Developing assays to address identity, potency, purity and safety: cell characterization in cell therapy process development

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

References

• 1  Mason C, Dunnill P. Translational regenerative medicine research: essential to discovery and outcome. Regen. Med.2(3),227–229 (2007).
  Google Scholar
• 2  James D. Therapies of tomorrow require more than factories from the past. Bioproc. Int.9,4–11 (2011).
  Google Scholar
• 3  Mason C, Hoare M. Regenerative medicine bioprocessing: the need to learn from the experience of other fields. Regen. Med.1(5),615–623 (2006).
  Google Scholar
• 4  Bravery C. Regulating interface science healthcare products: myths and uncertainties. J. R. Soc. Interface7,7 (2010).
  Google Scholar
• 5  Brandenberger R, Burger S, Campbell A, Fong T, Lapinskas E, Rowley J. Cell therapy bioprocessing integrating process and product development for the next generation of biotherapeutics. Bioproc. Int.9(Suppl. 1),30–37 (2011).
  Google Scholar
• 6  Regenerative medicine glossary. Regen. Med.4(Suppl. 4),S1–S88 (2009).▪ The regenerative medicine glossary defines key ideas and concepts associated with the fields of regenerative medicine and/or cell therapy.
  Google Scholar
• 7  Rayment EA, Williams DJ. Concise review. Mind the gap: challenges in characterizing and quantifying cell- and tissue-based therapies for clinical translation. Stem Cells28(5),996–1004 (2010).▪▪ Safety is the most important critical quality attribute of a product; this reference addresses safety concerns associated with cell therapy products, more completely than was possible in this manuscript.
  MedlineGoogle Scholar
• 8  US FDA. Guidance for FDA Reviewers and Sponsors. Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs). US Department of Health and Human Services, Rockville, MD, USA, 1,1–39 (2008).▪▪ The CMC guidance for human somatic cell therapy, issued by the US FDA, contains much of the information cell therapy product developers will need in order to develop a clinical-grade cell therapy product.
  Google Scholar
• 9  FDA summary for basis of approval: BLA Ref No. 96–0372, Carticel.
  Google Scholar
• 10  Mcintyre C, Flyg B, Fong T. Fluorescence-activated cell sorting for CGMP processing of therapeutic cells. Bioproc. Int.8,44–53 (2010).
  CASGoogle Scholar
• 11  Suni MA, Dunn HS, Orr PL et al. Performance of plate-based cytokine flow cytometry with automated data analysis. BMC Immunol.4,9 (2003).
  MedlineGoogle Scholar
• 12  Stroncek DF, Jin P, Wang E, Ren J, Sabatino M, Marincola FM. Global transcriptional analysis for biomarker discovery and validation in cellular therapies. Mol. Diagn. Ther.13(3),181–193 (2009).
  Medline CASGoogle Scholar
• 13  Kim KS, Kim JS, Lee MR, Jeong HS, Kim J. A study of microRNAs in silico and in vivo: emerging regulators of embryonic stem cells. FEBS J.276(8),2140–2149 (2009).
  Medline CASGoogle Scholar
• 14  D’amour KA, Agulnick AD, Eliazer S, Kelly OG, Kroon E, Baetge EE. Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat. Biotechnol.23(12),1534–1541 (2005).
  MedlineGoogle Scholar
• 15  Caplan AI. Why are MSCs therapeutic? New data: new insight. J. Pathol.217(2),318–324 (2009).
  Medline CASGoogle Scholar
• 16  Wang M, Crisostomo PR, Herring C, Meldrum KK, Meldrum DR. Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism. Am. J. Physiol. Regul. Integr. Comp. Physiol.291(4),R880–R884 (2006).
  Medline CASGoogle Scholar
• 17  US FDA. Final Guidance for Industry. Potency Tests for Cellular and Gene Therapy Products. US Department of Health and Human Services, Rockville, MD, USA, 1,1–19 (2011).▪▪ The FDA guidance for potency tests is a great reference for product developers struggling to determine how to develop a test to measure the biological activity of their product.
  Google Scholar
• 18  Liu CH, Hwang SM. Cytokine interactions in mesenchymal stem cells from cord blood. Cytokine32(6),270–279 (2005).
  Medline CASGoogle Scholar
• 19  Yagi H, Soto-Gutierrez A, Parekkadan B et al. Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant.19(6),667–679 (2010).
