NWX-HHS FDA (US)

Moderator: Irene Aihie

9-04-14/12:00 pm CT

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NWX-HHS FDA (US)

Moderator: Irene Aihie

September 4, 2014

12:00 pm CT

Coordinator: Welcome and thank you for standing by. At this time all participants are in a 

listen only mode until the question and answer session of today's call. At that 

time if you would like to ask a question please press star 1.

Today's conference is being recorded. If you have any objections please 

disconnect at this time. I would like now like to turn the meeting over to your 

host Ms. Irene Aihie. You may begin.

Irene Aihie: Hello and welcome to today's FDA Webinar. I am Irene Aihie of CDRH's 

Office of Communications and Education. Today we will be discussing the 

final guidance document FDA Decisions for Investigational Device 

Exemption, IDE, Clinical Investigations which was published on August 18, 

2014.

The final guidance described the FDA's decision making and communications 

regarding applications from companies that want to conduct medical device 

clinical trials in the US. It also described more flexible options for clinical 

study approval that allow clinical studies to begin sooner while ensuring 

patient protection.
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Today Owen Faris Acting Clinical Trial Director and CDRH's Office of 

Device Evaluation will present an overview of the guidance document 

including what has changed from draft to final. And will answer questions 

following the presentation.

Also with us today to assist the Q&A portion of our Webinar are other subject 

matter experts from the Office of Device Evaluation, and Office of 

Communication and Education.

We have become aware of a typo in the original email announcement and 

guidance and webinar. We apologize for this error. If you are having difficulty 

logging in to the Web portion of today's webinar, you can log in with the link 

and conference number available in the email.

However, please use pass code 1405152. Additionally the slide presentation is 

available on the CDRH Learn section of the FDA Web site at 

fda.gov/training/cbrhlearn under the heading How to Market your Device.

Following the webinar the audio recording and written transcript of today's 

program will be available on the CDRH Learn. Now I give you Owen.

Owen Faris: Good afternoon. My name is Owen Faris and I'm the Acting Clinical Trials 

Director in the Center for Devices and Radiological Health. And I was also 

the lead author on the first two drafts of this guidance as well as the final 

guidance.

So let me just start with an overview of what we're going to discuss today.

First we're going to talk a little bit about what this is all about and how this 

guidance fits into our FDA strategic priority.
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I'm going to define what a guidance document means very briefly and define 

what an investigational device exemption study is. I'm going to talk a little bit 

about the history and the original goals of this guidance because there is quite 

a lengthy history to this guidance.

I'm going to talk a little bit about some changes in the law that occurred 

during the writing and draft period of this guidance that impacted what we 

have in our final document. I'm going to talk about what has changed in the 

final document compared to the draft guidance.

And then I'm going to walk through some of the meat of the guidance itself. In 

particular the decisions that we make for different IDEs and some of the bases 

of those decisions. And then I'm going to close with talking about how we 

communicate our decisions in our letters.

So first our strategic priorities. So CBRH has identified a strategic priority, the 

goal of improving US patient access to new devices by strengthening and 

streamlining the clinical trial enterprise so that medical device clinical trials 

are conducted in the US in efficient cost effective manner while maintaining 

appropriate patient protections.

So this guidance really fits into that in that it introduces processes that allow a 

more efficient study enrollments to reduce the time and cost associated with 

the conduct of clinical trials. Provides information regarding our decision 

making process in order to improve predictability of the regulatory process.

And it introduces communications intended to improve the transparency of 

FDA's decision making process to study sponsors and other stakeholders.
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So what is a guidance document? A guidance document explains our current 

thinking on a topic. But it's important to note that it doesn't establish legally 

enforceable responsibilities. And what we say in that document really should 

be viewed as recommendations unless there are specific regulatory or 

statutory requirements cited.

So what is an IDE or an Investigational Device Exemption? It's established in 

Section 520 of the FD&C Act. An FDA approval of an IDE is required for US 

human study of a significant risk device which is not improved or cleared for 

the indication being study.

It exempts sponsors from certain provisions of the FD&C Act. For example 

requirement of a marketing application and compliance with full GMPs. There 

are requirements for informed consent, labeling, monitoring of the study and 

records and reporting. And initiation of the study also requires approval by an 

institutional review board or IRB.

So as I mentioned this guidance has quite a lengthy history. It was originally 

published on November 10 of 2011 and explained each of the possible FDA 

decisions that we can make when reviewing an IDE.

