(260 days)
Not Found
No
The summary describes a diagnostic test based on bacteriophage amplification and immunoassay, with no mention of AI or ML.
No.
The device is described as a qualitative in vitro diagnostic test for the identification of Staphylococcus aureus and determination of methicillin susceptibility or resistance directly from positive blood cultures. It aids in diagnosis rather than providing treatment or therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is a "qualitative in vitro diagnostic test for the timely identification of Staphylococcus aureus (S. aureus) and determination of methicillin susceptibility (MSSA) or methicillin resistance (MRSA) directly from positive blood cultures." It also mentions it is "an aid in the detection of MRSA/MSSA from positive blood cultures."
No
The device description clearly outlines a biological assay using bacteriophage amplification and an immunoassay with a visible signal, indicating a physical test kit and not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The very first sentence explicitly states: "The KeyPath™ MRSA/MSSA Blood Culture Test - BT is a qualitative in vitro diagnostic test..." This directly identifies the device as an IVD.
- Device Description: The description details how the test works by analyzing a biological sample (positive blood cultures) outside of the body to detect the presence of specific organisms and their characteristics. This is the core function of an in vitro diagnostic device.
- Performance Studies: The document describes a clinical trial where the device's performance was evaluated against a standard method using patient samples. This is a typical requirement for demonstrating the effectiveness of an IVD.
- Key Metrics: The document provides metrics like sensitivity, specificity, PPV, and NPV, which are standard measures used to evaluate the performance of diagnostic tests.
- Predicate Device(s): The listing of predicate devices, which are other legally marketed devices used for similar diagnostic purposes, further confirms the device's classification as an IVD.
All of these elements strongly indicate that the KeyPath™ MRSA/MSSA Blood Culture Test - BT is an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
The KeyPathTM MRSA/MSSA Blood Culture Test - BT is a qualitative in vitro diagnostic test for the timely identification of Staphylococcus aureus (S. aureus) and determination of methicillin susceptibility (MSSA) or methicillin resistance (MRSA) directly from positive blood cultures.
The Test uses bacteriophage amplification to identify the presence of S. aureus and assess the phenotypic response of the target organism to cefoxitin, an indicator of oxacillin (a methicillin analog) resistance.
The assay is performed directly on positive blood culture specimens that are determined as Gram Positive Cocci in singles (GPC) or as Gram Positive Cocci in Clusters (GPCC) by Gram stain.
The KeyPathTM MRSA/MSSA Blood Culture Test - BT is performed directly on positive blood culture specimens from BD BACTECTM blood culture bottles (Plus Aerobic/F and Plus Anaerobic/F).
The Test is indicated for use in conjunction with other laboratory and clinical data available to the physician as an aid in the detection of MRSA/MSSA from positive blood cultures.
Subculturing of positive blood cultures is necessary for additional susceptibility test determinations, differentiation of mixed growth and for epidemiological typing.
Product codes (comma separated list FDA assigned to the subject device)
OUS
Device Description
The KeyPathTM MRSA/MSSA Blood Culture Test – BT uses lytic bacteriophage, specific for Staphylococcus aureus, as an amplification technology for detection of S. aureus and determination of methicillin resistance or susceptibility in positive blood cultures. To detect S. aureus (ID Reaction Tube), the bacteriophage infect the S. aureus (if present), replicate within the host (culminating in bacterial lysis) and over the incubation period, produce several cycles of bacteriophage amplification. In a separate Reaction Tube (RS), the Test uses cefoxitin (an oxacillin and methicillin analog) which inhibits bacteriophage amplification for susceptible organisms (MSSA) and fails to inhibit bacteriophage amplification when the organism is resistant to methicillin (MRSA). The Test then uses a self-performing immunoassay (Detector) to detect the increase in concentration of bacteriophage using antibodies specific to the Test bacteriophage, and calibrated such that at above a threshold concentration, it produces a visible signal.
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
Clinical patients (18 years of age or older in the clinical study)
Intended User / Care Setting
Professional Use
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
The clinical comparison study used prospective clinical trial data.
Sample size: 1116 paired samples (366 S. aureus) tested for MRSA/MSSA.
Data source: Positive blood cultures from a BACTECTM blood culture system (9000 series or F/X) from subjects 18 years of age or older. Samples were tested on the KeyPathTM MRSA/MSSA Blood Culture Test – BT within 24 hours of positive determination on BACTECTM System.
Annotation protocol: For S. aureus identification, standard culture identification methods were used, including Catalase positive, Tube Coagulase positive, and Remel Staphaurex® positive. For antimicrobial susceptibility determination, a 30 μg cefoxitin disk diffusion test was performed in accordance with CLSI M100-S19.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Comparison Study:
Study Type: Prospective clinical trial.
Sample Size: 1116 paired samples (366 S. aureus).
Standalone performance: Not Found (compared against standard methods).
