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 Report of the AAPS Guidance Forum on the FDA Draft Guidance for Industry: “Drug Products, Including Biological Products, that Contain Nanomaterials”.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
Report: Regulatory research needs for new and follow-on nanomedicines
Following the 2019 Global Summit on Regulatory Science (GSRS19) on Nanotechnology and Nanoplastics, the European Commission's Joint Research Centre (JRC) has released a technical report summarizing the discussions of almost 200 international scientists, regulators and policy makers present at the Summit.
You can read more here.
Regulations for complex drug products; is global alignment in sight?
Jon de Vlieger, Director of Business Development and Coordinator of the Non-Biological Complex Drugs (NBCD) Working Group at Lygature, was invited to present at two high-profile international meetings, where he shared his views on regulations for complex drug products. Read more in his blog below.
Nowadays, globalization is integrated in the way we think, act and plan for new activities. Major health and environmental challenges can no longer be solved on a ‘country-by-country’ basis. They demand coordinated global action. To solve these challenges, we must discuss how to arrive at joint policies and regulations. Over the last two months, I was fortunate to be able to speak at two high-profile meetings – the Global Summit on Regulatory Science (GSRS) in Stresa, Italy, and the American Association of Pharmaceutical Scientists (AAPS) PharmSci 360 meeting in San Antonio, USA. Both meetings provided an excellent platform for discussions with all the relevant parties, including representatives from regulatory authorities and industry, other scientific experts, and stakeholders from countries around the world. Collectively, we shared the latest insights, discussed bottlenecks in current practice, and started to brainstorm what future regulations for complex drug products might look like.
My presentations focused on regulations for nanomedicines, nanosimilars and non-biological complex drugs (NBCDs). For these complex products, different regulatory approaches are currently used in different parts of the world, leading to different regulatory requirements for the admission of such products to individual countries. This is suboptimal, because it creates uncertainty among those involved about how these products should be developed.
One thing we could do is build upon our collective experience of regulation for other complex products, such as biologics and their similars. In my opinion, we should use that experience. In order to do so, I strongly believe it is crucial that all the involved parties meet early on in the development process to shape a coordinated global approach. When it comes to topics such as the use of new technologies in the development of medicines, we should grasp the opportunity to do just that. Let’s have the discussion and jointly shape new policies and regulatory guidance before everyone has already taken their own position on the topic.
Looking to the future, I expect that the increasing complexity and diversity of medical products will demand that we thoroughly review our current practices. In particular, these complex modalities will continue to challenge current regulatory frameworks for new and off-patent drugs. There are several questions that we need to find answers to. Which product characteristics are essential for the intended therapeutic performance? How do we determine these characteristics, and which scientific approaches are appropriate to establish similarity between a follow-on product and the reference listed drug?
The GSRS 2019 meeting in Stresa clearly provided food for thought, and the lively discussions at the event demonstrated the collective energy to continue the dialogue on this important topic. The AAPS PharmSci 360 meeting convinced me that a very strong technology push, in terms of developing new therapeutic modalities as well as new analytical tools to characterize complex products, will continue to challenge current regulatory frameworks. I’m also convinced that the efforts of international experts, such as those convening in the NBCD Working Group, really can make a difference when it comes to ensuring the implementation of science-based regulations worldwide.
Colleague Jon de Vlieger speaking about NBCDs at AAPS 2019 PharmSci 360
After speaking at the Global Summit on Regulatory Science 2019 in September, Jon de Vlieger, our Director Business Development and Coordinator of the NBCD Working Group, will also be presenting at the American Association of Pharmaceutical Scientists (AAPS) 2019 PharmSci 360 conference in San Antonio, Texas, on November 4. He will update you on the current state of the debate on non-biological complex drug (NBCD) products and share recommendations for advancing the science-based discussions on an international level.
The AAPS PharmSci 360, a large scientific conference for pharmaceutical science, has been split into five tracks that cover all aspects of the pharmaceutical sciences and that cover both chemical and biomolecule areas. Jon’s talk is part of the Formulation and Quality track and is titled ‘The Similarity Question for Non-Biological Complex Drugs; Advances in Characterization, Regulation and Global Harmonization’.
Read more about Jon’s talk and its learning objectives here.