Skip to main content
SpringerLink
Log in
Book cover

Cell Therapy pp 3–25Cite as

Regulation of Cell Product Manufacturing and Delivery: A United States Perspective

  • Chapter
  • First Online:

Abstract

Regulation of cellular therapy products in the United States is challenging and will continue to be so as long as advancements in the cell therapy field continue. As the field of cell therapy has advanced, and products are moving toward licensure, the regulation of these products has become increasingly complicated. The general principles involved in filing and maintaining an Investigational New Drug (IND) and interacting with the Food and Drug Administration (FDA) are described in addition to common reasons why INDs are put on hold. As the majority of cell therapy products are unique, the manufacturer must understand both the science behind the specific cell product and the regulations in order to successfully communicate with the FDA. Though the regulations are written in general terms to be applied to all cell therapy products, they can be tailored to an individual product with good communication and sound, data-driven scientific justification. Additionally, the components of Good Manufacturing Practice (GMP) will be discussed in detail as they relate to the interpretation of U.S regulations.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, “The Road to the Biotech Revolution: Highlights of 100 Years of Biologics Regulation.” FDA Consum Mag. Jan–Feb, 2006; 40(1):50–57.

    Google Scholar 

  2. Mauro A. Satellite cells of skeletal muscle fibers. J Biochem Biophys Cytol. 1961; 9: 493–498.

    Article  CAS  Google Scholar 

  3. Henderson ES. Treatment of acute leukemia. Semin Hematol. 1969 Jul; 6(3): 271–319.

    CAS  PubMed  Google Scholar 

  4. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981 Jul 9; 292 (5819): 154–156.

    Google Scholar 

  5. Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA. 1981 Dec; 78(12): 7634–7638.

    Article  CAS  PubMed  Google Scholar 

  6. Lacy PE. Islet cell transplantation for insulin-dependent diabetes. Hosp Pract (Minneap). 1995 Jun 15; 30(6): 41–45.

    Google Scholar 

  7. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, “Product Approval Information – Licensing Action.” August 22, 1997. http://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm171702.htm. Date accessed November 27, 2007.

  8. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, “About CBER.” July 19, 2007. http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm123340.htm.

  9. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, “References for the Regulatory Process for the Office of Cellular, Tissue and Gene Therapies (OCTGT).” July 23, 2007. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/OtherRecommendationsforManufacturers/ucm094338.htm.

  10. U.S. Food and Drug Administration, “FDA History.” http://www.fda.gov/AboutFDA/WhatWeDo/History/Origin/default.htm.

  11. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, “Guidance on Applications for Products Comprised of Living Autologous Cells Manipulated Ex Vivo and Intended for Structural repair or reconstruction.” May 1996. http://www.bcg-usa.com/regulatory/docs/1996/FDA199605B.pdf. Date accessed January 26, 2008.

  12. “Human tissue intended for transplantation.” Title 21 Code of Federal Regulations, Part 1270.10 2007 edition.

    Google Scholar 

  13. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, “Information on Submitting an Investigational New Drug Application.” September 25, 2007. http://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/InvestigationalNewDrugINDorDeviceExemptionIDEProcess/default.htm.

  14. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, Guidance for Industry: “Formal Meetings Between the FDA and Sponsors or Applicants.” May 2009. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM153222.pdf. Date accessed May, 2009.

  15. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research. SOPP 8101.1 – “Scheduling and Conduct of Regulatory Review Meetings with Sponsors and Applicants.” May 8, 2007. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/ProceduresSOPPs/ucm079448.htm. Date accessed November 21, 2007.

  16. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, Guidance for FDA Review Staff and Sponsors: “Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs).” April 9, 2008. http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/ucm078694.pdf.

  17. “IND content and format.” Title 21 Code of Federal Regulations, Pt. 312.23 2005 edition, 83–90.

    Google Scholar 

  18. “Labeling of an investigational new drug.” Title 21 Code of Federal Regulations, Pt. 312.6 2005 edition, 79.

    Google Scholar 

  19. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research. SOPP 8201 – “Issuance of and Response to Clinical Hold Letters for Investigational New Drug Applications.” April 27, 1999. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/ProceduresSOPPs/ucm063377.htm.

  20. “Annual reports.” Title 21 Code of Federal Regulations, Pt. 312.33 2005 edition, 104–106.

    Google Scholar 

  21. “Adulterated substance.” Title 21 Code of Federal Regulations, Pt. 351 Section 501(a)(2)(B) 2007 edition.

