The BD BACTEC Plus PRIME Aerobic/F blood culture medium is used in a qualitative procedure for the aerobic culture and recovery of microorganisms (bacteria and yeast) from blood. The principal use of this medium is with the BD BACTEC fluorescent series instruments.

Device Description

The sample to be tested is inoculated into one or more vials which are inserted into the BACTEC fluorescent series instrument for incubation and periodic reading. Each vial contains a chemical sensor which can detect increases in CO2 produced by the growth of microorganisms. The sensor is monitored by the instrument every ten minutes for an increase in its fluorescence, which is proportional to the amount of CO2 present. A positive reading indicates the presumptive presence of viable microorganisms in the vial. Detection is limited to microorganisms that will grow in a particular type of medium.

Resins have been described for the treatment of blood specimens both prior to and after their inoculation into culture media. Resins have been incorporated into BACTEC culture media to enhance recovery of organisms without a need for special processing.

AI/ML Overview

Here's an analysis of the provided text regarding the BD BACTEC Plus PRIME Aerobic/F medium:

Key Takeaway: This document is a 510(k) summary for a medical device (blood culture medium) seeking FDA clearance. It's a "substantial equivalence" claim, meaning the device is compared to a legally marketed predicate device rather than a ground-up demonstration of safety and effectiveness as in a PMA. Therefore, the "acceptance criteria" and "study that proves the device meets the acceptance criteria" are framed within this comparison to the predicate device. The performance data focuses on demonstrating that the new device performs equivalently or, in some cases, better than the predicate.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by achieving performance that is not significantly different or clinically equivalent to the predicate device, or statistically better where a difference is desirable (like antimicrobial neutralization).

Acceptance Criteria (Implicit)	Reported Device Performance
Time to Detection (TTD): No clinically relevant difference compared to predicate.	Median TTD difference: 0.92 hours (55 minutes) between new and predicate device (for 333 paired positive sets). For 10-100 CFU inoculum, ~80% of 244 paired sets had TTD difference < 10%. 18% had TTD increases, 2% had TTD decreases with the new device. A few specific organisms showed more rapid TTD in the predicate (e.g., Streptococcus sanguinis 8.12 h faster, Kingella kingae 4.38 h faster). Leuconostoc spp. showed a 10.00h (14.45%) increase in TTD in the new device. Conclusion: "minimal" effect of differences on TTD, new device performs "equivalently."
Percent Recovery: No significant difference in recovery compared to predicate.	Paired sets positive in both: 244 out of 246 (99.2%) evaluated. McNemar p-value: 0.1573. Conclusion: No statistically significant difference, new device performs "equivalently."
False Positive Rate: No false positives (similar to predicate).	Total paired sets: 120 (40 bottles from each of 3 lots). Result: All 120 paired sets completed protocol with no positive results observed in either new or predicate devices.
False Negative Rate: Low or acceptable false negative rate (similar or better than predicate).	Total paired sets: 93. Result: Two false negative results with the new device for Kingella kingae (3 mL blood, 31 CFU). These replicates failed to recover. Subsequent testing of 5 K. kingae isolates (including the false negative one) showed expected growth/recovery over 3 lots.
Antimicrobial Neutralization Capability: Equivalent or superior recovery compared to predicate (especially with additional resin).	At MIC level: Equivalent performance. 100% recovery in 10 out of 11 drug classes for both devices. For aztreonam, new device: 55.6% recovery, predicate: 66.7% recovery. McNemar p-value: 0.5637 (no statistically significant difference). At Peak Serum Level: 150 paired sets. Concentrations at ~20x MIC. McNemar p-value: < 0.0001. Conclusion: Significant difference between new and predicate devices in favor of the new device. This indicates improved performance in high antimicrobial concentrations.

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

Time to Detection:
- 333 paired sets (positive in both new and predicate devices).
- 244 paired sets (at 10-100 CFU inoculum level).
Percent Recovery: 246 paired sets.
False Positive Rate: 120 paired sets (comprised of 40 bottles from each of 3 lots).
False Negative Rate: 93 paired sets.
Antimicrobial Neutralization Capability:
- MIC level: No specific count of paired sets provided, but "Eleven drugs representative of their classes were evaluated."
- Peak serum level: 150 paired sets.

