K Number

Device Name

Alinity m BKV

Manufacturer

Abbott Molecular Inc.

Date Cleared

2025-03-24

(266 days)

Product Code

QMI OHZ QLX

Regulation Number

866.3183

Intended Use

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.

Device Description

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)

More Information

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Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

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ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K203220

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard real-time PCR assay and automated system for detecting and quantifying BKV DNA. There is no mention of AI or ML in the device description, intended use, or performance studies. The result calculation is based on a calibration curve, which is a standard method in quantitative assays, not indicative of AI/ML.

Therapeutic

No.
The device is an in vitro nucleic acid amplification test intended to quantify BK virus DNA as an aid in diagnosis and management, indicating its use for diagnostic purposes rather than directly providing therapy.

Diagnostic

Yes

Explanation: The Intended Use/Indications for Use section explicitly states that "Alinity m BKV is intended for use as an aid in the diagnosis and management of BKV in transplant patients." This directly indicates its role in diagnosis.

SaMD (Software as a Medical Device)

The device is an in vitro diagnostic (IVD) test that utilizes hardware components (Alinity m System, assay kits, transport kits, tubes, caps, solutions) and reagents to perform nucleic acid amplification and detection. While it includes system software, it is not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The "Intended Use / Indications for Use" section explicitly states that the Alinity m BKV is an "in vitro nucleic acid amplification test for the quantitation of BK virus (BKV) DNA in human EDTA plasma... and urine". It is intended for use as an aid in the diagnosis and management of BKV in transplant patients. This clearly indicates that the device is used to test samples taken from the human body in vitro (outside the body) to provide information for diagnosis and management.
Device Description: The description details how the device processes human specimens (plasma and urine) using laboratory techniques (nucleic acid amplification, real-time PCR) to detect and quantify BKV DNA. This is a hallmark of an in vitro diagnostic device.
Components: The device utilizes various reagents, controls, and calibrators specifically designed for testing biological samples, which are typical components of IVDs.
Performance Studies: The document describes analytical and clinical performance studies conducted using human specimens to evaluate the device's accuracy and reliability in a diagnostic context.

The definition of an In Vitro Diagnostic device is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or a congenital abnormality, or to monitor therapeutic measures. The Alinity m BKV fits this definition perfectly.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

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.

Product codes (comma separated list FDA assigned to the subject device)

QMI

Device Description

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)

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Limit of Detection (LoD):

Plasma: Determined by testing dilutions of the 1st WHO International Standard for BKV (NIBSC code: 14/212, subgroup Ib) in BKV-negative human EDTA plasma. Tested with 3 lots of amplification reagents across multiple days, with 30 replicates per concentration.
- Claimed LoD: 50 IU/mL (1.70 Log IU/mL).
- Probit analysis of least sensitive lot (Lot 2) showed 95% probability of detection at 18.13 IU/mL (95% CI: 11.82 to 41.99 IU/mL).
Urine: Determined by testing dilutions of the 1st WHO International Standard for BKV (NIBSC code: 14/212, subgroup Ib) in BKV negative urine stabilized in transport buffer. Tested with 3 lots of amplification reagents across multiple days, with 30 replicates per concentration.
- Claimed LoD: 50 IU/mL (1.70 log IU/mL) in neat urine.
- Probit analysis of least sensitive lot (Lot 2) showed 95% probability of detection at 16.97 IU/mL (95% CI: 11.42 to 39.14 IU/mL).

Limit of Detection for Genotypes:

Plasma: BKV armored DNA for subgroup Ic and subtype II and clinical specimens for BKV subgroup Ia and subtypes III and IV were diluted to 3 different concentrations in BKV-negative human EDTA plasma. One lot of amplification reagents used across multiple days.
- Results: Detected 95% or greater of BKV samples at and above 30 IU/mL (1.48 Log IU/mL).
Urine: BKV armored DNA for subgroup Ic and subtype II and clinical specimens for BKV subgroup Ia and subtypes III and IV were diluted to 5 different concentrations in BKV-negative stabilized urine. One lot of amplification reagents used across multiple days.
- Results: Detected 95% or greater of BKV samples at and above 45 IU/mL (1.65 Log IU/mL).

Linear Range:

Plasma: Quantitation range: 50 IU/mL (1.70 Log IU/mL) to 1,000,000,000 IU/mL (9.00 Log IU/mL). Linearity assessed with a dilution series of BKV subgroup Ib in BKV-negative human EDTA plasma (15 panel levels, 30 IU/mL to 2,000,000,000 IU/mL).
- Results: Linear across the quantitation range for subgroup Ib (r=1.000). Linear for genotypes Ia, Ic, II, III, and IV across the quantitation range.
Urine: Quantitation range: 50 IU/mL (1.70 Log IU/mL) to 1,000,000,000 IU/mL (9.00 Log IU/mL). Linearity assessed with a dilution series of BKV subgroup Ib in BKV-negative stabilized urine (16 panel levels, 30 IU/mL to 3,000,000,000 IU/mL).
- Results: Linear across the quantitation range for subgroup Ib (r=1.000). Linear for genotypes Ia, Ic, II, III, and IV across the quantitation range.

Precision:

Plasma: 7-member panel in BKV-negative human plasma. Each member tested in 4 replicates, twice daily for 12 days, on 3 Alinity m Systems (3 operators, 3 AMP kit lots).
- Key Result: Within-laboratory SD 0.4% w/v and PBMCs >1 × 10^5 cells/mL.

Carryover:

Plasma: 0.0% (95% CI: 0.0% to 1.1%) based on 360 BKV-negative replicates processed alternating with high BKV-positive samples.
Urine: 0.0% (95% CI: 0.0% to 1.1%) based on 360 BKV-negative replicates processed alternating with high BKV-positive samples.

Clinical Reproducibility:

Plasma: 9-member reproducibility panel (8 positive, 1 negative) in human EDTA plasma. Tested at 3 clinical sites (5 non-consecutive days, 6 replicates per panel member). Total of 3 AMP, CAL, CTRL, and Sample Prep Kit 2 lots used.
- Negative: 100.0% (176/176) (95% CI: 97.9%, 100.0%).
Urine: 9-member reproducibility panel (8 positive, 1 negative) in urine stabilized in transport buffer. Tested at 3 clinical sites (5 non-consecutive days, 6 replicates per panel member). Total of 3 AMP, CAL, CTRL, and Sample Prep Kit 2 lots used.
- Negative: 99.4% (173/174) (95% CI: 96.8%, 99.9%).

Clinical Performance:

Plasma: Comparison to an FDA-cleared BKV nucleic acid test. 579 EDTA plasma clinical specimens (555 neat, 24 diluted) from 556 SOT/HSCT subjects. Tested at 4 clinical sites with 4 Alinity m BKV reagent lots.
- Agreement based on concentration intervals.
- Agreement at different clinical thresholds:
  - Target Not Detected: 100.0% (=Threshold)
  - LLoQ (1.70 Log IU/mL): 100.0% (=Threshold)
  - 3.00 Log IU/mL: 99.0% (=Threshold)
  - 4.00 Log IU/mL: 98.7% (=Threshold)
- Negative Percent Agreement (NPA): 100.0% (29/29) (95% CI: 88.3% to 100.0%) for confirmed BKV DNA negative specimens.
- Deming regression (n=268, within common quantitation range): Slope = 1.07, Intercept = -0.37, r = 0.953.
- Mean bias: -0.12 Log IU/mL (95% CI: -0.16 to -0.09 Log IU/mL).
Urine: Comparison to an FDA-cleared BKV nucleic acid test. 380 urine specimens from SOT/HSCT subjects. Tested at 3 clinical sites with 3 Alinity m BKV reagent lots.
- Agreement based on concentration intervals.
- Agreement at different clinical thresholds:
  - Target Not Detected: 100.0% (=Threshold)
  - LLoQ (2.30 Log IU/mL): 100.0% (=Threshold)
  - 4.00 Log IU/mL: 99.2% (=Threshold)
  - 7.00 Log IU/mL: 99.7% (=Threshold)
- Negative Percent Agreement (NPA): 95.5% (64/67) (95% CI: 87.6% to 98.5%) for confirmed BKV DNA negative specimens.
- Deming regression (n=140, within common quantitation range): Slope = 1.04, Intercept = -0.35, r = 0.921.
- Mean bias: -0.16 Log IU/mL (95% CI: -0.25 to -0.07 Log IU/mL).

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Sensitivity: Not Found
Specificity: Not Found
PPV: Not Found
NPV: Not Found
Detection Rate:

Plasma LoD: 100% at 50 IU/mL, decreasing with lower concentrations.
Urine LoD: 100% at 50 IU/mL, decreasing with lower concentrations.
Agreement to comparator for plasma:
Column Agreement (%): 100.0% for TND (270/270), 100.0% for =4.40 (30/30).
Agreement to comparator for urine:
Column Agreement (%): 100.0% for TND (177/177), 100.0% for =7.00 (37/37).

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K203220

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.3183 Quantitative viral nucleic acid test for transplant patient management.

