[Federal Register Volume 62, Number 114 (Friday, June 13, 1997)]
[Notices]
[Pages 32355-32358]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-15450]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 94N-0417]


Order for Certain Class III Devices; Submission of Safety and 
Effectiveness Information; Group 2

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is revising the 
schedule for submission of summaries and citations for 3 devices 
included in the order requiring manufacturers of 31 class III devices 
(Group 2) to submit to FDA a summary of, and a citation to, all 
information known or otherwise available to them respecting such 
devices, including adverse safety or effectiveness information 
concerning the devices that have not been submitted under the Federal 
Food, Drug, and Cosmetic Act (the act). In response to comments 
received on the August 14, 1995, order and in order to facilitate the 
review process, FDA is grouping three cardiovascular devices with 
related uses together and is changing the date by which summaries and 
citations are to be submitted for them to February 14, 1998. As a 
reminder to device manufacturers, FDA is also reprinting the due dates 
for all other devices listed in the August 14, 1995, order.

DATES: Summaries and citations must be submitted by the dates listed 
below.


[[Page 32356]]


ADDRESSES: Submit summaries and citations to the Document Mail Center 
(HFZ-401), Food and Drug Administration, Center for Devices and 
Radiological Health, 9200 Corporate Blvd., Rockville, MD 20850.

FOR FURTHER INFORMATION CONTACT: Doreen M. Melling, Center for Devices 
and Radiological Health (HFZ-404), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 301-594-2186.

SUPPLEMENTARY INFORMATION:

I. Background

    Section 513 of the act (21 U.S.C. 360c) requires the classification 
of medical devices into one of three classes: Class I (general 
controls), class II (special controls), and class III (premarket 
approval). Generally, devices that were on the market before May 28, 
1976, the date of enactment of the Medical Device Amendments of 1976 
(the amendments) (Pub. L. 94-295), and devices marketed on or after 
that date that are substantially equivalent to such devices, have been 
classified by FDA. This notice refers to both the class III devices 
that were on the market before May 28, 1976, and the substantially 
equivalent devices that were marketed on or after that date, as 
``preamendment devices''.
    Section 515(b) of the act (21 U.S.C. 360e(b)) establishes the 
requirement that a preamendments device that FDA has classified into 
class III is subject to premarket approval. However the submission of a 
premarket approval application (PMA), or a notice of completion of a 
product development protocol (PDP), is not required until 90 days after 
FDA issues a final rule requiring premarket approval for the device, or 
30 months after final classification of the device, whichever is later. 
Also, such a device is exempt from the investigational device exemption 
(IDE) regulations (21 CFR part 812) until the date stipulated by FDA in 
the final rule requiring premarket approval for that device. If a PMA 
or a 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 only for investigational use if the 
manufacturer, importer, or other sponsor of the device complies with 
the IDE regulations.
    To date, FDA has issued final rules requiring the submission of 
PMA's for 52 preamendment class III devices. Additionally, FDA has 
issued proposed rules for 12 other devices. There are 68 remaining 
preamendment class III devices for which FDA has not yet initiated any 
action requiring the submission of PMA's. The original number of 
approximately 140 preamendments class III devices can be accounted for 
by past reclassification actions.
    The Safe Medical Devices Act of 1990 (the SMDA) (Pub. L. 101-629) 
changed the definition of class II devices from those for which a 
performance standard is necessary to provide reasonable assurance of 
safety and effectiveness to those for which there is sufficient 
information to establish special controls to provide such assurance. 
Special controls include performance standards, postmarket 
surveillance, patient registries, guidelines (including guidelines for 
the submission of clinical data in premarket notification submissions 
in accordance with section 510(k) of the act (21 U.S.C. 360(k)), 
recommendations, and other appropriate actions the agency deems 
necessary to provide such assurance. Thus, the SMDA modified the 
definition of class II devices to permit reliance on special controls, 
rather than performance standards alone, to provide reasonable 
assurance of safety and effectiveness.
    The SMDA also added new section 515(i) to the act. This section 
requires FDA to order manufacturers of preamendment class III devices 
for which no final regulation requiring the submission of PMA's has 
been issued to submit to the agency a summary of, and a citation to, 
any information known or otherwise available to them respecting such 
devices, including adverse safety and effectiveness information which 
has not been submitted under section 519 of the act (21 U.S.C. 360i). 
Section 519 of the act requires manufacturers, importers, or 
distributors to maintain records and to report information that 
reasonably suggests that one of its marketed devices may have caused or 
contributed to a death or serious injury or that a malfunction of the 
device is likely to cause death or serious injury on recurrence. 
Section 515(i) of the act also directs FDA to publish a regulation 
before December 1, 1995, for each device subject to section 515(i), 
either revising the classification of the device into class I or class 
II or requiring the device to remain in class III. Finally, section 
515(i) of the act requires that, within 12 months after publication of 
a regulation retaining a device in class III, FDA is to establish a 
schedule for the promulgation of a rule requiring the submission of 
PMA's for the device.
    In the Federal Register of May 6, 1994 (59 FR 23731), FDA announced 
its strategy for addressing the 116 remaining preamendment class III 
devices. In this notice, FDA made available a document setting forth 
its strategy for implementing the provisions of the SMDA that require 
FDA to review the classification of certain class III devices, and 
either reclassify the devices into class I or class II or retain them 
in class III. Under this plan, the agency divided the universe of 
preamendment class III devices into three groups: Group 1 devices are 
devices that FDA believes raise significant questions of safety and/or 
effectiveness, but are no longer used or are very limited in use; Group 
2 devices are devices that FDA believes have a high potential for being 
reclassified into class II; and Group 3 devices are devices that FDA 
believes are currently in commercial distribution and are not likely 
candidates for reclassification. There are a total of 43, 31, and 42 
(15 high priority) devices in Groups 1, 2, and 3, respectively.
    In the May 6, 1994, notice, FDA announced its intention to call for 
the submission of PMA's for the 15 highest priority devices in Group 3, 
and for all Group 1 devices. In the Federal Register of September 27, 
1996 (61 FR 50704), was published a final rule requiring the filing of 
a PMA or a notice of completion of a PDP for 41 class III devices 
(Group 1 device). In the Federal Register of May 6, 1994, notice, the 
agency also announced its intention to issue an order under section 
515(i) of the act for the remaining Group 3 devices and all of the 
Group 2 devices.
    In the Federal Register of August 14, 1995 (60 FR 41986), FDA 
issued an order requiring manufacturers of the 31 devices in Group 2 to 
submit a summary of, and citation to, all safety and effectiveness 
information known or otherwise available to them respecting such 
devices, including adverse safety and effectiveness information 
concerning the devices which had not been submitted under section 519 
of the act. Under section 515(i) of the act, FDA is authorized to 
require the submission of the adverse safety and effectiveness 
information identified in the summary and citation submitted in 
response to this order, if such information is available. In this 
notice, FDA is grouping three devices with related uses together and is 
revising the date by which summaries and citations are to be submitted. 
The summaries for the cardiopulmonary bypass arterial line blood filter 
(originally due by August 14, 1997), the cardiopulmonary bypass 
pulsatile flow generator (originally due by August 14, 1998), and the 
cardiopulmonary bypass oxygenator (originally due by August 14, 1997) 
are now due by February 14, 1998. Based upon the information submitted 
in