Data Provenance: The document does not specify the country of origin of the data. Given it's a submission to the FDA, it's typically assumed to be North American, but this is not explicitly stated. The studies described are prospective in nature, as they involve inoculating fresh human blood and organisms into the new and predicate devices under controlled test conditions to evaluate performance parameters.

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

This type of study for a blood culture medium does not typically involve human experts in the way clinical diagnostic imaging or pathology studies do. The "ground truth" is established through laboratory methods (e.g., known bacterial/yeast cultures, plate counts for CFU, confirmation of growth via subculture) and comparison against the results of a legally marketed predicate device (BD BACTEC Plus Aerobic/F medium).

4. Adjudication Method for the Test Set

Not applicable. This is not a study assessing human reader performance. "Ground truth" is based on laboratory results and instrumental readings.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC study was not done. This study pertains to the performance of a culture medium and an instrument's ability to detect microbial growth, not human interpretation of medical images or data.

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

Yes, the studies described are standalone in nature. The "device" (BD BACTEC Plus PRIME Aerobic/F medium used with the BACTEC fluorescent series instruments) operates without human intervention once the sample is inoculated and inserted into the instrument. The instrument's algorithm (detection of CO2 increase via fluorescence) determines a positive result. The performance metrics (TTD, recovery, false positive/negative rates) are based solely on the device's output.

7. The Type of Ground Truth Used

The ground truth is based on microbiological assay results and instrumental detection of microbial growth, compared against the performance of a well-established predicate device. Specifically:

Known organisms and inoculum levels: Organisms are spiked into the blood samples at controlled concentrations (e.g., 10-100 CFU).
Positive/negative status: Determined by the instrument's detection of metabolic activity (CO2 production) or confirmed by terminal subcultures.
Comparison to predicate: The predicate device serves as the primary benchmark for "expected" performance under similar conditions.

8. The Sample Size for the Training Set

The document does not provide information about a "training set" in the context of machine learning or AI models. This device is a culture medium, and its development and validation are based on traditional microbiology and analytical studies, not a machine learning approach that would typically involve distinct training and test sets for an algorithm. If there were implicit "training" it would have been the historical data and R&D leading to the formulation, which is not detailed here.

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

As mentioned above, the concept of a "training set" and associated ground truth establishment (as in AI/ML) is not applicable to this type of device and study. The development of such a medium relies on biochemical principles, empirical formulation, and iterative testing in a laboratory setting.

Summary

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7 2012

AUG

510(k) SUMMARY SUBMITTED BY: BECTON, DICKINSON AND COMPANY 7 LOVETON CIRCLE

SPARKS, MD 21152 Phone: 410-316-4905 Fax: 410-316-4499

Paul Swift, Regulatory Affairs Specialist CONTACT NAME: DATE PREPARED: August 7. 2012 DEVICE TRADE NAME: BD BACTEC Plus PRIME Aerobic/F

DEVICE COMMON NAME: Aerobic blood culture medium

DEVICE CLASSIFICATION: 21 CFR§866.2560, Class I

PREDICATE DEVICE: BD BACTEC PLUS Aerobic/F medium (K083572)

INTENDED USE:

The BD BACTEC Plus PRME Aerobic/F medium is used in a qualitative procedure for the aerobic culture and recovery of microorganisms (bacteria and yeast) from blood. The principal use of this medium is with the BD BACTEC fluorescent series instruments.

DEVICE DESCRIPTION:

Resins have been described for the treatment of blood specimens both prior to and affer their inoculation into culture media. Resins have been incorporated into BACTEC culture media to enhance recovery of organisms without a need for special processing. 12-3.4

BD Diagnostic Systems Becton, Dickinson and company Page 1

1 Wallis, C. et al. 1980. Rapid isolation of bacteria from septicemic patients by use of an antimicrobial agent removal device. J. Clin.Microbiol. 11:462-464.

2 Applebaum, P.C. et al. 1983. Enhanced detection of bacteremia with a new BACTEC resin blood culture medium. J. Clin. Microbiol. 17:48-51.

