[Federal Register Volume 60, Number 144 (Thursday, July 27, 1995)]
[Rules and Regulations]
[Pages 38480-38482]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-18446]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
21 CFR Part 866
[Docket No. 91N-0063]
Immunology and Microbiology Devices; Revocation of the Exemption
From Premarket Notification; Blood Culturing System Devices
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is revising the
microbial growth monitor classification regulation by revoking the
exemption from the premarket notification requirements for automated
blood culturing system devices used in testing blood and other normally
sterile body fluids for bacteria, fungi, and other microorganisms.
Revocation of the exemption is necessary because of the importance of
these devices in providing rapid diagnosis of potentially life-
threatening conditions. Devices using traditional manual methods
employing turbidity measurements or direct counts, included under this
classification regulation, will continue to be exempt from the
requirement of premarket notification.
DATES: The final rule is effective October 25, 1995. A premarket
notification submission is required for any automated blood culturing
system intended to be introduced or delivered for introduction into
commerce on or after October 25, 1995, under section 510(k) of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360(k)), and the
procedures in subpart E of 21 CFR part
[[Page 38481]]
807. A manufacturer or an initial distributor of an imported blood
culturing device that has already begun commercial distribution under
the existing exemption from premarket notification is required to
submit a premarket notification on or before October 25, 1995 and must
have a premarket notification cleared by FDA by April 22, 1996.
FOR FURTHER INFORMATION CONTACT: Joseph M. Sheehan, Center for Devices
and Radiological Health (HFZ-84), Food and Drug Administration, 2094
Gaither Rd., Rockville, MD 20850, 301-594-4765, Ext. 157.
SUPPLEMENTARY INFORMATION:
I. Background
Blood culturing system devices are diagnostic devices used in
clinical settings to detect the presence or growth of bacteria, fungi,
or other microorganisms from blood samples or from samples of other
body fluids that are normally sterile. The process involves testing for
these microorganisms by inoculating the patient's sample directly into
broth media or by inoculating a processed sample concentrate onto agar
media. Microbial growth is monitored either by traditional manual
methods (visual inspection, microscopic evaluation, and/or
subculturing) or by instrument-assisted (automated) monitoring of
microbial metabolic activities, such as the detection of increased
presence of carbon dioxide or changes in fluorescence, bioluminescence,
or ATPase activities.
In the Federal Register of November 9, 1982 (47 FR 50814 at 50826),
FDA classified blood culturing system devices into class I (21 CFR
866.2560). In the Federal Register of June 12, 1989 (54 FR 25042 at
25046), FDA published a final rule exempting microbial growth monitors,
subject to certain limitations, from the requirement of premarket
notification. In the Federal Register of April 26, 1991 (56 FR 19333),
FDA proposed to revoke this exemption for blood culturing system
devices because of safety and effectiveness considerations. FDA
determined, on reconsideration, that blood culturing system devices do
not meet the criteria for exemption identified in the regulation
published in the Federal Register of June 12, 1989.
Although current efforts have been directed toward streamlining the
regulation of in vitro diagnostic devices, FDA's revocation of the
blood culturing system devices exemption is necessary because it is
based on significant safety and effectiveness considerations.
Subsequent to June 12, 1989, through the medical/scientific
literature, FDA became aware of a significant number of problems
related to these devices. These problems include: (1) Failure of media
to support growth of certain organisms; (2) false negative and false
positive results; and (3) cross contamination of cultures. Also, in the
early 1990's, the use of instrument assisted microbial growth monitors,
originally intended for blood culturing, started to be commonly used to
detect, recover, and provide a complete panel of susceptibility results
for Mycobacterium tuberculosis.
Since these devices are relied upon for rapid diagnosis of
bacterial or fungal infection, and are commonly used to detect,
recover, and determine susceptibility of Mycobacterium tuberculosis,
the reported failure of these devices raises significant questions of
safety and effectiveness. Bacterial or fungal infections of the
bloodstream may be life-threatening. Tuberculosis is a disease of
serious health consequences for the patient and its potential for quick
dissemination is a very significant public health concern. Malfunction
of these devices, therefore, could result in misdiagnosis and
mistreatment, thus endangering patients, health care professionals, and
the public at large.
