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The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious isolates.

This 510(k) is for amikacin in the dilution range of 0.25-256 µg/mL for testing non-fastidious gram-negative isolates on The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System. Testing is indicated for Acinetobacter spp., Enterobacterales, and Pseudomonas aeruginosa, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC) webpage.

The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Amikacin in the dilution range of 0.25-256 µg/mL demonstrated acceptable performance with the following organisms:

Acinetobacter spp. (Acinetobacter baumannii)

Enterobacterales (Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marcescens)

Pseudomonas aeruginosa

Not Found

The provided FDA 510(k) clearance letter pertains to The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Amikacin. This device is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious isolates, specifically for amikacin in the dilution range of 0.25-256 µg/mL for testing non-fastidious gram-negative isolates on the system. The indications for use specify its application for Acinetobacter spp., Enterobacterales, and Pseudomonas aeruginosa.

Unfortunately, the provided document does not contain the detailed information required to specifically answer your questions about acceptance criteria, study methodology (sample size, data provenance, expert qualifications, adjudication), MRMC studies, standalone performance, or training set details. This clearance letter is a formal notification of substantial equivalence and outlines the intended use and regulatory classifications, but it does not include the full summary of safety and effectiveness data that would typically contain such study specifics.

To get the information you're looking for, you would generally need to refer to the 510(k) Summary document, which is usually part of the full 510(k) submission and is publicly available through the FDA's 510(k) database. This summary typically provides a more detailed overview of the performance studies conducted to support the clearance.

Therefore, I cannot populate the table or answer most of your specific questions based solely on the provided text.

However, I can extract what is implied about acceptable performance:

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

Based only on the statement "The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Amikacin in the dilution range of 0.25-256 µg/mL demonstrated acceptable performance with the following organisms," we can infer that the device met the manufacturer's internal acceptance criteria for performance for these organisms, as the FDA has cleared it. Without the 510(k) summary, specific numeric thresholds for performance metrics (e.g., Essential Agreement, Category Agreement) for in vitro diagnostic susceptibility tests are not provided in this letter.

• Acinetobacter spp. (Acinetobacter baumannii)
• Enterobacterales (Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marcescens)
• Pseudomonas aeruginosa |

The following questions cannot be answered from the provided document:

2. Sample size used for the test set and the data provenance.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts.
4. Adjudication method for the test set.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, and the effect size of how much human readers improve with AI vs without AI assistance. (Note: This device is an in vitro diagnostic for antimicrobial susceptibility testing, not typically an AI-assisted diagnostic read by a human expert in the context of imaging or pathology. An MRMC study is highly unlikely for this type of device.)
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done. (The device itself is the "standalone" test; human interpretation is involved in setting up the test and reading the results, although it's an automated or semi-automated system. Performance is typically measured against a reference method.)
7. The type of ground truth used. (For AST devices, the ground truth is typically a reference method like broth microdilution or agar dilution, performed according to CLSI guidelines.)
8. The sample size for the training set. (While there might be "training" in the sense of model development for an automated reader, a primary training set in the AI/ML sense is not typically discussed for this type of in vitro diagnostic device, which relies on chemical reactions and optical detection.)
9. How the ground truth for the training set was established. (Similar to point 8, this question's premise might not directly apply to this type of device.)

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The MTS (MIC Test Strip) Sulbactam-Durlobactam 0.004/4-64/4 μg/ml is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/ml of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. MTS Sulbactam- Durlobactam at concentrations of 0.004/4-64/4 μg/ml should be interpreted at 16-20 hours of incubation.

Testing with MTS Sulbactam-Durlobactam at concentrations of 0.004/4-64/4 μg/mL is indicated for Acinetobacter baumannii calcoaceticus complex as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC).

The MTS Sulbactam-Durlobactam 0.004/4-64/4 μg/mL has demonstrated acceptable performance with the following organisms:

Acinetobacter baumannii calcoaceticus complex

MTS Sulbactam-Durlobactam 0.004/4 - 64/4 μg/mL is made of special high-quality paper impregnated with a predefined concentration of gradient sulbactam across 15 two-fold dilutions like those of a conventional MIC method and durlobactam at a fixed concentration of 4 μg/mL. One side of the strip is labeled with the sulbactam-durlobactam code (SUD) and the MIC reading scale in μg/mL. When the MTS is applied onto an inoculated agar surface, the performed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip (MTS) is single use only.

Sulbactam-durlobactam is an intravenous beta-lactam combination antibiotic used to treat hospital-acquired pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.
MTS is supplied in 3 different packaging options (no additional reagents are included). There is a 10- test box, a 30- test box and a 100-test box.

Here is a description of the acceptance criteria and the study proving the device meets those criteria, based on the provided FDA 510(k) clearance letter for the MTS Sulbactam-Durlobactam device:

Device: MTS Sulbactam-Durlobactam 0.004/4 - 64/4 µg/mL (SUD)
Intended Use: Quantitative method for in vitro determination of antimicrobial susceptibility of Acinetobacter baumannii calcoaceticus complex using MIC Test Strips with manual reading after overnight incubation.

1. Acceptance Criteria and Reported Device Performance

The study evaluated the performance of the MTS Sulbactam-Durlobactam device against a reference broth microdilution MIC method. The primary metrics for performance were Essential Agreement (EA) and Category Agreement (CA), along with an analysis of errors (very major, major, minor). While explicit "acceptance criteria" percentages are not directly stated in the summary, typical FDA criteria for AST systems are implied by the reported results. The guidance document referenced "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems, August 28, 2009" would contain the specific acceptance thresholds. Based on the provided summary, the device performance is reported as follows:

Table of Device Performance

Implied Acceptance Criteria (based on typical FDA AST requirements, generally >90% for EA and CA, and strict limits on major/very major errors):
The reported performance values of 97.3% EA and 92.7% CA, along with very low major errors and zero very major errors, indicate that the device met the acceptance criteria as determined by the FDA. Specifically, the zero very major errors are critical for patient safety, as they avoid situations where a resistant infection might be incorrectly identified as susceptible, leading to inappropriate treatment.

2. Sample Size and Data Provenance

• Test Set Sample Size: 588 isolates for the combined clinical and challenge organism groups.
• Data Provenance:
  • Clinical Testing: Performed at three (3) sites. The precise country of origin is not explicitly stated for the clinical sites, but the submitter (Liofilchem s.r.l.) is based in Italy, and their contact person for the 510(k) is in Westlake, Ohio, USA. The FDA clearance suggests testing was appropriate for the US market.
  • Challenge Isolate Testing: Performed at one site (Laboratory Specialists, Inc., which is the 510(k) preparer's company in Westlake, Ohio).
  • Nature of Data: The data combines retrospective (challenge isolates specifically selected to ensure MIC range coverage, including resistant isolates) and prospective (fresh clinical isolates tested at multiple sites) elements.

