(85 days)
The BACT/ALERT® MP Reagent System consists of the BACT/ALERT® MP culture bottle with a removable closure used in conjunction with the BACT/ALERT® MP Antimicrobial Supplement and the BACT/ALERT® MP Nutrient Supplement. The BACT/ALERT® MP Reagent System is designed for use with BACT/ALERT® 3D Mycobacteria Detection Systems for recovery and detection of mycobacteria from sterile body specimens other than blood, and from digested/decontaminated clinical specimens.
BACT/ALERT® MP Reagent System consists of three reagents: BACT/ALERT® MP Culture Bottle, the BACT/ALERT® MP Antimicrobial Supplement and the BACT/ALERT® MP Nutrient Supplement.
The provided text describes the performance characteristics of the BACT/ALERT® MP Reagent System, comparing it to a predicate device (BACT/ALERT® MP Culture Bottle) for the recovery and detection of mycobacteria.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a table format with pass/fail thresholds. However, it presents the performance of the new device and the predicate device, implying that the new device aims to be equivalent or superior, particularly in Time To Detection. The study demonstrates that the new device has increased sensitivity and specificity and a faster time to detection for certain mycobacteria species.
For the purpose of this response, I will interpret the performance metrics presented as the "reported device performance" and infer that the device meets implied acceptance criteria by being equivalent or better than the predicate.
| Performance Metric | BACT/ALERT® MP Reagent System (REF 419744) (Test Device) | BACT/ALERT® MP Culture Bottle (REF 259797) (Predicate Device) | Implied Acceptance Criterion (e.g., must be equivalent or better than predicate) |
|---|---|---|---|
| Analytical Sensitivity: LoD | |||
| M. avium | ≤ 15 CFU/bottle (100% detection) | Not explicitly stated for predicate in LoD section | Low LoD (e.g., ≤ the predicate device's LoD) |
| M. kansasii | ≤ 4 CFU/bottle (100% detection) | Not explicitly stated for predicate in LoD section | Low LoD (e.g., ≤ the predicate device's LoD) |
| M. tuberculosis | ≤ 14 CFU/bottle (100% detection) | Not explicitly stated for predicate in LoD section | Low LoD (e.g., ≤ the predicate device's LoD) |
| Analytical Sensitivity: Growth Performance | 100% detection at high (10^6^ CFU/bottle) and low (10^2^ CFU/bottle) inoculum levels | Not explicitly stated for predicate | 100% detection for tested organisms at varying inoculum concentrations |
| Within-Laboratory Precision - Recovery Rate | 100% recovery for all test events and concentrations | Not explicitly stated for predicate | 100% recovery rate |
| Reproducibility - Overall Recovery Rate (Pleural Fluid) | 99.6% | Not explicitly stated for predicate | High recovery rate (e.g., ≥ 95%) |
| Reproducibility - Overall Recovery Rate (Simulated Sputum) | 99.9% | Not explicitly stated for predicate | High recovery rate (e.g., ≥ 95%) |
| Clinical Performance - Sensitivity | 86.58% (95% CI: 81.50%, 90.70%) | 81.39% (95% CI: 75.76%, 86.19%) | Equivalent or superior to predicate; the test device showed a 5.19% increase in sensitivity. |
| Clinical Performance - Specificity | 96.75% (95% CI: 95.49%, 97.74%) | 93.79% (95% CI: 92.16%, 95.18%) | Equivalent or superior to predicate; the test device showed a 2.96% increase in specificity. |
| Clinical Performance - Overall Recovery Rate (Positive Mycobacteria Samples) | 94.34% | 88.68% | Equivalent or superior to predicate; the test device showed a 5.66% increase. |
| False Negative Rate (Clinical Samples) | 0.13% (2/1,488) | Not explicitly stated for predicate | Low false negative rate (e.g., ≤ predicate's or a clinically acceptable threshold). |
| False Positive Rate (Clinical Samples) | 2.28% (34/1,488) | Not explicitly stated for predicate | Low false positive rate (e.g., ≤ predicate's or a clinically acceptable threshold). |
| Time to Detection (TTD) - M. tuberculosis complex species | Mean: 11.6 days | Mean: 14.4 days | Faster than predicate (demonstrated -2.7 days mean difference). |
| Time to Detection (TTD) - Non-tuberculous Mycobacteria Rapid Growers | Mean: 7.3 days | Mean: 7.4 days | Faster than or equivalent to predicate (demonstrated -0.1 days mean difference, considered faster). |
| Time to Detection (TTD) - Non-tuberculous Mycobacteria Slow Growers | Mean: 11.5 days | Mean: 11.8 days | Faster than or equivalent to predicate (demonstrated -0.3 days mean difference, considered faster). |
2. Sample size used for the test set and data provenance:
-
Clinical Performance Studies (for Sensitivity, Specificity, Recovery Rates):
- Sample Size: 1,488 specimens obtained from 1,162 patients.