Those would be approval, approval with conditions, and disapproval. And it 

provides examples of reasons that could support IDE disapproval or approval 

with conditions. And it also explained a new mechanism that we termed stage 

approval which allows some studies to begin while issues are addressed 

concurrently.

However during the draft period of that guidance, actually shortly following 

the closure of the comment period for that first draft, the law was changed 
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under FDASIA 601. Section 601 amends 520G Part 4 Part C of the FD&C 

Act and became law in July 9 of 2012.

And specifically there was an element of that that targeted some elements that 

were somewhat inconsistent with the current draft of the guidance. And I'll 

reference the specific language which was FDA shall not disapprove an IDE 

because the investigation may not support a substantial equivalence or de 

novo classification determination, or approval of a device.

The investigation may not meet a requirement including a data requirement 

relating to the approval or clearance of a device. Or an additional or a 

different investigation may be necessary to support clearance or approval of a 

device.

So what does that mean? That essentially means that an IDE cannot be

disapproved on the basis of FDA's belief that the study design is inadequate to 

support a future PMA, 510K, HDE, or de novo classification.

Of note the standards for market approval or clearance of a 510K did not 

change under FDASIA.

So once that law changed FDA and CDRH in particular had to sort of spend a 

little time thinking about how we were going to modify our guidance to be 

consistent with the changes to the law.

So we formed a working group that developed some policies around IDE 

decision making. We made modifications to our IDE decision letters that 

would be consistent with the new requirements under the law. We considered 

other mechanisms to encourage sponsors to work with FDA to develop pivotal 

trials that were appropriately designed to support marketing applications.
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So the thinking being that we were no longer in a position to disapprove those 

studies if they were adequately protecting subjects. But we and other 

stakeholders and sponsors still have an interest in developing the right study to 

support future marketing applications.

So we were exploring ways to do that in an appropriate way that would be 

consistent with the law.

We re-issued guidance for public comment in June of 2013. That closed in 

September of 2013. We received a lot of very good comments. And based on 

those comments and our considerations of those comments we made some 

modifications that I'm about to discuss in issuing the final guidance.

So first off I'll start with what is nearly unchanged from the draft guidance. So 

our explanation for the reasons for which FDA may disapprove an IDE was 

not substantially changed.

Our explanation for the mechanisms of approving an IDE was not 

substantially changed. So approval, approval with conditions were nearly 

identical between the most recent draft and our current final document.

We did make some minor modifications to our explanation of staged approval.

They were mainly for clarification. And I'm going to walk through all of these 

mechanisms in the next few slides.

So what did change from the most recent draft to the final document? We did 

change how study design considerations and future considerations will be 

communicated to sponsors. And I'm going to explain that.
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And we removed a proposal that we had put in the most recent draft, a new 

voluntary comprehensive, interactive review process to assist sponsors in 

development of appropriately designed pivotal studies. We termed that 

process the pre-decisional IDE. And based on the comments we decided to 

remove that. And I will explain why in the preceding slides.

So let's dig into the meat a little bit of what this guidance has to offer. So I'll 

start by talking about what are the three main decisions that FDA can render 

when an IDE is reviewed by CDRH.

So there is approval. And that can be approval of the full study cohort or 

staged approval. And I'll explain what that means. There is approval with 

conditions. And that, again, can be approval of the full study cohort or staged 

approval. And then there's disapproval. And we're going to walk through each 

of those.

So first off let's talk about approval. FDA approval, also called full approval, 

means that we don't have any remaining questions that must be addressed 

prior to enrollment of the approved number of subjects.

The study's approved for a specified number of subjects and investigational 

centers. And the study can be initiated upon IRB approval. Our letter wouldn't 

convey any outstanding questions that need to be addressed in order for the 

study to move forward.

So that was the easy one. Now we'll start getting into the more complicated 

ones. So approval with conditions. Approval with conditions means that FDA 

has determined that despite some outstanding issues the information provided 

is sufficient to justify human clinical evaluation of the device. And the 
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proposed study design is acceptable with regard to protection of study of 

subjects.

Resolution of the outstanding issues isn't required prior to the initiation of 

enrollment in the study with exception of certain issues related to the 

influence and consent which must be corrected prior to enrollment.

And the sponsor can begin the study upon receipt of IRB approval on the 

condition that within 45 days from the date of FDA's decision letter the 

sponsor submits information addressing the issues identified in FDA's letter.

