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Antimicrobial susceptibility test discs are used for semi-quantitative susceptibility testing of bacteria by standardized agar diffusion. Cefotaxime/Clavulanic Acid, BBL™ Sensi-Disc™ and Ceftazidime/Clavulanic Acid BBL™ Sensi-Disc™ are intended for use for confirmatory tests for organisms that secrete Extended-spectrum ß-lactamases (ESBL)s as indicated in the Results section of the package insert and indicated below.

Use of Cefotaxime/Clavulanic Acid, BBL™ Sensi-Disc™ and Ceftazidime/Clavulanic Acid BBL ™ Sensi-Disc™ together with Cefotaxime and Ceftazidime susceptibility discs for in vitro agar diffusion susceptibility testing are indicated when there is a need to perform a confirmatory test for ESBLs in Klebsiella spp. and Escherichia coli.

Cefotaxime/Clavulanic Acid and Ceftazidime/Clavulanic Acid susceptibility test discs are prepared by impreanating high quality absorbent paper with accurately determined amounts of Cefotaxime, supplied by Marion Roussel, Inc., Kansas City, MO, and Ceftazidime, supplied by Glaxo Wellcome Operations, Cumbria, UK, respectively. Both discs are also impregnated with specific amounts of Clavulanic Acid supplied by SmithKline Beecham Pharmaceuticals, Piscataway, NJ.

The disks are clearly marked with the agents: CTX/CLA and CAZ/CLA. Cefotaxime/Clavulanic Acid and Ceftazidime/Clavulanic Acid susceptibility test discs are provided in cartridges of 50 disks each and packaged separately.

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-S92 (1/99).

Disks containing an antimicrobial agent are applied to the surface of Mueller Hinton Agar plates 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 the antimicrobial agents in order to determine which is most suitable for use in therapy. The determination as to whether the organism is susceptible (S), intermediate (I), or resistant (R) to an antimicrobial agent is made by comparing zone sizes to the interpretive criteria defined in the tables of NCCLS document M100-S9.

Here's a breakdown of the acceptance criteria and the studies performed for the Cefotaxime/Clavulanic Acid and Ceftazidime/Clavulanic Acid BBL™ Sensi-Discs, based on the provided text:

Acceptance Criteria and Device Performance

• Inter-individual Reproducibility: "All results met the acceptance criteria" for variability between individual tests by the same person and between participants. |
  | Performance with NCCLS M100-S9 Challenge Set (Jacoby) | "Expected results were obtained in all cases." |
  | Accuracy (Comparison to Laboratory-Prepared Disks for ESBL Confirmation)
• Correlation with laboratory disks
• Expected outcomes for genotypic and non-ESBL strains
• Overall performance accuracy (acceptance criteria for this specific accuracy study is implied to be 95% or higher based on the text "Overall performance accuracy was 95% and meets the acceptance criteria as outlined in the study protocol.") | * Correlation: "All production disks results correlated with laboratory disks with 100% equivalency in performance."
• Genotypic/Non-ESBL Strains: "Expected outcomes were met for all of the genotypic and non-ESBL strains."
• Phenotypic Strains: "The phenotypic strains performed as expected with the exception of four K. oxytoca strains. These four strains were not detected as ESBL by the reference or test disks."
• Overall Performance Accuracy: "Overall performance accuracy was 95% and meets the acceptance criteria as outlined in the study protocol."
• QC Testing: "QC testing over the course of the study was acceptable. All expected outcomes were achieved during the screening test." |

Study Details

The provided document describes several performance studies, primarily for validation and comparative equivalence to predicate devices, rather than a single comprehensive clinical trial.

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

• Reproducibility Studies:
  • Multisite/Multilot: Tested with NCCLS recommended negative and positive Quality Control organisms. Performed in triplicate at three test sites for ten days using three lots of disks. Specific number of QC organisms not provided.
  • Inter-individual: Ten organism strains of various resistance mechanisms. Three individuals tested the ten strains on three different days in triplicate, using one lot of test disks.
• Jacoby Challenge Set: The study used the Jacoby challenge set of organisms. Specific number of organisms not provided.
• Accuracy Testing: Involved "genotypic and phenotypic ESBL strains and non-ESBL strains." Specific number of strains not provided.
• Data Provenance: Not explicitly stated, but given the context of a 510(k) submission to the US FDA and the mention of NCCLS standards, it's highly probable the studies were conducted in the US. The studies appear to be prospective, laboratory-based performance evaluations.

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

Not applicable. The ground truth for these in vitro diagnostic devices is established by standardized laboratory methods (NCCLS M100-S9) and the inherent biological characteristics of the bacterial strains (e.g., genotypic ESBL producers, phenotypic ESBL characteristics). Human experts were involved in performing the tests and reading the results, but they were not adjudicating a "ground truth" in the sense of subjective interpretation of images or clinical outcomes.

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

Not applicable for establishing ground truth. The "adjudication" for the in vitro test results is based on objective measurements (zone diameters) and comparison to established interpretive criteria (≥5mm increase for ESBL confirmation). Variability between individuals reading zones was assessed in the inter-individual reproducibility study.

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 susceptibility disc, not an AI-powered diagnostic tool for human readers. The study focuses on the performance of the physical disk, not on comparative effectiveness for human readers using AI.

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

Yes, in essence. The Sensi-Discs themselves (the "device") are used to generate a physical result (zone of inhibition) that is then interpreted according to standardized criteria. The "performance" being evaluated is the ability of the discs to accurately produce these results and differentiate ESBL-producing organisms according to the NCCLS guidelines. The interpretation of the measured zone sizes is a standardized, objective process, not a subjective human interpretation that would require a "human-in-the-loop" assessment in the way AI applications are often evaluated.

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

The ground truth was established by:

• Standardized interpretative criteria: NCCLS M100-S9 document, defining a ≥5mm increase in zone diameter as indicative of ESBL production.
• Known characteristics of organism strains: This includes NCCLS recommended Quality Control organisms, the Jacoby challenge set organisms, and specifically characterized "genotypic and phenotypic ESBL strains and non-ESBL strains." This implies that the true ESBL status for these strains was determined through established laboratory methods (e.g., genetic sequencing for genotypic ESBLs, or other phenotypic gold standards).

