(245 days)
Not Found
No
The device description outlines a purely chemical and manual process for detecting carbapenemase enzymes based on a color change reaction. There is no mention of any computational analysis, image processing, or algorithmic interpretation of results, which are typical indicators of AI/ML involvement in diagnostic devices.
No
Explanation: The device is an in vitro diagnostic test for detecting carbapenemase enzymes, which aids in preventing and controlling infection. It is explicitly stated that the device is "not intended to guide or monitor the treatment for these bacterial infections," indicating that it does not directly treat or prevent disease, which is the definition of a therapeutic device.
Yes
The device "RAPIDEC® CARBA NP" is explicitly stated as an "in vitro diagnostic test for the qualitative detection of carbapenemase enzymes". It is also intended as an "aid in the prevention and control of infection".
No
The device description clearly outlines a physical test strip with wells containing reagents and accessories for performing a chemical reaction, indicating it is a hardware-based in vitro diagnostic test, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "RAPIDEC® CARBA NP is a phenotypic (colorimetric) in vitro diagnostic test for the qualitative detection of carbapenemase enzymes..."
This statement clearly identifies the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
RAPIDEC® CARBA NP is a phenotypic (colorimetric) in vitro diagnostic test for the qualitative detection of carbapenemase enzymes in Enterobacteriaceae and Pseudomonas aeruginosa colonies that have elevated MIC values to any carbapenem. RAPIDEC® CARBA NP is performed on pure colonies grown on non-selective sheep blood agar culture media.
RAPIDEC® CARBA NP is intended as an aid in the prevention and control of infection caused by carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa.
RAPIDEC® CARBA NP is not intended to guide or monitor the treatment for these bacterial infections. A negative result does not preclude the presence of carbapenemase enzymes. The ability of RAPIDEC® CARBA NP to detect carbapenemase enzymes encoded by genetic markers other than KPC, NDM, OXA-48, VIM, and IMP has not been established. RAPIDEC® CARBA NP testing should be used in conjunction with other laboratory tests including antimicrobial susceptibility testing.
Product codes (comma separated list FDA assigned to the subject device)
PTJ
Device Description
The RAPIDEC® CARBA NP strip is composed of 5 wells prepared with premeasured portions of the necessary substrates for the reactions. In addition, the kit contains the necessary accessories for performing the test.
In order to rehydrate the dry reagents and initiate the reactions, wells a, b and c are filled with 100 uL of API Suspension Medium (purified water). The strip is left at room temperature for 4-10 minutes to allow the dry reagents to reconstitute in the wells. The bacterial inoculum suspension is prepared in well c until the turbidity equals well b. Well c contains the lysis buffer. In order to achieve lysis of the inoculum suspension, which enables the extraction of the enzyme, the strip is left at room temperature for additionally 30 minutes.
As the next step, 25 uL of the lysed inoculum suspension is transferred to wells d and e and 25 µL from well a (phenol red solution) is also transferred to wells d and e. The strip is incubated for 30 minutes at 33-38°C to allow for the hydrolysis to occur and change in color of the phenol red solution in case of presence of a carbapenemase enzyme. The initial reading is performed after 30 minutes of incubation. In case of a negative or doubtful reaction, the strip is re-incubated for an additional 1 hour and 30 minutes before performing the final reading.
The hydrolysis acidifies the medium which results in the change in color of the pH indicator. Reading is performed by comparing the colors in wells d and e. The test is positive when a significant variation in color is observed between the two wells. For example, the control well is red and the test well has changed to yellow.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Non-clinical (analytical) and clinical studies were performed for RAPIDEC® CARBA NP.
Analytical Performance:
- Quality Control: Two quality control organisms, Klebsiella pneumoniae ATCC® BAA-1705™ (positive) and Klebsiella pneumoniae ATCC® BAA-1706™ (negative), were tested daily at each study site. Results met pre-defined acceptance criteria (≥95% agreement) with expected results.