So let's talk about some of the examples of typical conditions that might be 

conveyed in an approval with conditions letters. Requests for additional 

information, data or changes that relate to protecting subjects in the study and 

can be addressed in a timely manner, 45 days but for which FDA determines 

that they do not need to be resolved prior to study initiation.

Late stage follow-up procedures and assessments that relate to the care of

study subjects but because they occur late in the study they'll likely be 

addressed prior to subjects reaching that point in the study. And minor issues 

relating to the informed consent document that must be corrected before study 

initiation but can be reviewed by FDA after initiation.

Let's talk about staged approval because that can apply both to approval or 

approval with conditions. And it's granted while certain outstanding questions 

are answered concurrently with the enrolment of a limited number of subjects.

So the thinking here is that if the benefit risk profile is sufficiently favorable 

to justify an enrollment of a portion of the study subjects, a staged clinical 

investigation allows initiation of the study that might otherwise be 
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disapproved while providing additional mitigation of risk by limiting exposure 

of the device to a smaller subject population.

The sponsor will be permitted to expand enrollment once an IDE supplement 

containing the necessary additional information is submitted to FDA and 

found to be acceptable.

So let me just go into a little bit of detail of how that might play out. We 

might receive an IDE application where the sponsor is asking for enrollment 

of say 300 subjects. And we may have some outstanding questions that will be 

answered during the course of the early stages of enrollment of that study 

either from external information, non-clinical information that can be gathered 

concurrently, or from the clinical information being gathered early in that 

study.

And we may not at this point feel comfortable exposing all 300 subjects but 

we may feel like there is a reasonable profile in terms of benefits and risks for 

subjects that it is reasonable to allow a limited exposure for say, 30 subjects.

And we might allow those 30 subjects to be enrolled while the additional 

information is being gathered. And when that information is gathered the 

sponsor could come to FDA and with an IDE supplement providing that 

information and request expansion of that study.

The staged approval might be appropriate when additional clinical 

information confirmation of the safety profile, the potential for benefit is 

obtained by reviewing initial data from subjects enrolled early in the clinical 

investigation before enrolling the entire subject cohort.
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Or when additional confirmatory non-clinical testing is needed to more fully 

characterize the device performance to adequately evaluate the potential for 

risk of the device before permitting the entire subject cohorts and it's 

conducted concurrently with early enrollment in the clinical investigation.

Now we can do staged approval with essentially any kind of study. But we 

frankly see this more commonly with pivotal studies where the device design 

is finalized. We know enough to design the study itself but we have some 

outstanding question that needs to be answered before the entire cohort is 

exposed to risk of the device in the study.

And there are some specific considerations for pivotal studies that are noted in 

the guidance that I'll walk through now. So when staged approval is applied to 

a pivotal study it's important to understand that successful support of a 

marketing application under staged approval really isn't expected until the full 

plan cohort is subject is studied.

Also a staged pivotal study really should only be considered if the additional 

information that's requested isn't expected to result in changes to important 

elements of the clinical investigations such as endpoints, sample size, stopping 

rules, or to the device design.

If we're still at the stage where we don't know fully how to design the clinical 

study or we haven't finalized the device design we're probably not ready for a 

pivotal study at that point. And probably a feasibility study is more 

appropriate than a staged pivotal.

Some additional considerations for pivotal studies. At the end we determine 

that a new feasibility - that new feasibility data are really needed prior to 

approval of the proposed pivotal study in order to allow for a more 
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comprehensive examination of the study outcomes related to device safety in

a small number of subjects prior to exposing a large group of subjects to the 

study.

So my point here is that staged approval really works best when there is a 

single specific question that can be answered in a concise manner. If we don't 

know enough to formulate that question and we really have a broad set of 

questions around the safety of the device that need to be answered in the 

smaller cohort of subjects.

Again that probably isn't the time for a staged pivotal study. We're probably 

talking about a feasibility study that can be more comprehensively examined.

The data requested by FDA also shouldn't inappropriately un-blind any of the 

relevant stakeholders including the sponsor, investigators, study management 

personnel, to critical study data.

So most of the time we're talking about data that are not directly related to the 

primary outcomes of the study. So we might have a particular safety question 

about certain adverse event rates associated with the implant procedure of the 

device or something along those lines.

But typically we're not asking for the outcome data that will be the primary 

endpoint of the study. And we're not asking for data that is so directly related 

to that that presentation of that data, knowledge of that data, would taint the 

quality of the data and start to lead to questions of data integrity.

