Search Results

The Diazyme Human Kappa Free Light Chain Assay is intended as a latex particle enhanced immunoturbidimetric assay for the quantitative determination of Kappa Free Light Chain (FLC) concentration in serum on Hitachi 917 analyzers. The measurement of Kappa FLC in conjunction with Lambda FLC aids in the diagnosis of multiple myeloma in conjunction with other laboratory findings. For in-vitro diagnostic use only.

The Diazyme Human Lambda Free Light Chain Assay is intended as a latex particle enhanced immunoturbidimetric assay for the quantitative determination of Lambda Free Light Chain (FLC) concentration in serum on Hitachi 917 analyzers. The measurement of Lambda FLC in conjunction with Kappa FLC aids in the diagnosis of multiple myeloma in conjunction with other laboratory findings. For in-vitro diagnostic use only.

Diazyme Human Kappa/Lambda FLC Calibrator (DZ169A-CAL) is intended for use in establishing the calibration curve for the Diazyme Human Kappa/Lambda Free Light Chain Assay. For in-vitro diagnostic use only.

Diazyme Human Kappa/Lambda FLC Control (DZ169A-CON) is intended for use in monitoring the quality control of results obtained with the Diazyme Human Kappa/Lambda Free Light Chain Assay. For in-vitro diagnostic use only.

Device Description

Diazyme Human Kappa (K) /Lambda (2) Free Light Chain Assay System consists of the following items:

Diazyme Human Kappa (k) Free Light Chain Assay: containing reagent R1 and Reagent R2. Reagent 1 contains 100 mmol/L tris buffer, and 0.09% sodium azide Reagent 2 containing anti-human Kappa Free Light Chain Ig fraction coated on polystyrene beads and 0.09% sodium azide.
Diazyme Human Lambda (λ) Free Light Chain Assay: containing reagent R1 and Reagent R2. Reagent 1 contains 100 mmol/L tris buffer, and 0.09% sodium azide Reagent 2 containing anti-human Lambda Free Light Chain Ig fraction coated on polystyrene beads and 0.09% sodium azide.
Diazyme Kappa and Lambda FLC Calibrator Set: 5 levels, serum based, liquid stable format, intended for use in establishing the calibration curve for the Diazyme Human Kappa (k) and Lambda (λ) Free Light Chain Assay.
Diazyme Kappa and Lambda FLC Control Set: 2 levels, serum based, liquid stable format, intended for use in monitoring the quality control of results obtained with the Diazyme Human Kappa (K) and Lambda (λ) Free Light Chain Assay.

Diazyme Human Kappa (k) /Lambda (2.) Free Light Chain Assays are run on clinical chemistry analyzers such as Roche Hitachi 917 analyzer (K023009). They never come into direct contact with patients. The patient's venous blood sample is first collected by a phlebotomist and then submitted for determination of Kappa and Lambda FLC concentration using Diazyme Human Kappa (k) and Lambda (λ) FLC Assay by trained professionals.

The Control Unit of the Roche Hitachi 917 analyzer uses a graphical interface to control all instrument functions. The computer, keyboard, and touchscreen monitor allows users to navigate through the software, enter assay, calibrator, and control information, and make test selections. The Diazyme Kappa and Lambda FLC Hitachi 917 application parameters provided are programmed into the Hitachi 917 analyzer. The reagents, calibrators and controls are loaded into the analyzer. The Roche Hitachi 917 stores Diazyme Human Kappa (k) /Lambda (λ) Free Light Chain Assay reagents in a refrigerated compartment. Reagent and sample pipettes automatically aspirate and dispense specified amounts of reagent or calibrators, controls, and sample into reaction cells. The change in absorbance is measured at specified wavelengths.

After a 6-point calibration, spline-fitting is used to smoothly fit polynomial functions through mean values of the response for calibrators of known concentrations. The Roche Hitachi 917 calculates the kappa and lambda FLC concentration of a patient sample by interpolation of the obtained signal to a stored 6-point calibration curve.

