And in Other News, Nothing Really Changed

Thursday, July 14, 2011

So the long awaited draft guidance document on in vitro companion diagnostics hit yesterday, and the big news is, well, it's not exactly news. Regular readers of our blogs, and attendees of our seminars, will be pleased to learn that everything we’ve shared from meetings with FDA on the subject has been faithfully represented in the draft guidance. In short, this guidance is more a clarification of the policy we’ve been hearing for a while now – develop the drug and diagnostic together.

Okay, there were a couple of surprises in the document. For one, there was the unexpected and liberal use of word "contemporaneous". We really liked that and have been using it in the office all day today. Though we’re less fond of the redundancy in the term "IVD companion diagnostic", which we would suggest truncating by one “D” to IVCD. Sounds kind of cool and even ominous, don’t you think?

All kidding aside, there were some noteworthy items in the draft guidance. So, for the benefit of those that hate reading guidance documents, even one that is only 12 pages long, here's a brief summary:

  • FDA didn't rule out that a companion diagnostic could be a 510(k), but they weren't real encouraging either. In the footnote at the bottom of page 9, they suggest that while they’ve never really seen a class II IVCD, they are open to the experience. Hmmm. Our advice is to expect a class III designation and be pleasantly surprised when they agree to class II.
  • There are circumstances where a therapeutic might get approved in the absence of a companion diagnostic. However, these are limited to already approved therapeutics that are adding another indication and novel products for serious or life-threatening diseases. So again, for strategic purposes, expect the diagnostic and therapeutic to be submitted at the same time (contemporaneously!).
  • For our pharma partners, if the plan includes using the IVCD in a drug trial, and treatment decisions will be made with the IVCD (includes placing patients in specific arms of the study or determining which choice of drugs will be made (ala Duke)), it is best to either:  a) file an IDE or b) incorporate IDE requirements in your IND, or c) if using an already cleared/approved device demonstrate that the intended use of the cleared/approved device didn’t change. Any diagnostic used for exclusion/inclusion, treatment selection, etc. should be considered a serious risk and therefore needs to be treated like an investigational device (i.e. made under GMP). And yes, that would apply to LDTs that are specifically linked to a drug clinical trial.
  • In general, diagnostic and drug development should be done contemporaneously (love that word but we’ll stop now as we may be getting annoying).  That will be especially true for novel therapeutic products. So if you are a drug company, don't wait until the last minute to find someone to develop that companion diagnostic for you. FDA will expect your IND studies to address validation of the intended use for the IVCD as well.


We have had several clients ask us about how this applies to LDTs that are currently performing testing of markers that could be useful when making drug selection choices but are not associated with a specific drug sponsor. Will these, based on this guidance document now require FDA approval?

Based on input from FDA we are offering the following interpretation:

  • This guidance is only intended to apply to the marketed tests that are coming in for approval along with the drug. It does not apply to LDTs that are performing tests that could be viewed as companion but are not specifically linked to a drug sponsor. For example, if a lab is performing a KRAS test as an LDT they should not expect to be taken off the market even after a PMA for a KRAS test is approved, and they will not be expected to file a PMA (at least for now until LDT regulation by FDA is clarified).
  • Should FDA begin regulating LDTs, the tests for markers that are associated with drugs would be considered at the top of the list for regulation. However, until a guidance document on regulation of LDTs is issued, enforcement action is not expected.

We have had some clients wondering about the nearly contemporaneous (ok, seriously that is truly the last time) issuing of the recent RUO/IUO draft guidance and this document. We don’t believe they are linked in any specific way but clearly signal the importance of diagnostic products of all types, and given this importance an increased scrutiny and requirements for performance and quality. These changes may be difficult to handle in some respects but ultimately we take it as an acknowledgement of the important work all of our clients and the industry as a whole are doing and the important ways that we are changing the practice of medicine.

Tags: CDRH, FDA, IVD

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