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GMP Facilities for Clinical Cell Therapy Product Manufacturing: A Brief Review of Requirements and Design Considerations

  • Hamid Reza Aghayan
  • Babak Arjmand
  • Scott R. BurgerEmail author
Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

The field of cell-based therapies is evolving quickly, and its potential for transformational new treatment modalities has generated great excitement in the scientific community. In the decade 2000–2010, for example, cell therapy products accounted for over 2700 clinical trials, for a broad range of clinical applications. A risk-based approach to regulation of cell therapy products has been widely adopted by regulatory agencies, to balance risks and potential benefits of these novel therapies. Good Manufacturing Practices (GMPs) are fundamental to product safety and quality. GMPs involve multiple elements covering all aspects of production, and although each element is equally important, the facility is the most obvious and tangible of these. This chapter summarizes basic requirements for cell therapy GMP facilities and provides an overview of facility planning and design, cleanroom classifications, and operating procedures.

Keywords

Aseptic processing Cell therapy Cleanroom Facility GMP Manufacturing 

References

  1. Ährlund-Richter L, De Luca M, Marshak DR, Munsie M, Veiga A, Rao M (2009) Isolation and production of cells suitable for human therapy: challenges ahead. Cell Stem Cell 4(1):20–26CrossRefPubMedGoogle Scholar
  2. Alici E, Blomberg P (2010) GMP facilities for manufacturing of advanced therapy medicinal products for clinical trials: an overview for clinical researchers. Curr Gene Ther 10(6):508–515CrossRefPubMedGoogle Scholar
  3. Arjmand B, Aghayan HR (2014) Cell manufacturing for clinical applications. Stem Cells 32(9):2557–2558. doi: 10.1002/stem.1751 CrossRefPubMedGoogle Scholar
  4. Arjmand B, Emami-Razavi SH, Larijani B, Norouzi-Javidan A, Aghayan HR (2012) The implementation of tissue banking experiences for setting up a cGMP cell manufacturing facility. Cell Tissue Bank 13(4):587–596. doi: 10.1007/s10561-011-9276-y CrossRefPubMedGoogle Scholar
  5. Bersenev A (2011) RegenMed and cell therapeutic products available on the market. Stem Cell Assays blog. http://stemcellassays.com/2011/04/regenmed-and-cell-therapeutic-products-available-on-the-market/. Accessed 13 April 2011
  6. Bersenev A (2012) Stem cell therapeutic products on the market. Stem Cell Assays blog. http://stemcellassays.com/2012/02/stem-cell-therapeutic-products-market/. Accessed 29 Feb 2012
  7. Bosse R, Kulmburg P, Von Kalle C, Engelhardt M, Dwenger A, Rosenthal F, Schulz G (2000) Production of stem-cell transplants according to good manufacturing practice. Ann Hematol 79(9):469–476CrossRefPubMedGoogle Scholar
  8. Brandenberger R, Burger S, Campbell A, Fong T, Lapinskas E, Rowley JA (2011) Cell therapy bioprocessing. BioProcess Int 9(Suppl 1):30–37Google Scholar
  9. Burger SR (2000) Design and operation of a current good manufacturing practices cell-engineering laboratory. Cytotherapy 2(2):111–122CrossRefPubMedGoogle Scholar
  10. Burger S (2002) Advanced cell and gene therapies: translational development and GMP production. BioProcessing 1:19–23CrossRefGoogle Scholar
  11. Burger S (2003) CTP/GMP cell engineering for cell and gene therapies. Bioprocessing J 2:1–4Google Scholar
  12. Burger SR (2009) Commercial manufacturing of cell therapy products—considering the options. World Stem Cell Report. Genetics Policy Institute, pp 149-153Google Scholar
  13. Culme-Seymour EJ, Davie NL, Brindley DA, Edwards-Parton S, Mason C (2012) A decade of cell therapy clinical trials (2000–2010). Regen Med 7(4):455–462CrossRefPubMedGoogle Scholar
  14. Davis-Sproul J (1999) cGMP and cell processing. Cytotherapy 1(6):431–432CrossRefPubMedGoogle Scholar
  15. Dawson L, Bateman-House AS, Agnew DM, Bok H, Brock DW, Chakravarti A, Greene M, King PA, O’Brien SJ, Sachs DH (2003) Safety issues in cell-based intervention trials. Fertil Steril 80(5):1077–1085CrossRefPubMedGoogle Scholar
  16. Dietz AB, Padley D, Gastineau D (2007) Infrastructure development for human cell therapy translation. Clin Pharmacol Ther 82(3):320–324CrossRefPubMedGoogle Scholar
  17. Eaker S, Armant M, Brandwein H, Burger S, Campbell A, Carpenito C, Clarke D, Fong T, Karnieli O, Niss K (2013) Concise review: guidance in developing commercializable autologous/patient-specific cell therapy manufacturing. Stem Cells Transl Med 2(11):871–883CrossRefPubMedPubMedCentralGoogle Scholar