(a)
Identification. A quantitative viral nucleic acid test for transplant patient management is identified as a device intended for prescription use in the detection of viral pathogens by measurement of viral DNA or RNA using specified specimen processing, amplification, and detection instrumentation. The test is intended for use as an aid in the management of transplant patients with active viral infection or at risk for developing viral infections. The test results are intended to be interpreted by qualified healthcare professionals in conjunction with other relevant clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The labeling required under § 809.10(b) of this chapter must include:
(i) A prominent statement that the device is not intended for use as a donor screening test for the presence of viral nucleic acid in blood or blood products.
(ii) Limitations which must be updated to reflect current clinical practice. These limitations must include, but are not limited to, statements that indicate:
(A) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with clinical signs and symptoms and other relevant laboratory results; and
(B) Negative test results do not preclude viral infection or tissue invasive viral disease and that test results must not be the sole basis for patient management decisions.
(iii) A detailed explanation of the interpretation of results and acceptance criteria must be provided and include specific warnings regarding the potential for variability in viral load measurement when samples are measured by different devices. Warnings must include the following statement, where applicable: “Due to the potential for variability in [analyte] measurements across different [analyte] assays, it is recommended that the same device be used for the quantitation of [analyte] when managing individual patients.”
(iv) A detailed explanation of the principles of operation and procedures for assay performance.
(2) Design verification and validation must include the following:
(i) Detailed documentation of the device description, including all parts that make up the device, ancillary reagents required for use with the assay but not provided, an explanation of the methodology, design of the primer/probe sequences, rationale for the selected gene target, and specifications for amplicon size, guanine-cytosine content, and degree of nucleic acid sequence conservation. The design and nature of all primary, secondary and tertiary quantitation standards used for calibration must also be described.
(ii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions;
(iii) Documentation and characterization (
e.g., determination of the identity, supplier, purity, and stability) of all critical reagents and protocols for maintaining product integrity throughout its labeled shelf-life.(iv) Stability data for reagents provided with the device and indicated specimen types, in addition to the basis for the stability acceptance criteria at all time points chosen across the spectrum of the device's indicated life cycle, which must include a time point at the end of shelf life.
(v) All stability protocols, including acceptance criteria.
(vi) Final lot release criteria along with documentation of an appropriate justification that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims.
(vii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Mode Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel viral stains (
e.g., regular review of published literature and annual in silico analysis of target sequences to detect possible primer or probe mismatches). All results of this protocol, including any findings, must be documented.(viii) Analytical performance testing that includes:
(A) Detailed documentation of the following analytical performance studies: limit of detection, upper and lower limits of quantitation, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, quality control, specimen stability studies, and additional studies as applicable to specimen type and intended use for the device;
(B) Identification of the viral strains selected for use in analytical studies, which must be representative of clinically relevant circulating strains;
(C) Inclusivity study results obtained with a variety of viral genotypes as applicable to the specific assay target and supplemented by in silico analysis;
(D) Reproducibility studies that include the testing of three independent production lots;
(E) Documentation of calibration to a reference standard that FDA has determined is appropriate for the quantification of viral DNA or RNA (
e.g., a recognized consensus standard); and(F) Documentation of traceability performed each time a new lot of the standardized reference material to which the device is traceable is released, or when the field transitions to a new standardized reference material.
(ix) Clinical performance testing that includes:
(A) Detailed documentation from either a method comparison study with a comparator that FDA has determined is appropriate, or results from a prospective clinical study demonstrating clinical validity of the device;
(B) Data from patient samples, with an acceptable number of the virus-positive samples containing an analyte concentration near the lower limit of quantitation and any clinically relevant decision points. If an acceptable number of virus-positive samples containing an analyte concentration near the lower limit of quantitation and any clinically relevant decision cannot be obtained, contrived samples may be used to supplement sample numbers when appropriate, as determined by FDA;
(C) The method comparison study must include predefined maximum acceptable differences between the test and comparator method across all primary outcome measures in the clinical study protocol; and
(D) The final release test results for each lot used in the clinical study.

Summary

March 24, 2025

FDA U.S. FOOD & DRUG
ADMINISTRATION

Abbott Molecular Inc. Gina Sammarco Associate Director Regulatory Affairs 1300 E Touhy Ave Des Plaines, Illinois 60018

Re: K241921

Trade/Device Name: Alinity m BKV Regulation Number: 21 CFR 866.3183 Regulation Name: Quantitative Viral Nucleic Acid Test For Transplant Patient Management Regulatory Class: Class II Product Code: OMI Dated: February 21, 2025 Received: February 21, 2025

Dear Gina Sammarco:

We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatory

assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

MARIA I. GARCIA -S

Maria Garcia, Ph.D. Assistant Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

Indications for Use

510(k) Number (if known) K241921

Device Name Alinity m BKV

Indications for Use (Describe)

Almity 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 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.

Type of Use (Select one or both, as applicable)
-------------------------------------------------

X Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

1.0	510(k) Summary	2
1.1	Submitter	2
1.2	Device Information	3
1.3	Predicate Device	3
1.4	Device Description	4
1.5	Intended Use	7
1.6	Similarities and Differences to Predicate Devices	7
1.7	Results and Interpretation	11
1.8	Performance Data	12
1.9	Conclusions Drawn from the Studies	47

1.0 510(k) Summary

This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirement of 21 CFR Section 807.92(c).

1.1 Submitter

Date Prepared:

| Applicant Name and Address: | Abbott Molecular Inc.
1300 E. Touhy Avenue
Des Plaines, IL 60018 |
|-----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Gina Sammarco
Associate Director Regulatory Affairs
Abbott Molecular, Inc.
1300 E. Touhy Avenue
Des Plaines, IL 60018
Phone: 224-361-7627
Fax: 224-361-7269 |

March 21, 2025

1.2 Device Information

Trade Name	Regulation Name	Product Code	Regulation No.	Class
Alinity m BKV	Quantitative viral nucleic acid test for transplant
patient management	QMI	21 CFR 866.3183	II

1.3 Predicate Device

Device Name	Predicate Device	510(k)	Cleared
Alinity m BKV	cobas® BKV	K203220	01/29/2021

1.4 Device Description

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.

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.

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)

1.5 Intended Use

Alinity m BKV AMP Kit:

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, and PPT) and urine stabilized using the Alinity m Urine Transport Kit on the automated Alinity m System.

In EDTA plasma (K2EDTA, 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 symptoms 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.

Alinity m Urine Transport Kit:

The Alinity m Urine Transport Kit is intended for the transportation and storage of urine specimens to stabilize nucleic acid in these specimens. The collected specimens are intended to be tested on the automated Alinity m System. Refer to the appropriate Alinity m assay package insert for additional information.

Similarities and Differences to Predicate Devices 1.6

The primary functional components of the Alinity m BKV assay are substantially equivalent to other legally marketed nucleic acid amplification tests (NAAT) intended for the quantitative detection of BKV DNA.

The Alinity m BKV assay has the same general intended use as the predicate device. Although there are some technological differences between the Alinity m BKV assay and

the predicate device, these differences do not raise new types of safety or effectiveness questions.

These devices are similar in that they are designed to prepare nucleic acids for amplification, amplify specific BKV DNA sequences, detect the amplified products, and report quantitative results.

The primary similarities and differences between the Alinity m BKV assay and the predicate device are shown in Table 1 and Table 2.

Table 1. Similarities Between Alinity m BKV and Predicate Device
Description	Subject Device	Predicate Device
	Alinity m BKV	cobas® BKV (K203220)
Intended Use	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.	cobas® BKV is an in vitro nucleic acid amplification test for the
quantitation of BK virus (BKV) DNA in human EDTA plasma and
urine stabilized in cobas® PCR Media on the cobas® 6800/8800
Systems.
	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 EDTA plasma, cobas® BKV is intended for use as an aid in the
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.
	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.	In urine stabilized in cobas® PCR Media, cobas® BKV is intended for
use as an aid in the management of BKV in transplant patients.
	The results from Alinity m BKV must be interpreted in conjunction
with clinical signs and symptoms and other relevant laboratory
findings.	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.
	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.	cobas® BKV is not intended for use as a screening test for blood or
blood products or human cells, tissues, and cellular and tissue-based
products (HCT/Ps).
Assay Type	Quantitative	Quantitative
Specimen Types	EDTA Plasma, Stabilized Urine	EDTA Plasma, Stabilized Urine
Sample Preparation
Procedure	Automated liquid handling and robotic manipulation platform	Automated liquid handling and robotic manipulation platform
Amplification
Technology	Real-time polymerase chain reaction	Real-time polymerase chain reaction
Assay Controls	Negative Control Low Positive Control High Positive Control Internal Control (IC)	Negative Control Low Positive Control High Positive Control DNA Quantitation Standard (DNA-QS)
Table 2. Differences Between Alinity m BKV and Predicate Device
Description	Subject Device	Predicate Device
	Alinity m BKV	cobas® BKV (K203220)
Assay Targets	Dual targets in the BKV genome
(2 highly conserved regions of the BKV genome)	Dual targets in the BKV genome
(small T-antigen and VP2 regions)

1.7 Results and Interpretation

The Alinity m System will report a result and interpretation for each specimen (refer

to Table 3). If applicable message codes or flags will also be displayed.

Table 3. Alinity m BKV Results and Interpretation
Alinity m System Reported
Result	Interpretation	Interpretation Additional Information
Not Detected	BKV DNA not detected	N/A
ULoQ	BKV DNA detected	BKV DNA concentration is above the
Upper Limit of Quantitation (ULoQ) of the assay.

1.8 Performance Data

The following performance data were provided in support of safety, effectiveness, and substantial equivalence determination of the device.

