Letter to Manufacturers of Antimicrobial Susceptibility Tests
VIA FED-EX
June 23rd, 2004
ADDRESS (List of recipients)
To Manufacturers of Antimicrobial Susceptibility Tests:
The Food and Drug Administration (FDA) and the Center for Disease Control and
Prevention (CDC) have become aware of a third documented clinical isolate of
vancomycin-resistant Staphylococcus aureus (VRSA) from a patient in
the United States (MMWR-April 23, 2004/ 53(15);322-323 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5315a6.htm).
Followup investigations with this isolate showed inconsistent detection of vancomycin
resistance by commercial automated susceptibility systems and raised the concern
that additional VRSA infections may occur and be missed when these systems are
used for reporting S. aureus resistance and susceptibility profiles.
Until automated and other commercial systems can be evaluated for reliability
with relevant organisms, clinical laboratories performing such testing should
be aware of this potential shortcoming of these systems and should use methods
that have been shown to reliably detect the strains that have been described.
At present, non-automated MIC methods (e.g., broth microdilution or agar dilution)
with a full 24-hours incubation before reading results are recommended. The
CDC previously reported that BHI agar supplemented with 6 ug/mL vancomycin is
useful for detecting staphylococci with reduced susceptibilities to vancomycin
(JCM 1998; 36:1020-7) and that this method is also reliable with the three recognized
VRSA isolates.
Because failure to detect VRSA is a significant clinical and public health
concern, the FDA is requesting that manufacturers of disc diffusion tests and
commercial automated antimicrobial susceptibility test devices take the following
actions to minimize the risk of failing to reliably detect VRSA:
- Immediately notify users via facsimile followed by a certified return receipt
requested letter of the need to use additional testing methods to enhance
capability of detecting vancomycin-resistant S. aureus, within 15
days of receipt of the facsimile of this letter.
- Within 30 days, send Warning/Caution labels to all customers; these labels
are to be affixed to the product/package. These labels will state that the
ability to detect VRSA is unknown and additional testing methods should be
used. An alternate method as recommended by CDC should be followed.
- Relabel future package inserts to state that the device should not be used
for detection of vancomycin resistance in S. aureus. Modify the Limitations
section of the package insert to clearly state this device limitation (e.g.,
not evaluated for detection of VRSA).
This revision to your labels and labeling should be made at the next printing
but no later than 6 months from the date of this letter. In addition, this labeling
change must be documented in your files but does not need to be submitted in
a new premarket notification (510(k)) application. See 21 CFR Part 820. Please
contact the District Office in your area regarding these labeling changes.
If you have any questions concerning these FDA requested actions including
the implementation of these labeling modifications please contact James L. Woods,
Deputy Director for Patient Safety and Product Quality, Office of In Vitro Diagnostic
Device Evaluation and Safety (OIVD), at (301) 594-2096.
A manufacturer may wish to evaluate its systems for reliability in detecting
VRSA when more strains become available. If this is the case, then you should
submit a new 510(k) and receive FDA clearance for this use. Please note, however,
that at this time there are insufficient numbers of VRSA strains to demonstrate
the reliable ability to detect vancomycin-resistance in S. aureus with
commercial systems.
Please respond in writing within 15 days of the date of this communication,
stating how you will modify your labeling and notify users (including the time
frame and a draft of the notification letter). Please cite your application
numbers and respond to:
Attn: James L. Woods
Food and Drug Administration
Center for Devices and Radiological Health
Office of In Vitro Diagnostic Device Evaluation and Safety
2098 Gaither Road
Rockville, MD 20850
We trust that a cooperative effort between FDA, CDC, and device manufacturers
will assure that effective devices will be available to users for detecting
bacterial resistance and assure recognition of the presence of resistant strains
to facilitate therapy, surveillance, and control measures. Failure to include
complete warnings, precautions, and limitations in the labeling of an IVD device
can result in noncompliance with 21 CFR 809.10 and may result in further action
being initiated by FDA without further notice.
If you have any technical questions concerning the contents of this letter
please contact Sally Selepak at (301)594-2096.
Sincerely yours,
/ S /
Steven I. Gutman, M.D., M.B.A.
Director
Office of In Vitro Diagnostic Device Evaluation and
Safety
Center for Devices and Radiological Health
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