In my experience, any protocol amendment, no matter how minor or substantial, should always be reviewed and approved by an IRB or ethics committee prior to implementation.
With respect to the FDA, in general, smaller/more administrative protocol amendments don't need prior approval from the FDA (but should still be approved by an IRB). However, a good practice is to submit the updated protocol with your annual report (if you didn't already submit it at the time of the amendment), just to make sure the FDA has access to the current version of the protocol.
As noted in 21 CFR 312.30, if your protocol amendment may significantly affect the safety of subjects (any phase), the scope of the investigation (phase 2 or 3), or the scientific quality of the study (phase 2 or 3), then you should submit the amendment to the FDA prior to implementation. Although it's not a specific regulatory requirement, most of the companies and colleagues I've worked with generally give the FDA a courtesy 30 calendar days to provide feedback on the amended protocol prior to implementation. You can note in the cover letter of your submission when you plan to implement the changes so the FDA knows that, if they have concerns, they should try to communicate them before that date.
My EU experience is limited, so I will defer to the comments of others regarding protocol amendment submissions to EU health authorities.
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Marissa Berry, Ph.D., RAC
Senior Manager, Regulatory Strategy
Durham, NC
United States
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Original Message:
Sent: 18-Jan-2023 04:23
From: Anonymous Member
Subject: Clinical Trial - Substantial amendments
This message was posted by a user wishing to remain anonymous
Thank you for your reply.
I'm referring to drugs and biologics. Would like to know more on the general process, especially clinical trial amendment process in regulated market like US and EU.
whether, an amendments to the clinical trials to be approved by FDA and/or IRB before implementation?
Guidance on general process would be appreciated.
Thanks and Regards.
Original Message:
Sent: 18-Jan-2023 03:54
From: Richard Vincins
Subject: Clinical Trial - Substantial amendments
Hello Anon,
It depends on the jurisdiction you are asking about because most countries have individual requirements for reporting on and changes to clinical trials/investigations. This also depends if you are talking about a drug or device. And if a device, what type of device because as example in the United States there are Non-Significant Risk devices and Significant Risk devices. While this does not depend so much on the substantial change being made, it can impact notification to Institutional Review Board (IRB) and/or FDA. Many of the regulated countries do have processes for making substantial change/amendments to clinical trials, but would have to know the country.
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Richard Vincins ASQ-CQA, MTOPRA, RAC
Vice President Global Regulatory Affairs
Original Message:
Sent: 17-Jan-2023 04:27
From: Anonymous Member
Subject: Clinical Trial - Substantial amendments
This message was posted by a user wishing to remain anonymous
Hi Team,
Can anyone please guide me on Clinical Trials - substantial amendments
These amendments are similar to post approval changes? any set guidelines for regulated market/s? are they the part of Clinical trial application procedure OR to be submitted separately as variation?
Any feedback would be greatly appreciated.
Thanks and Regards.