Key Results:
- Sensitivity for detection of S. aureus: 91.8%
- Specificity for detection of S. aureus: 98.3%
- Positive Predictive Value (PPV) for S. aureus: 96.3%
- Negative Predictive Value (NPV) for S. aureus: 96.1%
- Category agreement with cefoxitin disk diffusion test for methicillin resistance within S. aureus samples: 98.9%
- Category agreement with cefoxitin disk diffusion test for methicillin susceptibility within S. aureus samples: 99.4%
- Initial invalid rate: 0.3% (all resolved upon retest).
- No significant differences in performance across sites or between blood culture bottle types.
- No significant effect of antibiotic or antiviral treatments on performance.
Non-clinical Studies:
- Reproducibility: 99.4% reproducible in 648 runs at three sites over 6 days, tested with 2 MRSA, 2 MSSA, and 1 S. epidermidis strains.
- Inclusivity: Tested on 114 S. aureus strains (17 clonal complexes, 46 multilocus sequence types). Sensitivity for S. aureus detection was 91.8%. Category agreement for methicillin-resistance was 99%, and for methicillin-susceptibility was 100%.
- Interfering substances: No interference observed with lipemic, icteric, hemolytic blood samples, 5 antibiotics, 3 analgesics, an antiviral, an anticoagulant. Immunoassay component showed no cross-reaction with 20 RF-positive, HAMA-positive, heterophilic antibody sera, or 32 human viruses.
- Mixed culture: MRSA reliably detected in mixed cultures with ~90% (or greater) Gram negative rods and bacilli, Gram positive cocci in clusters (not S. aureus) and Gram positive rods.
- Analytical specificity: Tested on 163 isolates (33 Gram-negative, 58 Gram-positive not Staphylococci, 5 coagulase-positive Staphylococci, 60 coagulase-negative Staphylococci, 7 yeast). Showed 98.8% specificity.
- Evaluation of SCCmec Empty Cassette Variants: 28 mecA-positive (MRSA by PCR) strains that were MSSA by phenotypic culture methods were determined to be MSSA by the KeyPathTM Test.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity for detection of S. aureus: 91.8%
Specificity for detection of S. aureus: 98.3%
Positive Predictive Value (PPV) for S. aureus: 96.3%
Negative Predictive Value (NPV) for S. aureus: 96.1%
Category agreement for methicillin resistance: 98.9%
Category agreement for methicillin susceptibility: 99.4%
Reproducibility: 99.4%
Inclusivity Sensitivity for S. aureus detection: 91.8%
Inclusivity Category agreement for methicillin-resistance: 99%
Inclusivity Category agreement for methicillin-susceptibility: 100%
Analytical specificity: 98.8%
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.
BD GeneOhm™ StaphSR Assay (510(k)# K071026), K851949, K011710, (preAmendment), (preAmendment), (preAmendment)
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
§ 866.2050 Staphylococcal typing bacteriophage.
(a)
Identification. A staphylococcal typing bacteriophage is a device consisting of a bacterial virus intended for medical purposes to identify pathogenic staphylococcal bacteria through use of the bacteria's susceptibility to destruction by the virus. Test results are used principally for the collection of epidemiological information.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.
0
Image /page/0/Picture/0 description: The image shows the handwritten text "K102342" above a logo. The logo is a semi-circular shape with a dark gray section on the left and a lighter gray section on the right. The text appears to be written in black ink on a white background.
MIC ROP H A G E
510(k) Summary
As required by 21 CFR Section 807.92(c).
| Submitted by: | MicroPhage, Inc.
2400 Trade Centre Ave
Longmont, CO 80503 | MAY - 5 2011 |
|------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------|
| Phone number: | (303) 652-5049 | |
| Fax number: | (303) 652-5080 | |
| Contact: | Drew Smith, PhD | |
| Date of Preparation: | April 29, 2011 | |
| Device:
Trade name: | KeyPathTM MRSA/MSSA Blood Culture Test - BT | |
| Common name: | Bacterial Identification and Antimicrobial Susceptibility Test (ID/AST);
KeyPathTM AST; Methicillin-resistant Staphylococcus aureus (MRSA)
and Methicillin-sensitive Staphylococcus aureus (MSSA) from positive
blood culture bottles test. | |
| Type of Test: | Bacteriophage amplification, Methicillin-resistant
Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus
aureus (MSSA), qualitative | |
| Regulation section: | 866.2050 - Staphylococcal typing bacteriophage | |
| Classification: | I | |
| Product code: | OUS | |
| Panel: | 83 Microbiology | |
1
MicroPhage KeyPath™ MRSA/MSSA Blood Culture Test - BT: 510(k) Summary
| Predicate Devices: | BD GeneOhm™ StaphSR Assay | |
|---|---|---|
| K851949 | Wellcome (Remel) Staphaurex® ZL30 | |
| K011710 | Oxoid PBP2' Latex Agglutination | |
| (preAmendment) | BBL (BD) cefoxitin 30 µg Sensi-Disc | |
| (preAmendment) | BBL (BD) oxacillin 1 µg Sensi-Disc | |
| (preAmendment) | Coagulase Test (multiple manufacturers) | |
| (preAmendment) | Catalase Test (multiple manufacturers) |
Device Description:
The KeyPath™ MRSA/MSSA Blood Culture Test – BT uses lytic bacteriophage, specific for Staphylococcus aureus, as an amplification technology for detection of S. aureus and determination of methicillin resistance or susceptibility in positive blood cultures. To detect S. aureus (ID Reaction Tube), the bacteriophage infect the S. aureus (if present), replicate within the host (culminating in bacterial lysis) and over the incubation period, produce several cvcles of bacteriophage amplification. In a separate Reaction Tube (RS), the Test uses cefoxitin (an oxacillin and methicillin analog) which inhibits bacteriophage amplification for susceptible organisms (MSSA) and fails to inhibit bacteriophage amplification when the organism is resistant to methicillin (MRSA). The Test then uses a self-performing immunoassay (Detector) to detect the increase in concentration of bacteriophage using antibodies specific to the Test bacteriophage, and calibrated such that at above a threshold concentration, it produces a visible signal.
