After years in the making, Brexit has occurred, and the downstream ramifications on the clinical research industry are now starting to roll out.
If you are planning a clinical study that will enrol patients in the United Kingdom (U.K.), this article will aid your efforts and preparations. The U.K.’s departure from the European Union (E.U.) on 31st December 2020, following the end of the Brexit transition period, resulted in the implementation on 1st January 2021 of statutory instrument (S.I.) 2019 No. 77, “The Medicines for Human Use (Clinical Trials) (Amendment) (E.U. Exit) Regulations 2019”, amending provisions within S.I. 2004 No. 1031, “The Medicines for Human Use (Clinical Trials) Regulations 2004”. This article summarises the key impacts of these changes on the regulatory environment for conducting clinical trials in the U.K.
By and large, the changes introduced through S.I. 2019/77 were to limit and/or remove the previous reference to E.U. legislation, directives, and/or guidance; however, notable provisions were made concerning the responsibilities of qualified persons and approved countries for import. As a result of these changes and in combination with further guidance as issued by the Medicines and Healthcare products Regulatory Agency (MHRA), the following are identified as the key differences to the current regulatory environment for the conduct of clinical trials following the conclusion of Brexit.
Importation of Investigational Medicinal Product (IMP)
From 1 January 2022, it will be a requirement for clinical trial sponsors to appoint a U.K. Manufacturing and Import Authorisation (MIA[IMP]) holder to implement an assurance system to verify that Investigational Medicinal Products have been certified by a suitable qualified person (QP) prior to release to investigative sites. There is no requirement that a U.K.-based Q.P. recertify an IMP imported into the U.K. from a country on an approved list when certification has already been issued. It is therefore important that the Sponsor organisation consider their current vendor provisions with respect to batch release and, when conducting studies in the U.K., ensure that an appropriate assurance system is in place to facilitate distribution of IMP to sites.
Sponsor of a Clinical Trial
As of 1st January 2021, it is required that the Sponsor or the legal representative of a clinical trial conducted in the U.K. be established in the U.K. or a country listed by the MHRA as an “approved country.” The list of approved countries published by MHRA on 31st December 2020 currently lists all 27 E.U. Member State countries in addition to those that are members of the European Economic Area (EEA).
Therefore, it remains a requirement for Sponsor companies to appoint a legal representative when not established in the U.K., E.U., or EEA. For Sponsor organisations established in the E.U. and/or EEA, there shall be no requirement to establish a representative specifically for the U.K. For Sponsor organisations that are not established within the U.K., E.U. or EEA, it will be necessary to appoint a legal representative either in the U.K. or in a E.U. or EEA Member State.
Precision for Medicine continues to provide legal representative services to our clients and can discuss your needs as applicable.
Registration of Clinical Trials in a Publicly Accessible Database
As of 1st January 2021, Research Ethics Committee (REC) approvals will be subject to the condition that the clinical trial is registered in a publicly accessible database, such as the National Institutes of Health (NIH) Clinical Trials.gov or International Standard Randomised Controlled Trials Number (ISRCTN) registries. It should also be noted for multi-national trials, where a study may be registered within the E.U. Clinical Trials Register, that this registry would also satisfy this purpose. Registration of a newly approved clinical trial should occur before the first act of recruitment occurs, however, a deadline of no later than 6 weeks after the first patient has been recruited has been set. Where applicable, a request for deferral of registration can be made to the Health Research Authority (HRA) and must be based on the transparency rules set.
Requests for Clinical Trial Authorisation
At the point the U.K. left the E.U., access to the E.U. medicines regulatory network (EMRN) and the electronic systems made available to support communications was ended. Consequently, MHRA have implemented a new national portal to facilitate electronic submissions. Accordingly, Sponsor organisations should register for access to the portal to ensure applications can be filed in a timely manner, particularly as this pertains to both initial requests for clinical trial authorisation but equally in the processing of maintenance activities, such as amendments and safety reporting.
From 1st January 2022, the U.K. will implement a more streamlined clinical trial approval process that combines both MHRA and REC review. This in effect sees full adoption of the Combined Ways of Working (CWoW) submission model that has been in operation as a pilot procedure since March 2018. Precision has made extensive use of the CWoW submission model over the last 3 years, and this has proven to be both efficient and expedient. Adoption of this new submissions approach also represents steps taken by the U.K. to ensure a competitive yet comparable regulatory environment to that which will come into effect in the E.U. from 31st January 2021 with full implementation of the Clinical Trial Regulation (Regulation (E.C.) 536/204).
About the author
Chris Ingram, BSc (Hons) is Head of Regulatory Consultancy (Europe) for Precision for Medicine. Chris received his BSc(Hons) in immunology and pharmacology from the University of Strathclyde and has since spent over 21 years working in regulatory affairs with a focus on clinical development. Chris’ regulatory expertise covers clinical development across all phases, regulatory strategy, marketing authorisations, scientific advice, orphan drug designation and paediatric investigation plans across a wide variety of therapeutic areas, including but not limited to, oncology, CNS, metabolic, endocrinology, analgesia and cardiovascular.