Because of safety and effectiveness concerns presented by the
device, FDA believes it is necessary to revoke the exemption from the
premarket notification procedures to enable FDA to monitor the
introduction into commerce, by manufacturers and importers, of
automated blood culturing system devices, and to determine whether the
devices are as safe and effective as legally marketed devices. Devices
using traditional manual methods employing visual turbidity measurement
or direct counts are not affected by this final regulation.
FDA provided interested persons 60 days to submit written comments
on the proposal. FDA received two comments. A summary of these comments
and FDA's responses follows:
1. One comment requested clarification of the continued exemption
for traditional culture media used with manual blood culture methods.
The comment suggested that the amended section contain language that
makes it clear that traditional manual blood culture bottles in which
microbial growth is detected by visual reading and conventional
subculturing techniques are not affected by the revocation of the
exemption.
FDA agrees with this suggestion. Conventional media dispensed in
blood culture bottles (20 to 100 milliliter volume) with limited entry
seals that are used only with conventional manual blood culture
procedures (visual observation for signs of microbial growth and
routine subcultures and/or microscopic screening for presence of
bacteria and fungi) are not dependent on instrument-based monitoring
for detection of signs of microbial growth. However, media bottles used
with the automated system are an integral part of the system;
therefore, any new or modified media to be used with an automated blood
culturing system are also subject to the revocation.
2. A second comment objected to the continued exemption for blood
culture systems not using automated instrumentation.
FDA disagrees with the comment. Current traditional manual blood
culturing methods use media formulations and techniques that have been
in use for many years. The types of media used are often commercialized
for blood culturing by manual procedures developed and controlled by
individual laboratories. In contrast, devices or systems that specify
incubation and observation procedures based on a combination of
different media or for use with a monitoring component (other than
visual inspection for evidence of microbial growth and routine
subculture to solid media and microscopic examination) are not exempt
from premarket notification.
Closed systems that exclude routine microscopic examination and
subcultures would also be considered a microbial growth monitor and
would be subject to the revocation. Similarly, any media bottle
designed to be used with a microbial growth monitor (blood culture
instrument or detection mechanism other than direct observation/
subculture/microscopic inspection) for detection of microorganisms from
patient specimens would be considered a component of the microbial
growth monitor and also subject to the revocation.
II. References
The following information has been placed on display in the Dockets
management Branch (HFA-350), Food and Drug Administration, rm. 1-24,
12420 Parklawn Dr., Rockville, MD 20857, and may be seen by interested
persons between 9 a.m. and 4 p.m., Monday through Friday.
1. Aronson, M. D., and D. H. Bor, ``Blood Cultures,'' Annals of
Internal Medicine, 106:246-253, 1987.
2. Thorpe, T. C., et al., ``BacT/Alert: An Automated Calorimetric
Microbial Detection System,'' Journal of Clinical Microbiology,
28:1608-1612, 1990.
[[Page 38482]]
3. Wallis, C., and J. L. Melnick, ``Rapid, Calorimetric Method for
the Detection of Microorganisms in Blood Culture,'' Journal of Clinical
Microbiology, 21:505-508, 1985.
4. Washington, II, J. A., and D. M. Ilstrue, ``Blood Cultures:
Issues and Controversies,'' Reviews of Infectious Diseases, 8:792-802,
1986.
5. Welch, W. D., et al., ``Variability in CO2, O2, and pH
levels in Blood Culture Bottles from Five Different Manufacturers,''
Journal of Clinical Microbiology, 20:881-883, 1984.
III. Environmental Impact
The agency has determined under 21 CFR 25.24(a)(8) and (a)(10)
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.
IV. Analysis of Impacts
FDA has examined the impact of the final 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 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. Because this final rule revokes an exemption and
places manufacturers of these devices on a level with manufacturers of
other devices, the agency certifies that the final 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 on small entities.
List of Subjects in 21 CFR Part 866
Biologics, Laboratories, 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: Secs. 501, 510, 513, 515, 520, 701 of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 351, 360, 360c, 360e, 360j,
371).
2. Section 866.2560 is amended by revising paragraph (b) to read as
follows:
Sec. 866.2560 Microbial growth monitor.
* * * * *
(b) Classification. Class I. With the exception of automated blood
culturing system devices that are used in testing for bacteria, fungi,
and other microorganisms in blood and other normally sterile body
fluids, this device is exempt from the premarket notification
procedures in subpart E of part 807 of this chapter.
Dated: July 18, 1995.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 95-18446 Filed 7-26-95; 8:45 am]
BILLING CODE 4160-01-F