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Amending your trial protocol or other documentation

Only substantial amendments need to be submitted to the MHRA. Changes count as a substantial amendment to your clinical trial authorisation if the amendment is likely to affect to a significant degree

(a) the safety or physical or mental integrity of the subjects of the trial,

(b) the scientific value of the trial,

(c) the conduct or management of the trial, or

(d) the quality or safety of any investigational medicinal product used in the trial.

For clinical trials authorised via the combined review process you should prepare and submit using new part of Integrated Research Application System (IRAS).

For clinical trials not approved or yet transitioned over to the combined review process, you should continue to use MHRA submissions. Further details on how to register and submit via this platform.

You need to send the following documents to the Medicines and Healthcare products Regulatory Agency (MHRA):

• Covering letter detailing the trial reference numbers (IRAS ID,CTAnumber, EudraCT etc) along with Purchase Order Number, outlining the substantial changes (if there have been any non-substantial changes please also outline these separately)
• A PDF copy of the locked Amendment tool. You should ensure that the amendment tool contains a clear description of the substantial amendment and reasons for the proposed changes. Alternatively, for bulk amendments (where the same change affects many trials), the substantial amendment notification form** can be completed and submitted. The form is available here.
• PDF file of the Clinical Trial Authorisation application form* generated in IRAS with changes highlighted, if the amendment affects the information previously submitted.
• List of the proposed changes to the protocol or any other documents (e.g. IMPD) compared to the current MHRA-approved document, showing previous and new wording where applicable and a rationale to justify each substantial change. If applicable the following should be provided:
  • Summaries of data
  • Updated overall risk benefit assessment
  • Possible consequences for subjects already in the trial
  • Possible consequences for the evaluation of results

Assessment process

We will assess your application within 35 days. If you consider your trial requires an expedited assessment (for example, patient safety reasons), this should be stated in the covering letter along with the rationale for the expedited assessment request.

Invalid applications

If your application does not meet the requirements it will not be assessed. You will be told the reasons why your application is invalid.

Check the Common issues identified during clinical trial applications guidance (PDF, 43KB, 1 page) to ensure youre submitting a valid application.

For queries about electronic documents and submissions email CT.Submission@mhra.gov.uk.

Withdraw your application before the final decision

You may withdraw your application at any point before an assessment decision on your substantial amendment is reached. To withdraw your application you should send an email to clintrialhelpline@mhra.gov.uk.

For applications that have gone through the Combined Review process, please refer to the guidance on the HRA website.

Outcome of assessment

We will tell you the outcome of your application by email.

If your application is not successful, we will tell you why and you may resubmit your application.

Fees

There are different fees based on your type of clinical trial application.

Please see the Make a payment to MHRA page on how to pay relevant fees.

Invoices for Clinical Trial Authorisation applications, and Substantial Amendment applications are sent directly to the applicant shortly after a valid submission has been established. The covering letter for the application should clearly highlight your Purchase Order (PO) number where available. The applicant is the person listed in section C1 of the Clinical Trial Application form, or section D1 of the Amendment form. We are unable to address the invoice to someone other than those listed in the sections above.

It is the responsibility of the applicant to ensure timely payment of invoices for their submissions. Invoices must be settled on receipt of invoice. Penalty fees may be incurred for non-payment, details of the penalties are set out in the Fees Regulations. Non-payment may also result in suspension of any licence or authorisation, followed by legal proceedings for unpaid amounts, as a debt due to the Crown.

You can contact MHRA Finance Department on 020 3080 6533 or email Sales.Invoices@mhra.gov.uk for more information on how to pay fees.

Change your contact details

For applications that have gone through the Combined Review process, please refer to the HRA website.

You should send an email entitled Change to Contact Details of the contact person CTA Number XXXXX/XXXX/XXX-XXXX EudraCT Number XXXX/XXXXXX/XX IRAS ID XXXXXXX.

Email: CT.Submission@mhra.gov.uk

The email should be sent by the contact person listed on the current application form, or other authorised persons and must include:

• IRAS ID and/or EudraCT number
• CTA number
• details of the previous contact person and/or contact details
• details of the new contact person and/or contact details

The new contact person or details should be updated on an updated application form. A copy of the updated application form should be included in the next substantial amendment.

Change of legal representative

For applications that have gone through the Combined Review process, please refer to the 