1.8.1 Specific Performance Characteristics

1.8.1.1 Traceability to the WHO Standard

Primary calibrators and assay product calibrators with known concentrations were used throughout product development and product manufacturing to establish traceability to the 1st World Health Organization (WHO) International Standard for BK virus for Nucleic Acid Amplification Techniques (NIBSC code: 14/212). The concentrations tested for the WHO standard were 3.00 Log IU/mL and 5.00 Log IU/mL. The target concentrations tested for the primary calibrators were 2.91 Log IU/mL and 6.94 Log IU/mL. The Alinity m BKV product calibrators and controls were also tested along with the primary calibrators and the WHO standard. All the tested material had observed BKV concentrations similar to the target concentrations and were linear across the assay's quantitation range, as presented in Figure 1.

Figure 1. Traceability to the WHO Standard

Image /page/15/Figure/6 description: This image is a scatter plot that shows the relationship between target concentration and Alinity m BKV observed mean. The x-axis represents the target concentration in Log IU/mL, and the y-axis represents the Alinity m BKV observed mean in Log IU/mL. The plot includes data points for WHO, Primary Calibrator, Product Calibrator, and Control. The equation of the line is y = 1.00x - 0.02, with an R-squared value of 0.999.

1.8.1.2 Performance Characteristics for Plasma Sample Type

Limit of Detection 1.8.1.2.1

The Limit of Detection (LoD) was determined by testing dilutions of the 1st WHO International Standard for BK virus for Nucleic Acid Amplification Techniques (NIBSC code: 14/212, subgroup Ib) prepared in BKV-negative human EDTA plasma. Testing for each BKV DNA concentration was performed with 3 lots of amplification reagents across multiple days. The results, representative of the analytical sensitivity performance of Alinity m BKV in plasma, are summarized in Table 4 (Lot 1), Table 5 (Lot 2), and Table 6 (Lot 3). The claimed LoD of Alinity m BKV is 50 IU/mL (1.70 Log IU/mL) in plasma.

Probit analysis of the data for Lot 2 (least sensitive lot) determined that the concentration of BKV DNA in plasma detected with 95% probability (LoD by Probit) was 18.13 IU/mL (95% CI: 11.82 to 41.99 IU/mL).

Table 4. Alinity m BKV LoD in EDTA Plasma, Lot 1
BKV DNA
(IU/mL)	No. of Valid
Replicates	No. of Detected
Replicates	Detection Rate
(%)
60.000	30	30	100.0
50.000	30	30	100.0
40.000	30	30	100.0
30.000	30	30	100.0
15.000	30	29	96.7
7.500	30	27	90.0
3.750	30	16	53.3
1.875	30	9	30.0

Table 5. Alinity m BKV LoD in EDTA Plasma, Lot 2 (Least Sensitive Lot)
BKV DNA
(IU/mL)	No. of Valid
Replicates	No. of Detected
Replicates	Detection Rate
(%)
60.000	30	30	100.0
50.000	30	30	100.0
40.000	30	30	100.0
30.000	30	29	96.7
15.000	30	29	96.7
7.500	30	23	76.7
3.750	30	11	36.7
1.875	29	10	34.5

Table 6. Alinity m BKV LoD in EDTA Plasma, Lot 3
BKV DNA
(IU/mL)	No. of Valid
Replicates	No. of Detected
Replicates	Detection Rate
(%)
60.000	30	30	100.0
50.000	30	30	100.0
40.000	30	30	100.0
30.000	30	30	100.0
15.000	30	29	96.7
7.500	30	25	83.3
3.750	30	18	60.0
1.875	30	9	30.0

1.8.1.2.2 Limit of Detection for Genotypes

BKV armored DNA for subgroup Ic and subtype II and clinical specimens for BKV subgroup Ia and subtypes III and IV were diluted to 3 different concentrations in BKV-negative human EDTA plasma. Testing was performed using one lot of amplification reagents across multiple days. The results, representative of the analytical sensitivity performance of Alinity m BKV for BKV subgroups Ia and Ic and subtypes II, III, and IV, are summarized in Table 7 for plasma. Alinity m BKV detected 95% or greater of BKV samples at and above 30 IU/mL (1.48 Log IU/mL) in plasma. These results demonstrate the ability of Alinity m BKV to detect BKV subgroups Ia and Ic and subtypes II, III, and IV at the claimed LoD in plasma.

Genotype	BKV DNA (IU/mL)	No. of Valid Replicates	No. of Detected Replicates	Detection Rate (%)
Subgroup Ia	60	30	30	100.0
	50	30	30	100.0
	30	30	30	100.0
Subgroup Ic	60	28	28	100.0
	50	30	30	100.0
	30	30	30	100.0
Subtype II	60	30	30	100.0
	50	30	30	100.0
	30	29	29	100.0
Subtype III	60	30	30	100.0
	50	29	29	100.0
	30	30	30	100.0
Subtype IV	60	30	30	100.0
	50	30	30	100.0
	30	30	29	96.7

1.8.1.2.3 Linear Range

The quantitation range of Alinity m BKV for plasma is from the lower limit of quantitation (LLoQ) of 50 IU/mL (1.70 Log IU/mL) to the upper limit of quantitation (ULoQ) of 1,000,000,000 IU/mL (9.00 Log IU/mL). Linearity of Alinity m BKV was assessed by testing a dilution series of BKV subgroup Ib in BKV-negative

human EDTA plasma, consisting of 15 panel levels targeted in the range of 30 IU/mL to 2,000,000,000 IU/mL (1.48 Log IU/mL to 9.30 Log IU/mL).

Plasma panel was prepared either using the 1st WHO International Standard for BK virus (NIBSC code: 14/212, subgroup Ib) for multiple levels ranging from 30 IU/mL to 100.000 IU/mL (1.48 Log IU/mL to 5.00 Log IU/mL) or using armored DNA for the remaining levels ranging from 100 IU/mL to 2,000,000,000 IU/mL (2.00 Log IU/mL to 9.30 Log IU/mL).

Alinity m BKV was linear across the quantitation range from 50 IU/mL (1.70 Log IU/mL) to 1,000,000,000 IU/mL (9.00 Log IU/mL) in plasma. Representative results for Alinity m BKV linearity performance are shown in Figure 2.

Image /page/19/Figure/3 description: The image is a scatter plot titled "Figure 2. Alinity m BKV Linearity in EDTA Plasma." The x-axis is labeled "Expected Concentration (Log IU/mL)," and the y-axis is labeled "Alinity m BKV (Log IU/mL)." The plot shows a strong positive linear correlation between the expected concentration and the measured concentration of Alinity m BKV, with an r-value of 1.000.

Image /page/19/Figure/4 description: This image contains a note describing the markers in a plot. The note states that the markers represent the mean Alinity m BKV concentration, measured in Log IU/mL, for each panel level. The note is labeled with the letter 'a'.

1.8.1.2.4 Linearity for Genotypes

Linearity of Alinity m BKV for subgroups/subtypes Ia, Ic, II, III, and IV was confirmed by testing a dilution series in BKV-negative human EDTA plasma, consisting of 13 panel levels for subgroup/subtypes Ia, III, and IV and 12 panel levels for

subgroup/subtype Ic and II, targeted in the range of 30 IU/mL to 2,000,000,000 IU/mL (1.48 Log IU/mL to 9.30 Log IU/mL).

For subgroup/subtypes Ia, III, and IV, plasma panel was prepared either using clinical specimens for multiple levels ranging from 30 IU/mL to 100,000 IU/mL (1.48 Log IU/mL to 5.00 Log IU/mL) or using armored DNA for the remaining levels ranging from 200 IU/mL to 2,000,000,000 IU/mL (2.30 Log IU/mL to 9.30 Log IU/mL). For subgroup/subtype Ic and II, plasma panel was prepared using armored DNA for all levels ranging from 30 IU/mL to 2,000,000,000 IU/mL (1.48 Log IU/mL to 9.30 Log IU/mL).

Alinity m BKV was linear in plasma across the quantitation range from 50 IU/mL (1.70 Log IU/mL) to 1,000,000,000 IU/mL (9.00 Log IU/mL) for subgroups/subtypes Ia, Ic, II, III, and IV. Representative results for Alinity m BKV linearity performance for subgroups/subtypes Ia, Ic, II, III, and IV, along with results for subgroup Ib (Section 1.7.1.2.3), are shown in Figure 3.

Image /page/20/Figure/3 description: The image is a graph titled "Figure 3. Alinity m BKV Linearity for Genotypes in EDTA Plasma." The graph shows the relationship between Alinity m BKV (Log IU/mL) on the y-axis and Expected Concentration (Log IU/mL) on the x-axis. There are six different lines on the graph, each representing a different genotype: Ia, Ib, Ic, II, III, and IV. The lines are all relatively linear, indicating that the Alinity m BKV assay is linear for all of the genotypes tested.

4 Note: The markers in the plot represent the mean Alinity m BKV concentration (in Log IU/mL) for each panel level.

1.8.1.2.5 Precision

Precision of Alinity m BKV was determined by analyzing an 7-member panel prepared in BKV-negative human plasma. All panel members were prepared using clinical specimens. Each panel member was tested in 4 replicates, twice each day for 12 days, on 3 Alinity m Systems operated by 3 operator per instrument), using 3 AMP kit lots (one lot per instrument), for a total of 288 replicates per panel member.

The representative precision results in Table 9 demonstrated that Alinity m BKV within-laboratory standard deviation (SD) in plasma was less than or equal to 0.25 Log IU/mL for BKV DNA panels within the range of 2.70 Log IU/mL to 9.00 Log IU/mL (500 IU/mL to 1,000,000 IU/mL), and less than or equal to 0.50 Log IU/mL for BKV DNA panels within the range of 1.70 Log IU/mL to less than 2.70 Log IU/mL to less than 500 IU/mL).

