BacT/ALERT® FA Plus Culture Bottles are used with BacT/ALERT® Microbial Detection Systems in qualitative procedures for recovery and detection of aerobic microorganisms (bacteria and yeast) from blood and other normally sterile body fluids.

BacT/ALERT® PF Plus Culture Bottles are used with BacT/ALERT® Microbial Detection Systems in qualitative procedures for recovery and detection of aerobic microorganisms (bacteria and yeast) from blood.

Device Description

The BacT/ALERT® Microbial Detection Systems utilizes a colorimetric sensor and reflected light to monitor the presence and production of carbon dioxide (CO2) dissolved in the culture medium. If microorganisms are present in the test sample, carbon dioxide is produced as the microorganisms metabolize the 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 from blue-green to 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.

BacT/ALERT® Microbial Detection Systems are used to determine if microorganisms are present in blood or other normally sterile body fluid samples taken from a patient suspected of having bacteremia/fungemia. The BacT/ALERT® Systems and culture bottles provide both a microbial detection system and a culture medium with suitable nutritional and environmental conditions for organisms commonly encountered in blood infections and other normally sterile body fluid infections. An inoculated bottle is placed into the instrument where it is incubated and continuously monitored for the presence of microorqanisms that will grow in the BacT/ALERT® FA Plus or PF Plus Culture Bottle (The BacT/ALERT® PF Plus Culture Bottle provides for detection of microorganisms when a small volume of blood is available.).

AI/ML Overview

The provided text describes the performance characteristics of the BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles, which are microbial detection systems. The study aims to demonstrate the equivalency of a modified formulation of these devices to their predicate devices.

Here's an analysis of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria	Reported Device Performance and Notes
Growth Performance	Recovery Rate: Equivalent recovery rates based on Newcombe's Hybrid Score. Time to Detection (TTD): Equivalent TTD based on the mean percent difference in TTD.	Recovery Rate: Met criteria for equivalency for all 39 microorganisms in both presence and absence of blood. TTD (with blood): Met criteria for 38 of 39 microorganisms. A delay was observed for Haemophilus parainfluenzae, though both adjusted and predicate had <100% detection. TTD (without blood - FA Plus): Met criteria for 32 of 34 microorganisms. S. aureus and S. pneumoniae showed TTD delays of 1.7h and 5h, respectively (no delay with blood). C. albicans and C. glabrata showed faster TTD (3.6h and 36.6h, respectively).
Antimicrobial Neutralization	Not explicitly stated as a general criterion, but implied to demonstrate neutralization of claimed drug categories.	Neutralized penicillins, glycyclines, polyenes, macrolides, triazoles, echinocandins, aminoglycosides, fluoroquinolones, lincosamides, glycopeptides, and oxazolidinones. One echinocandin/microorganism combination (C. albicans/caspofungin) had <100% recovery (77.8% without blood, 97% with blood). Substantial equivalency for ceftaroline, cefoxitin, and cefazolin was observed to the previous formulation. S. aureus/cefoxitin initially showed 66% recovery but 100% on retest. E. coli/cefoxitin showed 100% recovery. Less than complete neutralization for cefazolin (neutralized at 50% peak serum level in PBS). Ceftazidime, cefepime, cefotaxime, and ceftriaxone were not evaluated due to prior incomplete neutralization.
Limit of Detection (LoD)	For each microorganism tested, ≥95% recovery and detection within the 5-day test period.	Met LoD criterion for equivalency for all 11 microorganisms tested, with ≥95% recovery and detection within 5 days.
Delayed Entry	Percent recovery for delayed entry-adjusted devices was 100% within 5 days for each claimed holding temperature. False positive rate for uninoculated bottles (without organism) was <3.4%.	Met Delayed Entry recovery for all 11 microorganisms tested and the false positive rate criteria.
Within Laboratory Precision (Repeatability)	100% recovery for all organisms/variables tested.	Met repeatability criterion with 100% recovery for all organisms/variables tested.

2. Sample Size Used for the Test Set and Data Provenance

Growth Performance: A panel of 39 clinically significant microorganisms.
Antimicrobial Neutralization: Representative antimicrobials from claimed drug categories. Specific numbers of combinations are mentioned (e.g., five echinocandin/microorganism combinations, specific antimicrobial/organism pairs).
Limit of Detection: A panel of 11 microorganisms listed in the IFU.
Delayed Entry: A panel of 11 microorganisms.
Repeatability: Multiple organisms and multiple organism/antimicrobial combinations, replicates from three bottle lots.

Data Provenance: The studies were described as "internal (bioMérieux) verification studies." This suggests the data was generated internally by the device manufacturer. The text does not specify the country of origin of the data or explicitly state if the studies were retrospective or prospective, but "verification studies" implies prospective testing of the modified devices.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

This document describes the performance of a microbial detection system (culture bottles). The "ground truth" here is the actual presence and growth of microorganisms in the culture media, which is determined by the inherent biological phenomenon and observed by the instrument. This type of device does not involve human expert interpretation for "ground truth" establishment in the same way an imaging or diagnostic AI device would. The performance metrics rely on comparison to established microbiological methods or the predicate device's performance.

