The BD BACTEC Plus 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

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

The provided submission describes a device comparison study rather than independent validation against a predefined acceptance criterion. The study aims to demonstrate substantial equivalence of the new device (BD BACTEC Plus Aerobic/F in a plastic bottle) to a predicate device (BD BACTEC Plus Aerobic/F in a glass bottle) in terms of performance. Therefore, the "acceptance criteria" are implicitly defined by the performance of the predicate device.

Here's an analysis based on your requested information:

1. A table of acceptance criteria and the reported device performance

Since specific, quantitative acceptance criteria are not explicitly stated in isolation (i.e., "device must achieve X accuracy"), the acceptance criteria are inferred as demonstrating statistical equivalence or non-inferiority to the predicate device in various performance metrics.

Performance Metric	Implied Acceptance Criteria (relative to predicate device)	Reported Device Performance (BD BACTEC Plus Aerobic/F (plastic))
Instrument Time to Detection (TTD)	No significant difference in recovery and TTD difference should be minimal.	Wilcoxon estimated median TTD difference of 0.083 hours (5 minutes) across 726 positive paired sets. A few organisms showed TTD differences >1 hour, but overall considered minimal.
Percent Recovery	No statistically detectable difference in percent recovery.	McNemar p-value of 1 for 738 paired sets (726 positive in both), indicating no statistically detectable difference.
False Positive Rate	No false positives within the recommended usage range (3-10 mL blood).	No false positive bottles observed within the recommended usage range. Two false positives with <3 mL blood (outside range).
False Negative Rate	Minimal false negatives, especially for clinically significant organisms.	One false negative (Leuconostoc spp. with 3 mL blood, 35 CFU), which is identified as a slow-growing organism and generally not clinically significant.
BACTEC Instrument Compatibility	Performance equivalent to the predicate device across different BACTEC fluorescent-series instruments.	McNemar p-value of 1.00 across BACTEC FX, 9240, and 9050 instruments for recovery. TTD equivalent for FX and 9240. BACTEC 9050 showed a statistically significant TTD difference of 0.417 hours (25 minutes) favoring the predicate.
Reproducibility (across lots)	No statistically significant difference in recovery and TTD across lots compared to the predicate.	No statistically significant difference in recovery for all lots. Lots 1 and 3 showed no significant TTD difference. Lot 2 showed a statistically significant TTD difference (10 minutes) due to the BACTEC 9050's performance.
Antimicrobial Neutralization Capability	No statistically significant difference in resin-dependent recovery compared to the predicate device.	All three lots of the new device detected more drug-bug combinations than the predicate. No statistically significant difference observed in resin-dependent recovery.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Instrument Time to Detection & Percent Recovery:
- Test Set Sample Size: 726 paired sets (for TTD), 738 paired sets (for Percent Recovery).
False Positive Rate:
- Test Set Sample Size: 240 paired sets (80 bottles from each of 3 lots).
False Negative Rate:
- Test Set Sample Size: 82 paired sets.
BACTEC Instrument Compatibility:
- Test Set Sample Size: 246 paired sets (new and predicate devices) tested in each of three BACTEC instruments.
Reproducibility:
- Test Set Sample Size: Not explicitly stated as a separate number, but implied to be based on the paired sets across different lots for TTD and recovery.
Antimicrobial Neutralization Capability:
- Test Set Sample Size: 377 drug-bug combinations per lot (for 3 lots).

Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective. Given the nature of a 510(k) submission for a medical device, these are typically prospective studies conducted under controlled laboratory conditions, often simulating clinical use. The use of "fresh human blood" indicates a simulated clinical environment for some tests.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This device is a culture medium for microbial recovery. The "ground truth" for each sample (i.e., presence/absence and identification of microorganisms) would typically be established through laboratory standard techniques such as subculturing and microbial identification (e.g., plating cultures, gram staining, biochemical tests). The document does not mention the use of human experts (like radiologists) for establishing ground truth, as that is not relevant for this type of in-vitro diagnostic device. The ground truth refers to the actual microbial content as determined by standard microbiological methods, rather than human interpretation.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. The ground truth is established by microbiological methods directly (e.g., isolation and identification of organisms), not by expert adjudication of interpretations.

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

Not applicable. This device is an in-vitro diagnostic culture medium, not an AI-assisted diagnostic tool that involves human readers/interpreters in the diagnostic process. The performance is assessed directly at the instrument and medium level.

