[Federal Register Volume 66, Number 4 (Friday, January 5, 2001)]
[Notices]
[Pages 1140-1141]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-260]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00N-1494]


Agency Information Collection Activities; Submission for OMB 
Review; Comment Request; Medical Devices; Classification/
Reclassification; Restricted Devices: Analyte Specific Reagents

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.

DATES: Submit written comments on the collection of information by 
February 5, 2001.

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: 
Wendy Taylor, 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 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Medical Devices: Classification/Reclassification; Restricted 
Devices; Specific Reagents--21 CFR Part 809 (OMB Control No. 0910-
0361)--Extension

    Section 502 of the Federal Food, Drug, and Cosmetic Act (the act) 
(21 U.S.C. 352) establishes certain labeling requirements for devices 
including requirements that the labeling not be false or misleading in 
any particular, that the labeling contain the established name for the 
device, and that the labeling contain adequate directions for use. 
Section 520(e) of the act (21 U.S.C. 360j(e)) provides that FDA may 
restrict the sale, distribution, or use of a device, if FDA determines 
that there cannot otherwise be reasonable assurance of its safety and 
effectiveness. Section 502(q) and (r) of the act authorizes FDA to 
regulate the advertising of devices that are restricted under section 
520(e) of the act.
    FDA restricts distribution of analyte specific reagents (ASR's) to 
laboratories certified under the Clinical Laboratory Improvement 
Amendments of 1988 (CLIA) as qualified to perform high complexity 
testing, to manufacturers of in vitro diagnostic products, and to 
organizations that use the tests for reasons other than providing 
diagnostic information to practitioners and patients. FDA has 
established certain labeling requirements for suppliers of ASR's and 
certain requirements regarding advertising and promotional materials 
for ASR's. FDA believes the labeling requirements and restrictions on 
advertising and promotion are necessary to ensure that laboratories 
developing tests from ASR's have sufficient information to use the 
ASR's appropriately and to limit specific claims by manufacturers, 
because these ASR's are intended to be used as ingredients in a variety 
of ways by laboratories qualified to do high complexity testing.
    The most likely respondents to this information collection will 
primarily be medical device manufacturers of in vitro products, 
clinical laboratories, and other manufacturers of ASR's.
    In the Federal Register of September 14, 2000 (65 FR 55633), the 
agency requested comments on the proposed collection of information. 
One comment, discussing three separate issues, was received.
    1. The comment first asked that medical device manufacturers 
provide basic laboratory instructions for use and warn against uses 
that are not appropriate for the particular ASR.
    FDA was not persuaded by this comment. The intention of the ASR 
rule is to ensure that laboratories using these products to develop in-
house or ``home brew'' tests take full responsibility for the 
development of the ``home brew'' test and for the characterization of 
test performance for the ASR based test. ASR use is restricted to high-
complexity laboratories under the CLIA which have the ability to 
develop tests based on their own experience or the medical literature. 
The instructions for use in different laboratories using ASR's would be 
expected to vary with the experience of the laboratory and with the 
information obtained during test development and characterization.
    If a medical device manufacturer wishes to provide laboratory 
instructions on product use, this is acceptable. However, this is 
evidence that a kit or system is being marketed rather than used as an 
ASR or building block for an assay. Such a device would not be exempt 
from premarket review by FDA.
    2. The comment further indicated that a guidance or written 
clarification as to the scope of appropriate warnings and precautions 
would be helpful.
    FDA does not believe such guidance or written clarification is 
necessary. The regulation in 21 CFR 809.10(e)(1)(v) requires ``A 
statement of warnings or precautions for users as established in the 
regulations contained in 16 CFR part

[[Page 1141]]

