Below are some detailed notes I jotted down on a running basis while listening to the interview - the notes below are NOT a transcript.
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20150126 Mendelspod Liz Mansfield FDA LDT
Interview with Liz Mansfield PhD, FDA, Personalized Medicine, on 1/26/2015.
Q
Things are getting interesting. Bring us up to date. Timeline?
A
We started out by notifying Congress in July. We published draft guidances on 9/30, with a 120 day comment period, closing February 2, 2015. We have just completed a 2 day public meeting, with 80 registered comments (not all appeared) and we had 6 panels with a wide variety of folks and opinions.
Right now, we heard many concepts and ideas, we're working on these, we're getting ready to analyze comments as they come in. We are working towards building out more information for laboratories, as they've requested. "What parts of an exception are CLIA, what FDA? Overlap? Etc." We'll make that clear with new documents.
Q
We had Amy Miller from PMC - they asked for more FDA, CLIA harmonization. Many backgrounds and stakeholders. If someone didn't comment, they had the chance.
A
Everyone who wanted a chance, was able to comment, no one was left off.
Q
February 2 closes the comment period. Not the issuance of new stuff.
February 2 closes the comment period. Not the issuance of new stuff.
A
That's the nominal end of the comment period. We'll definitively consider comments to that day. You can submit later comments. We could still consider them. We go through the whole analysis process. We'd do revisions of the guidance only after that.
Q
Is the final guidance the next milestone?
A
Our analysis, that's the milestone. Then we decide what to do, and we want to do a robust response to comments.
Our analysis, that's the milestone. Then we decide what to do, and we want to do a robust response to comments.
Q
Comment analysis before final guidance?
A
No, at the same time, traditionally.
No, at the same time, traditionally.
Q
Have you set a final guidance date?
A
No! We can't set a date. It depends on too many factors.
Q
You have enough time to go through the commetns.
A
Yes, all the time it requires. And decide what to do. There is no rush.
Q
You issued the draft with two components?
A
There are two documents. One is a "framework" for risk based regulation for LDTs, definitions, and the second is geared toward MDR (AE) reporting and notification (registration).
Q
About the actual meeting. To me, most of the pushback was from reference and pathology labs. They feel like the FDA "does not get it." Is there the guidance could cause fewer and lower quality tests?
A
Well, fewer might do LDTs. That is certainly a risk to account for. We would hope it wouldn't resultin lower quality but higher quality tests with independent pre market review, a third party has validated it.
Well, fewer might do LDTs. That is certainly a risk to account for. We would hope it wouldn't resultin lower quality but higher quality tests with independent pre market review, a third party has validated it.
Q
There were some examples...one made sense to me...the BRAF test. The Roche version is approved, but labs do variations, that's a known thing. They've done it before Roche. Based on the situation, the patients.
A
Right.
Q
So will that change? Will they have to stop? Because there is one approved version?
A
No. It depends on the intended use, but BRAF is generally a companion diagnostic. With the same IU as a companion diagnostic, high on our list for premarket review. Any lab with such a test, could come in and get approval for their test to be used for that purpose. For another purpose, the story might be different.
Q
How?
How?
A
In the meeting someone said the BRAF was for some rare disease, not a normal indication. That patient had a mutation, had a BRAF targeted drug [Zelboraf]. We don't object to a physician asking for that test and finding a BRAF offering lab and you get the result. That is practice of medicine.
So no, we wouldn't stop that. That is how testing occurs now with approved tests. Doctors can order them.
Q
In the real world, there is consult going back and forth? The lab director is telling the doctor what's possible, the lab director knows the latest, not the doctor. Do you see a challenge there? A gray area? Lab directors not supposed to promote off label use, yet, they're educating the doctor, is that tricky?
A
It can be, off label has been tricky for a long time, this issue on LDTs is not new. What is off label "promotion." In many cases, the laboratorian is working with the physician, the patient, you might try this or this. Then it's the physician's decision. That may look like practice of medicine. The laboratorian says, "This is great for this off label use!" that might be promotion, but, it's always been gray zones, not unique to LDTs.
Q
And you have to find that?
A
We don't look for doctors talking to each other about tests. But it's an issues for years with drugs and devices.
A
We don't look for doctors talking to each other about tests. But it's an issues for years with drugs and devices.
Q
So you're familiar, and try to do the best you can. You don't think it's so new for different thinking?
So you're familiar, and try to do the best you can. You don't think it's so new for different thinking?
A
No. Many analogies to what laboratories do today with cleared or approved tests. They may do something different on a situational basis. They're comfortable with that.
No. Many analogies to what laboratories do today with cleared or approved tests. They may do something different on a situational basis. They're comfortable with that.
Q
Was there any significant feedback? If you can answer, that you found new.
A
Yes there were. We thought that... we may have considered something, but now it's more specific suggestions. We asked about defining a rare disease - 4000. Many said no. You are talking about rare testing not rare disease. That may be right. A rare test is a test not performed frequently. A rare diseaes is like a newborn screening disease, you screen 100,000 kids to find 1 case of a genetic disorder. The test is not rare, the disease is. We want to focus on rare tests. There are economic forces in play there, will it be ever developed? How many patients needed to validate?
