Antimicrobial Susceptibility Test Disks are used for semi-quantitative in vitro susceptibility testing by standardized agar diffusion test procedures. Tigecycline 15ug BBL™ Sensi-Disc™ is intended for use in determining the susceptibility to Tigecycline of a wide range of bacteria, as described in the "Indications for Use" section. Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer and received FDA approval under NDA Number 21-821.

Use of Tigecycline 15µg BBL" Sensi-Disc "for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Tigecycline. The concentration of 15ug has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA approved drug insert for this antimicrobic.

Active In Vitro and in Clinical Infections Against:
Aerobic facultative Gram-positive microorganisms
Enterococcus faecalis (vancomycin-susceptible isolates only) Staphylococcus aureus -(methicillin susceptible and resistant isolates only) Streptococcus agalactiae Streptococcus anginosus grp. -(includes S. anginosus, S. intermedius, and S. constellatus Streptococcus pyogenes

Active In Vitro Against:
Aerobic and facultative Gram-positive microorganisms
Enterococcus avium Enterococcus casseliflavus Enterococcus faecalis (vancomycin-resistant isolates) Enterococcus faecium-(vancomycin-susceptible and -resistant isolates) Enterococcus gallinarum Listeria monocytogenes Stapvlococcus epidermidis -(methicillin-susceptible and -resistant isolates) Stapylococcus haemolyticus

Aerobic and facultativeGram-negative microorganisms
Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae

Aerobic and facultative Gram-negative microorganisms
Acinetobacter baumannii Aeromonas hydrophila Citrobacter koseri Enterobacter aerogenes Pasteurella multocida Serratia marcescens Stenotrophomonas maltophilia

Device Description

Tigecycline15ug BBL" Sensi-Disc" is prepared by impregnating high quality paper with accurately determined amounts of Tigecycline supplied by the drug manufacturer. Each Tigecycline disk is clearly marked on both sides with the agent and drug content. Tigecycline cartridges each contain 50 impregnated disks that are packed as either a single cartridge in a single box, or in a package containing ten cartridges. Tigecycline disks are used for semi-quantitative in vitro susceptibility evaluations by the agar diffusion test method.

Agar diffusion susceptibility methods employing dried filter paper disks impregnated with specific concentrations of antimicrobial agents were developed in the 1940s. In order to eliminate or minimize variability in the testing, Bauer et al. developed a standardized procedure in which Mueller Hinton Agar was selected as the test medium.

Various regulatory agencies and standards-writing organizations subsequently published standardized reference procedures based on the Bauer-Kirby method. Among the earliest and most widely accepted of these standardized procedures were those published by the U.S. Food and Drug Administration (FDA) and the World Health Organization (WHO). The procedure was adopted as a consensus standard by the Clinical and Laboratory Standards Institute (CLSI) [Formerly National Committee for Clinical Laboratory Standards (NCCLS)] and is periodically updated.

AI/ML Overview

The acceptance criteria and the study proving the device meets these criteria are detailed below, based on the provided 510(k) submission.

1. Table of Acceptance Criteria and Reported Device Performance

The submission refers to established standards rather than defining specific numerical acceptance criteria in the summary. The performance is demonstrated by conformance to these standards, specifically zone size interpretation for individual antimicrobial agents.

Acceptance Criterion	Reported Device Performance
Zone Sizes for Interpretation of Tests	Determined by the antimicrobic manufacturer and received FDA approval under NDA Number 21-821.
Control Organism Limits	Determined by the antimicrobic manufacturer and received FDA approval under NDA Number 21-821.
Categorical Interpretation (Susceptible, Intermediate, Resistant)	Established by comparing zone diameters to those found in respective organism tables of CLSI/NCCLS Document M2 ("Performance Standards for Antimicrobial Disk Susceptibility Tests") and CLSI/NCCLS Document M100 ("Performance Standards for Antimicrobial Susceptibility Testing"). The device's performance is implicit in its intended use, which is to allow for this comparison and interpretation.

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

The 510(k) summary references "Substantial Equivalence Testing Data: See the Tigecycline drug package insert, 'Susceptibility Tests: Diffusion Techniques' (Appendix 1)." This indicates that the specific data proving the performance of the Tigecycline 15µg BBL Sensi-Disc against the established zone size ranges and control limits would be found in the Tigecycline drug package insert.

