[Federal Register Volume 60, Number 9 (Friday, January 13, 1995)]
[Proposed Rules]
[Pages 3168-3171]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-971]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 892
[Docket No. 94N-0345]
Medical Devices; Classification of Transilluminators
(Diaphanoscopes or Lightscanners) for Breast Evaluation
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
classify the transilluminator (diaphanoscope or lightscanner) for
breast evaluation into class III (premarket approval). The agency is
also publishing in this document the recommendations of the Obstetrics
and Gynecology Devices Panel regarding the classification of the
device. After considering public comments on the proposed
classification, FDA will publish a final regulation classifying the
device. This action is being taken under the Federal Food, Drug, and
Cosmetic Act (the act), as amended by the Medical Device Amendments of
1976 (the 1976 amendments) and the Safe Medical Devices Act of 1990
(the SMDA).
DATES: Written comments by April 13, 1995. FDA proposes that any final
regulation that may issue based on this proposal become effective 30
days after the date of its publication in the Federal Register.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Robert A. Phillips, Center for Devices
and Radiological Health (HFZ-470), Food and Drug Administration, 1390
Piccard Dr., Rockville, MD 20850, 301-594-1212.
SUPPLEMENTARY INFORMATION:
I. Background
The act, as amended by the 1976 amendments (Pub. L. 94-295) and the
Safe Medical Devices Act of 1990 (Pub. L. 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). Under section 513 of the act, devices that were in
commercial distribution before May 28, 1976 (the date of enactment of
the 1976 amendments) are classified after FDA has: (1) Received a
recommendation from a device classification panel (an FDA advisory
committee); (2) published the panel's recommendations for comment,
along with a proposed regulation classifying the device; and (3)
published a final regulation classifying the device.
A device that is first offered in commercial distribution after May
28, 1976, and which FDA determines to be substantially equivalent to a
device classified under this scheme, is classified into the same class
as the device to which it is substantially equivalent. The agency
determines whether new devices are substantially equivalent to
previously offered devices by means of premarket notification
procedures in section 510(k) of the act (21 U.S.C. 360(k)) and part 807
of the regulations (21 CFR part 807). A device that was not in
commercial distribution prior to May 28, 1976, and that has not been
found by FDA to be substantially equivalent to a legally marketed
device, is classified automatically by statute (section 513(f) of the
act) into class III without any FDA rulemaking proceedings.
In 1980, when other obstetric and gynecological devices were
classified (45 FR 12684 through 12720, February 26, 1980), FDA was not
aware that transilluminators, also known as lightscanners or
diaphanoscopes, for breast evaluation were preamendments devices, and
inadvertently omitted them from the classification process. Based upon
the recommendations the Obstetrics and Gynecological Devices Panel made
during its January 11, 1991, meeting (Ref. 24), FDA is now proposing to
classify the transilluminator for breast evaluation into class III,
thereby requiring each manufacturer of the device to submit to FDA a
PMA by a date to be set in a future regulation under section 515(b) of
the act (21 U.S.C. 360e(b)). Specifically, a preamendments class III
device may be commercially distributed without an approved PMA until 90
days after FDA issues a final rule requiring premarket approval of the
device or 30 months after classification of the device under section
513 of the act, whichever is later. Each application must include
sufficient valid scientific evidence to provide reasonable assurance
that the device is safe and effective under the conditions of use
prescribed, [[Page 3169]] recommended, or suggested in its proposed
labeling.
II. The Obstetrics and Gynecology Devices Panel Recommendations
The Obstetrics and Gynecology Devices Panel, an FDA advisory
committee, made the following recommendations regarding the
classification of the transilluminator for breast evaluation.
A. Identification
A transilluminator, also known as a lightscanner or diaphanoscope,
is an electrically powered device that uses low intensity emissions of
visible light and near-infrared radiation (approximately 700 to 1050
nanometers (nm)), transmitted through the breast, to visualize
translucent tissue for the diagnosis of cancer, other conditions,
diseases, or abnormalities (Ref. 24).
B. Recommended Classification
Class III (premarket approval). The Obstetrics and Gynecology
Devices Panel recommended that the transilluminator for breast
evaluation be classified into class III and that a regulation requiring
submission of premarket approval applications for this device be a high
priority. The Obstetrics and Gynecology Devices Panel further
recommended that, at this time, the device should not be used for
breast examinations, either alone or in conjunction with other
techniques.
