Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
EU, UK Struggle to Reach Agreement on Notified Bodies During Brexit Transition
Brexit negotiators have failed to reach an early agreement on the role of notified bodies during the United Kingdom’s staged withdrawal from the EU. The section of the draft withdrawal agreement on the medical device certification groups is one of the areas in which negotiators are yet to make progress.
EU and UK negotiators presented the progress they made in talks over the weekend by releasing a marked-up version of the previously published draft document. Much of the document is now highlighted green to indicate negotiators have reached an agreement on its content and only technical legal revisions are needed. Another portion of the document is highlighted yellow, meaning the policy is agreed but drafting changes or clarifications are still needed.
The section on notified bodies is one of a limited number of paragraphs that are not highlighted in either color. That indicates “discussions are ongoing” about the text proposed by the EU and, “No agreement has been reached.”
The contentious text discusses the activities of notified bodies during the planned 21-month Brexit transition period. In those months, the UK will have officially left the EU but will retain some of the benefits and burdens of membership. The EU is proposing to place certain obligations on notified bodies on both sides of the divide during the transition.
“The United Kingdom shall ensure that, upon request by the certificate holder, information held by a conformity assessment body established in the United Kingdom in relation to its activities as a notified body under Union law before the end of the transition period is made available to a notified body established in a member state indicated by the certificate holder without delay,” the draft states. The draft features a similar section that applies to notified bodies in the EU.
While negotiators are yet to agree on the section, progress in other areas means they should be able to focus more time on the notified body question and other outstanding points of disagreement.
Other sections of relevance to drug and device regulation have already been agreed. Notably, the UK has signed off on a section that tasks it with making drug marketing authorization dossiers available “without delay” upon receiving a request from a member state or the European Medicines Agency (EMA).
EMA Adopts Pharmacogenomic Guideline to Support Conduct of Genomic Studies
EMA has adopted a final guideline on good pharmacogenomic practice. The document sets out how drug developers can design and run studies to show how genetic variability affects patient responses to their therapies.
EMA’s Pharmacogenomics Working Party released a draft version of the guideline in 2016 and closed a comment period later that year. Progress slowed after that, though, with the working group taking 13 months to agree on a revised version and another four months passing before the Committee for Medicinal Products for Human Use signed off on the final text.
The publication of the final, adopted text reveals the reasons behind the delay. The document has been through a substantial rewrite since the draft stage. Few sections of the text remain unchanged.
The result is a document that guides readers through the analysis of genomic germline DNA — and notably not the analysis of somatic DNA or genomic cancer biomarkers — by breaking the subject up into three sections. One section addresses genetic variation and drug response by delving into topics such as the correlations between phenotypes and genotypes. The heart of the document focuses on quality aspects of pharmacogenomic analyses, and the final major section covers clinical trial design.
In discussing the topics, EMA highlights best practices — such as the use of high-quality DNA and adequate minimum levels of next-generation sequencing coverage — while also pointing to areas in which further progress is needed. Specifically, EMA calls out the need for broader sequencing approaches that can identify “rare variants of functional importance for drug pharmacokinetics and drug response.”
EMA’s decision to exclude the analysis of somatic DNA and cancer biomarkers from the scope of the guideline means it may return to the topic of pharmacogenomic studies soon. The agency is considering writing an annex or seperate guideline to set out its thinking on those subjects.
The guideline on good pharmacogenomic practice for germline DNA comes into force in September.
GSK Outlines Brexit Regulatory Preparations, Predicts $70M Increase in Annual Costs
GlaxoSmithKline has warned investors Brexit could add $70 million a year to its ongoing costs. The UK pharma company made the forecast after deciding to expand its presence in the EU to mitigate the risk of Brexit disrupting drug supply.
GSK began implementing its Brexit contingency plan in January. Focusing initially on tasks that could affect its supply chain, GSK is adding capacity in the UK and EU for the re-testing and certification of drugs. Such capacity will be essential if the UK is treated as third country by the EU after Brexit.
Other teams at GSK are transferring its marketing authorizations from the UK to the EU, updating packaging, revising manufacturing and import licenses and bringing extra warehouse space online. GSK thinks these activities could cost it $100 million over the next two to three years, beyond which the additional annual outlay will settle at around $70 million.
Those sums are manageable for a firm of GSK’s size, and it does not expect Brexit to have a material impact on its operation long term. The risk lies in the potential for near-term disruption, particularly if the UK leaves the EU without a deal or transition period in 12 months.
“Delivering these necessary but complex changes by March 2019 will be ambitious and potentially disruptive in the short term,” GSK wrote in its annual report. “We support efforts to secure a status quo transition period to minimize disruption.”
The report also touched on the tax implications of Brexit. GSK expects the biggest hit to come from custom duty costs and administrative outlays associated with moving goods between the EU and UK.
EMA Provides Update on Status of Delayed Clinical Trial Portal, Database
EMA expects to have a version of its delayed clinical trial portal and database ready for audit early next year. The developer provided the timeline as part of a revised project plan designed to mitigate the complexity that has slowed progress so far.
EMA ordered the development of the portal and database to establish a single entry point for the filing of clinical trial information in the EU. The agency shared draft functional specifications in 2014 and signed off on them the following year, but progress has stuttered since then. EMA was forced to postpone the go-live date after the developer ran into “technical difficulties.”
To prevent further delays, the developer has created a revised plan designed to improve project management and other tasks. The developer has also added more contingency to the plan to increase the likelihood of it hitting its revised timeline.
The next big milestone on the plan is release 0.7 of the portal. EMA expects to receive that version for review early next year. In disclosing the target, EMA removed a statement from its website that said “development remains aligned to the schedule that enables the EU Clinical Trial Regulation to come into application in the second half of 2019.”