Guidance

The MHRA approval process for clinical investigations

Published 31 March 2026

The MHRA aims to process applications in the shortest time possible, while ensuring that any risk to the patient and user is minimised and the investigation is justified by the potential benefit to the participants in the proposed clinical investigation.

There are different rules depending on whether the clinical investigation is taking place in Great Britain or in Northern Ireland.

Clinical investigations being conducted in Great Britain need to meet the requirements of the Medical Devices Regulations 2002 (SI 2002 No 618, as amended) (UK MDR).

Clinical investigations in Northern Ireland must comply with EU rules for devices as set out in the Medical Device Regulation (EU) 2017/745 (EU MDR) and the In Vitro Diagnostic Medical Device Regulation (EU) 2017/746 (EU IVDR).

During the assessment, experts will assess the safety and performance of the investigational device as well as the design of the clinical investigation to be carried out.

Timeline

For Great Britain, we will to make and communicate our decision within 60 days. The 60-day clock does not stop when additional information is requested. This applies in all circumstances, including notifications spanning prolonged holiday periods such as Christmas or New Year.

For Northern Ireland, depending on whether we consult experts, we will provide a decision within 45 or 65 calendar days. This period may be suspended if we request additional information, until such time as a response to the request is received. The suspension may apply to the first request for additional information, but any further requests will not result in a clock stop.

Validating your application

The MHRA consider an application to be ‘valid’  when we have given formal acceptance of the application (‘notice’) under the relevant regulations and the review period has commenced.

An application is ‘invalid’ if the application has not received formal acceptance under these regulations.

If all the necessary documentation required as part of the original submission is complete, we will send a letter to the manufacturer including:

• an acknowledgement of receipt of the notice

• a reference number for the notice which should be quoted in all communications made to the MHRA pertaining to that application

• the starting date for the notification period

If the necessary documentation is incomplete, we will contact the manufacturer as soon as possible so that the missing information can be provided.

For clinical investigations in Great Britain, day 1 of the 60-day statutory review period is taken as being the first working day that follows the date the MHRA acknowledges receipt of a valid notification. Validation will be confirmed within 5 calendar days. If the notification is found to be invalid the 60 days will not commence.

For clinical investigations in Northern Ireland, once we have received your documents and validated them, we will write to you within 10 calendar days to confirm that the application is valid and the assessment has started or we will let you know if there are any issues.

If there are any issues raised, we will confirm these in writing and provide a 10-calendar day deadline for a response. The assessment will not start until we have received a valid response. If, after receipt of the response or the 10-day deadline has expired, the application is still considered to be invalid we will write to confirm this within 5 calendar days. Day 1 of the MHRA assessment is taken as being the date that we confirm that we have received a valid application.

Expert assessors

Copies of the documentation relevant to a proposed clinical investigation, will be sent to one or more assessors who have expert knowledge of aspects of clinical investigation of devices which may include:

• clinical aspects including clinical research

• biological safety, biological safety, biocompatibility and toxicology

• technology of the device

• statistics

• sterilisation

• electrical safety

• software aspects of the device

• radiation

• pharmacology and immunology

Assessors from outside the MHRA will have signed a statement of confidentiality incorporating a declaration of any conflicts of interest. Every effort will be made to ensure that no conflict of interest will arise for an expert assessor in relation to any aspect of the clinical investigation that we ask them to assess.

In the interests of confidentiality however, applicants may, at the time of the original submission, name the institutions or individuals whom they may not wish to act as assessors for the investigation in question and provide the rationale. The MHRA will, so far as possible, bear such views in mind when appointing assessors. Submitted documents are shared with assessors via a secure portal and all assessors are required not to retain any copies.

Additional information

We will write to you if we need more information during the review period.

If you do not understand a request for further information, you must contact us as soon as possible to request clarification. Where possible we will arrange a call to resolve any confusion and, if we have found possible grounds for objection, to find a resolution within the assessment period.

Each expert assessor will be allowed 14 days to request, through the MHRA, any further information that they think necessary for a proper assessment of the proposed clinical investigation to be made in their area of expertise.

