Event summary of “Nanomedicines and nanosimilars: the medical need for a centralised EMA regulatory process” held as a live webinar on 30th November 2021 10.00-11.30 CET
The European Alliance for Access to Safe medicines (EAASM) organised an online event on “Nanomedicines and nanosimilars: the medical need for a centralised EMA regulatory process” bringing together high-level speakers from the European Parliament, the European Commission, academia and other experts.
The objective was to discuss the need for a centralised regulatory framework specific to nanomedicines and nanosimilars as well as to provide useful recommendations so that regulatory support and enhancements can be developed urgently and thus provide medicines with the highest quality, safety and efficacy profiles to European patients.
The EAASM Executive Director Mike Isles introduced this very important topic by highlighting the complexity of nanomedicines and their follow-on products, the nanosimilars. The challenges raised by this complexity aren’t properly addressed as regulatory approvals for these medicines are currently decided on an ad-hoc basis by product category. With the accelerating progress in the development of clinically significant nanosimilars and in view of the recent policy developments related to the Pharmaceutical Strategy for Europe and the revision of the general EU pharmaceutical legislations, this is the right time to set the scene for building a consensus so that such regulatory weaknesses can be addressed, and, ultimately, for creating an innovative healthcare landscape across member states.
The webinar’s host, Socialists & Democrats, Bulgarian MEP Petar Vitanov, stressed that patient safety must always come first and should become a key pillar under the Pharmaceutical Strategy for Europe. He added that the EU has a major opportunity to lead the world in developing a centralised regulatory procedure. He justified this by explaining that nanomedicines offer potential solutions for several current treatment challenges including cancer, cardiovascular and neurodegenerative disorders. Furthermore, these medicines are proving to be very important in oncology treatments and have reduced mortality in cancer patients and also have had a positive impact in therapies that target specific cells.
Dr. Prof. Scott McNeil from the University of Basel (Switzerland) shared his views on why nanomedicines and nanosimilars require a centralised regulatory pathway. It is obvious that their complexity is directly linked to their size scale: 1 nanometer represents 10-9 meter, which is minuscule. Moreover, Prof. McNeil emphasised that a number of nanomedicines are already approved and commercialised – some since 1949 – but can more recently be found in the nano-based COVID-19 vaccines. Their nano-size unfortunately leads to challenges, as their physicochemical properties directly influence biocompatibility and product quality. Nanomedicines are complex formulations, so the challenge is to identify meaningful differences between the follow-on and the reference/innovator product. Prof. McNeil concluded by pointing out that the centralised regulatory approach is compulsory for many clinical indications, but optional for significant therapeutic, scientific or technical innovation.
Dr. Jon de Vlieger, Director Business Development and coordinator of the Working Group on non-biological complex drugs at Foundation Lygature, presented the profile of nanomedicines and their similars as non-biological complex drugs. He said that the rise of bio- and nanotechnologies has accelerated the development of complex medicines, and that this was catalysing an increase in regulatory guidance around the globe. The EMA and its US counterpart, the FDA, had launched a pilot programme in September 2021 aiming to provide parallel advice. Dr. de Vlieger informed the audience that because, each EU Member State has its own national authorisation procedures, the European regulatory landscape for this type of product is heterogenous. “There is a lot of variation in the regulatory approaches for NBCDs and their follow-on products in the EU, predominantly relying on non-centralised procedures. Nanomedicines would benefit from a mandatory centralised procedure, as this will guarantee consistency in the scientific evaluation of follow-on products,” said Dr de Vlieger. Currently the regulatory assessment is heterogenous, demonstrated by 85 follow-on products approved until 2018 by different regulatory pathways (from the generic, to biosimilars, hybrid as well as centralised and decentralised procedures). Not only does this give rise to different criteria being used for assessment, it means that multiple brand names proliferate thus making adverse event pharmacovigilance linkage difficult.
