Search Results

The MicroScan® Dried Gram-Positive MIC/Combo Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-positive bacteria. 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 Tigecycline at concentrations of 0.12 - 8 mcg/ml to the test panel. MicroScan® Dried Gram-Positive Tigecycline is a qualitative test.

Tigecycline has been shown to be active against the organisms listed below according to the FDA label for the antimicrobial.

Active in vitro and in clinical infections:

Enterococcus faecalis (vancomycin-susceptible isolates) Staphylococcus aureus (methicillin-susceptible and -resistant isolates)

Active in vitro but clinical significance unknown: Staphylococcus epidermidis (methicillin-susceptible and -resistant isolates)

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 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 MicroScan® Dried Gram-Positive MIC/Combo Panels with Tigecycline (0.12-8 mcg/ml) is a medical device designed to determine antimicrobial agent susceptibility. The device's performance was evaluated against a CLSI frozen Reference Panel to demonstrate substantial equivalence, as defined in the FDA document "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA."

Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Test Set Sample Size: The document mentions "fresh and stock Efficacy isolates and stock Challenge strains." However, the exact number of isolates/strains used in the external evaluation (test set) is not explicitly stated in the provided text.
• Data Provenance: The data was collected during an "external evaluation" designed to confirm acceptability. The specific country of origin is not mentioned, but it can be inferred that it aligns with FDA submission requirements, likely involving clinical or reference laboratories within the United States or equivalent international standards. The study appears to be retrospective in the sense that stock isolates and challenge strains were used, although fresh isolates were also included.

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

The document states the device's performance was compared to a "CLSI frozen Reference panel" and "Expected Results determined prior to the evaluation" for challenge strains. This implies that the ground truth for antimicrobial susceptibility was established through a standardized, well-defined method (likely CLSI M7 guidelines for broth microdilution) rather than relying on individual expert consensus.

• Number of Experts: Not applicable in the traditional sense of a consensus panel, as a CLSI frozen Reference Panel and pre-determined "Expected Results" were used as the gold standard.
• Qualifications of Experts: The CLSI (Clinical and Laboratory Standards Institute) methods themselves are developed by panels of experts in microbiology, infectious diseases, and laboratory medicine. However, the document does not specify individual experts for establishing the ground truth for this particular study.

4. Adjudication Method for the Test Set

The establishment of ground truth was based on comparison to a "CLSI frozen Reference panel" and "Expected Results" for challenge strains. This suggests a direct comparison method rather than an adjudication process among human readers.

• Adjudication method: None in the context of human reader disagreement, as the ground truth was a standardized reference method.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, and Effect Size

• MRMC Study: No, a multi-reader multi-case comparative effectiveness study was not done. This study focuses on the performance of an automated/semi-automated AST system against a reference method, not on the improvement of human readers with AI assistance.

• Effect Size: Not applicable, as no MRMC study was conducted.

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

• Standalone Study: Yes, the evaluation conducted was a standalone study of the device. The MicroScan Dried Gram-Positive MIC/Combo Panel, either read visually or with MicroScan instrumentation (autoSCAN®-4 and WalkAway®), operates as an algorithm/system to determine MIC values and categorical interpretations. Its performance was compared directly to a "CLSI frozen Reference panel" and "Expected Results," which represents its standalone capability without direct human interpretation being part of the primary performance metric for substantial equivalence (though human reading is an option for panel interpretation).

7. The Type of Ground Truth Used

• Ground Truth Type: The ground truth used was established by a CLSI frozen Reference Panel and pre-determined expected results for challenge strains. This is a highly standardized and well-accepted method for determining antimicrobial susceptibility, considered the gold standard in microbiology. It is essentially a form of reference standard data based on established protocol outcomes.

8. The Sample Size for the Training Set

The provided text does not contain any information about a specific training set or its sample size. This type of device (Microdilution MIC Panels) is typically developed based on established microbiological principles and validated against reference methods, rather than being a machine learning model that requires a discrete training set in the modern sense. The "development" would involve optimizing panel concentrations and reading algorithms.

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

Since no specific training set is mentioned as part of a machine learning paradigm, the establishment of ground truth for a "training set" is not applicable as described in the provided text. The overall design and optimization of such panels are based on extensive antimicrobial susceptibility testing literature, CLSI guidelines, and internal research and development following established microbiological practices.

Ask a specific question about this device

The IMMULITE® Anti-TG Ab Calibration Material (CVM) is for in vitro diagnostic use in the verification of callbration of the IMMULITE Anti-TG Ab assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.
The IMMULITE® Thyroglobulin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Thyroglobulin assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.
The IMMULITE® Anti-TPO Ab Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Anti-TPO Ab assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.

The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. LTGCVM i contains human serum/ buffer matrix with preservatives. LTGCVM2, LTGCVM3 and LTGCVM4 contain low, intermediate and high levels of Anti-TG Ab respectively, in human serum/ buffer matrix matrix with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. LTOCVM1 contains human serum/ buffer matrix with preservatives. LTOCVM2, LTOCVM3 and LTOCVM4 contain low, intermediate and high levels of Anti-TPO Ab respectively, in human serum/ buffer matrix matrix with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. LTYCVM1 in horse serum matrix with preservatives. LTYCVM2. LTYCVM3 and LTYCVM4 contain low, intermediate and high levels of Thyroglobulin respectively, in horse serum matrix with preservatives.

