Medicines Healthcare Products Regulatory Agency
Background
Haemophilia A is an inherited bleeding disorder caused by a lack of factor VIII, which causes blood clotting problems, such as bleeding in the joints, muscles, or internal organs.
Patients with haemophilia A are at an increased risk of surgical complications, such as the poor healing of wounds, infection, and internal bleeding. Treatments are in development to reduce this risk and are progressing through clinical trials.
One such study has been submitted through the MHRAs New Notification Scheme for low-risk phase 3 and 4 trials those trials that compare new treatments with the best currently available treatment (phase 3) and after a drug has been licensed (phase 4).
Nuwiq phase 4 trial
Octapharma AG is a pharmaceutical company that develops and produces human proteins from human plasma and human cell lines.
The company submitted an application to the MHRA for a phase 4 trial to evaluate the efficacy of Nuwiq, a fourth-generation recombinant FVIII produced in a human cell line, in preventing bleeding in patients with severe haemophilia A who are undergoing major surgery while receiving emicizumab prophylaxis.
Nuwiq contains the active substance simoctocog alfa (human coagulation factor VIII), which helps the blood to clot. Nuwiq is used to correct the factor VIII deficiency by replacing the missing factor VIII, which provides temporary control of the bleeding disorder. The medicine is made by cells into which a gene (DNA) has been introduced, enabling these cells to reproduce it.
A new, risk-proportionate process
The company applied for its phase 4 trial under the MHRAs new Notification Scheme for lower-risk clinical trials.
Introduced in October 2023, the new scheme aims to reduce the time taken by the MHRA to approve the lowest-risk clinical trials by more than 50%.
The introduction of the new Notification Scheme followed the agencys clinical trials consultation, which was endorsed by 74% of respondents. It forms a significant part of the MHRAs overhaul of clinical trials regulation.
About 20% of UK initial clinical trial applications are expected to be eligible for the scheme. It is underpinned by a risk proportionate approach that relies on the sponsor demonstrating that the trial meets certain key criteria.
To access the scheme, sponsors register their interest directly with the MHRA. Guidance is then sent to the sponsor, detailing the information that is needed in a cover letter and notification scheme criteria form. This information is then submitted in the usual way to the Integrated Research Application System (IRAS) the single system for applying for permissions and approvals in the UK.
Once received by the MHRA, the information is reviewed, and the trial is either accepted or objected to; the sponsor is updated within 14 days of the applications effective date. If the trial is objected, the application progresses through the full combined review CTA assessment route, which would include the co-assessment of the application by a Research Ethics Committee, as set out in the process below.
Clinical Trials Notification Scheme Application Lifecycle within the MHRA
Pre-submission of CT Notification application via IRAS
| Registration of Interest Sponsors register interest via GOV.UK webpage | ? | Application Submission pack email sent to sponsor providing guidance, the Cover Letter template and Notification Scheme Form template | ? | Submission Sponsor completes the templates and submits through the IRAS application portal. |
Post-submission of CT Notification application via IRAS
| Validation The CT Notification received by the MHRA, validated and passed onto the Clinical Trials Team. Sponsors sent a letter of acknowledgement | ? | Notification Accepted: Sponsor will be notified by day 14 Notification Objected: Sponsor will be notified by day 14 of the objection. The application will then continue for full assessment with an outcome communicated by day 30 |
Full details of the new scheme are set out in the MHRAs online guidance on clinical trials for medicines.
Taking advantage of shorter timelines
As the trial submitted by Octapharma met the criteria for low-risk phase 4 trials, it was eligible for the new Notification Scheme. After being reviewed, the MHRA was able to notify Octapharma that the trial was acceptable under the notification scheme, by day 14.
This case study demonstrates the effective operation of the MHRAs new, streamlined clinical trials system, in reducing the time taken to get the lowest-risk clinical trials up-and-running without undermining patient safety.
Clinical trials regulation should be flexible and risk-proportionate so that the regulatory requirements are geared to the risk that a trial presents.
This will help give UK patients quicker access to the potentially life-saving medicines being studied.
Andrea Manfrin, the MHRAs Deputy Director, Clinical Investigations and Trials
The Notification Scheme is open for applications, and the agencys message to all clinical trial sponsors is to use the new scheme for all eligible trials. See further information about the process, which sets out the criteria for eligible trials.
About the MHRA
An executive agency of the Department of Health and Social Care (DHSC), the Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for regulating all medicines and medical devices in the UK by ensuring they work and are acceptably safe. All the agencys work is underpinned by robust and fact-based judgements to ensure that the benefits justify any risks.