3. Experts Used for Ground Truth and Qualifications

This section does not directly apply as the device is an in vitro diagnostic (IVD) for antimicrobial susceptibility testing, not an imaging AI device requiring expert interpretation of images. The "ground truth" for antimicrobial susceptibility is established by a standardized laboratory method (broth microdilution) rather than human expert consensus on subjective data.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1, etc.) are typically used in studies involving human interpretation or subjective assessments. For this AST device, the ground truth is established by a quantitative, objective laboratory method (CLSI broth microdilution guidelines). Therefore, no human adjudication method was employed for establishing the ground truth of the MIC values. Minor discrepancies or errors between the device and the reference method are simply categorized as such (major, minor, very major errors).

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

An MRMC study is not applicable to this type of device. The MTS Sulbactam-Durlobactam is a manual antimicrobial susceptibility test system that determines the MIC directly. It is not an AI-assisted diagnostic imaging system where human readers interpret data with or without AI assistance. The performance is assessed by comparing the device's MIC readings to a gold standard laboratory method, not by comparing human reader performance.

6. Standalone (Algorithm Only) Performance

This concept is applicable, and the study provided details on the standalone performance of the MTS Sulbactam-Durlobactam device. The "performance data" table (Essential Agreement, Category Agreement, and Error Rates) directly refers to the device's ability to accurately determine MIC values and susceptibility categories when compared to the reference method, essentially its "algorithm-only" performance in the context of an IVD. There is no "human-in-the-loop" component for interpretation; the user manually reads the MIC from the strip.

7. Type of Ground Truth Used

The ground truth used for this study was reference broth microdilution MIC method, conducted according to CLSI M7-A11 guidelines. This is a well-established and standardized laboratory method for determining antimicrobial minimum inhibitory concentrations, considered the gold standard for AST.

8. Sample Size for the Training Set

The document does not specify a separate "training set" sample size for the development of the MTS Sulbactam-Durlobactam device. For IVDs like AST systems, the "training" typically refers to the initial development and optimization of the test strip's design, antimicrobial gradient, and manufacturing process to reliably produce specific drug concentrations and diffusion patterns. This is primarily a chemical and engineering development process, not a machine learning training process with a distinct data set. The 588 isolates discussed are for the performance validation (test set) rather than initial model training.

9. How Ground Truth for the Training Set Was Established

As noted above, a distinct "training set" and associated "ground truth establishment" in the machine learning sense are not described for this type of medical device. The "ground truth" for the performance validation was established by the CLSI broth microdilution reference method. For the initial development and optimization phase of such a device, the "ground truth" would implicitly be the accurate and precise measurement of drug concentration gradients and their biological effect on various bacterial strains, guided by established AST principles and drug properties.

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The MicroScan Dried Gram-Negative MIC/Combo Panel is used to determine quantitative and qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-negative bacilli. After inoculation, panels are incubated for 16-20 hours at 35°C ± 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the Package Insert.

This particular submission is for the addition of the antimicrobial cefepime at concentrations of 0.12-64 µg/mL to the test panel. Testing is indicated for Enterobacterales, Pseudomonas aeruginosa and Aeromonas spp., as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC) webpage.

The MicroScan Dried Gram-Negative MIC/Combo Panels with Cefepime (CPE) (0.12-64µg/mL) has demonstrated acceptable performance with the following organisms:

Enterobacterales (Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter koseri, (formerly Citrobacter diversus), Citrobacter freundii complex (Citrobacter freudnii, Citrobacter werkmanii and Citrobacter youngae), Klebsiella oxytoca, Morganella morganii, Proteus vulgaris, Providencia stuartii, Providencia rettgeri, Serratia marcescens)

Pseudomonas aeruginosa

Aeromonas spp.

MicroScan Dried Gram-Negative MIC/Combo Panels are designed for use in determining quantitative and qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-negative bacilli.

The principle of MicroScan panels with antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water after inoculation with a standardized suspension of the organism. After incubation in a non-CO2 incubator for 16-20 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.

The product is single-use and intended for laboratory professional use.

Device Performance Acceptance Criteria and Study Details for MicroScan Dried Gram-Negative MIC/Combo Panels with Cefepime

Based on the provided FDA 510(k) Clearance Letter, the device in question is the MicroScan Dried Gram-Negative MIC/Combo Panels with Cefepime (CPE) (0.12-64 µg/mL), which is an Antimicrobial Susceptibility Test (AST) System. The study described focuses on demonstrating the substantial equivalence of this new configuration (with Cefepime) to a predicate device.

Given the nature of the device (an AST System), the "acceptance criteria" are typically related to the accuracy of determining Minimum Inhibitory Concentration (MIC) and the resulting categorical agreement (Susceptible, Intermediate, Resistant) compared to a reference method. The "study that proves the device meets the acceptance criteria" refers to the performance evaluation conducted for the 510(k) submission.

1. Table of Acceptance Criteria and Reported Device Performance

For AST systems, the key performance metrics are Essential Agreement (EA) and Categorical Agreement (CA) when compared to a CLSI (Clinical and Laboratory Standards Institute) frozen reference panel. The FDA document "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", dated August 28, 2009, likely outlines the specific acceptance criteria thresholds for EA and CA. While the exact numerical acceptance criteria are not explicitly stated in the provided text, the performance "demonstrated acceptable performance" implies meeting these pre-defined thresholds.

Important Note: The document highlights some instances where the performance was "outside of essential agreement" for Enterobacterales with Prompt inoculation and "below 90%" for Aeromonas spp. with turbidity inoculation and WalkAway read method. These discrepancies are "mitigated with a limitation" in the product labeling, suggesting that while initial performance in those specific conditions did not meet implicit criteria, the overall robust performance with other methods/organisms, coupled with labeling limitations, made the device acceptable for clearance.

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

• Sample Size: The document does not explicitly provide a total number for the test set sample size (e.g., number of isolates tested). It refers to "contemporary and stock Efficacy isolates and stock Challenge strains" used for external evaluations.
• Data Provenance: The document does not specify the country of origin of the data. It mentions "external evaluations," which generally implies testing conducted at clinical sites or contract research organizations. The study appears to be retrospective in the sense that it uses "stock Efficacy isolates and stock Challenge strains" which are pre-existing collections of bacterial isolates. It also mentions "contemporary" isolates, suggesting some recent collection. It implies a laboratory-based performance study rather than a clinical trial with patient outcomes.