Device Intended Use:
The KeyPath™ MRSA/MSSA Blood Culture Test – BT is a qualitative in vitro diagnostic test for the timely identification of Staphylococcus aureus (S. aureus) and determination of methicillin susceptibility (MSSA) or methicillin resistance (MRSA) directly from positive blood cultures.
The Test uses bacteriophage amplification to identify the presence of S. aureus and assess the phenotypic response of the target organism to cefoxitin, an indicator of oxacillin (a methicillin analog) resistance.
The assay is performed directly on positive blood culture specimens that are determined as Gram Positive Cocci in singles (GPC) or as Gram Positive Cocci in Clusters (GPCC) by Gram stain.
The KeyPath™ MRSA/MSSA Blood Culture Test – BT is performed directly on positive blood culture specimens from BD BACTEC™ blood culture bottles (Plus Aerobic/F and Plus Anaerobic/F).
The Test is indicated for use in conjunction with other laboratory and clinical data available to the physician as an aid in the detection of MRSA/MSSA from positive blood cultures.
Subculturing of positive blood cultures is necessary for additional susceptibility test determinations, differentiation of mixed growth and for epidemiological typing.
2
Substantial Equivalence:
The KeyPath™ MRSA/MSSA Blood Culture Test - BT is substantially equivalent to the BD GeneOhm™ StaphSR Assay (510(k)# K071026). Both assays are indicated for the identification/detection of S. aureus from blood culture positives and both are indicated for determination/detection of MRSA. Though each use different technologies (bacteriophage amplification vs. RT - PCR), and the MicroPhage Test is phenotypic as opposed to genotypic, both perform with high sensitivity and specificity to their intended targets. Table 1 summarizes the major similarities and differences between these two methods.
Table 1 - Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test - BT and the BD GeneOhm™ StaphSR assay.
| SIMILARITIES | ||
|---|---|---|
| Item | KeyPath™ MRSA/MSSA Blood Culture Test - BT | BD GeneOhm™ StaphSR Assay |
| Intended Use | The KeyPath™ MRSA/MSSA Blood Culture Test - BT | |
| is a qualitative in vitro diagnostic test for the timely | ||
| identification of Staphylococcus aureus ( S. aureus ) and | ||
| determination of methicillin susceptibility (MSSA) or | ||
| methicillin resistance (MRSA) directly from positive | ||
| blood cultures. | The BD GeneOhm™ StaphSR | |
| Assay is a qualitative in vitro | ||
| diagnostic test for the rapid | ||
| detection of Staphylococcus | ||
| aureus ( SA ) and methicillin- | ||
| resistant Staphylococcus aureus | ||
| (MRSA) directly from positive | ||
| blood culture. | ||
| The Test uses bacteriophage amplification to identify the | ||
| presence of S. aureus and assess the phenotypic response | ||
| of the target organism to cefoxitin, an indicator of | ||
| oxacillin (a methicillin analog) resistance. | The assay utilizes polymerase chain | |
| reaction (PCR) for the amplification | ||
| of specific targets and fluorogenic | ||
| target-specific hybridization probes | ||
| for the real-time detection of the | ||
| amplified DNA. | ||
| The assay is performed directly on positive blood | ||
| culture specimens that are determined as Gram | ||
| Positive Cocci in singles (GPC) or as Gram Positive | ||
| Cocci in Clusters (GPCC) by Gram stain. | The assay is performed on gram | |
| positive cocci, identified by Gram | ||
| stain, from positive blood | ||
| cultures. The BD GeneOhm™ | ||
| StaphSR Assay is not intended to | ||
| monitor treatment for MRSA/SA | ||
| infections. Subculturing of positive | ||
| blood cultures is necessary for | ||
| The KeyPath™ MRSA/MSSA Blood Culture Test - BT | ||
| is performed directly on positive blood culture specimens | ||
| from BD BACTECTM blood culture bottles (Plus | ||
| Aerobic/F and Plus Anaerobic/F). | ||
| The Test is indicated for use in conjunction with other | ||
| laboratory and clinical data available to the physician as | ||
| an aid in the detection of MRSA/MSSA from positive | ||
| blood cultures. | StaphSR Assay is not intended to | |
| monitor treatment for MRSA/SA | ||
| infections. Subculturing of positive | ||
| blood cultures is necessary for | ||
| Subculturing of positive blood cultures is necessary for | ||
| additional susceptibility test determinations, | ||
| differentiation of mixed growth and for epidemiological | ||
| typing | further susceptibility testing. | |
| Single Use | Yes | Yes |
| Indication for | ||
| Use | Professional Use | Professional Use |
| Interpretation | ||
| of results | Visual | Visual |
| Patient | ||
| population | Clinical patients | Clinical patients |
| Specimen type | Positive blood culture | Positive blood culture |
3
| Assay controls | Pos Control 1: MRSA | Pos Control: MRSA |
|---|---|---|
| Pos Control 2: MSSA | Pos Control: SA | |
| Neg Control: NSA | Neg Control: NSA |
| DISSIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test - BT | BD GeneOhmTM StaphSR Assay |
| Time to result | 5 hours | 60-75 minutes |
| Mode of action | The test uses bacteriophage amplification with cefoxitin to quickly determine the presence of MRSA and MSSA in positive blood cultures. | The assay utilizes polymerase chain reaction (PCR) for the amplification of specific targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. |
| Assay format | Amplification: bacteriophage amplification | |
| Detection: Lateral flow immunoassay with colloidal gold particles with monoclonal antibodies specific to assay bacteriophage. | Amplification: polymerase chain reaction (PCR) | |
| Detection: Fluorogenic target-specific hybridization probes of the amplified DNA. |
*Bolded and underlined portions indicates similarities of intended use.