- Analytical Reactivity (Challenge testing): 43 carbapenemase producers (2 VIM P. aeruginosa, 41 carbapenemase-producing Enterobactericeae including 16 KPC, 10 NDM, 7 OXA-48, 5 VIM, and 3 IMP) were tested. An initial reading was at 30 minutes, and final reading at 2 hours (33-38°C incubation) if initial was negative.
- All 43 strains were detected positive, yielding an analytical sensitivity of 100% (43/43).
- Four negative results at 30 minutes became positive at 2 hours; eight initial positive results changed to negative at 2 hours.
- Cross-reactivity: 93 non-carbapenemase-producing strains with elevated carbapenem MICs were tested. This included 67 strains related to intended use (59 Enterobacteriaceae, 8 P. aeruginosa) and 26 other organisms.
- Analytical specificity was 97.9% (91/93) at 30 minutes (due to two intrinsic resistant Stenotrophomonas maltophilia).
- Analytical specificity was 93.6% (87/93) at 2 hours (1 AmpC-producing Morganella morganii, 3 intrinsic resistant Stenotrophomonas maltophilia, 1 Burkholderia cepaciae, 1 Sphingomonas paucimobilis gave positive reactions).
- For intended Enterobacteriaceae and Pseudomonas aeruginosa strains, analytical specificity was 100% (67/67) at 30 minutes and 98.5% (66/67) at 2 hours (due to AmpC-producing Morganella morganii).
- Agar Culture Media Compatibility Studies: RAPIDEC® CARBA NP results using strains isolated on Columbia agar + 5% sheep blood (COS) were compared with those on Trypticase Soy agar + 5% sheep blood (TSS). A total of 106 strains (92 carbapenemase producers and 14 non-carbapenemase producers) were tested.
- Positive rate for carbapenemase producers: 94.6% (87/92) for TSS and 92.4% (85/92) for COS at 30 minutes.
- Positive rate for carbapenemase producers: 98.9% (91/92) for both media at 2 hours.
- Negative rate for non-carbapenemase producers: 100% for both media at 30 minutes and 2 hours.
- No significant differences observed between TSS and COS.
Clinical Studies:
- Study Type: Clinical study across 5 sites using routine and short subculture procedures.
- Sample Size: 457 strains (394 Enterobacteriaceae and 63 P. aeruginosa).
- Reference Method: Carbapenemase determination by a composite reference method: carbapenem MIC (Imipenem, Meropenem, Ertapenem and/or Doripenem), CLSI® Carba NP, and carbapenemase genetic markers by Polymerase Chain Reaction (PCR). Final composite result based on agreement of at least two of the three tests.
- Key Results:
- Comparative Performance (All samples):
- Routine Subculture: Agreement 98.7% (451/457). False Positives: 5 (2.6%). False Negatives: 1 (0.4%).
- Short Subculture: Agreement 98.0% (440/449). False Positives: 5 (2.7%). False Negatives: 4 (1.5%).
- Performance with Carbapenemase Genetic Markers:
- For all samples, routine subculture agreement was 98.7% (451/457) and short subculture agreement was 98.0% (440/449).
- For positive samples (routine subculture): 99.6% (264/265). False negative was 1 KPC-producing Enterobacteriaceae.
- For positive samples (short subculture): 98.5% (257/261). False negatives were 1 each for KPC, NDM, VIM, and OXA-48 from Enterobacteriaceae.
- For negative samples (routine subculture): 97.4% (187/192). False positives were 5 Enterobactericeae.
- For negative samples (short subculture): 97.3% (183/188). False positives were 5 Enterobacteriaceae.
- Insufficient growth for 6 P. aeruginosa and 2 K. pneumoniae in short subculture procedure.
- Comparative Performance (All samples):
- Reproducibility: A panel of 9 Enterobacteriaceae and 1 P. aeruginosa (4 negative, 6 positive carbapenemases) subcultured on sheep blood agar. Performed in triplicates for 5 days at 3 sites by 2 blinded operators.