4. Adjudication Method for the Test Set

Not applicable. As described in point 3, the ground truth is based on the biological growth of microorganisms detected by the instrument, not on expert human interpretation that would require adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

Not applicable. This is a microbial detection system, not an AI-assisted diagnostic tool that involves human readers. Therefore, an MRMC study and a human-in-the-loop performance evaluation are not relevant in this context.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

The performance data presented here is effectively standalone performance of the device (BacT/ALERT® FA Plus and PF Plus culture bottles with the BacT/ALERT® Microbial Detection Systems). The device functions autonomously to detect microbial growth.

7. The Type of Ground Truth Used

The ground truth used in these studies is the microbiological growth and detection of specific microorganisms in the culture bottles. This is established by direct observation of microbial growth (either visually or primarily, through the instrument's detection of metabolic byproducts like CO2) and comparison to expected growth profiles for known inocula.

8. The Sample Size for the Training Set

The provided text describes verification studies for a modification to a microbial culture medium. It does not mention a "training set" in the context of machine learning or AI. The modified device's performance is compared against a predicate device and established criteria, not against a model trained on a dataset.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no "training set" mentioned or implied for this device type.

Summary

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February 11, 2019

bioMerieux, Inc. Mary Beth Anheuser Staff Regulatory Affairs Specialist 595 Anglum Road Hazelwood, Missouri 63042

Re: K183166

Trade/Device Name: BacT/ALERT FA Plus; BacT/ALERT PF Plus Regulation Number: 21 CFR 866.2560 Regulation Name: Microbial growth monitor Regulatory Class: Class I Product Code: MDB Dated: November 13, 2018 Received: November 15, 2018

Dear Mary Beth Anheuser:

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/cfpmn/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.

Steven R. Gitterman -S 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) K183166

Device Name BacT/ALERT® FA Plus BacT/ALERT® PF Plus

Indications for Use (Describe)

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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Traditional 510(k) SUMMARY

BacT/ALERT® FA Plus and BacT/ALERT® PF Plus Traditional 510(k): Device Modification

A. 510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Mary Beth AnheuserStaff, Regulatory Affairs Specialist
Phone Number:	314-731-8516
Fax Number:	314-731-8689
Date of Preparation:	December 13, 2018
Device Name:
Formal/Trade Name:	BacT/ALERT® FA Plus and PF Plus
Classification Name:	Blood Culturing System, Microbiology21 CFR 866.2560
Common Name:	BacT/ALERT® FA PlusBacT/ALERT® PF Plus
Predicate Device:	BacT/ALERT® FA Plus (K121461)BacT/ALERT® PF Plus (K121446)

D. 510(k) Summary:

Principle of the Test

Summarv and Explanation

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will grow in the BacT/ALERT® FA Plus or PF Plus Culture Bottle (The BacT/ALERT® PF Plus Culture Bottle provides for detection of microorganisms when a small volume of blood is available.).

Intended Use

BacT/ALERT® FA Plus Culture Bottles are used with BacT/ALERT® Microbial Detection Systems in qualitative procedures for recovery and detection of aerobic and facultative anaerobic microorganisms (bacteria and yeast) from blood and other normally sterile body fluids.

BacT/ALERT® PF Plus Culture Bottles are used with BacT/ALERT® Microbial Detection Systems in qualitative procedures for recovery and detection of aerobic and facultative anaerobic microorganisms (bacteria and yeast) from blood.

NOTE: This submission is the result of a modification to the BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture media formulation. The intended use of the BacT/ALERT® FA Plus and BacT/ALERT® PF Plus, as described in their labeling (package inserts), has not changed as a result of this modification to the common growth medium formulation. This modification does not affect the fundamental scientific technology of this device.

Device Comparison

The modified BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles have the same Intended Use & Indications for Use, Principle of the Test, Test Method and Specimen Sampling and Handling as the predicate devices (BacT/ALERT®FA Plus (K121461) and BacT/ALERT® PF Plus (K121446) culture bottles). The modified BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture media formulation has been adjusted to add essential elements and to remove non-essential trace components.

Substantial Equivalence

The BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles, modified through a formulation adjustment, demonstrated equivalent performance, which was established during internal (bioMérieux) verification studies performed on the BacT/ALERT Microbial Detection Systems. A substantial equivalence decision was determined when compared with the BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottle formulation cleared under K121461 and K121446. respectively.

Performance Characteristics

Analytical studies to evaluate the Growth Performance (percent recovery and time to detection). Antimicrobial Neutralization, Limit of Detection, Delayed Entry, Repeatability and Stability were conducted to verify the equivalency of the adjusted BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottle formulation to the BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles cleared under K121461 and K121446, respectively.