The KeyPath™ MRSA/MSSA Blood Culture Test – BT is substantially equivalent to combined Coagulase and Catalase Test (both pre-amendment). Both Coag/Cat and MicroPhage Tests are indicated for the identification or detection of S. aureus and are phenotypic tests. Table 2 summarizes the major similarities and differences between these two methods.
4
Table 2 – Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test – BT and the Coagulase Tube and Catalase Slide Tests.
| SIMILARITIES | ||
|---|---|---|
| Item | KeyPath™ MRSA/MSSA Blood Culture Test - BT | Coagulase Tube, Catalase Slide Tests (pre-amendment) |
| Intended Use | The KeyPath™ MRSA/MSSA Blood Culture Test - BT is a qualitative in vitro diagnostic test for the timely identification of Staphylococcus aureus (S. aureus) and determination of methicillin susceptibility (MSSA) or methicillin resistance (MRSA) directly from positive blood cultures. The Test uses bacteriophage amplification to identify the presence of S. aureus and assess the phenotypic response of the target organism to cefoxitin, an indicator of oxacillin (a methicillin analog) resistance. The assay is performed directly on positive blood culture specimens that are determined as Gram Positive Cocci in singles (GPC) or as Gram Positive Cocci in Clusters (GPCC) by Gram stain. The KeyPath™ MRSA/MSSA Blood Culture Test - BT is performed directly on positive blood culture specimens from BD BACTECTM blood culture bottles (Plus Aerobic/F and Plus Anaerobic/F). The Test is indicated for use in conjunction with other laboratory and clinical data available to the physician as an aid in the detection of MRSA/MSSA from positive blood cultures. Subculturing of positive blood cultures is necessary for additional susceptibility test determinations, differentiation of mixed growth and for epidemiological typing | The Coagulase Tube and Catalase Slide Tests (multiple manufacturers) are qualitative in vitro diagnostic test for the identification of Staphylococcus aureus (SA) directly from isolated colonies from a positive blood culture. "Positive" results for both catalase and coagulase are indicative of S. aureus. The assays contain rabbit serum with EDTA for Coagulase Test and peroxide (H2O2) for Catalase Test substrates which will react with coagulase and catalase enzymes expressed by S. aureus. A clumping of rabbit serum confirms the presence of coagulase and production of O₂ bubbles confirms the presence of catalase (i.e. both results indicating presence of S. aureus). The assay is performed on gram positive cocci which have been isolated by streaking on culture plates, identified by Gram stain, from positive blood cultures. Further subculturing of positive blood cultures are necessary for susceptibility testing. |
| Single Use | Yes | Yes |
| Indication for Use | Professional Use | Professional Use |
| Interpretation of results | Visual | Visual |
| Patient population | Clinical patients | Clinical patients |
Table 2 – Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test – BT and Coagulase/Catalase Tests for S. aureus determination.
| DISSIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture | |
| Test - BT | Coagulase Tube, Catalase | |
| Slide Tests | ||
| (pre-amendment) | ||
| Specimen type | Positive blood culture | Overnight purified plate culture (i.e. isolated |
| colonies) originating from a Positive blood |
5
| DISSIMILARITIES | ||
|---|---|---|
| Item | KeyPath™ MRSA/MSSA Blood Culture | |
| Test - BT | Coagulase Tube, Catalase | |
| Slide Tests | ||
| (pre-amendment) | ||
| Time to result | 5 hours | culture |
| Catalase: 5 minutes | ||
| Coagulase: 4-24 hours | ||
| Mode of action | The test uses bacteriophage amplification with | |
| cefoxitin to quickly determine the presence of | ||
| MRSA and MSSA in positive blood cultures. | The assays contain rabbit serum with EDTA | |
| for the Coagulase Test and peroxide ( $H_2O_2$ ) | ||
| for the Catalase Test, substrates which will | ||
| react with coagulase and catalase enzymes | ||
| expressed by S. aureus . A clumping of rabbit | ||
| serum confirms the presence of coagulase and | ||
| production of $O_2$ bubbles confirms the | ||
| presence of catalase. Both results indicate the | ||
| presence of S. aureus . | ||
| Assay format | Amplification: bacteriophage amplification |
Detection: Lateral flow immunoassay with
colloidal gold particles with monoclonal
antibodies specific to assay bacteriophage. | Amplification: none
Detection: Clumping of coagulase substrate
and $O_2$ gas production (i.e. bubbles) of
catalase substrate when metabolized by the
respective enzymes. |
*Bolded and underlined portions indicates similarities of intended use.