[[Page 32357]]

response to this order, FDA will issue a proposed regulation for each 
device either proposing its reclassification into class I or class II, 
or retaining the device in class III. The due dates for summaries and 
citations for the other Group 2 devices remain the same and are listed 
below.

II. Statutory Authority and Enforcement

    In addition to the provisions of section 515(i) of the SMDA 
described in section I of this document, this order is issued under 
section 519 of the act, as implemented by Sec. 860.7(g)(2) (21 CFR 
860.7(g)(2)). This regulation authorizes FDA to require reports or 
other information bearing on the classification of a device. Section 
519 of the act also requires the reporting of any death or serious 
injury caused by a device or by its malfunction.
    Failure to comply with this order is a prohibited act under section 
301(q) of the act (21 U.S.C. 331(q)), and the agency will use its 
enforcement powers to deter noncompliance. Violations under section 301 
of the act may be subject to seizure or injunction under sections 
302(a) and 304(a) of the act (21 U.S.C. 332(a) and 334(a)). In 
addition, violations under section 301 of the act may be subject to 
civil penalties under section 303(f) of the act (21 U.S.C. 333(f)) and 
criminal prosecution under section 303(a) of the act.

III. Order

    The agency is hereby issuing this order under sections 515(i) and 
519 of the act and Sec. 860.7(g)(1) of the regulations. Under the 
order, the required information shall be submitted by the dates listed 
below so that FDA may begin promptly the process established by section 
515(i) of the act to either revise or sustain the current 
classification of these devices. The three devices listed with a 
February 14, 1998, due date are the devices whose due date is being 
revised. The remaining due dates are reprinted here from the August 14, 
1995, order as a reminder to device manufacturers.