Table 8. Alinity m BKV Precision in Plasma (Log IU/mL)
Panel
Member	Na	Mean
Concentration
(Log IU/mL)		Within-Run		Between-Run		Between-Day		Within-
Laboratoryb		Between-
Instrumentc		Totald
			SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
07	288	7.99	0.047	0.6	0.028	0.3	0.000	0.0	0.054	0.7	0.028	0.4	0.061	0.8
06	286	5.95	0.054	0.9	0.007	0.1	0.019	0.3	0.057	1.0	0.014	0.2	0.059	1.0
05	288	4.89	0.054	1.1	0.024	0.5	0.015	0.3	0.061	1.2	0.015	0.3	0.063	1.3
04	288	3.87	0.070	1.8	0.020	0.5	0.015	0.4	0.075	1.9	0.015	0.4	0.076	2.0
03	287	2.83	0.066	2.3	0.026	0.9	0.000	0.0	0.071	2.5	0.029	1.0	0.077	2.7
02	287	2.32	0.100	4.3	0.027	1.2	0.029	1.2	0.107	4.6	0.035	1.5	0.113	4.9
01	96	1.81	0.103	5.7	0.025	1.4	0.000	0.0	0.106	5.9	0.000	0.0	0.106	5.9

a Valid replicates within the quantitation range.

b Within-Laboratory includes Within-Run, Between-Run, and Between-Day Components.

6 Alinity in System (Instrument), AMP Kit lot, and Operator are confounding effect is represented by Between-Instrument.

d Total includes Within-Run, Between-Run, Between-Day, and Between-Instrument Components.

| | | Mean
Concentrationb
(IU/mL) | %CVc | | | | | |
|----------------------|-----------------|-----------------------------------|------------|-------------|-------------|-------------------------|--------|------|
| Alinity m BKV 510(k) | Panel
Member | Na | Within-Run | Between-Run | Between-Day | Between-
Instrumentd | Totale | |
| | 07 | 288 | 98,734,723 | 10.7 | 6.4 | 0.0 | 6.5 | 14.1 |
| | 06 | 286 | 897,345 | 12.4 | 1.5 | 4.4 | 3.2 | 13.6 |
| | 05 | 288 | 78,731 | 12.5 | 5.5 | 3.4 | 3.4 | 14.5 |
| | 04 | 288 | 7,609 | 16.3 | 4.5 | 3.6 | 3.6 | 17.7 |
| | 03 | 287 | 679 | 15.2 | 6.1 | 0.0 | 6.8 | 17.8 |
| | 02 | 287 | 218 | 23.3 | 6.3 | 6.6 | 8.1 | 26.5 |
| | 01 | 96 | 66 | 24.1 | 5.7 | 0.0 | 0.0 | 24.8 |

a Valid replicates within the quantitation range.

b Titer data are considered to be log-normally distributed and the mean values for log-normal titer data are calculated as exp(mean*ht(10) + [SD'm(10]) '2/2/2 ° Titer data are considered to be log-normally distributed and the %CV values for log-normal titer data are calculated as sqr(10°[SD^2 * h(10]] – 1) * 100.

d Alinity m System (Instrument), AMP Kit tot, and Operator are confounding effect is represented by Between-Instrument Comport.

· Total includes Within-Run, Between-Run, Between-Day, and Between-Instrument Components.

1.8.1.2.6 Lower Limit of Quantitation (LLoQ)

The LLoQ is defined as the lowest concentration at which BKV DNA is reliably quantitated within an acceptable total error

of ≤ 1.00 Log IU/mL.

Total error was estimated for detected plasma samples from the LoD study by 2 methods:

Total Analytical Error (TAE) = |bias| + 2 × SD, and .
Total Error (TE) = SQRT(2) × 2 × SD .

The results of the calculations are shown in Table 10.

Panel members were dilutions of the 1* WHO International Standard for BK Virus (NIBSC code: 14/212, subgroup Ib) prepared in BKV-negative plasma.

The results of these analyses support a claimed LLoQ for Alinity m BKV of 50 IU/mL) in plasma, with an acceptable level of accuracy and precision (ie, TAE and TE less than or equal to 1.00 Log IU/mL).

Table 10. TAE and TE for Plasma
Target
Concentration
(Log IU/mL)	Mean
Concentration
(Log IU/mL)	Biasa
(Log IU/mL)	SD
(Log IU/mL)	TAE
(Log IU/mL)	TE
(Log IU/mL)
1.60	1.59	-0.01	0.22	0.45	0.63
1.70	1.71	0.01	0.22	0.44	0.61
1.78	1.79	0.01	0.21	0.43	0.59

ª Bias = Mean Concentration - Target Concentration

1.8.1.2.7 Alinity m BKV Plasma Testing Using Dilution Procedure

The 1:2.5 dilution procedure for plasma samples was evaluated by comparing quantitation of neat samples tested using the Alinity m BKV dilution procedure. Five plasma panel members with BKV levels targeted in the range of 375 U/mL to 1.000.000.000 IU/mL (2.57 Log IU/mL to 9.00 Log IU/mL) were tested. Each panel member was tested, neat and using the dilution procedure, in multiple replicates. The differences in mean (ie, diluted minus neat) ranged from -0.19 Log IU/mL to 0.27 Log IU/mL.

1.8.1.2.8 Precision of Alinity m BKV Plasma Testing Using Dilution Procedure

Precision of Alinity m BKV using the dilution procedure was determined by analyzing 3 EDTA plasma panel members. All panel members were prepared using clinical specimens. Each panel member was tested in 4 replicates, twice each day for 12 days, on 3 Almity m Systems with 3 Alinity m Specimen Dilution Kit I lots, and 3 Alinity m BKV AMP Kit lots by 3 operators (1 Specimen Diluent lot, 1 AMP kit lot, and 1 operator per instrument), for a total of 288 replicates. The results, representative of the precision of Alinity m BKV using the plasma dilution procedure, are summarized in Table 11 and Table 12.

| Panel
Member | Na | Mean
Concentration
(Log IU/mL) | Within-Run | | Between-Run | | Between-Day | | Within-
Laboratoryb | | Between-
Instrumentc | | Totald | |
|-----------------------------------------------------------------------------------------------|-----|--------------------------------------|------------|-----|-------------|-----|-------------|-----|------------------------|-----|-------------------------|-----|--------|-----|
| Table 11. Precision of Alinity m BKV EDTA Plasma Testing Using Dilution Procedure (Log IU/mL) | | | | | | | | | | | | | | |
| 01 | 287 | 3.50 | 0.054 | 1.5 | 0.050 | 1.4 | 0.038 | 1.1 | 0.083 | 2.4 | 0.000 | 0.0 | 0.083 | 2.4 |
| 02 | 286 | 4.82 | 0.112 | 2.3 | 0.067 | 1.4 | 0.065 | 1.3 | 0.146 | 3.0 | 0.000 | 0.0 | 0.146 | 3.0 |
| 03 | 287 | 7.98 | 0.049 | 0.6 | 0.030 | 0.4 | 0.000 | 0.0 | 0.057 | 0.7 | 0.021 | 0.3 | 0.061 | 0.8 |

a Valid replicates

b Within-Laboratory includes Within-Run, Between-Run, and Between-Day Components

f Almity m System (Instrument), AMP Kit Iot, and Opentor are confounded and the confounding effect is represented by Between Instrument Component. d Total includes Within-Run. Between-Run. Between-Dav. and Between-Instrument Components.

		Mean			%CVc
Panel
Member	Na	Concentrationb
(IU/mL)	Within-Run	Between-Run	Between-Day	Between-
Instrumentd	Totale
01	287	3,218	12.5	11.5	8.8	0.0	19.2
02	286	69,564	26.2	15.5	15.0	0.0	34.5
03	287	96,200,926	11.2	7.0	0.0	4.8	14.1

Table 12. Precision of Alinity m BKV EDTA Plasma Testing Using Dilution Procedure (IU/mL)

a Valid replicates

b Titer data are considered to be log-normal tite mean values for log-normal titer data are calculated as exp(mear*h(10) + SD*h(10.

"Titer data are considered to be log-normally distributed and the %CV values for log-normal titer data are calculated as sqr(10°[SD^2 * h(10]) – 1) * 100.

d Alinity m System (Instrument), AMP Kit I Iot, and Operator are confounded, and the confounding effect is represented by Between-Instrument Component. "Total includes Within-Run, Between-Run, Between-Day, and Between-Instrument Components.

1.8.1.2.9 Confirmation of LLoQ Using Plasma Dilution Procedure

Confirmation testing for Alinity m BKV LLoQ using the dilution procedure was performed by testing 2 panel members at 125 IU/mL (2.5 × LLoQ) and 1.50 IU/mL (3 ×LLoQ) with a dilution factor of 1:2.5. The BKV concentrations in the panel members were targeted at 50 IU/mL (LLoQ) and 60 IU/mL (near LLoQ) after dilution in Specimen Diluent. Panel members were dilutions of the 1ª WHO International Standard for BK Virus (NIBSC code: 14/212, subgroup Ib) prepared in BKV-negative EDTA plasma.

A minimum of 14 replicates per day of each panel level were tested using the dilution procedure in 3 runs across 3 days (one run per day). The study was performed using 1 Alinity m BKV AMP Kit lot, 1 Alinity m Specimen Dilution Kit I lot, and 1 Alinity m System. Total error was estimated by TAE and TE, as shown in Table 13. The accuracy and precision at 50 IU/mL and 60 IU/mL were confirmed for Alinity m BKV testing using the 1:2.5 dilution procedure.

