Skip to main content
SpringerLink
Log in
Book cover

Regenerative Medicine and Plastic Surgery pp 229–243Cite as

The Regulatory Landscape of Cell- and Tissue-Based Regenerative Medicine: Current Challenges and Emerging Issues

  • Chapter
  • First Online:

  • 737 Accesses

Abstract

Regenerative Medicine (RM) is shaped by rapid developments in science and technology that push the field on a daily basis. However, to provide a regulatory framework for the access to safe, effective, and traceable Regenerative Medicine Therapeutics (RMTs) on a global level, an international consensus must be reached to unify and streamline processes governing the translation of basic science into the clinic. The European Union (EU) and the United States (US) are two of the major players within the RM field. Hence, understanding their regulatory processes and some of the hurdles that currently face translation is paramount to prospective stakeholders.

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   109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   199.99
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

Change history

References

  1. Baptista PM, Atala A. Regenerative medicine: the hurdles and hopes. Transl Res. 2014;163(4):255–8.

    Article  Google Scholar 

  2. European Commission. Regulation (EC) No 1394/2007 of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004. 2007. https://ec.europa.eu/health//sites/health/files/files/eudralex/vol-1/reg_2007_1394/reg_2007_1394_en.pdf. Accessed 9 March 2018.

  3. European Medicines Agency. Legal Framework. Regulation EC 1394/2007: Europa EU; 2018.

    Google Scholar 

  4. Forgó N, Hildebrandt M. Joint conference on the impact of EU legislation on therapeutic advance. Cytotherapy. 2013;15(12):1444–8.

    Article  Google Scholar 

  5. Vestergaard HT, Apote LD, Schneider CK, Herberts C. The evolution of nonclinical regulatory science: advanced therapy medicinal products as a paradigm. Mol Ther. 2013;21(9):1294–6.

    Article  CAS  Google Scholar 

  6. Hurley P, Jurmeister S, Parsley K. Advanced therapy medicinal products — an evolving regulatory landscape. 2018. https://www.ppdi.com/-/media/Files/PPDI-Files/.../Regulatory-Focus-201702.ashx. Accessed 8 March 2018.

  7. European Medicines Agency. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001on the Community code relating to medicinal products for human use. www.ema.europa.eu/docs/en_GB/document_library/...and.../WC500004481.pdf. Accessed 10 March 2018.

  8. Paul-Ehrlich Institute Booklet. Arzneimittel für neuartige Therapien. ATMP—Advanced Therapy Medicinal Products” Regulatorische Anforderungen und prak-tische Hinweise: June 2012 [Internet]. Available from: https://www.pei.de/SharedDocs/Downloads/pu/innovationsbuero/broschuere-atmp-anforderungen-hinweise.pdf?__blob=publicationFile&v=1 https://www.pei.de/.../broschuere-atmp-anforderungen-hinweise. Accessed 10 March 2018.

  9. Izeta A, Herrera C, Mata R, Astori G, Giordano R, Hernández C, Leyva L, Arias S, Oyonarte S, Carmona G, Cuende N. Cell-based product classification procedure: what can be done differently to improve decisions on borderline products? Cytotherapy. 2016;18(7):809–15.

    Article  Google Scholar 

  10. U.S. Department of Health and Human Services. Regulatory considerations for human cells, tissues and cellular products: minimal manipulation and homologous use: Guidance for Industry and Food and Drug Administration Staff. 2017. https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM585403.pdf

  11. Lee MH, Au P, Hyde J, Gacchina Johnson C, Heidaran M, Karandish S, Boxer L, Mendicino M, Yoon D, Tull L, Arcidiacono J, McCright B, Kaplan DS, Fink D, Durfor CN, McFarland R, Witten C. Translation of regenerative medicine products into the clinic in the United States: FDA perspective. In: Atala A, Allickson J, editors. Translational regenerative medicine. Cambridge, MA: Academic Press; 2015.

    Google Scholar 

  12. U.S. Food and Drug Administration. FDA Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/P's) Product List. 2018 https://www.fda.gov/BiologicsBloodVaccines/TissueTissueProducts/RegulationofTissues/ucm150485.htm. Accessed 10 March 2018.

  13. U.S. Food and Drug Administration. FDA-How to study and market your device. 2018. https://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice. Accessed 10 March 2018.

  14. U.S. Department of Health and Human Services. Expedited programs for regenerative medicine therapies for serious conditions: draft guidance for industry. 2017. https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-bio-gen/documents/document/ucm585414.pdf. Accessed 16 Feb 2018.

  15. U.S. Food and Drug Administration. Regenerative Medicine Advanced Therapy Designation. 2018. https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ucm537670.htm. Accessed 16 Feb 2018.

