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The Alinity m CMV assay is an in vitro polymerase chain reaction (PCR) assay for use with the automated Alinity m System to quantitate cytomegalovirus (CMV) DNA in human EDTA plasma. The Alinity m CMV assay is intended for use as an aid in the management of Hematopoietic Stem Cell Transplant and Solid Organ Transplant patients who are undergoing anti-cytomegalovirus therapy. The Alinity m CMV assay can be used to assess virological response to anti-cytomegalovirus therapy.

The results from the Alinity m CMV test must be interpreted within the context of all relevant clinical and laboratory findings. The Alinity m CMV test is not intended as a screening test for the presence of CMV DNA in blood or blood products.

Alinity m CMV is an in vitro polymerase chain reaction (PCR) assay for the quantitation of CMV DNA in human EDTA plasma.

This device is similar to the predicate device originally approved (PMA P210022) with the exception that the subject device may use a new DNA Polymerase as an alternative to original DNA Polymerase in the reagent formulation of the assay. This formulation difference does not introduce any changes to sample processing, assay procedure, or data reduction.

Additional studies were initiated to support the formulation of the assay with alternative DNA Polymerase. Supplemental data from these studies were used with data previously obtained from the analytical and clinical testing studies submitted in P210022.

The steps of the Alinity m CMV consist of sample preparation, real-time PCR assembly, amplification/detection, result calculation, and reporting. All stages of the Alinity m CMV procedure are executed automatically by the Alinity m System. Manual dilutions may be performed for low-volume specimens to meet the minimum volume requirement.

The Alinity m System is designed to be a random-access analyzer that can perform the Alinity m CMV assay in parallel with other Alinity m assays on the same instrument.

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

• Alinity m CMV AMP Kit (List No. 09N46-095), consisting of 2 types of multi-well assay trays. The amplification trays (AMP TRAY 1) contain lyophilized, unit-dose PCR amplification/detection reagents and lyophilized, unit-dose IC in separate wells, and the activation trays (ACT TRAY 2) contain liquid unit-dose activation reagent. The intended storage condition for the Alinity m CMV AMP Kit is 2°C to 8°C.

• Alinity m CMV CTRL Kit (List No. 09N46-085), 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 CMV CTRL Kit is –25°C to –15°C.

• Alinity m CMV CAL Kit (List No. 09N46-075), consisting of 2 calibrator levels, each supplied as liquid in single-use tubes. The intended storage condition for the Alinity m CMV CAL Kit is –25°C to –15°C.

CMV DNA from human plasma is extracted automatically on-board in 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 nucleic acids are then combined with liquid unit-dose Alinity m CMV activation reagent and lyophilized unit-dose Alinity m CMV 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 CMV targets.

At the beginning of the Alinity m CMV sample preparation process, a lyophilized unit-dose IC on the AMP Tray is rehydrated 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 CMV amplification/detection reagents consist of enzymes, primers, probes, and activation reagents that enable polymerization and detection.

A CMV calibration curve is required for determination of CMV DNA concentration. Two levels of calibrators are processed through sample preparation and PCR to generate the calibration curve. The concentration of CMV 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 CMV assay also utilizes the following:

• Alinity m CMV Application Specification File, (List No. 09N46-05B)
• Alinity m System and System Software (List No. 08N53)
• 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):
  • Alinity m Lysis Solution (List No. 09N20-001)
  • Alinity m Diluent Solution (List No. 09N20-003)
  • 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)
  • Alinity m Transport Tubes Pierceable Capped (List No. 09N49-010)
  • Alinity m Transport Tube (List No. 09N49-011)
  • Alinity m Pierceable Cap (List No. 09N49-012)
  • Alinity m Aliquot Tube (List No. 09N49-013)

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided FDA 510(k) clearance letter for the Alinity m CMV assay:

The core of this submission is to demonstrate that a new formulation of the Alinity m CMV assay (using an "alternative DNA Polymerase") is substantially equivalent to the previously FDA-approved Alinity m CMV assay (using the "original DNA Polymerase"). Therefore, the acceptance criteria for the new formulation are implicitly that its performance characteristics (LoD, Linearity, Precision, Reproducibility, Method Comparison) are comparable to, and meet the established claims of, the original predicate device.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a submission demonstrating equivalence to an already approved device, the acceptance criteria are not explicitly stated as pass/fail thresholds in this document, but rather as meeting or being comparable to the performance of the predicate device (P210022). The reported performance shows that the new formulation did meet these implicit criteria.

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

The "test set" in this context refers to the samples used to evaluate the performance of the new formulation (alternative DNA Polymerase) against the established performance of the original formulation.

