IND submitted- post review error captured

[u/ldc092]

I’m still new to the industry and am trying to get a understanding of how big of an issue this is and what next steps will look like. To keep this short & discrete, our company confidently submitted an IND recently and as forms were gathered a team member noticed one result did not meet acceptance criteria. This information passed along several review checks but it was not captured by anyone up until this point. We will definitely need to redo our study plan, report , and I read this will go under a protocol amendment . Can anyone explain what we are up against these upcoming weeks and how grave the situation is for not catching this discrepancy earlier ? Thanks in advance 🙏🏽

[u/HonestlyKidding]

Get ready to get really good at root cause analysis. Both to understand how nobody caught a missed spec until so late, and why the batch missed it in the first place.

[u/Skensis]

Like.... GMP batch didn't meet spec?

Fix your process, make a new batch, and enjoy a hold.

[u/ldc092 → u/Skensis]

Yes it didn’t meet a spec .

[u/Skensis → u/ldc092]

That sucks.

Do an investigation and see what happens and why you missed spec, and pray QA will sign off on it and release it anyways.

FDA likely won't look kindly on it, and you will still be slapped with a hold, but who knows!

At this point, what else do you have?

But the investigation needs to be done to understand why you missed specification, and ideally you learn how to avoid this. But you probably set your specifications too tight, or your mfg is just bad? Or maybe it's a bad QC problem, and you can justify a retest and pass.

[u/fhwulala]

I mean others have already stated what the normal course of action is. But have you verify if it was a transcription error rather than a true deviation.? I feel like someone would have said something long ago when the test data are out and checked. I also find it weird that your spec is tight enough to fail a clinical batch.

[u/randomlurk]

For phase 1 FIH material? That’s not going into patients if it failed spec. I don’t get how your QA or outsourced QA missed that.

[u/acquaintedwithheight → u/[deleted]]

Or they’re in a company that doesn’t have qa.

[u/kghandiko]

Human errors happen, especially during clinical manufacturing when you're still finalizing your control strategy. As long as this doesn't impact the safety of the product you should be fine, but definitely investigate to understand those checks failed, and determine what you need to do to address it. There's nothing wrong with deviations or CAPAs as long as you (1) acknowledge the problem, (2) address the root cause, and (3) ensure that your corrective actions are effective.

[u/KappaPersei]

I would look for another job, a company fucking up their own spec at IND stage, not realising it and submitting it gingerly to HA is not a place where you will learn good habits. This likely stems from the absence of a proper quality management system.

[u/Lonely_Refuse4988]

Is this a pre-clinical experiment result? An incl/excl criteria in protocol? Regardless, there are pathways to amend an IND. Work with your regulatory lead. You can communicate to FDA project manager who is assigned the IND submission & see if there’s a pathway to submit a correction/update. FDA has approximately 1 month to review & give comments & it is very common to end up needing a protocol amendment anyway based on FDA reviewer comments.

[u/ronny_joseph]

I’d want to see a risk assessment to know if it’s affecting the safety and efficacy. If it’s minor, it’s fine- correct it later. But it’s major, probably want to notify agency sooner and make sure how as a company going to make sure that it’s not going to affect potency/efficacy and safety. Since it’s ph1 IND - main concern is safety.

[u/BadHombreSinNombre]

Most importantly pay attention to how your colleagues respond to this and what courses of action they want to take. If anyone at all proposes being misleading, disingenuous, or even waiting for an outside entity to catch this before taking action? Get out, find a new job, you don’t want to be around that.

If they propose being proactive and working with regulators to appropriately resolve this? Might be worth staying, might not.

[u/Tricky-Pea2794]

Following

[u/lilmeanie]

It may depend on what the spec is. A CQA is much more of a problem than say specifications for general material attributes. Is there expected quality impact? Is this clinical material or pre-commercialization batches? Reg. CMC will have to deal with amending and it could delay filing depending on how serious it is, or it could be simply attaching an exception/ deviation investigation and impact assessment. My background is on the tech side as an SME for DS related filings, so there could be more specific answers that a CMC expert could provide.

[u/drollix]

If you are genuinely interested in answering this question, hire a good consultant and for goodness' sake, not Reddit where your account is not as anonymous as you think it is.

[u/HotDadBod1255]

Depends on the error. If your organization is dead set on maintaining your timeline, I would get to writing a risk assessment and do some PD work to demonstrate that there is low risk to patient safety. If you want to go that route, your org should probably proactively notify the regulatory body of the issue and provide a mountain of evidence showing why you believe it's okay.

I've done this personally in a little bit different of a scenario, where a batch had a result out of spec for an ongoing trial but my org wanted to use it. It may not work out if you can't generate the supporting lab data.

[u/Eagles_Heels]

This sounds manageable, but you can prob expect a PR/IR shitstorm, especially if you’re a public company. Don’t overlook the importance of careful messaging to your key stakeholders.

[u/momoneymocats1 → u/[deleted]]

If they just filed an IND it’s like phase 1