Substantial amendments
Substantial amendments refer to amendments:
- Which change a local sponsor or principal investigator of the trial
- Which is likely to affect, to a significant degree:
- The safety, or physical or mental integrity, of any participant of the trial
- The scientific value of the trial
- The conduct or management of the trial
- The quality or safety of any investigational product used in the trial
Local sponsors should assess whether an amendment qualifies as a substantial amendment.
All substantial amendments must be submitted to us (for approval or acceptance of notification) prior to implementation. However, an exception may be made if the amendment is to protect trial participants against any immediate hazard to their health or safety (i.e. urgent safety measure). Any urgent safety measure taken should be reported to us as soon as possible and no later than 7 calendar days.
The sponsor of the clinical trial should also ensure that the details and rationale for the amendments are clearly described in the submission.
In addition, the sponsor is required to keep records of all substantial and non-substantial amendments to the trial, and provide such records to us if requested.
Supporting documents
Type of substantial amendments |
To be submitted |
Amendment to protocol |
- Clinical trial protocol amendment
- Summary of protocol amendment
- IRB approval letter (mandatory for CTN)
|
Amendment to informed consent form (ICF) |
- Revised ICF
- Track change version for ICF
- IRB approval letter (mandatory for CTN)
|
Change of local sponsor |
- Letter from current local sponsor indicating transfer of local sponsorship to the new local sponsor (this letter should be copied to the new local sponsor, and the respective trial site PI(s) and IRB(s))
- IRB approval letter (mandatory for CTN)
|
Change of Principal Investigator (PI)
|
- Curriculum vitae of new PI
- Revised ICF (if applicable)
- Track change version for ICF (if applicable)
- IRB approval letter (mandatory for CTN)
|
Addition of trial site
|
- Curriculum vitae of PI
- ICF for new trial site
- IRB approval letter (mandatory for CTN)
|
Change of manufacturer |
For change or addition of a manufacturer:
- Good Manufacturing Practice (GMP) certificate
- Where the GMP certificate is not available, a declaration by the manufacturer of its compliance with GMP
- Certificate of Analysis of the product manufactured by the new manufacturer (if applicable)
|
Change of Chemistry, Manufacturing, Controls (CMC) information (if CMC was submitted in the clinical trial application) |
Supporting CMC information, where relevant |
Refer to our Guidance on Determining Whether an Amendment to a Clinical Trial is a Substantial Amendment348 KB for more details.
Submission should be done via Amend CTA/CTN/CTC module in PRISM (view sample online forms here276 KB and here634 KB).
Turn-around-time
Standard turn-around-time:
- Substantial amendments to CTA/CTC: 15 working days
- Substantial amendments to CTN: 5 working days