8. The sample size for the training set

Not applicable. This device is a physical diagnostic disc used in an in vitro laboratory setting, not a machine learning or AI algorithm that requires a "training set" in the computational sense. The studies described are performance evaluations and validation studies.

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

Not applicable (as above).

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The BDProbeTec™ ET Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) Amplified DNA Assays, when tested with the BDProbeTec™ ET System, use Strand Displacement Amplification (SDA) technology for the direct, qualitative detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in endocervical swabs, male urethral swabs, and in female and male urine specimens as evidence of infection with C. trachomatis, N. gonorrhoeae, or of co-infection with C. trachomatis and N. gonorrhoeae. Specimens may be from symptomatic or asymptomatic females for the BDProbeTec ET CT and GC Assays, from symptomatic or asymptomatic males for the BDProbeTec ET CT Assay, and from symptomatic males for the BDProbeTec ET GC Assay. A separate Amplification Control is an option for inhibition testing (BDProbeTec ET CT/GC/AC Reagent Pack).

The BDProbeTec™ ET Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) amplified DNA assays utilize homogeneous SDA technology as the amplification method and fluorescent energy transfer (ET) as the detection method to test for the presence of CT and GC in clinical specimens.

For each assay, the SDA reagents are dried in two separate microwell strips. First, the processed sample is added to the Priming Microwell which contains the amplification primers, fluorescent labeled detector probe, and other reagents necessary for amplification. However, because no enzymes are present in the priming microwell strips, no amplification occurs at this step. After incubation, the reaction mixture is transferred to the Amplification Microwell, which contains two enzymes (a DNA polymerase and a restriction endonuclease) necessary for SDA. It is in this latter microwell in which amplification and detection occurs. The Amplification Microwells are sealed to prevent contamination and then incubated in a thermally controlled fluorescent reader which monitors each test well for the generation of amplified products. The presence of CT and GC is determined by relating the BDProbeTec ET MOTA (Method Other Than Acceleration) scores for the sample to pre-determined cutoff values. The MOTA score is a metric used to assess the magnitude of signal generated as a result of the reaction.

If the CT/GC Reagent Pack is used, each sample and control are tested in two discrete microwells: C. trachomatis and N. gonorrhoeae. Results are reported through an algorithm as positive or negative. If the CT/GC/AC Reagent Pack is used, each sample and control are tested in three discrete microwells: C. trachomatis, N. gonorthoeae, and the Amplification Control. The purpose of the Amplification Control is to identify a sample that may inhibit the SDA reaction. Results are reported through an algorithm as positive, negative, or indeterminate.

This document describes the regulatory submission for the BDProbeTec™ ET Chlamydia trachomatis and Neisseria gonorrhoeae Amplified DNA Assays.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the clinical performance results being deemed "substantially equivalent" to predicate devices by the FDA. The reported device performance is outlined in detail for both C. trachomatis (CT) and N. gonorrhoeae (GC) assays, with sensitivity and specificity values compared to both culture and "patient infected status." The tables below summarize these performances.

Table 1: BDProbeTec™ ET CT Assay Performance (Compared to Patient Infected Status)

Table 2: BDProbeTec™ ET GC Assay Performance (Compared to Patient Infected Status)

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

• Sample Size for Test Set: The final data analysis included 4108 C. trachomatis specimens and 4105 N. gonorrhoeae specimens, collected from 2109 patients. Paired specimens (swab and urine) were collected from 2020 of these patients.
• Data Provenance: The data was collected from a multicenter study at seven geographically diverse clinical sites in the United States (implied by the FDA 510(k) submission). The study was prospective in nature, as it involved specimen collection specifically for the evaluation of the new assay.

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

The document does not explicitly state the number of general medical experts or their specific qualifications (e.g., years of experience) who established the ground truth for the clinical study. However, the ground truth for C. trachomatis was established using:
* Cell culture as a primary reference.
* A "patient infected status" definition.

For N. gonorrhoeae, the ground truth was established using:
* Culture as a primary reference.
* A "patient infected status" definition.

These methods inherently involve expert interpretation (e.g., microbiologists for culture results, potentially infectious disease specialists or clinicians for patient infected status).

4. Adjudication Method for the Test Set

The document describes an adjudication method to define "patient infected status" when the primary culture method was negative but amplification assays were positive:

• For C. trachomatis: A patient was considered infected if (1) the culture was positive, OR (2) positive results were obtained for both AMP1 (a commercially available amplification method, in either swab or urine) and a DFA test (performed from cell culture transport medium), OR (3) AMP1 was positive in both swab and urine paired specimens.
• For N. gonorrhoeae: A patient was considered infected if (1) the culture was positive, OR (2) (in females) if AMP1 was positive in both swab and urine (paired specimens). For males, if AMP1 urine was positive and corresponding swabs were culture negative, a different commercially available amplification assay (AMP2) was performed from culture transport medium for confirmation.

This suggests that an expert consensus or a defined algorithm (rather than a simple 2+1 or 3+1 reader adjudication) was used to establish the "patient infected status" ground truth under specific conditions.

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

The study does not describe a multi-reader, multi-case (MRMC) comparative effectiveness study using a human-in-the-loop AI system. This device is a diagnostic assay, providing a qualitative (positive/negative) result, rather than an imaging or interpretive AI system requiring human reader assistance.

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

Yes, the clinical performance data presented in Tables 1 and 2 represent the standalone performance of the BDProbeTec™ ET assays. The "device performance" columns directly report the sensitivity and specificity of the BDProbeTec™ ET system compared to the established ground truth. There is no indication of human intervention in the interpretation of the assay's MOTA scores (Method Other Than Acceleration) to determine positive or negative results beyond the pre-determined cutoff values.

7. The Type of Ground Truth Used

The ground truth used was a combination of:

• Expert Reference Standard (Culture): C. trachomatis cell culture and N. gonorrhoeae culture were used as primary reference standards.
• Composite Reference Standard ("Patient Infected Status"): For cases where culture was negative but other amplification assays showed positivity, a "patient infected status" was derived using a predefined algorithm involving the predicate amplification assay (AMP1) and, for CT, a Direct Fluorescent Antibody (DFA) test, and for male GC, an additional amplification assay (AMP2). This composite reference standard aims to capture true infections that might be missed by culture alone.

