Good Manufacturing Practice (GMP) Translation of Advanced Cellular Therapeutics: Lessons for the Manufacture of Erythrocytes as Medicinal Products
Blood transfusion is a mainstay of modern medical practice. In many parts of the world the use of this life-saving therapy is hampered by issues of supply and the potential for transfusion transmitted infections. Accordingly, there are many studies seeking to find an alternative to donated red blood cells (RBCs) for transfusion, including large-scale production from adult and pluripotent stem cells, or erythroid cell lines. Translating basic studies, using any cell lineage, into protocols that are suitable for the generation of cellular therapies requires a wide range of biological and regulatory procedures to be put in place. Additionally, there are specific challenges for the production of RBCs caused by the number of cells needed for a single dose (approx. 1–2 × 1012). In this chapter, we will review critical areas in the development and good manufacturing practice (GMP) translation of cellular therapeutics through to early phase clinical trials and how this learning can be applied to in vitro RBC therapies.
Key wordsGood manufacturing practice (GMP) Cellular therapy Translation Red blood cells Regulatory requirements
- 3.Olivier EN, Marenah L, McCahill A, Condie A, Cowan S, Mountford JC (2016) High-efficiency serum-free feeder-free Erythroid differentiation of human pluripotent stem cells using small molecules. Stem Cells Transl Med 5(10):1394–1405. PubMed PMID: 27400796; PubMed Central PMCID: PMC5031182CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Norfolk D (ed) (2013) Handbook of transfusion medicine, 5th edn. TSO, Norwich. isbn:9780117068469Google Scholar
- 6.PAS 83:2012. Developing human cells for clinical applications in the European Union and the United States of AmericaGoogle Scholar
- 10.Campbell A, Brieva T, Raviv L, Rowley J, Niss K, Brandwein H, Oh S, Karnieli O (2015) Concise review: process development considerations for cell therapy. Stem Cells Transl Med 4(10):1155–1163. doi: 10.5966/sctm.2014-0294. Review. PubMed PMID: 26315572; PubMed Central PMCID: PMC4572896CrossRefPubMedPubMedCentralGoogle Scholar
- 15.US FDA (2015) Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Guidance for Industry. http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM359073.pdf