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

This type of device (AST System) does not typically rely on human expert interpretation for establishing the "ground truth" of the test set. The ground truth for antimicrobial susceptibility testing is established by a reference method, which for this device is stated as a "CLSI frozen Reference Panel."

Therefore:

• Number of Experts: Not applicable in the context of creating the ground truth for AST.
• Qualifications of Experts: Not applicable.

4. Adjudication Method for the Test Set

As the ground truth is established by a reference method (CLSI frozen Reference Panel), there is no human adjudication method like 2+1 or 3+1 typically used for image-based diagnostics. The device's results are directly compared to the quantitatively or qualitatively determined results from the CLSI reference method.

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

There is no indication that an MRMC comparative effectiveness study was performed. This type of study is not relevant for this device, which is an automated or manually read laboratory diagnostic for antimicrobial susceptibility, not an AI-assisted diagnostic tool that aids human readers in interpretation. The device itself performs the susceptibility test.

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

Yes, the performance data presented is effectively standalone performance of the device (MicroScan Dried Gram-Negative MIC/Combo Panels with Cefepime). The device "read either visually or with MicroScan instrumentation" and its performance (Essential Agreement, Categorical Agreement) is directly compared to the reference standard. The "human-in-the-loop" would be the laboratory professional reading the results, and the study evaluates the accuracy of the device itself in producing those results. Where visual reads are mentioned, it's about the device's ability to produce clear inhibition patterns for visual interpretation, not a human independently interpreting raw data without the device.

7. The Type of Ground Truth Used

The ground truth used was established by a CLSI frozen Reference Panel. This is a recognized and standardized method for determining antimicrobial susceptibility, often involving broth microdilution or agar dilution methods where organisms are tested against known concentrations of antimicrobials. It is a highly controlled and quantitative method to determine the true MIC value against which the device's performance is compared.

8. The Sample Size for the Training Set

The document does not mention a training set or any details about its sample size. This is consistent with the nature of the device. AST systems are generally rule-based or empirically derived systems based on established microbiological principles, rather than machine learning models that require distinct training sets. The development of such panels involves extensive empirical testing during the R&D phase to ensure the correct concentrations and formulations, but this isn't typically referred to as a "training set" in the context of an AI/ML model.

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

As no training set (in the AI/ML sense) is indicated, this point is not applicable.

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The MicroScan Dried Gram-Positive MIC/Combo Panel is used to determine quantitative and qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative gram-positive cocci, some fastidious aerobic gram-positive cocci and Listeria monocytogenes. After inoculation, panels are incubated for 16-20 hours at 35°C ± 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the Package Insert.

This particular submission is for the addition of the antimicrobial daptomycin at concentrations of 0.06-32 µg/mL to the test panel. Testing is indicated for Enterococcus faecium, Enterococcus spp. other than E. faecium, and Staphylococcus spp., as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC) webpage.

The MicroScan Dried Gram-Positive MIC/Combo Panels with Daptomycin (DAP) (0.06-32 µg/mL) has demonstrated acceptable performance with the following organisms:

• Enterococcus faecium
• Enterococcus spp. other than E. faecium (Enterococcus faecalis, Enterococcus avium, Enterococcus raffinosus, Enterococcus casseliflavus and Enterococcus durans)
• Staphylococcus spp. (Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus capitis, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus hominis, Staphylococcus warneri, Staphylococcus simulans, Staphylococcus saprophyticus, Staphylococcus intermedius, and Staphylococcus sciuri)

MicroScan Dried Gram-Positive MIC/Combo Panels are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-positive bacteria.

The principle of MicroScan panels with antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water after inoculation with a standardized suspension of the organism. After incubation in a non-CO2 incubator for 16-20 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.

This product is single-use and intended for laboratory professional use.

The provided text specifies the performance validation of the MicroScan Dried Gram-Positive MIC/Combo Panels with Daptomycin (DAP). Here's a breakdown of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the reported performance metrics against a CLSI (Clinical and Laboratory Standards Institute) frozen Reference Panel. The primary metrics are Essential Agreement (EA) and Categorical Agreement (CA).

Note: The document states "acceptable performance" without defining specific numerical thresholds for EA and CA as explicit "acceptance criteria." However, the reported values are presented as meeting this "acceptable performance." In antimicrobial susceptibility testing, typical FDA guidance for acceptable EA is generally $\geq$90% and for CA is general $\geq$90% to 95%, depending on the organism/drug combination and resistance rates.

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

The document mentions "external evaluations" conducted with:

• Fresh and stock Efficacy isolates
• Stock Challenge strains

It does not explicitly state the numerical sample size (number of isolates/strains) used for the test set.

The data provenance is not explicitly stated regarding country of origin or whether it was retrospective or prospective. Given the mention of "external evaluations," it implies that the testing was performed, but the location and study design (retrospective/prospective) are not detailed. Standard AST studies typically involve prospective collection of clinical isolates and/or the use of well-characterized reference strains.

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

The ground truth for the test set was established by comparison with a CLSI frozen Reference Panel. This implies that the reference standard, and thus the "ground truth," is determined by a highly standardized and validated laboratory method (broth microdilution or similar CLSI-recognized standard).

The document does not mention human experts being used directly to establish the ground truth for individual cases in the test set. Instead, the CLSI frozen Reference Panel itself serves as the gold standard.

4. Adjudication Method for the Test Set

No human adjudication method (e.g., 2+1, 3+1) is mentioned or implied, as the ground truth is established by the CLSI frozen Reference Panel, not by human interpretation or consensus.

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

This is not applicable to this device. This device is an Antimicrobial Susceptibility Test (AST) panel, which determines the Minimum Inhibitory Concentration (MIC) of an antimicrobial agent against bacteria. It does not involve human readers interpreting images, and therefore, an MRMC study is not relevant. The device measures a quantitative result (MIC) which is then interpreted categorically (susceptible, intermediate, resistant) based on established breakpoints.

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

Yes, this study represents a standalone performance evaluation of the device. The "MicroScan Dried Gram-Positive MIC/Combo Panels with Daptomycin" is a diagnostic test system. Its performance is evaluated against a recognized reference method (CLSI frozen Reference Panel) to determine its accuracy in reporting MIC values and categorical interpretations. While human operators inoculate and read the panels (either visually or with MicroScan instrumentation), the "performance" being assessed here is the device's ability to produce accurate results compared to the reference standard, not an AI algorithm's ability to interpret data without human input.

7. The type of Ground Truth Used

The ground truth used was comparison to a CLSI frozen Reference Panel. This is a laboratory-based gold standard for antimicrobial susceptibility testing, representing the accepted accurate measurement of MIC. It is a highly controlled and standardized method.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning or AI. This is an AST panel, not an AI/ML diagnostic algorithm that requires a training set. The performance validation is based on a comparison to a reference standard using a test set of bacterial isolates/strains.