  MedlineGoogle Scholar
• 20  Curti A, Trabanelli S, Salvestrini V, Baccarani M, Lemoli RM. The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology. Blood113(11),2394–2401 (2009).
  Medline CASGoogle Scholar
• 21  Dominici M, Le Blanc K, Mueller I et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy8(4),315–317 (2006).
  Medline CASGoogle Scholar
• 22  Debenedette MA, Calderhead DM, Tcherepanova IY, Nicolette CA, Healey DG. Potency of mature CD40L RNA electroporated dendritic cells correlates with IL-12 secretion by tracking multifunctional CD8⁺/CD28⁺ cytotoxic T cell responses in vitro. J. Immunother.34(1),45–57 (2011).
  Medline CASGoogle Scholar
• 23  Kasten P, Beyen I, Egermann M et al. Instant stem cell therapy: characterization and concentration of human mesenchymal stem cells in vitro. Eur. Cell. Mater.16,47–55 (2008).
  Medline CASGoogle Scholar
• 24  Yang H, Acker JP, Cabuhat M, Letcher B, Larratt L, Mcgann LE. Association of post-thaw viable CD34⁺ cells and CFU-GM with time to hematopoietic engraftment. Bone Marrow Transplant.35(9),881–887 (2005).
  Medline CASGoogle Scholar
• 25  Goltry K, Rowley J, Peters M, Burchardt E. Tissue repair cells for the treatment of cardiovascular diseases. Adv. Mol. Med.3(1),9 (2007).
  Google Scholar
• 26  Rich IN, Hall KM. Validation and development of a predictive paradigm for hemotoxicology using a multifunctional bioluminescence colony forming proliferation assay. Toxicol. Sci.87(2),427–441 (2005).
  Medline CASGoogle Scholar
• 27  Zhang YW, Denham J, Thies RS. Oligodendrocyte progenitor cells derived from human embryonic stem cells express neurotrophic factors. Stem Cells Dev.15(6),943–952 (2006).
  Medline CASGoogle Scholar
• 28  Kroon E, Martinson LA, Kadoya K et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat. Biotechnol.26(4),443–452 (2008).
  Medline CASGoogle Scholar
• 29  Klimanskaya I, Hipp J, Rezai KA, West M, Atala A, Lanza R. Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics. Cloning Stem Cells6(3),217–245 (2004).
  Medline CASGoogle Scholar
• 30  Ellington AA, Kullo IJ, Bailey KR, Klee GG. Antibody-based protein multiplex platforms: technical and operational challenges. Clin. Chem.56(2),186–193 (2009).
  MedlineGoogle Scholar
• 31  Goldring CE, Duffy PA, Benvenisty N et al. Assessing the safety of stem cell therapeutics. Cell Stem Cell8(6),618–628 (2011).
  Medline CASGoogle Scholar
• 32  Nelson PN, Carnegie PR, Martin J et al. Demystified. Human endogenous retroviruses. Mol. Pathol.56(1),11–18 (2003).
  Medline CASGoogle Scholar
• 33  Ryan FP. Human endogenous retroviruses in health and disease: a symbiotic perspective. J. R. Soc. Med.97(12),560–565 (2004).
  MedlineGoogle Scholar
• 34  International Conference on Harmonisation. Q5A Viral Safety Evaluation of Biotechnology Products Derived From Cell Lines of Human or Animal Origin. EMEA, Canary Wharf, London, UK, 1,1–33 (2006).
  Google Scholar
• 35  Morgan RA, Dudley ME, Rosenberg SA. Adoptive cell therapy: genetic modification to redirect effector cell specificity. Cancer J.16(4),336–341 (2010).
  Medline CASGoogle Scholar
• 36  US FDA. Guidance for Industry. Guidance for Human Somatic Cell Therapy and Gene Therapy. US Department of Health and Human Services, Rockville, MD, USA, 1,30 (1998).
  Google Scholar
• 37  Higano CS, Small EJ, Schellhammer P et al. Sipuleucel-T. Nature Rev. Drug Discov.9(7),513–514 (2010).
  Medline CASGoogle Scholar
• 38  Carpenter MK, Frey-Vasconcells J, Rao MS. Developing safe therapies from human pluripotent stem cells. Nat. Biotechnol.27(7),606–613 (2009).
