Skip to main content

Advertisement

SpringerLink
Log in

Regulatory considerations in production of a cell therapy medicinal product in Europe to clinical research

  • Review Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

The development of new drugs using stem cells has become a clinic alternative for the treatment of different diseases such as Alzheimer’s, diabetes and myocardial infarction. Similar to conventional medicines, stem cells as new medicinal products for cell therapy are subjected to current legislation concerning their manufacture process. Besides, their legality is determined by the Regulatory Agencies belonging to the Member State of the European Union in which they are being registered. With the evolution of therapy that uses cells as medicines, there is a need to develop the appropriate legislative and regulatory framework capable of ensuring their safety and effectiveness. However, few works have been published regarding the regulations that these products must comply through production and commercialization processes. The present work is focused on the description of key events during clinical development and cell production of stem cells as drugs. Such as the regulations, requirements and directives involved in the production of cell therapy medicinal products, from the clinical design stage to its commercialization in Europe.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Mason C, Manzotti E (2009) Regen: the industry responsible for cell-based therapies. Regen Med 4:783–785

    Article  PubMed  Google Scholar 

  2. Committee for Advanced Therapies (CAT) (2010) Challenges with advanced therapy medicinal products and how to meet them. Nat Rev Drug Discov 9:195–201

    Article  Google Scholar 

  3. Belardelli F, Rizza P, Moretti F, Carella C, Galli MC, Migliaccio G (2009) Translational research on advanced therapies. Ann Ist Super Sanita 47:72–78

    Google Scholar 

  4. Hughes-Wilson W, Mackay D (2007) European approval system for advanced therapies: good news for patients and innovators alike. Regen Med 2:5–6

    Article  PubMed  Google Scholar 

  5. Ottria G, Dallera M, Aresu O, Manniello MA, Parodi B, Spagnolo AM, Cristina ML (2010) Environmental monitoring programme in the cell therapy facility of a research centre: preliminary investigation. J Prev Med Hyg 51:133–138

    CAS  PubMed  Google Scholar 

  6. Hogarth S, Salter B (2010) Regenerative medicine in Europe: global competition and innovation governance. Regen Med 5:971–985

    Article  PubMed  Google Scholar 

  7. Chamberlain G, Fox J, Ashton B et al (2007) Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 25:2739–2749

    Article  CAS  PubMed  Google Scholar 

  8. Verfaillie CM, Pera A, Lansdorp PM (2002) Stem cells: hype and reality. Hematol Am Soc Hematol Educ Program 1:369–391

    Article  Google Scholar 

  9. Magee JA, Piskounova E, Morrison SJ (2012) Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 20:283–296

    Article  Google Scholar 

  10. Choi WY, Poss KD (2012) Cardiac regeneration. Curr Top Dev Biol 100:319–344

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Naujok O, Lenzen S (2012) Pluripotent stem cells for cell replacement therapy of diabetes. Dtsch Med Wochenschr 137:1062–1066

    Article  CAS  PubMed  Google Scholar 

  12. Cohen-Haguenauer O (2011) Gene therapy and rare diseases. Rev Med Interne 32:S210–S212

    Article  PubMed  Google Scholar 

  13. Singh MS, MacLaren RE (2011) Stem cells as a therapeutic tool for the blind: biology and future prospects. Proc Biol Sci 278:3009–3016

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Volarevic V, Ljujic B, Stojkovic P, Lukic A, Arsenijevic N, Stojkovic M (2011) Human stem cell research and regenerative medicine: present and future. Br Med Bull 99:155–168

    Article  PubMed  Google Scholar 

  15. Terzic A, Edwards BS, McKee KC, Nelson TJ (2011) Regenerative medicine: a reality of stem cell technology. Minn Med 94:44–47

    PubMed  Google Scholar 

  16. Sokal EM (2011) From hepatocytes to stem and progenitor cells for liver regenerative medicine: advances and clinical perspectives. Cell Prolif 44:39–43

    Article  PubMed  Google Scholar 

  17. Parenteau NL (2009) Commercial development of cell-based therapeutics: strategic considerations along the drug to tissue spectrum. Regen Med 4:601–611