8. The Sample Size for the Training Set

The document does not explicitly state a separate "training set" for the BDProbeTec™ ET assay's algorithm. For in vitro diagnostic devices like this, the "algorithm" (i.e., the cut-off value for the MOTA score) is typically established during analytical validation (including studies like Limit of Detection, reproducibility, and precision) using characterized samples, and then validated with clinical samples.

The analytical studies section describes using several panels for precision, reproducibility, and analytical sensitivity, which could be considered part of the development and optimization (training) process:

• Precision panel: Five-member panel (4 dilutions of CT and GC, and a negative) tested with 6 replicates twice a day for 3 days at 3 sites.
• Reproducibility panels: 30-member swab panels and 30-member urine panels (various seeded levels and unseeded samples) tested across 23 operators.
• Analytical sensitivity: 15 C. trachomatis serovars and 39 N. gonorrhoeae strains diluted and assayed in triplicate.

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

For the analytical studies that would contribute to establishing optimal parameters or "training" the assay:

• Known Concentrations: Samples were prepared with known concentrations of C. trachomatis (EBs/rxn) and N. gonorrhoeae (cells/rxn) through serial dilutions of quantitated cultures. This provides a clear, quantitative ground truth.
• Uninoculated Samples: Negative controls (sample diluent or unseeded samples) served as a known negative ground truth.
• Known Strains/Serovars: Specific serovars of C. trachomatis and strains of N. gonorrhoeae were used, characterized by standard microbiological methods.

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Use of BBL® Cefdinir Sensi-Discs® for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Cefdinir. Cefdinir has been shown to be active against most strains of microorganisms listed below, as described in the Parke-Davis package insert for this antimicrobic.

Active In Vitro and In Clinical Infections Against:
Aerobic Gram-Positive Microorganisms
Staphylococcus aureus (including ß-lactamase producing strains, but excluding methicillin-resistant staphylococci) Streptococcus pneumoniae (penicillin-susceptible strains only) Streptococcus pvogenes
Aerobic Gram-Neqative Microorganisms
Haemophilus influenzae (including ß-lactamase producing strains) Haemophilus parainfluenzae (including ß-lactamase producing strains) Moraxella catarrhalis (including ß-lactamase producing strains)

Active In Vitro Only Against:
Aerobic Gram-Positive Microorganisms Staphylococcus epidermidis (methicillin-susceptible strains only) Streptococcus agalactiae Viridans group streptococci Aerobic Gram Negative Microorganisms Citrobacter diversus Escherichia coli Klebsiella pneumoniae Proteus mirabilis

Antimicrobial Susceptibility Test Discs are used for semi-quantitative in vitro susceptibility testing by standardized agar diffusion test procedures. Cefdinir Sensi-Discs® are intended for use in determining the susceptibility to Cefdinir 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, Parke-Davis, a Division of Warner-Lambert Co., and received FDA approval under NDA Nos. 50-739 and 50-749.

Cefdinir Susceptibility Test Discs are prepared by impregnating high quality paper with accurately determined amounts of Cefdinir supplied by the manufacturer. Parke-Davis. Each Cefdinir disc is clearly marked on both sides with the agent and content. Cefdinir discs are furnished in cartridges of 50 discs each. Cefdinir 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-S8 (1/98).

Discs 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 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 National Committee for Clinical Laboratory Standards (NCCLS) Document M2-A6 ("Performance Standards for Antimicrobial Disk Susceptibility Tests - Sixth Edition, Approved Standard", 1/97) and of NCCLS Document M100-S8 ("Performance Standards for Antimicrobial Susceptibility Testing", Eighth Informational Supplement, 1/98).

Here's an analysis of the provided text regarding the acceptance criteria and study for the Cefdinir, 5 µg, Sensi-Discs:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document itself does not explicitly list numerical acceptance criteria in a pass/fail format. Instead, it refers to industry-standardized procedures and interpretation guidelines. The "reported device performance" is essentially that the device functions according to these standards, allowing for accurate interpretation.

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

• Test Set Sample Size: Not explicitly stated. The document refers to "pure cultures of clinical isolates" but does not give a number.
• Data Provenance: The document does not explicitly state the country of origin or if the data was retrospective or prospective. It refers to "clinical isolates," suggesting real-world samples.

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

• Number of Experts: Not explicitly stated.
• Qualifications of Experts: The ground truth for interpreting zone sizes and control organism limits was "determined by the antimicrobic manufacturer, Parke-Davis, a Division of Warner-Lambert Co., and received FDA approval" and by reference to "National Committee for Clinical Laboratory Standards (NCCLS) Document M2-A6" and "NCCLS Document M100-S8." This implies that the standards themselves, developed by expert committees and validated by regulatory bodies, serve as the "ground truth establishment." There is no mention of individual experts reviewing the test set results.

4. Adjudication method for the test set

• Adjudication Method: Not applicable in the traditional sense of human consensus for individual test results. The device's performance is adjudicated against pre-established, standardized criteria (NCCLS documents and manufacturer-defined zone sizes/control limits). Interpretation of results involves comparing measured zone sizes to these established standards.

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

• MRMC Study: No. This device is an antimicrobial susceptibility test disc, a consumable used in a laboratory procedure. It does not involve AI or human "readers" in the context of image interpretation or diagnostic scanning for which MRMC studies are typically performed.

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

• Standalone Performance: Not applicable in the context of an algorithm. The device itself is a physical disc. Its "standalone performance" is its ability to produce a measurable zone of inhibition when used according to standardized laboratory procedures. The interpretation of this zone into "susceptible," "intermediate," or "resistant" is a manual human step, guided by the NCCLS standards. There is no automated algorithm performing this interpretation described.

7. The type of ground truth used

• Type of Ground Truth: The primary ground truth is expert consensus/standardization as defined by the National Committee for Clinical Laboratory Standards (NCCLS) documents (M2-A6 and M100-S8) and manufacturer-established (Parke-Davis) zone size interpretation guidelines and control organism limits, which received FDA approval. This is essentially a standardized, accepted reference for what constitutes "susceptible," "intermediate," or "resistant."