C. Summary of Reasons for Recommendation
The Obstetrics and Gynecology Devices Panel recommended that
transilluminator devices for breast evaluation be classified into class
III because the Panel believes that premarket approval is necessary to
provide reasonable assurance of the safety and effectiveness of the
device. The Obstetrics and Gynecology Devices Panel concludes that
there are no published studies or clinical data demonstrating the
safety and effectiveness of the device. The Obstetrics and Gynecology
Devices Panel also believes that the device presents a potential
unreasonable risk of illness or injury to the patient if the clinician
relies on the device. Although the device's illumination level,
wavelength, and image quality can be controlled through tests and
specifications, the Obstetrics and Gynecology Devices Panel believes
that insufficient evidence exists to determine that special controls
can be established to provide reasonable assurance of the safety and
effectiveness of the device for its intended use. The Obstetrics and
Gynecology Devices Panel recommends, therefore, that the device be
subject to premarket approval to ensure that manufacturers of this
device demonstrate the device's safety and effectiveness in order to
market the device.
D. Summary of Data Upon Which the Recommendation is Based
The Obstetrics and Gynecology Devices Panel based its
recommendation on the review of the studies cited in this document, on
expert testimony presented to the Obstetrics and Gynecology Devices
Panel, and on the Panel members' personal knowledge of, and experience
with, the device.
E. Risks to Health
The following risks are associated with the use of
transilluminators: Missed diagnosis; delayed diagnosis; delayed
treatment; electrical shock; and optical radiation. Due to the
transilluminator's questionable performance, the use of the device
could result in missed or delayed diagnosis of breast cancer. Such
misdiagnoses could result in more traumatic treatment to the patient
and a potentially higher risk of death.
III. Proposed Classification
FDA agrees with the Obstetrics and Gynecology Devices Panel's
conclusions and recommendations. The National Cancer Institute (NCI)
also agrees that transilluminators have not been proven effective for
diagnosis of cancer. In a September 1990 issue of Cancer Facts, the NCI
states, ``Although this technique has been improved over the years, at
this time transillumination is not an effective technique for the
detection of early breast cancer,'' and, ``Transillumination is
especially poor at finding small tumors (less than 1 centimeter).'' NCI
supports the idea of further research, but states, ``* * * at this
time, transillumination has no role in breast cancer screening'' (Ref.
1).
A major study of transillumination involving 2,763 patients was
conducted by the National Institutes of Health in the late 1980's (Ref.
2). In a section entitled ``Combined Modality Results,'' the study
authors concluded: ``While the accuracy of clinical exam [in detecting
cancer] is 0.67 and that of lightscanning is 0.57, there is no
statistically significant difference between them.'' That is, there was
no difference between the use of lightscanning and clinical examination
(palpation). They also stated, ``When the results of lightscanning,
mammography and physical exam are added, no additional benefit is
seen'' as a result of light scanning. This study indicates that
transilluminators, at this time, do not have clinical benefits as an
alternative to mammography or as an adjunctive diagnostic tool to
mammography.
Following the January 1991 Obstetrics and Gynecology Devices Panel
meeting, FDA undertook a literature search to determine if any new and
significant studies had been performed, which would affect the proposed
classification. The agency reviewed approximately 20 references (Refs.
4 through 23) published since 1988. None of these studies recommend the
device for routine clinical use.
One of the largest studies conducted in a clinical setting was a
multicenter study in Sweden involving 2,568 women (Ref. 3). The study
concluded that lightscanning, as utilized in the study, is inferior to
mammography and produced a large number of false positive results.
In summary, FDA's review of recent technical and clinical papers
did not reveal any data that would influence the agency to adopt any
classification other than class III.
FDA believes that insufficient information exists to determine that
general controls, or special controls, such as postmarket surveillance,
the development of guidelines, the establishment of a performance
standard, or other actions will provide reasonable assurance of the
effectiveness of the transilluminator for breast evaluation. FDA
believes that use of the transilluminator for breast evaluation
presents a potential health risk because of the possibility of
misdiagnosis. The evident failure of transilluminator evaluations to
detect breast cancer in its earliest stages, when the chance for a cure
is highest, requires FDA to place this preamendment device in class III
in order to require manufacturers to provide data establishing
reasonable assurance of the device's safety and effectiveness.
FDA concurs with the Obstetrics and Gynecology Devices Panel's
recommendation that the agency should give high priority to a
regulation to establish premarket approval requirements for the
transilluminator because of the public health considerations involved.
Since the Obstetrics and Gynecology Devices Panel meeting of
January 1991, FDA has warned manufacturers of breast transillumination
devices that these devices are in violation of the act because their
labeling is false or misleading and fails to bear adequate direction
for use under section 502(a) and (f)(1) of the act (21 U.S.C. 352(a)
[[Page 3170]] and (f)(1)). FDA took this position following the
Obstetrics and Gynecology Devices Panel meeting, after considering the
Obstetrics and Gynecology Devices Panel's recommendation, after further
evaluation of the available scientific literature, and following
further consultation with outside medical experts. FDA concluded that
the transillumination devices are not clinically effective for the
diagnosis or detection of breast cancer or other breast abnormalities
or conditions, and that the use of the technique may contribute to the
delay of detection of lesions in the early stages of cancer, when the
disease is most treatable.