- Routine subculture: 98.2% (884/900).
- Short subculture: 99.1% (892/900).
- Conclusion: The studies support that RAPIDEC® CARBA NP is substantially equivalent to the composite reference method.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Analytical Sensitivity: 100% (43/43)
Analytical Specificity:
- 97.9% (91/93) at 30 minutes incubation (all strains)
- 93.6% (87/93) at 2 hours incubation (all strains)
- 100% (67/67) at 30 minutes incubation (intended strains)
- 98.5% (66/67) at 2 hours incubation (intended strains)
Clinical Performance (Agreement to Composite Reference Method):
- Routine Subculture: 98.7% agreement (451/457)
- False Positive Rate: 2.6% (5/192)
- False Negative Rate: 0.4% (1/265)
- Short Subculture: 98.0% agreement (440/449)
- False Positive Rate: 2.7% (5/188)
- False Negative Rate: 1.5% (4/257)
Reproducibility:
- Routine Subculture: 98.2% (884/900)
- Short Subculture: 99.1% (892/900)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Clearview® Exact PBP2a Test (K091766)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).
0
Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an image of three faces in profile, stacked on top of each other.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
April 27, 2017
BIOMERIEUX SA ASA KARLSSON SR. MANAGER, REGULATORY AFFAIRS MICROBIOLOGY 5 RUE DES AQUEDUCS CRAPONNE 69290 FRANCE
Re: K162385
Trade/Device Name: RAPIDEC CARBA NP Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: II Product Code: PTJ Dated: March 27, 2017 Received: March 28, 2017
Dear Ms. Karlsson:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Ribhi Shawar -A
For
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K162385
Device Name RAPIDEC® CARBA NP
Indications for Use (Describe)
RAPIDEC® CARBA NP is a phenotypic (colorimetric) in vitro diagnostic test for the qualitative detection of carbapenemase enzymes in Enterobacteriaceae and Pseudomonas aeruginosa colonies that have elevated MIC values to any carbapenem. RAPIDEC® CARBA NP is performed on pure colonies grown on non-selective sheep blood agar culture media.
RAPIDEC® CARBA NP is intended as an aid in the prevention and control of infection caused by carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa.
RAPIDEC® CARBA NP is not intended to guide or monitor the treatment for these bacterial infections. A negative result does not preclude the presence of carbapenemase enzymes. The ability of RAPIDEC® CARBA NP to detect carbapenemase enzymes encoded by genetic markers other than KPC, NDM, OXA-48, VIM, and IMP has not been established. RAPIDEC® CARBA NP testing should be used in conjunction with other laboratory tests including antimicrobial susceptibility testing.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
|---|---|
| --------------------------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------- |
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3
SECTION 8. 510(k) SUMMARY
510(k) SUMMARY RAPIDEC® CARBA NP
510(k) Submission Information:
| Submitter's Name: | bioMerieux SA |
|---|---|
| Address: | 5 rue des Aqueducs |
| 69290 Craponne, France | |
| Contact Person: | Asa Karlsson |
| Regulatory Affairs Sr. Manager | |
| Phone Number: | +33 (0)6 48 61 68 49 |
| Fax Number: | +33 (0)4 78 87 76 65 |
| asa.karlsson@biomerieux.com |
Date of Preparation: July 29, 2016
Device:
| Formal/Trade Name: RAPIDEC® CARBA NP | |
|---|---|
| Classification: | II |
| Regulation Number: | 21 CFR 866.1640 |
| Regulation Name: | Antimicrobial Susceptibility Test Powder |
| Product Code: | PTJ |
| Common Name: | RAPIDEC® CARBA NP |
| Predicate Device: | Clearview® Exact PBP2a Test (K091766) |
510(k) Summary:
Intended use:
RAPIDEC® CARBA NP is a phenotypic (colorimetric) in vitro diagnostic test for the qualitative detection of carbapenemase enzymes in Enterobacteriaceae and Pseudomonas aeruginosa colonies that have elevated MIC values to any carbapenem. RAPIDEC® CARBA NP is performed on pure colonies grown on non-selective sheep blood agar culture media.