8. The sample size for the training set

• Training Set Sample Size: Not applicable. This is not a machine learning or AI device that requires a "training set." The performance is based on chemical properties and standardized biological reactions, not statistical model training.

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

• Ground Truth for Training Set: Not applicable, as there is no training set for this type of device. The "ground truth" for the interpretation of the disc's results is established through the rigorous standardization process of the NCCLS and validation by the manufacturer and FDA.

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Use of BBL Trovafloxacin Sensi-Discs® for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Trovafloxacin has been shown to be active against most strains of microorganisms listed below, as described in the Roerig package insert for this antimicrobic.

Trovafloxacin Susceptibility Test Discs are prepared by impregnating high guality paper with accurately determined amounts of Trovafloxacin supplied by the manufacturer, Roerig. Each Trovafloxacin disc is clearly marked on both sides with the agent and content. Trovafloxacin discs are furnished in cartridges of 50 discs each. Trovafloxacin 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-S7 (1/97).

Discs 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 Aqar 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 National Committee for Clinical Laboratory Standards (NCCLS) Document M2-A6 ("Performance Standards for Antimicrobial Disk Susceptibility tests - Sixth Edition, Approved Standard", 1/97) and of NCCLS Document M100-S8 ("Performance Standards for Antimicrobial Susceptibility Testing", Eighth Informational Supplement, 1/98).

Based on the provided text, here's an analysis of the acceptance criteria and study information for the Trovafloxacin Sensi-Discs:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a quantitative, pass/fail table format that is typical for modern device submissions. Instead, it relies on alignment with established industry standards for antimicrobial susceptibility testing. The accepted performance is essentially defined by adherence to these standards and the established zone size ranges for Trovafloxacin.

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

The document refers to "Performance Data: See attached Roerig product insert section on Susceptibility Tests - Diffusion Techniques for TROVAN™ Tablets (trovafloxacin mesylate tablets) and TROVAN™ I.V. (alatrofloxacin mesylate injection) for intravenous infusion."

• Sample Size: The specific sample size for the test set is not provided in the excerpt. It defers to the Roerig product insert, which is not included.
• Data Provenance: The document does not specify the country of origin of the data. It seems to refer to data generated by Roerig (a division of Pfizer Inc.), which is a pharmaceutical company. The type of data would be related to clinical trials and in vitro susceptibility testing that formed the basis for the drug's FDA approval (NDA Nos. 20-759 and 20-760). This would implicitly be prospective data collected during the drug's development.

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

This information is not explicitly provided in the excerpt. The ground truth for antimicrobial susceptibility testing, especially for establishing zone size breakpoints, is typically determined through extensive in vitro and in vivo correlation studies, pharmacokinetic/pharmacodynamic modeling, and epidemiological cutoff values. This process involves numerous clinical microbiologists, pharmacologists, and infectious disease specialists, but their specific number and qualifications are not detailed for this submission. The document states that the zone sizes and control organism limits "were determined by the antimicrobic manufacturer, Roerig... and received FDA approval." This implies expert consensus and rigorous review by regulatory bodies.

4. Adjudication Method for the Test Set:

The document does not describe any adjudication method. For antimicrobial susceptibility testing, the "ground truth" (i.e., whether an organism is S, I, or R to an agent) is established by comparing measured zone sizes to predetermined interpretive criteria (breakpoints) set by standardized bodies like the NCCLS, which are themselves derived from extensive studies. It's not a subjective interpretation requiring adjudication in the way medical imaging might.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done or described. This type of study is highly relevant for subjective diagnostic interpretations (e.g., AI in radiology). Here, the device is a disc for in vitro laboratory testing, not a diagnostic imaging AI. The "readers" are laboratory technicians measuring zone diameters, which is a relatively objective measurement compared to interpreting complex clinical images.

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

The device itself (Trovafloxacin Sensi-Discs) is not an "algorithm" in the AI sense. It's a consumable product used in a manual laboratory procedure.

However, the "performance data" referred to in the Roerig product insert would represent the standalone performance of the antimicrobial agent (Trovafloxacin) in determining susceptibility, based on the established zone size breakpoints. This is a form of standalone performance in that it evaluates the accuracy of the drug's activity and the interpretive criteria, independent of the specific disc manufacturer, as long as the disc meets quality standards (e.g., accurate drug concentration).

7. The Type of Ground Truth Used:

The ground truth used is primarily expert consensus based on extensive in vitro (microbiological) and in vivo (clinical outcomes) correlation data, pharmacokinetic/pharmacodynamic studies, and epidemiological cutoff values. This is distilled into the standardized interpretive criteria (zone size breakpoints) published by organizations like the NCCLS and approved by the FDA (as indicated by the references to NDA approvals for the drug itself). The product relies on the established validity of these breakpoints.

8. The Sample Size for the Training Set:

This information is not provided in the excerpt. The concept of a "training set" in the context of machine learning doesn't directly apply to this device. For the drug itself (Trovafloxacin), the data used to establish its activity profile and breakpoints would have involved a very large number of microbial isolates tested in vitro and patients treated in vivo.

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

Similar to point 8, the concept of a "training set" ground truth is not directly applicable. However, for the underlying interpretive breakpoints, the ground truth was established through:

• Clinical Efficacy Studies: For the drug Trovafloxacin, its efficacy against various microorganisms would have been established through clinical trials (human outcomes data).
• Microbiological Studies: Extensive in vitro testing of thousands of bacterial isolates to determine Minimum Inhibitory Concentrations (MICs) and correlate them with zone diameters.
• Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling: Studies to understand how the drug behaves in the human body and how its concentration correlates with bacterial killing.
• Expert Panels: Review and approval by expert committees (e.g., NCCLS, FDA) who synthesize all available data to set the final interpretive criteria (susceptible, intermediate, resistant breakpoints).