So let's move on to disapproval. So disapproval essentially means that the 

sponsor may not initiate the clinical investigation until the sponsor submits an 

amendment to the IDE to respond to the deficiencies identified in FDA's letter 
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and subsequently receives a new letter from FDA granting approval or 

approval with conditions.

So again I'll remind you that FDASIA changed to a certain extent the criteria 

by which we might disapprove a study. And that was cause for the second 

draft of the guidance. But I will remind you also that the standards for 

protection for study subjects remain unchanged.

So issues regarding protection of subject whether they be related to study 

design or non-clinical testing still remain reasons for disapproval. And I'm 

going to go into some of the specifics of where we might fall out on that.

Also per FDASIA issues regarding the study design that are not related to 

protecting study subjects are not the basis for disapproval or an approval with 

conditions decision. And instead they would be conveyed as study design 

considerations. And I'm going to explain what that means as well.

So I'm going to go through some of the reasons that are associated in the 

regulations for disapproval. And I'm going to explain a little bit about what we 

think that means in terms of practical consequences.

So consistent with 24 CFR 812 Part 30B and Section 520G of the FD&C Act, 

FDA may disapprove an IDE for any of the following reasons. There has been 

a failure to comply with any requirements and 21 CFR Part 812 or 520G of 

the FD&C Act. Any other applicable regulation or statute or any condition of 

approval imposed by an IRB or FDA.

The application or report contains an untrue statement of material fact or 

omits material information required by a 21 CFR Part 812. The sponsor fails 
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to respond to a request for additional information within the time prescribed 

by FDA.

There is reason to believe that the risks to subjects are not outweighed by the 

anticipated benefits to subjects and the importance of the knowledge to be 

gained. So that really speaks to, you know, as the investigational plan 

adequately protecting study subjects.

Is it exposing the subjects to unacceptable probable risks? Or does it fail to 

adequately protect study subjects from probably risks?

Another reason, the informed consent requires changes to adequately inform 

subjects of the study and must be reviewed by FDA prior to study initiation.

So you'll note that I also talked about informed consent being a reason for 

approval with conditions decision which is very commonly the case.

If the informed consent has some essentially some very clear cut issues that 

we believe can be addressed by the sponsor prior to our review and 

implemented then that would typically be a reason for approval with 

conditions.

But if the informed consent contains an element that we are concerned about 

that we believe is so essential that we must review it prior to subjects being 

enrolled in that study then that would be a basis for disapproval.

The investigation as proposed is scientifically unsound because it does not 

pose a reasonable scientific question or the investigation does not include 

collection of data or information related to that scientific question.
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So I will point out that scientifically unsound doesn't include concerns that the 

study design will not support a marketing application.

There is reason to believe that the device as used is ineffective. So here we're 

talking about inadequate potential for benefit so the available data suggests 

the device is ineffective or no information has been provided to suggest the 

device as used may result in patient benefit and the generation of knowledge 

adequate to justify the risks.

It is otherwise unreasonable to begin or to continue the investigation only to 

the way in which the device is used or the adequacy of the report of prior 

investigations or the investigational plan, the methods, facilities, and controls 

used for the manufacturing, processing, packaging, storage, and where 

appropriate installation of the device or monitoring or reviewing the 

investigation.

So in large part we're talking about device safety here, the data and 

information provided are insufficient to adequately characterize a safety 

profile of the device such that human clinical investigation is not considered 

reasonable.

So the guidance goes into a little bit more detail and there are some examples 

of some of the reasons why we might disapprove the study.

So I'd like to talk a little bit about study design considerations. This is a 

mechanism that we implemented after the first draft of the guidance following 

the changes in the law. As a mechanism by which we could provide 

recommendations to a sponsor regarding changes that we believe should be 

made in order for the study to support its primary goals but that were not the 

basis for disapproval or an approval with conditions decision.
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So examples of those kinds of considerations include issues related to primary 

and secondary, major secondary endpoints, randomization control and 

blinding, follow-up duration in assessments, statistical analysis plans, and 

enrollment criteria if not related to subject protection.

And I'll just emphasize that anything that is related to subject protection even 

if it deals with study design may still be a basis for a deficiency. The bar for 

protecting subjects is not changed.

