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Alinity m BKV is an in vitro nucleic acid amplification test for the quantitation of BK virus (BKV) DNA in human EDTA plasma (K2 EDTA, K3 EDTA, and PPT) and urine stabilized using the Alinity m Urine Transport Kit on the automated Alinity m System.

In EDTA plasma (K2 EDTA, K3 EDTA, and PPT) and urine stabilized using the Alinity m Urine Transport Kit, Alinity m BKV is intended for use as an aid in the diagnosis and management of BKV in transplant patients.

In patients undergoing monitoring of BKV in EDTA plasma, serial DNA measurements can be used to indicate the need for potential treatment changes and to assess viral response to treatment.

The results from Alinity m BKV must be interpreted in conjunction with clinical signs and other relevant laboratory findings. Alinity m BKV is not cleared as a screening test for blood or blood products or human cells, tissues, and cellular and tissue-based products.

The Alinity m BKV assay utilizes real-time polymerase chain reaction (PCR) to amplify and detect BKV genomic DNA sequences that have been extracted from human EDTA plasma or urine specimens. The steps of the Alinity m BKV assay consist of sample preparation, real-time PCR assembly, amplification/detection, result calculation, and reporting. One transfer step of urine specimens into the Alinity m Urine Transport Kit by the user is required prior to placing urine specimens on the Alinity m System. Remaining steps of the Alinity m BKV assay procedure are executed automatically by the Alinity m System. Manual dilutions may be performed for low-volume plasma specimens to meet the minimum volume requirement. The Alinity m System is designed to be a randomaccess analyzer that can perform the Alinity m BKV assay in parallel with other Alinity m assays on the same instrument.

Alinity m BKV requires three separate assay specific kits as follows:

• . Alinity m BKV AMP Kit (List No. 09N85-095), consisting of 2 types of multi-well assay trays. The amplification tray (AMP TRAY 1) contains liquid, unit-dose PCR amplification/detection reagents and liquid, unit-dose Internal Control (IC) in separate wells; and the activation tray (ACT TRAY 2) contains liquid, unit-dose activation reagent. The intended storage condition for the Alinity m BKV AMP Kit is -25°C to -15°C.
• . Alinity m BKV CTRL Kit (List No. 09N85-085), consisting of negative controls, low positive controls, and high positive controls, each supplied as liquid in single-use tubes. The intended storage condition for the Alinity m BKV CTRL Kit is -25°C to -15°C.
• Alinity m BKV CAL Kit (List No. 09N85-075), consisting of 2 calibrator levels, . each supplied as liquid in single-use tubes. The intended storage condition for the Alinity m BKV CAL Kit is -25°C to -15°C.

The Alinity m BKV assay requires a transport kit for testing all urine specimens:

• Alinity m Urine Transport Kit (List No. 09N85-001) consisting of a transport tube . and transfer pipette. The transport tube contains transport buffer. The intended storage condition for the Alinity m Urine Transport Kit is 15℃ to 30℃.
  BKV DNA from human plasma or urine is extracted automatically on board the Alinity m System using the Alinity m Sample Prep Kit 2, Alinity m Lysis Solution, and Alinity m Diluent Solution. The Alinity m System employs magnetic microparticle technology to facilitate nucleic acid capture, wash, and elution. The resulting purified DNA is then combined with liquid unit-dose Alinity m BKV activation reagent and liquid unit-dose Alinity m BKV amplification/detection reagents and transferred into a reaction vessel. Alinity m Vapor Barrier Solution is then added to the reaction vessel which is then transferred to an amplification/detection unit for PCR amplification and real-time fluorescence detection of BKV DNA.

At the beginning of the Alinity m BKV sample preparation process, a liquid unit-dose IC on the AMP Tray is transferred by the Alinity m System and delivered into each sample preparation reaction. The IC is then processed through the entire sample preparation and real-time PCR procedure along with the specimens, calibrators, and controls to demonstrate proper sample processing and validity.

