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CDRH s Harper on the Impact of the FDA s New Guidance Document


The US Food and Drug Administration’s Center for Devices and Radiological Health last week released a guidance document that may serve as a roadmap for molecular diagnostics and the microarray firms they partner with to more skillfully navigate the FDA approval process for their diagnostic tests.

The document, Class II Special Controls Guidance Document: Drug Metabolizing Enzyme Genotyping System [], is a direct result of the process by which Roche’s AmpliChip CYP450 test for drug metabolism — which is run on Affymetrix’ GeneChip System 3000Dx instrument — was approved by the FDA, through its 510(k) protocol, on Dec. 23, 2004.

While, the AmpliChip is useful for determining how patients metabolize drugs that are dependent on the CYP2D6 and CYP2C19 genes, including anti-depressants, anti-psychotics, anti-arrhythmics, beta-blockers, analgesics, some anti-cancer drugs, anti-convulsants, and others, the new document is relevant to many companies that may be planning to bring their microarray-based in vitro diagnostic tests to market.

The fact that it was approved through the FDA’s 510 (k) process, rather than pre-market approval, is also enticing for companies because the 510(k) process is less stringent and time consuming.

To get a better understanding of how such a guidance document could impact the process of seeking FDA approval, BioArray News spoke last week with Courtney Harper, a reviewer at CDRH who helped prepare the guidance document. Harper gave BioArray News an inside look at how the documents are prepared and how they could impact a developing market such as this one.

What’s your job function and how did you put this document together?

I am the reviewer and primary contact for that document. We have a team that worked on it. We basically just put together the type of stuff that we needed to see in a submission and wrote it out into the form of a guidance. Most specially controlled guidance documents are very similar to each other.

Do you regularly release documents like this?

Special control documents are released whenever you have a pioneering technology approved. We have a program that’s called “de novo classification” and that’s under Section 5:13F, Section 2 of the Food, Drug, and Cosmetic Act. This is a process [that occurs when we have] a device which is a new type of device that would ordinarily require a pre-market approval — which is sort of the longer of the two main review routes for medical devices. If we know enough about that type of device and can mitigate the risk caused by a new device, we can classify the device into a lower class which in this case was class II, and issue a special control guidance document — special controls are the things that we would ask that mitigate the risk for a new kind of device

In this case the guidance document just spelled out what kinds of things someone would need to do to be able to show that a device that’s similar to this one is safe and effective.

I noticed that you are soliciting public comment for the document. How important is that comment and how is it used?

Unlike most of the guidances that we actually release, special control guidances are a little bit different than that, they first issue in final form. The one that issued last week was actually a final form of the document. We are always accepting comments on any of the guidance documents that we have. So anybody may submit comments at any time. If we feel that a comment should be addressed or incorporated, we can update guidances as we get comments.

These kinds of documents are non-binding, is that correct? Could they be altered in the future?

All guidance documents are non-binding, they basically just represent FDA’s point of view on certain subjects. So, basically, we can amend them at any time. Sometimes we update them when our thinking has changed on certain subjects or when things go out of date. But all guidance documents are non-binding — they just sort of help industry or other agencies — just let them know what our policy and our viewpoint is on certain subjects.

Is this document a direct result of the process of approving the AmpliChip?

Yes, since we did the AmpliChip through the de novo process we de novo classified it to class II — the special control document is part of that process.

How would this document benefit other companies seeking approval of a similar system?

If somebody that has a device that has a similar type of use, the guidance document will sort of give them information about the types of information that we want to look at for this type of device. They can use it to help them prepare their submissions and in addition they can use the AmpliChip as a predicate device and seek clearance for their device through the 510(k) process.

With this type of clearance, a company can compare their device to another device that’s already on the market and show that their device is substantially equivalent to another device that’s on the market. So now another company can come in and show that they are substantially equivalent to the AmpliChip in intended use and performance and will seek clearance in that manner.

Do you think companies are sometimes intimidated by the process of bringing a new product to market?

I can’t really comment on what the companies think — I don’t really know. Part of the point of guidance documents is to give as much information as we can to help people to know what is expected. We have other programs where we talk to companies before they are ready to submit information about devices that they have coming up so that they know and they can get some questions answered. One thing I should say is that we have timelines for review, and they’re different for the different types of devices. So when we talk about the pre-market approval our timeline for that is 180 days. And a 510(k) clearance is a shorter timeline, that timeline is 90 days — so, there is a very different timeline depending on the type of review. De novo reviews of this type usually follow the timeline of a 510(k) rather than a pre-market approval.

Do you think that this document could be used by companies that do not have a device exactly like the Amplichip but nevertheless they could follow the same procedure?

Sure. I think some concepts discussed in the guidance documents may be applicable to other types of similar devices. Especially the analytical data,which is usually similar with similar technologies, although sometimes it’s the clinical data that’s a little bit different.

How long did it take for the pioneer technology to go through the process?

I can’t give you an exact time, just because we aren’t allowed to discuss it. But as I said before the timelines for de novo are very similar to the 510(k) timelines and those timelines are around 90 days, so you’re talking a couple of months in the usual case, not along the lines of a couple of years.

Will these documents help people that are seeking approval cut back on the amount of preparation time they need before they formally seek approval?

I think that that is definitely one of the goals — to make it more transparent as to what we would look for in a submission. That is definitely one of the goals of guidance documents in general. I do know that I certainly have submissions where somebody followed one of our guidance documents fairly closely and ended up with a more complete submission that was along the lines of what we look for. So I think they can inform people as to what they need to do and sort of guide the type of studies they want to do, if they know what our point of view is. I should say though that, because it’s not binding, companies are certainly welcome to come and talk to us about other ways of doing things to demonstrate the same things.

Is it common for similar submissions to increase after the release of these documents?

We definitely see more communication about types of devices because people see the guidance documents, and once somebody has done the de novo classification, other people have a clearer path to follow to get similar products on the market, so in that way it would encourage a little bit more submissions, rather than less.

Doesn’t this help you out as well?

It helps us in two ways. In one way it takes [fewer] resources from us to review a 510(k) than to approve a pre-market approval application, and also a guidance document does help in that it basically sends the message out to everybody about what is needed so everybody is sort of on the same page.

Are there any other guidance documents you are working on that might benefit the industry?

We do have a couple of draft guidances that are close to being submitted. One is based on genetic testing with general and multiplex tests so that may be out in the next few months we hope, and that may be more general and provide guidance for people that make tests similar to this one.

Is that based on any specific technology?

No that particular document is just our general views on submissions for tests for heritable diseases. It would be a regular guidance document not a special control document, so where this one is connected to a new regulation that we made. The other one will just be a guidance document that gives our views on that topic.


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