Use of Synercid, 15 µg, BBL™ Sensi-Disc™ for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Synercid. Synercid indication whown to be active in vito against most strains of microorganisms listed below, as described in the Rhone Poulenc-Rorer package insert for this antimicrobic.

Active In Vitro Against:

Aerobic Gram Positive Microorganisms

Enterococcus facium (Vancomycin-resistant and multi-drug resistant strains only) Staphylococcus aureus (methiclilin-susceptible strains only) Straptococcus pyoganes

Device Description

Antimicrobial Susceptibility Test Discs are used for semi-quantitative in vitro susceptibility testing by standardized agar diffusion test procedures. Synercid BBL® Sensi-Disc™ are intended for use in determining the susceptibility to Synercid of a wide range of bacteria, as described under Indications For Use below. Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer, Rhone Poulenc-Rorer, and received FDA approval under NDA Nos. 50-747 and 50-748.

Synercid Susceptibility Test Discs are prepared by impregnating high quality paper with accurately determined amounts of Synercid supplied by the manufacturer, Rhone Poulenc-Rorer. Each Synercid disc is clearly marked on both sides with the agent and content. Synercid discs are furnished in cartridges of 50 discs each. Synercid cartridges are packed as either a single cartridge in a single box, or in a package containing ten cartridges.

Agar diffusion methods employing dried filter paper discs impregnated with specific concentrations of antimicrobial agents were developed in the 1940's. 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 National Committee for Clinical Laboratory Standards (NCCLS) and is periodically updated. The latest NCCLS documents are M2-A6 (1/97) and M100=S9 (1/99).

Discs containing a wide variety of antimicrobial agents are applied to the surface of Mueller Hinton Agar plates for Haemophilus Test Medium Agar for Haemophilus influenzae or Mueller Hinton Agar with 5% Sheep Blood for Streptococcus pneumoniae] inoculated with pure cultures of clinical isolates. Following incubation, the plates are examined and the zones of inhibition surrounding the discs 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 determination as to whether the organism in question is susceptible (S), intermediate (I), or resistant (R) to an antimicrobial agent is made by comparing zone sizes to those found in the respective organism tables of NCCLS Document M2-A6 ("Performance Standards for Antimicrobial Disk Susceptibility Tests - Sixth Edition, Approved Standard", 1/97) and of NCCLS Document M100-S9 ("Performance Standards for Antimicrobial Susceptibility Testing", Ninth Informational Supplement, 1/99).

AI/ML Overview

The acceptance criteria for the Synercid 15 µg, BBL™ Sensi-Disc™ are not explicitly stated as distinct "acceptance criteria" but are implicitly derived from the standardized procedures and interpretations of antimicrobial susceptibility testing. The performance of the device is assessed by comparing zone sizes of inhibition with established ranges.