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Antimicrobial Susceptibility Test Discs are used for semi-quantitative in vitro susceptibility testing by standardized agar diffusion test procedures. Grepafloxacin Sensi-Discs® are intended for use in determining the susceptibility to Grepafloxacin of a wide range of bacteria, including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae, Streptococcus pneumoniae. Streptococcus pyogenes, Citrobacter freundii, Citrobacter (diversus) koseri, Enterobacter aerogenes, Enterobacter cloacae,, Escherichia coli, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, and Proteus vulgaris. Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer, GlaxoWellcome, Inc., and received FDA approval under NDA No. 50-717.

Use of BBL® Grepafloxacin Sensi-Discs® for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Grepafloxacin.

Grepafloxacin has been shown to be active against most strains of microorganisms listed below, both in vitro and in clinical infections, as described in the GlaxoWellcome, Inc., package insert for this antimicrobic.

Aerobic Gram-Positive Microorganisms

Streptococcus pneumoniae (penicillin-susceptible strains) Aerobic Gram-Negative Microorganisms

Haemophilus influenzae Moraxella catarrhalis Neisseria gonorrhoeae Other microorganisms Chlamydia trachomatis Mycoplasma pneumoniae

Grepafloxacin exhibits in vitro minimum inhibitory concentrations (MICs) of 1 ug/ml or less against most (≥90%) strains of the microorganisms listed below: however, the safety and effectiveness of Grepafloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Aerobic Gram-Positive Microorganisms (/n Vitro Only)

Staphylococcus aureus (methicillin-susceptible strains) Staphylococcus epidermidis (methicillin-susceptible strains) Streptococcus agalactiae Streptococcus pneumoniae (penicillin-resistant strains) Streptococcus pyogenes

Aerobic Gram-Negative Microorganisms (/n Vitro Only)

Citrobacter freundii Citrobacter (diversus) koseri Enterobacter aerogenes Enterobacter cloacae Escherichia coli Haemophilus parainfluenzae Klebsiella oxytoca Klebsiella pneumoniae Morganella morganii Proteus mirabilis Proteus vulgaris

Antimicrobial Susceptibility Test Discs are used for semi-quantitative in vitro susceptibility testing by standardized agar diffusion test procedures. Grepafloxacin Sensi-Discs® are intended for use in determining the susceptibility to Grepafloxacin of a wide range of bacteria, including Staphylococcus aureus, Staphylococcus epidermidis. Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Citrobacter freundii, Citrobacter (diversus) koseri, Enterobacter aerogenes, Enterobacter cloacae,, Escherichia coli, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, and Proteus vulgaris. Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer, GlaxoWellcome, Inc., and received FDA approval under NDA No. 50-717.

Grepafloxacin Susceptibility Test Discs are prepared by impregnating high quality paper with accurately determined amounts of Grepafloxacin supplied by the manufacturer, GlaxoWellcome, Inc., Research Triangle Park, North Carolina. Each Grepafloxacin disc is clearly marked on both sides with the agent and content. Grepafloxacin discs are furnished in cartridges of 50 discs each. Grepafloxacin 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-S7 (1/97).

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 National Committee for Clinical Laboratory Standards (NCCLS) Document M2-A6 ("Performance Standards for Antimicrobial Disk Susceptibility tests - Sixth Edition, Approved Standard", 1/97) and of NCCLS Document M100-S7 ("Performance Standards for Antimicrobial Susceptibility Testing", Seventh Informational Supplement. 1/97).

This document describes the Grepafloxacin, 5 mcg, Sensi-Discs, an antimicrobial susceptibility test device. The information provided heavily references an attached product insert for RAXAR™ Tablets (grepafloxacin hydrochloride tablets) from GlaxoWellcome, Inc. However, this specific submission (K974578) from Becton Dickinson Microbiology Systems does not contain the detailed performance data or acceptance criteria that would typically be found in a study report proving the device meets those criteria.

The submission primarily focuses on the device description, intended use, indications for use, and a declaration of substantial equivalence to a predicate device. It states that "Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer, GlaxoWellcome, Inc., and received FDA approval under NDA No. 50-717." It also references NCCLS documents M2-A6 and M100-S7 for interpretation.

Therefore, many of the requested details about the study are not present in the provided text.

Based on the available information:

1. Table of acceptance criteria and the reported device performance:

The document states that zone sizes and control organism limits "were determined by the antimicrobic manufacturer, GlaxoWellcome, Inc., and received FDA approval under NDA No. 50-717." However, the specific quantitative acceptance criteria (e.g., accuracy percentages, major error rates) and reported device performance against these criteria are not provided in this submission. The submission refers to an attached GlaxoWellcome, Inc., product insert, which is not included in the provided text.

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

• Sample size: Not specified in the provided text. The submission mentions "clinical isolates" but gives no specific numbers.
• Data provenance: Not specified in the provided text. The testing procedures mentioned (Bauer-Kirby method, Mueller Hinton Agar) are standard laboratory practices, implying lab-generated data, but details on country of origin or whether it was retrospective/prospective are absent.

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

Not specified in the provided text. The ground truth would typically be established by comparing the disc diffusion results to a reference method like broth microdilution Minimum Inhibitory Concentration (MIC) testing. The involvement and qualifications of experts for this comparison are not mentioned.

4. Adjudication method for the test set:

Not specified in the provided text.

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 is a medical device for in vitro susceptibility testing (disc diffusion), not an AI-powered diagnostic device involving human readers for interpretation. The interpretation is based on measuring zones of inhibition and comparing them to established breakpoints.

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

Not applicable. This device is a physical disc impregnated with an antimicrobial agent, used in a traditional laboratory procedure. There is no "algorithm only" performance as it requires human setup, inoculation, incubation, and measurement of inhibition zones.

7. The type of ground truth used:

The ground truth for antimicrobial susceptibility testing is typically established by Minimum Inhibitory Concentration (MIC) values determined by a reference method (e.g., broth microdilution). The document mentions that "Grepafloxacin exhibits in vitro minimum inhibitory concentrations (MICs) of 1 ug/ml or less against most (≥90%) strains of the microorganisms listed below," implying MICs were used as a reference.

8. The sample size for the training set:

Not specified in the provided text. This type of device does not typically involve a "training set" in the context of machine learning. If this refers to the data used to initially establish the zone size breakpoints, those were determined by GlaxoWellcome, Inc., but the sample size is not stated here.

