papers, 3 blogs and 1 book published
partners from industry and academia
Non-biological complex drugs (NBCDs) consist of different (closely related and often nanoparticulate) structures that cannot be fully quantitated and characterized by physico-chemical analytical means. Examples include glatiramoids, iron-carbohydrate complexes, polymeric micelles, complex ocular emulsions and liposomes. The complex nature of NBCDs means that minute variations in the manufacturing process can substantially change the composition of final products, and this poses a challenge for the development of regulatory guidelines. The working group aims to ensure patient benefit through a science-based approach for the approval of NBCD products and follow-on versions.
- K.Klein, P.Stolk, M.L.De Bruin, H.G.M.Leufkens, D.J.A.Crommelin, J.S.B.De Vlieger. The EU regulatory landscape of non-biological complex drugs (NBCDs) follow-on products: Observations and recommendations. European Journal of Pharmaceutical Sciences
- Volume 133, 15 May 2019, Pages 228-235.
- de Vlieger, J.S.B., Crommelin, D.J.A., Tyner, K. et al. Report of the AAPS Guidance Forum on the FDA Draft Guidance for Industry: “Drug Products, Including Biological Products, that Contain Nanomaterials”. AAPS J 21, 56 (2019).
- Hussaarts et al. Equivalence of complex drug products: advances in and challenges for current regulatory frameworks; Ann N Y Acad Sci Apr 26. [Epub ahead of print] (2017)
- Crommelin and de Vlieger, 2015 (Eds.), Non-Biological Complex Drugs. The Science and the Regulatory Landscape; AAPS/Springer, Advances in the Pharmaceutical Sciences Series, NY.
- Crommelin et al. Different pharmaceutical products need similar terminology; AAPS J. 2014 Jan;16(1):11-14.
- Schellekens et al. How to Regulate Nonbiological Complex Drugs (NBCD) and Their Follow-on Versions: Points to Consider; AAPS J. 2014 Jan;16(1):15-21.
A list of NBCD-related publications co-authored by Lygature can be found on this page.
Driving science-based discussions
The NBCD Working Group was established following a scientific workshop organized by TI Pharma – now Lygature. The partnership brings together both industry partners and international experts, who engage in debate with a wide range of relevant stakeholders. Lygature provides the necessary support and scientific expertise, to ensure that discussions are inclusive and productive. Activities include:
- Scientific management. Lygature is responsible for scientific management and organizational aspects of the working group as a whole. Responsibilities include general project management, management of strategic alliances and alignment with relevant stakeholders.
- Provider of neutral ground. As an independent third party with no commercial interest, Lygature has hosted the NBCD Working Group from the beginning, and provides neutral ground to facilitate discussion between stakeholders.
- Communication & dissemination. An important contribution by Lygature is communication and dissemination, with the aims of establishing terminology and creating awareness of the challenges faced. Activities include: presenting at international conferences; (co-)writing of scientific articles, white papers and blogs; organization of conferences; and brand building.
The NBCD Working Group contributes strongly to Lygature’s mission of accelerating the launch of medicines that improve society's wellbeing. Since stakeholders often have different interests, the project has required extensive management capabilities, along with expertise in both science and the regulatory landscape.
Lygature together with
Biosimilar regulatory framework for nanosimilars
On March 20th, the European Alliance for Access to Safe Medicines (EAASM) and Member of the European Parliament José Inácio Faria (PT, EPP) co-hosted a breakfast meeting in the European Parliament to discuss the appropriateness of the current regulatory approval process for nanomedicines and their follow-on products, also known as nanosimilars.
During the breakfast meeting, Jon de Vlieger, coordinator of the Working Group of Non-Biological Complex Drugs (NBCDs) discussed the challenges for approval standards for nanomedicines and NBCDs.
One of the issues for these drugs is that it is impossible to ensure identical copy versions, leading to subsequent discussions whether these products are therapeutically equivalent.
Jon explained how Europe has been able to successfully pioneer and implement a solid regulatory framework for biosimilars. He argues that, ideally, this framework should serve as a model for the approval of nanosimilars and NBCDs. This would avoid potential confusion and ambiguity of having different policies or interpretations per country.
The complexity of medicines is increasing at a rapid pace and so are the questions around their quality, handling and affordability. Only with involvement of all stakeholders we can ensure a fit for purpose framework for regulatory approval. The breakfast meeting in the European Parliament identified that a consensus dialogue as well as alignment between all players in Europe and beyond are needed to further explore the field of nanomedicines at an EU and a national level.
Publication: Discussions on FDA Guidance on drug products containing nanomaterials
During the Guidance Forum of the American Association of Pharmaceutical Scientists on September 11, 2018, participants from industry, academia, and regulatory bodies came together to discuss the US Food and Drug Administration’s (FDA) draft guidance titled: “Drug Products, Including Biological Products, that Contain Nanomaterials”.
Most of the drug products containing nanomaterials are non-biological complex drugs (NBCDs). The NBCD Working Group was actively involved in the discussions and several members co-authored the official meeting report, which is now published in the AAPS Journal.
The lively discussions at the AAPS Guidance Forum provided developers of drug products containing nanomaterials important insights for New Drug Applications (NDA) and Abbreviated New Drug Applications (ANDA). The Forum served as an open discussion platform for scientists from industry, academia and regulatory bodies.
The Open Access publication in the AAPS Journal with conclusions and open issues resulting from the on the Forum can be found here.
Publication: Heterogeneity in Europe’s regulatory approach taken for NBCDs
On March 31st, 2019, the European Journal of Pharmaceutical Sciences published an article by colleague Kevin Klein and others describing the heterogeneity in the regulatory approach taken for non-biological complex drugs (NBCDs). This overview aims to stimulate the rethinking of regulatory pathways for NBCDs.
NBCD quality is highly dependent on a robust and well-controlled manufacturing process. Replicating these products therefore proves challenging for generic drug developers. Despite the challenges faced in setting up high-quality development, there is as of yet no formal regulatory pathway for approval of NBCDs, since they are not recognized as a distinct category of medicines.
At this moment, a ‘case-by-case’ approach is often applied for the regulatory approval of NBCDs. Furthermore, NBCD regulatory approval can also be left to national competent authorities. Almost all of the 85 NBCD follow-on products available in the EU in 2018 have been approved via various non-centralised procedures. These different pathways lead to heterogeneity in the regulatory approach and outcomes, as shown by the study. For some product classes, such as iron sucrose complexes, this has resulted in safety and efficacy implications.
Although the clinical implications of the findings need further investigation, the observed heterogeneity carries the risk of lack of predictability for NBCD developers and many other uncertainties for stakeholders. This paper tries to contribute to rethinking the regulatory approach for NBCDs and ultimately to design prudent regulatory pathways for NBCD follow-on products.
Read the full paper here.