RAPIDEC® CARBA NP is intended as an aid in the prevention and control of infection caused by carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa.
4
RAPIDEC® CARBA NP
Traditional 510(k) Submission
RAPIDEC® CARBA NP is not intended to guide or monitor the treatment for these bacterial infections. A negative result does not preclude the presence of carbapenemase enzymes. The ability of RAPIDEC® CARBA NP to detect carbapenemase enzymes encoded by genetic markers other than KPC, NDM, OXA-48, VIM and IMP has not been established. RAPIDEC® CARBA NP testing should be used in conjunction with other laboratory tests including antimicrobial susceptibility testing.
Device Description:
The RAPIDEC® CARBA NP strip is composed of 5 wells prepared with premeasured portions of the necessary substrates for the reactions. In addition, the kit contains the necessary accessories for performing the test.
In order to rehydrate the dry reagents and initiate the reactions, wells a, b and c are filled with 100 uL of API Suspension Medium (purified water). The strip is left at room temperature for 4-10 minutes to allow the dry reagents to reconstitute in the wells. The bacterial inoculum suspension is prepared in well c until the turbidity equals well b. Well c contains the lysis buffer. In order to achieve lysis of the inoculum suspension, which enables the extraction of the enzyme, the strip is left at room temperature for additionally 30 minutes.
As the next step, 25 uL of the lysed inoculum suspension is transferred to wells d and e and 25 µL from well a (phenol red solution) is also transferred to wells d and e. The strip is incubated for 30 minutes at 33-38°C to allow for the hydrolysis to occur and change in color of the phenol red solution in case of presence of a carbapenemase enzyme. The initial reading is performed after 30 minutes of incubation. In case of a negative or doubtful reaction, the strip is re-incubated for an additional 1 hour and 30 minutes before performing the final reading.
The hydrolysis acidifies the medium which results in the change in color of the pH indicator. Reading is performed by comparing the colors in wells d and e. The test is positive when a significant variation in color is observed between the two wells. For example, the control well is red and the test well has changed to yellow.
Substantial Equivalence:
The similarities and differences of the RAPIDEC® CARBA NP when compared to the predicate device, Clearview® Exact PBP2a Test (K091766), are described in the following table.
| Item | Device:
RAPIDEC® CARBA NP | Predicate:
Clearview® Exact PBP2a
Test (K091766) |
|-------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Similarities | | |
| Intended Use | RAPIDEC® CARBA NP is a
phenotypic (colorimetric) in vitro
diagnostic test for the qualitative | The Clearview® Exact PBP2a
Test is a qualitative, in vitro,
immunochromatographic assay |
| Traditional 510(k) Submission | | |
| Item | Device:
RAPIDEC® CARBA NP | Predicate:
Clearview® Exact PBP2a
Test (K091766) |
| | detection of carbapenemase
enzymes in Enterobacteriaceae
and Pseudomonas aeruginosa
colonies that have elevated MIC
values to any carbapenem.
RAPIDEC® CARBA NP is
performed on pure colonies
grown on non-selective sheep
blood agar culture media.
RAPIDEC® CARBA NP is
intended as an aid in the
prevention and control of
infection caused by
| for the detection of penicillin-
binding protein 2a (PBP2a) in
isolates identified as
Staphylococcus aureus, as an aid
in detecting methicillin-resistant
Staphylococcus aureus (MRSA).