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

Not specified in the provided text. The document refers to the antimicrobic manufacturer, GlaxoWellcome, Inc., for the determination of zone sizes and interpretation, which would have been based on correlation with MIC data (the ground truth).

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The BACTEC® MYCO/F Lytic culture vials when used with the 9000 Blood Culture series of instrumentation are intended as an adjunct to routine blood culture for patients suspected of having mycobacteria, yeast and fungi septicemia. Extended incubation times (7 days for yeast, 30 days for fungi, and 42 days for mycobacteria) will permit recovery of mycobacteria and fungi when more rapidly growing organisms are not present. This medium may also be used for the culture of sterile body fluids when yeast or fungi are suspected.

BACTEC MYCO/F LYTIC Culture medium is a Middlebrook 7H9 and Brain Heart Infusion broth formulation for the recovery of mycobacteria from blood specimens and fungi from blood and sterile body fluids. The range of specimen volume which can be cultured is one to five mL. with optimum recovery obtained at three to five mL. Specific modifications were made to enhance the growth and recovery of mycobacteria, veast, and fungi. These modifications include ferric ammonium citrate to provide an iron source for specific strains of mycobacteria and fungi, the addition of saponin as a blood lysing agent and the addition of specific proteins and sugars to provide nutritional supplements. Each vial contains a sensor which can detect decreases in oxygen concentration in the vial resulting from microorganism and growth. The sensor is monitored by the BACTEC 9000 Blood Culture Systems for increasing fluorescence which is proportional to the decrease in oxygen. A positive determination indicates the presumptive presence of viable microorganisms in the vial.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Device Performance

The BACTEC MYCO/F LYTIC Blood Culture Medium is deemed substantially equivalent to predicate devices (BACTEC 13A for mycobacteria and BACTEC NR FUNGAL for yeast/fungi) based on internal and clinical studies demonstrating "equivalent performance." While explicit numerical acceptance criteria for recovery rates or time to detection are not provided as fixed thresholds, the studies aim to show that the new device performs comparably or better than the predicate devices across various clinically relevant scenarios.

Table of Acceptance Criteria and Reported Device Performance

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The BACTEC ® MYCO/F LYTIC Culture vial when used with the BACTEC 9000MB System is a qualitative test for the culture and recovery of mycobacteria in human blood speciments from patients who are suspected of having septicemia.

BACTEC MYCO/F LYTIC blood culture medium is a non-selective growth medium intended for the culture and recovery of mycobacteria and designed for blood volumes of one to five mL. BACTEC MYCO/F LYTIC culture medium is a Middlebrook 7H9 and Brain Heart Infiusion broth formulation with specific formulation modifications made to enhance the growth of mycobacteria. It is used specifically with the BACTEC 9000MB instrument in the monitoring of clinical blood specimens for the presence of microorganisms. This medium contains the same fluorescence senor as the BACTEC MYCO/F Sputa culture medium and detection is based on changes in oxygen concentration in the vial resulting from metabolism and growth of microorganisms. The sensor is monitored by the BACTEC 9000MB System for increasing fluorescence which is proportinal to the decrease in oxygen. A positive determination indicates the presumptive presence of viable microorganisms in the vial.

Here's an analysis of the acceptance criteria and study details for the BACTEC MYCO/F LYTIC Culture Medium, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly define formal "acceptance criteria" with specific thresholds (e.g., "sensitivity must be >X%"). However, it implies acceptance criteria by comparing the performance of the BACTEC MYCO/F LYTIC medium to a predicate device (BACTEC 13A) and by reporting internal performance characteristics.

The implied objective is that the BACTEC MYCO/F LYTIC medium should be at least comparable to, or ideally better than, the predicate device in terms of mycobacteria recovery and detection, with acceptable false positive and false negative rates.

Since explicit acceptance criteria are missing as numerical targets, I will present the key performance metrics reported in the studies.

2. Sample Size and Data Provenance

• Clinical Test Set Sample Size: 284 blood specimens.
• Data Provenance: Prospective clinical study conducted at "two clinical sites considered large tertiary care teaching hospitals in geographically diverse areas." The specific country of origin is not mentioned but typically for FDA submissions of this era, the studies would be conducted in the United States.

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number of experts or their specific qualifications for establishing the "ground truth" (e.g., "smear and/or subculture-negative/positive") for the clinical test set. It mentions "microbiological workup" and validation against "smear and/or subculture." This implies standard laboratory practices performed by qualified laboratory personnel, but details on expertise (e.g., years of experience, specific certifications) are absent.

4. Adjudication Method

The document does not describe an explicit adjudication method (like 2+1 or 3+1) for resolving discrepancies in the ground truth for the clinical test set. The ground truth ("smear and/or subculture-negative/positive") appears to be determined by confirmed laboratory results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This study compares a device (the BACTEC MYCO/F LYTIC medium) directly against a predicate device (BACTEC 13A medium) in a clinical evaluation, but it is not a "human reader" study; it's a comparison of culture media performance. Therefore, an effect size of human readers improving with or without AI assistance is not applicable.

6. Standalone (Algorithm Only) Performance Study

Yes, a standalone performance study was conducted. The "INTERNAL PERFORMANCE" section and "Table 2: Detection of Mycobacteria in the Myco/F Lytic Medium" represent a standalone evaluation. This study assessed the recovery and time to detection of various mycobacteria species at different CFU levels specifically with the BACTEC MYCO/F LYTIC medium and the BACTEC 9000MB instrument, without direct comparison to human reading or other media as the primary objective.

7. Type of Ground Truth Used

• Clinical Study: The ground truth for the clinical performance evaluation was established through laboratory confirmation (smear and/or subculture results). This represents definitive microbiological results, which would fall under a form of "pathology" in a broader sense of laboratory diagnostics.
• Internal Study: The ground truth for the internal performance study (Table 2) was based on known mycobacteria strains and quantified CFU/bottle (Colony Forming Units per bottle), with the outcome being the time to detection by the BACTEC 9000MB instrument.

