Regulatory affairs experts at PPD, Alistair Davidson and Vincenzo Cannizzaro, reflect on how the United Kingdom's departure from the European Union might impact the pharmaceutical industry.
The United Kingdom’s withdrawal from the European Union (EU) could have a significant impact for the biopharmaceutical and pharmaceutical industry. With a pharmaceutical market valued at $24 billion, the U.K. ranks as the eighth largest in the world.
The most recent Heads of Medicines Agencies annual statistics show that the U.K. is the third most frequent choice for reference member state (RMS) for the mutual recognition process and the decentralized process.
The impact will be significant
Competent authorities, such as the European Medicines Agency (EMA), the Coordination Group for Mutual Recognition and Decentralised Procedures - Human and the European Commission, already have released various information on the changes that the bio/pharmaceutical industry will need to undertake to be compliant with current legislation when the U.K. leaves the EU.
Examples of the areas that will be impacted by the U.K.’s withdrawal include:
- Transposition of the new EU clinical trials regulation (CTR) from EU to U.K. law in 2018
- Supply chain management for investigational medicinal products especially around good manufacturing practices (GMP), import/export, and quality release and testing, as the U.K. will continue to be an important location for clinical research
- Ongoing trials management where the sponsor is U.K.-based and the trials are across the EU
- Continuing GxP inspections in which, for example, inspection findings that mandate global process change can be done without an increase in standards
- Access to data for U.K. trials held in EudraCT and the EU portal/database. The bio/pharmaceutical industry values access to EU portals/databases and supports the current level of trial and data transparency in the U.K. at present
- The marketing authorization holder (MAH) responsibilities. For example:
- Pharmacovigilance activities, which, if currently performed from the U.K., will need to be transferred to a country within the EU
- Quality activities, which, if currently performed from the U.K., will need to be transferred to a country within the EU as well as additional implications for the import of drug substance and product into the EU from the U.K.
- Need for MAHs who obtained their licenses via the centralized procedure (CP) to ensure their product retains the ability to sell in the U.K. or similarly change rapporteur/co-rapporteur if either role is current fulfilled by the Medicines and Healthcare products Regulatory Agency (MHRA)
- Similarly, the need for MAHs to adjust the role of the RMS and/or concerned member state, where the U.K. is part of a decentralized or mutual recognition procedure
In light of all these points, it’s important to constantly engage with health authorities, industry groups and other stakeholders to actively monitor and influence change, as well as reviewing and assessing the different scenarios — from different sources — that may result.
For example, there has been uncertainty about how the U.K. would treat upcoming EU legislation since the vote to leave the EU. Currently the MHRA is considering various scenarios for the timing of the implementation of the CTR (and its associated technology) with two options:
- The negotiation to stay in the EU CT network and access to the EU portal/database
- A “harder” approach in which, possibly, either the U.K.:
- Is a sovereign state with CTR on the statute book before Brexit, but without access/use of EU technology after Brexit or
- Is a sovereign state without CTR, with no implementation of CTR in the U.K. before Brexit
Regulation impacting the pharmaceutical industry always has been complex. Any changes in legislation often lead to a cascade of required updates, e.g., transfer of the MAH to an EU legal entity or changing the finished product manufacturing.
For instance, the fact that that U.K. is the third most frequent choice for RMS means that, at present, the MHRA is the RMS for some 3,400 human medicines evaluated through the decentralized process, while the U.K.’s Veterinary Medicines Directorate is the RMS for some 600. The remaining member states will have to deal with approximately 4,000 changes of RMS.
These incremental additions can be time critical and work intense, increasing the risk of expensive workarounds, errors in filings or delays in responding to health authorities that can lead to noncompliance. The consequences of noncompliance can include interruption of the supply chain, late filings or out-of-date registrations, which may lead to withdrawal of products from the market.
As such, it’s important to seek out a business partner who can provide the high-level scientific, regulatory and operational expertise necessary to navigate the changes in the regulatory and legislative landscape, like those that are being triggered by the U.K.’s withdrawal from the EU.
Alistair Davidson, senior director, and Vincenzo Cannizzaro, director, work in regulatory affairs for PPD.