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

As there is no concept of a training set for this type of device (AST panel based on traditional microbiological principles), this question is not applicable.

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The MicroScan Dried Gram-Negative MIC/Combo Panel is used to determine quantitative and qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-negative bacilli. After inoculation, panels are incubated for 16-20 hours at 35°C ± 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the Package Insert.

This particular submission is for the addition of the antimicrobial aztreonam at concentrations of 0.5-64 µg/mL to the test panel. Testing is indicated for Enterobacterales and Pseudomonas aeruginosa, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC) webpage.

The MicroScan Dried Gram-Negative MIC/Combo Panels with Aztreonam (AZT) (0.5-64 µg/mL) has demonstrated acceptable performance with the following organisms:

Enterobacterales (Citrobacter freundii complex, Citrobacter koseri, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii, Yersinia enterocolitica)

Pseudomonas aeruginosa

MicroScan Dried Gram-Negative MIC/Combo Panels are designed for use in determining quantitative and qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-negative bacilli.

The principle of MicroScan panels with antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water after inoculation with a standardized suspension of the organism. After incubation in a non-CO2 incubator for 16-20 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.

This product is single-use and intended for laboratory professional use.

The provided FDA 510(k) clearance letter pertains to an Antimicrobial Susceptibility Test (AST) system, specifically the MicroScan Dried Gram-Negative MIC/Combo Panels with Aztreonam. It is not an AI/ML medical device. Therefore, many of the requested criteria regarding AI-specific study design (like MRMC studies, number of experts for AI ground truth, training set details) are not applicable to this type of device and study.

However, I can extract the relevant acceptance criteria and performance data for this AST device based on the provided document.

Acceptance Criteria and Device Performance (for an AST System)

The study proves the device's performance through comparison with a CLSI (Clinical and Laboratory Standards Institute) frozen Reference Panel. The criteria primarily revolve around "Essential Agreement (EA)" and "Categorical Agreement (CA)" between the new device and the reference method.

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document implicitly refers to the "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", dated August 28, 2009. This guidance typically defines the statistical acceptance criteria for EA and CA for AST systems. The document states the device "demonstrated substantially equivalent performance when compared with a CLSI frozen Reference Panel, as defined in the FDA document..." meeting "acceptable performance."

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

• The document mentions "external evaluations were conducted with contemporary and stock Efficacy isolates and stock Challenge strains."
• Specific numerical sample sizes for the test set (number of isolates/strains) are not explicitly stated in the provided text.
• Data Provenance: The document does not specify the country of origin. It indicates the use of "contemporary and stock Efficacy isolates and stock Challenge strains," which suggests a mix of clinical and laboratory strains. The study appears to be prospective in nature, as new data was generated for this specific submission to demonstrate performance against a reference standard.

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

• This is an AST system, not an AI/ML device requiring expert radiological annotation.
• Ground Truth Establishment: The ground truth (reference MIC values and categorical interpretations) for the test set was established by a CLSI frozen Reference panel. This is a recognized standard method for AST device validation. The "experts" in this context are the established CLSI methodologies and laboratories that produce these reference panels, not individual human readers or annotators in the typical AI/ML sense.

4. Adjudication Method for the Test Set

• Adjudication, as typically described (e.g., 2+1, 3+1), is not applicable here because the ground truth is established by a standardized laboratory method (CLSI frozen Reference panel), not by consensus among human experts annotating medical images. The comparison is objective, based on measured MIC values.

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

• No, an MRMC comparative effectiveness study was not done. This type of study is specific to diagnostic imaging devices where human readers interpret medical images with and without AI assistance.
• This device is an in vitro diagnostic (IVD) antimicrobial susceptibility test system, where the output is a MIC value and a categorical interpretation for a bacterial isolate, not an image interpretation by a human observer.

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

• This question is framed for AI/ML algorithms. While the device automation ("MicroScan instrumentation," "WalkAway instrument") is a component, the "standalone performance" here refers to the device's ability to accurately determine MIC and categorize susceptibility when compared to the CLSI reference method.
• The study did evaluate the device's performance independently of human interpretation, as it explicitly states panels can be "read either visually or with MicroScan instrumentation." The reported EA and CA numbers reflect the system's performance, including automated reading where applicable.

7. The Type of Ground Truth Used

• Reference Standard: The ground truth used was a CLSI frozen Reference Panel. This is considered the gold standard for comparing the performance of new antimicrobial susceptibility test devices. It provides "true" Minimum Inhibitory Concentration (MIC) values for the bacterial isolates against the antimicrobial agent.

8. The Sample Size for the Training Set

• This is an IVD device, not an AI/ML system that undergoes a separate "training" phase with a large dataset in the sense of machine learning. The device's underlying "knowledge" is built into its design, chemistry, and reading algorithms (for automated methods).
• Therefore, the concept of a "training set" as understood in AI/ML is not applicable to this device.

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

• As the concept of a "training set" as in AI/ML does not apply here, this point is not applicable. The device's development involved standard microbiological and analytical chemistry principles, validated against established reference methods.

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The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious isolates.

This 510(k) is for ciprofloxacin in the dilution range of 0.002-64 ug/mL for testing non-fastidious gram-negative isolates on The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System. Testing is indicated for Enterobacterales and Pseudomonas aeruginosa, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC) webpage.

The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Ciprofloxacin in the dilution range of 0.002-64 ug/mL demonstrated acceptable performance with the following organisms:

Enterobacterales (C. freundii, C. koseri, E. cloacae complex, E. coli, K. aerogenes, K. oxytoca, K.pneumoniae, M. morganii, P. mirabilis, P. rettgeri, P. stuartii, P. vulgaris, S. marcescens)

Pseudomonas aeruginosa

Not Found

The provided FDA 510(k) clearance letter (K250990) for "The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Ciprofloxacin in the dilution range of 0.002-64 µg/mL" does not include detailed information about the acceptance criteria or the specific study that proves the device meets those criteria. The letter primarily serves as a notification of substantial equivalence and outlines regulatory requirements.

However, based on the nature of the device (Antimicrobial Susceptibility Test) and the context of FDA clearance for such products, we can infer the typical types of acceptance criteria and studies that would have been conducted. Please note that the specific numerical values for acceptance criteria and study details are not present in the provided document and would normally be found in the manufacturer's 510(k) submission summary.

Here's a breakdown of the requested information, with inferred details for sections not explicitly stated:

Acceptance Criteria and Device Performance

Note: The specific acceptance criteria (e.g., % Essential Agreement, % Category Agreement) and the reported device performance for the Sensititre system with Ciprofloxacin are not provided in the FDA clearance letter. For an AST device, these usually revolve around agreement with a reference method.