• Limit of Detection (LoD): 192 total replicates at 30 IU/mL (96 for Lot 1, 48 for Lot 2, 48 for Lot 3). CMV negative human plasma used as diluent.
• Linear Range: 17 panel members tested. Panel members were prepared from dilution of the 1st WHO International Standard, cultured virus, or clinical specimens.
• Precision: 8 panel members, 270 replicates per panel member (3 lots x 3 replicates x 2 runs/day x 15 days). Panel members prepared from CMV positive specimen, cultured virus, or CMV plasmid DNA diluted in human EDTA plasma.
• Lower Limit of Quantitation (LLoQ): Data from the LoD study was used. (Therefore, 192 replicates at 30 IU/mL etc. as per LoD). Prepared from 1st WHO International Standard diluted in CMV-negative plasma.
• Reproducibility: 9-member panel (8 positive, 1 negative). Tested at 3 clinical sites, over 5 non-consecutive days with 2 runs per day. 4 replicates of each panel member per day/run.
  • Positive Control: 111-119 total replicates per panel member.
  • Negative Control: 119 total replicates.
  • Panel members were prepared by spiking clinical specimen, cultured virus, or plasmid DNA into normal CMV negative K2EDTA plasma.
• Method Comparison: 141 samples. Source of these samples is not explicitly stated as clinical or contrived, but they are "samples with results that were within the common quantitation range of both [...] assays".

Data Provenance:

• The document implies the studies are part of the 510(k) submission, generally meaning prospective testing performed by the manufacturer.
• Country of Origin: Not explicitly stated for patient/specimen samples, but the study was conducted by Abbott Molecular Inc. in Des Plaines, Illinois, USA. The "3 clinical sites" for reproducibility are not named or localized.
• Retrospective or Prospective: All listed performance studies appear to be prospective analytical studies specifically designed to characterize the performance of the revised device. The P210022 PMA submission (predicate device) would have contained the primary clinical data, but this 510(k) focuses on analytical equivalence.

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

This device is an IVD (in vitro diagnostic) test for quantitating CMV DNA. The "ground truth" for quantitative nucleic acid tests is typically established using:

• Reference Materials: The 1st World Health Organization (WHO) International Standard for Human Cytomegalovirus for Nucleic Acid Amplification Techniques (NIBSC code 09/162) is repeatedly mentioned as the basis for quantitation and traceability. This is a highly standardized and globally recognized reference material, not expert consensus on individual patient samples.
• Analytical Methods: Dilutions of known concentrations (plasmids, cultured virus, clinical specimens) are used.

Therefore, for this type of quantitative IVD, the ground truth is established through analytical traceability to a well-characterized international standard and precise laboratory dilution/preparation methods, rather than by human rater consensus on individual cases. No human experts are reported as being used to establish a "ground truth" for the test set in the way a radiologist would for image analysis.

4. Adjudication Method for the Test Set

As the ground truth is established by analytical methods and reference standards, no adjudication method (like 2+1, 3+1) is relevant or mentioned for establishing the truth of the samples themselves. The studies measure the device's ability to consistently and accurately quantify CMV DNA relative to these known standards.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done

No MRMC comparative effectiveness study was done or is relevant for this device.

• This device is an in vitro diagnostic (IVD) assay, specifically a quantitative PCR test, not an AI-assisted diagnostic imaging tool.
• It provides a numerical output (CMV DNA concentration), not an interpretation that human readers would directly assist with or benefit from AI assistance.
• Therefore, the concept of "how much human readers improve with AI vs. without AI assistance" does not apply here.

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

This question is more applicable to AI/ML software as a medical device (SaMD). For a quantitative PCR assay:

• The device (Alinity m CMV) measures the quantity of CMV DNA independently and automatically on the Alinity m System.
• Its performance characteristics (LoD, linearity, precision, reproducibility) are inherently standalone (algorithm/device-only) measurements of its analytical capabilities, without human intervention in the result generation or analysis itself.
• Human interaction is primarily in sample loading, result review, and clinical interpretation in conjunction with other patient factors.

7. The Type of Ground Truth Used

The ground truth used for these analytical performance studies is based on:

• Reference Standards: Specifically, the 1st World Health Organization (WHO) International Standard for Human Cytomegalovirus for Nucleic Acid Amplification Techniques (NIBSC code 09/162).
• Contrived Samples: Highly characterized and precisely diluted samples using CMV positive clinical specimens, cultured virus, and plasmid DNA. The concentration of these contrived samples is "known" based on their preparation traceable to the WHO standard.

This is an analytical ground truth, not a clinical ground truth like pathology confirmation or patient outcomes data, nor is it expert consensus in the sense of a diagnostic interpretation.

8. The Sample Size for the Training Set

The provided document does not mention or describe a "training set" in the context of an AI/ML algorithm. This 510(k) is for a PCR assay, which is a chemical and enzymatic reaction-based test, not a machine learning model that undergoes a training phase.

If there were any internal optimization studies during the development of either the original or alternative polymerase formulations (e.g., to find optimal reagent concentrations), those might be analogous to "training" in a very broad sense, but they are not discussed in this 510(k) summary provided. The 510(k) focuses on the validation of the final product.

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

As there is no "training set" for an AI/ML algorithm for this PCR assay, this question is not applicable.

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