The Clearview® Exact PBP2a
Test is not intended to diagnose
MRSA nor to guide or monitor
treatment for MRSA infections. |
| Capability | Marker of antimicrobial
resistance | Same |
| Interpretation | Does not provide MIC
information | Same |
| Sample type | Bacterial isolates/colonial growth | Same |
| Culture media | Sheep blood agar | Same |
| Inoculum
preparation | By touching well isolated
colonies with an applicator stick | Same |
| Reaction | Lysis of bacterial cell wall | Same |
| Item | Device:
RAPIDEC® CARBA NP | Predicate:
Clearview® Exact PBP2a
Test (K091766) |
| preparation | | |
| Controls | Built-in procedural control on
every test strip | Same |
| Reading | Visual based on color change | Same |
| Differences | | |
| Technology | Manual hydrolyzing test for
qualitative detection of
carbapenemase enzymes (KPC,
NDM, OXA-48, VIM and IMP)
in Enterobacteriaceae and
Pseudomonas aeruginosa based
on change in color of a pH
indicator. | Immunochromatographic assay
for detection of penicillin-binding
protein 2a (PBP2a) in isolates
identified as Staphylococcus
aureus. |
5
RAPIDEC® CARBA NP Traditional 510(k) Submission
6
RAPIDEC® CARBA NP demonstrated substantially equivalence when compared to the predicate device, Clearview® Exact PBP2a Test (K091766) and substantially equivalent performance when compared to the composite reference method (CLSI Carba NP test, PCR characterization and carbapenemase MIC determinations). The performance was evaluated following information in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, issued August 28, 2009.
The Premarket Notification 510(k) presents data in support of RAPIDEC® CARBA NP.
Performance Characteristics:
Non-clinical (analytical) and clinical studies were performed for RAPIDEC® CARBA NP.
Analytical Performance
Quality Control
Two quality control organisms were tested at each study site by RAPIDEC® CARBA NP on each day of testing. The organisms tested were:
| Klebsiella pneumoniae ATCC® BAA-1705™ | (positive reaction) |
|---|---|
| Klebsiella pneumoniae ATCC® BAA-1706™ | (negative reaction) |
7
RAPIDEC® CARBA NP
Traditional 510(k) Submission
The results of QC testing with RAPIDEC® CARBA NP met the pre-defined acceptance criteria (≥95% agreement) when compared to the expected results as determined for the recommended QC strains.
Analytical Reactivity (Challenge testing)
A total of 43 carbapenemase producers as determined by the reference composite method were tested by the RAPIDEC® CARBA NP. There were (2) VIM producing Pseudomonas aeruginosa and 41 carbapenemase producing Enterobactericeae consisting of (16) KPC, (10) NDM, (7) OXA-48. (5) VIM and (3) IMP.
An initial reading was performed at 30 minutes and when the result was negative, the final reading was performed at a total of 2 hours of 33-38°C incubation.
All 43 strains were detected positive by RAPIDEC® CARBA NP following the reading protocol, with an analytical sensitivity of 100% (43/43)*.
- There were four negative results at the initial 30-minute read but became positive at the final 2-hour read; there were eight initial positive results that changed back to negatives when read again at 2 hours incubation.
Cross-reactivity
A total of 93 non-carbapenemase producing strains with elevated carbapenem MICs were tested on the RAPIDEC® CARBA NP test. The strains tested include 67 strains (i.e., 59 Enterobacteriaceae, 8 Pseudomonas aeruginosa) related to the intended use, 26 other organisms including non-fermenting gram negative rods, gram positive organisms and yeast. All strains were well-characterized. The resistance mechanisms were AmpC, high level AmpC, porin loss, ESBL, porin loss/ESBL, porin loss/AmpC, MRSA, and VRE. An initial reading was performed at 30 minutes and if the result was negative a final reading was performed at a total of 2 hours of 33-38°C incubation.
