SpringerLink
Log in

Regulatory Framework, Challenges, and Initial Strategic Planning for Advanced Therapy Products (PTAs) Development in Brazil

  • Review
  • Published:
Therapeutic Innovation & Regulatory Science Aims and scope Submit manuscript

Abstract

Advanced Therapies are a class of innovative complex biological products used for therapeutic purposes, encompassing cell therapy, tissue engineering, and gene therapy products. These are promising therapeutic strategies for several complex diseases with low or non-existent therapeutic alternatives. The proper transposition of basic research in this area into medicinal products must comply with regulatory requirements. Here we review the main regulatory recommendations, emphasizing on the Brazilian regulation. The critical points are the manufacturing process, challenges in characterizing the product, development of non-clinical trials, lack of adequate animal models representative of the clinical situation, and absence of valid and measurable therapeutic endpoints. Based on that, we propose a framework for strategic planning of pre-clinical studies in this field. The detailed example involves producing a nonviral vector-based gene editing product, but the regulations and methods may be extrapolated for develo** different types of advanced therapies.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Pimenta C, Bettiol V, Alencar-Silva T, Franco OL, Pogue R, Carvalho JL, Felipe MSS. Advanced therapies and regulatory framework in different areas of the globe: past, present, and future. Clin Ther. 2021;43:e103–38.

    Article  CAS  PubMed  Google Scholar 

  2. Iglesias-López C, Agustí A, Obach M, Vallano A. Regulatory framework for advanced therapy medicinal products in Europe and United States. Front Pharmacol. 2019;10:1–14.

    Article  Google Scholar 

  3. Iglesias-Lopez C, Obach M, Vallano A, Agustí A. Comparison of regulatory pathways for the approval of advanced therapies in the European Union and the United States. Cytotherapy. 2021;23:261–74.

    Article  CAS  PubMed  Google Scholar 

  4. Flory E, Reinhardt J. European regulatory tools for advanced therapy medicinal products. Transfusion Medicine and Hemotherapy. 2013;40:409–12.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bachtarzi H. Ex vivo and in vivo genome editing: A regulatory scientific framework from early development to clinical implementation. Regenerative Med. 2017;12:1015–30.

    Article  CAS  Google Scholar 

  6. Schacker M, Seimetz D. From fiction to science: clinical potentials and regulatory considerations of gene editing. Clin Transl Med. 2019. https://doi.org/10.1186/s40169-019-0244-7.

    Article  PubMed  PubMed Central  Google Scholar 

  7. European Parliament (2007) 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. https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2007:324:0121:0137:en:PDF. Accessed 31 Aug 2021

  8. Carvalho M, Sepodes B, Martins AP. Regulatory and scientific advancements in gene therapy: State-of-the-art of clinical applications and of the supporting european regulatory framework. Front Med (Lausanne). 2017. https://doi.org/10.3389/fmed.2017.00182.

    Article  PubMed  Google Scholar 

  9. López-Paniagua M, de la Mata A, Galindo S, Blázquez F, Calonge M, Nieto-Miguel T. Advanced therapy medicinal products for the eye: Definitions and regulatory framework. Pharmaceutics. 2021;13:1–18.

    Article  Google Scholar 

  10. European Medicines Agency (2009) ChondroCelect—characterised viable autologous cartilage-forming cells expanded ex vivo expressing specific marker proteins. https://www.ema.europa.eu/en/medicines/human/EPAR/chondrocelect. Accessed 31 Aug 2021

  11. Food and Drug Administration (2010) Provenge® (sipuleucel-T). 13 september 2021.

  12. ANVISA (2020) Carta de aprovação de Produto de Terapia Avançada—Luxturna®. https://www.gov.br/anvisa/pt-br/assuntos/sangue/terapias-avancadas/cartas-de-aprovacao/carta-de-aprovacao-luxturna.pdf/view. Accessed 13 Sep 2021

  13. RENETA (2020) Cenário de crescimento de produtos de terapias avançadas no Brasil e no mundo. https://bef226c9-51c9-4f4d-b45d-485faa781332.filesusr.com/ugd/92716b_1460bdc1e1da4d56813cb91f27c853d9.pdf.

  14. de Freitas DRC. The regulatory pathway for advanced cell therapy and gene therapy products in brazil: a road to be built. Adv Exp Med Biol. 2015. https://doi.org/10.1007/978-3-319-18618-4_4.