Table 13. Total Error Using Plasma Dilution Procedure
Panel
Member	Target
Concentration
Neat
(Log IU/mL)	Dilution
Factor	Target
Concentration in
Specimen Diluent
(Log IU/mL)	Mean
Concentrationa
(Log IU/mL)	Biasb
(Log IU/mL)	SD
(Log IU/mL)	TAE
(Log IU/mL)	TE
(Log IU/mL)
1	2.10	2.5	1.70	2.04	-0.06	0.17	0.40	0.49
2	2.18	2.5	1.78	2.13	-0.05	0.15	0.35	0.44

ª Reported concentration for neat samples

b Bias = Mean Concentration - Target Concentration Neat

1.8.1.2.10 Analytical Specificity - Potential Cross-Reactants

The analytical specificity of Alinity m BKV was evaluated with a panel of microorganisms (Table 14) in BKV-negative K2 EDTA plasma, positive plasma targeted to 150 IU/mL BKV DNA, and positive plasma targeted to 10,000 IU/mL BKV DNA. Microorganisms were tested at a final concentration of at least 105 Units/mL for viruses and fungi, or at least 106 Units/mL for bacteria. No cross-reactivity or interference in the performance of the Alinity m BKV assay was observed in the presence of the tested microorganisms.

Table 14. Microorganisms Tested in Plasma

Viruses
Adenovirus 5	Herpesvirus 8 (Kaposi's sarcoma associated virus)	Human T-cell Lymphotropic Virus (HTLV)
Cytomegalovirus (CMV)	Human Immunodeficiency Virus 1 (HIV-1)	Influenza A Virus
Epstein-Barr Virus (EBV)	Human Immunodeficiency Virus 2 (HIV-2)	JC Polyomavirus
Hepatitis B Virus (HBV)	Human Papillomavirus 16 (HPV-16)	Parvovirus B19
Hepatitis C Virus (HCV)	Human Papillomavirus 18 (HPV-18)	Simian Virus 40
Herpesvirus 6	Herpes Simplex Virus 1 (HSV-1)	Vaccinia Virus (VACV)
Herpesvirus 7	Herpes Simplex Virus 2 (HSV-2)	Varicella-Zoster Virus (VZV)
Bacteria		Fungi
Actinomyces israelii	Mycoplasma pneumoniae	Aspergillus niger
Chlamydia trachomatis	Neisseria gonorrhoeae	Candida albicans
Clostridium perfringens	Salmonella enterica	Cryptococcus neoformans
Cutibacterium acnes	Salmonella typhimurium
Enterococcus faecalis	Staphylococcus aureus
Escherichia coli	Staphylococcus epidermidis
Klebsiella pneumoniae	Streptococcus pneumoniae
Listeria monocytogenes	Streptococcus pyogenes
Mycobacterium avium

Analytical Specificity - Potentially Interfering Substances 1.8.1.2.11

The effects of endogenous substances, the presence of autoimmune diseases, and the presence of therapentic drugs commonly prescribed in transplant patients were evaluated. Potential interference on Alinity m BKV performance in EDTA plasma was assessed by testing a minimum of 8 samples at each BKV DNA level: negative, 150 IU/mL. No interference was observed in the presence of albumin (60 mg/mL), hemoglobin (10 g/L), triglycerides (16.94 mmol/L), conjugated bilirubin (475 umol/L), unconjugated bilirubin (684 umol/L), or human genomic DNA (2 µg/mL) that were introduced in the sample.

No interference was observed for speciments with the following disease states: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and anti-nuclear antibodies (ANA).

No interference was observed in the presence of drug compounds tested in Table 15 at a concentration of 3 times the reported Cmax or higher.

Table 15. Drug Compounds Tested in Plasma
Drug Pool	Drug Compounds
1	Abacavir Sulfate, Acyclovir, Amoxicillin, Atenolol, Azathioprine, Cefotetan, Cidofovir, Cyclosporine, Everolimus, Fluconazole, Ganciclovir,
Leflunomide, Letermovir, Micafungin, Mycophenolate Mofetil, Mycophenolic acid, Piperacillin, Prednisone, Sirolimus, Sulfamethoxazole,
Tacrolimus, Tazobactam Sodium, Trimethoprim, Valacyclovir, Valganciclovir, Vancomycin
2	Clavulanate, Foscarnet

Carryover in Plasma 1.8.1.2.12

The carryover rate for Alinity m BKV plasma protocol was determined by analyzing 360 valid replicates of BKY-negative samples processed from alternating positions with 360 valid replicates of high concentrated BKV-positive plasma samples targeted at 20,000,000 IUmL, across a total of 15 runs (15 AMP Trays). BKV DNA was not detected in any of the BKV-negative samples, resulting in an overall carryover rate of 0.0% (95% CI: 0.0% to 1.1%).

1.8.1.3 Performance Characteristics for Urine Sample Type

1.8.1.3.1 Limit of Detection

The LoD was determined by testing dilutions of the 1st WHO International Standard for BK virus (NIBSC code: 14/212, subgroup Ib) prepared in BKV negative urine stabilized in transport buffer (Alinity m Urine Transport Kit). Testing for each BKV DNA concentration was performed with 3 lots of amplification reagents across multiple days. The results, representative of the analytical sensitivity performance of Alinity m BKV in urine, are summarized in Table 16 (Lot 1), Table 17 (Lot 2) and Table 18 (Lot 3). The claimed LoD of Alinity m BKV is 50 IU/mL (1.70 log IU/mL) in neat urine.

Probit analysis of the data for Lot 2 (least sensitive lot) determined that the concentration of BKV DNA in urine detected with 95% probability (LoD by Probit) was 16.97 IU/mL (95% CI: 11.42 to 39.14 IU/mL).

Table 16. Alinity m BKV LoD in Urine, Lot 1
BKV DNA ª
(IU/mL)	No. of Valid
Replicates	No. of Detected
Replicates	Detection Rate
(%)
330.00	30	30	100.0
300.00	30	30	100.0
75.00	30	30	100.0
60.00	30	30	100.0
45.00	30	30	100.0
22.50	30	30	100.0
11.25	30	28	93.3
5.63	30	22	73.3
2.81	30	17	56.7

a Urine samples tested stabilized in transport buffer. BKV concentration based on neat urine input.

BKV DNA a	No. of Valid	No. of Detected	Detection Rate
(IU/mL)	Replicates	Replicates	(%)
330.00	29	29	100.0
300.00	30	30	100.0
75.00	30	30	100.0
60.00	30	30	100.0
45.00	30	30	100.0
22.50	30	29	96.7
11.25	30	28	93.3
5.63	30	19	63.3
2.81	30	14	46.7

Table 17. Alinity m BKV LoD in Urine. Lot 2 (Least Sensitive Lot)

ª Urine samples tested stabilized in transport buffer. BKV concentration based on neat urine input.

Table 18. Alinity m BKV LoD in Urine, Lot 3
BKV DNA ª
(IU/mL)	No. of Valid
Replicates	No. of Detected
Replicates	Detection Rate
(%)
330.00	30	30	100.0
300.00	30	30	100.0
75.00	30	30	100.0
60.00	30	30	100.0
45.00	30	30	100.0
22.50	29	27	93.1
11.25	29	28	96.6
5.63	30	24	80.0
2.81	29	14	48.3

4 Urine samples tested stabilized in transport buffer. BKV concentration based on neat urine input.

Limit of Detection for Genotypes 1.8.1.3.2

BKV armored DNA for subgroup Ic and subtype II and clinical specimens for BKV subgroup Ia and subtypes III and IV were diluted to 5 different concentrations in BKVnegative stabilized urine. Testing was performed using one lot of amplification reagents across multiple days. The results, representative of the analytical sensitivity performance of Alinity m BKV for BKV subgroups Ia and Ic and subtypes II, III, and IV, are

summarized in Table 19 for urine. Alinity m BKV detected 95% or greater of BKV samples at and above 45 IU/mL (1.65 Log IU/mL) in urine. These results demonstrate the ability of Alinity m BKV to detect BKV subgroups Ia and Ic and subtypes II, III, and IV at the claimed LoD in urine.

Table 19. Alinity m BKV LoD for Genotypes in Urine
Genotype	BKV DNA
(IU/mL)	No. of Valid
Replicates	No. of
Detected Replicates	Detection
Rate (%)
Subgroup Ia	330	30	30	100.0
	300	30	30	100.0
	90	30	30	100.0
	75	29	29	100.0
	45	30	30	100.0
Subgroup Ic	330	30	30	100.0
	300	29	29	100.0
	90	30	30	100.0
	75	30	30	100.0
	45	29	29	100.0
Subtype II	330	30	30	100.0
	300	30	30	100.0
	90	30	30	100.0
	75	30	30	100.0
	45	30	30	100.0
Subtype III	330	30	30	100.0
	300	30	30	100.0
	90	29	29	100.0
	75	30	30	100.0
	45	30	30	100.0
Subtype IV	330	30	30	100.0
	300	30	30	100.0
	90	30	30	100.0
	75	29	29	100.0
	45	30	30	100.0

1.8.1.3.3 Linear Range

The quantitation range of Alinity m BKV for urine is from the lower limit of quantitation (LLoQ) of 50 IU/mL (1.70 Log IU/mL) to the upper limit of quantitation (ULoQ) of 1,000,000,000 IU/mL (9.00 Log IU/mL). Linearity of Alinity m BKV was assessed by testing a dilution series of BKV subgroup Ib in

BKV-negative stabilized urine, consisting of 16 panel levels targeted in the range of 30 IU/mL to 3,000,000,000 IU/mL (1.48 Log IU/mL to 9.48 Log IU/mL).