- Data Provenance: Prospective clinical study conducted at 3 different sites. The document does not specify the country of origin, but generally, FDA submissions involve studies conducted in or for the US market, potentially with multi-national sites.
-
Analytical Performance Studies (LoD, Growth Performance, Precision, Reproducibility):
- Sample Size: Varies by study (e.g., LoD specified as lowest inoculum level with >95% recovery, Growth Performance at high and low inoculum levels, Precision on a minimum of 3 lots over 12 days, Reproducibility with 5 organisms at low and high concentrations in two matrices). Specific total sample numbers for these analytical studies are not given, but generally involve laboratory-controlled experiments.
- Data Provenance: In-house seeded studies and tests at clinical trial sites (for reproducibility). The specific country of origin is not mentioned for these internal studies.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided in the document. The ground truth for clinical samples appears to be established by laboratory results using both the test and predicate devices, and primary solid medium culture ("a sample has a positive patient infected status when one of the BACT/ALERT® MP (REF 419744 or 259797) subcultures is positive, or the primary solid medium is positive"). This implies a laboratory-based gold standard rather than expert clinical consensus or adjudication on imaging, for example.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
The document does not describe an adjudication method involving multiple human readers or a specific consensus process for reviewing diagnostic results in the test set. The ground truth seems to be determined by a combination of positive results from subcultures of both the test and predicate devices, and primary solid medium culture. This is a laboratory-based ground truth, not one requiring human expert adjudication.
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:
This device is a microbial growth monitor and not an AI-powered diagnostic imaging tool or a system that requires human "readers" in the context of an MRMC study. Therefore, an MRMC comparative effectiveness study, as typically understood for AI-assisted image interpretation, was not performed and is not applicable here. The comparison is between two laboratory systems (the new device vs. the predicate).
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The device (BACT/ALERT® MP Reagent System) is an automated system for detecting microbial growth. Its performance is inherently standalone in the sense that the instrument provides the detection signal without continuous human intervention for interpretation in the same way an AI algorithm for image analysis would. The "algorithm" here is the system's ability to detect CO2 production. The study evaluates the performance of this system directly.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth for the clinical performance studies (sensitivity, specificity, recovery) in the document is defined as follows:
- Positive Patient Infected Status: "A sample has a positive patient infected status when one of the BACT/ALERT® MP (REF 419744 or 259797) subcultures is positive, or the primary solid medium is positive."
- Negative Patient Infected Status: "A sample has a negative patient infected status when both BACT/ALERT® MP (REF 419744 and 259797) subcultures are negative and the primary solid media is negative (i.e. there is no growth of mycobacteria)."
This is a laboratory-based and culture-confirmed ground truth, relying on the isolation and identification of mycobacteria from subcultures and primary solid media.
8. The sample size for the training set:
The document does not mention a training set because this is a medical device for in-vitro diagnostics based on chemical reactions and optical detection, not typically a machine learning or AI algorithm that requires a separate training set. The "formulation changes" and "analytical performance studies" represent the development and validation of the reagent system itself.
9. How the ground truth for the training set was established:
As no training set is mentioned or applicable in the context of this device's type, there is no information on how ground truth for a training set was established.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
May 15, 2019
bioMerieux, Inc. Esther Hernandez Regulatory Affairs Specialist 595 Anglum Road Hazelwood, Missouri 63042
Re: K190405
Trade/Device Name: BACT/ALERT MP Reagent System Regulation Number: 21 CFR 866.2560 Regulation Name: Microbial growth monitor Regulatory Class: Class I Product Code: MDB Dated: February 15, 2019 Received: February 19, 2019
Dear Esther Hernandez:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmp/pmn.cfm identifies combination product submissions. 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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see
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https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
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) K190405
Device Name BACT/ALERT® MP Reagent System
Indications for Use (Describe)
The BACT/ALERT® MP Reagent System consists of the BACT/ALERT® MP culture bottle with a removable closure used in conjunction with the BACT/ALERT® MP Antimicrobial Supplement and the BACT/ALERT® MP Nutrient Supplement. The BACT/ALERT® MP Reagent System is designed for use with BACT/ALERT® 3D Mycobacteria Detection Systems for recovery and detection of mycobacteria from sterile body specimens other than blood, and from digested/decontaminated clinical specimens.
