Amendments to your clinical trial authorisation: What to send

What to send
Details on the documentation required in a clinical trial authorisation (CTA) application are available:

Detailed guidance on the request to the competent authorities for authorisation of a clinical trial on a medicinal product for human use, the notification of substantial amendments and the declaration of the end of trial (CT-1) (external link)

Key documents include:

• the signed notification of amendment (annex 2) form (PDF) available on the EudraCT: European Clinical Trials of the EMEA website (external link).
• an updated XML and PDF file of the Clinical Trial Application Form (Annex 1) with changes highlighted, if the amendment affects the information previously submitted
• description of the amendment
• reasons for the proposed amendment
• copy of the proposed changes to the protocol or any other documents (eg IMPD), showing previous and new wording, where applicable
• supporting data for the amendment, including as applicable:
• • summaries of data
  • updated overall risk benefit assessment
  • possible consequences for subjects already in the trial
  • possible consequences for the evaluation of results.
    

Please see our additional Information section for more guidance on these documents.

Amendments or end of trial declarations for clinical trials that were originally CTX/DDX/CTC/GTX applications
As limited information was required at the time of CTX/DDX/CTC/GTX studies, we have been unable to process amendments or end of trial notifications electronically. In order to remedy this situation, we ask that applicants fill out a CT Form UK 1. This should be sent along with the first amendment or end of trial submitted after the 1 October 2007. Please also include details of the current Sponsor in your cover letter (Organisation name; contact details) and any old reference numbers.

CT Form UK 1 (61Kb)

Submitting your application
Applicants are required to submit electronic documents on disk with one PDF file for each document. In exceptional cases where the use of PDF files is not feasible, (for example, in the case of small, non-commercial clinical trials) electronic documents using Microsoft Word are acceptable and will be processed to the same target timescales. Disks should be submitted with no subdirectory structure. The portal is not available for clinical trial submissions at this time. Updates on portal availability will be provided in due course.

Each disk should be labelled in the following manner:

• EudraCT number
• description of contents eg 'Substantial amendment'
• company name
• date sent.

The disk may be printed or labelled with an adhesive paper label or a permanent marker pen.

All disks should be sent to the address below:

Information Processing Unit
Area 6
Medicines & Healthcare products Regulatory Agency
151 Buckingham Palace Road
Victoria
SW1W 9SZ

When the MHRA receives an application for a CTA, it will be validated. If the application is not valid (eg incomplete information is supplied) then the person making the application will be contacted and told that there are deficiencies. If the deficiencies are minor, you may be asked to provide the missing information. Nothing will happen to the application until the missing components are provided, although once the application is complete it will be processed as normal.

If the deficiencies are major, you may be required to resubmit a complete application. Once the application is valid (ie complete) the assessment period will begin and an acknowledgement letter will be sent to the person submitting the application. This is the person named in section C1 of the clinical trial application form.

The assessment period starts from the date of receipt of a valid application. If you have not been told that your application is invalid or received an acknowledgement letter within 10 days of sending the application, please contact RIS.CT@mhra.gsi.gov.uk.

Guidance on preparing PDF documents
As far as possible all data should originate from electronic files rather than from scanned data. There may be circumstances where the data is only available in paper format, please advise us in advance if this is the case by sending an email to RIS.CT@mhra.gsi.gov.uk.

In order to process PDF documents efficiently MHRA assessors need to be able to easily navigate and manipulate the document (eg copy and pasting sections of the document or splitting a large document into multiple smaller documents). To facilitate this process the following points should be noted when creating PDF documents:

• all PDF documents should be created directly from Microsoft Word or undergo Adobe Acrobat optical character recognition (OCR) at the time of creation. PDF document scanned images should not be provided as it is not possible to cut-and-paste data in this format
• PDF documents should not be file protected as this prevents the printing and manipulation of the document
• fonts that are not supported by Microsoft Word should not be used on PDF documents
• all PDF documents should be appropriately bookmarked to ensure that assessors can jump directly to the sections of interest. Only the simplest of PDF documents (eg a letter) should be submitted without bookmarks. All documents larger than 50 pages should be bookmarked (bookmarking to primary headings is sufficient). Documents less than 50 pages should be considered for bookmarking if they are particularly complex and/or require frequent cross referencing within the document. In making this judgement consider whether bookmarking would help an assessor to work more efficiently
• supporting data and references should comply with the Vancouver convention (external link) where appropriate.

If historical documents are not available electronically, a scanned image which has undergone OCR is acceptable. Applicants should ensure that the highest quality scan image is produced.

Disk formats
The following disk formats are acceptable:

• CD-ROM
• CD-R
• CD-RW
• DVD-R
• DVD-RW.

The following formats are not acceptable:

• DVD-ROM
• DVD-RAM.
  

Naming documents

It is important that the individual document filenames allow our staff to quickly identify where the document should be indexed on our system. Please give the document a simple, relevant and descriptive name (eg Amendment form, End of Trial form, Clinical Study report etc).

Contacting us
All queries relating to electronic documents and submissions should be directed to: RIS.CT@mhra.gsi.gov.uk