Brexit and Regulatory Approval for Drugs in Europe - What Happens Now? 7 July 2016
Following the UK's European Union (EU) referendum, TranScrip has received many questions on what the impact is likely to be for pharmaceutical and biotech companies on the development and approval of future drugs. The following summarises TranScrip s responses to these questions. 1. How will leaving the EU affect the regulatory approval process? Since 1995, new medicines have been approved in the EU by one of three mechanisms: the Mutual Recognition Procedure, the Decentralised Procedure and the Centralised Procedure. In the Mutual Recognition Procedure, the applicant applies to a Reference Member State which assesses the application and then, having deemed it approvable, submits a report to other Concerned Member States who may accept it or make comments. Each member state then issues a national licence for the product, each with an identical Summary of Product Characteristics (SmPC). The Mutual Recognition Procedure has since been extended and, to some extent, replaced by the Decentralised Procedure. The main difference with the Decentralised Procedure is that the application is submitted simultaneously to all Concerned Member States. The subsequent steps are essentially identical. The important point in both these procedures is that National licences are issued by each Member State and are subsequently maintained nationally. These procedures were established by an EU Directive to bring the national laws in line across the EU. The framework for these procedures is thus currently enshrined in UK law and will still be so, irrespective of Brexit, until such time as the UK government changes the law. The third mechanism for approval of a medicine within the EU is the Centralised Procedure. In this process, a single application is made centrally to the European Medicines Agency (EMA), with scientific advice and dossier review conducted by the Committee for Medicinal Products for Human Use (CHMP). Subsequent to a positive opinion by CHMP, a licence is granted by the EMA. Crucially, this is a single licence, issued centrally, not a national one. Subsequent to Brexit, the position, and particularly the mechanism for maintenance of a centralised licence within the UK, will need to be clarified. It is entirely possible that the UK might opt to have observer status on CHMP following Brexit, akin to Iceland and Norway. This might require UK Law to be Page 2 of 6
tweaked to permit both the granting and maintenance of an EMA licence to continue to be valid in the UK for marketing purposes, despite the UK not being a member of the EU. However, if the UK has no relationship with the EMA structure, then all future submissions would need to be made separately to the Medicines and Healthcare products Regulatory Agency (MHRA) for a valid UK marketing licence to be given. This will need to be clarified and will obviously affect whether a centralised application can result in a right to sell a product within the UK. Therefore, in summary, the position for upcoming applications will not change in the short term, but any new process will necessarily be uncertain for some time. 2. Will Brexit have any effect on licences already granted? Licences already granted under the Mutual Recognition and Decentralised Procedures in the UK are national licences and will, therefore, remain in force irrespective of Brexit. With respect to licences already granted under the Centralised Procedure, either the MHRA has to re-review every previously submitted and approved application since 1995 and issue a UK licence for them or the UK Law will need to be changed to permit these licences to remain valid in the UK. It seems unlikely that the MHRA will want to re-review such applications and much more probable that some pragmatic solution will be adopted to allow these licences to remain valid, along with a mechanism for maintenance. 3. UK rapporteurs are frequently involved with the EMA approval process and are, therefore, consulted by us for scientific advice. Will it be better to go through other agencies in future? Currently, about 40% of all Marketing Authorisation Applications (MAA) submissions involve the UK as a rapporteur or co-rapporteur, and underlines the strength of the MHRA in making a valuable and respected contribution to the regulatory review of new medicines. In the short term, nothing will change. If the UK negotiates an observer status with the EMA, then there would be no reason for this situation to change or to revert to other agencies because of Brexit. Page 3 of 6
4. Is it likely that EMA staff currently based in the UK will be replaced? At the current time, it seems unlikely that the EMA would remain in a country which had exited the EU. However, exit negotiations have yet to be held and, therefore, it is not possible to predict what the situation will be in the future. 5. Will the UK be able to be a rapporteur in future? If the UK negotiates an observer status with the EMA, then this arrangement would likely allow the UK to bid for, and act as, a rapporteur much in the same way as Norway and Iceland. 6. As much of the EMA is populated by UK staff, is this likely to cause major delays and disruption within EMA? Until the exit process and conditions negotiated have been completed, it is unlikely that any major changes to the EMA processes will occur. For the immediate future, it is therefore unlikely that there will be any delay or disruption to the EMA activities. 7. Currently, some committees, working parties and scientific advisory groups within EMA involve UK staff. Is this likely to be affected? If the UK negotiates an associate status with the EU, then it is unlikely that membership of any EMA committee, working party or scientific advisory group would need to change. If no associate status is negotiated, then it seems likely that these contributors will be replaced by representatives from countries which continue to take part in the EMA process. 8. In the EU, biologicals have to go through the Centralised Procedure by law. Will the company submitting the application need to be located within in the EU? The Marketing Authorisation Holder (MAH) can be an entity or a person. Once the exit process and conditions negotiated have been completed, either the entity or the person will need to be established within the EU. Page 4 of 6
9. How will Brexit affect the new clinical trials regulation and will companies need to apply for separate Clinical Trial Authorisations (CTA)? A new EU Clinical Trials Regulation was agreed in 2014, introducing a raft of changes to the existing EU Clinical Trials Directive, which was often criticized for having excessive red tape. That said, these new EU rules will become applicable only in 2017/18 so as to allow sufficient time for the development and testing of the EU technology which supports its implementation. It is hoped that the new legislation will make it easier for researchers to conduct clinical trials in the EU, and arrest a marked decline of 25% over four years, by some counts in such work in the 28 member states. The new clinical trial regulation is an EU Regulation that will not automatically apply to the UK once it leaves the EU because the current treaties that state that the UK will accept EU Laws and Regulations will no longer apply. If the UK wishes to accept and abide by the new EU clinical trial regulation, then a new UK statutory instrument would need to be enacted to make provision for this to replace the current Directive which is enacted in British law. 10. What impact will Brexit have on Orphan Medicinal Products? If the UK negotiates an observer status with the EMA, then there would be no reason for this situation to change with respect to approval of Orphan Medicinal Products. 11. Will scientific advice meetings scheduled with the EMA in the next few months, or submissions planned for the near future, be affected and, if so, what should we do? Until the process of the UK leaving the EU has been completed, it is unlikely that any meetings currently scheduled, or occurring prior to exit, will be affected. For any company planning a submission within the next year, TranScrip advises that they should continue to plan to submit their application via the Centralised Procedure, if that was their intended strategy, and continue to use the MHRA for scientific advice or as a rapporteur if they wish to do so. Page 5 of 6
12. How can TranScrip help companies with drug development and approval? TranScrip has a history of working with clients worldwide to deliver scientific advice and global regulatory submissions, with notable success. We also maintain informal links with European Regulators, including MHRA. We look forward to continuing to work with established and new clients, and especially to help them navigate the changing regulatory environment which lies ahead in Europe. If you have any questions or concerns that are not covered above, or you wish to discuss further how TranScrip can assist you with your development or submission needs, please contact bob.milsted@transcrip-partners.com. Page 6 of 6