Quality experts test the cells prepared for reinjection into the patient to confirm their Identity, Purity, Safety and Potency
(*1).
Patients' lives depend on the quality of the immunotherapy product. In line with GLP, every production stage is subject to quality controls:
Control of production materials, in-process control and testing, release testing, validation of the production process, stability study, and more.
Good practices, recommendations and guidelines are issued by the European Medicines Agency and overseen by the Committee for Advanced Therapies (CAT), responsible for assessing the quality, safety and efficacy of advanced-therapy medicines.
Your challenges
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How do you check the purity and effect of other cell types and carry-over from manufacturing? What can you use as cell-based standards?
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Are you ready for automated high-throughput sample analysis and cell-culture automation?
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How precise is your automated handling of small sample volumes?
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Is your cell counting and viability analysis automated, easy and reliable? Can you answer auditors' data-integrity questions?
Our Solutions for your Workflow
Cell culture QC lab
- Air sampling for viable particle monitoring in clean rooms
- Laminar flow, CO2 Incubator, Centrifuge
- Cell counter and viability analyzer, Cell imager, Cell sizer, Cell culture media bioanalyzer, Cell Culture Automation
Flow cytometry QC Lab
Biochemistry QC lab
Molecular Biology QC lab
- Laminar flow cabinet, working with DNA, PCR Setup, qPCR
- Gel documentation, Microplate washer and microplate reader for ELISA
- Shaker, bath, microcentrifuge, high performance centrifuge
Microbiology QC Lab
- 20-25°C refrigerated incubator , Biosafety cabinet, centrifuge
Raw Material QC Lab
- Fume Hoods, Microwave Digestion System for leachable, extractable & trace testing of Pharmaceutical Packaging
- Fridges, freezers and deep-freezers +4°C to -80°C, Liquid N2 Cryogenic preservation
- Precision measurement of vial, syringe, injectors
- Stress resistance or hardness testing of containers
Lab Furniture
Quality control testing categories
In general, quality control testing is also classified into the following categories:
Control of production materials
The substances and materials used to prepare the cell therapy product include cells, gene-modification vectors, culture media, cytokines, various additives, cryoprotectants, excipients and more.
Because these materials directly affect product quality, researchers should set up a robust, standardised quality-management system for them — including risk assessment of their use, supplier auditing and quality testing.
In-process control & testing
This covers monitoring of process parameters, achievement of process-control objectives, and the quality of the cells during preparation.
The goal is to ensure the repeatability of the production process and batch-to-batch consistency of the final products.
Release testing
These final tests confirm that the product's identity, purity, safety and effectiveness meet requirements. The cell product's characteristics are assessed by various methods, and products are released only if they are qualified and certified.
For clinical trials, quality-control items generally include product identification, biological efficacy, purity, impurities, cell number (live-cell count, number of functional cells, etc.) and general testing (sterility, mycoplasma, endotoxin and appearance).
Validation of the production process
For the whole process, comprehensive process characterisation and process validation of several consecutive batches (at least three) are required.
Stability study
A well-controlled cold chain during transport and storage is key to maintaining cell-product quality and preventing bacterial and mycoplasma contamination. Recommended items to investigate include cell characteristics, biological potency, cell purity, the number and ratio of living cells, cell count and safety-related tests.
Definition
(*1) Potency test
Biological activity is the specific ability of the product to achieve a defined biological effect.
A potency test measures biological activity using a suitably quantitative biological assay (also called a potency assay or bioassay), based on the product attribute linked to its relevant biological properties.
One of the requirements included in
Directive 2003/63/EC (Annex I, part IV)
is that human somatic cell therapy medicinal products are made of a defined number (pool) of viable cells. Cell viability may also be an important element of the potency of cell-based products. However, it should be combined with other potency measures that demonstrate the product's potential biological activity, such as quantitative antigen expression or activity measured in the bioassay.
Cell Volume: One Crucial Indicator Among Many in White Blood Cell Health
Cell volume is an important indicator of white blood cell health and therapeutic potential – Beckman Coulter
Rich Jones, Ph.D., gave a talk at the Phacilitate Leaders Summit and World Stem Cell Summit titled 'Cell volume is an important indicator of white blood cell health and therapeutic potential.' Dr. Jones compares three technologies for determining cell volume.
Sources and references
Yonghong Li, Yan Huo, Lei Yu, Junzhi Wang, Quality Control and Nonclinical Research on CAR-T Cell Products: General Principles and Key Issues, Engineering, Volume 5, Issue 1, 2019, Pages 122-131, ISSN 2095-8099,
https://doi.org/10.1016/j.eng.2018.12.003
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Committee for medicinal products for human use (CHMP)
Guideline on potency testing of cell-based immunotherapy medicinal products for the treatment of cancer | European Medicines Agency (europa.eu)
. EMA/CHMP/BWP/271475/2006 rev.1 – Adopted 21 July 2016