A. Deadlines for Submission of Information

    For the following eight devices, the required information was to be 
submitted by August 14, 1996:
    1.  Sec. 864.7250 Erythropoietin assay.
    2. Sec. 864.7300 Fibrin monomer paracoagulation test.
    3. Sec. 876.3630 Penile rigidity implant.
    4. Sec. 878.5360 Tweezer-type epilator.
    5. Sec. 884.1060 Endometrial aspirator.
    6. Sec. 884.1100 Endometrial brush.
    7. Sec. 884.1185 Endometrial washer.
    8.  Sec. 886.3920 Eye valve implants.
    For the following nine devices, the required information was to be 
submitted by February 14, 1997:
    9. Sec. 866.3305 Herpes simplex virus serological reagents.
    10.  Sec. 866.3510 Rubella virus serological reagents.
    11.  Sec. 870.3620 Pacemaker lead adaptor.
    12.  Sec. 872.6080 Airbrush.
    13.  Sec. 876.4480 Electrohydraulic lithotriptor.
    14.  Sec. 878.3610 Esophageal prosthesis.
    15.  Sec. 878.3720 Tracheal prosthesis.
    16.  Sec. 884.4100 Endoscopic electrocautery and accessories.
    17.  Sec. 884.4150 Bipolar endoscopic coagulator-cutter and 
accessories.
    For the following eight devices, the required information shall be 
submitted by August 14, 1997:
    18.  Sec. 868.1150 Indwelling blood carbon dioxide partial pressure 
analyzer.
    19.  Sec. 868.1170 Indwelling blood hydrogen ion concentration. 
analyzer.
    20.  Sec. 868.1200 Indwelling blood oxygen partial pressure 
analyzer.
    21.  Sec. 870.3680 Cardiovascular permanent pacemaker electrodes.
    22.  Sec. 876.5860 High permeability hemodialysis system.
    23.  Sec. 878.5650 Topical 02 chamber.
    24.  Sec. 882.5940 Electroconvulsive therapy device.
    25.  Sec. 888.3660 Shoulder semi-constrained.
    For the following three devices, the required information shall be 
submitted by February 14, 1998:
    26. Sec. 870.4260 Cardiopulmonary bypass arterial line blood 
filter. (Originally due August 14, 1997.)1
    27. Sec. 870.4320 Cardiopulmonary bypass pulsatile flow generator. 
(Originally due on August 14, 1998.)1 
    28. Sec. 870.4350 Cardiopulmonary bypass oxygenator. (Originally 
due on August 14, 1997.)\1\
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    \1\ Revised due date.
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    For the following three devices, the required information shall be 
submitted by August 14, 1998:
    29.  Sec. 870.3710 Pacemaker repair or replacement material.
    30.  Sec. 870.5200 External cardiac compressor.
    31.  Sec. 876.5540 Implanted blood access device.

B. Required Contents of Submissions

    By the dates listed in section III. A of this document, all 
manufactures currently marketing preamendments class III devices 
subject to this order shall provide a summary of, and citation to, any 
information known or otherwise available to them respecting the 
devices, including adverse safety and effectiveness data which has not 
been submitted under section 519 of the act. FDA suggests that it may 
be in the best interest of submitters to summarize the information 
submitted under section 519 of the act to facilitate FDA's 
decisionmaking, even though such information is not required.
    The information should be submitted in one of the two following 
formats depending on whether the applicant is aware of any information 
that would support the reclassification of the device into class I 
(general controls) or class II (special controls). Information that 
would support the reclassification of the device must consist of 
adequate, valid scientific evidence showing that general controls alone 
(class I), or general controls and special controls (class II) will 
provide a reasonable assurance of the safety and effectiveness of the 
device.
    For manufacturers who are not aware of any information that would 
support the reclassification of their device into class I or class II, 
the information provided should be submitted in the following format:
    1. Indications for use. A general description of the disease or 
condition to be diagnosed, treated, cured, mitigated, or prevented, 
including a description of the patient population for which the device 
is intended.
    2.  Device description. An explanation of how the device functions, 
significant physical and performance characteristics of the device, and 
basic scientific concepts that form the basis for the device.
    3. Other device labeling. Other device labeling that includes 
contraindications, warnings and precautions and/or promotional 
materials.
    4. Risks. A summary of all adverse safety and effectiveness 
information and identification of the risks presented by the device as 
well as any mechanisms or procedures which will control the risk.
    5. Alternative practices and procedures. A description of 
alternative practices or procedures for diagnosing, treating, 
preventing, curing, or mitigating the disease or condition for which 
the device is intended.
    6. Summary of preclinical and clinical data. The summary of 
preclinical and clinical data should include the conclusions drawn from 
the studies which support the safety and effectiveness of the device as 
well as special controls, if any, which address the adverse effects of 
the device on health. The summary should include a

