Agency Information Collection Activities; Submission for OMB Review; Comment Request; Premarket Approval of Medical Devices

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.

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

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

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

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 Burden1

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

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.

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