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The Enzyme 5 Calibrator (ENZ 5 CAL) is an in vitro diagnostic product for the calibration of the lactate dehydrogenase (LDI) method on the Dimension Vista® System.

ENZ 5 CAL is a liquid, bovine serum albumin based product containing lactate dehydrogenase (chicken heart). The calibrator, one level (Calibrator A), comes packaged with three vials at 1.5 mL per vial. System water, the zero level calibrator does not come packaged with the calibrator.

The provided 510(k) summary for the Dimension Vista® System Enzyme 5 Calibrator (KC350) primarily focuses on establishing substantial equivalence to a predicate device, rather than defining specific acceptance criteria for performance metrics like sensitivity, specificity, or accuracy that would be typical for a diagnostic test.

Instead, the "acceptance criteria" here are related to the stability and traceability of the calibrator, which ensure its fitness for purpose as a calibration tool. The study presented is a series of laboratory experiments designed to demonstrate these characteristics.

Here’s a breakdown of the information based on your request, with an emphasis on how the provided document addresses "acceptance criteria" in this context:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Shelf-life Stability: The sample size is not explicitly stated in terms of number of vials or lots. It mentions comparing results of "the product" stored at 2-8°C with "control" stored at -20°C and -70°C. The study is prospective in nature, involving real-time storage and testing. The data provenance is internal to Siemens Healthcare Diagnostics Inc.
• Open Vial Stability: "Vials are opened on day zero." The number of vials tested is not specified but the testing schedule (days 0, 15, 32 with fresh vials at 15 and 32) indicates a controlled prospective study. Data provenance: Siemens Healthcare Diagnostics Inc.
• Punctured Vial Stability: "Four recapped vials are tested on day zero. Two recapped vials and eight punctured vials are tested on approximately days 3, 8 and 15. Two freshly opened vials are tested at each test point." This indicates a sample size of at least 14 vials for the punctured vial study (4 initial, 2+8 at day 3, 2+8 at day 8, 2+8 at day 15 – though some might be carried over). Data provenance: Siemens Healthcare Diagnostics Inc.
• Traceability/Value Assignment:
  • Anchor Pools: "Two levels of LD Anchor pools... using pooled human serum samples." The number of individual human serum samples contributing to the pools or the exact volume of the pools is not specified. Value assignment done by a "Reference Laboratory approved by the Joint Committee for Traceability in Laboratory Medicine (JCTLM)." This implies external, expert-validated data.
  • Masterpools: "Two levels of LD Masterpools... using an aqueous Bovine Serum Albumin matrix." "Three instruments and three lactate dehydrogenase (LDI) reagent lots... 9 curves... five replicates each of Level 2 and Level 3... resulting in 45 replicates each." This indicates a robust internal study process. Data provenance: Siemens Healthcare Diagnostics Inc.
  • Commercial Calibrator: "Three instruments and three LDI reagent lots... 9 standard curves. Five replicates of the commercial lot Calibrator A... yielding 45 replicates." Data provenance: Siemens Healthcare Diagnostics Inc.
  • All these studies are prospective relating to the development and validation of the calibrator.

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

• For Stability Studies: The document doesn't explicitly mention "experts" for establishing ground truth for the stability test sets in the same way one would for clinical image analysis. The "ground truth" for stability is defined by the initial state of the calibrator and its performance over time relative to that initial state, and often compared against a highly stable reference (like the -70°C control in the shelf-life study). The internal Siemens R&D/Quality Control personnel performing these tests would be the qualified individuals, but their specific qualifications are not detailed.
• For Traceability/Value Assignment: The "ground truth" for the LD values in the Anchor Pools is established by a JCTLM-approved Reference Laboratory using the IFCC LD Reference Measurement Procedure. This implies the highest level of expert qualification for method and procedure. The number of individual experts from that lab is not specified but the accreditation of the lab and the procedure itself serve as the expert validation.

4. Adjudication Method for the Test Set

• Adjudication methods like "2+1" are typically used for qualitative or subjective assessments (e.g., image interpretation). This device is a quantitative calibrator. Therefore, traditional adjudication methods are not applicable.
• For value assignment, the method involves:
  • Reference Laboratory adherence to IFCC LD RMP.
  • Multiple measurements (e.g., 45 replicates) on different instruments and reagent lots, with the assigned value being the mean of these replicates. This statistical approach across multiple test conditions serves as an objective method to establish the value, rather than subjective adjudication.

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

• No, an MRMC study was not done. MRMC studies are relevant for diagnostic devices where human readers interpret results (e.g., radiology, pathology). This device is a chemical calibrator; its performance is assessed through analytical accuracy, precision, and stability, not human interpretation.

6. Standalone (Algorithm Only Without Human-in-the-loop Performance) Study

• Yes, the studies described are standalone performance assessments of the calibrator itself. The calibrator's performance (stability, value assignment) is evaluated as a physical reagent product. While it's used with an instrument, the "human-in-the-loop" concept typically refers to human interpretation of diagnostic results, which is not applicable here. The instrument is a tool for measuring the calibrator's characteristics, not a diagnostic algorithm.

7. The Type of Ground Truth Used

• The primary ground truth for the lactate dehydrogenase (LD) concentration values is the IFCC LD Reference Measurement Procedure as performed by a JCTLM-approved Reference Laboratory. This is a highly robust, internationally recognized reference method for establishing the true value of an analyte.
• For stability studies, the "ground truth" for comparison is the initial, freshly-assigned value of the calibrator, often with highly stable reference materials (-70°C stored controls).

8. The Sample Size for the Training Set

• This device is a calibrator, not an AI/ML algorithm that requires a "training set" in the conventional sense. The process of "value assignment" involves careful measurement, but it's not a training phase for a predictive model.
• However, if we consider the "training" for the value assignment process, it involves:
  • "pooled human serum samples" for Anchor Pools (number not specified).
  • "appropriate volume of LD stock" for Masterpools.
  • "a stock solution" of LD for commercial calibrators.
  • The "training" of the instruments and reagent lots for these assignments involves 9 calibration curves (3 instruments x 3 reagent lots) for Masterpool assignment and another 9 standard curves for commercial calibrator assignment. This ensures robustness across manufacturing and operational variability.

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

• As above, given this is not an AI/ML device, a traditional "training set" with ground truth in that context is not applicable.
• For the value assignment process, which is analogous to establishing reference points:
  • Anchor Pools: Ground truth values were established by a JCTLM-approved Reference Laboratory using the IFCC LD Reference Measurement Procedure. This is the highest level of ground truth for quantitative chemical measurements.
  • Masterpools: Values were assigned based on calibration against the Anchor Pools, effectively transferring the ground truth established by the Reference Laboratory.
  • Commercial Calibrators: Values are assigned based on calibration against the Masterpools, further disseminating the traceability from the IFCC RMP.

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