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Alinity m EBV is an in vitro polymerase chain reaction (PCR) assay for the quantitation of Epstein-Barr Virus (EBV) DNA in human EDTA plasma on the automated Alinity m System.

Alinity m EBV is intended for use as an aid in the management of EBV in transplant patients. In patients undergoing monitoring of EBV, 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 EBV must be interpreted within the context of all relevant clinical and laboratory findings.

Alinity m EBV is not cleared for use as a screening test for donors of blood, blood products, or human cells, tissues, and cellular and tissue-based products (HCT/Ps) for EBV.

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

This device is similar to the predicate device originally cleared (K212778) with the exception that the subject device may use MomentaTaq DNA Polymerase as an alternative to KAPA2G 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 MomentaTaq DNA Polymerase. Supplemental data from these studies were used with data previously obtained from the analytical and clinical testing studies submitted in K212778.

The steps of the Alinity m EBV consist of sample preparation, real-time PCR assembly, amplification/detection, result calculation, and reporting. All stages of the Alinity m EBV procedure are executed automatically by the Alinity m System. No intermediate processing or transfer steps are performed by the user. The Alinity m System is designed to be a random-access analyzer that can perform the Alinity m EBV assay in parallel with other Alinity m assays on the same instrument.

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

• Alinity m EBV AMP Kit (List No. 09N43-095), 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 EBV AMP Kit is 2°C to 8°C.

• Alinity m EBV CTRL Kit (List No. 09N43-085), 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 EBV CTRL Kit is –25°C to –15°C.

• Alinity m EBV CAL Kit (List No. 09N43-075), consisting of 2 calibrator levels, each supplied as liquid in single-use tubes. The intended storage condition for the Alinity m EBV CAL Kit is –25°C to –15°C.

EBV 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 EBV activation reagent and lyophilized unit-dose Alinity m EBV 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 EBV targets.

At the beginning of the Alinity m EBV 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 EBV amplification/detection reagents consist of enzymes, primers, probes, and activation reagents that enable polymerization and detection.

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

• Alinity m EBV Application Specification File, (List No. 09N43-05B)
• 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):
  • 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)

This document, K243489, is a 510(k) clearance letter for the Alinity m EBV assay, specifically focusing on the use of MomentaTaq DNA Polymerase as an alternative to KAPA2G DNA Polymerase. The primary goal of the studies described is to demonstrate that the device formulated with MomentaTaq DNA Polymerase performs equivalently to the previously cleared device formulated with KAPA2G DNA Polymerase (K212778).

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

1. Table of Acceptance Criteria and Reported Device Performance

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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.

• ≤ 0.25 Log IU/mL for 500-100,000,000 IU/mL
• ≤ 0.50 Log IU/mL for 50-

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

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

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

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

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

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

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

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

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

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

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

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

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

The Alinity m BKV assay also utilizes the following:

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

1. Acceptance Criteria and Reported Device Performance

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Alinity m Resp-4-Plex is a multiplexed real-time in vitro reverse transcription polymerase chain reaction (RT-PCR) assay for use with the automated Alinity m System for the qualitative detection and differentiation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), influenza A virus, influenza B virus and Respiratory Syncytial Virus (RSV) in nasopharyngeal swab specimens collected from patients with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza B, and RSV can be similar.

The Alinity m Resp-4-Plex assay is intended for use in the differential detection of SARS-CoV-2, influenza B and/or RSV RNA and aids in the diagnosis of COVID-19, influenza and/or RSV infections if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza B and RSV viral RNA are generally detectable in nasopharyngeal swab specimens during the acute phase of infection. This test is not intended to detect influenza C virus infections.

Positive results are indication of the identified virus, but do not rule out bacterial infection or co-infection with other pathogens not detected by the test. The agent(s) detected by the Alinity m Resp-4-Plex assay may not be the definite cause of disease.