Here's an attempt to structure the information based on your request, inferring where specific details are not directly provided in the text.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Inferred)	Reported Device Performance
Zone Size Interpretation: Zones of inhibition surrounding the discs should be measurable and comparable with established zone size ranges for individual antimicrobial agents to determine susceptibility (S), intermediate (I), or resistance (R) to Synercid. These ranges are specified in NCCLS Document M2-A6 ("Performance Standards for Antimicrobial Disk Susceptibility Tests - Sixth Edition, Approved Standard", 1/97) and NCCLS Document M100-S9 ("Performance Standards for Antimicrobial Susceptibility Testing", Ninth Informational Supplement, 1/99). The antimicrobic manufacturer, Rhone Poulenc-Rorer, determined zone sizes for interpretation, including control organism limits, and received FDA approval under NDA Nos. 50-747 and 50-748.	Consistency with Established Standards: The Synercid BBL™ Sensi-Disc™ is intended for use in susceptibility testing by standardized agar diffusion test procedures, specifically those based on the Bauer-Kirby method and updated by the National Committee for Clinical Laboratory Standards (NCCLS). The device's performance relies on the use of Mueller Hinton Agar or modified versions (Haemophilus Test Medium Agar for Haemophilus influenzae or Mueller Hinton Agar with 5% Sheep Blood for Streptococcus pneumoniae) and incubation. The determination of S, I, or R is made by comparing measured zone sizes to the established tables in NCCLS Documents M2-A6 and M100-S9.
Accuracy of Synercid Content: Each disc must be prepared by impregnating high-quality paper with accurately determined amounts of Synercid.	Quality Control: Synercid Susceptibility Test Discs are prepared with "accurately determined amounts of Synercid supplied by the manufacturer." This implies internal quality control to ensure the correct concentration of the antimicrobial agent on the disc.
Activity Against Specified Microorganisms: The device should accurately reflect the susceptibility of bacteria to Synercid for the microorganisms listed in the "Active In-Vitro Against" section.	Indications for Use: The device is indicated for determining susceptibility to Synercid for organisms listed, including specific Corynebacterium jeikeium, Enterococcus faecium (Vancomycin-resistant and multi-drug resistant strains), Staphylococcus aureus (methicillin-susceptible and methicillin-resistant strains), Staphylococcus epidermidis (including methicillin-resistant strains), Streptococcus agalactiae, and Streptococcus pyogenes. The activity against these strains is "as described in the Rhone Poulenc-Rorer labeling for this antimicrobic."

2. Sample size used for the test set and the data provenance

The document states, "See Rhone Poulenc-Rorer labeling on Susceptibility Testing - Diffusion Techniques for Synercid" for Performance Data. This indicates that the specific details regarding the test set's sample size, and data provenance (e.g., country of origin, retrospective or prospective) for the studies establishing the zone size interpretations for Synercid are located within the Rhone Poulenc-Rorer labeling, which is not provided in this 510(k) summary.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided in the 510(k) summary. The document refers to "established zone size ranges" and "control organism limits" determined by Rhone Poulenc-Rorer and approved by the FDA under NDA Nos. 50-747 and 50-748. The NCCLS documents are also cited as the basis for interpretation. This suggests that the ground truth was established through a rigorous process involving expert consensus and clinical studies, but the specific number and qualifications of individuals involved in establishing those reference standards are not detailed here.

4. Adjudication method for the test set

The document does not describe an adjudication method for the test set. The methodology relies on comparing measured zones of inhibition to pre-established, standardized zone size tables from NCCLS documents (M2-A6 and M100-S9). This implies a direct comparison to a reference standard rather than an adjudication process between multiple readers.

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

No, an MRMC comparative effectiveness study involving AI assistance is not mentioned. This device is a traditional antimicrobial susceptibility test disc, not an AI-powered diagnostic tool. The "readers" in this context would be laboratory technicians or microbiologists measuring zone sizes, and the "improvement" would be their accuracy in interpreting those measurements against standardized charts.

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

This question is not applicable to the device described. The BBL™ Sensi-Disc™ is a physical diagnostic tool that requires human involvement for application, incubation, measurement of inhibition zones, and interpretation against reference standards. It is not an algorithm-only device.

7. The type of ground truth used

The ground truth used for interpreting the device's performance is expert consensus and established reference standards. Specifically:

Zone sizes and interpretive criteria (S, I, R) were determined by the antimicrobic manufacturer, Rhone Poulenc-Rorer, and received FDA approval under NDA Nos. 50-747 and 50-748.
These interpretations are aligned with the consensus standards published by the National Committee for Clinical Laboratory Standards (NCCLS), specifically M2-A6 and M100-S9.
The Bauer-Kirby method, a widely accepted standardized procedure, forms the basis.

This type of ground truth is analogous to a "reference standard" established through extensive clinical validation and expert agreement in the field of microbiology.

8. The sample size for the training set

The document does not explicitly mention a "training set" in the context of an algorithm. However, the development of the standardized zone size interpretations (which could be considered analogous to the "training" for the interpretation system) would have involved extensive testing by Rhone Poulenc-Rorer and the NCCLS with a large number of bacterial isolates and clinical correlations. The specific sample sizes for these historical "training" studies are not provided in this 510(k) summary but would be found in the foundational documents for Synercid and the NCCLS standards.

