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The EU Regulatory Landscape of Non-Biological Complex Drugs

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Non-Biological Complex Drugs

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 20))

Abstract

Non-biological complex drugs (NBCDs) present today and in the future therapeutic opportunities to, inter alia, target the delivery of active ingredients, reduce toxicity and improve efficacy. It has been widely debated whether the EU regulatory system is ready to embrace this group of medicinal products. This chapter introduces the EU pharmaceutical legislation and explains how NBCDs are already integrated into the existing legislative framework. Supported by a recent example of legislative measures constructed purposefully to account for a new class of medicinal products (Advanced Therapy Medicinal Products), we explain what is currently done by EU competent authorities to foster the development of NBCDs and what are the options and challenges faced by the regulatory system to evolve in parallel with the progress made with this innovative and promising class of medicinal products.

Note: Text in italics is transcription from EU legislation

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Notes

  1. 1.

    Communication from the European Commission from 03 October 2012 on Second Regulatory Review on Nanomaterials, http://ec.europa.eu/research/industrial_technologies/pdf/policy/communication-from-the-commission-second-regulatory-review-on-nanomaterials_en.pdf.

  2. 2.

    Medicinal product with combined diagnostic and therapeutic functions.

  3. 3.

    Article 6 of Directive 2001/83/EC of the European Parliament and the Council on the [Union] Code Relating to Medicinal Products for Human Use

  4. 4.

    EMA European expert list, http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/landing/experts.jsp&mid=WC0b01ac058043244a.

  5. 5.

    European Commission Recommendation of 18 October 2011 on the definition of nanomaterial, http://ec.europa.eu/research/industrial_technologies/pdf/policy/commission-recommendation-on-the-definition-of-nanomater-18102011_en.pdf.

  6. 6.

    EU Scientific Committee on Emerging and Newly Identified Health Risks. Scientific Basis for the Definition of the Term “Nanomaterial”. European Commission, Brussels, Belgium, 2010.

  7. 7.

    Assessment Report of Teicoplanin, Procedure no: EMEA/H/A-5(3)/1315. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2013/04/WC500142229.pdf.

  8. 8.

    Envarsus® Summary of CHMP positive webpage http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002655/WC500170414.pdf.

  9. 9.

    Sancuso® European Public Assessment Report, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002296/WC500127130.pdf.

  10. 10.

    EMA/CHMP/QWP/202350/2010, Concept paper on the revision of the note for guidance on quality of modified release oral dosage forms and transdermal dosage forms: Sect. I (quality). http://www.ema.europa.eu/ema/pages/includes/document/open_document.jsp?webContentId=WC500095366 and EMA/CHMP/EWP/1303/2010 Concept paper on the need for revision of the note for guidance on modified release oral and transdermal dosage forms: Sect. II (pharmacokinetic and clinical evaluation) http://www.ema.europa.eu/ema/pages/includes/document/open_document.jsp?webContentId=WC500091662.

  11. 11.

    http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003508.pdf and http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003568.pdf.

  12. 12.

    http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2013/08/WC500147978.pdf.

  13. 13.

    http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002455/WC500135054.pdf.

  14. 14.

    Adapted from Vamvakas et al. 2011.

  15. 15.

    Please see the recommend references for more information.

  16. 16.

    Consult Notice to Applicants Volume 2A, Chap. 1, Sect. 2.3 for the Notion of “global marketing authorisation”.

  17. 17.

    Reflection paper on considerations given to designation of a single stereo isomeric form (enantiomer), a complex, a derivative, or a different salt or ester as new active substance in relation to the relevant reference active substance, http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/11/WC500134993.pdf.

  18. 18.

    See example of Aubagio®, EPAR Sect. 2.9: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002514/WC500148684.pdf.

  19. 19.

    Expert discussion on Bawa 2008.

  20. 20.

    Myocet® product information, last consulted on 22 July 2014, http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000297/human_med_000916.jsp&mid=WC0b01ac058001d124.

  21. 21.

    AmBisome® product information, last consulted 22 July 2014, http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1399707080555.pdf.

  22. 22.

    Caelyx® product information, last consulted on 22 July 2014, http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000089/human_med_000683.jsp&mid=WC0b01ac058001d124.

  23. 23.

    http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000778/WC500020435.pdf.

  24. 24.

    Ibid. 6.

  25. 25.

    Draft of the Guideline on Similar Biological Medicinal Products consulted on 15 July 2014, http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/05/WC500142978.pdf.

  26. 26.

    EMA News item from 28/09/2012 on European Medicines Agency to accept biosimilar reference medicines sourced outside European Economic Area, http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/09/news_detail_001615.jsp&mid=WC0b01ac058004d5c1.

  27. 27.

    http://ec.europa.eu/health/files/eudralex/vol-1/reg_2008_1234/reg_2008_1234_en.pdf.

  28. 28.

