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.

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.

AI/ML Overview

The document provided describes the RAPIDEC® CARBA NP device, an in vitro diagnostic test for the qualitative detection of carbapenemase enzymes. This is a 510(k) submission, meaning the manufacturer is demonstrating that their new device is substantially equivalent to a legally marketed predicate device, rather than proving its safety and effectiveness de novo. Therefore, the study focuses on establishing performance characteristics compared to a reference method and demonstrating substantial equivalence.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. A table of acceptance criteria and the reported device performance

The document implicitly defines acceptance criteria through the reported analytical and clinical performance. While explicit numerical acceptance criteria (e.g., "sensitivity must be >X%") are not laid out in a dedicated table, the "Results of QC testing...met the pre-defined acceptance criteria (≥95% agreement)" suggests this was a criterion for analytical performance. For clinical performance, the reported agreement percentages themselves serve as the outcome against which an implicit set of criteria would have been measured.

Here’s a summary of the performance characteristics:

Acceptance Criteria (Implied) and Reported Device Performance for RAPIDEC® CARBA NP

Category	Performance Metric / Criterion (Implied/Explicit)	Reported Device Performance
Analytical Performance
Quality Control	≥95% agreement with expected results for QC strains.	Met. "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	Detection of carbapenemase producers (Sensitivity). No explicit numerical criterion, but 100% detection is the ideal.	100% (43/43) for 43 known carbapenemase producers (KPC, NDM, OXA-48, VIM, IMP and Pseudomonas aeruginosa) at the final 2-hour read.
Cross-reactivity	Specificity for non-carbapenemase producing strains. No explicit numerical criterion.	Overall:- 97.9% (91/93) at 30 minutes (2 false positives).- 93.6% (87/93) at 2 hours (6 false positives).For Intended Organisms (Enterobacteriaceae & P. aeruginosa):- 100% (67/67) at 30 minutes.- 98.5% (66/67) at 2 hours (1 false positive: AmpC producing Morganella morganii).
Agar Compatibility	No significant differences in performance when using different culture media (Trypticase Soy agar + 5% sheep blood (TSS) vs. Columbia agar + 5% sheep blood (COS)).	Positive rate for carbapenemase producers: 94.6% (87/92) for TSS and 92.4% (85/92) for COS at 30 min. Positive rate increased to 98.9% (91/92) for both media at 2 hours. Negative rate for non-carbapenemase producers: 100% for both media at both time points. "The results indicates no significant differences between TSS and COS."
Clinical Performance
Overall Agreement (Clinical)	High agreement with composite reference method. No explicit numerical criterion.	Overall (All samples):- Routine Subculture: 98.7% (451/457)- Short Subculture: 98.0% (440/449)Enterobacteriaceae:- Routine Subculture: 98.5% (388/394)- Short Subculture: 97.7% (383/392)Pseudomonas aeruginosa:- Routine Subculture: 100% (63/63)- Short Subculture: 100% (57/57)
Sensitivity (Clinical)	High sensitivity (agreement for positive samples). No explicit numerical criterion.	Overall (Positive samples):- Routine Subculture: 99.6% (264/265) (1 false negative, KPC-producing Enterobacteriaceae)- Short Subculture: 98.5% (257/261) (4 false negatives: 1 KPC, 1 NDM, 1 VIM, 1 OXA-48 from Enterobacteriaceae)
Specificity (Clinical)	High specificity (agreement for negative samples). No explicit numerical criterion.	Overall (Negative samples):- Routine Subculture: 97.4% (187/192) (5 false positives, all Enterobacteriaceae)- Short Subculture: 97.3% (183/188) (5 false positives, all Enterobacteriaceae).
Reproducibility	High reproducibility across sites and operators. No explicit numerical criterion.	Routine Subculture: 98.2% (884/900)Short Subculture: 99.1% (892/900)

2. Sample size used for the test set and the data provenance

Test Set Sample Size:
- Analytical Reactivity (Challenge testing): 43 carbapenemase producers.
- Cross-reactivity: 93 non-carbapenemase producing strains (67 Enterobacteriaceae/P. aeruginosa, 26 other organisms).
- Agar Culture Media Compatibility Studies: 106 strains (92 carbapenemase producers, 14 non-carbapenemase producers).
- Clinical Studies: 457 strains (394 Enterobacteriaceae, 63 P. aeruginosa).
- Reproducibility: A panel of 10 organisms (9 Enterobacteriaceae + 1 P. aeruginosa), tested in triplicates for 5 days at 3 sites (total 900 measurements per subculture procedure).
Data Provenance: The document does not explicitly state the country of origin for the clinical or analytical data. It mentions "5 sites" for the clinical study and "each study site" for QC, implying a multi-site study, but locations are not specified. The study appears to be prospective as it involves the evaluation of the device on collected strains and controlled experiments (e.g., QC, challenge testing, clinical evaluation).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document does not mention the number or qualifications of experts used to establish the ground truth. The ground truth for the clinical study was established by a composite reference method consisting of three laboratory tests: carbapenem MIC, CLSI® Carba NP, and PCR for carbapenemase genetic markers. The "final composite reference result based on agreement of at least two of the three tests" does not explicitly involve human expert review for establishing "ground truth," but rather relies on the combined results of established laboratory methods.

For the reproducibility study, results were interpreted by "2 operators" but their qualifications are not specified beyond being "operators."

4. Adjudication method for the test set

For the clinical study, the adjudication method for the composite reference ground truth was: agreement of at least two of the three tests (carbapenem MIC, CLSI® Carba NP, and PCR).

