Federal Register, Volume 63 Issue 193 (Tuesday, October 6, 1998)

[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]

-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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 Burden^{1
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Respondents Response Responses Response
----------------------------------------------------------------------------------------------------------------
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
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.

Table 2.--Estimated Annual Recordkeeping Burden^{1
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Recordkeepers Recordkeeping Records Recordkeeper
----------------------------------------------------------------------------------------------------------------
814.82(a)(5) and (a)(6) 814 1 814 16.7 13,594
Total 13,594
----------------------------------------------------------------------------------------------------------------
\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}}