[Federal Register Volume 63, Number 193 (Tuesday, October 6, 1998)]
[Notices]
[Pages 53675-53677]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-26649]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98N-0721]


Agency Information Collection Activities: Proposed Collection; 
Comment Request; Premarket Approval of Medical Devices

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing an 
opportunity for public comment on the proposed collection of certain 
information by the agency. Under the Paperwork Reduction Act of 1995 
(the PRA), Federal agencies are required to publish notice in the 
Federal Register concerning each proposed reinstatement of an existing 
information collection of information, and to allow 60 days for public 
comment in response to the notice. This notice solicits comments on 
requirements for premarket approval applications (PMA's).

DATES: Submit written comments on the collection of information by 
December 7, 1998.
ADDRESSES: Submit written comments on the collection of information to 
the Dockets Management Branch (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should 
be identified with the docket number found in brackets in the heading 
of this document.

FOR FURTHER INFORMATION CONTACT: Margaret R. Schlosburg, Office of 
Information Resources Management (HFA-250), Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-1223.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal 
agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
Collection of information is defined in 44 U.S.C. 3502(3) and 5 CFR 
1320.3(c) and includes agency requests or requirements that members of 
the public submit reports, keep records, or provide information to a 
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information, including 
each proposed reinstatement of an existing collection of information, 
before submitting the collection to OMB for approval. To comply with 
this requirement, FDA is publishing notice of the proposed collection 
of information listed below.
    With respect to the following collection of information, FDA 
invites comments on: (1) Whether the proposed collection of information 
is necessary for the proper performance of FDA's functions, including 
whether the information will have practical utility; (2) the accuracy 
of FDA's estimate of the burden of the proposed collection of 
information, including the validity of the methodology and assumptions 
used; (3) ways to enhance the quality, utility, and clarity of the 
information to be collected; and (4) ways to minimize the burden of the 
collection of information on respondents, including through the use of 
automated collection techniques, when appropriate, and other forms of 
information technology.

I. Premarket Approval of Medical Devices--21 CFR Part 814 and FDAMA 
Sections 201, 202, 205, 207, 208, 209, 216, 217, and 403 (OMB 
Control Number 0910-0231--Extension)

    Section 515 of the Federal Food, Drug, and Cosmetic Act (the act) 
(21 U.S.C. 360e) sets forth requirements for premarket approval of 
certain medical devices. Under section 515 of the act, an application 
must contain several pieces of information, including: Full reports of 
all information concerning investigations showing whether the device is 
safe and effective; a statement of components; a full description of 
the methods used in, and the facilities and controls used for, the 
manufacture and processing of the device; and labeling specimens. The 
implementing regulations, contained in part 814 (21 CFR part 814), 
further specify the contents of a PMA for a medical device and the 
criteria FDA will employ in approving, denying, or withdrawing approval 
of a PMA. The purpose of these regulations is to establish an efficient 
and thorough procedure for FDA's review of PMA's for class III 
(premarket approval) medical devices. The regulations will facilitate 
the approval of PMA's for devices that have been shown to be safe and 
effective and otherwise meet the statutory criteria for approval. The 
regulations will also ensure the disapproval of PMA's for devices that 
have not been show to be safe and effective and that do not otherwise 
meet the statutory criteria for approval.
    Under Sec. 814.15, an applicant may submit in support of a PMA 
studies from research conducted outside the United States, but an 
applicant must explain in detail any differences between standards used 
in a study to support the PMA's and those standards found in the 
Declaration of Helsinki. Section 814.20 provides a list of information 
required in the PMA, including: A summary of information in the 
application, a complete description of the device, technical and 
scientific information, and copies of proposed labeling. Section 814.37 
provides requirements for an applicant who seeks to amend a pending 
PMA. Section 814.82 sets forth postapproval requirements FDA may 
propose, including periodic reporting on safety effectiveness, and 
reliability, and display in the labeling and advertising of certain 
warnings. Other potential post approval requirements include the 
maintenance of records to trace patients and the organizing and 
indexing of records into identifiable files to enable FDA to determine 
whether there is

[[Page 53676]]

reasonable assurance of the device's continued safety and 
effectiveness. Section 814.84 specifies the contents of periodic 
reports.