AI/ML Overview

The provided document describes the performance testing and acceptance criteria for the Diazyme Human Kappa (κ) and Lambda (λ) Free Light Chain Assays. The study aims to demonstrate substantial equivalence to predicate devices (Freelite® Human Kappa Free Kit and Freelite® Human Lambda Free Kit).

Here's an analysis of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria (Predicate Device)	Reported Device Performance (Diazyme Assay)
Linear Range	Kappa: 6.0-180 mg/L (standard); 150-4,500 mg/L & 3,000–90,000 mg/L (extended)
Lambda: 8.0-270 mg/L (standard); 200-6750 mg/L & 4,000-135,000 mg/L (extended)	Kappa FLC: 4.5-150 mg/L (standard); 90-3000 mg/L (extended)
Lambda FLC: 6.1-200 mg/L (standard); 122-4000 mg/L (extended)
Precision (Within-run CV)	Kappa FLC: 3.1% to 4.84% (13.56 mg/L to 51.06 mg/L)
Lambda FLC: 5.2% to 8.4% (15.12 mg/L to 71.84 mg/L)	Kappa FLC: 1.4% to 7.6% (6.0 mg/L to 2588.6 mg/L) (One lot, three analyzers)
and 1.1% to 7.9% (5.81 to 2588.45 mg/L) (Three lots, one analyzer)
Lambda FLC: 0.8% to 6.5% (8.3 mg/L to 3472.6 mg/L) (One lot, three analyzers)
and 0.6% to 6.3% (8.16 to 3442.60 mg/L) (Three lots, one analyzer)
Precision (Between-run CV)	Kappa FLC: 6.27% to 8.38% (12.02 mg/L to 54.66 mg/L)
Lambda FLC: 4.72%-8.08% (18.43 mg/L to 71.71 mg/L)	Kappa FLC: 0.6% to 4.9% (One lot, three analyzers)
and 0.3% to 5.7% (Three lots, one analyzer)
Lambda FLC: 0.4% to 4.5% (One lot, three analyzers)
and 0.3% to 4.0% (Three lots, one analyzer)
Method Comparison (K-FLC)	Linear regression yielded y = 0.9818x + 4.5206 and r = 0.9956	Slope = 0.958; Correlation Coefficient (R²) = 0.977
95% CI Slope: 0.932 to 0.985; Intercept: -14.703 to 9.632
Agreement: PPA 96.67%, NPA 100%, TPA 97.62% (95% CI provided for each)
Method Comparison (L-FLC)	Linear regression yielded y = 0.9266x + 9.5556 and r = 0.9752	Slope = 1.054; Correlation Coefficient (R²) = 0.972
95% CI Slope: 1.021 to 1.086; Intercept: -20.746 to 22.018
Agreement: PPA 95.65%, NPA 94.74%, TPA 95.24% (95% CI provided for each)
Detection Limits (LOQ)	N/A (Predicate states ranges, not specific LOQ)	Kappa FLC: LOQ = 4.5 mg/L
Lambda FLC: LOQ = 6.1 mg/L
Interference	N/A (Predicate likely performs similar interference studies, but specific acceptance criteria for interferent levels are not stated)	Less than 10% deviation for:
Triglyceride: 1000 mg/dL
Ascorbic Acid: 10 mM
Bilirubin: 40 mg/dL
Bilirubin Conjugated: 40 mg/dL
Hemoglobin: 1000 mg/dL
Rheumatoid Factor: 100 IU/mL
Hook Effect	N/A	No high dose hook effect observed up to 100,000 mg/L for both Kappa and Lambda FLC.

