking practice, risk analysis should be conducted on the basis of existing experience with the type of cell line and should be updated throughout the cell line’s product life cycle as further knowledge is gained to characterize the associated risks. The risk criteria for good cell line banking practices should include such quality risk factors as:
Cell line history and origin
Cell line growth and characteristics (relevant phenotypic and genotypic markers)
Cell count
Viability
Authentication
Absence of adventitious agents (e.g., microbial, fungal, viral, and mycoplasma contaminants)
Genetic drift (e.g., transgene stability)
Loss of cell line characteristics of interest (such as the host cell transformations, surface antigens, or monoclonal antibody expression)
Process validation and capability
In-process controls,
Change controls
Cross contamination
Testing
Stability
Storage
Product/process trending that demonstrates the original cell line characteristics and resultant quality characteristics of the final product that are retained throughout the cell line and product’s life cycle
Over time and experience—through feedback from the quality systems, trending, post-marketing surveillance and pharmacovigilance systems—the risk assessment should continue to evolve to minimize the risks associated with the cell line’s performance during the product's life cycle.
Source from USP and Please refer to USP for details:
Polymer Vial for cell and gene therapies
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