1500 and any other warnings appropriate to the hazard presented by the 
product.'' Hazards in use of laboratory reagents are well known and the 
subject of multiple book chapters and a voluntary standard. The 
information required which includes, as appropriate, warnings regarding 
flammability, toxicity, teratogenicity, and carcinogenicity are well 
known by both manufacturers and laboratory users. Additional 
information on these would duplicate existing commonly used information 
sources and conditions of art.
    3. Finally, the comment indicated that product support dictates 
that information be provided to users on proper set up of instruments, 
preparation of samples, and the generation of good quality data.
    FDA agrees that the information cited is of key importance in test 
performance. For ``home brew'' tests, however, the responsibility for 
developing this information is clearly assigned to the laboratory, not 
to the manufacturer of the ASR. The only responsibility the ASR 
manufacturer has is to produce product according to the quality system 
regulations, to label it clearly as a building block for use in ``home 
brew'' assays, and to restrict sales to high complexity laboratories. 
These laboratories by law have the personnel standards, proficiency 
testing, quality control and quality assurance requirements, and 
requirements for controlled operating environments needed in the 
development of quality ``home brew'' tests.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1.--Estimated Annual Reporting Burden \1\
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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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809.10(e)                         300               25            7,500               1            7,500
809.30(d)                         300               25            7,500               1            7,500
Total                                                                                            15,000
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    The number of affected establishments was derived by asking five 
organizations for estimates and averaging their responses to arrive at 
an average number of establishments affected by this rule. These 
organizations included the largest trade association representing the 
in vitro diagnostic industry, the larger trade association for 
nonbiotechnology products, two of the largest organizations 
representing laboratory professionals, and the in vitro diagnostic 
company instrumental in providing industry input into the 
implementation of this rule. Three of the five organizations had access 
to data bases allowing them to project estimates of establishments 
likely to manufacture or supply ASR's. These estimates ranged from 100 
to 500. FDA therefore used the average of 300 ASR manufacturers and 
suppliers subject to the reporting requirements from these estimates.
    FDA relied upon the five trade organizations in estimating the 
number of ASR's manufactured. Again, three of the organizations offered 
information from their data bases. Estimates for the number of ASR's 
ranged from 5,000 to 10,000, with the average being 7,500. FDA 
therefore estimates that approximately 7,500 ASR's are currently being 
manufactured.
    In order to ascertain the number of ASR's manufactured by each 
respondent, FDA used the average number of ASR's manufactured and 
divided it by the number of ASR manufacturers (7,500  300). 
Consequently, the estimate of the number of ASR's manufactured by each 
respondent is approximately 25. (In the previously published final rule 
of November 21, 1997 (62 FR 62243), the total number of ASR's were 
listed as ``1,'' and the number of respondent burden hours associated 
with ASR's were ``25.'' These numbers were reversed in error.)
    FDA estimates that for each ASR, it would take approximately 1 hour 
to design a new label to conform with the new requirements and 
approximately 3 hours to provide management review and legal and 
marketing sign-off. Therefore, FDA estimates that the total number of 
hours needed to design/review labels is approximately 100 hours per 
respondent (25 x 4). The total number of hours to design/review labels 
by all establishments is estimated at 30,000 (100 x 300). However, 
these estimates do not take into account economies of scale in 
designing and revising the labeling on ASR's, which should reduce the 
time expended in ASR labeling by 75 percent. Consequently, FDA 
estimates that the total number of reporting hour burden for designing/
review of labeling is approximately 25 hours per respondent instead of 
100. FDA also estimates that the total reporting hour burden is 
approximately 7,500 hours instead of 30,000.
    FDA estimates for each ASR, it would take approximately 1 hour to 
rewrite the professional materials to ascertain compliance with the new 
requirements and approximately 4 hours to obtain management review of 
rewritten materials and legal and marketing sign-off. FDA therefore 
estimates that the total number of hours to rewrite/review promotional 
materials is approximately 125 hours per respondent (25 ASR's per 
respondent x 5 hours for review). The total reporting hours for all 
ASR's is estimated at 37,500 (125 hours x 300 manufacturer/suppliers). 
However, this estimate does not take into account economies of scale. 
Often the promotional materials are a catalogue of products. FDA 
estimates that entities spend approximately 20 percent of the time 
devoted to reporting ASR's (37,500 hours) ascertaining that the 
promotional materials meet the new requirements. Consequently, FDA 
estimates that the total number of reporting hour burden for rewriting/
reviewing promotional materials under 21 CFR 809.30(d) is approximately 
25 hours per respondent (125 x .20), and estimates that the total 
reporting hour burden for promotional materials is approximately 7,500 
hours (37,500 x .20).

    Dated: December 28, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-260 Filed 1-4-01; 8:45 am]
BILLING CODE 4160-01-F