  16. Itoh K, Kano S. Comparison of international guidelines for regenerative medicine: Knee cartilage repair and replacement using human-derived cells and tissues. Biologicals. 2016;44(4):267–70.

    Article  Google Scholar 

  17. Committee for Advanced Therapies (CAT). MA/CAT/285241/2010 rev.1-Reflection paper on classification of advanced therapy medicinal products. European Medicines Agency. 2015. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/06/WC50187744.pdf. Accessed 19 Feb 2018.

  18. Committee for Advanced Therapies (CAT). Reflection paper on classification of advanced therapy medicinal products [Internet]: European Medicines Agency. 2015. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/06/WC500187744.pdf. Accessed 20 Feb 2018.

  19. Yano K, Watanabe N, Tsuyuki K, Ikawa T, Kasanuki H, Yamato M. Regulatory approval for autologous human cells and tissue products in the United States, the European Union, and Japan. Regen Therapy. 2015:145–56.

    Google Scholar 

  20. U.S. Food and Drug Administration. Regulatory considerations for human cells, tissues, and cellular and tissue- based products: minimal manipulation and homologous use. 2017. https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM585403.pdf. Accessed 16 Feb 2018.

  21. Yano K, Tsuyuki K, Watanabe N, Kasanuki H, Yamato M. The regulation of allogeneic human cells and tissue products as biomaterials. Biomaterials. 2013;34(13):3165–73.

    Article  CAS  Google Scholar 

  22. 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.

    Google Scholar 

  23. Sakai D, Schol J, Foldager CB, Sato M, Watanabe M. Regenerative technologies to bed side: Evolving the regulatory framework. J Orthopaed Transl. 2017:91–7.

    Google Scholar 

  24. European Medicines Agency. Committee for Advanced Therapies (CAT) http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000266.jsp&mid=WC0b01ac05800292a4. Accessed 2 Dec 2017.

  25. Maciulaitis R, D’Apote L, Buchanan A, Pioppo L, Schneider CK. Clinical development of advanced therapy medicinal products in Europe: evidence that regulators must be proactive. Mol Ther. 2012;20(3):479–82.

    Article  CAS  Google Scholar 

  26. The International Council for Harmonisation of Technical Requirements for Pharmaceuticalsfor Human Use (ICH). ICH Harmonized Tripartite Guideline: Guideline for Good Clinical Practice E6(R1. 1996 https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf. Accessed 1 March 2018.

  27. Brennan Z. EMA, European Commission Look to Foster Development of Advanced Therapies Regulatory Affairs Professionals Society (RAPS). 2017. Available from: https://www.raps.org/regulatory-focus%E2%84%A2/news-articles/2017/10/ema,-european-commission-look-to-foster-development-of-advanced-therapies. Accessed 13 Feb 2018.

  28. U.S. Food and Drug Administration. The Drug Development Process. 2018 https://www.fda.gov/ForPatients/Approvals/Drugs/default.htm. Accessed 20 Feb 2018.

  29. U.S. Food and Drug Administration. Step 2: Preclinical Research. 2018. https://www.fda.gov/ForPatients/Approvals/Drugs/ucm405658.htm. Accessed 20 Feb 2018.

  30. Field MJ, Boat TF. Development of new therapeutic drugs and biologics for rare diseases: accelerating research and development. Washington, DC: National Academies Press; 2010.

    Google Scholar 

  31. Kellathur SN, Lou H-X. Cell and tissue therapy regulation: worldwide status and harmonization. Biologicals. 2012;40(3):222–4.

    Article  Google Scholar 

  32. U.S. Food and Drug Administration. CFR—Code of Federal Regulations Title 21-Regulations Under Certain Other Acts Administered by the Food and Drug Administration. 2017. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=1271.15 Accessed 15 Feb 2018.

  33. Lu L, Arbit HM, Herrick JL, Segovis SG, Maran A, Yaszemski MJ. Tissue engineered constructs: perspectives on clinical translation. Ann Biomed Eng. 2015;43(3):796–804.

    Article  Google Scholar 

  34. U.S. Food and Drug Administration. Step 3: Clinical Research. 2018 https://www.fda.gov/ForPatients/Approvals/Drugs/ucm405622.htm. Accessed 20 Feb 2018.

  35. van Schothorst M, Weeda J, Schiffers K, Oortwijn W, Hoekman J, Coppens D, L. De Bruin M. Study on the regulation of advanced therapies in selected jurisdictions. European Commission. 2016. https://ec.europa.eu/health//sites/health/files/human-use/docs/20147306_rfs_chafea_2014_health_24_060516.pdf. Accessed 20 Feb 2018.

  36. U.S. Food and Drug Administration. Institutional Review Boards Frequently Asked Questions—Information Sheet. 2016. https://www.fda.gov/RegulatoryInformation/Guidances/ucm126420.htm. Accessed 20 Feb 2018.