II. FDA Modernization Act of 1997

    The Food and Drug Administration Modernization Act of 1997 (FDAMA), 
enacted on November 21, 1997, to implement revisions to the act, 
streamlines the process of bringing safe and effective drugs, medical 
devices, and other therapies to the U.S. market. Several provisions of 
this act which affect the PMA process and impact collection of 
information have been or will be implemented by FDA and are discussed 
as follows.
    Section 201(b) of FDAMA amends section 515(d) of the act to allow 
submission of data from investigations of earlier versions of a device, 
in support of a safety and effectiveness determination for a PMA. The 
data is valid if modifications to earlier versions of the 
investigational device, whether made during or after the investigation, 
do not constitute a significant change that would invalidate the 
relevance of the data. This section also allows for the submission of 
data or information relating to an approved device that are relevant to 
the design and intended use of a device for which an application is 
pending, provided the data are available for use under the act (i.e., 
available by right of reference or in the public domain).
    Section 202 of FDAMA amends section 515(d) of the act to state that 
FDA will provide special review, which can include expedited processing 
of a PMA application, for certain devices intended to treat or diagnose 
life threatening or irreversibly debilitating diseases or conditions.
    Section 205(a) of FDAMA amends section 513(a)(3) of the act to 
allow sponsors planning to submit a PMA to submit a written request to 
FDA for a meeting to determine the type of information (valid 
scientific evidence) necessary to support the effectiveness of their 
device. FDA must meet with the requester and communicate in writing the 
agency's determination of the type of data that will be necessary to 
demonstrate effectiveness within 30 days after the meeting.
    Section 205(c) of FDAMA amends section 515(d) of the act to state 
that PMA supplements are required for all changes that affect safety or 
effectiveness, unless such change involves modifications in a 
manufacturing procedure or method of manufacturing. Clearance for this 
information collection, included within a proposed rule, has already 
been sought by FDA in an earlier document (63 FR 20558, April 27, 
1998).
    Section 205(c) of FDAMA amends section 515(d) of the act to allow 
for approval of incremental changes in design affecting safety and 
effectiveness based on nonclinical data that demonstrate the change 
creates the intended additional capacity, function, or performance of 
the device; and clinical data included in the original PMA application 
or any supplement to that application that provides reasonable 
assurance of safety and effectiveness. If needed, FDA may require a 
sponsor to submit new clinical data to demonstrate safety and 
effectiveness.
    Section 207 of FDAMA amends section 513 of the act to allow an 
applicant who submits a premarket notification submission [510(k)] and 
receives a not substantially equivalent (NSE) determination, placing 
the device into a Class III category, to request FDA to classify the 
product into Class I or II. The request must be in writing and sent 
within 30 days from the receipt of the NSE determination. Within 60 
days from the date the written request is submitted to FDA, the agency 
must classify the device by written order.
    If FDA classifies the device into Class I or II, this device can be 
used as a predicate device for other 510(k)s. However, if FDA 
determines that the device will remain in Class III, the device cannot 
be distributed until the applicant has obtained an approved PMA or an 
approved investigational device exemption (IDE).
    Section 208 of FDAMA amends section 513 of the act to allow PMA 
applicants to have the same access as FDA to data and information 
submitted by FDA to a classification panel, except data not available 
for public disclosure; the opportunity to submit information based on 
the PMA, through FDA, to the panel; and the same opportunity as FDA to 
participate in panel meetings.
    Section 209(b) of FDAMA amends section 515(d) of the act to state 
that FDA must, upon the written request of the applicant, meet with 
that party within 100 days of receipt of the filed PMA application to 
discuss the review status of the application. With the concurrence of 
the applicant, a different schedule may be established. Prior to this 
meeting, FDA must inform the applicant in writing of any identified 
deficiencies and what information is required to correct those 
deficiencies. FDA must also promptly notify the applicant if FDA 
identifies additional deficiencies or of any additional information 
required to complete agency review.
    FDA estimates the burden of this collection of information is as 
follows:

                                  Table 1.--Estimated Annual Reporting Burden1
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                                                      Annual
         21 CFR Section               No. of       Frequency per   Total Annual      Hours per      Total Hours
                                    Respondents      Response        Responses       Response
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814.15, 814.20, and 814.37             52               1              52             837.28       43,539
814.82                                 37               1              37             134.68        4,983
814.84                                 37               1              37              10             370
Total                                                                                              48,892
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


