[Federal Register Volume 69, Number 120 (Wednesday, June 23, 2004)]
[Rules and Regulations]
[Pages 34917-34920]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-14126]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 868, 870, and 882

[Docket No. 2003N-0468]


Medical Devices; Effective Date of Requirement for Premarket 
Approval for Three Class III Preamendments Devices

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is requiring the filing 
of a premarket approval application (PMA) or a notice of completion of 
a product development protocol (PDP) for the following three class III 
preamendments devices: Indwelling blood oxyhemoglobin concentration 
analyzer, cardiopulmonary bypass pulsatile flow generator, and the 
ocular plethysmograph. The agency also is summarizing its proposed 
findings regarding the degree of risk of illness or injury designed to 
be eliminated or reduced by requiring the devices to meet the statute's 
approval requirements and the benefits to the public from the use of 
the devices. This action implements certain statutory requirements.

DATES: This rule is effective June 23, 2004. Under the final rule, a 
PMA or a notice of completion of a PDP is required to be filed on or 
before September 21, 2004, for any indwelling blood oxyhemoglobin 
concentration analyzer, cardiopulmonary bypass pulsatile flow 
generator, or ocular plethysmograph that was in commercial

[[Page 34918]]

distribution before May 28, 1976, or that has been found by FDA to be 
substantially equivalent to such a device on or before September 21, 
2004.

FOR FURTHER INFORMATION CONTACT: Joseph M. Sheehan, Center for Devices 
and Radiological Health (HFZ-215), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 301-827-2974.

SUPPLEMENTARY INFORMATION:

I. Background--Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the act), as amended by 
the Medical Device Amendments of 1976 (the 1976 amendments) (Public Law 
94-295) and the Safe Medical Devices Act of 1990 (the SMDA) (Public Law 
101-629), established a comprehensive system for the regulation of 
medical devices intended for human use. Section 513 of the act (21 
U.S.C. 360c) established three categories (classes) of devices, 
depending on the regulatory controls needed to provide reasonable 
assurance of their safety and effectiveness. The three categories of 
devices are class I (general controls), class II (special controls), 
and class III (premarket approval).
    Section 515(b)(1) of the act (21 U.S.C. 360e(b)(1)) established the 
requirement that a preamendments device that FDA has classified into 
class III is subject to premarket approval. A preamendments class III 
device may be commercially distributed without an approved PMA or a 
notice of completion of a PDP until 90 days after FDA issues a final 
rule requiring premarket approval for the device, or 30 months after 
final classification of the device under section 513 of the act, 
whichever is later. Also, a preamendments device subject to the 
rulemaking procedure under section 515(b) of the act is not required to 
have an approved investigational device exemption (IDE) (see part 812 
(21 CFR part 812)) contemporaneous with its interstate distribution 
until the date identified by FDA in the final rule requiring the 
submission of a PMA for the device. At that time, an IDE is required 
only if a PMA has not been submitted or a PDP completed.
    When a rule to require premarket approval for a preamendments 
device is finalized, section 501(f)(2)(B) of the act (21 U.S.C. 
351(f)(2)(B)) requires that a PMA or notice of completion of a PDP for 
any such device be filed within 90 days of the date of issuance of the 
final rule or 30 months after the final classification of the device 
under section 513 of the act, whichever is later. If a PMA or notice of 
completion of a PDP is not filed by the later of the two dates, 
commercial distribution of the device is required to cease.
    The device may, however, be distributed for investigational use if 
the manufacturer, importer, or other sponsor of the device complies 
with the IDE regulations. If a PMA or notice of completion of a PDP is 
not filed by the later of the two dates, and no IDE is in effect, the 
device is deemed to be adulterated within the meaning of section 
501(f)(1)(A) of the act, and subject to seizure and condemnation under 
section 304 of the act (21 U.S.C. 334) if its distribution continues. 
Shipment of devices in interstate commerce will be subject to 
injunction under section 302 of the act (21 U.S.C. 332), and the 
individuals responsible for such shipment will be subject to 
prosecution under section 303 of the act (21 U.S.C. 333). In the past, 
FDA has requested that manufacturers take action to prevent the further 
use of devices for which no PMA has been filed and may determine that 
such a request is appropriate for the class III devices that are the 
subjects of this regulation.
    The act does not permit an extension of the 90-day period after 
issuance of a final rule within which an application or a notice is 
required to be filed. The House Report on the 1976 amendments states 
that:
    [t]he thirty month `grace period' afforded after classification 
of a device into class III * * * is sufficient time for 
manufacturers and importers to develop the data and conduct the 
investigations necessary to support an application for premarket 
approval (H. Rept. 94-853, 94th Cong., 2d sess. 42 (1976)).
    In the Federal Register of November 18, 2003 (68 FR 65014) (the 
November 18, 2003, proposed rule), FDA issued a proposed rule to 
require the filing of a PMA or a notice of completion of a PDP for the 
indwelling blood oxyhemoglobin concentration analyzer, the 
cardiopulmonary bypass pulsatile flow generator, and the ocular 
plethysmograph. In accordance with section 515(b)(2)(A) of the act, FDA 
included in the preamble to the proposed rule the agency's proposed 
findings regarding the degree of risk of illness or injury intended to 
be eliminated or reduced by requiring the device to meet the statute's 
approval requirements as well as the benefits to the public from use of 
the device.
    The November 18, 2003, proposed rule also provided an opportunity 
for interested persons to submit comments on the proposed rule and the 
agency's proposed findings. In accordance with section 515(b)(2)(A) of 
the act, FDA also provided an opportunity for interested persons to 
request a change in the classification of the device based on new 
information relevant to its classification. Any petition requesting a 
change in the classification of these devices was required to be 
submitted by December 3, 2003. The comment period closed February 17, 
2004.
    FDA received no petitions requesting a change in the classification 
of any of the three devices. One comment was addressed to the docket of 
the proposed rule. This comment inquired as to when FDA would approve a 
certain device that was not one of the devices that were the subject of 
the November 18, 2003, proposed rule. The comment was irrelevant and 
FDA addressed it outside of the rulemaking process.