Q
You'd be more hands off on rare tests?
A
In the proposal, we propose to continue to exercise enforcement discretion for rare disease testing. Just notification. (And AE reporting).
A
In the proposal, we propose to continue to exercise enforcement discretion for rare disease testing. Just notification. (And AE reporting).
Q
We had Amy Miller on. She outlined what she asked for at the meeting. The first, you publish either as a supplement, or in the final, some help in determining how you determine risk.
We had Amy Miller on. She outlined what she asked for at the meeting. The first, you publish either as a supplement, or in the final, some help in determining how you determine risk.
A
Right. It makes sense. We're very cognoscent our language is different than labs, and what we and they say is high risk may be different. We're putting together some materials. We think of risk of serious injury.
Right. It makes sense. We're very cognoscent our language is different than labs, and what we and they say is high risk may be different. We're putting together some materials. We think of risk of serious injury.
Q
And Amy mentioned CLIA harmonization. Labs currently speak the language of CLIA after decades.
And Amy mentioned CLIA harmonization. Labs currently speak the language of CLIA after decades.
A
And our language is different, different regulations and purposes. We think with some help labs can learn FDA language. We know they're different so we'll address that.
Q
The meeting overall?
A
Lots of interesting information. Many things we think aren't necessary right, so people have to understand us better, we have to explain better. And the panels were very informative, they did a great job.
The meeting overall?
A
Lots of interesting information. Many things we think aren't necessary right, so people have to understand us better, we have to explain better. And the panels were very informative, they did a great job.
Q
AMP members like Roger Klein - an attorney. We might bring him on. He saw some contradictions. When a test is both Class III and Class II. He was concerned that FDA was using medical device guidance and superimposing it on labs, a quite different world. Some said, "How can this, really, go through?"
Do you ever think, this is so complex?
A
It is unbelievably complex. We run into folks from the labs want clarity on issues that aren't clear NOW. Everything is complicated and situational. Really, if people want to understand, it's pretty easy to see. Lab developed tests are devices. When you understand that, and understand "the device" it starts to make sense. Labs ask "what is the device?" We have to make that very clear.
It is unbelievably complex. We run into folks from the labs want clarity on issues that aren't clear NOW. Everything is complicated and situational. Really, if people want to understand, it's pretty easy to see. Lab developed tests are devices. When you understand that, and understand "the device" it starts to make sense. Labs ask "what is the device?" We have to make that very clear.
Q
Elaine Lyon of ARUP calls them "processes". I may use a kit, but I do a long professional process. Have you thought more on that?
Elaine Lyon of ARUP calls them "processes". I may use a kit, but I do a long professional process. Have you thought more on that?
A
We have in individual settings explained what we think the device is, and they say, "OK, now I understand." We think there are lab developed procedures, and a professional runs them, under prescription use, in a CLIA lab. We know. But we don't think assembling products with specific instructions for use is a procedure, we think, it is manufacturing a device. So it's hard for us to understand them, too, we would "not not" call it a device.
Q
Paradigm shifts.
A
Probably in the end we won't all be happy. I think Dr Shuren said everyone will be a little unhappy including us!
Q
When the final guidance comes out, the clock ticks.
When the final guidance comes out, the clock ticks.
A
As set up, as proposed, we would start with notification by 6 months. We laid out in the MDR guidance the notification draft elements. We are considering other mechanisms, that labs may have already provided to the Genetic Testing Registry at NIH or to New York State and we could just import it.
As set up, as proposed, we would start with notification by 6 months. We laid out in the MDR guidance the notification draft elements. We are considering other mechanisms, that labs may have already provided to the Genetic Testing Registry at NIH or to New York State and we could just import it.
Q
Speaking of NY State. Someone, Hank Greeley sponsored at Stanford, a representative from NY State. "We do this!" - already, and for many tests.
Speaking of NY State. Someone, Hank Greeley sponsored at Stanford, a representative from NY State. "We do this!" - already, and for many tests.
A
We have looked at the NY State process, and it does a lot of the same things. When a device is "new" with a "new" intended use, NY doesn't have the statisticians, all he validations we do, but it's similar.
We have looked at the NY State process, and it does a lot of the same things. When a device is "new" with a "new" intended use, NY doesn't have the statisticians, all he validations we do, but it's similar.
Q
The next workshop is only sequencing.
The next workshop is only sequencing.
A
We have worked for the last several years to look at NGS, how it works, the error models, to understand if we regulate it, what is the best approach, allowing innovation in more or less real time. That's how NGS is pushing. We put out a discussion paper. It's out there. It asks a lot of questions to stakeholders, how about this, advantages, disadvantages, how about that. This will be February 20. We hope we have all the right people there. Help us formulate the new strategies for oversight that will be much more nimble. With very quick innovation.
We have worked for the last several years to look at NGS, how it works, the error models, to understand if we regulate it, what is the best approach, allowing innovation in more or less real time. That's how NGS is pushing. We put out a discussion paper. It's out there. It asks a lot of questions to stakeholders, how about this, advantages, disadvantages, how about that. This will be February 20. We hope we have all the right people there. Help us formulate the new strategies for oversight that will be much more nimble. With very quick innovation.
Q
Thanks.
Thanks.
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