Search Results

The IDS-iSYS Intact PTH+ assay is an in vitro diagnostic device intended for the quantitative determination of intact PTH in human serum or plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in the differential diagnosis of hypercalcemia and hypocalcemia resulting from disorders of calcium metabolism.

The IDS-iSYS Intact PTH" assay is based on chemiluminescence technology. 100 uL of patient sample is incubated with a biotinylated polyclonal anti-PTH (39-84) antibody and an acridinium labelled PTH (13-34) antibody. Streptavidin labelled magnetic particles are added prior to a second incubation step. The magnetic particles are captured using a magnet and a wash step performed to remove any unbound analyte. Trigger reagents are added; the resulting light emitted by the acridinium label is directly proportional to the concentration of Intact PTH in the original sample.

IDS-iSYS Intact PTH reagent kit consists of one (1) Immunoassay Cartridge, two (2) vials each of 2 concentration Calibrator levels and a mini-CD containing the Instructions For Use (IFU), CRY files and Certificate of Analysis.

IDS-iSYS Intact PTHN Cartridge, sufficient for 100 tests, consists of reagents provided in individual compartment within a plastic container called the Cartridge. The IDS-iSYS Intact PTHN Cartridge contains the following ready to use reagents:

• · Magnetic particles coated with streptavidin in a phosphate buffer containing sodium azide as preservative (<0.1%), 1 bottle.
• Goat polyclonal antibody against 13-34 PTH labelled with an acridinium ester derivative, in buffer containing goat serum with sodium azide as preservative (<0.1%), 1 bottle.
• Goat polyclonal antibody against 39-84 PTH 1abelled with biotin, in buffer containing bovine and goat proteins with sodium azide as preservative (<0.1%), 1 bottle.

IDS-iSYS Intact PTH Calibrators are included in the reagent kit.

• · Calibrator A: Two vials of lyophilized porcine serum matrix buffer containing low level PTH and sodium azide as preservative >1% (w/w%).
• · Calibrator B: Two vials of lyophilized porcine serum matrix buffer containing high level PTH and sodium azide as preservative >1% (w/w%).

The submission is due to a new source of antibody for the assay.

This document describes the performance characteristics of the IDS-iSYS Intact PTHN assay, an in vitro diagnostic device for quantitative determination of intact PTH.

Here's an analysis of the acceptance criteria and study information provided:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets but are implicitly defined by the reported performance and the comparison to the predicate device. The information below summarizes the performance characteristics provided, which in a regulatory context, demonstrate the device meets its intended use and is substantially equivalent to the predicate.

2. Sample Sizes and Data Provenance for Test Sets

• Method Comparison:

  • Sample Size: 312 serum samples (291 native, 21 spiked).
  • Data Provenance: Not explicitly stated but clinical samples are generally considered prospective or retrospective from a clinical laboratory setting. The use of "commercially available quantitative chemiluminescence Intact PTH assay" as the comparator suggests real-world clinical samples.

• Sample Matrix Comparison:

  • Sample Size: 52 matched samples (45 native, 7 spiked).
  • Data Provenance: Not explicitly stated, but clinical samples are typically used for this type of evaluation.

• Reference Interval:

  • Sample Size: 129 individuals (67 males, 62 females; 21 to 89 years of age).
  • Data Provenance: K2 EDTA plasma samples collected from individuals with normal calcium, phosphate, and TSH values from the north, central and south regions of the United States. This is prospective or a well-characterized retrospective collection.

• Sensitivity (LoB, LoD, LoQ):

  • Sample Size: 60 blanks and 10 low-level serum samples.
  • Data Provenance: Lab-prepared samples and low-level serum samples, likely from internal or commercially acquired biobanks.

• Precision:

  • Sample Size: 7 samples (tested multiple times, N=80 for each sample).
  • Data Provenance: Lab-prepared controls and potentially pooled clinical samples ("Serum Sample," "EDTA Plasma Sample").

• Linearity:

  • Sample Size: Not explicitly stated as a single number, but involved diluting high patient samples with low patient samples. Each sample was measured in 4 replicates.
  • Data Provenance: High and low intact PTH human K2 EDTA plasma and serum samples.

• High Dose Hook Effect:

  • Sample Size: 3 samples (1 EDTA Plasma, 2 Serum) per spiked concentration.
  • Data Provenance: Spiked samples, likely from a laboratory setting using clinical matrices.