The analytical specificity was 97.9% (91/93) at 30 minutes of incubation due to the two intrinsic resistant Stenotrophomonas maltophilia. The analytical specificity was 93.6% (87/93) at 2 hours of incubation. The results demonstrated one Enterobacteriaceae (Morganella morganii) with an AmpC resistance and 5 non-fermenting gram negative rods (three intrinsic resistant Stenotrophomonas maltophilia, one each for Burkholderia cepaciae and Sphingomonas paucimobilis) have given a positive reaction with the RAPIDEC® CARBA NP.
For intended Enterobacteriaceae and Pseudomonas aeruginosa strains, the analytical specificity was 100% (67/67) at 30 minutes of incubation and 98.5% (66/67) at 2 hours of incubation because of the AmpC producing Morganella morganii.
Agar Culture Media Compatibility Studies
RAPIDEC® CARBA NP results with strains isolated on Columbia agar + 5% sheep blood (COS) were compared with those strains isolated on Trypticase Soy agar + 5% sheep blood (TSS). A total of 106 strains (92 carbapenemase producers and 14 noncarbapenemase producers) were tested. The carbapenemase producers included 19 IMP, 20 KPC, 20 VIM, 17 NDM, and 16 OXA-48. The positive rate for the carbapenemase producers was 94.6% (87/92) and 92.4% (85/92) for TSS and COS
8
respectively at the initial 30-minute read. There were five (4 OXA-48 producing K. pneumoniae and one KPC producing K. pneumoniae) that were negative for both media and two NDM producing Providencia spp. for COS at the 30-minute read. The positive rate was 98.9% (91/92) for both media due to one negative KPC producing K. pneumoniae at the final 2-hour read. The negative rate for non-carbapenemase producers was 100% for both media at 30-minute and 2-hour reads. The results indicates no significant differences between TSS and COS.
Clinical Studies
In the RAPIDEC® CARBA NP clinical study, a total of 457 strains consisting of 394 Enterobacteriaceae and 63 P. aeruginosa were evaluated across 5 sites using both the routine and the short subculture procedures.
Carbapenemase determination was determined by a composite reference method composed of three tests: carbapenem MIC (Imipenem, Meropenem, Ertapenem and/or Doripenem), CLS1® Carba NP and carbapenemase genetic markers by Polymerase Chain Reaction (PCR).
Results from the three different tests were used to determine the carbapenemase positive/negative status of an isolate, with the final composite reference result based on agreement of at least two of the three tests. Agreement between RAPIDEC® CARBA NP and composite reference method was assessed. When a RAPIDEC® CARBA NP result was not in agreement with the composite reference result, it was further evaluated. A negative RAPIDEC® CARBA NP result was considered as a false negative when the composite reference result was determined to be positive, indicating a false noncarbapenemase producer. A positive RAPIDEC® CARBA NP result was considered as a false positive when the composite reference result was determined to be negative, indicating a false carbapenemase producer. The comparative performance is shown in Table 1. The performance of RAPIDEC® CARBA NP with Enterobacteriaceae and Pseudomonas aeruginosa expressing the indicated carbapenemase genetic markers is shown in Table 2.
