Goals and Initiatives for the IDE Program #D95-1 (blue book memo) (Text Only)

This guidance was written prior to the February 27, 1997 implementation of FDA’s Good Guidance Practices, GGP’s. It does not create or confer rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both. This guidance will be updated in the next revision to include the standard elements of GGP’s.

IDE Memorandum - #D95-1

Office of Device Evaluation (HFZ-400)

Goals and Initiatives for the IDE Program

ODE Review Staff

Purpose

The purpose of this memorandum is to establish procedures for the efficient 
review of IDEs and to identify performance goals for the IDE Program.

Background

The Office of Device Evaluation (ODE) has traditionally approved 
approximately one third of the original investigational device exemption 
(IDE) applications in the first 30 day review cycle.  In recent times 
(fiscal years (FY) 1993 and 1994), however, only 25% of the original IDE 
applications were approved during this initial review period.  In addition, 
the average total time from receipt of the application to approval increased 
to 242 days after averaging 178 days for the last 5 years.

The reasons for non-approval may be summarized as relating to inadequate 
characterization of the device being investigated, poorly designed clinical 
trials, and inadequate subject protection measures.  In all cases, ODE's 
intent has been to improve the quality of the information derived from the 
investigations and to protect the well-being of those participating in the 
clinical trials.  We must recognize, however, that our approach has had some 
unintended effects such as discouraging the conduct of the clinical trials 
and thus the generation of potentially useful information or causing the 
trials to be conducted outside the United States without guidance from FDA.  
ODE staff has also been expending considerable resources in reviewing 
multiple amendments over an extended period of time.    

If the performance goals presented below are achieved, the gain to be 
realized by both the regulated industry and ODE staff would be significant.  
Increasing the approval rate and reducing the time to approval for original 
IDEs to more reasonable levels will encourage the medical device industry to 
conduct their clinical investigations in the       

United States (U.S.) rather than overseas.  If the clinical trials are 
conducted domestically, and thus with FDA guidance, the quality of the 
trials and the data generated from them should be more congruent with 
premarket approval requirements than if the investigations were conducted 
overseas without input from FDA review.  In addition, the data resulting 
from the domestic trials will be representative of medical practice in the 
U.S.  Thus, the review process for the marketing applications should proceed 
more expeditiously, saving time and resources for the regulated industry and 
FDA.  Finally, if the device trials are conducted here, U.S. physicians will 
have earlier access to and experience with these new technologies, while 
U.S. patients participating in the trials will also have the potential 
benefit of these novel therapies.     

Below, the performance goals for the IDE Program and the initiatives to be 
implemented to help reach these goals are presented.  

1)  During FY95, increase the approval rate for original IDEs from its 
    current rate of 27% (FY94) to approximately 66% in the first 30 day 
    review cycle, especially for those submissions for which there was FDA-
    Industry interaction during the process (e.g., pre-IDE meetings, 
    submissions, etc.).

2)  During FY95, reduce the average number of review cycles to approval to 
    less than two cycles.  Currently, more than two amendments per IDE are 
    required before approval of the application.  Thus, at least three 
    review cycles are generally required before the initiation of a device 
    clinical trial.


Procedures

In order to help ODE's reviewing divisions reach these performance goals, 
the following initiatives will be implemented.

1)  Pre-IDE meetings.  Sponsors should be encouraged to meet with ODE staff 
    before the IDE application is submitted for review.  Meeting with the 
    regulated industry before the IDE application is submitted should serve 
    to increase the sponsor's understanding of various FDA requirements, 
    regulations, and guidance documents and thus lead to more complete 
    original IDE applications.  (See attached policy entitled, "Procedures 
    for Pre-IDE Meetings and Submissions.")
 
2)  Pre-IDE applications.  Sponsors should be encouraged to submit 
    preliminary information for ODE review before making the formal IDE 
    submission.  Sponsors should submit those sections of the IDE 
    application for which they require FDA guidance (e.g., clinical protocol 
    design, pre-clinical testing, etc.) while preparing the remainder of the 
    IDE submission.  This will allow ODE staff to provide informal guidance 
    to the industry on troublesome parts of the IDE application before the 
    official submission is made.  In addition, since this informal review 
    will be conducted while other parts of the application are being 
    prepared, it should not extend the total preparation time for the IDE 
    application. (See attached policy entitled, "Procedures for Pre-IDE 
    Meetings and Submissions.")