II. Devices Subject to This Proposal

A. Indwelling Blood Oxyhemoglobin Concentration Analyzer (21 CFR 
868.1120)

    An indwelling blood oxyhemoglobin concentration analyzer is a photo 
electric device used to measure, in vivo, the oxygen carrying capacity 
of hemoglobin in blood to aid in determining the patient's 
physiological status.

B. Cardiopulmonary Bypass Pulsatile Flow Generator (21 CFR 870.4320)

    A cardiopulmonary bypass pulsatile flow generator is an 
electrically and pneumatically operated device used to create pulsatile 
blood flow. The device is placed in a cardiopulmonary bypass circuit 
downstream from the oxygenator.

C. Ocular Plethysmograph (21 CFR 882.1790)

    An ocular plethysmograph is a device used to measure or detect 
volume changes in the eye produced by pulsations of the artery, to 
diagnose carotid artery occlusive disease (restrictions on blood flow 
in the carotid artery).

III. Findings With Respect to Risks and Benefits

    Under section 515(b)(3) of the act, FDA is adopting the findings as 
published in the November 18, 2003, proposed rule. As required by 
section 515(b) of the act, FDA published its findings regarding the 
following information: (1) The degree of risk of illness or injury 
designed to be eliminated or reduced by requiring that these devices 
have an approved PMA or a declared completed PDP, and (2) the benefits 
to the public from the use of the device.
    These findings are based on the reports and recommendations of the

[[Page 34919]]

advisory committees (panels) for the classification of these devices 
along with any additional information that FDA has discovered. 
Additional information can be found in the following proposed and final 
rules published in the Federal Register on these dates: Anesthesiology 
devices, 21 CFR part 868 (44 FR 63292, November 2, 1979, and 47 FR 
31130, July 16, 1982); cardiovascular devices, 21 CFR part 870 (44 FR 
13284, March 9, 1979 and 45 FR 7903, February 5, 1980); and 
neurological devices, 21 CFR part 882 (43 FR 55639, November 28, 1978, 
and 44 FR 51725, September 4, 1979).

