title: Quality Control Assays for Clinical-Grade Human Mesenchymal Stromal Cells: Methods for ATMP Release.
abstract: Mesenchymal stromal/stem cells (MSC) are promising candidates for the development of cell-based therapies for various diseases and are currently being evaluated in a number of clinical trials (Sharma et al., Transfusion 54:1418-1437, 2014; Ikebe and Suzuki, Biomed Res Int 2014:951512, 2014). MSC for therapeutic applications are classified as advanced therapy medicinal products (ATMP) (Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004) and must be prepared according to good manufacturing practices ( http://ec.europa.eu/health/documents/eudralex/vol-4 ). They may be derived from different starting materials (mainly bone marrow (BM), adipose tissue, or cord blood) and applied as fresh or cryopreserved products, in the autologous as well as an allogeneic context (Sharma et al., Transfusion 54:1418-1437, 2014; Ikebe and Suzuki, Biomed Res Int 2014:951512, 2014; Sensebé and Bourin, Transplantation 87(9 Suppl):S49-S53, 2009). In any case, they require an approved and well-defined panel of assays in order to be released for clinical use.This chapter describes analytical methods implemented and performed in our cell factory as part of the release strategy for an ATMP consisting of frozen autologous BM-derived MSC. Such methods are designed to assess the safety (sterility, endotoxin, and mycoplasma assays) and identity/potency (cell count and viability, immunophenotype and clonogenic assay) of the final product. Some assays are also applied to the biological starting material (sterility) or carried out as in-process controls (sterility, cell count and viability, immunophenotype, clonogenic assay).The validation strategy for each analytical method is described in the accompanying Chapter 20 .
authors.affiliation: Lugano Cell Factory, Cardiocentro Ticino - Swiss Institute of Regenerative Medicine (SIRM), Via Tesserete 48, Lugano, 6900, Switzerland.
authors.forename: Marina
authors.initials: M
authors.lastname: Radrizzani
authors.affiliation: Lugano Cell Factory, Cardiocentro Ticino - Swiss Institute of Regenerative Medicine (SIRM), Via Tesserete 48, Lugano, 6900, Switzerland.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Soncin
authors.affiliation: Lugano Cell Factory, Cardiocentro Ticino - Swiss Institute of Regenerative Medicine (SIRM), Via Tesserete 48, Lugano, 6900, Switzerland.
authors.forename: Viviana
authors.initials: V
authors.lastname: Lo Cicero
authors.affiliation: Lugano Cell Factory, Cardiocentro Ticino - Swiss Institute of Regenerative Medicine (SIRM), Via Tesserete 48, Lugano, 6900, Switzerland.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Andriolo
authors.affiliation: Lugano Cell Factory, Cardiocentro Ticino - Swiss Institute of Regenerative Medicine (SIRM), Via Tesserete 48, Lugano, 6900, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Bolis
authors.affiliation: Lugano Cell Factory, Cardiocentro Ticino - Swiss Institute of Regenerative Medicine (SIRM), Via Tesserete 48, Lugano, 6900, Switzerland. lucia.turchetto@cardiocentro.org.
authors.forename: Lucia
authors.initials: L
authors.lastname: Turchetto
mesh_terms: D002452:Cell Count; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D015925:Cryopreservation; D004731:Endotoxins / Q000032:analysis; D019983:Guideline Adherence; D017408:Guidelines as Topic; D006801:Humans; D016130:Immunophenotyping; D008420:Manufactured Materials / Q000592:standards*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000382:microbiology; D008828:Microbiological Techniques / Q000379:methods; D011786:Quality Control
chemical_list: D004731:Endotoxins
keywords: Advanced therapy medicinal product; Analytical methods; Cell-based medicinal product; Good manufacturing practices; Mesenchymal stromal/stem cell