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

The ground truth for establishing the interpretive criteria (zone sizes for S, I, R) was established through extensive microbiological studies and clinical correlation.

The antimicrobic manufacturer (Rhone Poulenc-Rorer) conducted studies for Synercid to correlate minimum inhibitory concentrations (MICs) with zone diameters, and clinical outcomes. This process involved determining the breakpoints that differentiate susceptible, intermediate, and resistant organisms based on pharmacokinetic/pharmacodynamic data and clinical efficacy. These results were submitted to the FDA for approval under the New Drug Applications (NDAs).
The NCCLS (now CLSI) then develops and updates its "Performance Standards for Antimicrobial Disk Susceptibility Tests" (M2-A6) and "Performance Standards for Antimicrobial Susceptibility Testing" (M100-S9) based on a comprehensive review of data, including that from drug manufacturers, academic institutions, and public health laboratories. This involves expert committees reviewing vast amounts of microbiological data, epidemiological cut-off values, and clinical outcome data to establish the universally accepted zone size breakpoints.

Summary

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NOV - 3 1999

993186

Date: September 22, 1999

510(k) SUMMARY

SUBMITTED BY:

Bradford M. Spring Manager, Regulatory Affairs Becton Dickinson and Company 7 Loveton Circle Sparks, MD 21152-0999

NAME OF DEVICE:

Trade Name:	Synercid, 15 µg, BBL™ Sensi-Disc™Catalog Numbers 4331720 and 4331721
Common Name/Description:	Antimicrobial Susceptibility Test Discs
Classification Name:	Susceptibility Test Discs, Antimicrobial
PREDICATE DEVICE:	Other BBL™ Sensi-Disc™ such asCiprofloxacin, 5 µg, BBL™ Sensi-Disc™

DEVICE DESCRIPTION:

INTENDED USE:

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INDICATIONS FOR USE:

Use of Synercid BBL™ Sensi-Disc™ for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Synercid. Synercid has been shown to be active against most strains of microorganisms listed below, as described in the Rhone Poulenc-Rorer labeling for this antimicrobic.

Active In-Vitro Against:

Aerobic Gram-Positive Microorganisms

Cornyebacterium ieikeium Enterococcus faecium (Vancomycin-resistant and multi-drug resistant strains only) Staphylococcus aureus (methicillin-susceptible and methicillin-resistant strains) Staphylococcus epidermidis (including methicillin-resistant strains) Streptococcus agalactiae Streptococcus pyogenes

PRODUCT DESCRIPTION:

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PERFORMANCE DATA:

See Rhone Poulenc-Rorer labeling on Susceptibility Testing - Diffusion Techniques for Synercid

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Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a stylized eagle with its wings spread, symbolizing protection and service. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.

Nov - 3 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Bradford M. Spring Manager, Regulatory Affairs Becton Dickinson and Company 7 Loveton Circle Sparks. Maryland 21152

Re: K993186 Trade Name: Synercid 15ug, BBL TM Sensi-DiscTM Regulatory Class: II Product Code: JTN Dated: September 22, 1999 Received: September 23, 1999

Dear Mr. Spring:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours.

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page 1 of 1

510(k) Numbor (if known): K993186

Device Name: Synarcid, 15 ug, BBL" Sensi-Disc"

Indications for Use:

Active In Vitro Against:

Aerobic Gram Positive Microorganisms

Enterococcus facium (Vancomycin-resistant and multi-drug resistant strains only) Staphylococcus aureus (methiclilin-susceptible strains only) Straptococcus pyoganes

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

Concurrence of CORH, Office of Device Evaluation (ODE)

Woody Dubose

Division of Clinical Laboratory Devices 510(k) Number

Prescription Use
Per 21 CFR 801.109

Over-The-Counter Use Optional Format 1-2-96

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).