  Medline CASGoogle Scholar
• 39  Strauss S. Geron trial resumes, but standards for stem cell trials remain elusive. Nat. Biotechnol.28(10),989–990 (2010).
  Medline CASGoogle Scholar
• 40  Sun X, Long X, Yin Y et al. Similar biological characteristics of human embryonic stem cell lines with normal and abnormal karyotypes. Hum. Reprod.23(10),2185–2193 (2008).
  Medline CASGoogle Scholar
• 41  Gore A, Li Z, Fung HL et al. Somatic coding mutations in human induced pluripotent stem cells. Nature471(7336),63–67 (2011).
  Medline CASGoogle Scholar
• 42  US FDA. Guidance for Industry. Process Validation: General Principles and Practices. US Department of Health and Human Services, Rockville, MD, USA, 1,1–22 (2011).
  Google Scholar
• 43  International Conference on Harmonisation. Q5E. Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process. EMEA, Canary Wharf, London, UK, 1,1–11 (2003).
  Google Scholar
• 44  International Conference on Harmonisation. Q5C. Guideline for Industry: Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products. EMEA, Canary Wharf, London, UK, 1,1–12 (1996).
  Google Scholar
• 45  Thomas RJ, Hourd PC, Williams DJ. Application of process quality engineering techniques to improve the understanding of the in vitro processing of stem cells for therapeutic use. J. Biotechnol.136(3–4),148–155 (2008).
  Medline CASGoogle Scholar
• 46  Julien C, Whitford W. The biopharmaceutical industry’s new operating paradigm. Bioproc. Int.8,6–14 (2008).
  Google Scholar
• 47  Rowley J. Developing cell biomanufacturing processes. Chem. Eng. Prog.SBE(Suppl.),6 (2010).
  Google Scholar
• 48  Fensten R. Understanding Animal Sera: Considerations for Use in the Production of Biological Therapeutics. John Wiley and Sons Ltd, West Sussex, UK, 45–58 (2007).
  Google Scholar
• 49  Dahl JA, Duggal S, Coulston N et al. Genetic and epigenetic instability of human bone marrow mesenchymal stem cells expanded in autologous serum or fetal bovine serum. Int. J. Dev. Biol.52(8),1033–1042 (2008).
  Medline CASGoogle Scholar
• 50  Shahdadfar A, Fronsdal K, Haug T, Reinholt FP, Brinchmann JE. In vitro expansion of human mesenchymal stem cells: choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability. Stem Cells23(9),1357–1366 (2005).
  Medline CASGoogle Scholar
• 101  Greenwood J. How do drugs and biologics differ? Biotechnology Industry Organization, Washington, DC, USA (2010). www.bio.org/healthcare/followonbkg/DrugsVBiologics.asp
  Google Scholar
• 102  Interactive cell characterization tool (2011). www.advbiols.com/documents/ImportanceofCharacterisation.swf
  Google Scholar
• 103  Burger S, Bravery C. ISCT webinar: potency testing. International Society for Cellular Therapy (2011). www.celltherapysociety.org
  Google Scholar
• 104  Geron^®. www.geron.com
  Google Scholar
• 105  ViaCyte^®. http://viacyte.com
  Google Scholar
• 106  Advanced Cell Technology^®. http://advancedcell.com
  Google Scholar
• 107  US FDA. 21 CFR 610.15. Code of Federal Regulations, general biological products standards, constituent materials (2002). www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=610.15
  Google Scholar
• 108  US FDA. 21 CFR 610.12. Code of Federal Regulations, general biological products standards, sterility (2010). www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=610.12
  Google Scholar
• 109  US FDA. 21 CFR 600; 610; 680 (Docket No FDA-2011-N-0080). Code of Federal Regulations, biological products: general; general biological products standards; additional standards for miscellaneous products, amendments to sterility test requirements for biological products. www.accessdata.fda.gov/scripts/oc/ohrms/dailylist.cfm?yr=2011&mn=6&dy=21
  Google Scholar
• 110  Geron. About GRNOPC1. Preclinical safety studies: animal toxicology testing of GRNOPC1. www.geron.com/GRNOPC1Trial/grnopc1-sec3.html
  Google Scholar
• 111  Clinical Trials registry and database. www.clinicaltrial.gov/
  Google Scholar