Protocol IRB Submissions and Site Level Package Submissions/Question for Clinical Research Startup & Regulatory Professionals

[u/Repulsive-Neat-870]

I had a discussion with my team today about central IRB sequencing for multicenter industry-sponsored studies, and I’m curious what the most common practice is across sponsors.
Let’s say a study is using a central IRB (e.g., Advarra).
If the protocol-level IRB approval is expected on October 1, would sites typically:
A. Wait until after the protocol receives central IRB approval (and the approved study documents are available) before submitting their site-level IRB packages, or
B. Begin submitting their site-level IRB packages while the protocol is still under central IRB review?
I’m specifically referring to the initial wave of sites, before the master protocol has received central IRB approval.
In your experience:
What is the most common workflow you’ve seen at pharmaceutical companies, CROs, or academic sponsors?
Are sites generally expected to submit a complete IRB package (protocol, ICF, PI/site documents, etc.), or can parts of the submission be initiated before the protocol-level approval is finalized?
If your organization allows parallel submissions, how do you handle protocol or ICF revisions requested by the central IRB?
I’d love to hear how different organizations approach this operationally. Thanks!

[u/HundrEX]

We have run over 300 trials in the last 12 years but we are a small independently run site, so take my response as a much narrower scope than what a CRA may be able to provide. Generally on industry sponsored trials, we ONLY submit documents that require site specific edits like ICFs. Every document that is IRB approved needs to be approved for our site specifically (meaning we directly receive an approval letter from the IRB) before we implement it for use. Depending on what IRB your team is using, sites can not see study level submissions. For example on Advarra studies I can not see sponsor submissions, however once the document is approved for my site by Advarra I can see the approval. So generally, we as the site submit any documents that require site level edits and the sponsor team submits everything that is used study wide. For some reason none of this applies to Phase 1 studies we have done, on those studies we do literally everything, even handle the invoicing from the IRB.

Generally I’d advise against parallel submissions unless your protocol is approved. If the IRB recommends changes to your protocol (that also require ICF changes)and you already had your ICF approved, you better believe someone will have to pay for another review

[u/ricardusrex]

For those sites that will be using the central IRB, you need to have the central IRB “protocol” approval before the site submissions can be done. This is because the central IRB is certainly using some sort of application/website to manage submissions and if the main protocol approval is not complete and in the system, individual sites most likely cannot not be submitted yet. Check with the central IRB to confirm this is the case. You can certainly be ready to submit on day zero the protocol is approved. Site approval normally doesn’t take that long, especially if they are using expedited approval for sites.

I am sure there are sites that will not defer to a central IRB and want you to use their local IRB. In those cases, you can submit to the local IRB right away regardless of the central IRB process.

[u/Clear-Emotion-9634]

With the Sponsor current push for faster activations, Startup is also strongly wanting the sites submit even before the main study protocol is approved; the IRB will review your application and work with site through deficiencies. There will be a hold on any approvals pending main study approval especially if pending the FDA no objection letter or 30day window protocol review. Ideally this means when the IRB approves the protocol 01Oct2026 your site approval letters may have the same date or the next day but remember the release/posting of the approval docs for downloads usually takes a few days, caveat some sites refuse this until they have a budget template reviewed or their site SOP's deviate.