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FDA s IPRG Director Felix Frueh on VGDS So Far and PGx in 2006

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Name: Felix Frueh

Position: Head of the Interdisciplinary Pharmacogenomic Review Group; Associate Director for Genomics, FDA/CDER

Background: Founder and Managing Partner, Stepoutside Consulting — 2002-2004; Pharmacogenetics Research Director, Transgenomic — 2001-2002; Assistant Director, Protogene Laboratories — 1999-2000

Education: : PhD in Biochemistry from the University of Basel, Switzerland — 1995; MS in Biology from the University of Basel, Switzerland — 1991


Pharmacogenomics Reporter this week spoke to Felix Frueh, head of the Interdisciplinary Pharmacogenomic Review Group and associate director for Genomics at the FDA's Center for Drug Evaluation and Research, to hear how voluntary pharmacogenomic data submissions have progressed approximately one year into the effort, and to find out about the US Food and Drug Administration's plans for pharmacogenomics going into 2006.

How has the voluntary pharmacogenomic data submissions process fared, up to this point?

It's been going extremely well, and if I may say so, I should give you a couple of reasons why I say that.

First of all, the number of submissions that we have currently is approximately 25, of which we have had 15 meetings so far. So, we've had a few submissions in which there was no meeting request, and then secondly we are reviewing a few submissions [for which] we haven't had the meeting yet. I think the number speaks for how well the program is going.

Secondly, we have sent out to all sponsors after the meeting a fairly formal feedback-form of survey, where we ask them about several different aspects — scientific but also formal aspects — about how these meetings are being received. The feedback is excellent; I mean, we're getting a 4.5 out of 5, if you want to look at numbers. Overall, we've heard specific comments about what sponsors like, and what they think could be improved. So, that's another indication that the feedback tells us that we're doing OK with this program.

Third, we have several sponsors that [have] actually either already submitted a second or even a third voluntary data submission, or followed up with a second submission after their initial submission. To me, this is probably the single-most important indication that the program is going well, because if we didn't perform, I wouldn't think that anybody would come back. In particular, with a follow-on, they have new questions based on feedback they got on the first time around.

So, it's really a program that looks at the exploratory stages in such a way that a dialog between industry and FDA to look at such genomic information can be used most effectively in the drug development process.

The last point that I think is important is that we've also had two joint meetings with the European regulatory agency, the EMEA, and requests for these meetings [between the agencies and industry] also have gone out. So, besides the fact that we here at the FDA think that this is a good thing to do, there has been a new dimension added to it, which is sort of the international aspect of how Europe looks at this genomic information from a voluntary perspective.

The way it has been working is that the sponsor submitted the same information package to both EMEA and FDA, and we then, from a regulatory perspective are reviewing these submissions. We have pre-meetings via teleconference and videoconference, and then have joint meetings with the sponsor, where the sponsor is visiting us in the US, as well as in the UK in London at the EMEA. So that was also something that was very successful, and we've gotten more requests for these meetings also.

Is there any major difference in the way that the EMEA is approaching this kind of data?

That's a very interesting point. The answer is, from a scientific perspective, basically no. It was very surprising to us that few, if any, actually different points of view would have to evaluate the data. Moreover, I would even say that the reviews have actually been better, and the feedback that we provide to sponsors has been better because of joint review of the information.

What has been different has been the bureaucratic or administrative portion of it — how the meeting minutes are written and who has to sign off on it. We're setting up a document that spells out, based on our experience, how we would like to do that in the future, as bilateral meetings go.

What's been the largest hurdle so far in VGDS?

It's difficult to pinpoint to one specific thing. The beauty of this exercise is that we identify various issues, most of which are really minor. The one thing that perhaps is sticking out is the format in which data is being submitted to us, and the extent to which data is submitted to us. It kind of shows the limitations of current data submissions — for example, having printouts being submitted is not really helpful if you're talking about microarray data. You can't, of course, do that.

What we're also doing based on this experience is revising our best practices — not specifically for voluntary data submissions, but for microarray data submissions. So, we've gotten experience along the way to be able to come up with recommendations on how it could be done to facilitate the analysis of this data.

Can you tell me what the status is of the drug-test co-development guidance?

We are working on transforming [the drug-test co-development concept paper, which the agency produced last year] into a draft guidance; It … will be issued as a draft in which stakeholders have the opportunity to comment on it. It's currently being worked on by different parties, including the legal department, so it is in the works.

Somebody once coined the phrase, 'It's going to be released in terms of FDA-soon.' We hope it's going to come out within the first or second quarter of this year, but it's difficult to say because of the experience that we had with the pharmacogenomic guidance, which was delayed simply because it was a much more difficult clearing process than we anticipated because of the variety of centers that were involved.

You can imagine if four or five parties are working on a document — not everybody's sitting in the same room and can say, 'I agree' or 'I do not.' It bounces back and forth a couple of times. We experienced the same with this particular draft guidance as well — the different comments from the device center and from CDER and from CBER, as well as from the Office of the Commissioner, are being considered.

What we do know is that it will come out; I just can't give you a precise date.

[Comments on the concept paper] were mostly to the effect of the timing of the development of a diagnostic versus a drug, and how strategically it poses a challenge to the industry to coordinate these two efforts.

From our perspective also, the new document is going to tell a little bit more about the clinical portion. So, talking about the clinical validity and the clinical usefulness of the drug-device combination versus the more analytical perspective of the current concept paper.

Are there other FDA documents or policies you expect to affect the development of pharmacogenomics in the coming year?

We don't have any formal plans at this point. As I mentioned, we're discussing revising some best practices regarding microarray data submissions. But it's not going to come in the form of a guidance, [but rather in a peer-reviewed journal].

We have a draft on how to best validate a preclinical biomarker to assess drug safety — this is also something that most likely is going to be published in a peer-reviewed journal. Potentially, what we're doing is trying to make people aware of what we have learned through these voluntary data submissions and sort of give it back to the community, in a sense, so that we can build upon that and also get additional feedback — because of course, you realize that there are many more stakeholder besides the ones that so far have submitted a voluntary data submission.

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