Growth Performance

A panel of 39 clinically significant microorganisms were tested in a direct comparison between the adiusted and predicate BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles in the presence and absence of blood. Equivalency was established if:

. the recovery rates of the adjusted devices were determined to be equivalent based on the Newcombe's Hybrid Score.

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the time to detection (TTD) of the strains tested was determined to be equivalent . based on the mean percent difference in TTD between the adjusted and predicate devices.
The recovery rate for the39 microorqanisms evaluated in both the presence and absence of blood in the adiusted BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles met the criteria for equivalency to the predicate BacT/ALERT® FA Plus (K121461) and BACT/ALERT® PF Plus (K121446) culture bottles.

The time-to-detection (TTD) for 38 of the 39 microorganisms evaluated for growth performance in the adjusted BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles, in the presence of blood, met the criteria for equivalency to the predicate BacT/ALERT® FA Plus (K121461) and BacT/ALERT®PF Plus (K121446) culture bottles. A delay in TTD was observed for Haemophilus parainfluenzae in the adjusted BacT/ALERT FA Plus and the PF Plus bottles, although both the adjusted and predicate had less than 100% detection.

The TTD for 32 out of 34 microorganisms evaluated for growth performance in the adjusted BacT/ALERT® FA Plus culture bottles, in the absence of blood, met the criteria for equivalency to the predicate BacT/ALERT® FA Plus (K121461) culture bottle. In the absence of blood, S. aureus and S. pneumoniae had a mean TTD delay of 1.7 hours and 5 hours, respectively, when tested in the adjusted BacT/ALERT FA Plus bottle. However, it should be noted that in the presence of blood there was no delay in TTD for S. aureus and S. pneumoniae. In the absence of blood. C. albicans and C. glabrata had a faster mean TTD of 3.6 and 36.6 hours. respectively. when tested in the adjusted BacT/ALERT FA Plus.

Antimicrobial Neutralization

After formulation adjustments, representative antimicrobials from the claimed drug categories were tested in the adjusted BacT/ALERT FA Plus and PF Plus culture bottles. in the absence of blood, unless otherwise noted.

Antimicrobials from the following categories were neutralized by the adjusted medium: penicillins, glycyclines, polyenes, macrolides, triazoles, echinocandins, aminoglycosides, fluoroquinolones, lincosamides, glycopeptides, and oxazolidinones. Five echinocandin/ microorganism combinations were tested; one combination had a recovery rate of less than 100%. In the absence of blood, a 77.8% recovery rate was observed in the adjusted BacT/ALERT FA Plus and PF Plus bottles for C. albicans/caspofungin. In the presence of blood, a 97% recovery rate was observed in the adjusted BacT/ALERT FA Plus and PF Plus bottles for C. albicans/caspofungin. In addition, substantial equivalency for ceftaroline, cefoxitin, and cefazolin was observed between the adjusted and previous formulation for neutralization of the individual drugs. For S. aureus/cefoxitin, 66% recovery was observed initially, however, retest results showed 100% recovery. For E. coli/cefoxitin, a 100% recovery was observed. Less than complete neutralization was observed for cefazolin. which was neutralized at 50% peak serum level (PSL) when tested in PBS. Ceftazidime, cefepime, cefotaxime, and ceftriaxone were not evaluated in the adjusted formulation as less than complete neutralization was achieved in the previous formulation.

Limit of Detection

The equivalency of the adjusted BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles for Limit of Detection (LoD) was established using a panel of 11 microorganisms listed in the IFU at a target concentration within a factor of two (+2 fold) of the established LoD reported. Equivalency for LoD was established if:

For each microorganism tested, ≥95% recovery and detection was observed within . the 5 day test period.

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The adjusted BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles met the LoD criterion for equivalency with ≥95% recovery and detection within the 5 day test period for the 11 microorganisms tested.

Delayed Entry

Delayed entry is defined as a greater than 2-hour lapse in time between bottle inoculation and bottle loading. The equivalency of the adjusted BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles for delayed entry testing was established using a panel of 11 microorganisms. Inoculated bottles were tested with and without blood and were held at specified temperatures and times prior to loading into the instruments. Equivalency for Delayed Entry was established if:

Percent recovery for delayed entry-adjusted devices was 100% within 5 days for each . claimed holding temperature.
The false positive rate for uninoculated bottles (those without organism) was <3.4% .

The adjusted BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles met the Delayed Entry recovery for the 11 microorganisms tested and the false positive rate criteria to establish equivalency.

Within Laboratory Precision (Repeatability)

The equivalency of the adjusted BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles for repeatability was established using multiple organisms and multiple organism/antimicrobial combinations tested over multiple test days, operators, in the presence and absence of blood, and replicates from three bottle lots.

The adjusted BacT/ALERT® FA Plus and BacT/ALERT® PF Plus culture bottles met the repeatability criterion with 100% recovery for all organisms / variables tested.

Regulation Number and Section

§ 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.