Cell Line Characterization and Product Testing for CHO-Derived Biopharmaceutical Products
Cell line characterization (CLC) must be performed on all Master Cell Banks (MCB), working Cell Banks (WCB), and Cells at Limit of in vitro age (CAL), or End of Production (EOP) cells in accordance with global regulations. This ensures the identity, purity, and safety of the cells and resulting biologic product.
The regulatory expectations and guidance for characterization testing of cell banks are outlined in various documents from the FDA, EMA, World Health Organization (WHO), and International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). Eurofins BioPharma Product Testing’s recommendations for cell line characterization, safety evaluation, and product testing for a CHO-derived biopharmaceutical product are summarized in this document. It outlines a testing strategy that should satisfy the latest guidance of global regulatory authorities, including the FDA and EMA.
A global leader in biopharmaceutical laboratory services, Eurofins BioPharma Product Testing network of laboratories provides clients with the tools and support to better manage their biopharmaceutical drug development process. Our vast capacity and extensive capabilities provide the greatest breadth of cGMP-compliant biopharmaceutical services in the industry.
The combination of our cell banking capabilities with our extensive characterization services provide clients with a single-source solution for all cell line, product, and package testing needs.
Why Choose Eurofins BioPharma Product Testing?
- We offer capabilities to prepare and characterize a wide variety of mammalian, insect, and avian cell banks, including master, working, research, bioassay, and ready-to-use cell banks.
- Our cGMP-compliant facilities include multiple Grade A/B suites with Animal Origin Free options and ISO 7 clean rooms with ISO 5 critical areas designed to meet current FDA/EMEA aseptic processing guidelines.
- We also offer a comprehensive package of safety testing services in the areas of microbiology, mycoplasma, genetic stability, viral safety, and biochemistry to support our cell banking capabilities. All of these services are provided with strict adherence to cGMP requirements and are designed to fully support the testing of biopharmaceutical products, including the testing of raw materials, cell lines, unprocessed bulk, purified bulk, and final product.
Cell Line Characterization and Product Testing
The MCB is the starting material for the entire GMP production process which makes the on time testing performed on these cells of great importance. MCB and EOP testing require the most extensive testing, including exogenous and endogenous viruses, and microbial contaminants. The EOP/CAL represents the worst case scenario in which endogenous viral contaminants may be amplified. Genetic characterization is performed to ensure identity and the stability of the cells throughout the production process. The MCB genetic profile is compared against the results of the EOP/CAL genetic profile.
WCB testing is performed to ensure that the bank is free from adventitious agents (i.e., bacteria, viruses, mycoplasma, fungi) that may have been introduced in production of the WCB. Full characterization is not required at this stage although the cell identity should be confirmed.
It may not be necessary to conduct all of the tests listed. We highly recommend a discussion to evaluate those factors that can influence which tests can be omitted or whether additional testing might be required. Sharing the testing strategy with your regulatory reviewer is always highly recommended to ensure regulatory expectations will be satisfied.
CHO-derived Product Testing
Testing for the release of unprocessed bulk (UPB), drug substance (DS), and drug product (DP) are also recommended. Lot release testing of UPB includes assurance of freedom from adventitious virus by in vitro screening and retroviral particle quantitation by TEM analysis. Mouse minute virus (MMV) has also been known to contaminant CHO manufacturing process and MMV by PCR testing should be considered for your UPB testing strategy.
As the industry is progressing, and the CHO manufacturing process is maturing, speed has become a substantial influencer in UPB release testing. Regulators are receiving more filings using faster test methods in place of the longer traditional 28 day test methods. For instance, regulatory bodies are seeing the industry move away from the 28 day in vitro adventitious agent, 28 day compendial mycoplasma test, and move to a 14 day in vitro adventitious agent test (in some cases adding a 4th detector cell line) and the 5 day rapid mycoplasma PCR method. This dynamic shift enables our manufacturing partners to move from a 35 day UPB release to a 21 day UPB release. We always recommend our clients speak with their regulatory reviewer prior to bridging to the shorter assay test methods.
Final product testing should include a final microbial sterility test, residual DNA, and host cell protein testing, as well as key compendial methods such as pH, appearance, osmolality, etc… Protein/mAb concentration will need to be performed, as well as other product specific test methods. Eurofins BioPharma Product Testing has a wide variety of instruments to conduct all compendial and product specific test methods. Phase appropriate validation should be considered for early stage clinical development while a full GMP product/matrix validation should be assessed for late stage and commercialization of any regulatory approved product. Eurofins BioPharma Product Testing can help navigate the early and late stage testing requirements.
Lastly, ICH stability programs will need to be considered to determine shelf life of your product candidate. Eurofins BioPharma Product Testing network of laboratories provides the GMP storage chambers, compendial test methods, and will transfer and validate any product specific test methods to ensure proper stability per ICH timelines.