Sample Size for Test Set: Not explicitly stated in the provided 510(k) summary. It would be detailed in Appendix 1, the Tigecycline drug package insert.
Data Provenance: Not explicitly stated in the provided 510(k) summary. The data would originate from the studies performed to establish the zone sizes and control limits for Tigecycline, as detailed in the drug package insert. These studies are typically prospective clinical and laboratory studies involving a range of bacterial isolates.

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

The ground truth for defining interpretable zone sizes and control limits for antimicrobial susceptibility testing is established through extensive scientific research and standardization efforts by organizations like CLSI (Clinical and Laboratory Standards Institute, formerly NCCLS) and regulatory bodies like the FDA.

Number of Experts: Not explicitly stated in the provided 510(k) summary. However, the establishment of such standards involves numerous clinical microbiologists, infectious disease physicians, and pharmacologists from academic institutions, industry, and government agencies and is a consensus-driven process.
Qualifications of Experts: These experts would typically be highly qualified professionals in microbiology, infectious diseases, and pharmacology, with significant experience in antimicrobial susceptibility testing and clinical outcomes.

4. Adjudication Method for the Test Set

The concept of "adjudication" in the traditional sense of multiple reviewers resolving discrepancies isn't directly applicable to the establishment of predefined zone size interpretive criteria for antimicrobial susceptibility discs. The ground truth (zone size breakpoints) is established through large-scale correlation studies involving minimum inhibitory concentration (MIC) testing, pharmacokinetic/pharmacodynamic (PK/PD) data, and clinical outcomes.

Instead of adjudication, the method involves:

Correlation Studies: Comparing disk diffusion zone diameters to MIC values, which are considered the gold standard for antimicrobial susceptibility.
Clinical Efficacy Data: Ensuring that the breakpoints correlate with successful clinical outcomes in patients treated with the antimicrobial.
Consensus Process: CLSI (formerly NCCLS) and similar bodies use a consensus process involving expert committees to review and approve these breakpoints.

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

No, an MRMC comparative effectiveness study in the context of human readers improving with AI vs without AI assistance was not performed. This device is an antimicrobial susceptibility test disk, not an AI-assisted diagnostic tool for image interpretation. Its function is to provide a physical measurement (zone of inhibition) that is then interpreted against established standards, not to assist human interpretation of complex medical images or data.

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

This refers to a standalone performance of the device itself (the antimicrobial disk) which is then interpreted by a human against a standard. The device's performance as a "standalone" system is in producing a consistent zone of inhibition that can be accurately measured. The interpretation of that zone (Susceptible, Intermediate, Resistant) always involves a human reading against established criteria.

The "standalone" performance of the disk would be assessed through studies ensuring:

Accurate and consistent impregnation of Tigecycline at 15µg.
Stability of the antimicrobial agent on the disk.
Reproducibility and accuracy of zone diameters when tested with control strains.

7. The Type of Ground Truth Used

The ground truth for the Tigecycline 15µg BBL Sensi-Disc is based on:

Expert Consensus / Standardized Breakpoints: Established by organizations like CLSI/NCCLS, which define the zone diameters corresponding to Susceptible, Intermediate, and Resistant categories. These breakpoints are derived from extensive research.
Correlation with MIC Values: The gold standard for antimicrobial susceptibility, where disk diffusion results are correlated with Minimum Inhibitory Concentrations.
Clinical Outcome Data: The breakpoints are designed to predict clinical efficacy.
Pathology/Microbiological Confirmation: The isolates used in the studies would be pure cultures of confirmed bacterial species.

8. The Sample Size for the Training Set

The concept of "training set" as it relates to machine learning algorithms is not directly applicable here. In the context of antimicrobial susceptibility testing, the "training set" would indirectly refer to the vast amount of data and isolates used over many years to establish the general principles of disk diffusion, the Mueller Hinton Agar method, and later, the specific breakpoints for new antimicrobial agents like Tigecycline. This would encompass thousands of isolates across numerous studies. The specific number of isolates used to determine the breakpoints for Tigecycline would be in the drug package insert (Appendix 1).