The KeyPath™ MRSA/MSSA Blood Culture Test – BT is substantially equivalent to Remel Staphaurex® (510(k)# K851949). Both assays are indicated for the identification or detection of S. aureus and are phenotypic tests. Additionally, both use antibody-based detection methods (lateral flow immunoassay vs. latex agglutination). Table 3 summarizes the major similarities and differences between these two methods.
Table 3 - Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test - BT and Wellcome (Remel) Staphaurex for S. aureus determination.
| SIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test – BT | Remel Staphaurex® |
| Intended Use | The KeyPathTM MRSA/MSSA Blood Culture Test - BT is a | |
| qualitative in vitro diagnostic test for the timely | ||
| identification of Staphylococcus aureus ( S. aureus ) and | ||
| determination of methicillin susceptibility (MSSA) or | ||
| methicillin resistance (MRSA) directly from positive blood | ||
| cultures. |
The Test uses bacteriophage amplification to identify the
presence of S. aureus and assess the phenotypic response of
the target organism to cefoxitin, an indicator of oxacillin (a
methicillin analog) resistance.
The assay is performed directly on positive blood culture
specimens that are determined as Gram Positive Cocci in
singles (GPC) or as Gram Positive Cocci in Clusters
(GPCC) by Gram stain.
The KeyPathTM MRSA/MSSA Blood Culture Test - BT is
performed directly on positive blood culture specimens
from BD BACTECTM blood culture bottles (Plus Aerobic/F | Staphaurex® is a rapid slide
agglutination procedure for
differentiating staphylococci
which possess clumping factor
and/or protein A, particularly
Staphylococcus aureus , from
staphylococci which possess
neither of these factors. |
6
| SIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test – BT | |
| and Plus Anaerobic/F). |
The Test is indicated for use in conjunction with other
laboratory and clinical data available to the physician as an
aid in the detection of MRSA/MSSA from positive blood
cultures.
Subculturing of positive blood cultures is necessary for
additional susceptibility test determinations, differentiation
of mixed growth and for epidemiological typing | Remel Staphaurex® |
| Single Use | Yes | Yes |
| Indication for
Use | Professional Use | Professional Use |
| Interpretation
of results | Visual | Visual |
| Patient
populations | Clinical patients | Clinical patients |
| Assay
controls | Pos Control 1: MRSA
Pos Control 2: MSSA
Neg Control: NSA | Pos Control: SA
Neg Control: NSA |
| DISSIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test - | |
| BT | Remel Staphaurex® | |
| Specimen type | Positive blood culture | Overnight Purified Culture |
| (16-24hr) | ||
| Time to result | 5 hours | 10 - 15 minutes |
| Mode of action | The test uses bacteriophage amplification with | |
| cefoxitin to quickly determine the presence of | ||
| MRSA and MSSA in positive blood cultures. | The test detects the presence of clumping | |
| factor and protein A using coated latex | ||
| particles which agglutinate in a rapid | ||
| slide procedure. | ||
| Assay format | Amplification: bacteriophage amplification | |
| Detection: Lateral flow immunoassay with | ||
| colloidal gold particles with monoclonal | ||
| antibodies specific to assay bacteriophage. | Amplification: none | |
| Detection: Agglutination of latex | ||
| particles. |
- Bolded and underlined portions indicates similarities of intended use.
The KeyPath™ MRSA/MSSA Blood Culture Test – BT is substantially equivalent to the Oxoid PBP2' Latex Agglutination test (510(k)# K011710). Both assays are indicated for the determination or identification of MRSA by surrogate markers (bacteriophage amplification vs. penicillin binding protein 2'). Additionally, both use antibody-based detection methods (lateral flow immunoassay vs. latex agglutination) and are phenotypic tests. Table 4 summarizes the major similarities and differences between these two methods.