8. Sample Size for the Training Set

The document does not mention a training set for the BACTEC MYCO/F LYTIC culture medium. This type of device (a culture medium for microbial growth detection) does not typically involve machine learning algorithms that require explicit "training sets" in the conventional sense. The "internal performance" study (Table 2) could be considered an initial validation or characterization of the medium's performance with known isolates under controlled conditions, serving a similar purpose to testing the device's inherent capabilities before clinical evaluation.

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

Since there is no explicit mention of a "training set" in the context of machine learning, this question is not directly applicable. If the "internal performance" study is considered a foundational or characterization study, the ground truth was established by using known, cultured mycobacteria strains with quantified concentrations (CFU/bottle).

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MYCO/F-Sputa culture media BACTEC Supplement /F when used with the BACTEC Brand 9000MB fluorescent series instrument is a qualitative procedure for the in vitro culture and recovery of mycobacteria from digested decontaminated clinical specimens and sterile body fluids other than blood.

MYCO/F-Sputa culture media with the addition of BACTEC Supplement/F when used with the BACTEC Brand 9000MB fluorescent series instrument is a qualitative test for the in-vitro culture and recovery of mycobacteria from digested decontaminated clinical specimens and sterile body fluids other than blood from patients suspected of pulmonary or disseminated mycobacterial infection.

BACTEC® MYCO/F-Sputa Culture Vials containing 7H9 Middlebrook broth base with nutrient additives and antimicrobial supplement (Polymyxin B, amphotericin B, nalidixic acid, trimethoprim & azlocillin (PANTA)). Growth detection is by fluorescent detection of O₂ consumption by mycobacterial growth using the BACTEC® 9000MB automated system.

Here's the analysis of the provided text regarding the BACTEC® MYCO/F-Sputa Culture Vials, structured according to your request:

Acceptance Criteria and Study Performance for BACTEC® MYCO/F-Sputa Culture Vials

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by comparing the new device against two predicate devices: BACTEC 12B Culture Vials (using the BACTEC 460TB system) and Conventional Media (Lowenstein-Jensen agar slants). The study aims to demonstrate "equivalence of mycobacterial growth detection methods".

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

• Test Set Sample Size:
  • Time to Detection Study: The document mentions "Paired t-tests were performed to compare time to detection...". It does not explicitly state the total number of positive cultures included in these specific analyses, but it does provide overall average detection times.
  • Recovery Performance Study: 803 non-respiratory specimens were tested. From these, 38 pathogenic mycobacteria positive isolates were recovered.
• Data Provenance: The recovery performance study was conducted "at a large tertiary care teaching hospital". This suggests a real-world clinical setting. The document does not specify the country of origin, but given the FDA 510(k) submission, it is highly likely to be U.S.-based. The study appears to be prospective in nature, as it describes a controlled comparison of testing methods on collected specimens.

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

The document does not specify the number of experts or their qualifications for establishing the ground truth. However, for mycobacterial culture and identification, ground truth is typically established by:

• Standard microbiological culture techniques and subsequent identification methods (e.g., biochemical tests, genetic probes).
• Clinician's diagnosis and patient outcomes.

Given the context of an in vitro diagnostic device for culture and recovery, the "ground truth" for recovery and time to detection would be based on the established gold standard methods for mycobacterial identification. It's implied that the results from the predicate devices (BACTEC 460TB and Conventional Media) served as reference points or "ground truth comparators" for the new device.

4. Adjudication Method for the Test Set

The document does not describe a formal "adjudication method" in the sense of multiple independent reviewers resolving discrepancies. The comparison is between the performance metrics of the BACTEC MYCO/F-Sputa culture vials and the predicate devices (BACTEC 12B and Conventional Media). Statistical tests (paired t-tests and McNemar's paired comparison) were used to determine the significance of observed differences, which is a form of objective comparison rather than expert adjudication of individual case disagreement.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Readers Improvement with AI vs. Without AI Assistance

This question is not applicable. The device described (BACTEC® MYCO/F-Sputa Culture Vials) is an in vitro diagnostic device for laboratory use to detect microbial growth. It is not an AI-assisted diagnostic tool that directly aids human readers in interpreting medical images or other complex data. Therefore, an MRMC study and effects on human reader performance with AI assistance are outside the scope of this device.

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

Yes, the studies described are essentially "standalone" performance evaluations of the device. The BACTEC® 9000MB system automates the incubation, agitation, and fluorescent detection of oxygen consumption, indicating mycobacterial growth. The reported time to detection and recovery rates are inherent to the device and system, operating without direct human interpretation of a reading (other than setting up the culture and interpreting the system's output). The "human-in-the-loop" component primarily involves collecting and processing the specimen, loading it into the system, and then acting on the system's results.

7. The Type of Ground Truth Used

The ground truth used for these studies is based on:

• Microbial Culture and Identification: The actual recovery and identification of mycobacteria from clinical specimens by established laboratory methods, including conventional culture and the predicate BACTEC 12B system. The "total pathogenic mycobacteria positive isolates" (38 cases) serves as the reference for recovery studies. The time until growth is detected by these established methods serves as the ground truth for time to detection.

8. The Sample Size for the Training Set

The document does not explicitly state a sample size for a "training set." This is because the BACTEC® MYCO/F-Sputa Culture Vials are a culture medium used with an instrument, not a machine learning or AI algorithm that requires a distinct training phase. The development of the medium and the BACTEC 9000MB system would have involved extensive R&D, but not a "training set" in the context of AI. The described studies are performance validation studies.

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

As there is no distinct "training set" in the AI sense for this type of device, this question is not applicable. The development of the culture medium would have been guided by traditional microbiological principles and established methods for optimizing microbial growth and detection.

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Antimicrobial Susceptibility Test Discs are used for semi-quantitative in vitro susceptibility testing by standardized agar diffusion test procedures. Fosfomycin Sensi-Discs® are intended for use in determining the susceptibility to Fosfomycin of a wide range of bacteria, including Enterococcus faecalis, Enterococcus faeclum, Escherichia coli, Citrobacter diversus, Citerobacter freundii, Entercbacter aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, and Serratia marcesceus. Zone sizes used tor interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer, Forest Pharmaceuticals, Inc., and received FDA approval under NDA No. 50-717.