So what are future considerations? So future considerations have been around 

for a long time but are also an important element that we described in the 

guidance. Future considerations are intended to provide helpful advice to 

sponsors regarding important elements of the future application of the IDE 

may not specifically address.

So some examples. Known limitations of the IDE clinical investigation with 

regard to supporting certain claims or indications. Specific non-clinical testing 

that while not necessary to support approval of the IDE would be needed to 

support the marketing application.

So here we're going to get into some of the changes that we have implemented 

in the guidance most recently. So the draft guidance proposed that study 

design considerations be included in the section of the IDE decision letter 

itself.

We specifically requested comment on that proposal and we received quite a 

few. So FDA received comments from several stakeholders that proposed that 

FDA provide study design considerations and FDA's assessment of the study 

design as a separate communication and not in an IDE decision letter itself.
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However some other stakeholders expressed support for inclusion of the study 

design considerations in the letter. And others really didn't discuss where the 

study design considerations go. But they did focus on ensuring that they 

decision letter clearly conveys whether or not FDA believes that the study 

design is adequate to support goals.

So based on the comments received FDA believes that when study design 

considerations are included in the body of a decision letter there is the 

potential for study design considerations to be misinterpreted by sponsors and 

other stakeholders as issues that are required to be addressed rather than as 

recommendations.

Therefore FDA intends to convey study design considerations in a separate 

attachment included with the decision letter rather than in the body of the 

letter. And the decision letter itself will state whether FDA believes that the 

study design is adequate to support the study goals or whether FDA 

recommends study design considerations in order for the study to do so.

And if we do recommend study design considerations our letter will note the 

following. These recommendations do not relate to the safety, rights, or 

welfare of study subjects. And they do not need to be addressed in order for 

you to conduct your study.

So essentially we're trying to make sure that everyone, all stakeholders 

involved in reading this letter and making decisions related to this letter 

understand our intention here which is to convey elements that we believe are 

important.
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And we strongly believe the sponsor should address to support the study being 

as meaningful as possible and as useful as possible in the future iterations of 

this device.

We think that it's very important to have the sponsor be fully informed of the 

extent of FDA's review. And be able to consider these recommendations so 

that whatever is next whether that be a future pivotal study if this is a 

feasibility study.

Or whether that be a future marketing application that the sponsor is as well 

informed as possible about how to move a potentially important technology 

forward. And such that the study itself is ideally designed to be, to make the 

most of the information gathered and be as useful and meaningful as possible.

So I also note that we will continue to engage with stakeholders on this issue 

and make modifications to approach them in the future depending on our 

experience thus far.

So similarly with future considerations we received comments proposing that 

the agency provide future considerations as a separate communication not in 

the decision letter. And we think there are good reasons for this as well.

So based on the comments received we intend to convey the future 

considerations as a separate attachment similarly to design considerations.

And that attachment will again be included with the decision letter rather than 

in the body of the letter itself.

So I'm going to briefly touch on a proposal that is not in this final guidance.

The most recent draft of the guidance proposed a new mechanism for review 

and interaction for pivotal IDEs.
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We called this the pre-decisional IDE. This process was comprehensive FDA 

review of a draft IDE prior to formal IDE submission, followed by written 

feedback from FDA in an interactive discussion between FDA and the 

sponsor.

And the goal of the pre-decisional IDE was to facilitate the development of an 

approved IDE submission that would be more likely to be approved and 

include a study design that would be adequate to support a future marketing 

application. This was focused on pivotal studies.

However FDA received relatively mixed comments. We received several 

comments expressing concern that the pre-decisional IDE process itself might 

be too time consuming or require extensive FDA resources that could be 

better allocated elsewhere.

And upon further consideration we also believe that our pre-submission 

process which is a very active and meaningful process can address many of 

the same goals. And so based on the comments received and FDA's 

considerations of the points raised, FDA will not pursue the pre-decisional 

IDE at this time.

I provided a link for the guidance. And I think that is probably my last slide. I 

think we are ready for questions.

Coordinator: Thank you. And we will now begin the question and answer session. If you 

would like to ask a question please press star 1 and record your first and last 

name clearly when prompted.
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Your name is required to introduce your question. To withdraw your question 

you may press star 2. Once again if you would like to ask a question please 

press star 1. One moment please for our first question.

Our first question is from (Amy Harold). Your line is open.

(Amy Harold): My question is what constitutes a feasibility study versus a staged pivotal 

study? And is there a difference in the FDA review processes for these two 

different studies?

