[Federal Register Volume 64, Number 17 (Wednesday, January 27, 1999)]
[Notices]
[Pages 4112-4114]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-1852]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 98N-0721]


Agency Information Collection Activities; Submission for OMB 
Review; 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 that the 
proposed collection of information listed below has been submitted to 
the Office of Management and Budget (OMB) for review and clearance 
under the Paperwork Reduction Act of 1995 (the PRA).

DATES:  Submit written comments on the collection of information by 
February 26, 1999.

ADDRESSES:  Submit written comments on the collection of information to 
the Office of Information and Regulatory Affairs, OMB, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: 
Desk Officer for FDA.

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

SUPPLEMENTARY INFORMATION: In compliance with section 3507 of the PRA 
(44 U.S.C. 3507), FDA has submitted the following proposed collection 
of information to OMB for review and clearance. In the Federal Register 
of October 6, 1998 (63 FR 53675), the agency requested comments on the 
proposed collection of information. No comments were received.
    Due to a clerical error, the title of the information collection 
that appeared in the Federal Register of October 6, 1998, was 
incorrect. The correct title follows.

I. Premarket Approval of Medical Devices--21 CFR Part 814 and FDAMA 
Sections 201, 202, 205, 207, 208, 209 (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 premarket approval application (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 shown 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 postapproval 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 reasonable assurance of the device's continued safety 
and effectiveness. Section 814.84 specifies the contents of periodic 
reports.

[[Page 4113]]

II. FDA Modernization Act of 1997

     The FDA 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 that 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 (21 
U.S.C. 360c(a)(3)) 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.
    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 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.
Note: Statutory burden is not included on the burden chart.


[[Page 4114]]

III. Reporting/Disclosure

     The reporting burden can be broken out by certain sections of the 
PMA regulation: (1) Sec. 814.15--Research conducted outside the United 
States, (2) Sec. 814.20--Application, and (3) 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's 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 postapproval 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--Reports

     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. As 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 will 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/quality systems 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: January 20, 1999.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 99-1852 Filed 1-26-99; 8:45 am]
BILLING CODE 4160-01-F