3)  An interactive review process.  By communicating frequently with 
    industry during the review process, rather than only at the completion 
    of the review, deficient information can be addressed within fewer 
    review cycles.  This would be of significant benefit to both industry 
    and ODE staff.  ODE reviewers, with the concurrence of their 
    supervisors, should feel free to use the telephone or telefacsimile to 
    aid in the interactive review.  Documentation of this communication must 
    be included in the IDE record, and hardcopies of information transmitted 
    by telefacsimile must be logged into the IDE database.  (See attached 
    policy entitled,"IDE Telefacsimile Policy.")

4)  Use of new strategies in the clinical development of devices.  If the 
    original IDE application does not support the initiation of the 
    substantive (pivotal) clinical trial, ODE staff should consider the use 
    of feasibility/pilot studies.  Such trials may be used to:  provide 
    investigators with initial device experience; help address specific 
    safety concerns; permit initial assessment of device design; better 
    define the clinical endpoints, success/failure criteria, the intended 
    patient population, and appropriate follow-up period; assess the 
    therapeutic effect of the device and estimate the required patient 
    population size; and clarify the possible medical claims before the 
    multi-centered trial is initiated.  The type of device, the risks posed 
    by the device, what is known about these risks, and the questions to be 
    addressed in the limited study must all be considered when deciding 
    whether a feasibility/pilot study is appropriate, and if so, the size of 
    the study.  Thus, the use of this type of strategy in the conduct of 
    clinical trials not only permits a trial which may have otherwise been 
    disapproved to be initiated on a limited basis but also provides for a 
    better designed substantive trial for the marketing application.

Effective Date

This memorandum is effective immediately.




                              _______________________________
                              Susan Alpert, Ph.D., M.D.

IDE Memorandum - #D95-1
                                                  Attachment A - Page 1

                               PROCEDURES FOR

                      PRE-IDE MEETINGS AND SUBMISSIONS


In order to facilitate the initiation of clinical trials under the 
Investigational Device Exemptions (IDE) regulations, FDA is encouraging 
sponsors to begin communicating with the reviewing division prior to the 
submission of the original IDE application.  This communication may take the 
form of a "Pre-IDE" meeting and/or a Pre-IDE submission.  Pre-IDE meetings 
should occur early in the IDE preparation process so that any advice/guidance 
provided by ODE staff can be used in the development of supporting pre-
clinical data or incorporated into the IDE application.  These meetings may 
take the form of telephone conference calls, video conferences, or face-to-
face discussions.  In addition to the general requirements set forth in Blue 
Book Memorandum #I89-3, "Meetings with the Regulated Industry," and #I93-1, 
"Telephone Communications Between ODE Staff and Manufacturers," the following 
requirements apply specifically to the IDE program.  All pre-IDE meetings 
should be recorded by the division and reported on a quarterly basis to 
senior ODE management.  Minutes of the meeting should include the date of the 
meeting, the attendees (FDA and industry), whether material was submitted 
prior to the meeting for discussion/review by ODE staff, a summary of the 
discussion, and any recommendations or guidance provided by FDA.

Pre-IDE submissions may consist of a draft clinical protocol, a proposal for 
pre-clinical testing, pre-clinical test results, or other information for 
which the sponsor wishes to obtain preliminary FDA review and comment in 
order to facilitate the IDE application process.  Pre-IDE submissions may 
also consist of protocols for foreign studies when the studies will be used 
to support future marketing applications to be submitted to FDA.

Pre-IDE submissions will receive the same confidentiality of data and 
information as provided for IDE applications under 21 CFR 812.38.  Therefore, 
FDA will not disclose the existence of a pre-IDE submission unless its 
existence has previously been publicly disclosed or acknowledged, until FDA 
approves an application for marketing approval of the device subject to this 
submission.

Pre-IDE submissions must be recorded and tracked, and so should be submitted 
in triplicate to the Document Mail Center (DMC) for processing.  The DMC will 
assign the document a Pre-IDE number (PIDE), record it in the Pre-IDE 
logbook, and forward it to the appropriate division for review.  (At this 
time, the IDE database cannot track Pre-IDE submissions.)  If a Pre-IDE 
submission is received by the division without going through the DMC, the 
division is responsible for taking the document to the DMC so that it can be 
properly processed.  At the time of log-in, the document mail clerk will also 
record the dates of submission and receipt, the sponsor's name, the name of 
the device, and the division to which it is assigned.  The Pre-IDE number 
will be recorded on the top right corner of the submission, just as is done 
for official IDE applications.  

