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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 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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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)

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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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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 Imipenem/Relebactam P. aeruginosa (IRPA) (0.008/4-128/4 µg/mL) is indicated for Pseudomonas aeruginosa, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC).

The ETEST Imipenem/Relebactam P. aeruginosa (IRPA) (0.008/4-128/4 µg/mL) demonstrated acceptable performance with the following microorganism:
• Pseudomonas aeruginosa

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 Imipenem/Relebactam P. aeruginosa (IRPA) with a concentration range of 0.008/4-128/4 µg/mL is specially designed and formulated for testing P. aeruginosa.

This document describes the regulatory clearance for the ETEST® Imipenem/Relebactam P. aeruginosa (IRPA) device, which is an antimicrobial susceptibility test. Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are defined by established performance metrics in antimicrobial susceptibility testing, specifically Essential Agreement (EA) and Category Agreement (CA), compared to a reference method. The reported performance demonstrates the device meets these criteria.

Study Details Proving Device Meets Acceptance Criteria

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

   • Sample Size: 437 strains of Pseudomonas aeruginosa.
   • Data Provenance: The study involved external evaluations conducted with fresh and stock clinical isolates, as well as a set of challenge strains. The specific country of origin is not mentioned, but "external evaluations" imply samples from clinical settings. The nature of "fresh" and "stock clinical isolates" suggests a mix of retrospective and prospective data, where fresh isolates would be prospective and stock isolates could be retrospective.

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

   • This information is not explicitly provided in the document. Antimicrobial Susceptibility Testing (AST) generally relies on established laboratory methods rather than expert consensus for ground truth, but the personnel performing the reference method would be trained laboratory technicians.

3. Adjudication Method for the Test Set:

   • None explicitly stated as it's a comparison to a reference laboratory method (CLSI M07-11th Ed broth microdilution). Discrepancy resolution (adjudication) is typically less relevant for quantitative laboratory assays where results are directly compared to a gold standard.

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

   • No, a MRMC study was not done. This is an automated/manual laboratory test for determining Minimum Inhibitory Concentration (MIC), not an imaging device requiring human reader interpretation in a diagnostic workflow. The "human-in-the-loop" aspect for this device is the application of the strip and reading the MIC, which is part of the validation for the device's accuracy against a gold standard method.

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

   • This concept does not directly apply to this type of device. The ETEST device itself is a "standalone" test. The performance reported (EA and CA) is the performance of the ETEST system (strip + reading methodology) compared to the reference broth microdilution method. It inherently involves a human reading the result by interpreting the inhibition ellipse on the strip. The note "b) In the ETEST® Imipenem/Relebactam clinical studies, swabs were used for plate inoculation/streaking and forceps were used for ETEST® strip application. Testing with the optional Inoculator RETRO C80™, Vacuum Pen NEMA C88™ and Applicator SIMPLEX C76™ was not evaluated during the clinical studies" suggests that human manual steps were involved in the performance evaluation.

6. The Type of Ground Truth Used:

   • Reference Method: The ground truth was established by the CLSI M07-11th Ed (January 2018) broth microdilution reference method, following specifications as defined in CLSI M100 34th Ed. (February 2024). This is considered the gold standard for antimicrobial susceptibility testing. Outcomes data or pathology are not relevant for this type of in vitro diagnostic device.

7. The Sample Size for the Training Set:

   • The document does not mention a training set in the context of machine learning or AI models. This device is a manual, quantitative laboratory test (an ETEST strip system) and not an AI/ML-driven diagnostic. Therefore, there's no "training set" in the typical sense of AI development. The "strains" mentioned are for the performance evaluation against the reference method.

8. How the Ground Truth for the Training Set was Established:

   • As there is no mention of a training set for an AI/ML model, this question is not applicable. The device's performance is validated against a well-established reference laboratory method using a test set of clinical isolates and challenge strains.

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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 moxifloxacin in the dilution range of 0.008-16 µg/mL for testing non-fastidious gram-positive isolates on the Sensititre 18-24 hour MIC or Breakpoint Susceptibility System. Testing is indicated for Staphylococcus spp. and Enterococcus faecalis, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC) webpage.

The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Moxifloxacin in the dilution range of 0.008-16 µg/mL demonstrated acceptable performance with the following organisms:

• Staphylococcus spp. (S. aureus, S. epidermidis, S. haemolyticus, S. hominis, S. lugdunensis, and S. saprophyticus)
• Enterococcus faecalis

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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. The letter confirms the clearance of the device and its intended use, but it does not include any information regarding acceptance criteria, study methodologies, sample sizes, expert qualifications, ground truth establishment, or specific performance data (such as a table of described acceptance criteria vs. reported device performance, MRMC studies, or standalone algorithm performance).

The letter is a regulatory document stating that the device is "substantially equivalent" to predicate devices, which means it meets the safety and effectiveness requirements for marketing. However, it does not provide the underlying study details that led to this determination.

To answer your questions, I would need access to the actual study reports or summaries submitted by Thermo Fisher Scientific to the FDA, which are not present in this clearance letter.

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

This 510(k) is for penicillin in the dilution range of 0.015-32 ug/mL for testing fastidious isolates on The Sensitire 20-24 hour Haemophilus influenzae/Streptococcus pneumoniae (HP) MIC or Breakpoint Susceptibility System.

Penicillin has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label:

Streptococcus pneumoniae

Streptococus spp. ß-hemolytic group (Streptococus agalactiae, Streptococcus dysgalactiae, Streptococus pyogenes) Streptococcus spp. Viridans group

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This document does not contain the information required to populate the acceptance criteria and study details. This correspondence from the FDA primarily focuses on the regulatory aspects of a medical device (a susceptibility testing system) including substantial equivalence, applicable regulations, and administrative requirements. While it confirms the device's name, intended use, and the specific drug (Penicillin) and its dilution range being cleared, it does not provide any data from a study demonstrating the device's performance against specific acceptance criteria.

To answer the request, information such as the sensitivity, specificity, accuracy, or any other performance metrics derived from a clinical or laboratory study would be needed, along with details about the study design, sample sizes, ground truth establishment, and expert involvement.

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