[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