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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510(k) SUMMARY
BACT/ALERT® MP Reagent System
A. 510(k) Number: K190405
B. Purpose for Submission: To establish substantial equivalence for the BACT/ALERT MP Reagent System, consisting of the following components: BACT/ALERT MP Culture Bottle, BACT/ALERT MP Nutrient Supplement, and BACT/ALERT MP Antimicrobial Supplement. The BACT/ALERT MP Reagent System component formulations were modified to decrease Time To Detection for mycobacteria compared to the previously cleared BACT/ALERT® MP Culture Bottle (K031737).
C. Measurand: See Intended Use
D. Type of Test: The BACT/ALERT® MP Reagent System consists of three components: the BACT/ALERT MP Culture Bottle, Antimicrobial Supplement and Nutrient Supplement. All three components are used together for the culture and recovery of mycobacteria from sterile or nonsterile (digested/decontaminated) specimens, other than blood.
E. Applicant:
| Submitter's Name: | bioMérieux, Inc.100 Rodolphe StreetDurham, NC 27712 |
|---|---|
| Contact Person: | Esther HernandezRegulatory Affairs Specialist595 Anglum Rd.Hazelwood, MO 63042314-731-8841 |
| Alternative Contact: | Nathan HardestySenior Manager, Regulatory Affairs595 Anglum Rd.Hazelwood, MO 63042314-731-8666 |
| Fax Number: | 314-731-8689 |
| Date of Preparation: | February 8, 2019 |
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F. Proprietary and Established Names:
| Formal/Trade Name: | BACT/ALERT® MP Reagent System |
|---|---|
| Common Name: | BACT/ALERT® MP |
| G. Regulatory Information: | |
| 1. Regulation Section: | 21 CFR 866.2560 |
| 2. Device Classification /Requlation Name: | Blood Culturing System - Microbiology /Microbial Growth Monitor |
| 3. Product Code: | MDB |
| 4. Predicate Device: | BACT/ALERT® MP Culture Bottle (K031737) |
H. Intended Use:
The BACT/ALERT® MP Reagent System consists of the BACT/ALERT® MP Culture Bottle with a removable closure used in conjunction with the BACT/ALERT® MP Antimicrobial Supplement and the BACT/ALERT® MP Nutrient Supplement. The BACT/ALERT® MP Reagent System is designed for use with the BACT/ALERT® 3D Mycobacteria Detection Systems for recovery and detection of mycobacteria from sterile body specimens other than blood, and from digested/decontaminated clinical specimens.
l. Device Description:
BACT/ALERT® MP Reagent System consists of three reagents: BACT/ALERT® MP Culture Bottle, the BACT/ALERT® MP Antimicrobial Supplement and the BACT/ALERT® MP Nutrient Supplement.
SUMMARY AND EXPLANATION
BACT/ALERT® Mycobacteria Detection Systems, used in conjunction with the BACT/ALERT® MP Reagent System, provide both a microbial detection system and a culture media with suitable nutritional and environmental conditions to recover mycobacterial species commonly isolated from patient specimens other than blood. The BACT/ALERT® MP Antimicrobial Supplement is intended to reduce the incidence of break through contamination due to bacteria which may survive the digestion/decontamination process. Reconstituted
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BACT/ALERT® MP Antimicrobial Supplement must be added to BACT/ALERT® MP bottles prior to inoculation of all non-sterile specimens. For recovery of mycobacteria present in sterile specimens, only the BACT/ALERT® MP Nutrient Supplement should be added to the BACT/ALERT® MP bottles. BACT/ALERT® MP Nutrient Supplement contains components which are necessary to ensure optimal growth of mycobacteria present in the patient sample and is used for reconstitution of BACT/ALERT® MP Antimicrobial Supplement. Inoculated bottles are loaded into the instrument where they are incubated and continuously monitored for the presence of mycobacteria that will grow in the BACT/ALERT® MP culture bottle.