Negative results do not preclude SARS-CoV-2, influenza B and/or RSV infections and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

The Alinity m Resp-4-Plex assay requires two separate assay-specific kits: Alinity m Resp-4-Plex AMP Kit and Alinity m Resp-4-Plex CTRL Kit. The assay utilizes real-time PCR to amplify and detect genomic RNA sequences of influenza A (flu A), influenza B (flu B), RSV, and/or SARS-CoV-2 from nasopharyngeal (NP) swab specimens. The assay targets 2 different genes within the SARS-CoV-2 genome. Fluorescently labeled probes allow for simultaneous detection and differentiation of amplified products of all 4 viruses and Internal Control (IC) in a single reaction vessel. All steps of the assay procedure are executed automatically by the Alinity m System, which is a continuous random-access analyzer. The system performs automated sample preparation using magnetic microparticle technology. The IC is introduced into each specimen at the beginning of sample preparation. Purified RNA is combined with activation and amplification/detection reagents and transferred to a reaction vessel for reverse transcription, PCR amplification, and real-time fluorescence detection. A positive and negative control are tested to ensure performance. Patient results are automatically reported. The assay also utilizes the Alinity m Resp-4-Plex Assay Application Specification File, Alinity m System and System Software, Alinity m Sample Prep Kit 2, Alinity m Tubes and Caps, and Alinity m System Solutions.

The provided text is a 510(k) Summary for the Abbott Molecular Inc. Alinity m Resp-4-Plex assay, a multiplexed real-time RT-PCR assay for the qualitative detection and differentiation of SARS-CoV-2, influenza A, influenza B, and RSV.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided document:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are demonstrated through various analytical and clinical studies, primarily focusing on analytical sensitivity (Limit of Detection), inclusivity, precision, reproducibility, analytical specificity (interfering substances and cross-reactants), competitive interference, carryover, and clinical performance (Positive Percent Agreement - PPA, and Negative Percent Agreement - NPA).

The document implicitly defines the acceptance criteria as the successful demonstration of performance metrics that are typically expected for such in vitro diagnostic devices, often compared to highly sensitive FDA-cleared or EUA assays. While specific numerical acceptance criteria (e.g., PPA > X%, NPA > Y%) are not explicitly stated as "acceptance criteria," they are demonstrated by the reported results. The conclusion statement (Section 5.0) explicitly states that the "analytical and clinical study results demonstrate that the Alinity m Resp-4-Plex assay... performs comparably to the predicate device... the results support a substantial equivalence decision." This implies that the demonstrated performance values met the FDA's criteria for substantial equivalence to the predicate device.

Here's a table summarizing the reported device performance, which implicitly met the acceptance criteria:

Table 1: Acceptance Criteria (as Demonstrated Performance) and Reported Device Performance

Study Details

Here's the breakdown of the study details as requested:

1. A table of acceptance criteria and the reported device performance: Already provided above.

2. Sample sizes used for the test set and the data provenance:

   • Analytical Studies (Test Set):

     • LoD: For each virus (Flu A, Flu B, RSV, SARS-CoV-2), preliminary LoD involved testing a minimum of 3 levels, each in a minimum of 3 replicates. Final LoD confirmation involved testing a minimum of 3 panel members with target concentrations bracketing the preliminary LoD, each panel member in a minimum of 20 replicates. (Total specific sample numbers not provided per virus, but this describes the method and minimums). Specimens were pooled negative NP clinical specimens.
     • Inclusivity: Each individual virus isolate or strain was tested in replicates of 5. (Total specific sample numbers not provided per virus, but 16 Flu A strains, 9 Flu B, 6 RSV, 9 SARS-CoV-2). Specimens were pooled negative clinical NP swab matrix.
     • Precision: 5 panel members (1 negative, 4 positive) tested with 4 replicates twice each day for 5 days, on 3 Alinity m Systems operated by 3 operators using 3 reagent lots. This leads to:
       • Flu A: 120 positive replicates for each level, 360 negative replicates.
       • Flu B: 120 positive replicates for each level, 357 negative replicates.
       • RSV: 120 positive replicates for moderate, 117 for low, 360 negative.
       • SARS-CoV-2: 120 positive replicates for each level, 357 negative.
     • Reproducibility: 5 panel members tested at 3 external clinical testing sites. Each site tested 2 Alinity m Resp-4-Plex AMP Kit lots, on 5 non-consecutive days for each lot. Four replicates of each panel member were tested on each of 5 days. This leads to:
       • Flu A: 120 positive replicates for each level, 360 negative replicates.
       • Flu B: 120 positive replicates for each level, 359 negative replicates.
       • RSV: 120 positive replicates for moderate, 119 for low, 360 negative.
       • SARS-CoV-2: 120 positive replicates for moderate, 117 for low, 359 negative.
     • Analytical Specificity (Interfering Substances): 34 substances evaluated in 2 different positive panel members (PM1 & PM2), each containing multiple analytes at 3xLoD. (Replicate number not specified).
     • Analytical Specificity (Cross-Reactants): 74 microorganisms added to pooled negative clinical NP swab matrix (replicate number not specified) and also to positive samples (replicate number not specified).
     • Competitive Interference: 4 panel members, each containing 3 viruses at low concentrations and one at high concentration. (Replicate number not specified).
     • Carryover: Negative and high positive samples tested in alternating positions, across 3 Alinity m Systems. 360 negative samples total.