| Pseudomonas aeruginosa | ||||||||
|---|---|---|---|---|---|---|---|---|
| Incubation | Total |
| Agreement
| Agreement
% | Negative
| Positive
| False Positivea
(%) | False Negativeb
(%) | |
| | Routine
Subculture | 457 | 451 | 98.7 | 192 | 265 | 5 (2.6) | 1 (0.4) |
| Short
Subculture | 449 | 440 | 98.0 | 188 | 261 | 5 (2.7) | 4 (1.5) | |
Table 1: Comparative Performance of RAPIDEC® CARBA NP Enterobacteriaceae and
ನಿ False positive for carbapenemase; RAPIDEC CARBA NP positive result for a non-carbapenemase producing Enterobacteriaceae or P. aeruginosa
6 False negative for carbapenemase; RAPIDEC CARBA NP negative result for a carbapenemase producing Enterobacteriaceae or P. aeruginosa
9
RAPIDEC® CARBA NP
Traditional 510(k) Submission
| Carbapenemase
determination
by composite reference
| method | RAPIDEC® CARBA NP performance | ||||
|---|---|---|---|---|---|
| Routine subculture/incubation | Short subculture/incubation | ||||
| N | Agreement (%) | N* | Agreement (%) | ||
| Enterobacteriaceae | 388/394 | 98.5% | 383/392 | 97.7% | |
| Pseudomonas aeruginosa | 63/63 | 100% | 57/57 | 100% | |
| All samples | 451/457 | 98.7% | 440/449 | 98.0% | |
| Positive samples | 264/265a | 99.6% | 257/261c | 98.5% | |
| Enterobacteriaceae | KPC | 143/144 a | 99.3% | 142/143c | 99.3% |
| NDM | 51/51 | 100% | 50/51c | 98.0% | |
| VIM | 15/15 | 100% | 14/15c | 93.3% | |
| IMP | 12/12 | 100% | 12/12 | 100% | |
| OXA- | |||||
| 48 | 23/23 | 100% | 22/23c | 95.7% | |
| Total | 244/245 | 99.6% | 240/244 | 98.4% | |
| Pseudomonas | |||||
| aeruginosa | KPC | 3/3 | 100% | 3/3 | 100% |
| NDM | 1/1 | 100% | 1/1 | 100% | |
| VIM | 11/11 | 100% | 8/8 | 100% | |
| IMP | 5/5 | 100% | 5/5 | 100% | |
| Total | 20/20 | 100% | 17/17 | 100% | |
| Negative samples | 187/192b | 97.4% | 183/188d | 97.3% | |
| Enterobacteriaceae | 144/149b | 96.6% | 143/148d | 96.6% | |
| Pseudomonas aeruginosa | 43/43 | 100% | 40/40 | 100% |
Table 2: Performance of RAPIDEC® CARBA NP with Enterobacteriaceae and Pseudomonas aeruginosa Expressing the Indicated Carbapenemase Genetic Markers
- Insufficient growth/biomass for six P. aeruginosa and two K. pneumoniae in the short subculture procedure. They were three VIM producing P. aeruginosa, and one KPC producing K. pneumoniae; four negative samples including three P. aeruginosa and one K. pneumoniae.
4 Routine subculture false negative (false non-carbapenemase producer) rate was 0.4% (1/265) for claimed carbapenemases; the false negative was KPC-producing Enterobacteriaceae
b Routine subculture false positive (false carbapenemase producer) rate was 2.6% (5/192) for P. aeruginosa and Enterobacteriaceae; the five false positives were from Enterobactericeae
ﻦ Short subculture false negative (false non-carbapenemase producer) rate was 1.5% (4/257) for claimed carbapenemases; one false negative each for KPC, NDM, VIM, and OXA-48 from Enterobacteriaceae
d Short subculture false positive (false carbapenemase producer) rate was 2.7% (5/188); the five false positives were from Enterobacteriaceae
Reproducibility
A panel of 9 Enterobacteriaceae and 1 P. aeruginosa including 4 negative and 6 positive carbapenemases was tested. Each organism was subcultured onto sheep blood agar and incubated for 18-24 hours for the routine subculture procedure and at least 4 hours for the
10
Traditional 510(k) Submission
short subculture procedure. RAPIDEC® CARBA NP was performed on each organism in triplicates for 5 days at 3 sites and interpreted by 2 operators with the RAPIDEC® CARBA NP results blinded to each other.
The reproducibility was 98.2% (884/900) with the routine subculture procedure and 99.1% (892/900) with the short subculture procedure.
Conclusion
The results of the non-clinical and clinical performance studies support that RAPIDEC® CARBA NP is substantially equivalent to the composite reference method composed of three tests: carbapenem MIC (Imipenem, Meropenem, Ertapenem and/or Doripenem), CLSI® Carba NP and carbapenemase genetic markers by Polymerase Chain Reaction (PCR).