This document describes the acceptance criteria and supporting studies for three calibration verification materials (CVMs): IMMULITE® 2000 Anti-TG Ab, IMMULITE® 2000 Anti-TPO Ab, and IMMULITE® 2000 Thyroglobulin.

1. Table of Acceptance Criteria and Reported Device Performance

This information is derived from the "Stability Acceptance Criteria Summary" and "Expected Values/Reference Range" sections for each device.

IMMULITE® 2000 Anti-TG Ab Calibration Verification Material

IMMULITE® 2000 Anti-TPO Ab Calibration Verification Material

IMMULITE® 2000 Thyroglobulin Calibration Verification Material

Study Information for All Devices (IMMULITE® 2000 Anti-TG Ab, Anti-TPO Ab, and Thyroglobulin CVMs)

The studies described are primarily stability and value assignment studies to establish the shelf-life and assigned values of the Calibration Verification Materials.

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

The "test set" for performance evaluation consists of the replicates used to determine the CVMs' target values and assess their stability.

• Sample Size: For each CVM (Anti-TG Ab, Anti-TPO Ab, Thyroglobulin), the CVMs were tested on 27 replicates in total, comprised of nine runs and three replicates per run.
• Data Provenance: The data appears to be prospective as it involves controlled testing in a laboratory setting to assign values and assess stability over time. The origin of the patient samples used for validation is not specified (e.g., country of origin).

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

The concept of "experts" in the traditional sense (e.g., radiologists) is not applicable here as these are in-vitro diagnostic calibration materials. The "ground truth" or reference values are established through rigorous laboratory procedures and traceability to international standards.

• Number of Experts: Not applicable in the context of expert consensus for diagnostic interpretation.
• Qualifications of Experts: The ground truth is established through qualified technical staff and validated measurement procedures traceable to WHO International Reference Preparations or Certified Reference Materials (e.g., WHO 1st IRP 65/93 for Anti-TG Ab, WHO 15 IRP 66/387 for Anti-TPO Ab, and BCR 457 for Thyroglobulin).

4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set

Adjudication methods like 2+1 or 3+1 are typically used for subjective diagnostic interpretations by multiple readers. This is not applicable to the quantitative measurements performed for these CVMs.

• Adjudication Method: Not applicable. The process involves calculating average values across multiple runs and instruments.

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

MRMC studies involving human readers are designed for diagnostic interpretation tasks, which is not the function of these CVMs.

• MRMC Study: No, a Multi-Reader Multi-Case comparative effectiveness study was not performed.

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

These devices are calibration verification materials for automated immunoassay systems. Their "standalone performance" is exactly what is tested: their ability to provide stable and accurate reference values when processed by the IMMULITE 2000 systems. The performance data presented (target means, SDs, and stability) represents the standalone performance of the CVMs in conjunction with the IMMULITE 2000 systems.

• Standalone Performance: Yes, the described stability and value assignment studies represent the standalone performance of the CVMs when used with the IMMULITE 2000 systems.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth for these CVMs is based on traceability to international reference standards and rigorous value assignment procedures.

• Type of Ground Truth:
  • Traceability to International Standards:
    • IMMULITE® 2000 Anti-TG Ab CVMs are traceable to WHO 1st IRP 65/93.
    • IMMULITE® 2000 Anti-TPO Ab CVMs are traceable to WHO 15 IRP 66/387.
    • IMMULITE® 2000 Thyroglobulin CVMs are traceable to Certified Reference Material from human thyroglobulin (BCR 457).
  • Value Assignment Procedure: The CVMs are manufactured using qualified materials and measurement procedures. Their dose values are generated using curves from assigned reference calibrators, which are themselves traceable to the international standards.

8. The Sample Size for the Training Set

The concept of a "training set" typically applies to machine learning algorithms. For these CVMs, the "training" equivalent would be the extensive manufacturing and internal calibration processes that establish the reference calibrators and assigned values.

• Sample Size for Training Set: Not explicitly defined in terms of a "training set" like in AI/ML. However, the internal manufacturing and value assignment processes involve various calibrator lots and materials that indirectly serve this purpose. The document mentions "8 level Anti-TG Ab calibrators," "7 level Anti-TPO Ab calibrators," and "9 level Thyroglobulin calibrators" used internally during manufacture and release testing. These calibrators would form the basis for the "training" of the system's ability to measure the analytes.

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

Similar to point 8, the "ground truth for the training set" refers to the establishment of the reference for the internal calibrators that are used to assign values to these CVMs.

• Ground Truth for Training Set: The ground truth for the internal reference calibrators is established through:
  • Traceability to WHO International Reference Preparations or Certified Reference Materials: As detailed in point 7.
  • Use of Qualified Materials and Measurement Procedures: The calibrators are prepared using specific antibody stocks (e.g., Anti-TG antibody stock, Anti-TPO antibody stock) and are carefully manufactured.
  • Validation with Patient Samples and Controls: For value assignment validation, the documents state:
    • Anti-TG Ab: "Two levels of commercially available controls, and 30 patient samples (10 spiked normal patients samples, two patient samples and 18 spiked samples) are used to validate CVM value assignments."
    • Anti-TPO Ab: "Two levels of commercially available controls, and 30 patient samples and 25 spiked samples) are used to validate CVM value assignments."
    • Thyroglobulin: "Three levels of commercially available controls, and 30 patient samples (5 normal patients samples and 25 spiked samples) are used to validate CVM value assignments."

This indicates a thorough process of establishing reliable reference values for the materials.

Ask a specific question about this device