• Interferences:

  • Sample Size: Two K2-EDTA samples (low and high Intact PTH levels) and two serum samples (different Intact PTH concentrations).
  • Data Provenance: Spiked samples, using clinical matrices (K2-EDTA and serum).

• Cross-Reactivity:

  • Sample Size: A serum sample and a zero calibrator matrix.
  • Data Provenance: Spiked samples, using clinical serum matrix.

3. Number of Experts and Qualifications for Ground Truth

This device is an in vitro diagnostic assay, where the "ground truth" for performance characteristics such as sensitivity, precision, linearity, and interference is established by:

• Reference Methods: Comparison against established, commercially available, and often FDA-cleared or gold-standard assays (e.g., the predicate device or a "commercially available quantitative chemiluminescence Intact PTH assay" for method comparison).
• Analytical Standards/Spikes: Precisely known concentrations of analyte or interfering substances are used to create "spiked" samples, where the "true" concentration is known by design.
• Clinical Laboratory Standard Institute (CLSI) Guidelines: Adherence to these guidelines (EP-9A2, EP9-A3, C28-A3, EP17-A, EP-5A2, EP-6A, EP7-A2) dictates the experimental design and statistical analysis which are considered "best practice" for establishing performance characteristics in IVDs.

There are no "experts" in the sense of physicians or radiologists directly assessing images or patient data to establish ground truth for this type of analytical device performance. The "ground truth" is analytical and derived from established laboratory practices and reference methods.

4. Adjudication Method for the Test Set

Not applicable for this type of in vitro diagnostic device study. Adjudication methods like "2+1" or "3+1" are typically used in clinical studies, particularly for diagnostic imaging or subjective clinical assessments, where consensus among multiple expert readers is needed to establish a ground truth for a disease state. For IVD analytical performance, the ground truth is either the value from a reference method or a gravimetrically/volumetrically determined "true" concentration.

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

No, an MRMC comparative effectiveness study was not done. This type of study is primarily relevant for diagnostic imaging AI algorithms where multiple human readers interpret cases with and without AI assistance. This document describes an in vitro diagnostic assay for a biochemical marker, not an imaging device or an AI application that assists human interpretation.

6. Standalone Performance

Yes, the studies described are standalone performance assessments of the IDS-iSYS Intact PTHN assay. The device is an automated system for measuring PTH levels, and the performance characteristics (method comparison, precision, linearity, etc.) directly evaluate the algorithm/assay's ability to accurately quantify PTH in patient samples. There is no human-in-the-loop component being evaluated in these tests; the device's output is directly compared to established analytical standards or reference methods.

7. Type of Ground Truth Used

• Reference Method Results: For method comparison, the results from a "commercially available quantitative chemiluminescence Intact PTH assay" served as the ground truth comparator.
• Assigned Values of Controls/Standards: For precision, linearity, sensitivity, interference, and cross-reactivity studies, the ground truth was based on:
  • Known concentrations: Spiked samples with precisely known concentrations of analyte or interfering substances.
  • Expected values: Derived from dilution series or preparation of controls.
  • Blank matrices: For limit of blank determination.
• Clinical Criteria: For the reference interval study, the ground truth for "normal" individuals was based on clinical criteria (normal calcium, phosphate, and TSH values).

8. Sample Size for the Training Set

The document does not specify a "training set" in the context of machine learning. This is an analytical medical device, not an AI/ML algorithm that is "trained" on data. The characteristics and parameters of the assay (e.g., antibodies, reagent concentrations, calibration curve algorithm) are developed and optimized during the product development phase, which is analogous to "training" in AI, but it's not described in terms of a distinct dataset.

9. How Ground Truth for the Training Set Was Established

As explained above, there isn't a "training set" in the common AI/ML sense. The "ground truth" for the development and optimization of the assay's chemical and instrumental parameters typically comes from:

• Biochemical principles: Understanding of antigen-antibody interactions, chemiluminescence, and PTH biology.
• Calibration materials: Use of international standards or highly characterized primary calibrators with assigned values.
• Internal validation studies: Extensive testing during R&D to optimize reagent formulations, incubation times, and instrumental settings to achieve desired performance characteristics against known samples and reference methods.
• Iterative development and testing: Performance data from pilot studies or earlier assay versions would inform adjustments to achieve acceptable analytical performance compared to the established medical consensus for PTH measurement.

Ask a specific question about this device