3 Pohlman, J.K. et al. 1995: Controlled clinical comparison of Isolator and BACTEC 9240 Aerobic/F resin bottle for detection of bloodstream infections. J. Clin. Microbiol. 33:2525-2529.

4 Flayhart, D. et al. 2007. Comparison of BACTEC Plus blood culture media to BacT/Alert FA blood culture media for detection of bacterial pathogens in samples containing therapeutic levels of antibiotics. J. Clin. Microbiol. 45:816-821.

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DEVICE COMPARISON:

The BD BACTEC Plus PRIME Acrobic/F medium differs from the BD BACTEC Plus Aerobic/F (K083572) medium in the following ways:

The resin blend in the modified device consists of two hydrophobic adsorbing . resins and one cationic exchange resin; whereas, the current legally marketed device contains one hydrophobic adsorbing resin and one cationic exchange resin.
The percent of total resin blend per weight volume is lower in the modified device . compared to the current legally marketed device.
The concentration of sodium polyanetholsulfonate (SPS) is 0.085% per weight . volume in the modified device; whereas, the current legally marketed device contains 0.05% SPS per weight volume.

The BD BACTEC Plus PRIME Aerobic/F medium is similar to the BD BACTEC Plus Acrobic/F (K083572) medium in the following ways:

Both the new and predicate devices are used for the qualitative aerobic culture ● and recovery of microorganisms from human blood.
Both devices are intended to be used with the BD BACTEC fluorescent-series of . blood culture instruments.
. The BD BACTEC fluorescent-series of blood culture instruments apply the same incubation and agitation parameters to both devices.
The BD BACTEC fluorescent-series of blood culture instruments apply the same . growth and detection algorithms to both devices.
Both devices are incubated at 35°C (± 1.5°C) for a period of up to 120 hours. o
. Both devices incorporate resins for the adsorption of antimicrobials that may be present in clinical samples.
. Both devices incorporate a sensor that detects increases in CO2 within the bottle as a result of organism growth. Both devices require a sample volume of 3 - 10 mL of blood.
Both devices utilize 30 mL of enriched soybean casein digest broth as the growth ● medium.
. Both devices have a maximum blood to broth ratio of 1:4.
Both devices are contained in glass vials. .

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SUMMARY OF PERFORMANCE DATA

Analytical Studies:

Instrument Time to Detection

A total of 333 paired sets were positive in both the new and predicate devices. There was no clinically relevant difference in recovery hours between the BD BACTEC Plus PRIME Aerobic/F blood culture medium and the predicate device. The estimated median TTD difference for the 333 positive sets is 0.92 hours (55 minutes). At the 10 to 100 CFU inoculum level, approximately 80% of 244 paired sets had a time to detection difference of less than 10%: 18% of the paired sets that had time to detection increases, and approximately 2% had time to detection decreases with the BD BACTEC Plus PRIME Aerobic/F medium when comparing to the predicate device.

The following organisms had a mean TTD difference that was more rapid in the predicate device: Abiotrophia defectiva (2.39 h), Acinetobacter Iwoffii (0.97), Cardiobacterium hominis (3.11 h), Haemophilus influenzae (3.70 h), Streptococcus sanguinis (8.12 h), Candida albicans (0.75 h), Enterococcus faecalis (0.62 h), Granulicatella spp. (1 h), Kingella kingae (4.38 h), Micrococcus luteus (1.06 h), Pediococcus acidilactici (1.08 h) and Streptococcus pneumoniae (0.81 h). Leuconostoc spp. exhibited a mean TTD difference increase of 10.00 h compared to the predicate device (mean TTD of 69.21 h), an increase of 14.45% in the new device.

The data indicate that the effect of differences between the new and predicate devices on TTD under these test conditions was minimal and that the new device performs equivalently to the predicate device.

Percent Recovery

A total of 246 paired sets were evaluated in the Percent Recovery comparison. There was no significant difference in recovery between the BD BACTEC Plus PRIME Aerobic/F blood culture medium and the predicate device. Of those, 244 paired sets were positive in both the new and predicate devices (99.2%). The McNemar p-value for this data set equals 0.1573. The data indicate that the effect of differences between the new and predicate devices on percent recovery under these test conditions was not statistically significant and that the new device performs equivalently to the predicate device.