IV. The Final Rule

    Under section 515(b)(3) of the act, FDA adopts the findings as 
published in the preamble of the November 18, 2003, proposed rule and 
issues this final rule to require premarket approval of the indwelling 
blood oxyhemoglobin concentration analyzer, cardiopulmonary bypass 
pulsatile flow generator, and the ocular plethysmograph. This final 
rule revises parts 868, 870, and 882 (21 CFR parts 868, 870, and 882).
    Under the final rule, a PMA or a notice of completion of a PDP is 
required to be filed within 90 days after date of publication of this 
rule in the Federal Register (see DATES), for any indwelling blood 
oxyhemoglobin concentration analyzer, cardiopulmonary bypass pulsatile 
flow generator, or ocular plethysmograph that was in commercial 
distribution before May 28, 1976, or that has been found by FDA to be 
substantially equivalent to such a device on or before that date. If a 
PMA or notice of completion of a PDP is filed for any such device 
within this time limit, the applicant will be permitted to continue 
marketing its device during FDA's review of its submission. Any other 
indwelling blood oxyhemoglobin concentration analyzer, cardiopulmonary 
bypass pulsatile flow generator, or ocular plethysmograph that was not 
in commercial distribution before May 28, 1976, is required to have an 
approved PMA or a declared completed PDP in effect before it may be 
marketed.
    If a PMA or a notice of completion of a PDP for an indwelling blood 
oxyhemoglobin concentration analyzer, cardiopulmonary bypass pulsatile 
flow generator, or ocular plethysmograph is not filed on or before 90 
days after date of publication of this rule in the Federal Register, 
that device is deemed adulterated under section 501(f)(1)(A) of the 
act, and commercial distribution of the device must cease immediately. 
The device may, however, be distributed for investigational use, if the 
requirements of the investigational device exemption (IDE) regulations 
(part 812) are met.
    The exemptions in Sec.  812.2(c)(1) and (c)(2) from the 
requirements of the IDE regulations for preamendments class III devices 
cease to apply to any indwelling blood oxyhemoglobin concentration 
analyzer, cardiopulmonary bypass pulsatile flow generator, or ocular 
plethysmograph that is: (1) Not legally on the market 90 days after 
date of publication of this rule in the Federal Register; or (2) 
legally on the market by, but for which a PMA or notice of completion 
of a PDP is not filed by 90 days after date of publication of this rule 
in the Federal Register, or for which PMA approval has been denied or 
withdrawn. FDA cautions that manufacturers who are not immediately 
planning to submit a PMA or notice of completion of a PDP should submit 
IDE applications to FDA by 60 days after date of publication of this 
rule in the Federal Register, to minimize the possibility of 
interrupting shipment of the device. At this time, FDA is not aware of 
any firm that is marketing these devices.

V. PMA Requirements

    A PMA for these devices must include the information required by 
section 515(c)(1) of the act. Such a PMA should also include a detailed 
discussion of the risks identified previously, as well as a discussion 
of the effectiveness of the device for which premarket approval is 
sought. In addition, a PMA must include all data and information on the 
following requirements: (1) Any risks known, or that should be 
reasonably known, to the applicant that have not been identified in 
this document; (2) the effectiveness of the device that is the subject 
of the application; and (3) full reports of all preclinical and 
clinical information from investigations on the safety and 
effectiveness of the device for which premarket approval is sought.
    A PMA should include valid scientific evidence ``obtained from 
well-controlled clinical studies, with detailed data,'' in order to 
provide reasonable assurance of the safety and effectiveness of the 
device for its intended use. (See 21 CFR 860.7(c)(2)).)
    Information about the premarket approval process is available from 
FDA's Center for Devices and Radiological Health (CDRH) on the Internet 
at http://www.fda.gov/cdrh/devadvice/pma/.

VI. PDP Requirements

    A PDP for any of these devices may be submitted in lieu of a PMA, 
and must follow the procedures outlined in section 515(f) of the act. A 
PDP should provide the following information: (1) A description of the 
device, (2) preclinical trial information (if any), (3) clinical trial 
information (if any), (4) a description of the manufacturing and 
processing of the devices, (5) the labeling of the device, and (6) all 
other relevant information about the device. In addition, the PDP must 
include progress reports and records of the trials conducted under the 
protocol on the safety and effectiveness of the device for which the 
completed PDP is sought.
    Information about the PDP process is also available from CDRH on 
the on the Internet at http://www.fda.gov/cdrh/devadvice/pma/app_methods.html#product_dev.