PRINCIPLE OF THE TEST
BACT/ALERT® Mycobacteria Detection Systems utilize the same principle to detect microorganisms in cultures taken from processed patient samples as is described for the BACT/ALERT® Microbial Detection System with respect to blood cultures. BACT/ALERT® Mycobacteria Detection Systems utilize a colorimetric sensor and reflected light to monitor the presence and production of carbon dioxide (CO2) dissolved in the culture medium. If microorqanisms are present in the test sample, carbon dioxide is produced as the organisms metabolize substrates in the culture medium. When growth of the microorganisms produces CO2, the color of the gas-permeable sensor installed in the bottom of each culture bottle changes to lighter green or yellow. The lighter color results in an increase of reflectance units monitored by the system. Bottle reflectance is monitored and recorded by the instrument every 10 minutes. At the time of detection, approximate colony forming units (CFUs) per mL are 10° -107.
J. Substantial Equivalence Information:
The BACT/ALERT® MP Reagent System, which consists of the BACT/ALERT® MP Culture Bottle (REF 419744), and the BACT ALERT® MP Antimicrobial Supplement (MAS) kit (REF 414997), that contains the BACT/ALERT® MP Nutrient Supplement and the BACT/ALERT® MP Antimicrobial Supplement, demonstrated substantially equivalent performance to the predicate BACT/ALERT® MP Culture Bottle (REF 259797), and the MP Antimicrobial Supplement Kit (REF 259760). A comparison between the BACT/ALERT® MP Reagent System and predicate device is provided in the following table:
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| Major Similarities | ||
|---|---|---|
| Characteristic | Test DeviceBACT/ALERT®MPReagent System(K190405) | Predicate DeviceBACT/ALERT® MPCulture Bottle (K031737) |
| Classification | Classification Name: Blood CulturingSystem - MicrobiologyRegulation Number: 21CFR866.2560 (Microbial Growth Monitor) | Classification Name: BloodCulturing System - MicrobiologyRegulation Number: 21CFR866.2560 (Microbial Growth Monitor) |
| Product Code | MDB | MDB |
| Intended Use | The BACT/ALERT® MP ReagentSystem consists of the BACT/ALERT®MP Culture Bottle with a removableclosure used in conjunction with theBACT/ALERT® MP AntimicrobialSupplement and the BACT/ALERT®MP Nutrient Supplement. TheBACT/ALERT® MP Reagent System isdesigned for use with theBACT/ALERT® 3D MycobacteriaDetection System for recovery anddetection of mycobacteria from sterilebody specimens other than blood, andfrom digested-decontaminated clinicalspecimens. | The BACT/ALERT® MP CultureBottle consists of the BACT/ALERT®MP Culture Bottle with a removableclosure used in conjunction with theMB/BacT Antimicrobial Supplement(and /or the MB/BacT ReconstitutionFluid). The BacT/ALERT MP Systemis designed for use with the MB/BacTor the BacT/ALERT® 3D MycobacteriaDetection Systems for recovery anddetection of mycobacteria from sterilebody specimens other than blood,and from digested-decontaminatedclinical specimens. |
| Sample Type | Sterile body specimen other thanblood and digested/decontaminatedclinical specimens. | Sterile body specimen other thanblood and digested/decontaminatedclinical specimens. |
| Technology | Reflectance | Reflectance |
| Color changebased on CO2production | Yes | Yes |
| Growth ofmicroorganism | Yes | Yes |
| Differences | ||
| Characteristic | Test Device BACT/ALERT"" MPReagent System(K190405) | Predicate Device BACT/ALERT""MP Culture Bottle (K031737) |
| Storage Temperature: 15°- 30°C | Storage Temperature: 2°- 8°C | |
| Formulation Changes | ||
| MP CultureBottle | Not Present | Pancreatic digest of casein |
| Not Present | Bovine Serum Albumin (BSA) | |
| Not Present | Catalase in Purified Water | |
| Magnesium | Not Present | |
| Formulation Changes | ||
| MPAntimicrobialSupplement | Not Present | Azlocillin |
| Addition of Fosfomycin | Not Present | |
| Polymixin B (in trace amounts)increased by approximately 20% ascompared to thepredicate device | Polymixin B | |
| Trimethoprim (in trace amounts)increased by approximately 350% ascompared to the predicate device | Trimethoprim | |
| Not Present | Vancomycin | |
| Formulation Changes | ||
| MP NutrientSupplement | Addition of Fatty Acids (in traceamounts) | Not Present |
| Addition of Pancreatic Digest ofCasein (in trace amounts) | Not Present | |
| Use of Fatty Acid free Bovine SerumAlbumin (BSA) | Bovine Serum Albumin (BSA) | |
| Addition of a-ketoglutarate | Not Present |
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K. Performance Characteristics:
External (i.e. a clinical performance evaluation) and internal (i.e., analytical studies) studies were conducted to validate the performance of the BACT/ALERT MP Reagent System. The following tables show the results of the BACT/ALERT® MP tested on the BACT/ALERT® 3D.
