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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:

1. 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.
    
2. 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.
    
3. 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

Updated June 29, 2004