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

For antimicrobial susceptibility testing, the "ground truth" for establishing the interpretive criteria (analogous to a training set's ground truth) is established through:

Minimum Inhibitory Concentration (MIC) Testing: This is the reference method, determining the lowest concentration of an antimicrobial agent that inhibits the visible growth of a microorganism.
Pharmacokinetic/Pharmacodynamic (PK/PD) Studies: These studies correlate drug concentrations in the body with their antimicrobial effect and help predict clinical success.
Clinical Outcome Studies: Observing patient responses to treatment to ensure that the in vitro susceptibility results accurately predict therapeutic efficacy.
Regression Analysis: Statistical methods are used to correlate zone diameters obtained from disk diffusion with MIC values to establish the interpretive breakpoints (zone diameter cutoffs).
Expert Review and Consensus: As mentioned before, committees of experts review all available data (MICs, PK/PD, clinical outcomes) to arrive at the final standardized breakpoints.

Summary

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510(k) Submission

Tigecycline 15ug BBL T4 Sensi-Disc

NOV 1 7 2005

510(k) SUMMARY

SUBMITTED BY:	Becton Dickinson and Company7 Loveton CircleSparks, MD 21152Phone 410-316-4905Fax: 410-316-4499
CONTACT NAME:	Dainelle N. Clark, Regulatory Affairs Specialist
DATE PREPARED:	October 10, 2005
DEVICE TRADE NAME:	Tigecycline 15µg, BBL™ Sensi-Disc™ AntimicrobialSusceptibility Test Disks
DEVICE COMMON NAME:	Antimicrobial Susceptibility Test Disks
DEVICE CLASSIFICATION:	21 CFR§866.1620, Class II (Product Code JTN), SusceptibilityTest Disks, Antimicrobial
PREDICATE DEVICE:	Other BBL™ Sensi-Disc™(eg, Ciprofloxacin 5 µg, BBL™ Sensi-Disc™)

INTENDED USE:

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510(k) SUMMARY

Indications for Use:

Active In Vitro and in Clinical Infections Against:

Aerobic facultative Gram-positive microorganisms

Enterococcus faecalis (vancomycin-susceptible isolates only) Staphylococcus aureus -(methicillin susceptible and resistant isolates only) Streptococcus agalactiae Streptococcus anginosus grp. -(includes S. anginosus, S. intermedius, and S. constellatus Streptococcus pyogenes

Active In Vitro Against:

Aerobic and facultative Gram-positive microorganisms

Enterococcus avium Enterococcus casseliflavus Enterococcus faecalis (vancomycin-resistant isolates) Enterococcus faecium-(vancomycin-susceptible and -resistant isolates) Enterococcus gallinarum Listeria monocytogenes Stapvlococcus epidermidis -(methicillin-susceptible and -resistant isolates) Stapylococcus haemolyticus

Aerobic and facultativeGram-negative microorganisms

Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae

Aerobic and facultative Gram-negative microorganisms

Acinetobacter baumannii Aeromonas hydrophila Citrobacter koseri Enterobacter aerogenes Pasteurella multocida Serratia marcescens Stenotrophomonas maltophilia

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DEVICE DESCRIPTION:

DEVICE PRINCIPLE:

Disks containing a wide variety of antimicrobial agents are applied to the surface of Mueller Hinton Agar plates [or Haemophilus Test Medium Agar for Haemophilus influenzae or Mueller Hinton Agar with 5% Sheep Blood for Streptococcus species] inoculated with pure cultures of clinical isolates. Following incubation, the plates are examined and the zones of inhibition surrounding the disks are measured and compared with established zone size ranges for individual antimicrobial agents in order to determine the agent(s) most suitable for use in antimicrobial therapy. The categorical interpretation [susceptible (S), intermediate (I), or resistant (R)] for the organism being tested with the antimicrobial agent is made by comparing zone diameters to those found in the respective organism tables of CLSVNCCLS Document M2 ("Performance Standards for Antimicrobial Disk Susceptibility Tests) and of CLSI/NCCLS Document M100 ("Performance Standards for Antimicrobial Susceptibility Testing").