Analytical Performance Studies
Analytical Sensitivity: Limit of Detection (LoD):
Data in the following table represent results from in-house seeded studies to determine the LoD. For this study, seeded samples were tested in the presence of reconstituted Antimicrobial Supplement, representing the reagent system as a whole. The lowest inoculum level with a recovery rate of > 95% was defined as the LoD. For all organisms listed, 100% detection was achieved at LoD.
| Microorganism | Strain ID | LoD (CFU/bottle) |
|---|---|---|
| Mycobacterium avium | ATCC® 25291™ | ≤ 15 |
| Mycobacterium kansasii | ATCC® 12478™ | ≤ 4 |
| Mycobacterium tuberculosis | ATCC® 25177™ | ≤ 14 |
Analytical Sensitivity: Growth Performance:
In-house seeded studies were conducted at high (10° CFU/bottle) and low (102 CFU/bottle) target inoculum concentrations in the presence of either Nutrient Supplement and Antimicrobial Supplement or Nutrient Supplement alone. The organism panel consisted of clinical and environmental mycobacteria species based on clinical prevalence. For all organisms tested, 100% detection was achieved for both inoculum concentrations in the presence and absence of the Antimicrobial Supplement.
Within-Laboratory Precision - Repeatability:
Internal seeded studies were conducted on a minimum of 3 lots over 12 days in multiple matrices (i.e., simulated sputum and pleural fluid) by multiple operators. Organisms were spiked into the matrices at high (1000 CFU/bottle) and low (300 CFU/bottle) target inoculums. 100% recovery was observed for all test events and concentrations.
Reproducibility:
Each clinical trial site tested a sample panel which consisted of 5 organisms at low (300 CFU/bottle) and high (1000 CFU/bottle) target concentrations in two different matrices; simulated sputum and pleural fluid.
The overall BACT/ALERT® MP Reagent System recovery rate for all the tested microorganisms from pleural fluid was 99.1% for the 300 CFU/bottle concentration, and 100% for the 1000 CFU/bottle concentration. The overall recovery rate from pleural fluid for both concentrations was 99.6%.
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The overall BACT/ALERT® MP Reagent System recovery rate for all the microorganisms from simulated sputum was 99.8% for the 300 CFU/bottle concentration, and 100% for the 1000 CFU/bottle concentration. The overall recovery rate from simulated sputum for both concentrations was 99.9%.
Clinical Performance Studies
Device Performance Relative to Positive Patient Infected Status - Sensitivity: To demonstrate that the device performance of BACT/ALERT® MP Reagent System (REF 419744) relative to positive patient infected status is equivalent to BACT/ALERT® MP Culture Bottle (REF 259797), a prospective clinical study was conducted at 3 different sites. A total of 1,488 specimens (matched pair design) were obtained from 1,162 patients suspected of mycobacterial infection, of which 231 had a positive patient infected status.
A sample has a positive patient infected status when one of the BACT/ALERT® MP (REF 419744 or 259797) subcultures is positive, or the primary solid medium is positive. The sensitivity was calculated as the number of positive samples with mycobacteria organisms isolated (BACT/ALERT® MP (REF 419744) or BACT/ALERT® MP (REF 259797)) out of the total number of samples with a positive patient infected status.