    Article  PubMed  Google Scholar 

  15. Parca RM, Takao MRM, da Silva JB. Proposal of regulatory framework for advanced therapy medicinal products in Brazil. Vigilância Sanitária em Debate. 2018;6:15–22.

    Article  Google Scholar 

  16. Batista J, Junior S, Rodrigues E Silva AA, Cunha Melo C, Kumoto MC, Parca RM (2021) Produtos de terapias avançadas no Brasil: panorama regulatório. Consenso da Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular sobre Células Geneticamente Modificadas Agosto:

  17. Anvisa (2016) Portaria No 1.731, de 9 de Setembro de 2016. 2016

  18. Anvisa (2021) Resolução da Diretoria Colegiada—RDC No 505, de 27 de Maio de 2021. https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-505-de-27-de-maio-de-2021-323002775.

  19. Anvisa (2021) Resolução da diretoria Colegiada—RDC No 506, de 27 de Maio de 2021. https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-506-de-27-de-maio-de-2021-323008725.

  20. Anvisa (2021) Resolução da diretoria Colegiada—RDC No 508, de 27 de Maio de 2021. https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-508-de-27-de-maio-de-2021-323013606#:~:text=Dispõe sobre as Boas Práticas,clínica%2C e dá outras providências.&text=1° Esta Resolução estabelece,Uso Terapêutico e pesquisa clínica.

  21. da Silva JB, Takao MRM, Parca RM. Advanced therapy medicinal products: an introduction to risk management. Vigilância Sanitária em Debate. 2018;6:23–31.

    Google Scholar 

  22. Shim G, Kim D, Park GT, ** H, Suh SK, Oh YK. Therapeutic gene editing: Delivery and regulatory perspectives. Acta Pharmacol Sin. 2017;38:738–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Fachel FNS, Frâncio L, Poletto É, Schuh RS, Teixeira HF, Giugliani R, Baldo G, Matte U. Gene editing strategies to treat lysosomal disorders: The example of mucopolysaccharidoses. Adv Drug Deliv Rev. 2022. https://doi.org/10.1016/j.addr.2022.114616.

    Article  PubMed  Google Scholar 

  24. Pramod K, Ma T, Charoo N, Ansari S, Ali J. Pharmaceutical product development: A quality by design approach. Int J Pharm Investig. 2016;6:129.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Barkholt L, Voltz-Girolt C, Raine J, Salmonson T, Schüssler-Lenz M. European regulatory experience with advanced therapy medicinal products. Nat Rev Drug Discov. 2018;18:8–9.

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by grants from the National Council for Scientific and Technological Development (312714/2018–1 UM; 403587/2021–2, RSS; 442425/2020–1 FNSF, PBG and UM).

Author information

Authors and Affiliations

  1. Células, Tecidos e Genes (CTG), Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, R. Ramiro Barcelos 2350, Porto Alegre, RS, 90035-903, Brazil

    Flávia Nathiely Silveira Fachel, Roselena Silvestri Schuh, Patrícia Bencke Grudzinski, Helder Ferreira Teixeira, Guilherme Baldo & Ursula Matte

  2. Programa de Pós-Graduação em Ciências Farmacêuticas da Universidade Federal do Rio Grande Do Sul (UFRGS), Faculdade de Farmácia, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil

    Flávia Nathiely Silveira Fachel, Roselena Silvestri Schuh & Helder Ferreira Teixeira

  3. Programa de Pós-Graduação em Fisiologia da Universidade Federal do Rio Grande do Sul (UFRGS), Instituto de Ciências Básicas da Saúde, R. Sarmento Leite, n° 500, Porto Alegre, RS, 90050-170, Brazil

    Guilherme Baldo

  4. Programa de Pós-Graduação em Genética e Biologia Molecular da Universidade Federal do Rio Grande do Sul (UFRGS), Campus do Vale, Av. Bento Gonçalves 9500, Porto Alegre, RS, 91501-970, Brazil

    Guilherme Baldo & Ursula Matte

Authors
  1. Flávia Nathiely Silveira Fachel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roselena Silvestri Schuh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrícia Bencke Grudzinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helder Ferreira Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guilherme Baldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ursula Matte
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Flávia Nathiely Silveira Fachel.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fachel, F.N.S., Schuh, R.S., Grudzinski, P.B. et al. Regulatory Framework, Challenges, and Initial Strategic Planning for Advanced Therapy Products (PTAs) Development in Brazil. Ther Innov Regul Sci 58, 21–33 (2024). https://doi.org/10.1007/s43441-023-00578-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43441-023-00578-2

Keywords

Search

Navigation