Inferred Acceptance Criteria and Hypothetical/Typical Reported Performance for AST Devices:

Explanation of Terms (for AST devices):

• Essential Agreement (EA): The Minimum Inhibitory Concentration (MIC) result of the test device is within ±1 doubling dilution of the reference method's MIC result.
• Category Agreement (CA): The interpretive category (Susceptible, Intermediate, Resistant) assigned by the test device matches the interpretive category assigned by the reference method.
• Minor Errors (mE): One method (test or reference) interprets as Intermediate, and the other interprets as Susceptible or Resistant.
• Major Errors (ME): The test device interprets as Susceptible, but the reference method interprets as Resistant. This is a critical error as it could lead to ineffective treatment.
• Very Major Errors (VME): The test device interprets as Resistant, but the reference method interprets as Susceptible. This is also a critical error as it could lead to unnecessary use of broader-spectrum antibiotics.

Study Details (Inferred/Typical for AST Devices)

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

   • Sample Size (Test Set): Not specified in the clearance letter. For AST devices, test sets typically involve hundreds to thousands of unique isolates for each organism-antibiotic combination to ensure statistical significance across various resistance mechanisms and phenotypes. This would include both common and challenging strains.
   • Data Provenance: Not specified. For FDA submissions, the data provenance is usually a mix of prospective and retrospective clinical isolates, often collected from diverse geographical regions (e.g., multiple centers across the United States) to represent a broad range of clinically relevant strains. The clearance letter mentions testing for "Enterobacterales" and "Pseudomonas aeruginosa," indicating a focus on these specific bacterial groups.

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

   • Number of Experts: Not specified. For AST devices, ground truth is typically established by reference laboratory personnel highly experienced in microbiology, particularly in performing and interpreting reference AST methods (e.g., broth microdilution or agar dilution as per CLSI guidelines). These are not usually "experts" in the sense of clinicians reading images, but rather highly skilled microbiologists.
   • Qualifications of Experts: Clinical microbiologists, medical technologists, or laboratory scientists with extensive experience (e.g., 5-10+ years) in a clinical microbiology reference laboratory, proficient in CLSI (Clinical and Laboratory Standards Institute) methodologies for antimicrobial susceptibility testing.

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

   • Adjudication Method: Not applicable in the traditional sense for AST devices when comparing to a recognized reference method. The "ground truth" (reference method results) is considered definitive. If initial discrepancies occur between the test device and the reference method, these are typically re-tested by the reference method for confirmation rather than adjudicated by human readers. The reference method (e.g., CLSI broth microdilution) is itself the gold standard.

4. 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: Not applicable. This type of study (MRMC) is relevant for diagnostic imaging devices where human readers interpret images, sometimes with AI assistance. The Sensititre system is an in vitro diagnostic device for antimicrobial susceptibility testing, which directly measures bacterial growth inhibition at various antibiotic concentrations (MICs). It does not involve human "readers" interpreting output in the same way as an imaging device, nor does it typically involve AI assistance in its core mechanism for determining MICs.

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

   • Standalone Performance: Yes, the core evaluation of an AST device like Sensititre is a standalone performance study. The device, when operated according to its instructions for use, generates MIC results and interpretive categories. These results are then compared directly to the reference method. There isn't typically a "human-in-the-loop" for the determination of the MIC or category by the device itself, although human laboratory personnel perform the setup and interpretation of the result in the clinical workflow. The performance data presented in the 510(k) submission would reflect this intrinsic performance of the device.

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

   • Type of Ground Truth: For AST devices, the ground truth is established by a recognized reference method, typically the CLSI (Clinical and Laboratory Standards Institute) reference broth microdilution method or agar dilution method. This is considered the "gold standard" for determining MICs and susceptibility categories. It is a highly standardized and reproducible laboratory procedure.

7. The sample size for the training set:

   • Sample Size (Training Set): Not applicable in the same way as for AI/machine learning algorithms. The Sensititre system is a phenotypic AST system, not an AI-based diagnostic algorithm that requires a "training set" of data. Its "training" is inherent in its design and manufacturing, based on established microbiological principles for detecting bacterial growth and inhibition. Any "development" data would be internal to the manufacturer for optimizing plate format, reagent concentrations, and reading algorithms, but not a "training set" in the context of deep learning.

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

   • Ground Truth for Training Set: Not applicable for this type of device. As explained above, the device does not use a "training set" with established ground truth in the AI sense. Its underlying principles are based on microbiological standards and reference methods.

Summary of Information from the FDA Letter:

• Device Name: The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Ciprofloxacin in the dilution range of 0.002-64 µg/mL
• Intended Use: In vitro diagnostic product for clinical susceptibility testing of non-fastidious isolates, specifically for Ciprofloxacin in the stated dilution range against Enterobacterales (C. freundii, C. koseri, E. cloacae complex, E. coli, K. aerogenes, K. oxytoca, K.pneumoniae, M. morganii, P. mirabilis, P. rettgeri, P. stuartii, P. vulgaris, S. marcescens) and Pseudomonas aeruginosa.
• Performance: "demonstrated acceptable performance" (no specific metrics or values provided in the clearance letter).

To obtain the detailed acceptance criteria and study specifics, one would need to review the manufacturer's 510(k) summary, which is typically a public document available through the FDA's 510(k) database.

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The Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC (HP) or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of fastidious isolates.

This 510(k) is for ceftobiprole in the dilution range of 0.008-16 µg/mL for testing fastidious isolates on the Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC (HP) or Breakpoint Susceptibility System. Testing is indicated for Streptococcus pneumoniae and Streptococcus pyogenes, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC) webpage.

The Sensititre 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae MIC (HP) or Breakpoint Susceptibility System with Ceftobiprole in the dilution range of 0.008-16 µg/mL demonstrated acceptable performance with the following organisms:

• Streptococcus pneumoniae
• Streptococcus pyogenes

Not Found

I am sorry, but the provided text from the FDA 510(k) Clearance Letter does not contain the detailed information necessary to answer your request regarding acceptance criteria and the study proving the device meets those criteria.

The letter explicitly states: "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..."

This means the FDA has determined the device is substantially equivalent to a previously cleared device, rather than requiring the submission of a de novo study including specific acceptance criteria and detailed study results. The letter does not describe the specific study design, sample sizes, expert qualifications, or ground truth methods used to establish the performance of the device itself against predefined acceptance criteria. Instead, it focuses on the administrative aspects of the 510(k) clearance process, regulatory compliance, and the device's intended use.