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- . Sensitivity for BACT/ALERT® MP Reagent System (REF 419744) is 200/231 = 86.58% (95% Cl: 81.50%, 90.70%)
- . Sensitivity for BACT/ALERT® MP Culture Bottle (REF 259797) is 188/231 =81.39% (95% Cl: 75.76%, 86.19%)
The increase in sensitivity for the BACT/ALERT®® MP Reagent System (REF 419744) is 5.19% (95% Cl: -1.83%, 12.19%) as compared to the BACT/ALERT® MP Culture Bottle (REF 259797).
Device Performance Relative to Negative Patient Infected Status - Specificity:
To demonstrate that the device performance of BACT/ALERT® MP Reagent System (REF 419744) relative to negative patient infected status is equivalent to BACT/ALERT® MP Culture Bottle (REF 259797), a total of 1,488 specimens (in a matched pair design) were prospectively collected from 1,162 patients suspected of mycobacterial infection, of which 1047 specimens had a negative patient infected status.
A sample has a negative patient infected status when both BACT/ALERT® MP (REF 419744 and 259797) subcultures are negative and the primary solid media is negative (i.e. there is no growth of mycobacteria). The specificity was calculated as the number of negative samples with no mycobacteria organisms isolated (BACT/ALERT® MP (REF 419744) or BACT/ALERT® MP (REF 259797)) out of the total number of samples with a negative patient infected status.
- . Specificity for BACT/ALERT® MP Reagent System (REF 419744) is 1013/1047 = 96.75% (95% CI: 95.49%, 97.74%)
- Specificity for BACT/ALERT® MP Culture Bottle (REF 259797) is 982/1047 = . 93.79% (95% Cl: 92.16%, 95.18%)
The increase in specificity for the BACT/ALERT® MP Reagent System (REF 419744) is 2.96% (95% Cl: 1.08%, 4.89%) as compared to the BACT/ALERT® MP Culture Bottle (REF 259797).
Total Number of Positive Mycobacteria Samples and Recovery Rates:
To demonstrate that the recovery of mycobacteria from BACT/ALERT® MP Reagent System (REF 419744) is equivalent to BACT/ALERT® MP Culture Bottle (REF 259797), a total of 1,488 specimens (in a matched pair design) were collected from 3 different sites to obtain a total of 212 positive mycobacteria samples. Recovery rate was calculated as the number of positive samples with mycobacteria organisms isolated (BACT/ALERT® MP (REF 419744) or BACT/ALERT® MP (REF 259797) culture bottle) out of the total number of positive samples with mycobacteria organisms recovered. The overall BACT/ALERT® MP (REF 419744) recovery rate is 94.34%, and the overall BACT/ALERT® MP (REF 259797) recovery rate is 88.68%, with a difference in recovery rates of 5.66%.
The following table displays the total number of samples positive for mycobacteria that were recovered at each site by both BACT/ALERT® MP (REF 419744) and BACT/ALERT® MP (REF
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Image /page/11/Picture/0 description: The image shows the logo for bioMérieux. The logo consists of a blue circle at the top, with the company name "BIOMÉRIEUX" in white, sans-serif font. Below the company name is a white horizontal bar, and below that is a gradient circle that transitions from yellow to green.
259797), BACT/ALERT® MP (REF 419744) only, and BACT/ALERT® MP (REF 259797) only, as well as the recovery rate for each culture bottle and the difference in recovery rates between the culture bottles.
| BACT/ALERT®MP (REF419744) andBACT/ALERT®MP (REF259797) | BACT/ALERT®MP (REF419744) Only | BACT/ALERT®MP (REF259797) Only | TotalNumber ofPositives | BACT/ALERT®MP (REF419744) | BACT/ALERT®MP (REF259797) | Differencein RecoveryRate | |
|---|---|---|---|---|---|---|---|
| Total | 176 | 24 | 12 | 212 | 94.34% | 88.68% | 5.66% |
The recovery rate for BACT/ALERT® MP (REF 419744) is greater than the recovery rate for BACT/ALERT® MP (REF 259797).