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

This refers to the performance of the device itself (the culture medium and its interaction with the BACTEC instrument's detection system), independent of human interpretation. Yes, standalone performance was assessed. The studies described (TTD, Percent Recovery, False Positive/Negative, Instrument Compatibility, Reproducibility, Antimicrobial Neutralization) are all evaluations of the intrinsic performance of the medium and the automated instrument detection system. There is no human interpretation component in the primary detection process that would require a human-in-the-loop study.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth for this device is based on microbiological isolation and identification via laboratory standard methods. This involves:

For positive samples: Confirmation of microbial growth and identification of the specific organisms present.
For negative samples: Confirmation of the absence of microbial growth over the incubation period by subculture or other means.
For false negative cases, like the Leuconostoc example, the "ground truth" that an organism was present but undetected by the device would be established by post-protocol subculture results.

8. The sample size for the training set

The document does not report a "training set" sample size. This is because the studies described are device performance validation studies for a modified culture medium, not machine learning model development. The device itself (the medium and its sensor) is designed to detect CO2 changes, and the "algorithms" mentioned in the device description refer to the instrument's pre-programmed growth and detection algorithms, which would have been developed and validated previously, and are applied consistently across both new and predicate devices.

9. How the ground truth for the training set was established

Not applicable, as there is no mention of a "training set" in the context of machine learning for this device. The ground truth for the validation studies was established via standard microbiological techniques as described in point 7.

Summary

{0}------------------------------------------------

510(k) SUMMARY

MAR 1 6 2012

SUBMITTED BY:

BECTON, DICKINSON AND COMPANY 7 LOVETON CIRCLE SPARKS, MD 21152 Phone: 410-316-4905 410-316-4499 Fax:

CONTACT NAME: DATE PREPARED: Paul Swift, Regulatory Affairs Specialist March 7, 2012

BD BACTEC Plus Aerobic/F (plastic) DEVICE TRADE NAME:

DEVICE COMMON NAME: Aerobic blood culture medium

DEVICE CLASSIFICATION: 21 CFR §866.2560, Class I

PREDICATE DEVICE: BD BACTEC PLUS Aerobic/F medium (K921133)

INTENDED USE:

DEVICE DESCRIPTION:

BD Diagnostic Systems Becton, Dickinson and company Page 1

1 Wallis, C. et al. 1980. Rapid isolation of bacteria from septicents 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.

{1}------------------------------------------------

DEVICE COMPARISON:

The BD BACTEC Plus Aerobic/F (plastic) differs from the BD BACTEC Plus Aerobic/F (K921133) in the following ways:

The medium in the new device is contained in a plastic bottle; whereas, the . medium in the predicate device is contained in a glass bottle.
: The new device's sensor has been adjusted to obtain equivalent performance to that of the predicate device.
. The sugar concentration of the growth medium in the new device has been increased by 0.2%.
The new device weighs approximately 60% less than predicate device. .
The new device measures 5.0 inches high compared to the predicate device height . of 5.6 inches.

The BD BACTEC Plus Aerobic/F (plastic) is similar to the BD BACTEC Plus Aerobic/F (K921133) 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. .
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.

{2}------------------------------------------------

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. ●

BD Diagnostic Systems Becton, Dickinson and company

{3}------------------------------------------------

SUMMARY OF PERFORMANCE DATA

Analytical Studies:

Instrument Time to Detection

A total of 726 paired sets were positive in both the new and predicate devices. There was no significant difference in recovery between the BD BACTEC Plus Aerobic/F blood culture medium contained in plastic bottles and the predicate device contained in glass bottles. The Wilcoxon estimated median TTD difference for the 726 positive sets is 0.083 hours (5 minutes).

The following organisms exhibited TTD differences of greater than 1 hour (plastic vials minus glass vials): Candida glabrata (-2.83), Cryptococcus neoformans (-1.67), Haemophilus parainfluenzae biotype I (1.33). Micrococcus luteus (2.83), Leuconostoc spp. (8.00) (i.e., Candida glabruta and Cryptococcus neoformans recovered faster in the new device; whereas Haemophilus parainfluenzae biotype I, Micrococcus luteus and Leuconostoc spp. recovered faster in the predicate device). Micrococcus luteus is rarely implicated as a cause of human infections and is usually considered a contaminant of clinical specimens. Leuconostoc spp. is very rarely isolated in blood culture specimens and when it is, it is often not clinically significant.

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 738 paired sets were evaluated in the Percent Recovery comparison. Of those, 726 paired sets were positive in both the new and predicate devices (98.4%). The McNemar p-value for this data set equals 1. The data indicate that the effect of differences between the new and predicate devices on percent recovery under these test conditions was not statistically detectable and that the new device performs equivalently to the predicate device.

Leuconostoc spp. was recovered in nearly all replicates of the new device (17 of 18) and the predicate device (16 of 18). This organism is rarely associated with human disease and is usually considered a probable contaminant.