Owen Faris: So that's a great question. So first off I'll take the second part of your question 

first. There aren't any differences in the review process. From a time 

prospective all IDEs are reviewed within 30 days.

We have a similar team that would review either a feasibility or a pivotal 

study. And so from a review process and the decisions that we can make in all 

of that there really aren't any fundamental differences.

But I think there are differences in terms of what the intent of that study is.

And so I think there are times when, there, when you have a device design 

that is essentially final. And you know enough to design your pivotal study.

But you - there may be some outstanding questions that we believe and 

potentially the sponsor believes as well should be answered before the entire 

pivotal study cohort is exposed to the risks of the device in the study.

And that's the perfect time to do a staged pivotal study where there is a 

discreet question being asked that might be a non-clinical question. So it could 

be the case that in one area of non-clinical testing you've done almost 
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everything that needs to be done to support the pivotal study. But there's one 

element or two elements that haven't quite been completed.

Maybe they're going to take three or four months to be completed. We have a 

lot of other information that is very encouraging with regard to that missing 

element. So we feel relatively comfortable in that area. And we say okay. You 

can start your study. But you need to finish up this area of non-clinical testing 

before the entire study cohort is exposed.

Essentially we are asking for the confirmation of what we believe is already a 

relatively positive safety profile in that regard. And that's done concurrently 

with the study moving forward.

It might also be the case that we are asking for something that is internal to the 

study. So we want to see how the first 30 patients perform with regard to some 

particular adverse event before we feel comfortable moving forward.

The only way we're going to get that is by starting to have patients be 

enrolled. But if we know enough about how to design that study there isn't 

necessarily a reason to force that to be its own feasibility study.

So let me contrast that with what might be more appropriate with the 

feasibility study. So in a feasibility study we think that, you know, we're in an 

earlier stage. We probably don't know enough to design every element of that 

pivotal study. So something is likely to change at the end of that study that is 

meaningful. Or there's potential for something to change.

So maybe something's going to change within the device itself. And in which 

case it's time for a feasibility study so that we can open that entire, that data 
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set entirely up at the end of the day and understand it better. Both the sponsor 

and FDA to inform that future design.

It's also possible that in many cases the device design is finalized but the study 

design - so that pivotal study isn't. So we might not know enough to design 

the appropriate primary endpoint for safety or for effectiveness. Or how best 

to treat patients in certain elements of use of the device. And we're going to 

learn that during that feasibility study.

And it wouldn't be appropriate to learn that during the feasibility study and 

then have those same feasibility study patients part of a pivotal data set. So 

that's sort of the contrast to a staged pivotal study.

If you need to learn something from the feasibility in order to inform either 

the device design or something about the testing for that device that we don't 

fully know. Or something about the clinical trial itself, the design of that study 

then you probably need to have a feasibility study that informs that. That we 

can open up entirely and explore before moving forward.

If there is just a single specific question that is not limiting in terms of the 

design of the device or the study itself, then in some circumstances it's 

appropriate to ask that single specific question concurrently with early 

enrollment in the study if we believe that subjects are adequately protected 

based on everything we know.

Coordinator: Our next question is from (Cathy McNeil). Your line is open.

(Cathy McNeil): Hi. Could you repeat the Web site where we can obtain copies of the slides?

Owen Faris: Just one moment.
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Irene Aihie: Yes. You can find it on the CDRH Learn Section of FDA's Web site.

(Cathy McNeil): Thank you.

Irene Aihie: And you'll find it under How to Market your Device.

Coordinator: Our next question is from (Lee Aires). Your line is open.

(Lee Aires): Hi. My name is (Lee Aires) from Oxford Performance Materials. I have a 

question regarding the pre-IDE review process. I understood from your 

presentation that it's no longer available. Or did I understand that correctly or 

incorrectly?

Owen Faris: So you did misunderstand to a certain extent. And I'm glad you asked the 

question because maybe others misunderstood as well. So I didn't use the term 

pre-IDE. We've changed that name.

And we no longer use the term pre-IDE because it applies more broadly than 

just to IDEs. Pre-IDE is part of our Q-submission process. We now call the

pre-IDE pre-submission instead.

And it applies to other types of files other than just IDEs. So now that will be 

termed a pre-submission. So that is alive and well. And we very much 

encourage sponsors to utilize the pre-submission process.