Urine panel was prepared either using the 1st WHO International Standard for BK virus (NIBSC code: 14/212, subgroup Ib) for multiple levels ranging from 30 IU/mL to 150,000 IU/mL (1.48 Log IU/mL to 5.18 Log IU/mL) or using armored DNA for the remaining levels ranging from 150 IU/mL to 3,000,000,000 IU/mL (2.18 Log IU/mL to 9.48 Log IU/mL).

Alinity m BKV was linear across the quantitation range from 50 IU/mL (1.70 Log IU/mL) to 1,000,000,000 IU/mL (9.00 Log IU/mL). Representative results for Alinity m BKV linearity performance are shown in Figure 4.

Image /page/32/Figure/3 description: The image is a graph titled "Figure 4. Alinity m BKV Linearity in Urine". The graph plots "Alinity m BKV (Log IU/mL)" on the y-axis versus "Expected Concentration (Log IU/mL)" on the x-axis. The data points form a linear relationship, and the correlation coefficient, r, is equal to 1.000.

ª Note: The markers in the plot represent the mean Alinity m BKV concentration (in Log IU/mL) for each panel level.

1.8.1.3.4 Linearity for Genotypes

Linearity of Alinity m BKV for subgroups/subtypes Ia, Ic, II, III, and IV was confirmed by testing a dilution series in BKV-negative stabilized urine, consisting of 14 panel levels for subgroup/subtypes Ia. III, and IV and 13 panel levels for subgroup/subtype Ic and II,

targeted in the range of 30 IU/mL to 3,000,000,000 IU/mL (1.48 Log IU/mL to 9.48 Log IU/mL).

For subgroup/subtypes Ia, III, and IV, urine panel was prepared either using clinical specimens for multiple levels ranging from 30 IU/mL to 150,000 IU/mL (1.48 Log IU/mL to 5.18 Log IU/mL) or using armored DNA for the remaining levels ranging from 300 IU/mL to 3,000,000,000 IU/mL (2.48 Log IU/mL to 9.48 Log IU/mL). For subgroup/subtype Ic and II, urine panel was prepared using armored DNA for all levels ranging from 30 IU/mL to 3,000,000,000 IU/mL (1.48 Log IU/mL to 9.48 Log IU/mL).

Alinity m BKV was linear in urine across the quantitation range from 50 IU/mL (1.70 Log IU/mL) to 1,000,000,000 IU/mL (9.00 Log IU/mL) for subgroups/subtypes Ia, Ic, II, III, and IV. Representative results for Alinity m BKV linearity performance for subgroups/subtypes Ia, Ic, II, III, and IV, along with results for subgroup Ib (Section 1.7.1.3.3), are shown in Figure 5.

Image /page/33/Figure/3 description: The image is a graph titled "Figure 5. Alinity m BKV Linearity for Genotypes in Urine." The graph plots expected concentration (Log IU/mL) on the x-axis and Alinity m BKV (Log IU/mL) on the y-axis, ranging from 0 to 10. There are six lines on the graph, labeled Ia, Ib, Ic, II, III, and IV, each representing a different genotype. The lines show a linear relationship between the expected concentration and the measured concentration for each genotype.

a Note: The markers in the plot represent the mean Alinity m BKV concentration (in Log IU/mL) for each panel level.

1.8.1.3.5 Precision

Precision of Alinity m BKV was determined by analyzing an 8-member panel in BKV-negative stabilized human urine. All panel members were prepared using clinical specimens. Each panel member was tested in 4 replicates, twice each day for 12 days, on 3 Alinity m Systems operated by 3 operator per instrument), using 3 AMP kit lots (one lot per instrument), for a total of 288 replicates per panel member.

The representative precision results in Table 21 demonstrated that Alinity m BKV within-laboratory standard deviation (SD) in urine was less than or equal to 0.25 Log IU/mL for BKV DNA panels within the range of 2.70 Log IU/mL to 9.00 Log IU/mL (500 IU/mL to 1,000,000 IU/mL) and less than or equal to 0.50 Log IU/mL for BKV DNA panels within the range of 1.70 Log IU/mL to less than 2.70 Log IU/mL to less than 500 IU/mL).

Table 20. Alinity m BKV Precision in Urine (Log IU/mL)
Panel
Member	Na	Mean
Concentration
(Log IU/mL)	Within-Run		Between-Run		Between-Day		Within-
Laboratoryb		Between-
Instrumentc		Totald
			SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
08	287	8.23	0.051	0.6	0.033	0.4	0.000	0.0	0.060	0.7	0.041	0.5	0.073	0.9
07	287	6.19	0.056	0.9	0.031	0.5	0.000	0.0	0.064	1.0	0.021	0.3	0.067	1.1
06	283	5.11	0.077	1.5	0.037	0.7	0.021	0.4	0.088	1.7	0.009	0.2	0.088	1.7
05	284	4.11	0.066	1.6	0.028	0.7	0.030	0.7	0.078	1.9	0.000	0.0	0.078	1.9
04	283	3.05	0.088	2.9	0.043	1.4	0.015	0.5	0.099	3.3	0.000	0.0	0.099	3.3
03	285	2.53	0.081	3.2	0.039	1.6	0.029	1.1	0.094	3.7	0.001	0.1	0.094	3.7
02	177	1.83	0.085	4.6	0.027	1.5	0.019	1.0	0.091	5.0	0.021	1.1	0.093	5.1
01	54	1.79	0.054	3.0	0.040	2.2	0.000	0.0	0.067	3.8	0.000	0.0	0.067	3.8

ª Valid replicates within the quantitation range.

6 Within-Laboratory includes Within-Run, Between-Run, and Between-Day Components.

6 Alinity m System (Instrument), AMP Kit lot, and Operator are confounding effect is represented by Between-Instrument Component.

d Total includes Within-Run, Between-Run, Between-Day, and Between-Instrument Components.

| Panel
Member | Na | Mean
Concentrationb
(IU/mL) | %CVc | | | | |
|-----------------|-----|-----------------------------------|------------|-------------|-------------|-------------------------|--------|
| | | | Within-Run | Between-Run | Between-Day | Between-
Instrumentd | Totale |
| 08 | 287 | 170,547,602 | 11.7 | 7.5 | 0.0 | 9.6 | 17.0 |
| 07 | 287 | 1,572,305 | 12.8 | 7.2 | 0.0 | 4.8 | 15.5 |
| 06 | 283 | 131,873 | 17.9 | 8.5 | 4.8 | 2.1 | 20.6 |
| 05 | 284 | 13,156 | 15.2 | 6.5 | 6.9 | 0.0 | 18.0 |
| 04 | 283 | 1,160 | 20.5 | 9.9 | 3.5 | 0.0 | 23.2 |
| 03 | 285 | 348 | 18.8 | 9.1 | 6.6 | 0.3 | 22.0 |
| 02 | 177 | 69 | 19.7 | 6.1 | 4.3 | 4.8 | 21.7 |
| 01 | 54 | 62 | 12.5 | 9.2 | 0.0 | 0.0 | 15.5 |

ª Valid replicates within the quantitation range.

' Titer data are considered to be log-normal tite mean values for log-normal titer data are calculated as exp(mean*hr(10) + [SD'm(10]) '22). "Titer data are considered to be log-normally distributed and the %CV values for log-normal titer data are calculated as sqr(10°[SD^2 * In(10] – I) * 100.

4 Alinity m System (Instrument), AMP Kit lot, and Operator are confounding effect is represented by Between-Instrument Compons. CTotal includes Within-Run, Between-Run, Between-Day, and Between-Instrument Components.

ob.TANIT.Comments (x) 0 (x) 0 (x) 0 (x) 0 ) 5 1 00 S. 1 26 (x) 0 0 x 1 x 1 0 x 1 x 1 x 2 x 4 x 1 x 2 x 4 x 1 x 2 x 4 x 1 x 2 x 4 x 1 x 2 x 4 x 2 x 4 x 2 x 4 x 2 x 4 x 2 x 4 x

1.8.1.3.6 Lower Limit of Quantitation (LLoQ)

The LLoO is defined as the lowest concentration at which BKV QNA is reliably quantitated within an acceptable total error of ≤ 1.00 Log IU/mL. Total error was estimated for detected urine samples from the LoD study by 2 methods:

Total Analytical Error (TAE) = |bias| + 2 × SD, and .
Total Error (TE) = SQRT(2) × 2 × SD ●

The results of the calculations are shown in Table 22.

Panel members were dilutions of the 1* WHO International Standard for BK Virus (NIBSC code: 14/212, subgroup Ib) prepared in BKV-negative urine stabilized in transport buffer (Alinity m Urine Transport Kit).

The results of these analyses support a claimed LLoQ for Alinity m BKV of 50 IU/mL (1.70 Log IU/mL) in urine, with an acceptable level of accuracy and precision (ie, TAE and TE less than or equal to 1.00 Log IU/mL).

