PDF herunterladen
CC BY-NC-ND 4.0 · Planta Med 2021; 87(12/13): 1110-1116
DOI: 10.1055/a-1511-8558
Formulation and Delivery Systems of Natural Products
Reviews

Medical Devices Made of Substances: Possible Innovation and Opportunities for Complex Natural Products[ # ]

Anna Rita Bilia
1   Department of Chemistry “Ugo Schiff,” University of Florence, Sesto Fiorentino, Florence, Italy
,
Enrico Stefano Corazziari
2   IRCCS Humanitas Research Hospital, Department of Gastroenterology, Rozzano, Milan, Italy
,
Stefano Govoni
3   Department of Drug Sciences, University of Pavia, Pavia, Italy
,
Alessandro Mugelli
4   Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy
,
Marco Racchi
3   Department of Drug Sciences, University of Pavia, Pavia, Italy
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints

Abstract

The novel Regulation 2017/745/EC on medical devices introduces and strengthens the role of “medical devices made of substances”, which mostly include substances of natural origin. Natural products may follow different regulations, from food to therapeutics. Concerning their isolated constituents, extracts are characterized by a complexity that is not easily tackled from both a scientific and a regulatory point of view, but more importantly, from a therapeutic point of view. The evidence-based approach applied to isolated molecules requires appropriate evidence of quality, efficacy, and safety. The same needs must be reached for complex substances by finding appropriate methods to generate this evidence, and in addition, defining an appropriate regulatory field for them. From a scientific point of view, new methods, such as those proposed by systems biology, are available and applicable to complex substances. From a regulatory point of view, Directive 2001/83/EC on medicinal products seems to be modeled on single (or combinations of single) molecule products. On the other hand, Regulation 2017/745/EC on medical devices seems to apply to complex substances without derogating on quality, efficacy, and safety. The regulation specifically names and strengthens medical devices that include substances, mostly of natural origin, introducing the official term “medical devices made of substances”. This paper discusses and proposes an interpretation of important terms connected to this legislation, regarding both scientific and regulatory issues, and the opportunities the regulation may give for innovation and therapeutic improvement with natural complex substances.

Key words

herbal medicinal products - medical devices - medical devices made of substances - Regulation 2017/745/EC - systems biology - pharmacological action

