[Federal Register Volume 62, Number 242 (Wednesday, December 17, 1997)]
[Rules and Regulations]
[Pages 66003-66005]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-32876]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. 95P-0136]
Medical Devices; Reclassification of Tumor-Associated Antigen
Immunological Test Systems
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing that it
is codifying the reclassification of tumor-associated antigen
immunological test systems intended as an aid in monitoring patients
for disease progression or response to therapy or for the detection of
recurrent or residual disease from class III (premarket approval) to
class II (special controls). FDA is also announcing that it has issued
an order in the form of a letter to Centocor, Inc., reclassifying serum
tumor markers into class II. This action is being taken under the
Federal Food, Drug, and Cosmetic Act (the act), as amended by the
Medical Device Amendments of 1976 and the Safe Medical Devices Act of
1990.
EFFECTIVE DATES: The reclassification was effective September 19, 1996.
The codification becomes effective December 17, 1997.
FOR FURTHER INFORMATION CONTACT: Joseph M. Sheehan, Center for Devices
[[Page 66004]]
and Radiological Health (HFZ-215), Food and Drug Administration, 1350
Piccard Dr., Rockville, MD 20850, 301-827-2974.
SUPPLEMENTARY INFORMATION:
I. Background
On April 18, 1995, FDA filed a petition submitted by Centocor,
Inc., requesting reclassification from class III to class II of tumor-
associated antigen immunological test systems, commonly called serum
tumor markers, indicated for use in the monitoring of tumor-associated
antigen levels in patient serum samples. The tumor-associated antigen
immunological test system was a class III ``transitional'' device under
section 520(l) of the act (21 U.S.C. 360j(l)). The petition, was
seeking reclassification under the procedures set forth in section
520(l)(2) of the act and 21 CFR 860.136 of the agency's regulations.
FDA consulted with the Immunology Devices Panel (the Panel). During
the open public meeting on December 1, 1995, the Panel recommended that
FDA reclassify the tumor-associated antigen immunoassay systems for use
in monitoring from class III to class II. It further recommended that
those tumor markers used for screening indications remain in class III.
Based on its consultation with the Panel, review of the data and
information contained in the petition and presented before the Panel,
published studies and professional standards, FDA concurred with the
Panel's recommendation that tumor-associated antigen immunoassay
systems should be reclassified from class III into class II with
implementing special controls. FDA further concurred that markers used
for screening indications will remain in class III.
On September 19, 1996, FDA issued an order (Ref. 1) in the form of
a letter to Centocor, Inc., reclassifying the generic type of device,
tumor-associated antigen immunological test systems intended as an aid
in monitoring patients for disease progression or response to therapy
or for the detection of recurrent or residual disease, from class III
to class II. The order identified the generic type of tumor-associated
antigen immunological test system as a device that consists of the
reagents used to qualitatively or quantitatively measure, by
immunochemical techniques, tumor-associated antigens in serum, plasma,
urine, or other body fluids. This generic type of device does not
include tissue receptor assays, immunohistochemical stains, or direct
tests for oncogenes or other genetic markers associated with a
predisposition to development of certain cancers.
Measurement of tumor-associated antigen levels aid in the
monitoring of certain cancers. Monitoring is defined here as assessing
disease progression, recurrence, or response to therapy. This includes
the serial measurement of antigens in patients with histologically
confirmed diagnoses who are undergoing therapy for residual or advanced
disease. Increasing tumor marker concentrations are indicative of
progressive disease, decreasing concentrations are indicative of
response to therapy, and constant serial tumor marker concentrations
are associated with a stable disease state. Monitoring is further
defined as single or serial measurements used as an aid in the
detection of recurrent or residual disease in patients following
primary curative treatment. Sustained elevations in marker
concentrations are suggestive of residual disease, whereas increasing
concentrations are indicative of recurring disease.
The order also identified FDA's designated special controls as a
premarket notification, section 510(k) (21 U.S.C. 360(k)), guidance
document for tumor-associated antigens (Ref. 2), and existing voluntary
standards for assay performance by the National Committee for Clinical
Laboratory Standards (the NCCLS) (Ref. 3). The guidance document
provides the review criteria and data requirements for a 510(k)
submission. The guidance document also provides suggestions for non-
clinical laboratory studies and the design, conduct, and analysis of
appropriate clinical studies to support the performance of these
devices. The NCCLS assay performance standards provide evaluative
techniques to assure the accurate performance of the antigen tests. FDA
believes that these special controls provide the necessary control to
reasonably assure the safety and effectiveness of these devices.