Table 4 - Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test - BT and Oxoid PBP2' Latex Agglutination for MRSA determination.
| SIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test – BT | Oxoid PBP2' Latex |
| Agglutination Test | ||
| Intended Use | The KeyPathTM MRSA/MSSA Blood Culture Test – BT is | This test is a rapid latex |
7
| SIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test – BT | Oxoid PBP2' Latex Agglutination Test |
| a qualitative in vitro diagnostic test for the timely | ||
| identification of Staphylococcus aureus ( S. aureus ) and | ||
| determination of methicillin susceptibility (MSSA) or | ||
| methicillin resistance (MRSA) directly from positive | ||
| blood cultures. | ||
| The Test uses bacteriophage amplification to identify the | ||
| presence of S. aureus and assess the phenotypic response | ||
| of the target organism to cefoxitin, an indicator of oxacillin | ||
| (a methicillin analog) resistance. | ||
| The assay is performed directly on positive blood culture | ||
| specimens that are determined as Gram Positive Cocci in | ||
| singles (GPC) or as Gram Positive Cocci in Clusters | ||
| (GPCC) by Gram stain. | ||
| The KeyPathTM MRSA/MSSA Blood Culture Test – BT is | ||
| performed directly on positive blood culture specimens | ||
| from BD BACTECTM blood culture bottles (Plus | ||
| Aerobic/F and Plus Anaerobic/F). | ||
| The Test is indicated for use in conjunction with other | ||
| laboratory and clinical data available to the physician as an | ||
| aid in the detection of MRSA/MSSA from positive blood | ||
| cultures. | ||
| Subculturing of positive blood cultures is necessary for | ||
| additional susceptibility test determinations, differentiation agglutination assay, detecting | ||
| PBP2' (also called PBP2a), in | ||
| isolates of Staphylococcus , as an | ||
| aid in identifying methicillin- | ||
| resistant Staphylococcus aureus | ||
| (MRSA) and methicillin-resistant | ||
| coagulase-negative staphylococci. | ||
| Single Use | Yes | Yes |
| Indication for | ||
| Use | Professional Use | Professional Use |
| Interpretation | ||
| of results | Visual | Visual |
| Patient | ||
| populations | Clinical patients | Clinical patients |
| Assay controls | Pos Control 1: MRSA | |
| Pos Control 2: MSSA | ||
| Neg Control: NSA | Pos Control: MRSA | |
| Neg Control: NSA |
| DISSIMILARITIES | ||
|---|---|---|
| Item | KeyPath™ MRSA/MSSA Blood Culture Test - | |
| BT | Oxoid PBP2' Latex Agglutination | |
| Test | ||
| Specimen | Positive blood culture | Overnight Purified Culture (16 - 24 |
| hrs) | ||
| Time to result | 5 hours | 45 minutes |
| Mode of action | The test uses bacteriophage amplification with | |
| cefoxitin to determine the presence of MRSA and | ||
| MSSA in positive blood cultures. | Latex particles sensitized with a | |
| monoclonal antibody against PBP2' | ||
| specifically react with methicillin- | ||
| resistant staphylococci to cause | ||
| agglutination visible to the unaided | ||
| eye. | ||
| Assay format | Amplification: bacteriophage amplification | |
| Detection: lateral flow immunoassay with | Amplification: none |
.
8
| DISSIMILARITIES | |||
|---|---|---|---|
| ltem | KevPath "31 MRSA/MSSA Blood Culture Test - | Oxoid PBP2' Latex Agglutination | |
| BT | Test | ||
| colloidal gold particles with monoclonal | Detection: | ||
| antibodies specific to assay bacteriophage. | Agglutination of latex particles | ||
| Controller Company Controller Company Company Company Company Company Company Company Company Company Company Company Company Company Company Company Company Company Company | Company of the country of the country of the county of the county of the county of the county of the county of the county of the county of the county of the county of the cou | ||
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- Bolded and underlined portions indicates similarities of intended use.
The KeyPath™ MRSA/MSSA Blood Culture Test - BT is substantially equivalent to the BD BBL 30 µg cefoxitin Sensi-Disc and BD BBL 1 µg oxacillin Sensi-Disc (both pre-Amendment devices). All three assays are indicated for the phenotypic determination of MRSA. Additionally, all use a viable culture of bacteria (e.g., S. aureus) to guide interpretation of results. though the MicroPhage Test does not require a subculture of the isolate. All methods produce highly sensitive and specific results for their indicated determinations with low rates of major and very major discrepancies. Table 5 summarizes the major similarities and differences between these two methods.
Table 5 - Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test - BT, the BD BBL 30 ug cefoxitin Sensi-Disc, and the BD BBL 1 ug oxacillin Sensi-Disc for MRSA/MSSA breakpoint determinations.