The Alinity m BKV amplification/detection reagents consist of enzymes, primers, probes, and activation reagents that enable amplification and detection of dual targets in the BKV genome. Amplification and detection of the two BKV targets ensures sensitive detection of the viral genome even at low levels. In addition to the BKV primers and probes, the assay utilizes an IC primer/probe set for amplification and detection of the IC target sequence, which is not related to BKV. The IC probe is labeled with a different fluorophore than the BKV probes. This allows for simultaneous detection and discrimination of both the BKV and IC amplified products within the same reaction vessel.

A BKV calibration curve is required for determination of BKV DNA concentration. Two levels of calibrators are processed through sample preparation and PCR to generate the calibration curve. The concentration of BKV DNA in specimens and controls is then calculated from the stored calibration curve.

Assay controls are tested at or above an established minimum frequency to help ensure that instrument and reagent performance remains satisfactory. During each control event, a negative control, a low-positive control, and a high positive control are processed through sample preparation and PCR procedures that are identical to those used for specimens.

The Alinity m BKV assay also utilizes the following:

• Alinity m BKV Application Specification File (List No. 09N85-05A) .
• Alinity m System and System Software (List No. 08N53-002)
• Alinity m Sample Prep Kit 2 (List No. 09N12-001)
• . Alinity m Specimen Dilution Kit I (List No. 09N50-001)
• . Alinity m System Solutions, (List No. 09N20):
  • o Alinity m Lysis Solution (List No. 09N20-001)
  • o Alinity m Diluent Solution (List No. 09N20-003)
  • o Alinity m Vapor Barrier Solution, (List No. 09N20-004)
• Alinity m Tubes and Caps (List No. 09N49): •
  • Alinity m LRV Tube (List No. 09N49-001) o
  • o Alinity m Transport Tubes Pierceable Capped (List No. 09N49-010)
  • o Alinity m Transport Tube (List No. 09N49-011)
  • o Alinity m Pierceable Cap (List No. 09N49-012)
  • o Alinity m Aliquot Tube (List No. 09N49-013)

1. Acceptance Criteria and Reported Device Performance

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cobas® BKV is an in vitro nucleic acid amplification test for the quantitation of BK virus (BKV) DNA in human EDTA plasma on the cobas® 6800/8800 Systems.

cobas® BKV is intended for use as an aid in the management of BKV in transplant patients. In patients undergoing monitoring of BKV, serial DNA measurements can be used to indicate the need for potential treatment changes and to assess viral response to treatment.

The results from cobas® BKV are intended to be read and analyzed by a qualified licensed healthcare professional in conjunction with clinical signs and symptoms and relevant laboratory findings. Test results must not be the sole basis for patient management decisions.

cobas® BKV is not intended for use as a screening test for blood products or human cells, tissues, and cellular and tissue-based products (HCT/Ps).

cobas® BKV is based on fully automated sample preparation (nucleic acid extraction and purification) followed by PCR amplification and detection. The cobas® 6800/8800 Systems consist of the sample supply module, the transfer module, the processing module, and the analytic module. Automated data management is performed by the cobas® 6800/8800 software which assigns test results for all tests as either target not detected, BKV DNA detected ULoQ (upper limit of quantitation), or a value in the linear range LLoQ

The provided document is a 510(k) Summary for the cobas® BKV test for use on the cobas® 6800/8800 Systems. This document focuses on demonstrating substantial equivalence to a predicate device through non-clinical performance evaluation, rather than an AI/ML device requiring a comparative effectiveness study with human readers. Therefore, several of the requested sections (e.g., sample size for test set, number of experts, adjudication method, MRMC study, standalone performance, ground truth for test set, training set details) are not directly applicable or explicitly stated in the context of this In Vitro Diagnostic (IVD) device submission for a quantitative nucleic acid amplification test.

However, I will extract relevant information to address the applicable criteria based on the provided text.

Acceptance Criteria and Device Performance for cobas® BKV

The acceptance criteria for this diagnostic device are primarily defined by various performance characteristics required for quantitative viral nucleic acid tests. The study proves the device meets these criteria through a series of non-clinical performance evaluations.