False Negative Rate for the BACT/ALERT® MP (REF 419744):
The false negative rate was calculated as the number of BACT/ALERT® MP (REF 419744) bottles that had negative instrument results when viable mycobacterial organisms were present in the bottle as confirmed by subculture and identification, out of the total number of bottles tested. See the following table for the false negative rate for BACT/ALERT® MP (REF 419744),
| False NegativeBACT/ALERT® MP(REF 419744) | Total Samples Collected | Percentage of False NegativeBACT/ALERT® MP(REF 419744) | |
|---|---|---|---|
| Clinical Samples | 2 | 1,488 | 0.13% |
False Positive Rate for the BACT/ALERT® MP (REF 419744):
The false positive rate was calculated as the number of BACT/ALERT® MP (REF 419744) bottles that had positive instrument results when no viable orqanisms were present in the bottle as confirmed by subculture out of the total number of bottles tested. See the following table for the false positive rate for BACT/ALERT® MP (REF 419744).
| False PositiveBACT/ALERT® MP(REF 419744) | Total Samples Collected | Percentage of False PositiveBACT/ALERT® MP(REF 419744) | |
|---|---|---|---|
| Clinical Samples | 34 | 1,488 | 2.28% |
Summary of Time to Detection - BACT/ALERT® MP (REF 419744) vs BACT/ALERT® MP (REF 259797):
Time to detection summary was calculated for M. tuberculosis complex species, nontuberculous Mycobacteria rapid growers, and non-tuberculous Mycobacteria slow growers recovered from clinical specimens by both BACT/ALERT® MP (REF 419744) and BACT/ALERT® MP (REF 259797) in a bottle pair.
The mean time to detection for M. tuberculosis complex species was 11.6 days for BACT/ALERT® MP Reagent System (REF 419744), and 14.4 days for BACT/ALERT® MP Culture Bottle (REF 259797), with a mean time to detection difference of 2.7 days.
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Image /page/12/Picture/0 description: The image shows the logo for bioMérieux, a French multinational biotechnology company. The logo consists of a circle divided into two sections. The top section is a dark blue color and contains the company name "BIOMÉRIEUX" in white, sans-serif font. The bottom section is a gradient of yellow and green.
The mean time to detection for non-tuberculous Mycobacteria rapid growers was 7.3 days for BACT/ALERT® MP Reagent System (REF 419744), and 7.4 days for BACT/ALERT® MP Culture Bottle (REF 259797), with a mean time to detection difference of 0.1 days. The mean time to detection for non-tuberculous Mycobacteria slow growers was 11.5 days for BACT/ALERT® MP Reagent System (REF 419744), and 11.8 days for BACT/ALERT® MP Culture Bottle (REF 259797), with a mean time to detection difference of 0.3 days.
| Group | NumberofIsolates | Time to Detection (days)BACT/ALERT® MP(REF 419744) | Time to Detection (days)BACT/ALERT® MP (REF259797) | Mean TTD Diff.(BACT/ALERT® MP(REF 419744) -BACT/ALERT® MP(REF 259797))(in Days) | 95% CI forMean Diff.in TTD | ||
|---|---|---|---|---|---|---|---|
| Mean | 95% CI for themean | Mean | 95% CI for themean | ||||
| M. tuberculosiscomplexspecies | 50 | 11.6 | 10.0 - 13.3 | 14.4 | 12.4 - 16.3 | -2.7 | (-4.2, -1.3) |
| Non-tuberculousmycobacteriaRapidGrowers | 30 | 7.3 | 6.4 – 8.2 | 7.4 | 6.4 – 8.5 | -0.1 | (-0.7, 0.5) |
| Non-tuberculousmycobacteriaSlowGrowers | 83 | 11.5 | 10.1 – 12.8 | 11.8 | 10.6 - 12.9 | -0.3 | (-1.3, 0.7) |
Using the mean difference in time to detection for all bottle pairs positive for M. tuberculosis complex species, the BACT/ALERT® MP Reagent System (REF 419744) had a significantly faster time to detection than the BACT/ALERT® MP Culture Bottle (REF 259797). Using the mean differences in time to detection for all bottle pairs positive for non-tuberculous mycobacteria rapid growers and for non-tuberculous mycobacteria slow growers, BACT/ALERT® MP (REF 419744) had a faster time to detection than BACT/ALERT® MP (REF 259797).
§ 866.2560 Microbial growth monitor.
(a)
Identification. A microbial growth monitor is a device intended for medical purposes that measures the concentration of bacteria suspended in a liquid medium by measuring changes in light scattering properties, optical density, electrical impedance, or by making direct bacterial counts. The device aids in the diagnosis of disease caused by pathogenic microorganisms.(b)
Classification. Class I. With the exception of automated blood culturing system devices that are used in testing for bacteria, fungi, and other microorganisms in blood and other normally sterile body fluids, this device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter.