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For in-vitro diagnostic use only.

For the quantitative measurement of procalcitonin (PCT) in human serum and plasma (lithium heparin and EDTA) using the VITROS 3600 Immunodiagnostic System.

Used in conjunction with other laboratory findings and clinical assessments, the VITROS B R A PA - M S PCT test is intended for use as follows:

· to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock,

· to aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, using a change in PCT level over time,

· to aid in decision making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) - in an inpatient setting or an emergency department,

· to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.

The VITROS B·R·A·H·M·S PCT test is performed using the VITROS B·R·A·H·M·S PCT Reagent Pack and the VITROS B·R·A·H·M·S PCT Calibrators on the VITROS Systems.

Reagent Pack Contents
1 reagent pack containing:

• 100 coated wells (rat monoclonal anti-procalcitonin antibody, 1.0 µg/mL) ●
• 10.20 mL assay reagent (buffer containing bovine gamma globulin, bovine serum ● albumin and antimicrobial agent)
• . 13.10 mL conjugate reagent (HRP-conjugated mouse monoclonal procalcitonin antibody. 1.65 ug/mL in buffer with bovine serum albumin and antimicrobial agent)

Calibrator Contents

• . 3 sets of VITROS B•R•A•H•M•S PCT Calibrators 1 and 2, 1.0 mL, procalcitonin in buffer with antimicrobial agent, nominal values 0.080 and 75.0 ng/mL (ug/L)
• . Lot calibration card
• Protocol card ●
  • 16 calibrator bar code labels (8 for each calibrator) ●

The provided text is a 510(k) Summary for the VITROS B·R·A·H·M·S PCT Reagent Pack and Calibrators, intended for quantitative measurement of procalcitonin (PCT). This document describes the device's performance characteristics and clinical studies to establish substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a 510(k) summary for an in vitro diagnostic device, the "acceptance criteria" are implied by the comparison to the predicate device and established analytical performance metrics. The key criterion is demonstrating substantial equivalence to the predicate device, B·R·A·H·M·S PCT sensitive KRYPTOR (K171338), especially at critical clinical decision points.

2. Sample Sizes and Data Provenance

• Test Set (Method Comparison with Predicate):

  • Sample Size: 266 patient samples were used for the regression analysis comparing the VITROS B·R·A·H·M·S PCT test to the B·R·A·H·M·S PCT sensitive KRYPTOR assay. 246 samples were within the measuring range.
  • Data Provenance: Not explicitly stated for analytical studies, but for the clinical performance study, samples were "retrospective samples from a study of 858 adult patients diagnosed with severe sepsis or septic shock recruited across 13 investigational sites in the United States." The original MOSES Study (DEN150009) collected samples from patients admitted to ICU from emergency departments, other wards, or directly from out of the hospital. EDTA samples were used.

• Test Set (Clinical Concordance):

  • Sample Size: 2168 samples (evaluating concordance at various PCT decision points).
  • Data Provenance: "serial sample sets obtained from the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study collection, a well-characterized sample collection in 13 sites across the United States." This indicates a prospective collection used retrospectively for this specific device's evaluation.

• Test Set (28-Day Mortality Prediction):

  • Sample Size: 858 adult patients in the study, with an analysis population of 598 subjects.
  • Data Provenance: Retrospective samples from the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study collection in 13 sites across the United States.

3. Number of Experts and Qualifications for Ground Truth

• For an in vitro diagnostic device measuring an analyte (procalcitonin), the "ground truth" for analytical studies is typically established by reference methods or gravimetric preparation with known concentrations. Experts are not typically involved in establishing ground truth for analytical performance like precision, linearity, LoD/LoQ, and interference.
• For clinical studies (concordance and mortality prediction), the primary "ground truth" for the device's performance against clinical decision points is the predicate device's measurement (B.R.A.H.M.S PCT sensitive KRYPTOR assay). Physician discretion and clinical assessments were used for patient diagnosis and mortality outcomes in the MOSES study, which provided the samples. While physicians made clinical diagnoses, they were not experts establishing a "ground truth score" for the device; rather, clinical outcomes (mortality, diagnosis of sepsis/septic shock) were endpoints. No individual "experts" were formally used to establish a ground truth for the test set, but rather the clinical outcomes and the predicate device's results served as the reference.

4. Adjudication Method

• Not applicable in the context of this 510(k) summary for an in vitro diagnostic device assessing an analyte level. Adjudication methods like 2+1 or 3+1 are typically used for subjective evaluations (e.g., imaging interpretation) where expert consensus is needed to determine the correct ground truth for a given case. Here, the ground truth for analytical performance is quantitative, and for clinical performance, it is the predicate device's measurement and observed clinical outcomes (e.g., 28-day mortality).

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

• No, an MRMC comparative effectiveness study was not performed. This device is an in vitro diagnostic assay, not an AI-assisted diagnostic tool for human readers. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" does not apply.

6. Standalone Performance Study

• Yes, the performance described is a standalone performance study of the VITROS B·R·A·H·M·S PCT Reagent Pack and Calibrators. The "algorithm only" in this context refers to the assay's ability to quantitatively measure PCT levels. All analytical performance studies (precision, linearity, detection limits, analytical specificity, matrix comparison, high-dose hook, sample auto-dilution, carry-over) were conducted to demonstrate the standalone performance of the VITROS B·R·A·H·M·S PCT test. The clinical concordance with the predicate device also serves as a standalone performance benchmark.

7. Type of Ground Truth Used

• Analytical Ground Truth: For analytical performance studies (precision, linearity, LoD/LoQ, interference, matrix equivalence, high dose hook, carry over), the ground truth was established by:
  • Reference calibrators: Traceable to in-house reference calibrators, which were value-assigned to correlate to B·R·A·H·M·S PCT sensitive KRYPTOR.
  • Known concentrations: Prepared by gravimetric spiking with recombinant PCT.
  • Validated analytical methods: Following CLSI guidelines (e.g., EP05-A3 for precision, EP17-A2 for detection limits, EP06-A for linearity, EP07-A3 for interference).
• Clinical Ground Truth:
  • Predicate device results: For clinical concordance, the measurements from the B·R·A·H·M·S PCT sensitive KRYPTOR assay were considered the reference for comparison.
  • Outcomes data: For the 28-day mortality prediction claim, the vital status (mortality) of patients at Day 28 was the ground truth. This outcome data was collected during the original MOSES study.

8. Sample Size for the Training Set

• This 510(k) document describes a traditional in vitro diagnostic device clearance, not an AI/ML software submission that often explicitly details "training sets."
• However, the device's calibration is "traceable to in-house reference calibrators, which have been value-assigned to correlate to B·R·A·H·M·S PCT sensitive KRYPTOR." The development of these in-house reference calibrators and the assay itself would have involved some form of "training" or optimization using an internal dataset, but its size and specific characteristics are not provided in this regulatory summary.
• The clinical study samples from the MOSES study were used for validation (evaluation) of the device's clinical performance, not as a training set for the assay's underlying methodology.

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

• As noted above, a formal "training set" in the AI/ML sense is not described. The ground truth for the development of the assay (e.g., for calibrator assignment) would have been established through a combination of:
  • Reference materials: Highly characterized procalcitonin standards.
  • Defined analytical methods: Using established laboratory practices and potentially comparing to existing, well-regarded PCT assays during the R&D phase to create the "in-house reference calibrators."
  • Value assignment: A process where the concentration of an analyte in a calibrator is accurately determined. This often involves multiple measurements using reference methods or by gravimetric preparation.

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