    Article  PubMed  Google Scholar 

  18. Dietz AB, Padley DJ, Gastineau DA (2007) Infrastructure development for human cell therapy translation. Clin Pharmacol Ther 82:320–324

    Article  CAS  PubMed  Google Scholar 

  19. Hampton JR (1983) The end of clinical freedom. Br Med J 287:237–1238

    Article  Google Scholar 

  20. Patel SA, King CC, Lim PK et al (2010) Personalizing stem cell research and therapy: the arduous road ahead or missed opportunity? Curr Pharmacogen Person Med 8:25–36

    Article  CAS  Google Scholar 

  21. Directive 2004/10/EC of the European parliament and of the council of 11 February 2004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances. Official J Eur Union L 50:44–59

  22. Directive 2004/9/EC of the European parliament and of the council of 11 February 2004 on the inspection and verification of good laboratory practice (GLP). Official J Eur Union L 50:28–43

  23. Directive 2001/20/EC the European parliament and of the council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Official J Eur Union L 121:34–44

  24. Yim R (2005) Administrative and research policies required to bring cellular therapies from the research laboratory to the patient’s bedside. Transfusion 45:144–148

    Article  Google Scholar 

  25. Trounson A, Thakar RG, Lomax G, Gibbons D (2011) Clinical trials for stem cell therapies. BMC Med 9:52

    Article  PubMed Central  PubMed  Google Scholar 

  26. Commission directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products. Official J Eur Union L 91:13–19

  27. Commission directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use. Official J Eur Union L 262:22–26

  28. EudraLex—EU GMP Volume 4 (2009) Good manufacturing practice (GMP) guidelines-annex 1: manufacture of sterile medicinal products.EU GMP-Annex 1: Manufacture of Sterile Medicinal Products http://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htm. Accessed 15 April 2012

  29. ICH Harmonised Tripartite Guideline Q2(R1) (1994) Validation of analytical procedures: text and methodology. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf. Accessed 15 April 2012

  30. EudraLex—EU GMP Volume 4 (2001) Good manufacturing practice (GMP) guidelines-annex 15: qualification and validation http://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htm. Accessed 15 April 2012

  31. Soncin S, Lo Cicero V, Astori G et al (2009) A practical approach for the validation of sterility, endotoxin and potency testing of bone marrow mononucleated cells used in cardiac regeneration in compliance with good manufacturing practice. J Transl Med 7:78

    Article  PubMed Central  PubMed  Google Scholar 

  32. Regulation (EC) No 726/2004 of the European parliament and of the council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency. Official J Eur Union L 136:1–51

  33. Ruiz S, Abad-Santos F (2010) Regulation and evaluation of clinical trials of cell therapy. Med Clin 135:35–39

    Article  Google Scholar 

  34. Celis P (2010) CAT-the new committee for advanced therapies at the European Medicines Agency. Bundesgesundheitsblatt-Gesund 53:9–13

    Google Scholar 

  35. Woods EJ, Bagchi A, Goebel WS et al (2010) Container system for enabling commercial production of cryopreserved cell therapy products. Regen Med 5:659–667

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have not any conflict of interest concerning this article.

Author information

Authors and Affiliations

  1. Cellular Production Unit, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Americo Vespucio Avenue s/n, 41092, Seville, Spain

    Patricia Gálvez Martín

  2. Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Campus of Cartuja, 18071, Granada, Spain

    Adolfina Ruiz Martinez, Visitación Gallardo Lara & Beatriz Clares Naveros

Authors
  1. Patricia Gálvez Martín
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adolfina Ruiz Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Visitación Gallardo Lara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beatriz Clares Naveros
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patricia Gálvez Martín.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martín, P.G., Martinez, A.R., Lara, V.G. et al. Regulatory considerations in production of a cell therapy medicinal product in Europe to clinical research. Clin Exp Med 14, 25–33 (2014). https://doi.org/10.1007/s10238-012-0213-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-012-0213-6

Keywords

Search

Navigation