# Dedicated to Professor Arnold Vlietinck on the occasion of his 80th birthday.




Publikationsverlauf

Eingereicht: 28. Oktober 2020

Angenommen nach Revision: 13. Mai 2021

Artikel online veröffentlicht:
06. August 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Bilia AR. Botanical-sourced products and herbal medicinal products: the Italian status and positioning and the European Regulation. Modern Fitofarmakot 2010; 1: 22-33
    PubMedGoogle Scholar
  • 2 Bilia AR. Herbal medicinal products versus botanical-food supplements in the European market: state of art and perspectives. Nat Prod Commun 2015; 10: 125-131
    PubMedGoogle Scholar
  • 3 Europe Herbal Industry Market Research Report–Maia Research 2020. Accessed January 28, 2021 at: https://www.industryresearch.co/TOC/12591998%23TOC
    PubMedGoogle Scholar
  • 4 Bilia AR, Costa MC. Medicinal plants and their preparations in the European market: why has the harmonization failed?. Phytomedicine 2021; 81: 153421 DOI: 10.1016/j.phymed.2020.153421.
    CrossrefPubMedGoogle Scholar
  • 5 European Union. Directive 93/42/EEC of 14 June 1993 concerning medical devices. Official Journal of the European Communities no. L-169 of 12 July 1993. Accessed June 1, 2021 at: http://data.europa.eu/eli/dir/1993/42/oj
    PubMedGoogle Scholar
  • 6 European Union. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No. 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC. Official Journal of the European Union no. L 117/1 of May 5, 2017. Accessed June 1, 2021 at: http://data.europa.eu/eli/reg/2017/745/oj
    PubMedGoogle Scholar
  • 7 European Union. Regulation (EU) 2020/561 of the European Parliament and of the Council of 23 April 2020 amending Regulation (EU) 2017/745 on medical devices, as regards the dates of application of certain of its provisions OJ L 130/18, 2020 Apr 24. Accessed June 1, 2021 at: http://data.europa.eu/eli/reg/2020/561/oj
    PubMedGoogle Scholar
  • 8 European Union. Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements. Official Journal of the European Communities no. L-183/51 of 12 July 2002. Accessed June 1, 2021 at: http://data.europa.eu/eli/dir/2002/46/oj
    PubMedGoogle Scholar
  • 9 European Union. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the community code relating to medicinal products for human use. Official Journal of the European Communities no. L-311/67 of 28 November 2001. Accessed June 11, 2021 at: http://data.europa.eu/eli/dir/2001/83/oj
    PubMedGoogle Scholar
  • 10 European Union. Council directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products. Official Journal of the European Communities no. P-022 of 9 February 1965. Accessed June 1, 2021 at: http://data.europa.eu/eli/dir/1965/65/oj
    PubMedGoogle Scholar
  • 11 European Union. Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending directive 2001/83/EC on the community code relating to medicinal products for human use. Official Journal of the European Union no. L-136/34, 2004 Apr 30. Accessed June 1, 2021 at: http://data.europa.eu/eli/dir/2004/27/oj
    PubMedGoogle Scholar
  • 12 European Medicines Agency. Herbal medicinal products. Accessed 2020 September 30 at: https://www.ema.europa.eu/en/human-regulatory/herbal-medicinal-products
    PubMedGoogle Scholar
  • 13 European Commission DG Enterprise and Industry. Medical devices: guidance document – borderline products, drug-delivery products and medical devices incorporating, as an integral part, an ancillary medicinal substance or an ancillary human blood derivative. Guidelines relating to the application of: The Council Directive 90/385/EEC on active implantable medical devices; the Council Directive 93/42/EEC on medical devices. Meddev 2.1/3 rev3. Ref. Ares(2015)2062695 – 18/05/2015; Accessed June 11 2021 at http://www.meddev.info/_documents/2_1_3_rev_3-12_2009_en.pdf
    Google Scholar
  • 14 European Union. Directive 2007/47/EC of the European Parliament and of the Council of 5 September 2007 amending Council Directive 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices, Council Directive 93/42/EEC concerning medical devices and Directive 98/8/EC concerning the placing of biocidal products on the market. Official Journal of the European Union no. L-247/21, 2007 Sept 29. Accessed June 11, 2021 at: http://data.europa.eu/eli/dir/2007/47/oj
    PubMedGoogle Scholar
  • 15 Bilia AR. Science meets regulation. J Ethnopharmacol 2014; 158 Pt B: 487-494
    CrossrefPubMedGoogle Scholar
  • 16 Racchi M, Govoni S, Lucchelli A, Capone L, Giovagnoni E. Insights into the definition of terms in European medical device regulation. Expert Rev Med Devices 2016; 13: 907-917 DOI: 10.1080/17434440.2016.1224644.
    CrossrefPubMedGoogle Scholar
  • 17 Racchi M, Govoni S. The concept of non-pharmacological mechanism of action in medical devices made of substances in practice: what pharmacology can do to promote the scientific implementation of the European medical device regulation. Pharmadvances 2020; 01s: 4-12 DOI: 10.36118/pharmadvances.01.2020.02s.
    CrossrefPubMedGoogle Scholar
  • 18 Wanjek C. Systems Biology as Defined by NIH. An Intellectual Resource for Integrative Biology. NIH Catal 2011; 19: 1 Accessed June 11, 2021 at: https://irp.nih.gov/catalyst/v19i6/systems-biology-as-defined-by-nih
    PubMedGoogle Scholar
  • 19 Thomford NE, Senthebane DA, Rowe A, Munro D, Seele P, Maroyi A, Dzobo K. Natural products for drug discovery in the 21st century: innovations for novel drug discovery. Int J Mol Sci 2018; 19: 1578 DOI: 10.3390/ijms19061578.
    CrossrefPubMedGoogle Scholar
  • 20 Verwaltungsgericht Köln. Aktenzeichen: 7K 4442/16. Searched as “Bionorica Urteil 07.11.2017”. Accessed September 30, 2020 at: https://www.justiz.nrw.de/nrwe/ovgs/vg_koeln/j2017/7_K_4442_16_Urteil_20171107.html
    PubMedGoogle Scholar
  • 21 Dunbar KB, Agoston AT, Odze RD, Huo X, Pham TH, Cipher DJ, Castell DO, Genta RM, Souza RF, Spechler SJ. Association of acute gastroesophageal reflux disease with esophageal histologic changes. J Am Med Assoc 2016; 315: 2104-2112
    CrossrefPubMedGoogle Scholar
  • 22 Souza RF, Baveh L, Spechler SJ, Tambar UK, Bruick RK. A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2α: a potential role for targeting HIF-2α to prevent and treat reflux esophagitis. Curr Opin Pharmacol 2017; 37: 93-99
    CrossrefPubMedGoogle Scholar
  • 23 Neri L, Basilisco G, Corazziari E, Stanghellini V, Bassotti G, Bellini M, Bellini M, Perelli I, Cuomo R. LIRS Study Group. Constipation severity is associated with productivity losses and healthcare utilization in patients with chronic constipation. United European Gastroenterol J 2014; 2: 138-147 DOI: 10.1177/2050640614528175.
    CrossrefPubMedGoogle Scholar
  • 24 Touw K, Ringus DL, Hubert N, Wang Y, Leone V, Nadimpalli A, Theriault BR, Huang YE, Tune JD, Herring PB, Farrugia G, Kashyap PC, Antonopoulos DA, Chang EB. Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models. Physiol Rep 2017; 5: e13182 DOI: 10.14814/phy2.13182.
    CrossrefPubMedGoogle Scholar
  • 25 Akbarali HI, Dewey WL. The gut-brain interaction in opioid tolerance. Curr Opin Pharmacol 2017; 37: 126-130 DOI: 10.1016/j.coph.2017.10.012.
    CrossrefPubMedGoogle Scholar
  • 26 Official website of the European Commission. Accessed October 19, 2020 at: https://ec.europa.eu/health/md_eudamed/overview
    PubMedGoogle Scholar