[Federal Register Volume 60, Number 156 (Monday, August 14, 1995)]
[Notices]
[Pages 41986-41989]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-19945]



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[Docket No. 94N-0417]


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

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is issuing an order 
requiring manufacturers of 31 class III devices 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 which has not been 
submitted under the Federal Food, Drug, and Cosmetic Act (the act). FDA 
is requesting this information in order to determine, for each device, 
whether the classification of the device should be revised, or whether 
a regulation requiring the submission of premarket approval 
applications (PMA's) for the device should be promulgated. Based on 
preliminary information, FDA believes these 31 devices have a higher 
potential for reclassification.

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

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

[[Page 41987]]

FOR FURTHER INFORMATION CONTACT: Melpomeni K. Jeffries, 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 regulatory 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 ``preamendments devices.''
    Section 515(b)(1) of the act (21 U.S.C. 360e(b)(1)) establishes the 
requirement that a preamendments device that FDA has classified into 
class III is subject to premarket approval. However, submission of a 
PMA, or a notice of completion of a product development protocol (PDP), 
is not required until 90 days after FDA promulgates 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 
of part 812 (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 nine preamendment class III devices. Additionally, FDA has 
issued proposed rules for 10 other devices. There are 116 remaining 
preamendment class III devices for which FDA has not yet initiated 
action requiring the submission of PMA's.
    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)), 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) (21 U.S.C. 360e(i)) to the 
act. This section requires FDA to order manufacturers of preamendment 
class III devices for which no final regulation has been issued 
requiring the submission of PMA's 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 (21 U.S.C. 360i) 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 
either revise the classification of the device into class I or class II 
or require the device to remain in class III; and for devices remaining 
in class III, 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 remaining preamendment class III 
devices. In that notice, FDA made available a document setting forth 
its strategy for implementing the provisions of the SMDA which require 
FDA to review the classification of certain class III devices, and 
either reclassify them into class I or class II or retain them in class 
III. Pursuant to this plan, the agency divided the universe of 
preamendment class III devices into the following 3 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. 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 intent to call for the 
submission of PMA's for the 15 highest priority devices in Group 3 and 
for all Group 1 devices. The agency also announced its intent to issue 
an order under section 515(i) of the act for the remaining Group 3 
devices and all of the Group 2 devices. 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. 
Based upon the information submitted in response to this order, FDA 
will either propose reclassification of some or all of these devices 
into class I or class II, or propose retaining some or all of them in 
class III.
    In this document, FDA is requiring manufacturers of all 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 information concerning the 
devices which has not been submitted under section 519 of the act. As 
noted above, FDA believes that these devices have a higher potential 
for reclassification provided that manufacturers collect, analyze, and 
submit the necessary supporting information in response to this notice.
    Elsewhere in this issue of the Federal Register, FDA is publishing 
a similar notice with respect to the 27 remaining Group 3 devices.

II. Statutory Authority and Enforcement

    In addition to the provisions of section 515(i) of the SMDA 
described above, 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 furnish the information required by this order results 
in the device being misbranded under section 502(t) of the act (21 
U.S.C. 352 (t)) and is a prohibited act under sections 301(a) and (q) 
of the act (21 U.S.C. 331(a) and (q)). The agency will use its 
enforcement 

[[Page 41988]]
powers to deter noncompliance. Violations of section 301 of the act may 
be subject to seizure or injunction under sections 304(a) and 302(a) of 
the act (21 U.S.C. 334(a) and 332(a) respectively). 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 (21 U.S.C. 
333(a)).

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.

A. Deadlines for Submission of Information

    For the following 8 devices, the required information shall 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 implant.
    For the following 9 devices, the required information shall 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 10 devices, the required information shall be 
submitted by August 14, 1997.
    18. Sec. 868.1150 Indwelling blood carbon dioxide partial pressure 
(Pco2) analyzer.
    19. Sec. 868.1170 Indwelling blood hydrogen ion concentration (pH) 
analyzer.
    20. Sec. 868.1200 Indwelling blood oxygen partial pressure (Pco2) 
analyzer.
    21. Sec. 870.3680(b) Cardiovascular permanent pacemaker electrode.
    22. Sec. 870.4260 Cardiopulmonary bypass arterial line blood 
filter.
    23. Sec. 870.4350 Cardiopulmonary bypass oxygenator.
    24. Sec. 876.5860 High permeability hemodialysis system.
    25. Sec. 878.5650 Topical oxygen chamber for extremities.
    26. Sec. 882.5940 Electroconvulsive therapy device.
    27. Sec. 888.3660 Shoulder joint metal/polymer semi-constrained 
cemented prosthesis.
    For the following 4 devices, the required information shall be 
submitted by August 14, 1998.
    28. Sec. 870.3710 Pacemaker repair or replacement material.
    29. Sec. 870.4320 Cardiopulmonary bypass pulsatile flow generator.
    30. Sec. 870.5200 External cardiac compressor.
    31. Sec. 876.5540(b)(1) Implanted blood access device.

B. Required Contents of Submissions

    By the dates listed above, all manufacturers 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 decision making, 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 
which would support the reclassification of the device into class I 
(general controls) or class II (special controls). Information which 
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 do not believe that existing information 
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 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 believe that existing information 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.

[[Page 41989]]

    2. Risks to health. An identification of the risks to health should 
be provided. This section should summarize all adverse safety and 
effectiveness information, which have 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 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, pursuant 
to 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 through 87P-0215/CP0013, 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 
a reclassification petition. 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: July 13, 1995.
Joseph A. Levitt,
Deputy Director for Regulations Policy, Center for Devices and 
Radiological Health.
[FR Doc. 95-19945 Filed 8-11-95; 8:45 am]
BILLING CODE 4160-01-F