                                Table 2.--Estimated Annual Recordkeeping Burden1
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                                                      Annual
         21 CFR Section               No. of       Frequency per   Total Annual      Hours per      Total Hours
                                   Recordkeepers   Recordkeeping      Records      Recordkeeper
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814.82(a)(5) and (a)(6)               814               1             814              16.7        13,594
Total                                                                                              13,594
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


[[Page 53677]]

III. Reporting/Disclosure

    The reporting burden can be broken out by certain sections of the 
PMA regulation.
    Sec. 814.15--Research conducted outside the United States
    Sec. 814.20--Application
    Sec. 814.37--PMA amendments and resubmitted PMA's
    The bulk of the burden is due to the previous three requirements. 
Included in these three requirements are the conduct of laboratory and 
clinical trials as well as the analysis, review, and physical 
preparation of the PMA application. FDA estimate of the hours per 
response (837.28) was derived through FDA's experience and consultation 
with industry and trade associations. Included in these three 
requirements are the conduct of laboratory and clinical trials as well 
as the analysis, review, and physical preparation of the PMA 
application. FDA estimates, based on the 1985 study, that these 
requirements account for the bulk of the burden identified by 
manufacturers.

IV. Sec. 814.39--PMA Supplements

    Clearance for this information collection, included within a 
proposed rule, has already been sought by FDA in an earlier document 
(63 FR 20558).

V. Sec. 814.82-Postapproval Requirements

    Postapproval requirements concern approved PMA's for devices that 
were not reclassified and require an annual report. In the last decade 
(1988 to 1997), the range of PMA's which fit this category averaged 
approximately 37 per year (70 percent of the 52 annual submissions). 
Most approved PMA's have been subject to some restriction. 
Approximately half of the average submitted PMA's (26) require 
associated post approval information (i.e. clinical trials or 
additional preclinical information) that is labor-intensive to compile 
and complete, and the other PMA's require minimal information. Based on 
its experience and on consultation with industry, FDA estimates that 
preparation of reports and information required by this section 
requires 4,983 hours (134.68 hours per respondent).

VI. Sec. 814.84

    Postapproval requirements described in Sec. 814.82 require a 
periodic report. FDA has determined respondents meeting the criteria of 
Sec. 814.84 will submit reports on an annual basis. A stated 
previously, the range of PMA's fitting this category averaged 
approximately 37 per year. These reports have minimal information 
requirements. FDA estimates that respondents will construct their 
report and meet their requirements in approximately 10 hours. This 
estimate is based on FDA's experience and on consultation with 
industry. FDA estimates that the periodic reporting required by this 
section take 370 hours.

VII. Recordkeeping

    The recordkeeping burden in this section involves the maintenance 
of records to trace patients and the organization and indexing of 
records into identifiable files to ensure the device's continued safety 
and effectiveness. These requirements are to be performed only by those 
manufacturers who have an approved PMA and who had original clinical 
research in support of that PMA. For a typical year's submissions, 70 
percent of the PMA's are eventually approved and close to 100 percent 
of those have original clinical trial data. Therefore, about 37 PMA's a 
year (52 annual submissions times 70 percent) would be subject to these 
requirements. Also, because the requirements apply to all active PMA's, 
all holders of active PMA applications must maintain these records. 
PMA's have been required since 1976, so there are around 814 active 
PMA's that could be subject to these requirements (22 years x 37 per 
year). Each study has approximately 200 subjects, and, at an average of 
5 minutes per subject, there is a total burden per study of 1,000 
minutes, or 16.7 hours. The aggregate burden for all 814 holders of 
approved original PMA's, therefore, is 13,594 hours.
    The applicant determines which records should be maintained during 
product development to document and/or substantiate the device's safety 
and effectiveness. Records required by the current good manufacturing 
practice (CGMP)/quality systems (QS) regulation (21 CFR part 820) may 
be relevant to a PMA review and may be submitted as part of an 
application. In individual instances, records may be required as 
conditions to approval to ensure the device's continuing safety and 
effectiveness.
    Respondents to this information collection are persons filing an 
application with the Secretary of Health and Human Services for 
approval of a Class III medical device. Part 814 defines a person as 
any individual, partnership, corporation, association, scientific or 
academic establishment, government agency or organizational unit, or 
other legal entity. These respondents include manufacturers of 
commercial medical devices in distribution prior to May 28, 1976 (the 
enactment date of the Medical Device Amendments).

    Dated: September 28, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-26649 Filed 10-5-98; 8:45 am]
BILLING CODE 4160-01-F