Quality experts conduct tests on the cells ready for injection back into the patient to confirm Identity, Purity, Safety and Potency (*1).
The life of patients relies on the quality of the immunotherapy product. In accordance with GLP, each stage of production is subject to quality controls:
Control of production materials, In-process control & testing, release testing, validation of the production process, stability study, …
Good practices, recommendations and guidelines are provided by the European Medicines Agency and controlled by the Committee for Advanced Therapies (CAT) who is responsible for assessing the quality, safety and efficacy of advanced-therapy medicines.
Your challenges
- How to check purity and effect of other cell types and carry over from manufacture? What can I use as Cell based standards?
- Are you prepared to automated high throughput sample analysis and cell culture automation?
- How precise is your automated handling of small sample volumes?
- Is your cell counting and viability analysis method automated, easy and reliable? Can you answer data integrity questions from auditors?
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 or materials used in the preparation of the cell therapy product includes cells, vectors for gene modification, culture mediums, cytokines, various additive components, cryoprotectants, excipients, and so forth. The materials used for production are directly related to the quality of the products. Therefore, researchers should establish a good and standardized quality management system for production materials, including risk assessment of their use, auditing of suppliers, and quality testing.
In-process control & testing
These control and testing includes monitoring process parameters and achieving the objectives of process control, and the quality of cells during the preparation process.
Goal is to ensure the
repeatability
of the production process and
batch-to-batch consistency
of the final products.
Release testing
These final tests are conducted in order to ensure that the product’s identity, purity, safety, and effectiveness meet the requirements. These characteristics of the cell products should be tested by means of various methods, with the products being released only if they are qualified and certificated. Also for clinical trials, quality control items should generally include product identification, biological efficacy, purity, impurities, cell number (i.e., live cell count, number of functional cells, etc.), and general detection (e.g., sterility, mycoplasma, endotoxin, and appearance).
Validation of the production process
For the whole process, comprehensive process characterization and process validation of multiple continuous batches (at least three batches) of production are required.
Stability study
Well-controlled cold chain transport and storage play an important role in ensuring the quality of cell products and preventing the occurrence of bacteria and mycoplasma contamination. It is recommended that the investigative items include cell characteristics, biological potency, cell purity, number and ratio of living cells, cell count, and safety-related tests.
Definition
(*1) Potency test
Biological activity is the specific ability or capacity of the product to achieve a defined biological effect.
Potency test is the measure of the biological activity using a suitably quantitative biological assay (also called potency assay or bioassay), based on the attribute of the product, which is linked to the 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 is an important parameter of product integrity and may be used as an in-process control after manipulation of certain cell characteristics e.g. up-regulation of cell surface expression of specific antigens after cytokine treatment. Cell viability may also be an important element of the potency of cell based products. However, it should be linked with other measures of potency that demonstrate the potential for biological activity of the product, such as quantitative antigen expression or biological activity as 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 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 3 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
.
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