FDA notes that the risks associated with the use of tumor markers
are relatively low in comparison to the benefits that result from their
use for patient monitoring. Furthermore, the risks and benefits
associated with the use of tumor markers in the practice of medical
oncology are well understood by clinicians. The use and performance
characteristics of these devices have been addressed in thousands of
peer-review scientific reports and the evaluative techniques used to
establish acceptable performance are well described and referenced in
the special controls. Additionally, FDA has 20 years of scientific
review experience to draw upon in the evaluation of new tumor markers,
and believes that tumor antigen immunoassay systems are well
characterized.
Consistent with the act and the regulations, FDA is announcing that
on September 19, 1996, an order in the form of a letter was sent to
Centocor, Inc., reclassifying the generic type tumor-associated antigen
immunoassay system that is intended as an aid in monitoring patients
for disease progression or response to therapy or for the detection of
recurrent or residual disease from class III to class II. Additionally,
FDA is codifying the reclassification of this device, by amending 21
CFR 866.6010.
II. 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.
III. Analysis of Impacts
FDA has examined the impacts of this final rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612) (as
amended by subtitle D of the Small Business Regulatory Fairness Act of
1996 (Pub. L. 104-121)), and the Unfunded Mandates Reform Act of 1995
(Pub. L. 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 consistent with
the regulatory philosophy and principles identified in the Executive
Order. In addition, the final 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. Reclassification of this devices from class III to
class II will relieve manufacturers of the device of the cost of
complying with the premarket approval requirements of section 515 of
the act (21 U.S.C. 360e), and may permit small potential competitors to
enter the marketplace by lowering their costs. The Commissioner of Food
and Drugs, certifies that this final rule will not have a significant
economic impact on a
[[Page 66005]]
substantial number of small entities. This final rule also does not
trigger the requirement for a written statement under section 202(a) of
the Unfunded Mandates Reform Act because it does not impose a mandate
that results in an expenditure of $100 million of more by State, local,
or tribal governments in the aggregate, or by the private sector, in
any 1 year.
IV. References
The following references have been placed on display in the
Dockets Management Branch (HFA-305), Food and Drug Administration,
12420 Parklawn Dr., rm. 1-23, Rockville, MD 20857, and may be seen
by interested persons between 9 a.m. and 4 p.m., Monday through
Friday.
1. FDA letter (order) to Centocor, Inc., dated September 19,
1996.
2. Guidance Document for the Submission of Tumor Associated
Antigen Premarket Notifications (510(k)) to FDA, September 19, 1996.
3. The National Committee for Clinical Laboratory Standards:
Document EP5-T2, Evaluation of Precision Performance of Clinical
Chemistry Devices; Document EP9-A, Method Comparison and Bias
Estimation Using Patient Samples; Document EP7-P, Interference
Testing in Clinical Chemistry.
List of Subjects in 21 CFR Part 866
Medical Devices.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
866 is amended as follows:
PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES
1. The authority citation for 21 CFR part 866 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
2. Section 866.6010 is revised to read as follows:
Sec. 866.6010 Tumor-associated antigen immunological test system.
(a) Identification. A tumor-associated antigen immunological test
system is a device that consists of reagents used to qualitatively or
quantitatively measure, by immunochemical techniques, tumor-associated
antigens in serum, plasma, urine, or other body fluids. This device is
intended as an aid in monitoring patients for disease progress or
response to therapy or for the detection of recurrent or residual
disease.
(b) Classification. Class II (special controls). Tumor markers must
comply with the following special controls: (1) A guidance document
entitled ``Guidance Document for the Submission of Tumor Associated
Antigen Premarket Notifications (510(k)s) to FDA,'' and (2) voluntary
assay performance standards issued by the National Committee on
Clinical Laboratory Standards.
Dated: November 6, 1997.
Joseph A. Levitt,
Deputy Director for Regulations Policy, Center for Devices and
Radiological Health.
[FR Doc. 97-32876 Filed 12-16-97; 8:45 am]
BILLING CODE 4160-01-F