    Note for guidance on biotechnological/ biological products subject to changes in their manufacturing process, http://www.ema.europa.eu/ema/pages/includes/document/open_document.jsp?webContentId=WC500002805.

  29. 29.

    http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/04/WC500125400.pdf.

  30. 30.

    Reflection Paper on the Nanotechnology-based medicinal products for human use, http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2010/01/WC500069728.pdf.

  31. 31.

    European Commission, Medical Devices Borderline and classification issues webpage http://ec.europa.eu/health/medical-devices/documents/borderline/index_en.htm.

  32. 32.

    Guidance on Legislation—Borderlines Between medical devices and medicinal products, June 2013—MHRA, consulted on 14 July 2014, http://www.mhra.gov.uk/home/groups/dts-bs/documents/publication/con286964.pdf.

  33. 33.

    European Commission Medical Devices Regulatory Framework webpage http://ec.europa.eu/health/medical-devices/regulatory-framework/index_en.htm

  34. 34.

    ITF webpage, http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000334.jsp&mid=WC0b01ac05800ba1d9.

  35. 35.

    EMA Guidelines as published in EudraLex Volume 3, http://ec.europa.eu/health/documents/eudralex/vol-3/index_en.htm.

  36. 36.

    Procedure for European Union guidelines and related documents within the pharmaceutical legislative framework, http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/10/WC500004011.pdf.

  37. 37.

    Ibid. 45.

  38. 38.

    Ibid. 17 and 29.

  39. 39.

    Development of product-specific guidance on demonstration of bioequivalence, http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/07/WC500147001.pdf.

  40. 40.

    Ibid. 1.

  41. 41.

    Adapted from Vamvakas et al. 2011.

  42. 42.

    European Medicines Agency guidance for companies requesting scientific advice and protocol assistance, http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000049.jsp&mid=WC0b01ac05800229b9#.

  43. 43.

    Guidance to Applicants, http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004201.pdf.

  44. 44.

    ITF webpage, http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000334.jsp&mid=WC0b01ac05800ba1d9.

  45. 45.

    SME office webpage, http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000059.jsp&mid=WC0b01ac05800240cc.

  46. 46.

    2010 Nanomedicines Workshop webpage, http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/events/2009/12/event_detail_000095.jsp&mid=WC0b01ac058004d5c3.

  47. 47.

    Recital 1 and 2 of Regulation 1394/2007 on Advanced Therapy Medicinal Products.

  48. 48.

    REPORT FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT AND THE COUNCIL in accordance with Article 25 of 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, http://ec.europa.eu/health/files/advtherapies/2014_atmp/atmp_en.pdf. European Commission Recommendation of 18 October 2011 on the Definition of nanomaterial, http://ec.europa.eu/research/industrial_technologies/pdf/policy/commission-recommendation-on-the-definition-of-nanomater-18102011_en.pdf.

Abbreviations

API:

Active pharmaceutical ingredient

ATMP:

Advanced therapy medicinal products

CHMP:

Committee for medicinal products for human use

COMP:

Committee for orphan medicinal products;

ECHA:

European chemicals agency

EEA:

European environment agency economic area

EMA:

European medicines agency

EFSA:

European food safety authority

EU:

European Union, formerly European community

FDA:

US Food and Drug Agency

HTA:

Health technology assessment

ICH:

International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use

INN:

International nonproprietary name

ITF:

Innovation Task Force

LVEF:

Left ventricular ejection fraction

MAA:

Marketing authorisation application

MAH:

Marketing authorisation holder

MUGA:

Multiple gated acquisition

NBCD:

Non-biological complex drugs

ODD:

Orphan Drug Designation; Pharm: Pharmaceutical Development; PhV,

PSE:

Pharmacovigilance, product safety evaluation;

PIP:

Paediatric investigation plan

SA:

Scientific advice

SAWP:

Scientific advice working party

SME:

Small and medium sized enterprises

SME:

Small and medium enterprises

SmPC:

Summary of product characteristics

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Author information

Authors and Affiliations

  1. European Medicine Agency, EMA, London, UK

    Ruben Pita Pharm.D, LLM

Authors
  1. Ruben Pita Pharm.D, LLM
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Correspondence to Ruben Pita Pharm.D, LLM .

Editor information

Editors and Affiliations

  1. Utrecht University, Utrecht, Utrecht, The Netherlands

    Daan J.A. Crommelin

  2. Top Institute Pharma NBCD Working Group, Leiden, The Netherlands

    Jon S. B. de Vlieger

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Pita, R. (2015). The EU Regulatory Landscape of Non-Biological Complex Drugs. In: Crommelin, D., de Vlieger, J. (eds) Non-Biological Complex Drugs. AAPS Advances in the Pharmaceutical Sciences Series, vol 20. Springer, Cham. https://doi.org/10.1007/978-3-319-16241-6_11

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