Dr. Josep Maria Guiu from the International Pharmaceutical Federation introduced the practical issues around interchangeability in relation to future nanomedicines and nanosimilars. Dr Guiu described the challenges around interchangeability of similar medicines for healthcare professionals. He stated that it is important that clear guidelines should be laid down and that healthcare professionals require education to ensure any switching of medication is carried out carefully in order not to compromise the patient’s safety. He proposed actions in the field of hospital pharmacy, which includes a harmonised and rational use of medicines, including nanosimilars, as hospital pharmacy substitution policies for generic, hybrid and biosimilar drugs vary from a country to another.
The debate continued with the presentation of European Commission’s DG SANTE Dr Andrzej Rys, Director on Health systems, medical products and innovation. Dr Rys pointed out that we are at a crucial moment in shaping the European pharmaceuticals legislation, and that patient safety should be the central point of the European Union’s pharmaceutical policy. The strategy published by the EMA in 2020 already facilitates the implementation and the control of new technologies. Dr Rys further added that future options should consider an adaptation to the current system of authorisation, and the introduction of new regulatory pathways and requirements. Dr Rys concluded his speech by mentioning that the European Commission indeed aims to address unmet medical needs, and wants to facilitate the development of high-quality, effective, and safe medicines while harnessing the benefits of digital emerging sciences.
MEP Vitanov concluded by highlighting key messages from the meeting and specifically referenced the recent, significant Resolution of 24 November 2021 on the Pharmaceutical Strategy for Europe whereby the European Parliament:
25. Calls on the Commission to build on the work of Europe’s Beating Cancer Plan and ensure that Europe becomes the worldwide centre of excellence for R&D in emerging, innovative fields of medicine; underlines that state-of-the art technologies, such as nanomedicines, stand to provide solutions to current treatment challenges in areas such as cancer and cardiovascular diseases; highlights that these innovative fields of medicine should be authorised by the centralised approval framework for nanomedicines
101. Urges the Commission and the EMA to consider the full lifecycle of all innovative medicines and therapies, including gene and cell therapies, personalised medicine, nanotechnology and next-generation vaccines, and ensure a fit-for-purpose framework for off-patent competition at the time of loss of exclusivity; calls on the Commission to establish a regulatory framework for nanomedicines and nanosimilar medicines, and calls for these products to be approved through a compulsory centralised procedure.
Overall, the experts agreed that a centralised approval process is the logical scientific approach to ensure a robust fit for purpose regulatory pathway, as echoed in MEP Vitanov’s recent article published in the Parliament Magazine which stated that “it is critical that we as policymakers, together with patient representatives, healthcare professionals, and the pharmaceutical sector, contribute to the creation of a resilient and sustainable healthcare landscape that ensures innovative medicines for all citizens in the EU”.
The scientific proposition for an EMA centralised regulatory procedure can be summarised as follows:
- Nanomedicines and nanosimilars are highly complex products that rely on a robust and well controlled manufacturing process – as such follow-on nanomedicines can only ever be similar and require clinical evidence to ensure an adequate level of similarity from a safety and efficacy standpoint. A group of experts in fact, concluded “This very complex molecular and/or product structure makes it practically impossible to develop generic alternatives, i.e. products with an identical molecular composition…and so…a simple authorization referencing another product, solely supported by evidence of pharmacokinetic bioequivalence based on a single ingredient, is definitely not acceptable”. In addition, “…interchangeability of such medicines requires clear clinical oversight based on evidence and so “…substitution can therefore – analogous to biosimilars – not be recommended until confirmation of “therapeutic interchangeability” is available”
- Currently the regulatory assessment is heterogenous, demonstrated by 85 follow-on products approved until 2018 were by different regulatory pathways (from the generic, to biosimilars, hybrid as well as centralised and decentralised procedures). Not only does this give rise to different criteria being used for assessment, it means that multiple brand names proliferate thus making adverse event pharmacovigilance linkage difficult.
We invite you to join the Nanomedicines Regulatory Coalition and sign the Petition with a view to endorse more collaborative actions for a new robust regulatory framework for nanomedicines and nanosimilars.