The term that I used is pre-decisional IDE which was something that we 

developed as a concept and articulated in the most recent draft and have 

decided not to implement. But the pre-IDE - formerly known as pre-IDE 

process, now the pre-submission process is alive and well and (unintelligible).
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(Lee Aires): So that means if we were developing a protocol for an IDE we could use the 

pre-submission process for that?

Owen Faris: Absolutely. We strongly encourage that.

(Lee Aires): Okay.

Owen Faris: Thank you for the question.

(Lee Aires): Thank you. Thank you very much.

Coordinator: Our next question is from (Ken Lupe). Your line is open.

(Ken Lupe): Yes. When is the class of a device determined? And are all IDEs 

automatically a class three device?

Owen Faris: I think I'm going to defer this question to (Soma Kalb) who's our IDE 

Director.

(Soma Kalb): Hello. So the class of the device can be determined through a few different 

mechanisms. We can discuss that during the pre-submission process and 

through the pre-submissions process.

There's also a formal process called the 513G Process and there's information 

- there's a guidance about the 513G Process. And there's also a guidance about 

the pre-submission process as well that's available.
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Not all studies requiring IDEs are class three devices. Significant risk studies 

are those that require IDEs and that considers not only the risk of the device 

but the risk that might be introduced by the study itself.

If you are unsure about whether your device or study requires an IDE you can 

submit a, what's called a study risk determination submission. And that is also 

outlined in our guidance document called pre-submission and meetings with 

FDA.

So basically that's the answer to the question.

Owen Faris: And I'll just - just follow up with that by saying that, you know, we do even 

have some class three devices for which the proposed study we determined it 

is a non-significant risk study and there's no IDE required.

(Ken Lupe): Thank you.

Coordinator: Our next question is from (Velotte). Your line is open.

(Velotte): Hello. I'm (Velotte Unintelligible). And the question I have, patient 

enrollment protocol and consent approval by IRB. Also protocol amendment 

approval by IRB for a follow-up change in assessment, followed by another 

amendment for changing endpoint.

So the question here is that if the protocol is approved and the consent is 

approved by the IRB, one can patient enrollment begin? Because the second 

amendment affects the follow-up assessment and at that point it will have an 

amendment protocol approved by IRB and a consent form.
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And the patient will be consented before the assessment is done. And can all 

these patients that are enrolled before the amendment approval, can they be 

included as, into the patient population?

Owen Faris: So I'm going to suggest - this sounds like a very specific question that I'm 

happy to follow-up with you offline. And so I'm going to suggest that you 

email me at the email address that's on the last slide. And either Soma or I will 

be happy to work with you on the specifics of the question.

(Velotte): Wonderful. Thank you.

Coordinator: Our next question is from (Argie). Your line is open. And participant your line 

is open. If your line is muted you can press star 6 to un-mute your line. Again 

your line is open. We'll go to our next participant. This participant was not 

able to mention their name. But participant your line is open.

Man: Hi this is (Unintelligible). Can you hear me?

Owen Faris: Yes.

Man: Hi. The question is, when you do IDE approvals they're assigned a Category 

A or Category B. Now I understand that Category A is by definition an 

experimental device, while Category B there is some understanding of the 

safety risk associated with the device.

By categorizing a device as Category A are you automatically implying that 

they will have post-approval study requirement when a PMA submitted after 

the fact?

Owen Faris: No...
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Man: There is no pre-decision based on post-approval requirement on a Category A 

device?

Owen Faris: No. We may or may not have post-approval requirements for either a 

Category A or a Category B device. And that is something that can be 

discussed during the pre-submission process.

And often we have a pretty good idea as to whether we're likely to require 

post-approval requirements. But it's essentially unrelated to that designation.

Man: Great. Thank you.

Irene Aihie: We'll go ahead and take the next question. Operator are you there? Operator 

are you there? Unfortunately we're having some technical difficulties. So as a

reminder if you have any questions please email your questions to DICE, 

that's D-I-C-E @fda.hhs.gov.

We do apologize for the technical difficulties. Thank you. This is Irene Aihie 

again. We appreciate and thank you for your participation in today's webinar.

Again we apologize for the technical difficulty.

Please remember that this presentation will be available on the CDRH 

Learning Section of fda.gov. The written transcript will take a couple of days 

but should be posted no later than Wednesday, September 10th.

If you have any additional questions please use the contact information 

provided at the end of the slide presentation. As always we appreciate your 

feedback on today's presentation. Again thank you for participating and this 

concludes today's webinar.
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END