   • Clinical Performance (Test Set):

     • Prospective Clinical Study:
       • Flu A/B, RSV: 2,753 valid results initially, 2,504 (Flu A), 2,710 (Flu B), 2,700 (RSV) used in analysis.
         • Data Provenance: Multicenter study using prospectively collected nasopharyngeal swab specimens. 4 US clinical sites for testing. Specimens collected during 2021-2022 flu season at 7 geographically distributed locations in the US and during the 2020 flu season at 1 location in the Southern Hemisphere.
       • SARS-CoV-2: 826 valid results initially, 698 used in analysis.
         • Data Provenance: Specimens collected at 10 geographically distributed locations in the US over 2 time periods (Dec 2020 - Feb 2021 and May 2023).
     • Retrospective Clinical Study:
       • Flu A/B, RSV: 515 valid results initially, 506 (Flu A), 504 (Flu B), 505 (RSV) used in analysis.
         • Data Provenance: Preselected archived flu B positive NP swab specimens in UVT or UTM collected during the 2017-2018 and 2019-2020 flu seasons. Randomly mixed with known negative specimens.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The ground truth for the clinical test sets (both prospective and retrospective) was established using a Composite Comparator (CC). This CC was based on results from "2 to 3 FDA cleared assays for flu A, flu B, and RSV" and "2 to 3 highly sensitive EUA SARS-CoV-2 molecular assays."
   • The document does not specify the number or qualifications of human experts (e.g., radiologists, pathologists) involved in establishing this ground truth. The ground truth method described is entirely based on laboratory comparator assays, not expert human interpretation of results.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

   • The ground truth was established by a Composite Comparator (CC) method:
     • A specimen was categorized as CC positive if a minimum of 2 comparator positive results were reported.
     • A specimen was categorized as CC negative if a minimum of 2 comparator negative results were reported.
     • A specimen was categorized CC indeterminate if a CC could not be determined due to missing results from the comparator assays.
   • This functions as a type of "majority rule" adjudication or consensus, but strictly between other molecular assays, not human experts.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

   • No, an MRMC comparative effectiveness study was not done.
   • This device is an in vitro diagnostic (RT-PCR assay) that provides a qualitative (positive/negative) result directly. It does not involve human "readers" interpreting images or other complex data that would typically benefit from AI assistance or an MRMC study design. Therefore, there's no data on human reader improvement with or without AI assistance.

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

   • Yes, the primary performance evaluation is a standalone algorithm-only performance.
   • The Alinity m Resp-4-Plex assay is an automated RT-PCR system. Its performance (PPA, NPA) in both analytical and clinical studies is the performance of the "algorithm only" in generating positive/negative results from the sample. Human intervention is limited to sample collection and system operation, not interpretation of the primary diagnostic output.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):

   • The ground truth for the clinical studies was established using a Composite Comparator (CC) method based on the results of other FDA-cleared molecular diagnostic assays (or EUA high-sensitivity molecular assays for SARS-CoV-2).
   • It was not based on expert consensus, pathology, or outcomes data directly.

8. The sample size for the training set:

   • The document describes a de novo device, or a device for which substantial equivalence is being sought, not an AI/ML device that requires a distinct "training set" and "test set" in the context of model development.
   • The studies presented are primarily verification and validation studies to demonstrate the device's analytical and clinical performance after its development.
   • Therefore, the concept of a separate "training set" as understood in machine learning (where data is used to train a model) is not applicable to this RT-PCR assay. The assay's "knowledge" is embedded in its reagents, primers, probes, and system parameters, which were likely optimized during development using various analytical samples, but these are not typically referred to as a "training set" in the context of a 510(k) for an RT-PCR assay.