Therefore, I cannot provide:

1. A table of acceptance criteria and reported device performance: This information is not present.
2. Sample sizes used for the test set and data provenance: Not detailed in the letter.
3. Number of experts used to establish ground truth and their qualifications: Not detailed in the letter.
4. Adjudication method: Not detailed in the letter.
5. MRMC comparative effectiveness study details or effect size: This type of study is typically for AI/imaging devices, not for an antimicrobial susceptibility test system as described. Even if it were relevant, the information is not present.
6. Standalone (algorithm only) performance: Not applicable to this type of device and not mentioned.
7. Type of ground truth used: Not detailed in the letter.
8. Training set sample size: Not detailed in the letter.
9. How ground truth for the training set was established: Not detailed in the letter.

The primary purpose of this FDA letter is to inform the manufacturer of the clearance and the associated regulatory requirements, not to disseminate the specifics of the underlying performance studies that led to the substantial equivalence determination.

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ETEST® is a manual, quantitative technique for the determination of antimicrobial susceptibility of non‑fastidious Gram‑negative and Gram‑positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in μg/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.

Testing with ETEST® Aztreonam/Avibactam (AZA) (0.016/4-256/4 μg/mL) is indicated for Enterobacterales, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC).

The ETEST® Aztreonam/Avibactam (AZA) (0.016/4-256/4 μg/mL) demonstrated acceptable performance with the following microorganisms:

• Enterobacterales:

• Escherichia coli
• Klebsiella pneumoniae
• Klebsiella aerogenes
• Citrobacter freundii complex
• Citrobacter koseri
• Enterobacter cloacae complex
• Proteus mirabilis
• Proteus vulgaris
• Morganella morganii
• Providencia stuartii
• Serratia marcescens

ETEST® is a thin, inert and non-porous plastic strip carrying the MIC reading scale in μg/mL on one side and a predefined antibiotic gradient on the other side.

When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of μg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.

ETEST® Aztreonam/Avibactam (AZA) (0.016/4-256/4 µg/mL) contains a range of Aztreonam from (0.016-256 µg/mL), overlaid with a fixed concentration of 4 µg/mL of Avibactam.

The provided FDA 510(k) clearance letter describes the acceptance criteria and the study proving the ETEST Aztreonam/Avibactam (AZA) device meets these criteria for determining antimicrobial susceptibility.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for antimicrobial susceptibility test (AST) systems, as outlined by the FDA and CLSI (Clinical and Laboratory Standards Institute), are primarily based on Essential Agreement (EA) and Category Agreement (CA) with a reference method.

The acceptance criteria are implicitly met if the reported performance metrics achieve or exceed the established thresholds (though the exact numerical acceptance thresholds for EA and CA are not explicitly stated as "acceptance criteria" values in this document, standard FDA guidance for AST devices typically requires EA ≥ 90% and CA ≥ 90% for overall performance).

Note: The document also states that the device "demonstrated substantially equivalent performance when compared with the CLSI M07-11th Ed (January 2018) broth microdilution reference method, following rules as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, issued on August 28, 2009 and following specifications as defined in CLSI M100 35th Ed. (January 2025)." This indicates adherence to established regulatory and standard-setting body guidelines for performance.

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

• Sample Size for Test Set: A total of 602 strains of Enterobacterales were used for the performance evaluation.
  • This included:
    • Escherichia coli (150 strains)
    • Klebsiella pneumoniae (118 strains)
    • Enterobacter cloacae complex (67 strains, including E. cloacae, E. hormaechei, E. asburiae, E. roggenkampii, E. ludwigii)
    • Citrobacter freundii complex (50 strains, including C. freundii, C. braakii, C. murliniae, C. portucalensis)
    • Citrobacter koseri (30 strains)
    • Klebsiella aerogenes (32 strains)
    • Morganella morganii (30 strains)
    • Proteus mirabilis (32 strains)
    • Providencia stuartii (30 strains)
    • Proteus vulgaris (30 strains)
    • Serratia marcescens (33 strains)
  • Additionally, 12 Enterobacterales resistant isolates with high MIC values (≥ 16 µg/mL) were specifically included: Klebsiella pneumoniae (2), Escherichia coli (8), Serratia marcescens (1) and Enterobacter cloacae complex (1).
• Data Provenance: The document states "External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This implies a mix of retrospective (stock clinical isolates, challenge strains) and prospective (fresh clinical isolates) data. The country of origin of the data is not specified in this document.

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

This document describes the validation of an in vitro diagnostic device for antimicrobial susceptibility testing, not an imaging AI device requiring expert human reads. Therefore, the concept of "experts" to establish ground truth in the context of human readers is not directly applicable.

Instead, the ground truth was established by a reference method: the CLSI (Clinical and Laboratory Standards Institute) M07-11th Ed (January 2018) broth microdilution reference method. This method is considered the gold standard for determining Minimum Inhibitory Concentrations (MICs) in microbiology. The qualifications of personnel performing this reference method would be standard microbiology laboratory technicians or scientists trained in CLSI methods, rather than clinical experts like radiologists. The number of individuals/laboratories involved in performing the reference method is not specified.

4. Adjudication Method for the Test Set

Not applicable in the context of in vitro diagnostic device validation using a reference laboratory method. Adjudication methods (like 2+1 or 3+1) are typically used in clinical studies where human readers provide subjective interpretations, and conflicts need resolution. Here, the ground truth is a quantitative, standardized microbiology assay.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement with AI Assistance

Not applicable. This is an in vitro diagnostic device (a test strip) for determining antimicrobial susceptibility, not an AI-assisted diagnostic tool for human image interpretation. Therefore, no MRMC study or assessment of human reader improvement with AI assistance was conducted.

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

The device itself is a manual, quantitative technique. It is a physical strip that produces a visual inhibition zone from which a Bacterial MIC value is read. It does not involve a software algorithm in the way an AI diagnostic tool would. Therefore, the concept of "standalone performance" of an "algorithm" is not directly applicable in the same sense as for an AI product.

The performance evaluation (which can be considered analogous to "standalone performance" in that it assesses the device's accuracy without a human "interpretation" component beyond reading the scale) was done by comparing the ETEST Aztreonam/Avibactam (AZA) strip's results to the CLSI broth microdilution reference method. This demonstrates the device's inherent capability to accurately determine MIC values.

7. The Type of Ground Truth Used

The ground truth used was the CLSI M07-11th Ed (January 2018) broth microdilution reference method. This is a highly standardized and accepted laboratory reference method for determining the Minimum Inhibitory Concentration (MIC) of an antimicrobial agent against a microorganism. It serves as the definitive 'truth' against which the performance of the ETEST device is measured.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning model development. This is an in vitro diagnostic device, not a software algorithm that undergoes a distinct training phase. The development of such devices typically involves extensive R&D, formulation optimization, and internal testing before external clinical evaluations. The "training" in this context would refer to the development and optimization of the test strip's chemical gradient to accurately reflect MIC values, rather than training a data-driven model. The document focuses on the validation (test set) for regulatory clearance.