  18. Fitzpatrick I (2008) Cellular therapy success through integrated automation. BioProcess Int 6(9)Google Scholar
  19. Gee A (2009a) Baylor College of Medicine—Center for Cell and Gene Therapy (CAGT). In: Gee A (ed) Cell therapy: cGMP facilities and manufacturing. Springer, Boston, pp 67–77CrossRefGoogle Scholar
  20. Gee A (2009b) Design of a new GMP facility—lessons learned. In: Gee A (ed) Cell therapy: cGMP facilities and manufacturing. Springer, Boston, pp 79–84CrossRefGoogle Scholar
  21. Gee A, Lyon DL (2009) Cleaning procedures. In: Gee A (ed) Cell therapy: cGMP facilities and manufacturing. Springer, Boston, pp 135–144CrossRefGoogle Scholar
  22. Giancola R, Bonfini T, Iacone A (2012) Cell therapy: cGMP facilities and manufacturing. Muscles Ligaments Tendons J 2(3):243–247PubMedPubMedCentralGoogle Scholar
  23. Hampson B, Rowley J, Venturi N (2008) Manufacturing patient-specific cell therapy products. BioProcess Int 6(8)Google Scholar
  24. International Organization for Standardization (1999) ISO 14644-1, Cleanrooms and associated controlled environments—part 1: classification of air cleanlinessGoogle Scholar
  25. ISPE Baseline Guide (2011) Sterile product manufacturing facilities, 1st edn. ISPE, TampaGoogle Scholar
  26. Kirouac DC, Zandstra PW (2008) The systematic production of cells for cell therapies. Cell Stem Cell 3(4):369–381CrossRefPubMedGoogle Scholar
  27. Larijani B, Aghayan HR, Goodarzi P, Arjmand B (2015a) GMP-grade human fetal liver-derived mesenchymal stem cells for clinical transplantation. Methods Mol Biol 1283:123–136CrossRefPubMedGoogle Scholar
  28. Larijani B, Arjmand B, Ahmadbeigi N, Falahzadeh K, Soleimani M, Sayahpour FA, Aghayan HR (2015b) A simple and cost-effective method for isolation and expansion of human fetal pancreas derived mesenchymal stem cells. Arch Iran Med 18(11):770–775PubMedGoogle Scholar
  29. Lindblad RW (2009) Regulation of cell product manufacturing and delivery: a United States perspective. In: Gee A (ed) Cell therapy: cGMP facilities and manufacturing. Springer, Boston, pp 3–25CrossRefGoogle Scholar
  30. Odum JN (2004) Sterile product facility design and project management, 2nd edn. CRC Press, Boca RatonGoogle Scholar
  31. US Pharmacopoeia (2008) Chapter <1116> Microbiological evaluation of clean rooms and other controlled environmentsGoogle Scholar
  32. US Pharmacopoeia (2012) Chapter <1046> Cellular and tissue-based productsGoogle Scholar
  33. PIC/S Secretariat (2015) Guide to good manufacturing practice for medicinal products—Annex 1Google Scholar
  34. Ramstorp M (2008) Introduction to contamination control and cleanroom technology. Wiley, New YorkGoogle Scholar
  35. Sensebé L, Bourin P, Tarte K (2010) Good manufacturing practices production of mesenchymal stem/stromal cells. Hum Gene Ther 22(1):19–26CrossRefPubMedGoogle Scholar
  36. Sharp J (2005) Good pharmaceutical manufacturing practice: rationale and compliance. CRC Press, Boca RatonGoogle Scholar
  37. Signore AA, Jacobs T (2005) Good design practices for GMP pharmaceutical facilities. Taylor & Francis Group, Boca RatonCrossRefGoogle Scholar
  38. von Tigerstrom BJ (2008) The challenges of regulating stem cell-based products. Trends Biotechnol 26(12):653–658CrossRefGoogle Scholar
  39. White E (2009) Cleanroom design, construction, and qualification. J Validat Technol 15(4):30Google Scholar
  40. Whyte W (1999) Cleanroom design, 2nd edn. Wiley Online Library, Chichester, pp 21–49CrossRefGoogle Scholar
  41. Whyte W (2001) Cleanroom technology: fundamentals of design, testing and operation, 2nd edn. Wiley Online Library, Chichester, pp 1–20CrossRefGoogle Scholar
  42. Zhang J, Huang X, Wang H, Liu X, Zhang T, Wang Y, Hu D (2015) The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy. Stem Cell Res Ther 6(1):1–7CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Hamid Reza Aghayan
    • 1
  • Babak Arjmand
    • 2
    • 3
  • Scott R. Burger
    • 4
    Email author
  1. 1.Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
  2. 2.Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
  3. 3.Brain and Spinal Cord Injury Research CenterTehran University of Medical SciencesTehranIran
  4. 4.Advanced Cell & Gene Therapy, LLCChapel HillUSA

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