Agency Information Collection Activities; Submission for OMB Review; Comment Request

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 97N-0385]

Agency Information Collection Activities; Submission for OMB

Review; Comment Request

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

October 30, 1997.

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: Margaret R. Wolff, 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:

Premarket Approval of Medical Devices--Part 814 (OMB Control Number

0910-0231--Reinstatement)

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, in order to 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 and to 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. Under Sec. 814.39, an applicant must submit a supplement to the

PMA before making a change affecting the safety or effectiveness of the

device. Section 814.82 sets forth postapproval requirements FDA may

propose, including periodic reporting on safety, effectiveness,

reliability, and display in the labeling and advertising of certain

warnings. Section 814.82 requires the maintenance of records to trace

patients and the organizing and indexing of records into identifiable

files to enable

[[Page 51113]]

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. The applicant determines what 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 practices for medical devices regulation

part 820 (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 to be maintained as conditions of approval to ensure

the device's continuing safety and effectiveness.

Respondents to this information collection are persons filing an

application 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).

FDA estimates the burden of this collection of information as

follows:

Table 1.--Estimated Annual Reporting Burden

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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

814.39 493 1 493 73.15 36,063

814.82 545 1 545 9.14 4,983

814.84 545 1 545 18.29 9,966

Total 94,551

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There are no capital costs or operating and maintenance costs associated with this collection of information.

In March 1997, while completing work on the CDRH Annual Information

Collection Budget, an error was discovered on this information

collection's burden hours by CDRH program staff. This error was not

discovered until after the publishing of this information collection's

60-day notice in the Federal Register of January 7, 1997 (62 FR 995),

Docket No. 96N-0491. The narrative portion of the Federal Register

notice correctly stated that 52 original PMA's and 493 PMA Supplements

were processed each year. The burden chart, however, incorrectly stated

that 545 original PMA's and 545 PMA Supplements were processed each

year (the 545 figure was derived by adding the 52 original and 493 PMA

supplements together). When the correct number of respondents was

plugged into the burden hour table and the numbers recalculated, the

new total burden hours equals 104,020 hours, a savings of 416,583 hours

from the original 1997 figure of 520,603.

Table 2.--Estimated Annual Recordkeeping Burden

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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) 567 1 567 16.7 9,469

Total 9,469

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There are no capital costs or operating and maintenance costs associated with this collection of information.

FDA estimates that the cost to device manufacturers to comply with

the requirements for premarket approval of medical devices is

approximately $34.95 million per year. The industry-wide cost estimate

for PMA's is based on an average fiscal year annual rate of receipt of

52 PMA original applications and 493 PMA supplements, using fiscal

years 1991 through 1995 data.

The cost data for PMA's is based on data provided by manufacturers

in 1985 by device type and cost element. The specific cost elements for

which FDA has data are as follows:

(1) Clinical investigations: 67 percent of total cost estimate,

(2) Submitting additional data or information to FDA during a PMA

review: 12 percent,

(3) Additional device development cost (e.g., testing): 10 percent

and,

(4) PMA and PMA supplement preparation and submissions, and

development of manufacturing and controls data: 11 percent.

A weighted average calculation in 1985 produced a total cost of

$280,000 for a PMA application. These cost estimates are considered to

be solely attributable to PMA requirements. FDA does not have more

recent data on the cost to manufacturers of collecting, analyzing, and

preparing the data needed for a PMA submission. FDA has adjusted the

1985 estimate for inflation (using an average of 7.5 percent per year

for the health care sector) and multiplied it by 52 (the average number

of PMA's submitted annually) to yield an annual cost attributable to

PMA's of $32,323,200 ($280,000 x index of 2.22 x 52).

FDA estimates that 493 PMA supplements will be submitted annually.

No recent information on the cost of PMA supplements has been collected

from medical device manufacturers. However, the agency has taken an

earlier cost estimate for PMA supplements ($2,400 per supplement) and

adjusted it for inflation. The annual cost of PMA supplements is

estimated to be $2,626,704 (493 x $2,400 x 2.22 index factor).

Thus, the cost estimate for PMA's and PMA supplements is

$34,949,904. This figure represents the burden on industry due to the

PMA approval requirement. This cost includes both the effect of the

statutory requirement and the effect of the agency's implementation of

the statute.

The recordkeeping burden in this section requires the maintenance

of

[[Page 51114]]

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 75 percent of those

have original clinical trial data. Therefore, about 27 PMA's a year

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 567 active PMA's that could be subject to these requirements

(21 years x 27 per year). Each study has about 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 567 holders of approved original PMA's, therefore, is 9,469

hours (567 approved PMA's with clinical data x 16.7 hours per PMA).

The applicant determines what 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

Practices for medical devices regulation 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.

With the additional 9,469 hours or recordkeeping, the total annual

burden is 104,020 hours.

Dated: September 23, 1997.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 97-25938 Filed 9-29-97; 8:45 am]

BILLING CODE 4160-01-F