    Google Scholar 

  22. “Current Good Manufacturing Practice in Manufacturing, Processing, Packing, Holding of Drugs, and Finished Pharmaceuticals.” Title 21 Code of Federal Regulations, Pt. 210 and 211. 2007 edition.

    Google Scholar 

  23. “Quality systems regulations.” Title 21 Code of Federal Regulations, Pt. 820 2007 edition.

    Google Scholar 

  24. “Human cells, tissue, and cellular and tissue-based products.” Title 21 Code of Federal Regulations, Part 1271 2007 edition.

    Google Scholar 

  25. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research. Guidance for Industry: “CGMP for Phase 1 Investigational Drugs” July 15, 2008. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070273.pdf.

  26. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research. Federal Register. 21 CFR Parts 16, 1270, and 1271 Current Good Tissue Practice for Human Cell, Tissue, and Cellular and Tissue-Based Product Establishments; Inspection and Enforcement; Final Rule. November 24, 2004. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/ActsRulesRegulations/TissueProposedFinalRules/default.htm. Date accessed January 8, 2008.

  27. “Personnel qualifications.” Title 21 Code of Federal Regulations, Pt. 211.25. 2007 edition.

    Google Scholar 

  28. “General biological products standards.” Title 21 Code of Federal Regulations, Pt. 610. 2007 edition.

    Google Scholar 

  29. “Tracking from donor to consignee or final disposition.” Title 21 Code of Federal Regulations, Pt. 1271.290(e). 2007 edition.

    Google Scholar 

  30. “Hazardous materials regulations.” Title 49 Code of Federal Regulations, Pt. 171. 2007 edition.

    Google Scholar 

  31. Barker JW, Davies SM, DeFor T, et al. Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis. Blood. 2001; 97:2957–2961.

    Article  CAS  PubMed  Google Scholar 

  32. Rocha V, Cornish J, Sievers EL, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood. 2001; 97: 2962–2971.

    Article  CAS  PubMed  Google Scholar 

  33. Laughlin MJ, Eapen M, Rubinstein P, et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med. 2004; 351: 2265–2275.

    Article  CAS  PubMed  Google Scholar 

  34. Draft Guidance for Industry: Minimally Manipulated, Unrelated, Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution in Patients with Hematological Malignancies. US Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research, December 2006.

    Google Scholar 

  35. Net Cord – Foundation for the Accreditation of Cellular Therapy (FACT),. International standards for cord blood collection, processing, testing, banking, selection, and release. 3rd edition, Version 3.1, December 2008.

    Google Scholar 

  36. AABB Standards for Cellular Therapy Product Services. 3rd edition, Bethesda MD, 2008.

    Google Scholar 

  37. Rubinstein P, Dobrila L, Rosenfield RE, et al. Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution. Proc Natl Acad Sci USA. 1995; 92(22): 10119–10122.

    Article  CAS  PubMed  Google Scholar 

  38. Food and Drug Administration. Current good tissue practice for human cell, tissue and cellular and tissue based products establishments; inspection and enforcement; final rule. Docket NO. 1997 N-484P. Federal Register. 2004; 69:68612–68688.

    Google Scholar 

  39. Barker JN, Krepski TP, DeFor TE, et al. Searching for unrelated donor hematopoietic stem cells: Availability and speed of umbilical cord blood versus bone marrow. Biol Blood Marrow Transplant. 2002; 8(5): 257–260.

    Article  PubMed  Google Scholar 

  40. International Air Transport Association (IATA). Dangerous Goods Regulations. 44th edition. Montreal, Canada, 2007: 106–107, 171, 199, 418–419, 451–452.

    Google Scholar 

  41. Code of Federal Regulations. Hazardous Materials Regulations. 49 CFR subpart 171–180. 2004.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. PACT Group, The EMMES Corporation, 20850, Rockville, MD, USA

    R.W. Lindblad MD, FACEP

Authors
  1. R.W. Lindblad MD, FACEP
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R.W. Lindblad MD, FACEP .

Editor information

Editors and Affiliations

  1. Baylor College of Medicine, Baylor Plaza 1, Houston, 77030, U.S.A.

    Adrian Gee

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Lindblad, R. (2009). Regulation of Cell Product Manufacturing and Delivery: A United States Perspective. In: Gee, A. (eds) Cell Therapy. Springer, Boston, MA. https://doi.org/10.1007/b102110_1

Download citation

Publish with us

Policies and ethics

Search

Navigation