| SIMILARITIES | |||
|---|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture | ||
| Test - BT | BD BBL cefoxitin | ||
| 30 μg Sensi-disc | BD BBL oxacillin | ||
| 1 μg Sensi-disc | |||
| Intended Use | The KeyPathTM MRSA/MSSA Blood | ||
| Culture Test - BT is a qualitative in vitro | |||
| diagnostic test for the timely identification | |||
| of Staphylococcus aureus (S. aureus) and | |||
| determination of methicillin | |||
| susceptibility (MSSA) or methicillin | |||
| resistance (MRSA) directly from positive | |||
| blood cultures. | |||
| The Test uses bacteriophage amplification | |||
| to identify the presence of S. aureus and | |||
| assess the phenotypic response of the target | |||
| organism to cefoxitin, an indicator of | |||
| oxacillin (a methicillin analog) resistance. | |||
| The assay is performed directly on positive | |||
| blood culture specimens that are | |||
| determined as Gram Positive Cocci in | |||
| singles (GPC) or as Gram Positive Cocci in | |||
| Clusters (GPCC) by Gram stain. | |||
| The KeyPathTM MRSA/MSSA Blood | |||
| Culture Test - BT is performed directly on | |||
| positive blood culture specimens from BD | |||
| BACTECTM blood culture bottles (Plus | |||
| Aerobic/F and Plus Anaerobic/F). | |||
| The Test is indicated for use in conjunction | |||
| with other laboratory and clinical data | |||
| available to the physician as an aid in the | |||
| detection of MRSA/MSSA from positive | |||
| blood cultures. | These discs are used for | ||
| semi-quantitative *in | |||
| vitro susceptibility* | |||
| testing by the agar disc | |||
| diffusion test procedure | |||
| of common, rapidly | |||
| growing and certain | |||
| fastidious bacterial | |||
| pathogens. | These discs are used for | ||
| semi-quantitative *in | |||
| vitro susceptibility* | |||
| testing by the agar disc | |||
| diffusion test procedure | |||
| of common, rapidly | |||
| growing and certain | |||
| fastidious bacterial | |||
| pathogens. |
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| SIMILARITIES | |||
|---|---|---|---|
| Item | KeyPath™ MRSA/MSSA Blood Culture | ||
| Test - BT | BD BBL cefoxitin | ||
| 30 μg Sensi-disc | BD BBL oxacillin | ||
| 1 μg Sensi-disc | |||
| Subculturing of positive blood cultures is | |||
| necessary for additional susceptibility test | |||
| determinations, differentiation of mixed | |||
| growth and for epidemiological typing | |||
| Single Use | Yes | Yes | Yes |
| Indication | |||
| for Use | Professional Use | Professional Use | Professional Use |
| Interpretatio | |||
| n of results | Visual | Visual | Visual |
| Patient | |||
| populations | Clinical patients | Clinical patients | Clinical patients |
| Assay | |||
| controls | Pos Control 1: MRSA | ||
| Pos Control 2: MSSA | |||
| Neg Control: NSA | Pos Control: MRSA | ||
| Neg Control: MSSA | Pos Control: MRSA | ||
| Neg Control: MSSA |
| DISSIMILARITIES | |||
|---|---|---|---|
| Item | KeyPath™ MRSA/MSSA Blood | ||
| Culture Test - BT | BD BBL cefoxitin 30 µg | ||
| Sensi-disc | BD BBL oxacillin | ||
| 1 µg Sensi-disc | |||
| Specimen | Positive blood culture | Overnight Culture | Overnight Culture |
| Time to result | 5 hours | 18-24 hours | 18-24 hours |
| Mode of action | The test uses bacteriophage | ||
| amplification with cefoxitin to | |||
| quickly determine the presence of | |||
| MRSA and MSSA in positive blood | |||
| cultures. | Diffusion of antibiotic | ||
| into lawn of S. aureus. | Diffusion of antibiotic | ||
| into lawn of S. aureus. | |||
| Assay format | Amplification: bacteriophage | ||
| amplification | |||
| Detection: lateral flow immunoassay | |||
| with colloidal gold particles with | |||
| monoclonal antibodies specific to | |||
| assay bacteriophage. | Amplification: none | ||
| Detection: | |||
| Visual interpretation of | |||
| zone of inhibition. | Amplification: none | ||
| Detection: | |||
| Visual interpretation of | |||
| zone of inhibition. |
- Bolded and underlined portions indicates similarities of intended use.
Clinical Comparison Study
MicroPhage conducted a prospective clinical trial on the KeyPath™ MRSA/MSSA Blood Culture test - BT to assess the performance characteristics across four clinical sites against culture and predicate methods.
Subjects included individuals with positive blood cultures on a BACTEC™ blood culture system (9000 series or F/X). Samples were included if they were from subjects 18 years of age or older and the sample was tested on the KeyPath™ MRSA/MSSA Blood Culture Test – BT within 24 hours of positive determination on BACTECTM System (i.e. alarm). Aliquots of the blood culture were used to perform a standard culture identification for S. aureus (Catalase positive, Tube Coagulase positive, Remel Staphaurex® positive) and antimicrobial susceptibility determination (30 µg cefoxitin disk diffusion) in accordance with CLSI M100-S19.
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MicroPhage KeyPath™ MRSA/MSSA Blood Culture Test - BT: 510(k) Summary
There were a total of 1116 (366 S. aureus) paired samples tested for MRSA/MSSA by the KevPath™ MRSA/MSSA Blood Culture Test - BT and the standard methods across all study sites.
Sensitivity and specificity of the MRSA/MSSA Blood Culture Test - BT vs. the standard method for detection of S. aureus were 91.8% and 98.3%, respectively. The positive predictive value was 96.3%, and the negative predictive value was 96.1%.
For samples determined to be S. aureus, category agreement with the cefoxitin disk diffusion test was 98.9% for determination of methicillin resistance, and 99.4% for determination of methicillin susceptibility.