Table 22. TAE and TE for Urine
Target
Concentration
(Log IU/mL)	Mean
Concentration
(Log IU/mL)	Biasa
(Log IU/mL)	SD
(Log IU/mL)	TAE
(Log IU/mL)	TE
(Log IU/mL)
1.35	1.39	0.04	0.25	0.54	0.70
1.65	1.70	0.05	0.18	0.40	0.50
1.78	1.84	0.06	0.14	0.34	0.41

ª Bias = Mean Concentration - Target Concentration

1.8.1.3.7 Analytical Specificity - Potential Cross-Reactants

The analytical specificity of Alinity m BKV was evaluated with a panel of microorganisms (Table 23) in BKV-negative unine, positive urine targeted to 150 IU/mL BKV DNA, and positive urine targeted to 1,000,000 IU/mL BKV DNA. Microorganisms were tested at final concentrations of at least 10 Units/mL for viruses and fungi or at least 10% Units/mL for bacteria and protozoa. No cross-reactivity or interference in the Alinity m BKV assay was observed in the presence of the tested microorganisms.

Table 23. Microorganisms Tested in Urine

Bacteria
Bacillus cereus	Lactobacillus acidophilus	Staphylococcus aureus
Bacillus subtilis	Lactobacillus crispatus	Staphylococcus epidermidis
Chlamydia trachomatis	Lactobacillus jensenii	Staphylococcus saprophyticus
Corynebacterium diphtheriae	Lactobacillus vaginalis	Streptococcus agalactiae
Enterobacter cloacae	Morganella morganii	Streptococcus bovis
Enterococcus faecalis	Mycoplasma genitalium	Streptococcus oralis/viridans
Enterococcus faecium	Neisseria gonorrhoeae	Streptococcus pneumoniae
Escherichia coli	Proteus mirabilis	Treponema palliduma
Klebsiella pneumoniae	Pseudomonas aeruginosa	Ureaplasma urealyticum
Fungi	Viruses	Protozoa
Candida albicans	Herpes Simplex Virus-2 (HSV-2)	Trichomonas vaginalis
Candida glabrata	Human Papillomavirus 16 (HPV-16)
Candida parapsilosis

Candida tropicalis

a T. pallidum was not a whole organism and was only attainable as synthetic partial genome

Analytical Specificity - Potentially Interfering Substances 1.8.1.3.8

The effects of endogenous substances and the presence of high levels of therapeutic drugs commonly prescribed in transplant patients were evaluated. Potential interference on Alinity m BKV performance in urine was assessed by testing a minimum of 8 samples at each BKV DNA level: negative, 150 IU/mL, and 1,000,000 IU/mL. No interference was observed in the presence of albumin (90 mg/mL), conjugated bilirubin (1000 mg/dL), glucose (1500 mg/dL), mucus (0.4% w/v), acidic pH (pH 4.0), basic pH (pH 9.0), semen (5.0% v/v), whole blood (10% v/v), sodium (450 mEq/L) or peripheral blood mononuclear cells (PBMCs) (1 × 10° cells/mL) that were introduced in the sample. Interference was observed with mucus at >0.4% w/v and with PBMCs at >1 × 105 cells/mL.

No interference was observed in the presence of drug compounds tested in pools or individually at the concentrations shown

Drug Pool	Drug Compound	Tested Concentration
1	Metronidazole	1079 μmol/L
	Phenazopyridine Hydrochloride	300 µg/mL
	Acetaminophen	1986 μmol/L
	Acetylsalicylic Acid (Aspirin)	5.43 mmol/L
	Naproxen	3255 μmol/L
	Ibuprofen	3638 μmol/L
	Talc	0.15% w/v
2	Clotrimazole	150 µg/mL
3	Propylene Glycol	1500 µg/mL
4	Beta Estradiol	6.62 nmol/L
5	Abacavir sulfate	0.014 mg/mL
	Amoxicillin	0.905 mg/mL
	Atenolol	0.050 mg/mL
	Azathioprine	0.337 mg/mL
	Cefotetan	5.36 mg/mL
	Cyclosporine	0.0002 mg/mL
	Everolimus	0.001 mg/mL

Drug Pool	Drug Compound	Tested Concentration
5 (continued)	Ganciclovir	0.137 mg/mL
	Leflunomide	0.1 mg/mL
	Micafungin	0.002 mg/mL
	Sirolimus	0.000088 mg/mL
	Sulfamethoxazole	2.88 mg/mL
	Tacrolimus	0.0003 mg/mL
	Trimethoprim	1.152 mg/mL
	Valacyclovir	4.095 mg/mL
	Valganciclovir HCl	0.1365 mg/mL
	Vancomycin	3 mg/mL
6	Cidofovir	6.75 mg/mL
	Fluconazole	2.24 mg/mL
	Piperacillin	19.20 mg/mL
	Tazobactam sodium	2.4 mg/mL
7	Clavulanate potassium	0.0343 mg/mL
	Foscarnet	12.83 mg/mL
8	Letermovir	0.019 mg/mL

Table 24, Drug Compounds Tested in Urine

1.8.1.3.1 Carryover in Urine

The carryover rate for Alinity m BKV urine protocol was determined by analyzing 360 valid replicates of BKV-negative samples processed from alternating positions with 360 valid replicates of high concentrated BKV-positive stabilized urine samples targeted at 1,500,000,000 IU/mL, across a total of 15 runs (15 AMP Trays). BKV DNA was not detected in any of the BKV-negative samples, resulting in an overall carryover rate of 0.0% (95% CI: 0.0% to 1.1%).

1.8.2 Clinical Performance Characteristics

Clinical Reproducibility for Plasma Sample Type 1.8.2.1

Reproducibility performance of Alinity m BKV was evaluated by testing a 9-member reproducibility panel, including 8 positive panel members and 1 negative panel members were prepared using a BKV positive clinical specimen or cultured virus diluted in human EDTA plasma. A total of 3 Alinity m BKV AMP Kit lots, 3 Alinity m BKV CAL Kit lots, 3 Alinity m BKV CTRL Kit lots, and 3 Alinity m Sample Prep Kit 2 lots were used. Three clinical sites each tested 2 Alinity m BKV AMP Kit lots on 5 non-consecutive days for each lot. Six replicates of each panel member were tested on each of the 5 days. Each of the 3 clinical sites used different lots of Alinity m BKV CTRL Kit, and Alinity m Sample Prep Kit 2. The reproducibility results are summarized in Table 26 (for the positive panel members) and Table 27 (for the negative panel member).

Table 25. Reproducibility for Positive Panel Members – EDTA Plasma (Log IU/mL)
Panel
Member	Na	Mean
Concentration
(Log IU/mL)	Within-
Run/Day		Between-
Run/Day		Within-
Laboratoryc		Between-Lot		Between-Site/
Instrument		Totald
			SDb	%CV	SDb	%CV	SDb	%CV	SDb	%CV	SDb	%CV	SDb	%CV
1	178	8.13	0.06	0.7	0.03	0.3	0.06	0.8	0.07	0.9	0.00	0.0	0.09	1.2
2	180	7.40	0.05	0.7	0.02	0.3	0.06	0.8	0.08	1.1	0.00	0.0	0.10	1.3
3	177	5.87	0.06	1.0	0.03	0.5	0.07	1.1	0.05	0.8	0.00	0.0	0.08	1.4
4	179	4.91	0.06	1.2	0.02	0.5	0.07	1.3	0.03	0.6	0.00	0.0	0.07	1.5
5	178	3.94	0.07	1.7	0.06	1.4	0.09	2.2	0.01	0.3	0.06	1.5	0.11	2.7
6	178	3.03	0.09	2.9	0.03	0.8	0.09	3.0	0.02	0.6	0.06	2.1	0.11	3.7
7	167	1.95	0.11	5.5	0.05	2.5	0.12	6.1	0.00	0.0	0.06	3.1	0.13	6.8
8	47	1.77	0.07	4.2	0.00	0.0	0.07	4.2	0.02	0.9	0.02	1.2	0.08	4.4

a Number of valid replicates within the quantitation range.

Standard deviations (SD) are in Log IU/mL.

6 Within-Laboratory includes Within-Run/Day and Between-Run/Day Components.

d Total includes Within-Run/Day, Between-Run/Day, Between-Site/Instrument Components.

| Panel
Member | Na | Mean
Concentrationb
(IU/mL) | %CVc | | | | |
|-----------------|-----|-----------------------------------|--------------------|---------------------|-------------|-----------------------------|-------|
| | | | Within-
Run/Day | Between-
Run/Day | Between-Lot | Between-Site/
Instrument | Total |
| 1 | 178 | 138,532,920 | 12.8 | 6.2 | 16.4 | 0.0 | 21.8 |
| 2 | 180 | 25,521,653 | 12.2 | 4.8 | 18.2 | 0.0 | 22.6 |
| 3 | 177 | 759,793 | 13.5 | 6.6 | 11.5 | 0.0 | 19.1 |
| 4 | 179 | 82,823 | 14.1 | 5.7 | 6.4 | 0.0 | 16.5 |
| 5 | 178 | 9,024 | 15.6 | 13.0 | 2.8 | 13.7 | 24.9 |
| 6 | 178 | 1,103 | 20.2 | 5.9 | 4.3 | 14.6 | 26.2 |
| 7 | 167 | 94 | 25.2 | 11.3 | 0.0 | 14.2 | 31.4 |
| 8 | 47 | 60 | 17.1 | 0.0 | 3.6 | 5.1 | 18.3 |

Table 26. Reproducibility for Positive Panel Members – EDTA Plasma (IU/mL)

ª Number of valid replicates within the quantitation range.