9. How the ground truth for the training set was established:

   • As explained in point 8, there isn't a "training set" in the AI/ML sense for this RT-PCR assay. The ground truth for any samples used during the development or optimization phases would similarly be established using well-characterized samples (e.g., cultured viruses, positive clinical samples confirmed by reference methods, synthetic nucleic acids, negative clinical samples).

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The Alinity m HSV 1 & 2 / VZV assay is an in vitro real-time polymerase chain reaction (PCR) assay for the qualitative detection and differentiation of Herpes Simplex Virus 1 (HSV-1), Herpes Simplex Virus 2 (HSV-2) and Varicella Zoster Virus (VZV) DNA from clinician-collected cutaneous or mucocutaneous lesion swab specimens from symptomatic patients suspected of active herpes simplex virus 2 and/or varicella-zoster infection. The Alinity m HSV 1 & 2 / VZV assay is intended to aid in the diagnosis of herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster active cutaneous or mucocutaneous infections. Negative results do not preclude herpes virus type 1, herpes simplex virus type 2 or varicella-zoster virus infections and should not be used as the sole basis for diagnosis, treatment or other management decisions.

The Alinity m HSV 1 & 2 / VZV assay is not intended for use with cerebrospinal fluid (CSF) or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Alinity m HSV 1 & 2 / VZV assay is not intended for use in prenatal screening.

The Alinity m HSV 1 & 2 / VZV assay is an in vitro real-time polymerase chain reaction (PCR) assay for the qualitative detection and differentiation of Herpes Simplex Virus 1 (HSV-1), Herpes Simplex Virus 2 (HSV-2) and Varicella Zoster Virus (VZV) DNA from clinician--collected cutaneous or mucocutaneous lesion swab specimens from symptomatic patients suspected of active herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster infection. This assay is intended for use with the automated Alinity m System.

The steps of the Alinity m HSV 1 & 2 / VZV assay consist of sample preparation, PCR assembly, amplification/detection, and result calculation and reporting. The steps involved in all stages of the Alinity m HSV 1 & 2 / VZV assay procedure are executed automatically by the Alinity m System. No intermediate processing or transfer steps are performed by the user. The Alinity m System is designed to be a random access analyzer that can perform the Alinity m HSV 1 & 2 / VZV assay in parallel with other Alinity assays on the same instrument.

The Alinity m HSV 1 & 2 / VZV assay requires two separate assay specific kits as follows:

1. The Alinity m HSV 1 & 2 / VZV AMP Kit (List No. 09N61-095) is comprised of 2 types of multi-well trays:

TRAY 1: Alinity m HSV 1 & 2 / VZV AMP TRAY 1 TRAY 2: Alinity m HSV 1 & 2 / VZV ACT TRAY 2.

TRAY 1 - Alinity m HSV 1 & 2 / VZV AMP is individually packed in a foil pouch and contains 48 unit-dose liquid amplification reagent wells and 48 unitdose liquid IC wells. One well of each is used per test.

· Amplification reagent wells consist of synthetic oligonucleotides, DNA Polymerase, dNTPs, and 0.15% ProClin® 950 in a buffered solution with a reference dye. IC wells consist of plasmid DNA with unrelated IC sequences and poly dA:dT in a TE buffer containing 0.15% ProClin 950 as a preservative.

TRAY 2 - Alinity m HSV 1 & 2 / VZV ACT is individually packed in a foil pouch and contains 48 unit-dose liquid activation reagent wells. One reagent well is used per test.

· Activation reagent wells consist of magnesium chloride, potassium chloride, and tetramethylammonium chloride. Preservative: 0.15% ProClin 950.

2. The Alinity m HSV 1 & 2 / VZV CTRL Kit (09N61-085) consists of negative controls and positive controls, each supplied as liquid in single-use tubes.

Alinity m HSV 1 & 2 / VZV Negative CTRL (List No. 9N61Z) consists of Negative Diluent / TE buffer (containing 0.085% Sodium Azide and 0.087% ProClin 950).

Alinity m HSV 1 & 2 / VZV Positive CTRL (List No. 9N61W) consists of linearized plasmid DNA containing HSV-1, HSV-2 and VZV DNA sequences in Negative Diluent / TE buffer (containing 0.085% Sodium Azide and 0.087% ProClin 950).

