(85 days)
Not Found
No
The summary describes a reagent system for detecting mycobacteria and does not mention any AI or ML components.
No
The device is designed for the recovery and detection of mycobacteria from specimens, which is a diagnostic purpose, not a therapeutic one.
Yes
The device is designed for the "recovery and detection of mycobacteria" from clinical specimens, which indicates its use in identifying the presence of a disease-causing agent, thus falling under the definition of a diagnostic device.
No
The device description explicitly states it consists of three reagents: a culture bottle and two supplements. These are physical components, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the system is designed for the "recovery and detection of mycobacteria from sterile body specimens other than blood, and from digested/decontaminated clinical specimens." This involves testing samples taken from the human body to provide information for diagnostic purposes.
- Device Description: The device consists of reagents (culture bottle and supplements) used in a laboratory setting to perform a test on a biological sample.
- Performance Studies: The document describes clinical and analytical performance studies conducted to validate the device's ability to accurately detect mycobacteria in clinical specimens. This is a key characteristic of IVDs, which require validation of their performance for diagnostic use.
- Key Metrics: The document provides key performance metrics like sensitivity and specificity, which are standard measures used to evaluate the accuracy of diagnostic tests.
- Predicate Device: The mention of a predicate device (K031737; BACT/ALERT® MP Culture Bottle) further indicates that this device is being compared to an existing device used for similar diagnostic purposes, which is common in the regulatory process for IVDs.
All these factors align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for 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 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.
Product codes (comma separated list FDA assigned to the subject device)
MDB
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.
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 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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
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 (100 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%.
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:
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.
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:
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:
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%.
False Negative Rate for the BACT/ALERT® MP (REF 419744):
| False Negative BACT/ALERT® MP (REF 419744) | Total Samples Collected | Percentage of False Negative BACT/ALERT® MP (REF 419744) | |
|---|---|---|---|
| Clinical Samples | 2 | 1,488 | 0.13% |
False Positive Rate for the BACT/ALERT® MP (REF 419744):
| False Positive BACT/ALERT® MP (REF 419744) | Total Samples Collected | Percentage of False Positive BACT/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):
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.
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 | Number of Isolates | Time to Detection (days) BACT/ALERT® MP (REF 419744) Mean | 95% CI for the mean | Time to Detection (days) BACT/ALERT® MP (REF 259797) Mean | 95% CI for the mean | Mean TTD Diff. (BACT/ALERT® MP (REF 419744) - BACT/ALERT® MP (REF 259797)) (in Days) | 95% CI for Mean Diff. in TTD |
|---|---|---|---|---|---|---|---|
| M. tuberculosis complex species | 50 | 11.6 | 10.0 - 13.3 | 14.4 | 12.4 - 16.3 | -2.7 | (-4.2, -1.3) |
| Non-tuberculous mycobacteria Rapid Growers | 30 | 7.3 | 6.4 – 8.2 | 7.4 | 6.4 – 8.5 | -0.1 | (-0.7, 0.5) |
| Non-tuberculous mycobacteria Slow Growers | 83 | 11.5 | 10.1 – 12.8 | 11.8 | 10.6 - 12.9 | -0.3 | (-1.3, 0.7) |
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity for BACT/ALERT® MP Reagent System (REF 419744) is 86.58% (95% Cl: 81.50%, 90.70%)
Sensitivity for BACT/ALERT® MP Culture Bottle (REF 259797) is 81.39% (95% Cl: 75.76%, 86.19%)
Specificity for BACT/ALERT® MP Reagent System (REF 419744) is 96.75% (95% CI: 95.49%, 97.74%)
Specificity for BACT/ALERT® MP Culture Bottle (REF 259797) is 93.79% (95% Cl: 92.16%, 95.18%)
Overall BACT/ALERT® MP (REF 419744) recovery rate is 94.34%
Overall BACT/ALERT® MP (REF 259797) recovery rate is 88.68%
False Negative BACT/ALERT® MP (REF 419744) percentage: 0.13%
False Positive BACT/ALERT® MP (REF 419744) percentage: 2.28%
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.
BACT/ALERT® MP Culture Bottle (K031737)
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
§ 866.2560 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.
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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
1
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
2
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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Image /page/3/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle with a blue semi-circle at the top and a green semi-circle at the bottom. The word "BIOMÉRIEUX" is written in white letters in the center of the blue semi-circle. The green semi-circle has a gradient, with the color fading from yellow to green.
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 Street
Durham, NC 27712 |
|----------------------|----------------------------------------------------------------------------------------------------------------|
| Contact Person: | Esther Hernandez
Regulatory Affairs Specialist
595 Anglum Rd.
Hazelwood, MO 63042
314-731-8841 |
| Alternative Contact: | Nathan Hardesty
Senior Manager, Regulatory Affairs
595 Anglum Rd.
Hazelwood, MO 63042
314-731-8666 |
| Fax Number: | 314-731-8689 |
| Date of Preparation: | February 8, 2019 |
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Image /page/4/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle with a blue top half and a yellow-green bottom half. The word "BIOMÉRIEUX" is written in white letters across the center of the blue half of the circle.