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

Method Comparison (Test Set):
- Sample Size: 126 serum samples for both Kappa and Lambda FLC assays.
- Data Provenance: The document states "clinical patient samples" but does not specify the country of origin. The samples included a mix of:
  - 39 Multiple Myeloma (MM)
  - 12 Monoclonal Gammopathy of Undetermined Significance (MGUS)
  - 34 Abnormal (due to other disease states)
  - 41 Normal (no disease)
- Retrospective/Prospective: Not explicitly stated, but the sample categorization (MM, MGUS, Abnormal, Normal) suggests these were existing samples collected from patients with known diagnoses, implying a retrospective collection for the purpose of this method comparison study.
Precision Studies (Test Set):
- Sample Size:
  - Kappa FLC: Eight levels of serum specimens + two levels of serum-based controls. Each sample/control was tested with 2 runs per day, duplicates, over 20 working days. The "n=240" for mean column likely refers to the total number of measurements for each ID (8 levels + 2 controls x 2 runs/day x 2 duplicates/run x 20 days = 800 measurements * n=240 is likely the total of measured values per ID across the entire study design, for example, 20 working days * 2 runs/day * 2 duplicates * total samples (8) = 640. No, it is 240, there are 8 levels of serum specimens, 2 levels of serum-based controls, 2 runs/day with duplicates over 20 working days. Therefore, n=240 possibly corresponds to (8+2) samples * 20 days * (2 runs/day * replicates). The precision studies involve 240 data points per ID item when using one lot of reagent across three analyzers (240 measurements for each S1-S8, Con1, Con2) and 240 for three lots of reagent on one analyzer.
  - Lambda FLC: Eight levels of serum specimens + two levels of serum-based controls. Same testing procedure as Kappa FLC, resulting in "n=240" for mean calculations.
- Data Provenance: Not specified, but likely laboratory-prepared serum pools and controls.
- Retrospective/Prospective: Prospective (laboratory conducted study).

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

Not applicable. This is an in-vitro diagnostic device measuring quantitative concentrations of analytes (Kappa and Lambda Free Light Chains). The "ground truth" for the test set in this context is the quantitative value determined by the predicate device, or in the case of analytical performance, the known concentration of the analyte in prepared control materials or spiked samples. This does not involve human expert interpretation of images or clinical cases that would require adjudication.

4. Adjudication Method for the Test Set

Not applicable. See point 3. The "ground truth" for method comparison is the measurement from the predicate device. For analytical performance studies (precision, linearity, detection limits, interference), the ground truth is either the known concentration in spiked samples/controls or derived through standard laboratory methodologies (e.g., gravimetric dilutions for linearity).

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

Not applicable. This is an in-vitro diagnostic assay for quantitative measurement of analytes in serum, not an AI-based imaging or diagnostic tool requiring human reader interpretation or MRMC studies.

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

Yes, the performance data presented (linearity, precision, method comparison, detection limits, interference, hook effect) are all standalone performance characteristics of the Diazyme assay system itself, without human interpretation of results as a primary outcome. The system quantitatively determines FLC concentration.

7. The Type of Ground Truth Used

Method Comparison: The "ground truth" for the test set was the quantitative measurement obtained from the predicate device (Freelite® Human Kappa Free Kit and Freelite® Human Lambda Free Kit).
Analytical Performance (Precision, Linearity, Detection Limit, Interference, Hook Effect): The "ground truth" was established using known concentrations of Kappa and Lambda FLC in serum specimens and controls, often prepared by spiking or dilution, and evaluated against established analytical methods (e.g., CLSI guidelines).

8. The Sample Size for the Training Set

Not directly applicable in the conventional sense of an AI/machine learning training set. This is a traditional immunoturbidimetric assay. However, developmental and optimization work for such assays would involve testing numerous samples and conditions to establish reagent formulations, reaction kinetics, and calibration curves. The document does not specify a distinct "training set" for the assay itself, but rather samples used in validation studies. The calibration curve is essentially "trained" using a 6-point calibration, for which the document states "calibrators of known concentrations" are used.

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

Again, not applicable for a "training set" in the AI sense. For the calibration curve of the assay, the "ground truth" (known concentrations) is established using:

Diazyme Human Kappa/Lambda FLC Calibrator Set: 5 levels, serum based, liquid stable format, containing purified Kappa Free Light Chains. The concentrations of these calibrators are presumably assigned through a validated process against reference methods or materials, though the specific method for assigning these values is not detailed in this document.

Ask a Question

Ask a specific question about this device

Page 1 of 1