VII. Environmental Impact

    The agency has determined under 21 CFR 25.30(h) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

VIII. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and 
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive 
Order 12866 directs agencies to assess all costs and benefits of 
available regulatory alternatives and, when regulation is necessary, to 
select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The agency believes that 
this final rule is not a significant regulatory action under the 
Executive order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because there have been no premarket submissions for 
these devices in the past 5 years, and because FDA is not aware of any 
firms marketing these devices, the agency has concluded that there is 
little or no interest in marketing these devices. The agency, 
therefore, certifies that the final rule will not have a significant 
economic impact on a substantial number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that agencies prepare a written statement, which includes an assessment 
of anticipated costs and

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benefits, before proposing ``any rule that includes any Federal mandate 
that may result in the expenditure by State, local, and tribal 
governments, in the aggregate, or by the private sector, of 
$100,000,000 or more (adjusted annually for inflation) in any one 
year.'' The current threshold after adjustment for inflation is $110 
million. FDA does not expect this final rule to result in any 1-year 
expenditure that would meet or exceed this amount.

IX. Paperwork Reduction Act of 1995

    This final rule contains information collection provisions that are 
subject to review by the Office of Management and Budget (OMB) under 
the Paperwork Reduction Act of 1995 (the PRA). The burden hours 
required for Sec.  884.5320(c), included in the collection entitled 
``Premarket Approval of Medical Devices--21 CFR Part 814,'' are 
reported and approved under OMB control number 0910-0231. Therefore, 
clearance by OMB under the PRA is not required.

List of Subjects in 21 CFR Parts 868, 870, and 882

    Medical devices.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR parts 
868, 870, and 882 are amended as follows:

PART 868--ANESTHESIOLOGY DEVICES

0
1. The authority citation for 21 CFR part 868 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

0
2. Section 868.1120 is amended by revising paragraph (c) to read as 
follows:


Sec.  868.1120  Indwelling blood oxyhemoglobin concentration analyzer.

* * * * *
    (c) Date PMA or notice of completion of PDP is required. A PMA or 
notice of completion of a PDP is required to be filed with the Food and 
Drug Administration on or before September 21, 2004, for any indwelling 
blood oxyhemoglobin concentration analyzer that was in commercial 
distribution before May 28, 1976, or that has, on or before September 
21, 2004, been found to be substantially equivalent to an indwelling 
blood oxyhemoglobin concentration analyzer that was in commercial 
distribution before May 28, 1976. Any other indwelling blood 
oxyhemoglobin concentration analyzer shall have an approved PMA or 
declared completed PDP in effect before being placed in commercial 
distribution.

PART 870--CARDIOVASCULAR DEVICES

0
3. The authority citation for 21 CFR part 870 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

0
4. Section 870.4320 is amended by revising paragraph (c) to read as 
follows:


Sec.  870.4320  Cardiopulmonary bypass pulsatile flow generator.

* * * * *
    (c) Date PMA or notice of completion of PDP is required. A PMA or 
notice of completion of a PDP is required to be filed with the Food and 
Drug Administration on or before September 21, 2004, for any 
cardiopulmonary bypass pulsatile flow generator that was in commercial 
distribution before May 28, 1976, or that has, on or before September 
21, 2004, been found to be substantially equivalent to any 
cardiopulmonary bypass pulsatile flow generator that was in commercial 
distribution before May 28, 1976. Any other cardiopulmonary bypass 
pulsatile flow generator shall have an approved PMA or declared 
completed PDP in effect before being placed in commercial distribution.

PART 882--NEUROLOGICAL DEVICES

0
5. The authority citation for 21 CFR part 882 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

0
6. Section 882.1790 is amended by revising paragraph (c) to read as 
follows:


Sec.  882.1790  Ocular plethysmograph.

* * * * *
    (c) Date PMA or notice of completion of PDP is required. A PMA or 
notice of completion of a PDP is required to be filed with the Food and 
Drug Administration on or before September 21, 2004, for any ocular 
plethysmograph that was in commercial distribution before May 28, 1976. 
Any other ocular plethysmograph shall have an approved PMA or declared 
completed PDP in effect before being placed in commercial distribution.

    Dated: June 14, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-14126 Filed 6-22-04; 8:45 am]
BILLING CODE 4160-01-S