Applicants should supply any additional information that we request as soon as possible, so that an adequate assessment of all relevant data can be completed. For Great Britain, the 60-day clock will not stop while the additional information is being assembled.

For clinical investigations in Northern Ireland, depending on whether we consult experts, MHRA will provide a decision within 45 or 65 calendar days. This period may be suspended if we request additional information, until we receive a response. The suspension may apply to the first request for additional information, but any further requests will not result in a clock stop. A letter will be sent to the sponsor by the final day or before with a decision as to whether or not the proposed clinical investigation has been authorised and can be carried out.

The MHRA decision

If, after consideration of all the evidence provided, the MHRA considers that there are no grounds relating to health or safety or public policy whereby the proposed clinical investigation should not proceed, we will notify the applicant of this decision.

If, after the assessment, we consider that the proposed clinical investigation may present unjustifiable risks to public health or safety, we will notify the applicant of this objection.

Unjustifiable risks to public health or safety may include:

• where there are reasonable grounds to suspect that a device does not satisfy relevant essential requirements, general safety and performance requirements

• where there are reasonable grounds to suspect that the clinical investigation is not subject to controls equivalent to the requirements of ISO 14155:2020

• where there exists expert professional opinion on the proposed clinical investigation that the risk benefit analysis given by or on behalf of the manufacturer is inaccurate and that, were the investigation to take place, there would be a significant probability of serious illness, injury or death to the patient or user

• where there is inadequate or incomplete pre-clinical or animal data, making it unreasonable for clinical testing to commence

• where insufficient information has been submitted to enable a proper assessment of the safety aspects of the proposed clinical investigation to be made

• where the manufacturer or sponsor has delivered any documentation necessary for the assessment so late that insufficient time remains within the assessment period for the MHRA to complete an assessment

For clinical investigations in Northern Ireland, if the MHRA raises grounds for objection, we will notify the EU Competent Authorities and the European Commission, where necessary, of the decision and grounds for objection. The grounds for objection will otherwise remain confidential between the expert assessors, the manufacturer, the Health Research Authority  (HRA) and the ethics committee.

Re-submitting documentation

You may re-submit revised documentation about your proposed clinical investigation, provided the reason for refusal of the original application has been addressed. You will need to submit documentation to address the grounds for objection and pay a fee.  

You can find out about the fees for resubmission.

The documentation must be submitted using the application process on the Integrated Research Application System (IRAS) portal. You should do this in the original project on IRAS to reflect changes made to address the grounds for objection. This will keep the IRAS reference number the same for the re-submission

Any further questions or issues raised by the MHRA will only be in relation to the information supplied to address the original grounds for objection. This, however, is only valid provided the documentation remains the same with the exception of that addressing the grounds for objection, unless the further information raises safety issues or a significant change to the risk and benefit analysis which impinge on the original protocol. Therefore, a covering letter should be provided with the resubmission stating that the documentation does not differ from that provided with the original submission or as amended during the MHRA assessment, except in sections that address the original grounds for objection.

For clinical investigations in Northern Ireland, where a resubmission is being made for an application originally submitted under the UK Medical Device Regulations, the MHRA may also request changes are made to the study documentation to bring the study into compliance with the EU Medical Device Regulations 2017/745.

When making a resubmission you should provide:

• any necessary documents to address the grounds for objection including red lined (showing changes made) and clean copies of all amended study documentation

• a covering letter stating that the documentation does not differ from that provided with the original submission or as amended during the MHRA assessment, except in sections that address the original grounds for objection, including an explanation as to how the grounds for objection have been addressed within the documentation

• a revised clinical investigation application form, updated in IRAS

• a copy of the original notification documentation (if it has not been amended) for reference only

Applicants or sponsors are advised to arrange a meeting or conference call with the MHRA before re-drafting a clinical investigation resubmission to ensure that they understand the original concerns. This also provides an opportunity to discuss possible means of addressing the grounds of objection.