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

As noted above, the concept of a "training set" and associated ground truth establishment methods for it, as typically applied to machine learning, is not directly relevant to this type of in vitro diagnostic device. The 'ground truth' for validating the performance of this device is consistently the CLSI broth microdilution reference method, which is the gold standard for antimicrobial susceptibility testing. Any internal development or optimization of the ETEST strip formulation would also rely on this or similar established reference methods to guide product development.

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NG-Test® CTX-M MULTI is an in vitro rapid and visual immunochromatographic assay for the qualitative detection of CTX-M enzymes (groups 1, 2, 8, 9, and 25) from pure colonies of Enterobacterales suspected of ESBL production when grown on the following media:

• 5% sheep blood agar or MacConkey agar (16-24 hours)
• HardyCHROM™ ESBL agar (18-24 hours)

The NG-Test® CTX-M MULTI is intended as an aid for infection control in the detection of CTX-M enzymes-producing organisms (Enterobacterales) in healthcare settings. NG-Test® CTX-M MULTI is not intended to guide or monitor treatment. A positive or negative NG-Test® CTX-M MULTI test result does not rule out the presence of other mechanisms of antibiotic resistance. NG-Test® CTX-M MULTI should be used in conjunction with other laboratory tests including phenotypic antimicrobial susceptibility testing.

NG-Test® CTX-M MULTI is an in vitro rapid and visual immunochromatographic assay for the qualitative detection of CTX-M enzymes (groups 1, 2, 8, 9, and 25) from pure colonies of Enterobacterales suspected of ESBL production after culturing on agar and processed in an extraction buffer. The device consists of a sample port, sample and conjugate pad, and nitrocellulose test strip, which are contained within a plastic cassette, in addition to reagents for liquid extraction. The result can be read 15 minutes after adding the sample to the sample well. A positive result on the NG-Test® CTX-M MULTI occurs when two red lines appear, one on the control (C) region and one on the test (T) region. A negative result occurs when only the control line is observed and indicates the sample does not contain any target CTX-M enzymes, or the CTX-M enzymes are present at a non-detectable level. If the control line does not appear, the test result is invalid.

Monoclonal antibodies that recognize the five major CTX-M groups are immobilized on a nitrocellulose membrane. Free monoclonal antibodies are present in the conjugate pad and labeled with colloidal gold. Upon addition of the processed sample to the sample pad, the capillary action of the nitrocellulose draws the sample through the mobile antibodies in the conjugate pad and the immobile antibodies on the test strip. The immobilized control antibodies capture any mobile antibodies that do not bind to the test line.

This document describes the performance of the NG-Test® CTX-M MULTI device, an in vitro rapid immunochromatographic assay for detecting CTX-M enzymes.

Here is a breakdown of the requested information:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the device are implied by the reported sensitivity and specificity values. While explicit "acceptance criteria" are not listed as target percentages, the study results demonstrate high performance that led to clearance.

Table of Performance Data (Clinical Study - Blood and MacConkey Agar):

Table of Performance Data (Seeded Study - HC ESBL Agar):

Note: The lower bound of the specificity for HC ESBL agar (87.9%) is acknowledged as being below 90% due to a lower quantity of CTX-M negative isolates in this specific part of the study, and additional CTX-M negative isolates were evaluated in the cross-reactivity study to compensate.

2. Sample Size and Data Provenance

• Test Set Sample Size:
  • Clinical Study (Blood and MacConkey Agar): 309 Enterobacterales isolates.
  • Seeded Study (HardyCHROM™ ESBL Agar): 193 clinical isolates.
• Data Provenance:
  • Country of Origin: Not explicitly stated, but the study was conducted at "three geographically diverse hospitals," implying the data is from a clinical setting.
  • Retrospective or Prospective: A mix was used:
    • "Prospectively-collected" bacterial isolates were used for the performance evaluation.
    • "Stock bacterial isolates" were also used. This suggests a combination of prospective collection and retrospective use of archived isolates.

3. Number of Experts and Qualifications for Ground Truth

• The document does not specify the number of experts used to establish ground truth or their qualifications. The ground truth relies on laboratory methods (PCR and AST).

4. Adjudication Method for the Test Set

• The document does not describe an adjudication method for the test set results. The comparison is between the device's reading and the reference method (PCR and AST).

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

• A MRMC comparative effectiveness study involving human readers with vs. without AI assistance was not conducted. This device is an immunochromatographic assay, not an AI-based diagnostic with human-in-the-loop performance.
• However, a reproducibility study involved multiple readers: "The testing was done with one operator and two readers, blinded to each other's results, per site." This was to demonstrate reproducibility of the device's results, not to compare human performance with and without the device.

6. Standalone (Algorithm Only) Performance

• This device is a standalone diagnostic test (an immunochromatographic assay). Its performance is evaluated directly without a human-in-the-loop component for result interpretation beyond visual reading. The reported sensitivity and specificity refer to the device's performance as a standalone test.

7. Type of Ground Truth Used

• Reference standard:
  • PCR (Polymerase Chain Reaction): Used to detect blaCTX-M genes, considered the definitive molecular method. Isolates with a positive PCR result were also sequenced to determine the CTX-M variant.
  • Antimicrobial Susceptibility Testing (AST): Performed according to CLSI M100, 34th edition breakpoints. A positive comparator method result was defined as any Enterobacterales that produced a positive PCR result and was not susceptible to at least one of the antimicrobial agents.
  • Identification (ID): Performed using FDA-cleared ID systems.

8. Sample Size for the Training Set

• The document does not specify a separate "training set" size. As this is an immunochromatographic assay, it doesn't involve machine learning model training in the typical sense. The analytical reactivity study and analytical specificity study essentially serve as extensive performance characterization using known strains, which could be conceptually similar to a "development" or "characterization" set for more traditional devices.
  • Analytical Reactivity: 57 strains of Enterobacterales characterized to harbor CTX-M enzymes.
  • Analytical Specificity: 55 organisms with other resistance mechanisms.

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

• For the analytical reactivity and analytical specificity studies (which characterize the device's performance with known strains, akin to a training/development set in ML contexts):
  • Strains were "characterized to harbor CTX-M enzymes" or "exhibit antimicrobial resistance mechanisms other than CTX-M." This characterization would typically involve established molecular methods (e.g., PCR, sequencing) and phenotypic susceptibility testing performed by a reference lab or research institution. The document states "Each organism was incubated..." and tested, implying these were well-characterized isolates.