[[Page 32358]]

brief description of the objective of the studies, the experimental 
design, how the data were collected and analyzed, and a brief 
description of the results of the studies, whether positive, negative, 
or inconclusive. The summary of the clinical study(ies) should also 
include a discussion of the subject inclusion and exclusion criteria, 
the study population, reasons for patient discontinuations, and results 
of statistical analyses.
    7. Bibliography. A copy of the key references, a brief summary of 
the salient features of each key reference, and a brief discussion of 
why the reference is relevant to an evaluation of the safety and 
effectiveness evaluation of the device.
    Manufacturers who are aware of information that would support the 
reclassification of their device into class I or class II may either 
submit information using the format described below or may submit a 
formal reclassification petition, which should include the information 
described below in addition to the information required under 21 CFR 
860.123:
    1. Identification. A brief narrative identification of the device. 
This identification should be specific enough to distinguish a 
particular device from a generic type of device. Where appropriate, 
this identification should include a listing of the materials, and the 
component parts, and a description of the intended use of the device.
    2. Risks to health. An identification of the risks to health should 
be provided. This section should summarize all adverse safety and 
effectiveness information that has not been submitted under section 519 
of the act, particularly the most significant. The mechanisms or 
procedures which will control the risk should be described. A list of 
the general hazards associated with the device and a bibliography with 
copies of the referenced material should be provided.
    3. Recommendation. A statement whether the manufacturer believes 
the device should be reclassified into class I or class II.
    4. Summary of reasons for recommendation. Each manufacturer should 
include a summary of the reasons for requesting reclassification of its 
device and an explanation of why it believes the device meets the 
statutory criteria for reclassification into class I or class II. Each 
manufacturer should also identify the special controls that it believes 
would be sufficient to provide reasonable assurance of the safety and 
effectiveness of its device if it believes the device should be 
reclassified into class II.
    5. Summary of valid scientific evidence on which the recommendation 
is based. Manufacturers are advised that, when considering a formal 
reclassification petition, FDA will rely only upon valid scientific 
evidence to determine that there is reasonable assurance of the safety 
and effectiveness of the device, if regulated by general controls alone 
(class I) or by general controls and special controls (class II). Valid 
scientific evidence consists of evidence from well-controlled 
investigations, partially controlled studies, studies and objective 
trials without matched controls, well-documented case histories 
conducted by qualified experts, and reports of significant human 
experience with a marketed device, from which it can fairly and 
responsibly be concluded by qualified experts that there is reasonable 
assurance of the safety and effectiveness of a device under its 
conditions of use. The evidence required may vary according to the 
characteristics of the device, its conditions of use, the existence and 
adequacy of warnings and other restrictions, and the extent of 
experience with its use. Isolated case reports, random experience, 
reports lacking sufficient details to permit scientific evaluation, and 
unsubstantiated opinions are not regarded as valid scientific evidence 
to show safety or effectiveness (see Sec. 860.7(c)(2)).
    According to Sec. 860.7(d)(1), there is reasonable assurance that a 
device is safe when it can be determined, based upon valid scientific 
evidence, that the probable benefits to health from use of the device 
for its intended uses and conditions of use, when accompanied by 
adequate directions and warnings against unsafe use, outweigh any 
probable risks. The valid scientific evidence used to determine the 
safety of a device shall adequately demonstrate the absence of 
unreasonable risk of illness or injury associated with the use of the 
device for its intended uses and conditions for use. Moreover, under 
Sec. 860.7(e)(1), there is reasonable assurance that a device is 
effective when it can be determined, based upon valid scientific 
evidence, that in a significant portion of the target population, the 
use of the device for its intended uses and conditions of use, when 
accompanied by adequate directions for use and warnings against unsafe 
use, will provide clinically significant results.
    Manufacturers submitting a formal reclassification petition may 
wish to request two petitions as examples of successful 
reclassification petitions. Magnetic resonance imaging devices, Docket 
Nos. 87P-0214/CP-1 through CP-13, and Nd:YAG Laser for posterior 
capsulotomy devices, Docket No. 86P-0083, were both reclassified from 
class III to class II subsequent to the submission of reclassification 
petitions. Both petitions are available upon submission of a Freedom of 
Information request to the Dockets Management Branch (HFA-305), Food 
and Drug Administration, 12420 Parklawn Dr., rm. 1-23, Rockville, MD 
20850.

IV. Submission of Required Information

    The summary of, and citation to, any information required by the 
act must be submitted by the dates listed above to the Document Mail 
Center (address above).

    Dated: June 4, 1997.
 Joseph A. Levitt,
 Deputy Director for Regulations Policy, Center for Devices and 
Radiological Health.
[FR Doc. 97-15450 Filed 6-12-97; 8:45 am]
BILLING CODE 4160-01-F