False Positive Rate

A total of 240 paired sets were used to execute this study. The 240 paired sets were comprised of 80 bottles from each of 3 lots. The paired sets were inoculated with fresh human blood at varving levels as specified by the test protocol and entered into the BACTEC blood culture instrument. It was expected that each bottle would be instrumentnegative following the complete protocol (120 hours). There were no false positive bottles of the new device observed within the recommended usage range of blood

BD Diagnostic Systems Becton, Dickinson and company Page 4

{4}------------------------------------------------

volumes (3 to 10 mL). Two false positive bottles were observed when inoculated with a blood volume outside of the recommended usage range for the device (<3 mL).

False Negative Rate

A total of 82 paired sets were evaluated for the determination of the False Negative Rate of the new device. There was one false negative result with the new device: Leuconostoc spp. with 3 mL of blood (plate count 35 CFU). The Leuconostoc species that failed to recover in the new device was a false negative based on the post-protocol subculture results. The Leuconostoc species is a slow-growing organism in both the new and predicate devices that typically detects late in protocol. Leuconostoc spp. was recovered in nearly all replicates of the new device (17 of 18). Leuconostoc is rarely isolated in blood culture specimens and, when it is, it is often not clinically significant.

BACTEC Instrument Compatibility

A total of 246 paired sets (new and predicate devices) were tested in each the BACTEC FX. BACTEC 9240 and BACTEC 9050 fluorescent-series blood culture instruments. A recovery comparison of the new device versus the predicate device results in a McNemar p-value of 1.00 across instruments, demonstrating that the performance of the new device is equivalent to the predicate device in each of the BACTEC fluorescent series blood culture instruments.

The BACTEC 9240 and BACTEC FX both did not have a statistically significant difference in time to detection between the new and predicate devices. The BACTEC 9050 exhibited a statistically significant difference in time to detection between the new and predicate devices. In the BACTEC 9050, the Wilcoxon median time to detection difference estimate is 0.417 hours (25 minutes) in favor of the predicate device.

Reproducibility

The new device was evaluated for reproducibility across lots in terms of time to detection and recovery. For each lot, there was no statistically significant difference observed in recovery comparing the new and predicate devices. Both Lots 1 and 3 exhibited no statistically significant difference in time to detection between the new and predicate devices. Lot 2 exhibited a statistically significant difference in time to recovery between the new and predicate devices due to the increased time to detection exhibited in the BACTEC 9050 instrument. The median time to detection difference exhibited by Lot 2 was 10 minutes.

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. A total of 18 drugs were tested with organisms that would be clinically treated with the antimicrobials. The battery of drugs selected was based on clinical importance and use and were intended to be representative of a wide variety of antimicrobial classes. The amount of antimicrobial added to each bottle represents the amount found in 7 mL of blood at or near the peak

{5}------------------------------------------------

serum level. Additionally, a supplemental study was conducted with representative class drugs tested at the level each selected organism for that particular drug is susceptible to.

A total of 377 drug-bug combinations per lot were tested. The results indicate that all three lots of the new device detected more drug-bug combinations than the predicate device. No statistically significant difference was observed in resin-dependent recovery with the new device compared to the predicate device. The following antimicrobials were included in this study:

• Amoxicillin/Clavulanate	• Aztreonam	• Ceftazidime
• Ciprofloxacin	• Ceftriaxone	• Cefotaxime
• Ertapenem	• Fluconazole	• Cefepime
• Gentamicin	• Imipenem	• Levofloxacin
• Meropenem	• Tetracycline	• Tigecycline
• Ticarcillin/Clavulanate	• Piperacillin/Tazobactam	• Vancomycin

{6}------------------------------------------------

Image /page/6/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of an eagle or bird with outstretched wings.

10903 New Hampshire Avenue Silver Spring, MD 20993

Becton Dickinson and Company c/o Mr. Paul Swift Regulatory Affairs Specialist/ Regulatory Affairs 7 Loveton Circle, Mail Code 614 Sparks, MD 21152

MAR 1 6 2012

Re: K113558

Trade/Device Name: BD BACTEC Plus Aerobic /F (plastic) Regulation Number: 21 CFR§866.2560 Regulation Name: Microbial Growth Monitor Regulatory Class: Class I Product Code: MDB Dated: March 9, 2012 Received: March 15, 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 controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

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

{7}------------------------------------------------

Page- 2 - Mr. Paul Swift

of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration

and listing (21 CFR Part 807): labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

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

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Sayattmo

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

Enclosure

{8}------------------------------------------------

Indication for Use

510(k) Number (if known): K ||3558

Device Name: BD BACTEC Plus Aerobic/F (plastic)

Indication For Use:

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 (OVD)

Freddie W. Poole

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

510(k): K113558

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.