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DEVICE COMPARISON:

The BBL " Sensi-Disc" Antimicrobial Susceptibility Test Disks - Tigercycline15ug is similar to the BBL Sensi-Disc " Antimicrobial Susceptibility Test Disks - Ciprofloxacin 5 ug in that:

Both methods are for antimicrobial susceptibility testing using paper disks impregnated with an . antimicrobial agent.
. Both methods have the same intended use.
Both methods provide the user with antimicrobic minimum inhibitory concentration (MIC) results . based on measurements of zone diameters.
Both methods require the user to determine categorical interpretations (S/I/R) using the measured . zone diameters against CLSI/NCCLS Approved Standards M2 and M100.
. Both methods use pure cultures of bacterial isolates.

The BBL™ Sensi-Disc" Antimicrobial Susceptibility Test Disks - Tigecycline 15ug differs from the BBL™ Sensi-Disc™ Antimicrobial Susceptibility Test Disks - Ciprofloxacin 5 µg in that:

BBL™ Sensi-Disc™ Antimicrobial Susceptibility Test Disks Tigecycline 15μg is a susceptibility test . that uses disks impregnated with the antimicrobic Tigecycline at a concentration of 15ug while the BBL™ Sensi-Disc Antimicrobial Susceptibility Test Disks - Ciprofloxacin 5 µg is a susceptibility test that uses disks impregnated with the antimicrobic Ciprofloxacin at a concentration of 5 ug.
BBL " Sensi-Disc" Antimicrobial Susceptibility Test Disk Tigecycline 15 µg is a susceptibility test . used to test a different battery of microorganisms than the BBL" Sensi-Disc " Antimicrobial Susceptibility Test Disk - Ciprofloxacin 5 ug.

SUBSTANTIAL EQUIVALENCE TESTING DATA:

See the Tigecycline drug package insert, "Susceptibility Tests: Diffusion Techniques" (Appendix 1).

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is an abstract image of an eagle or other bird-like figure, with three stylized wing or feather shapes.

NOV 1 7 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Dainelle N. Clark Regulatory Affairs Specialist BD Diagnostics Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152

K052853 Re: Trade/Device Name: BBL™ Sensi-Disc ™ Antimicrobial Susceptibility Test Disks, Tigecycline 15 µg Regulation Number: 21 CFR 866.1620 Regulation Name: Antimicrobial Susceptibility Test Disc Regulatory Class: Class II Product Code: JTN Dated: October 10, 2005 Received: October 11, 2005

Dear Ms. Clark:

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. Iisting 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 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 –

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours.

Sally, a Hogg

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

Enclosure

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INDICATIONS FOR USE

K052853 510(k) Number (if known):

Device Name: BBL" Sensi-Disc" Antimicrobial Susceptibility Test Disks, Tigecycline I Sug

Indications for Use:

Use of Tigecycline 15ug, BBL" Sensi-Disc" for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Tigecycline. The concentration of 15ug has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA approved drug insert for this antimicrobic.

Active In Vitro and in Clinical Infections Against:

Aerobic facultative Gram-positive microorganisms

Active In Vitro Against:

Aerobic and facultative Gram-positive microorganisms

Aerobic and facultativeGram-negative microorganisms Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae

Aerobic and facultative Gram-negative microorganisms Acinetobacter baumannii Aeromonas hydrophila Citrobacter koseri Enterobacter aerogenes

Pasteurella multocida Serratia marcescens Stenotrophomonas maltophilia

Prescription Use (Per 21 CFR 801 Subpart D)

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________ AND/OR (Per 21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Freddi tu. Poole
Division Sign Off

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

3510(k) KD5.2853

Becton, Dickinson and Company

Regulation Number and Section

§ 866.1620 Antimicrobial susceptibility test disc.

(a)
Identification. An antimicrobial susceptibility test disc is a device that consists of antimicrobic-impregnated paper discs used to measure by a disc-agar diffusion technique or a disc-broth elution technique the in vitro susceptibility of most clinically important bacterial pathogens to antimicrobial agents. In the disc-agar diffusion technique, bacterial susceptibility is ascertained by directly measuring the magnitude of a zone of bacterial inhibition around the disc on an agar surface. The disc-broth elution technique is associated with an automated rapid susceptibility test system and employs a fluid medium in which susceptibility is ascertained by photometrically measuring changes in bacterial growth resulting when antimicrobial material is eluted from the disc into the fluid medium. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).