Quality System and Regulatory Requirements for Stem Cell Banking: A Case Study for Mesenchymal Stem Cells

Background: Stem cells are highly promising resources for ap-plication in advanced therapy medicinal products (ATMPs) and drug discovery. That s why stem cell banks have been increas-ingly established all over the world in order to use in basic and translational research, as well as current and future clinical ap-plication. Research to ensure the quality, safety and efficacy of the final cell preparations intended for transplantation, nationaland international guidelines and regulations have been issued. Herein the implementation of a quality assurance system in-cluding the principles of Good Manufacturing Practice (GMP), Quality Risk Management (QRM) and a Quality Control (QC) system is one major concern. Quality assurance system regula-tions apply to all phases of cell collection, processing and stor-age as well as premises and equipment, documentation, per-sonnel training, quality control and the compliant handling. QC measures have to be taken to ensure that products have consist-ent potency, purity, safety and quality.Materials and Methods: A risk based approach and quality by design paradigm was used to define the Critical Quality Attrib-utes (CQAs) and Critical Process Parameters (CPPs) in mesen-chymal stem cells proliferation and banking. Risk Analysis and Mitigation Matrix (RAMM) was created and used to provide a parametric compromise where other risk tools.Results: The RAMM tool was applied to an example mesen-chymal stem cells banking process. The tool was applied in six stages as part of a risk management system. The first step was selecting the right team to be involved in the process de-velopment, product development, analytical method develop-ment, manufacturing and facilitator. Then CQAs was defined as the following: viral contamination, identity, viability, cellular count, sterility, mycoplasma, endotoxin, morphology and kary-otype. Process steps and material was defined in next steps. The RAMM was created and used a matrix of process input factors and quality attributes to assess risk and impact. The final step was to assist in defining which action would help mitigate risk for these process parameters.Conclusion: As a case study, we investigated the risk based mesenchymal stem cells banking process. However, strict regu-lations during banking processing have to be followed in order to guarantee the highest quality and safety for the patients.

Keywords:

Mesenchymal Stem Cells , Risk Analysis , Good Man-ufacturing Practice