Since the IDE database base cannot track Pre-IDEs, the divisions will be 
responsible for tracking the submissions and ensuring that a timely  
response is issued.  A Pre-IDE boilerplate acknowledgment letter is available 
on the LAN (P-01) and should be sent to the sponsor upon receipt of the Pre-
IDE submission.  This letter indicates that FDA will attempt to provide a 
response to the sponsor in a timely manner, usually within 60 days of 
receipt.  ODE's response may take the form of a written letter, or comments 
may be provided in a meeting or during a telephone conference call.  
Whichever method of response is used, it should be documented in the Pre-IDE 
file.  (A copy of the letter, meeting minutes, or memorandum of the telephone 
conversation should be securely attached to the Pre-IDE submission.)  There 
is a shelf in DMC where Pre-IDE submissions may be stored.  

When the original IDE application is submitted, the division must note in the 
comments section of the IDE Tracking Sheets the Pre-IDE number assigned by 
the DMC if a Pre-IDE had been reviewed for this submission.  This will allow 
a method of connecting the Pre-IDE to the original IDE application. 

IDE Memorandum - #D95-1
                                                  Attachment B - Page 1

                          IDE TELEFACSIMILE POLICY

General guidance for the acceptance of telefacsimile (FAX) telecommunications 
is provided in ODE's Blue Book Memorandum #I90-3 "Document Control 
Procedures."  In this memorandum, it is stated that "As a general rule, 
information and data required to review and reach a decision on a submission 
may not be accepted via fax."  In addition, according to the IDE regulations 
(21 CFR 812.20(a)(3)), all correspondence concerning an application or a 
supplemental application must be submitted by registered mail or by hand.   
The intent of this section of the regulations was to ensure that in order for 
information to be considered an official part of the IDE file, that 
information must be submitted in writing.  At the time the IDE regulations 
were developed, however, the technology which permits communication via 
telefacsimile did not exist.  Therefore, ODE has requested an official ruling 
from the Office of General Counsel on the acceptability of FAXed information, 
i.e., the need for a follow-up hardcopy.  Until a definitive response is 
received, the policy presented below will serve as the official IDE FAX 
policy for the Office.

As stated above, past Office policy regarding use of FAXed information, as 
outlined in Blue Book Memorandum #I90-3 and as amplified in a February 17, 
1994 memorandum by ODE's Integrity Officer, dictated that FAXed information 
could be used for purposes such as to facilitate the exchange of ideas and 
clarify points of discussion but could not serve as the basis of a decision 
without a confirmatory hardcopy.  While the above policy statements remain in 
effect, ODE is encouraging more liberal use of the FAX machine as an aid to 
resolving deficiencies in the IDE application.  Thus, a sponsor could submit 
information addressing deficiencies in areas such as the pre-clinical 
testing, the investigational plan, the risk analysis, the informed consent 
document, manufacturing procedures, etc., which had previously been discussed 
by phone with the reviewer.  Although a follow-up hardcopy of the FAXed 
information still needs to be added to the administrative record and thus 
must be submitted to the Document Mail Center (DMC), early receipt of the 
information by FAX should permit a more expeditious review of the information 
and resolution of the deficiencies. 

A follow-up hardcopy of the FAXed information should be received in the DMC 
by the 30th day of the review cycle so that it can be properly logged in as 
an IDE amendment.  Therefore, reviewers must notify the sponsor that any 
information which is FAXed to ODE must also be sent in triplicate by 
overnight mail to the DMC for receipt by the next business day.  If multiple 
FAXes are received by the division during the course of the review, 
hardcopies of all of the information may be submitted in one mailing rather 
than after each individual FAX.  When the follow-up hardcopies are received 
by the DMC, one copy will be added to Copy 1 of the IDE file and one copy 
will be forwarded to the division for verification that the hardcopy is in 
fact a duplicate of the FAXed information.  The hardcopy and a note stating 
that the hardcopy is a duplicate of the previously received FAX should be 
added to the file by the reviewer.  The third copy of the hardcopy is the 
reviewer's deskcopy and can be added to Copy 3 of the IDE file or discarded.

If the follow-up hardcopy is expected to arrive after day 30, reviewers must 
FAX the Duplicate Information Sheet (see attachment) to the sponsor.  This 
sheet is to be used as a cover sheet to the hardcopy to ensure that when the 
information is received by the DMC, it will be correctly logged in as an IDE 
amendment to the original IDE application rather than as a supplement.  
Subsequent processing of the hardcopy will be as above.

                                     FAX

                                  DUPLICATE
IDE Number:____________________

I certify that the information contained in this submission is an exact 
duplicate of information which was previously provided by telefacsimile on 
the date(s) listed below.   (That is, no new information which has not been 
previously provided is contained in this submission.)  

Submitted by: ____________________   _______________________
              (Name)                 (Signature and date)

              ____________________
              (Title)

              ____________________
              (Company Name)

              ____________________
              (Street Address)

              ____________________
              (City, State and Zip Code)

              ____________________
              (Phone Number)