  37. U.S. Food and Drug Administration. CFR - Code of Federal Regulations Title 21. 2017. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=56. Accessed 20 Feb 2018.

  38. Sd W, Guchelaar H-J, Herberts C, Lowdell M, Hildebrandt M, Zandvliet M, Meij P. Development of cell therapy medicinal products by academic institutes. Drug Discov Today. 2016;21(8):1206–12.

    Article  Google Scholar 

  39. Hildebrandt M, Sethe S. Caught in the gap: ATMP manufacture in Academia. Telegraft. 2012;19:1.

    Google Scholar 

  40. Morrow D, Ussi A, Migliaccio G. Addressing pressing needs in the development of advanced therapies. Front Bioeng Biotechnol. 2017;5:55.

    Article  Google Scholar 

  41. U.S. Food and Drug Administration. DA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm581216.htm. Accessed 1 March 2018.

  42. U.S. Food and Drug Administration. FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss. 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm589467.htm. Accessed 1 March 2018.

  43. Denis A, Mergaert L, Fostier C, Cleemput I, Simoens S. Issues surrounding orphan disease and orphan drug policies in Europe. Appl Health Econ Health Policy. 2010;8(5):343–50.

    Article  Google Scholar 

  44. Ginty PJ, Rayment EA, Hourd P, Williams DJ. Regenerative medicine, resource and regulation: lessons learned from the remedi project. Regen Med. 2011;6(2):241–53.

    Article  Google Scholar 

  45. Plagnol AC, Rowley E, Martin P, Livesey F. Industry perceptions of barriers to commercialization of regenerative medicine products in the UK. Regen Med. 2009;4(4):549–59.

    Article  Google Scholar 

  46. Lysaght MJ, Jaklenec A, Deweerd E. Great expectations: private sector activity in tissue engineering, regenerative medicine, and stem cell therapeutics. Tissue Eng Part A. 2008;14(2):305–15.

    Article  Google Scholar 

  47. Arcidiacono JA, Blair JW, Benton KA. US Food and Drug Administration international g collaborations for cellular therapy product regulation. Stem Cell Res Ther. 2012;3(5):38.

    Article  Google Scholar 

  48. Hildebrandt M, Busch D. Innovative Medicines Initiative consultation: Facilitating the translation of advanced therapies to patients in Europe. EuroTech Universities Alliance https://www.imi.europa.eu/sites/default/files/archive/uploads/documents/ATMPconsultation2016/ATMPresponse_Org_EuroTechUniversitiesAlliance.pdf. Accessed 28 Feb 2018.

  49. European Compliance Academy ATMP Interest Group. ATMP GMP Open Access Research Alliance. European Compliance Academy. http://www.atmp-group.org/agora.html. Accessed 28 Feb 2018.

  50. European Society for Blood and Marrow Transplantation (EBMT). About EBMT https://www.ebmt.org/Contents/About-EBMT/Pages/About-EBMT.aspx. Accessed 28 Feb 2018.

  51. Joint Accreditation Committee-ISCT & EBMT (JACIE) Accreditation. About JACIE. 2004–2017. http://www.jacie.org/about. Accessed 1 March 2018.

  52. European Commission. EudraLex The Rules Governing Medicinal Products in the European Union Volume 4 Good Manufacturing Practice -Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products. 2017. https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2017_11_22_guidelines_gmp_for_atmps.pdf. Accessed 3 Jan 2018.

  53. European Commission. Horizon 2020. 2018 http://ec.europa.eu/programmes/horizon2020/en/what-horizon-2020. Accessed 1 March 2018.

Download references

Author information

Authors and Affiliations

  1. Department for Plastic and Hand Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    Sarah Khalid Alageel

  2. TUM Cells Interdisciplinary Center for Cellular Therapies, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    Sarah Khalid Alageel, Martin Hildebrandt & Ana Valéria Gouveia de Andrade

  3. Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    Martin Hildebrandt

Authors
  1. Sarah Khalid Alageel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin Hildebrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Valéria Gouveia de Andrade
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ana Valéria Gouveia de Andrade .

Editor information

Editors and Affiliations

  1. Department for Plastic Surgery and Hand Surgery, Division of Experimental Plastic Surgery, Technical University of Munich, Munich, Germany

    Dominik Duscher

  2. Private Practice, Tustin, CA, USA

    Melvin A. Shiffman

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Alageel, S.K., Hildebrandt, M., de Andrade, A.V.G. (2019). The Regulatory Landscape of Cell- and Tissue-Based Regenerative Medicine: Current Challenges and Emerging Issues. In: Duscher, D., Shiffman, M.A. (eds) Regenerative Medicine and Plastic Surgery. Springer, Cham. https://doi.org/10.1007/978-3-030-19958-6_22

Download citation

Publish with us

Policies and ethics

Search

Navigation