The initial invalid rate was 0.3%, and all invalids were resolved upon retest.
No significant differences in performance were observed across sites, or between blood culture bottle types.
No significant effect was observed in the performance of the KeyPath™ Test in the presence or absence of antibiotic or antiviral treatments.
Non-clinical Studies
Reproducibility - The KeyPath™ Test was found to be 99.4% reproducible in 648 runs at three sites (2 operators per site) over 6 days, when tested against 2 MRSA, 2 MSSA and 1 S. epidermidis strains.
Inclusivity - A panel of 114 S. aureus strains representing the phylogenetic diversity of S. aureus was tested in duplicate with the KeyPath™ Test. The panel included representatives of 17 clonal complexes and 46 multilocus sequence types. The sensitivity for detection of S. aureus was 91.8%. Category agreement was 99% for determination of methicillin-resistance and 100% for determination of methicillin-susceptibility.
Interfering substances – The KeyPath™ Test showed no interference when tested against lipemic, icteric and hemolytic blood samples. A panel of 5 antibiotics, 3 analgesics, an antiviral and an anticoagulant was tested and showed no interference. The immunoassay component (the Detector) was tested against a panel of 20 RF-positive, HAMA-positive and heterophilic antibody sera and showed no cross-reaction to any. The Detector was also tested against a panel of 32 human viruses and showed no cross-reaction.
Mixed culture – MRSA could be reliably detected by the KeyPath™ Test in mixed cultures comprised of ~90% (or greater) Gram negative rods and bacilli, Gram positive cocci in clusters (not S. aureus) and Gram positive rods.
Analytical specificity - A panel of 163 isolates comprised of 33 Gram-negative isolates (29 species), 58 Gram-positive not Staphylococci (49 species), 5 coagulase-positive Staphylococci (5 species), 60 coagulase-negative Staphylococci (9 species) and 7 yeast (7 species) was tested and showed 98.8% specificity.
Evaluation of SCCmec Empty Cassette Variants - A panel of 28 strains determined to be mecApositive (MRSA) by commercial and laboratory PCR tests but MSSA by phenotypic culture methods was tested. All 28 strains were determined to be MSSA by the KeyPath™ Test.
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We conclude that the performance of the KeyPath™ MRSA/MSSA Blood Culture Test – BT is substantially equivalent to:
- Coagulase/catalase and Staphaurex® Test for detection of S.aureus from positive 1) BACTECTM blood cultures,
- BD BBL Cefoxitin 30ug and BD BBL Oxacillin 1ug Sensi-disc Tests for determination of 2) MRSA and MSSA from S. aureus positive Bactec™ blood cultures,
- Oxoid PBP2' Latex Agglutination Test for determination of MRSA from S. aureus positive 3) BactecTM blood cultures, and
- BD GeneOhm™ StaphSR Assay for determination of S. aureus and MRSA from positive 4) blood cultures.
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Image /page/12/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized graphic of a human figure, represented by three curved lines, suggesting a person in motion or flight.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
MicroPhage, Inc. c/o Drew Smith, Ph. D. Chief Science Officer 2400 Trade Centre Avenue Longmont, Colorado 80503
- 5 2011 MAY
Re: K102342
Trade/Device Name: MicroPhage MRSA/MSSA Blood Culture Test-BT Regulation Number: 21 CFR 866.2050 Regulation Name: Staphylococcal typing bacteriophage Regulatory Class: Class I Product Code: OUS Dated: May 3, 2011 Received: May 3, 2011
Dear Dr. Smith:
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.
13
Page 2 - Dr. Drew Smith
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 Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801). please go to
http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/ReportalProblem/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 Small Manufacturers, International and Consumer Assistance 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.
Sincerely yours.
Uwe Schilf fw
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
14
MicroPhage, Inc. 2400 Trade Centre Ave. Longmont, CO 80503
510(k) Number: Device Name:
K102342 KeyPath™ MRSA/MSSA Blood Culture Test - BT
Indications for Use Statement
The KeyPath 100 MRSA Blood Culture Test - BT is a qualitative in vitro diagnostic test for the timely identification of Staphylococcus aureus (S. aureus) and determination of methicillin susceptibility (MSSA) or methicillin resistance (MRSA) directly from positive blood cultures.
The Test uses bacteriophage amplification to identify the presence of S. aureus and assess the phenotypic response of the target organism to cefoxitin, an indicator of oxacillin (a methicillin analog) resistance.
The assay is performed directly on positive blood culture specimens that are determined as Gram Positive Cocci in singles (GPC) or as Gram Positive Cocci in Clusters (GPCC) by Gram stain.
The KeyPath™ MRSA/MSSA Blood Culture Test - BT is performed directly on positive blood culture specimens from BD BACTEC™ blood culture bottles (Plus Aerobic/F and Plus Anaerobic/F).
The Test is indicated for use in conjunction with other laboratory and clinical data available to the physician as an aid in the detection of MRSA/MSSA from positive blood cultures.
Subculturing of positive blood cultures is necessary for additional susceptibility test determinations, differentiation of mixed growth and for epidemiological typing.
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510(k) K id 2342