' Titer data are considered to be log-normaly distributed and the mean values for log-normal titer data are calculated as exp(mean*ht(10) + [SD'm(10]) '22). STiter data are considered to be log-normally distributed and the %CV values for log-normal titer data are calculated as sqr(10°[SD^2 * In(10] – 1) * 100.

d Total includes Within-Run/Day, Between-Run/Day, Between-Reagent Lot,, and Between-Site/Instrument Components.

Table 27. Reproducibility for Negative Panel Member – EDTA Plasma
Expected BKV DNA
Concentration	No. of Replicates
Total	Negative	Negative Rate (%)	95% Confidence Interval
Negative	176	176	100.0 % (176/176)	(97.9%, 100.0%)

ປະ 10 8E ອອນຈາ

1.8.2.2 Clinical Reproducibility for Urine Sample Type

Reproducibility performance of Alinity m BKV was evaluated by testing a 9-member reproducibility panel, including 8 positive panel members and 1 negative panel member in urine stabilized in transport buffer (Alinity m Urine Transport Kit). The positive panel members were prepared using a BKV positive clinical specimen, cultured virus, or plasmid DNA diluted with urine stabilized in transport buffer. A total of 3 Alinity m BKV AMP Kit lots, 3 Alinity m BKV CAL Kit lots, 3 Alinity m BKV CTRL Kit lots, and 3 Alinity m Sample Prep Kit 2 lots were used. Three clinical sites each tested 2 Alinity m BKV AMP Kit lots on 5 non-consecutive days for each lot. Six replicates of each panel member were tested on each of the 3 clinical sites used different lots of Alinity m BKV CAL Kit, Alinity m BKV CTRL Kit, and Alinity m Sample Prep Kit 2. The reproducibility results are summarized in Table 28 and Table 29 (for the positive panel members) and Table 30 (for the negative panel member).

| Panel
Member | Na | Mean
Concentration
(Log IU/mL) | Within-
Run/Day | | Between-
Run/Day | | Within-
Laboratoryc | | Between-Lot | | Between-Site/
Instrument | | Totald | |
|-----------------|-----|--------------------------------------|--------------------|------|---------------------|-----|------------------------|------|-------------|-----|-----------------------------|-----|--------|------|
| | | | SDb | %CV | SDb | %CV | SDb | %CV | SDb | %CV | SDb | %CV | SDb | %CV |
| 1 | 178 | 8.69 | 0.05 | 0.5 | 0.02 | 0.3 | 0.05 | 0.6 | 0.01 | 0.1 | 0.11 | 1.3 | 0.12 | 1.4 |
| 2 | 180 | 7.29 | 0.05 | 0.7 | 0.02 | 0.3 | 0.06 | 0.8 | 0.02 | 0.3 | 0.08 | 1.1 | 0.10 | 1.4 |
| 3 | 179 | 5.91 | 0.05 | 0.9 | 0.02 | 0.4 | 0.06 | 1.0 | 0.01 | 0.2 | 0.06 | 1.0 | 0.08 | 1.4 |
| 4 | 178 | 5.45 | 0.06 | 1.1 | 0.04 | 0.7 | 0.07 | 1.3 | 0.01 | 0.3 | 0.07 | 1.3 | 0.10 | 1.9 |
| 5 | 177 | 4.47 | 0.06 | 1.4 | 0.03 | 0.8 | 0.07 | 1.6 | 0.04 | 0.8 | 0.07 | 1.6 | 0.11 | 2.4 |
| 6 | 179 | 3.00 | 0.17 | 5.6 | 0.05 | 1.7 | 0.18 | 5.9 | 0.00 | 0.0 | 0.04 | 1.3 | 0.18 | 6.0 |
| 7 | 175 | 2.29 | 0.08 | 3.6 | 0.02 | 1.0 | 0.08 | 3.7 | 0.01 | 0.6 | 0.06 | 2.4 | 0.10 | 4.4 |
| 8 | 169 | 1.95 | 0.23 | 11.6 | 0.00 | 0.0 | 0.23 | 11.6 | 0.03 | 1.7 | 0.00 | 0.0 | 0.23 | 11.7 |

a Number of valid replicates within the quantitation range.

b Standard deviations (SD) are in Log IU/mL.

& Within-Laboratory includes Within-Run/Day and Between-Run/Day Components.

d Total includes Within-Run/Day, Between-Run/Day, Between-Site/Instrument Components.

| Panel
Member | Na | Mean
Concentrationb
(IU/mL) | %CVc | | | | |
|-----------------|-----|-----------------------------------|--------------------|---------------------|-------------|-----------------------------|--------|
| | | | Within-
Run/Day | Between-
Run/Day | Between-Lot | Between-Site/
Instrument | Totald |
| 1 | 178 | 512,317,248 | 10.9 | 5.5 | 1.3 | 26.3 | 29.2 |
| 2 | 180 | 20,177,082 | 11.8 | 5.3 | 5.0 | 18.3 | 23.1 |
| 3 | 179 | 828,919 | 12.4 | 5.5 | 2.1 | 13.1 | 19.0 |
| 4 | 178 | 291,864 | 13.8 | 8.9 | 3.4 | 17.0 | 24.0 |
| 5 | 177 | 30,237 | 14.9 | 8.0 | 8.2 | 16.0 | 25.0 |
| 6 | 179 | 1,090 | 40.3 | 11.7 | 0.0 | 9.2 | 43.4 |
| 7 | 175 | 202 | 18.9 | 5.2 | 3.0 | 12.8 | 23.8 |
| 8 | 169 | 102 | 55.5 | 0.0 | 7.8 | 0.0 | 56.2 |

ª Number of valid replicates within the quantitation range.

d Total includes Within-Run/Day, Between-Run/Day, Between-Reagent Lot,, and Between-Site/Instrument Components.

Table 30. Reproducibility for Negative Panel Member – Urine
		No. of Replicates
Expected BKV DNA
Concentration	Total	Negative	Negative Rate (%)	95% Confidence Interval
Negative	174	173	99.4% (173/174)	(96.8%, 99.9%)

បែប (0 0+ ១១៩៨

1.8.2.3 Clinical Performance for Plasma Sample Type

Almity m BKV results were compared to those of an FDA-cleared BKV nucleic acid test in a representative study. A total of 579 EDTA plasma clinical specimens (555 neat and 24 diluted clinical specimens from 556 subjects) collected from solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) subjects were included in the analysis. The Alinity m BKV assay testing was performed at 4 clinical testing sites with 4 Alinity m BKV reagent lots. The agreement between Alinity m BKV and comparator results is shown in Table 31.

	Comparator BKV (Log IU/mL)
Alinity m BKV (Log IU/mL)	Target not detected (TND)

Intended Use / Indications for Use

Product codes (comma separated list FDA assigned to the subject device)

Device Description

Mentions image processing

Mentions AI, DNN, or ML

Input Imaging Modality

Anatomical Site

Indicated Patient Age Range

Intended User / Care Setting

Description of the training set, sample size, data source, and annotation protocol

Description of the test set, sample size, data source, and annotation protocol

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

§ 866.3183 Quantitative viral nucleic acid test for transplant patient management.

MARIA I. GARCIA -S

Indications for Use

Indications for Use (Describe)

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510(k) Summary

Table of Contents

1.0 510(k) Summary

1.1 Submitter

1.2 Device Information

1.3 Predicate Device

1.4 Device Description

1.5 Intended Use

Alinity m BKV AMP Kit:

Alinity m Urine Transport Kit:

Similarities and Differences to Predicate Devices 1.6

1.7 Results and Interpretation

1.8 Performance Data

1.8.1 Specific Performance Characteristics

1.8.1.1 Traceability to the WHO Standard

Figure 1. Traceability to the WHO Standard

1.8.1.2 Performance Characteristics for Plasma Sample Type

Limit of Detection 1.8.1.2.1

1.8.1.2.2 Limit of Detection for Genotypes

1.8.1.2.3 Linear Range

1.8.1.2.4 Linearity for Genotypes

1.8.1.2.5 Precision

1.8.1.2.6 Lower Limit of Quantitation (LLoQ)

1.8.1.2.7 Alinity m BKV Plasma Testing Using Dilution Procedure

1.8.1.2.8 Precision of Alinity m BKV Plasma Testing Using Dilution Procedure

Table 12. Precision of Alinity m BKV EDTA Plasma Testing Using Dilution Procedure (IU/mL)

1.8.1.2.9 Confirmation of LLoQ Using Plasma Dilution Procedure

1.8.1.2.10 Analytical Specificity - Potential Cross-Reactants

Table 14. Microorganisms Tested in Plasma

Analytical Specificity - Potentially Interfering Substances 1.8.1.2.11

Carryover in Plasma 1.8.1.2.12

1.8.1.3 Performance Characteristics for Urine Sample Type

1.8.1.3.1 Limit of Detection

Limit of Detection for Genotypes 1.8.1.3.2

1.8.1.3.3 Linear Range

1.8.1.3.4 Linearity for Genotypes

1.8.1.3.5 Precision

1.8.1.3.6 Lower Limit of Quantitation (LLoQ)

1.8.1.3.7 Analytical Specificity - Potential Cross-Reactants

Analytical Specificity - Potentially Interfering Substances 1.8.1.3.8

Table 24, Drug Compounds Tested in Urine

1.8.1.3.1 Carryover in Urine

1.8.2 Clinical Performance Characteristics

Clinical Reproducibility for Plasma Sample Type 1.8.2.1

1.8.2.2 Clinical Reproducibility for Urine Sample Type

1.8.2.3 Clinical Performance for Plasma Sample Type