Cited by 144Nanoparticle-Based Drug DeliveryPharmaceutical studies and practicesNanotechnology research and applications

Nanopharmaceutics: part I-Clinical trials legislation and good manufacturing practices (GMP) of nanotherapeutics in the EU

Open access
Souto, Eliana B., Silva, Gabriela F., Dias-Ferreira, João, Zielinska, Aleksandra, Ventura, Fátima, Durazzo, Alessandra, Lucarini, Massimo, Novellino, Ettore +1 more·2020·Pharmaceutics

Abstract

The latest advances in pharmaceutical technology are leading to the development of cutting edged approaches to produce what is now known as the "Holy Grail" of medicine-nanopharmaceutics. Over the latest decade, the pharmaceutical industry has made important contributions to the scale up of these new products. To ensure their quality, efficacy, and safety for human use, clinical trials are mandatory. Yet, regulation regarding nanopharmaceuticals is still limited with a set of guidelines being recently released with respect to compliance with quality and safety. For the coming years, updates on regulatory issues about nanopharmaceuticals and their use in clinical settings are expected. The use of nanopharmaceuticals in clinical trials depends on the approval of the production methods and assurance of the quality of the final product by implementation and verification of the good manufacturing practices (GMP). This review addresses the available legislation on nanopharmaceuticals within the European Union (EU), the GMP that should be followed for their production, and the current challenges encountered in clinical trials of these new formulations. The singular properties of nanopharmaceuticals over their bulk counterparts are associated with their size, matrix composition, and surface properties. To understand their relevance, four main clinical trial guidelines, namely, for intravenous iron-based nanopharmaceuticals, liposomal-based nanopharmaceuticals, block copolymer micelle-based nanopharmaceuticals, and related to surface coating requirements, are described here.

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  • Continuous manufacturing approaches like microfluidic assembly offer promising pathways to enhance reproducibility and scalability, yet demand considerable investment and process optimization.

    “Continuous manufacturing approaches like microfluidic assembly offer promising pathways to enhance reproducibility and scalability, yet demand considerable investment and process optimization [217].”

    From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [217]

    The Introduction describes scale-up as challenging, and the Conclusions say a reproducible, scalable production method must be developed and validated. Those passages support the general need for reproducibility and scalability, but they do not identify continuous manufacturing or microfluidic assembly as a promising approach, or discuss the investment such approaches require. No page numbers were available in our copy. (LLM, conf=0.82)

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  1. [23]Official Journal of the European Communities—DIRECTIVE 2001/20/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 4 April 2001 2001 Available online: http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32001L0020&from=EN (accessed on 5 March 2017)
  2. [24]Official Journal of the European Communities—COMMISSION DIRECTIVE 2003/94/EC of 8 October 2003 2003 Available online: http://ec.europa.eu/health/sites/health/files/files/eudralex/vol-1/dir_2003_94/dir_2003_94_en.pdf (accessed on 7 March 2017)
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  5. [48]EMA Issues Draft Reflection Paper for Iron-Based Nano-Colloidal Products. Belgium: 11 February 2014 Available online: http://gabi-journal.net/news/ema-issues-draft-reflection-paper-for-iron-based-nano-colloidal-products (accessed on 3 September 2019)

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Authors
Souto, E. B., Silva, G. F., Dias-Ferreira, J., Zielinska, A., Ventura, F., Durazzo, A., Lucarini, M., Novellino, E., & Santini, A.
Affiliations
  • University of Coimbra (PT)
  • Department of Pharmaceutical Technology, Faculty of Pharmacy (FFUC), University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
  • University of Lisbon (PT)
  • Consiglio per la ricerca in agricoltura e l’analisi dell’economia agraria (IT)
  • University of Naples Federico II (IT)
Corresponding author
  • Souto, Eliana B.
  • Santini, Antonello
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2020-02-11
Volume
12
Issue
2
Pages
146
ISSN
1999-4923 (ISSN-L)
OpenAlex
W3005713586
Cited by
144
References
61
Citations by year
2026: 28 · 2025: 30 · 2024: 9 · 2023: 19 · 2022: 25 · 2021: 15 · 2020: 17 · 2019: 1
FWCI
1.27
Type
journal article
Language
en
Open access
Locations
  • Pharmaceutics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
Funders
Fundação para a Ciência e a Tecnologia (UIDB/04469/2020, COMPETE, PT2020, M-ERA-NET-0004/2015-PAIRED, UIDB/04469)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
  • Physical Sciences › Engineering › Biomedical Engineering › Nanotechnology research and applications
Keywords
nanotherapeutics, regulatory legislation, good manufacturing practices, clinical trials, European Union regulation, liposomal drug delivery, block copolymer micelles, scale-up production

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