Use of BBL Fosfomycin Sensi-Discs®.for in .vitro .agar diffusion.susceptibility. testing is indicated when there is a need to determine the susceptibility of bacteria to Fosfomycin. Fosfomycin has been shown to be active against most strains of microorganisms listed below, as described in the Forest Pharmaceuticals, Inc., package insert for this antimicrobic.

Active In Vitro and In Clinical Infections Against: Aerobic Gram-Positive Microorganisms Enterococcus faecalis Aerobic Gram-Negative Microorganisms Escherichia coli Active In Vitro Only Against: Aerobic Gram-Positive Microorganisms Enterococcus faeclum Aerobic Gram-Negative Microorganisms Citrobacter diversus Citerobacter freundii Enterobacter aerogenes Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Proteus vulgaris Serratia marcesceus

Antimicrobial Susceptibility Test Discs

The provided text describes a 510(k) submission for "Fosfomycin, 200 mcg, Sensi-Discs" and provides a "Summary of Safety and Effectiveness." However, it does not include detailed acceptance criteria or a study proving the device meets those criteria in the format requested. The document primarily focuses on the device's labeling, intended use, and substantial equivalence to a predicate device, rather than detailed performance study results with specific metrics.

Therefore, most of the information requested in your prompt cannot be extracted directly from the provided text.

Here's what can be gathered and what is missing:

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

• Acceptance Criteria: Not explicitly stated in terms of quantitative performance metrics for the device itself. The document mentions "Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer, Forest Pharmaceuticals, Inc., and received FDA approval under NDA No. 50-717." This implies that the acceptance criteria for the interpretation of the device's results are based on established standards for Fosfomycin, but the performance of this specific Sensi-Disc against those criteria is not detailed.
• Reported Device Performance: Not provided in a quantitative form (e.g., accuracy, sensitivity, specificity, reproducibility).

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

• Sample Size for Test Set: Not specified.
• Data Provenance (e.g., country of origin of the data, retrospective or prospective): Not specified.

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. The ground truth seems to be implicitly linked to the "Forest Pharmaceuticals, Inc., package insert for this antimicrobic" but how this was established in the context of the Sensi-Disc's performance is not detailed.

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

• Not specified.

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

• This device is an antimicrobial susceptibility test disc (a physical laboratory consumable), not an AI-assisted diagnostic tool. Therefore, an MRMC study comparing human readers with and without AI assistance is not applicable and not mentioned.

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

• Again, this is not an algorithm or AI device. It's a laboratory consumable. Standalone performance as an algorithm is not applicable.

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

• The ground truth is implied to be based on the established clinical breakpoints and susceptibility interpretations for Fosfomycin, as determined by the antimicrobic manufacturer (Forest Pharmaceuticals, Inc.) and FDA-approved under NDA No. 50-717. This would typically involve correlation with minimum inhibitory concentration (MIC) testing (a gold standard for antibiotic susceptibility) and clinical outcomes data from the drug's initial approval. However, the specific method for establishing ground truth for this particular Sensi-Disc performance study is not detailed.

8. The sample size for the training set

• Not specified. This device is not an AI/machine learning model, so the concept of a "training set" in that context does not apply.

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

• As above, not applicable in the context of AI/machine learning training.

In summary, the provided document is a regulatory approval letter and a summary of the device's intended use and relationship to a predicate device. It lacks the detailed performance study data, acceptance criteria, and methodology that would typically be found in a clinical or validation study report.

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Antimicrobial Susceptibility Test Discs are used for semi-quantitative in vitro susceptibility testing by standardized agar diffusion test procedures. Sparfloxacin Sensi-Discs® are intended for use in determining the susceptibility to Sparfloxacin of a wide range of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae (penicillin-susceptible strains), Enterobacter cloacae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer, Rhone Poulenc Rorer Pharmaceuticals, Inc., and received FDA approval under NDA No. 20-677.

Use of BBL® Sparfloxacin Sensi-Discs® for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Sparfloxacin. Sparfloxacin has been shown to be active against most strains of microorganisms listed below, both in vitro and in clinical infections, as described in the Rhone Poulenc Rorer Pharmaceuticals, Inc., package insert for this antimicrobic.

Sparfloxacin Susceptibility Test Discs are prepared by impregnating high quality paper with accurately determined amounts of Sparfloxacin supplied by the manufacturer, Rhone Poulenc Rorer Pharmaceuticals, Inc., Collegeville, Pennsylvania. Each Sparfloxacin disc is clearly marked on both sides with the agent and content. Sparfloxacin discs are furnished in cartridges of 50 discs each. Sparfloxacin 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-A5 (12/93) and M100-S6 (12/95).

Discs containing a wide variety of antimicrobial agents are applied to the surface of Mueller Hinton Agar plates [or Haemophilus Test Medium Agar for H. influenzae or Mueller Hinton Agar with 5% Sheep Blood for S. 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 National Committee for Clinical Laboratory Standards (NCCLS) Document M2-A5 ("Performance Standards for Antimicrobial Disk Susceptibility tests - Fifth Edition, Approved Standard", 12/93) and of NCCLS Document M100-S6 ("Performance Standards for Antimicrobial Susceptibility Testing", Sixth Informational Supplement, 12/95).

This document describes the BBL® Sparfloxacin Sensi-Discs® for antimicrobial susceptibility testing. The data provided focuses on the clinical effectiveness of Sparfloxacin itself, rather than the performance of the Sensi-Discs® as a diagnostic device. The Sensi-Discs® are intended to determine the susceptibility of bacteria to Sparfloxacin using standardized agar diffusion tests.

Here's an analysis of the provided information regarding acceptance criteria and supporting studies, contextualized for the device (Sparfloxacin Sensi-Discs®) where possible, and acknowledging that much of the performance data relates to the drug Sparfloxacin:

1. Table of Acceptance Criteria and Reported Device Performance

For the Sparfloxacin Sensi-Discs®, the acceptance criteria are not explicitly detailed in terms of a device-specific performance study with metrics like accuracy, sensitivity, or specificity against a reference method. Instead, the performance is tied to zone size interpretation and quality control ranges provided by the drug manufacturer (Rhone Poulenc Rorer Pharmaceuticals) and standardized by NCCLS.

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