For the reproducibility study, the results were interpreted by "2 operators" and their interpretations were then compared ("blinded to each other"), suggesting a form of comparative adjudication for reproducibility but not for establishing primary ground truth.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done for this device. This is an in vitro diagnostic device (a laboratory test kit), not an AI-assisted imaging device or a device that directly supports human reader interpretation in a complex diagnostic task like radiology. Therefore, questions regarding "human readers improve with AI vs without AI assistance" are not applicable to this device type. The device provides a direct result (positive/negative for carbapenemase) which then informs downstream clinical decisions.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This refers to an in vitro diagnostic device, not typically an "algorithm only" device in the context of imaging or clinical decision support AI. The device itself is a test kit where reactions occur and a visual color change is observed. The "performance" described is of the device as a whole. While human operators perform the test and interpret the "visual based on color change," the core "algorithm" is the biochemical reaction itself. The analytical and clinical studies assess the performance of this system (device + human interpretation). No separate "algorithm only" study is described because the "algorithm" here is the chemical reaction and visual readout, which inherently involves human observation.

7. The type of ground truth used

The ground truth used was a composite reference method comprised of:

Carbapenem MIC (Imipenem, Meropenem, Ertapenem and/or Doripenem).
CLSI® Carba NP (a standardized carbapenemase test).
Carbapenemase genetic markers by Polymerase Chain Reaction (PCR).

This is a form of expert consensus based on the agreement of established laboratory tests, rather than, for example, pathology or outcomes data.

8. The sample size for the training set

The document does not explicitly describe a separate "training set". In the context of a 510(k) submission for an in vitro diagnostic device, often the manufacturer develops and refines the device, and then tests its performance on a "test set" (clinical and analytical studies) to demonstrate substantial equivalence. If any internal development/optimization data was used, it's not detailed or referred to as a "training set" in this regulatory submission. The reported studies are validation studies on a specific set of samples.

9. How the ground truth for the training set was established

Since a distinct "training set" is not described, the method for establishing its ground truth is also not detailed. Any internal development ground truth would likely have been established using similar reference methods to the ones described for the validation set.

Summary

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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.

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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

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Indications for Use

510(k) Number (if known) K162385

Device Name RAPIDEC® CARBA NP

Indications for Use (Describe)

RAPIDEC® CARBA NP is intended as an aid in the prevention and control of infection caused by carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa.

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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SECTION 8. 510(k) SUMMARY

510(k) SUMMARY RAPIDEC® CARBA NP

510(k) Submission Information:

Submitter's Name:	bioMerieux SA
Address:	5 rue des Aqueducs69290 Craponne, France
Contact Person:	Asa KarlssonRegulatory Affairs Sr. Manager
Phone Number:	+33 (0)6 48 61 68 49
Fax Number:	+33 (0)4 78 87 76 65
E-mail	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 intended as an aid in the prevention and control of infection caused by carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa.

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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:

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 PBP2aTest (K091766)
Similarities
Intended Use	RAPIDEC® CARBA NP is aphenotypic (colorimetric) in vitrodiagnostic test for the qualitative	The Clearview® Exact PBP2aTest is a qualitative, in vitro,immunochromatographic assay
Traditional 510(k) Submission
Item	Device:RAPIDEC® CARBA NP	Predicate:Clearview® Exact PBP2aTest (K091766)
	detection of carbapenemaseenzymes in Enterobacteriaceaeand Pseudomonas aeruginosacolonies that have elevated MICvalues to any carbapenem.RAPIDEC® CARBA NP isperformed on pure coloniesgrown on non-selective sheepblood agar culture media.RAPIDEC® CARBA NP isintended as an aid in theprevention and control ofinfection caused by	for the detection of penicillin-binding protein 2a (PBP2a) inisolates identified asStaphylococcus aureus, as an aidin detecting methicillin-resistantStaphylococcus aureus (MRSA).The Clearview® Exact PBP2aTest is not intended to diagnoseMRSA nor to guide or monitortreatment for MRSA infections.
Capability	Marker of antimicrobialresistance	Same
Interpretation	Does not provide MICinformation	Same
Sample type	Bacterial isolates/colonial growth	Same
Culture media	Sheep blood agar	Same
Inoculumpreparation	By touching well isolatedcolonies with an applicator stick	Same
Reaction	Lysis of bacterial cell wall	Same
Item	Device:RAPIDEC® CARBA NP	Predicate:Clearview® Exact PBP2aTest (K091766)
preparation
Controls	Built-in procedural control onevery test strip	Same
Reading	Visual based on color change	Same
Differences
Technology	Manual hydrolyzing test forqualitative detection ofcarbapenemase enzymes (KPC,NDM, OXA-48, VIM and IMP)in Enterobacteriaceae andPseudomonas aeruginosa basedon change in color of a pHindicator.	Immunochromatographic assayfor detection of penicillin-bindingprotein 2a (PBP2a) in isolatesidentified as Staphylococcusaureus.

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RAPIDEC® CARBA NP Traditional 510(k) Submission

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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)

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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

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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# (%)
	RoutineSubculture	457	451	98.7	192	265	5 (2.6)	1 (0.4)
ShortSubculture	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

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RAPIDEC® CARBA NP

Traditional 510(k) Submission

Carbapenemasedeterminationby composite referencemethod		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%
Pseudomonasaeruginosa	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

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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).

Regulation Number and Section

§ 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).