Table of Acceptance Criteria and Reported Device Performance

• Subgroups Ia, Ic and Subtypes II, III and IV: Verified detection at 21.5 IU/mL with a ≥ 95% hit rate for all tested genotypes (e.g., Subgroup Ia at 21.5 IU/mL: 100.0% hit rate, 63/63 positives; Subgroup Ic at 21.5 IU/mL: 100.0% hit rate, 62/62 positives). |
  | Traceability | Demonstrate proportionality and correlation to the 1st WHO International Standard for BKV DNA. | - Calibration and standardization process provides quantitation values for panels and standards similar to expected values.
• Maximum deviation from expected values was not more than 0.19 log10 IU/mL.
• Deming regression for BKV WHO Standard showed Y = 0.951x + 0.208 with R² = 0.973. |
  | Linear Range | Demonstrate linearity of quantification within a specified range with acceptable deviation and accuracy. | - Demonstrated linear from 1.01E+01 to 1.97E+08 IU/mL.
• Absolute deviation from non-linear regression ≤ ± 0.1 log10 in human EDTA plasma.
• Accuracy within ± 0.2 log10 across the linear range.
• Verified for subgroups Ia, Ic and subtypes II, III and IV: maximum deviation between linear and higher order non-linear regression ≤ ± 0.2 log10. |
  | Lower Limit of Quantitation (LLoQ) | Determine the lowest titer meeting acceptance criteria for Total Analytical Error (TAE ≤ 1.0 log10 IU/mL) and difference between two measurements. | - Established as 21.5 IU/mL.
• At 19.0 IU/mL (nominal concentration, lowest tested for LLoQ), all three lots combined showed TAE of 0.69 and difference between measurements (SD) of 0.73, both within 1.0 log10 IU/mL. |
  | Precision – Within Laboratory | Demonstrate high precision across specified concentration ranges, instruments, operators, and days. | - High precision shown across 5.90E+01 IU/mL to 9.83E+05 IU/mL.
• Total %CV ranged from 8% to 36% across the concentrations tested (e.g., 8% at 9.83E+05 IU/mL, 36% at 5.90E+01 IU/mL).
• Results represent all aspects of the test procedure. |
  | Analytical Specificity | No interference or cross-reactivity with common microorganisms and endogenous/exogenous substances. | - Microorganisms: None of 17 viruses, 13 bacteria, and 3 yeast species interfered at tested concentrations (1.00E+05 to 1.00E+06 units/mL). Negative results for BKV-negative samples, positive for BKV-spiked samples. Titer within ± 0.5 log10 of control.
• Interfering Substances: Elevated triglycerides, bilirubin (conjugated/unconjugated), albumin, hemoglobin, human DNA, and 17 drug compounds (including antimicrobials and immune suppressants) did not interfere. Titer within ± 0.5 log10 of control. |
  | Cross-Contamination | Demonstrate a low or zero cross-contamination rate. | - 0% cross-contamination rate (0/240 negative replicates) with an upper one-sided 95% CI of 1.24%. |
  | Reproducibility | Demonstrate consistent performance across different reagent lots, test sites, batches, and testing days. | - Evaluated at 3 testing sites using 3 reagent lots per site by 2 operators over 5 days.
• Total Precision Standard Deviation ranged from 0.068 to 0.304 log10 IU/mL.
• Lognormal CV(%) for Total Precision ranged from 15.74% to 79.43%.
• 100% detection of 3 x LLoQ samples.
• Equivalence shown between cobas® 6800 and 8800 systems.
• Negative percent agreement (NPA) for reproducibility study: 100% (270/270 samples negative), 95% Exact CI: 98.6% to 100%. |
  | Clinical Concordance | Demonstrate agreement with a well-established laboratory-developed test (LDT). | - Total of 550 valid samples (217 neat, 303 diluted clinical, 30 contrived) from 129 transplant subjects were evaluable.
• Agreement with Comparator BKV LDT (IU LDT): High concordance shown across different concentration ranges.
• Negative Percent Agreement (NPA): 100% (43/43 samples negative) with 95% Exact CI of 91.8% to 100%.
• At thresholds, percent agreement was high (e.g., ≥ threshold 2.3 Log10 IU/mL: 87.7%;

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