Ex Vivo Expanded Mesenchymal Stromal Cell Minimal Quality Requirements for Clinical Application

Abstract

Mesenchymal Stromal Cells (MSC), as advanced therapy products, must satisfy all the requirements for human use of medicinal products, aiming to maintain the quality and safety of the cells. The MSC manufacturing process for clinical use should comply with the principles of Good Manufacturing Practice (GMP). This ensures that cell preparations are produced and controlled, from the collection and manipulation of raw materials, through the processing of intermediate products, to the quality controls, storage, labelling and packaging, and release.The objective of this document is to provide the minimal quality requirements for the MSC production and its delivery for clinical use, so the safety of the final cell therapy product will not be compromised. For this purpose, the document evaluates the most important steps of GMP-compliant MSC production: the isolation and expansion process; the validation phase of the process, including all quality controls for the characterization, functionality, potency and safety of MSCs; the quality control at the batch release to guarantee the safety of patient infusion. This opinion paper reflects the consensus viewpoint of the authors and scientists participating the GISM Working Group*.

Mesenchymal stem cells – A new hope for radiotherapy-induced tissue damage?

“…Several publications have proposed minimal requirements regarding microbiological safety, preservation of the phenotype and functional potentials, and the absence of any transformation, e.g. due to genetic instability [115,[128][129][130]. If MSCs are to be widely used for patient treatment in the future, stringent and standardized quality control measures will have to be established to guarantee patient safety and reproducible treatment efficacy.…”

The Challenge of Human Mesenchymal Stromal Cell Expansion: Current and Prospective Answers

“…In addition to the regulatory framework, different societies and institutes have listed product characteristics that must be fulfilled [17]. One definition of hMSCs is provided by the International Society for Cell Therapy (ISCT) in their "minimal criteria for defining multipotent mesenchymal stromal cells" [18].…”

“…Prior to the product release, intensive quality control is required to confirm cell identity and safety according to validated protocols that comply with GMP, the International Conference on Harmonization (ICH) Guidelines and/or the European Pharmacopoeia [17].…”

Dental Stem Cells in Regenerative Medicine: Clinical and Pre-clinical Attempts

“…In addition, to be in compliance with GCP, the stem cell clinical manufacturing process should follow the principles of good manufacturing practice (GMP) [ 61 ], and clinical testing requires strict observance of good clinical laboratory practice (GCLP) [ 62 ]. In summary, to satisfy GMP protocols, cells must be strictly controlled starting from the collection and manipulation of raw materials (isolation), through the intermediate product processing (expansion process), to the quality controls (characterization, functionality, multipotency, and safety), storage (storage, labeling, packaging) and therapeutic use (transplantation, infusion into the patient) [ 63 ] (Fig. 13.3 ).…”