False Positive Rate

A total of 120 paired sets were used to execute this study. The 120 paired sets were comprised of 40 bottles from each of 3 lots. The paired sets were inoculated with fresh human blood at varying levels as specified by the test protocol and entered into the the BACTEC blood culture instrument. It was expected that each bottle would be instrumentnegative following the complete protocol (120 hours). All 120 paired sets completed the protocol with no positive results observed in either the new or predicate devices.

BD Diagnostic Systems Becton, Dickinson and company Page 3

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False Negative Rate

A total of 93 paired sets were evaluated for the determination of the False Negative Rate of the new device. There were two false negative results with the new device: Kingella kingae with 3 mL of blood (plate count 31 CFU). The K. kingae replicates that failed to recover in the new device were determined to be false negative based on the expected test results. Terminal subcultures of both replicates resulted in no growth. Subsequent testing of five isolates of K. kingae, including the false negative isolate noted above, under the same test conditions and over three lots all demonstrated growth and recovery as expected.

Antimicrobial Neutralization Capability

Both the new and predicate devices incorporate resins to enhance the recovery of microorganisms by adsorption of antibiotics in the blood sample. The new device incorporates a third resin for additional antimicrobial neutralization capability. Eleven drugs representative of their classes were evaluated at the MIC level of selected strains to demonstrate equivalent performance of the new device to the predicate device. At the MIC level, both devices demonstrated complete recovery (100%) in 10 out of 11 drug classes. With aztreonam, observed recovery rates were 55.6% and 66.7% for the BD BACTEC Plus PRIME Aerobic/F medium and the BD BACTEC Plus Aerobic/F medium, respectively. There was no statistically significant difference in recovery between the new and predicate devices observed during this evaluation (McNemar's test p-value = 0.5637).

A total of 150 paired sets were evaluated at the peak serum level. Concentrations of antimicrobials in test vials were at an average of 20x the MIC of the test organisms. The P-value for the peak serum level drug-bug challenge as calculated with the McNemar's test was less than (<) 0.0001, indicating a significant difference between the new and predicate devices at peak serum levels, in favor of the new device.

The following antimicrobial classes were evaluated in this study:

Aminoglycosides .
3rd gen. Cephalosporins .
4" gen. Cephalosporins
Glycylcvcline
Carbapenems
Glycopetides
- Tetracyclines Triazoles
Monobactams

' Fluoroquinolones

Penicillins / ß-lactamase inhibitors
BD Diagnostic Systems Becton, Dickinson and company Page 4

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the text "Food and Drug Administration". The text is written in a simple, sans-serif font and is left-aligned. The words are arranged on a single line and are evenly spaced.

10903 New Hampshire Avenue Silver Spring, MD 20993

Becton, Dickinson and Company c/o Paul Swift 7 Loveton Circle Sparks, MD. 21152

AUG 7 2012

K120994 Rc:

Trade Name: BD BACTEC Plus PRIME Aerobic/F Regulation Number: 21 CFR §866.2560 Regulation Name: Microbial growth monitor Regulatory Class: Class I Product Codes: MDB Dated: July 27, 2012 Received: July 30, 2012

Dear Mr. Swift:

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 approvisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 modified in any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

Image /page/4/Picture/11 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized image of an eagle or bird with outstretched wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird image.

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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760 -- For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRI's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Uve Saf for

Sally A. Hojvat, M.Sc., Ph.D Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

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INDICATION FOR USE

_510(k) Number (if.known): 12-19-09-94

Device Name: BD BACTEC Plus PRIME Aerobic/F Blood Culture Medium

Indication For Use:

The BD BACTEC Plus PRIME Aerobic/F blood culture medium is used in a qualitative procedure for the aerobic culture and recovery of microorganisms (bacteria and yeast) from blood. The principle use of this medium is with BD BACTEC Fluorescent Series Instruments.

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Ludolie tu-Coole

ision Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K120994

BD Diagnostic Systems Becton, Dickinson and company

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.