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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Image /page/6/Picture/0 description: The image shows the logo for bioMerieux. The logo is a circle that is split into two halves. The top half is blue and contains the word "BIOMERIEUX" in white letters. The bottom half of the circle is a gradient of yellow and green.
| Major Similarities | ||
|---|---|---|
| Characteristic | Test Device | |
| BACT/ALERT®MP | ||
| Reagent System | ||
| (K190405) | Predicate Device | |
| BACT/ALERT® MP | ||
| Culture Bottle (K031737) | ||
| Classification | Classification Name: Blood Culturing | |
| System - Microbiology | ||
| Regulation Number: 21CFR | ||
| 866.2560 (Microbial Growth Monitor) | Classification Name: Blood | |
| Culturing System - Microbiology | ||
| Regulation Number: 21CFR | ||
| 866.2560 (Microbial Growth Monitor) | ||
| Product Code | MDB | MDB |
| 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 System for recovery and | ||
| detection of mycobacteria from sterile | ||
| body specimens other than blood, and | ||
| from digested-decontaminated clinical | ||
| specimens. | The BACT/ALERT® MP Culture | |
| Bottle consists of the BACT/ALERT® | ||
| MP Culture Bottle with a removable | ||
| closure used in conjunction with the | ||
| MB/BacT Antimicrobial Supplement | ||
| (and /or the MB/BacT Reconstitution | ||
| Fluid). The BacT/ALERT MP System | ||
| is designed for use with the MB/BacT | ||
| or 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. | ||
| Sample Type | Sterile body specimen other than | |
| blood and digested/decontaminated | ||
| clinical specimens. | Sterile body specimen other than | |
| blood and digested/decontaminated | ||
| clinical specimens. | ||
| Technology | Reflectance | Reflectance |
| Color change | ||
| based on CO2 | ||
| production | Yes | Yes |
| Growth of | ||
| microorganism | Yes | Yes |
| Differences | ||
| Characteristic | Test Device BACT/ALERT"" MP | |
| Reagent System | ||
| (K190405) | Predicate Device BACT/ALERT"" | |
| MP Culture Bottle (K031737) | ||
| Storage Temperature: 15°- 30°C | Storage Temperature: 2°- 8°C | |
| Formulation Changes | ||
| MP Culture | ||
| Bottle | Not Present | Pancreatic digest of casein |
| Not Present | Bovine Serum Albumin (BSA) | |
| Not Present | Catalase in Purified Water | |
| Magnesium | Not Present | |
| Formulation Changes | ||
| MP | ||
| Antimicrobial | ||
| Supplement | Not Present | Azlocillin |
| Addition of Fosfomycin | Not Present | |
| Polymixin B (in trace amounts) | ||
| increased by approximately 20% as | ||
| compared to the | ||
| predicate device | Polymixin B | |
| Trimethoprim (in trace amounts) | ||
| increased by approximately 350% as | ||
| compared to the predicate device | Trimethoprim | |
| Not Present | Vancomycin | |
| Formulation Changes | ||
| MP Nutrient | ||
| Supplement | Addition of Fatty Acids (in trace | |
| amounts) | Not Present | |
| Addition of Pancreatic Digest of | ||
| Casein (in trace amounts) | Not Present | |
| Use of Fatty Acid free Bovine Serum | ||
| Albumin (BSA) | Bovine Serum Albumin (BSA) | |
| Addition of a-ketoglutarate | Not Present |
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Image /page/7/Picture/0 description: The image shows the logo for bioMerieux. The logo is a circle that is split into two halves. The top half is blue and contains the word "BIOMERIEUX" in white, sans-serif font. The bottom half of the circle is yellow and green, with the yellow fading into green.
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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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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 (REF
419744) and
BACT/ALERT®
MP (REF
259797) | BACT/ALERT®
MP (REF
419744) Only | BACT/ALERT®
MP (REF
259797) Only | Total
Number of
Positives | BACT/ALERT®
MP (REF
419744) | BACT/ALERT®
MP (REF
259797) | Difference
in Recovery
Rate |
|-------|----------------------------------------------------------------------------|----------------------------------------|----------------------------------------|---------------------------------|-----------------------------------|-----------------------------------|-----------------------------------|
| 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 Negative
BACT/ALERT® MP
(REF 419744) | Total Samples Collected | Percentage of False Negative
BACT/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 Positive
BACT/ALERT® MP
(REF 419744) | Total Samples Collected | Percentage of False Positive
BACT/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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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 | Number
of
Isolates | Time to Detection (days)
BACT/ALERT® MP
(REF 419744) | | Time to Detection (days)
BACT/ALERT® MP (REF
259797) | | Mean TTD Diff.
(BACT/ALERT® MP
(REF 419744) -
BACT/ALERT® MP
(REF 259797))
(in Days) | 95% CI for
Mean Diff.
in TTD |
|---------------------------------------------------------|--------------------------|------------------------------------------------------------|------------------------|------------------------------------------------------------|------------------------|-----------------------------------------------------------------------------------------------------|------------------------------------|
| | | Mean | 95% CI for the
mean | Mean | 95% CI for the
mean | | |
| M. tuberculosis
complex
species | 50 | 11.6 | 10.0 - 13.3 | 14.4 | 12.4 - 16.3 | -2.7 | (-4.2, -1.3) |
| Non-
tuberculous
mycobacteria
Rapid
Growers | 30 | 7.3 | 6.4 – 8.2 | 7.4 | 6.4 – 8.5 | -0.1 | (-0.7, 0.5) |
| Non-
tuberculous
mycobacteria
Slow
Growers | 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).