At this time, therefore, the distribution of breast
transillumination devices or any multipurpose transillumination device
that is labeled, promoted, or intended for use in the breast is in
violation of the law, regardless of whether the device is labeled for
independent use or adjunctive use with mammography. FDA has initiated
enforcement actions against manufacturers who have continued to
distribute transilluminators.
When these devices become subject to the premarket approval
process, the manufacturer of each individual device will have an
opportunity to demonstrate the safety and effectiveness of the device
for its indicated use. Any further decision on adjunctive use versus
stand alone use will be based on valid scientific data presented by
manufacturers in the PMA's they submit at that time.
FDA intends to publish pursuant to section 515(b) of the act, a
proposed rule to establish the effective date of the requirement for
premarket approval for transilluminators. Such a rule will be published
after the effective date of a final classification regulation based on
this proposed rule. A PMA may be required 30 months after the effective
date of the final rule classifying the device in class III under
section 513 of the act or 90 days after publication of the final rule
requiring premarket approval under section 515(b), whichever is later.
After the establishment of an effective date for the requirement of PMA
submissions for these devices, any transilluminators for use on breast
tissue that are being marketed without a PMA will be considered
adulterated under section 501(f)(2) of the act (21 U.S.C. 351(f)(2).
However, as noted earlier, FDA has determined, in light of scientific
data that has become available, that transilluminators for use in the
breast are already misbranded under sections 502(a) and 502(f)(1) of
the act and should not be marketed at this time.
FDA concludes that because the transilluminator is a diagnostic
imaging device, it would be more appropriately classified as a
radiological device. The agency therefore proposes to classify it in
part 892 (21 CFR part 892) of the regulations (radiology devices)
instead of part 884 (21 CFR part 884) of the regulations (obstetrical
and gynecological devices).
IV. References
The following references have been placed on display in the Dockets
Management Branch (address above) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
1. ``Transillumination Not Effective for Early Breast Cancer
Detection,'' National Cancer Institute, Office of Cancer
Communications, September 1990.
2. ``Breast Cancer Diagnosis by Lightscan (Revised),'' final
report, Grant No. CA37970-04, Myron Moskowitz, principal
investigator, Breast Imaging Center, University of Cincinnati
Medical Center, December 1989.
3. Alveryd, A. et al., ``Lightscanning Versus Mammography for
the Detection of Breast Cancer in Screening and Clinical Practice: A
Swedish Multicenter Study,'' Cancer (U.S.A.), vol. 65/8 1671-1677,
April 15, 1990.
4. Key, H., P. C. Jackson, and P. N. T. Wells, ``New Approaches
to Transillumination Imaging,'' Journal of Biomedical-Engineering,
vol. 10, No. 2, 113-118, 1988.
5. Zhou, X., and R. Gordon, ``Detection of Early Breast Cancer:
An Overview and Future Prospects,'' Critical Reviews in Biomedical
Engineering, vol. 17, issue 3, 230-232, 1989.
6. Adams, D. L., ``Reassessment of Transillumination Light
Scanning for the Diagnosis of Breast Cancer,'' National Center for
Health Services Research and Health Care Technology Assessment, U.S.
Department of Health and Human Services, Public Health Service,
Springfield, VA. Available from National Technical Information
Services, Health Technology Assessment Report; No. 2, 1988.
7. Hebden, J. C., and R. A. Kruger, ``Transillumination Imaging
Performance: A Time-of-Flight-Imaging System,'' Medical Physics,
vol. 17, No. 3, 1990.
8. Jarlman, O., R. Berg, and S. Svanberg, ``Time-Resolved
Transillumination of the Breast,'' Acta Radiological, vol. 33, 1992.
9. Key, H., E. R. Davies, P. C. Jackson, and P. N. T. Wells,
``Optical Attenuation Characteristics of Breast Tissue at Visible
and Near Infrared Wavelengths,'' Physics in Medicine and Biology,
vol. 36, No. 5, 1991.
10. Peters, V. G., D. R. Wyman, M. S. Patterson, and G. L.
Frank, ``Optical Properties of Normal and Diseased Human Breast
Tissue in the Visible and Near Infrared,'' Physics in Medicine and
Biology, vol. 35, No. 9, 1990.
11. Profio, A. E., G. A. Navarro, and O. W. Sartorius,
``Scientific Basis of Breast Diaphanography,'' Medical Physics, vol.
16, No. 1, 1989.
12. Key, H., E. R. Davies, P. C. Jackson, and P. N. T. Wells,
``Monte Carlo Modelling of Light Propagation in Breast Tissue,''
Physics in Medicine and Biology, vol. 36, No. 5, 1991.
13. Navarro, G. A., and A. Edward Profio, ``Contrast in
Diaphanography of the Breast,'' Medical Physics, 15(2), March/April
1988.
14. Watmough, D. J., ``Breast Compression to Increase the
Sensitivity of Lightscanning for the Detection of Carcinoma:
Potential Hazard?'' Letter to the editor, Journal of Biomedical
Engineering, vol. 14, March 1992.
15. Economou, S. G. et al., eds., Imaging Techniques in Adjuncts
to Cancer Surgery. Lea and Febiger, 51-126, 1991.
16. ``Is Lightscanning a Viable Alternative to Mammography for
Detecting Breast Cancer?'' in News Briefs, New York State Journal of
Medicine, June 1990.
17. Jarlman, O., I. Anderson, G. Balldin, and S. A. Larsson,
``Diagnostic Accuracy of Lightscanning and Mammography in Women with
Dense Breasts,'' Acta Radiological 33, fasc. 1, 1992.
18. He, Ping, Kaneko, Maseo, et al., ``Breast Cancer Diagnosis
by Laser Transmission Photo-scanning with Spectro-Analysis'' (Report
4), Radiation Medicine, vol. 8 No. 1, 1-5, 1990.
19. Braddick, M. R., ``Audit of a Breast Cancer Screening
Programme Using Clinical Examination and Lightscanning,'' Health
Bulletin 49/6 299-303, November 1991.
20. Gordenne, W., and E. Bauduin, ``Diagnostic Accuracy of New
Imaging Techniques in Breast Diseases,'' Journal Belge de
Radiologie, 72:35-38, 1989.
21. Heywang-Kobrunner, ``Nonmammographic Breast Imaging
Techniques,'' Current Opinion in Radiology, vol. 4, 146-154, 1992.
22. Jarlman, O. et al., ``Relation Between Lightscanning and the
Histologic and Mammography Appearance of Malignant Breast Tumors,''
Acta Radiological 33, 63-68, fasc. 1992.
23. Monsees, B., J. M. Destouet, and D. Gersell, ``Lightscanning
of Monpalpable Breast Lesions: Reevaluation,'' Radiology, 167:352,
1988.
24. Obstetrics and Gynecology Devices Obstetrics and Gynecology
Panel, Forty-fifth Meeting. Transcript and Meeting Minutes, January
11, 1991.
V. Environmental Impact
The agency has determined under 21 CFR 25.24(e)(2) 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.
VI. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354).
Executive Order 12866 directs agencies to assess all costs and benefits
of available regulatory alternatives and, when regulation is necessary,
to select regulatory [[Page 3171]] 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 proposed rule is consistent with the
regulatory philosophy and principles identified in the Executive Order.
In addition, the proposed rule is not a significant regulatory action
as defined by the Executive Order and so is not subject to review 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 the agency believes only a small number of
firms will be affected by this rule when finalized, the agency
certifies that the proposed rule will not have a significant economic
impact on a substantial number of small entities. Therefore, under the
Regulatory Flexibility Act, no further analysis is required.
VII. Request for Comments
Interested persons may, on or before April 13, 1995, submit to the
Dockets Management Branch (address above) written comments regarding
this proposal. Two copies of any comments are to be submitted except
that individuals may submit one copy. Comments are to be identified
with the docket number found in brackets in the heading of this
document. Received comments may be seen in the office above between 9
a.m. and 4 p.m., Monday through Friday.
List of Subjects in 21 CFR Part 892
Medical devices, Radiation protection, X-rays.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 892 be amended as follows:
PART 892--RADIOLOGY DEVICES
1. The authority citation for 21 CFR part 892 continues to read as
follows:
Authority: Secs. 501, 510, 513, 520, 701 of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 351, 360, 360c, 360e, 360j, 371).
2. New Sec. 892.1990 is added to subpart B to read as follows:
Sec. 892.1990 Transilluminator for breast evaluation.
(a) Identification. A transilluminator, also known as a
diaphanoscope or lightscanner, is an electrically powered device that
uses low intensity emissions of visible light and near-infrared
radiation (approximately 700-1050 nanometers (nm)), transmitted through
the breast, to visualize translucent tissue for the diagnosis of
cancer, other conditions, diseases or abnormalities.
(b) Classification. Class III (premarket approval).
(c) Date premarket approval (PMA) or notice of completion of a
product development protocol (PDP) is required. The effective date of
the requirement for premarket approval has not been established. See
Sec. 892.3.
Dated: December 23, 1994.
D.B. Burlington,
Director, Center for Devices and Radiological Health.
[FR Doc. 95-971 Filed 1-12-95; 8:45 am]
BILLING CODE 4160-01-F