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The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious isolates.

This 510(k) is for vancomycin in the dilution range of 0.25-128 ug/mL for testing non-fastidious gram-positive isolates on the Sensititre 18-24 hour MIC or Breakpoint Susceptibility System. Testing is indicated for Staphylococcus aureus, Staphylococci other than Staphylococcus aureus, and Enterococcus spp., as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC) webpage.

The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Vancomycin in the dilution range of 0.25-128 ug/mL demonstrated acceptable performance with the following organisms:

Staphylococcus aureus (including MRSA)
Staphylococci other than Staphylococcus aureus (S. epidermidis, S. haemolyticus, S. hominis, S. lugdunensis, S. saprophyticus)
Enterococcus spp. (E. faecalis, E. faecium)

Not Found

The provided FDA 510(k) clearance letter pertains to an Antimicrobial Susceptibility Test (AST) System (The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Vancomycin). This type of medical device is designed to determine the susceptibility of bacteria to various antimicrobial agents.

It's crucial to understand that the information typically requested in your prompt (especially regarding AI/ML models, MRMC studies, expert consensus on ground truth for medical images, etc.) is NOT APPLICABLE to this type of device. The FDA clearance letter describes a traditional in vitro diagnostic product, not a software-as-a-medical-device (SaMD) or an AI/ML-powered diagnostic aid.

Therefore, the following points address the questions to the extent they are relevant to a traditional AST system, while clarifying where the requested information is not applicable.

Description of Acceptance Criteria and Study Proving Device Performance for The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Vancomycin

This device is an in vitro diagnostic product used for clinical susceptibility testing of non-fastidious bacterial isolates against Vancomycin. The performance of such systems is typically evaluated based on their ability to accurately determine the Minimum Inhibitory Concentration (MIC) or breakpoint susceptibility, which is compared to a reference method.

1. Table of Acceptance Criteria and Reported Device Performance

For Antimicrobial Susceptibility Test (AST) systems, acceptance criteria are generally based on agreement rates with a reference method (e.g., broth microdilution or agar dilution as per CLSI standards). The key performance metrics are:

• Essential Agreement (EA): The MIC result obtained by the test device is within ±1 doubling dilution of the reference method MIC.
• Categorical Agreement (CA): The interpretation (Susceptible, Intermediate, Resistant) obtained by the test device agrees with the interpretation from the reference method.
• Minor Errors (mE): The test device classifies a sample as Susceptible when the reference method classifies it as Intermediate or Resistant, or as Intermediate when the reference method classifies it as Susceptible or Resistant.
• Major Errors (ME): The test device classifies a sample as Resistant when the reference method classifies it as Susceptible.
• Very Major Errors (VME): The test device classifies a sample as Susceptible when the reference method classifies it as Resistant.

Typical Acceptance Criteria (General for AST, specific values are submission-dependent):

The clearance letter states: "The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Vancomycin in the dilution range of 0.25-128 µg/mL demonstrated acceptable performance with the following organisms: Staphylococcus aureus (including MRSA), Staphylococci other than Staphylococcus aureus (S. epidermidis, S. haemolyticus, S. hominis, S. lugdunensis, S. saprophyticus), Enterococcus spp. (E. faecalis, E. faecium)." This statement confirms that the specific performance criteria (EA, CA, mE, ME, VME) were met for these organisms, although the exact percentages are not provided in the public clearance letter.

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

The clearance letter does not specify the exact sample size used for the test set. For AST systems, the test set typically includes a significant number of clinical isolates (hundreds to thousands, often including challenge strains with known resistance mechanisms) to ensure robustness across various resistance profiles.

• Data Provenance: For in vitro diagnostic devices, data is typically collected from prospective and/or retrospective clinical samples from laboratories, often from multiple geographically diverse sites within the country of submission (e.g., the United States for FDA clearance) to represent real-world clinical populations. Some isolates may also come from culture collections.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This question is not applicable in the context of an AST system being cleared.

• Ground truth for AST systems is established by validated reference methods (e.g., CLSI broth microdilution, agar dilution, or molecular methods for specific resistance genes) run by trained laboratory personnel, not by expert interpretation of images or clinical data. There are no "experts" in the sense of physicians or radiologists reviewing and labeling data.

4. Adjudication Method for the Test Set

This question is not applicable.

• Since ground truth is established by a quantitative laboratory method, there is no "adjudication" in the sense of multiple human readers resolving disagreements. Discrepancies between the test device and the reference method would be analyzed, and repeated testing or further characterization of the isolate might occur if needed during the study design, but it's not a consensus-based adjudication process.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size

This question is not applicable.

• MRMC studies are relevant for devices that involve human interpretation of medical images or complex data (e.g., AI-powered CADe/CADx devices for radiology). An AST system is an automated or semi-automated laboratory instrument that provides a direct result (MIC value, interpretation) based on bacterial growth or lack thereof. There is no "human reader" component in the direct output of the device that would be assisted by AI, nor is there a direct human comparative effectiveness study for its primary function.

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

This question is not applicable in the sense of an AI algorithm.

• The Sensititre 18-24 hour system is primarily a "standalone" device in that it produces susceptibility results without requiring human "interpretation" of a complex output like an image. Its performance is evaluated independently against a reference method. However, it's not an "algorithm only" in the sense of a software-driven AI solution; it is a laboratory instrument that performs a specific biological assay.

7. The Type of Ground Truth Used

• The ground truth for AST systems is based on reference antimicrobial susceptibility testing methods, typically broth microdilution or agar dilution as per a recognized standard (e.g., Clinical and Laboratory Standards Institute - CLSI guidelines). This is considered the "gold standard" for determining MIC values and categorical interpretations. In some cases, molecular methods (e.g., PCR for resistance genes) might be used to confirm certain resistance mechanisms, which indirectly supports the "ground truth" for specific resistant phenotypes.

8. The Sample Size for the Training Set

This question is not applicable for a traditional AST system.

• Traditional AST systems are not "trained" in the way AI/ML models are. They are designed and validated based on established microbiological principles. There is no distinct "training set" of data used to iteratively improve an algorithm's performance. Instead, the device is developed, and its performance is then validated against a large test set to ensure accuracy and reproducibility.

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

This question is not applicable for a traditional AST system, as there is no "training set" in the AI/ML sense.

In summary, the FDA clearance for The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Vancomycin is based on the device's ability to accurately determine antimicrobial susceptibility by comparing its results to established reference methods using a statistically significant number of relevant bacterial isolates. The concepts of AI/ML model training, human expert consensus for image interpretation, and MRMC studies are not relevant to the validation of this traditional in vitro diagnostic device.

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