The Alinity m HSV 1 & 2 / VZV assay is to be run on the Alinity m System which is a fully integrated, sample to result automated system that performs real-time PCR test using the Alinity m HSV 1 & 2 / VZV AMP Kit along with the Alinity m HSV 1 & 2 / VZV CTRL Kit.

The provided text describes the performance of the "Alinity m HSV 1 & 2 / VZV" assay, which is an in vitro real-time PCR assay for detecting and differentiating Herpes Simplex Virus 1 (HSV-1), Herpes Simplex Virus 2 (HSV-2), and Varicella Zoster Virus (VZV) DNA.

Here's an analysis of the acceptance criteria and study proving the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the clinical agreement and analytical performance values demonstrated to establish substantial equivalence to a predicate device. For clinical agreement, the performance is measured by Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a commercially available NAAT comparator method.

The acceptance criteria typically would be pre-defined statistical thresholds for PPA and NPA (e.g., PPA ≥ 95% and NPA ≥ 95%). Based on the reported results, the device successfully meets high performance metrics, suggesting that the implicit acceptance criteria were met for substantial equivalence.

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

• Prospective Study Test Set:
  • Sample Size: 1,258 results (1,257 for HSV-1, 1,257 for HSV-2, and 1,257 for VZV) from unique specimens.
  • Data Provenance: Multicenter, prospective clinical study conducted in the United States. Specimens were clinician-collected from symptomatic individuals.
• Retrospective Study Test Set:
  • Sample Size: 411 specimens (410 for HSV-1, 410 for HSV-2, and 411 for VZV).
  • Data Provenance: Retrospective study using archived, leftover lesion swab specimens from routine clinical testing. The location is not explicitly stated, but given it follows a prospective US study and is for US FDA clearance, it is highly likely to be from the US.

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

• The document does not specify the number or qualifications of experts used to establish the ground truth.
• The ground truth was established by comparison to a "commercially available NAAT comparator method (NAAT 1)". For discordant results, a "second commercially available RT-PCR comparator method (NAAT 2)" was used for informational purposes only (not for the primary analysis of device performance). This means the ground truth is essentially defined by the predicate/comparator device(s).

4. Adjudication Method for the Test Set

• The primary ground truth was established by a single comparator method (NAAT 1).
• For specimens with discordant results between the Alinity m assay and NAAT 1, a second NAAT method (NAAT 2) was used. However, the results of this second test were "not included in the analysis of device performance and are considered for information purposes only." This implies that the primary PPA/NPA calculations are based solely on the agreement with NAAT 1, and there was no formal 2+1 or 3+1 adjudication to establish a "resolved" ground truth for discordant cases that would then be used in the performance calculations.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and what was the effect size of how much human readers improve with AI vs without AI assistance

• This is not applicable as the device is an in vitro diagnostic (IVD) assay detecting viral DNA, not an AI-assisted diagnostic imaging device requiring human reader interpretation. There are no "human readers" in the context of this device.

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

• Yes, this is a standalone device performance study. The Alinity m HSV 1 & 2 / VZV assay is an automated system described as "fully integrated, sample to result." The performance data presented (clinical agreement, analytical sensitivity, specificity, precision, reproducibility, carryover) represent the performance of the algorithm/assay system without direct human interpretation of raw data being a variable. The "results are calculated and reported" automatically by the Alinity m System.

7. The Type of Ground Truth Used

• The ground truth was established by comparison to a "commercially available NAAT comparator method (NAAT 1)." For discordant cases, a second NAAT (NAAT 2) was used, but its results were for informational purposes only. This is a form of clinical surrogate ground truth, relying on an established and legally marketed diagnostic method. It is not pathology, expert consensus (in the traditional sense of multiple human interpretations), or outcomes data.

8. The Sample Size for the Training Set

• The document does not provide information regarding a specific training set size or how the device's algorithms (if any, beyond PCR signal processing) were trained. Regulatory submissions for IVD assays primarily focus on analytical and clinical validation of the final, locked-down device performance, rather than algorithm development specifics. The device seems to be a PCR assay, where the "training" would be more akin to assay design and optimization, not machine learning model training on large datasets in the way an AI imaging model is.

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

• As the document does not mention a training set in the context of machine learning, there is no information on how a ground truth for such a set would have been established. For a PCR assay, the development process involves extensive analytical characterization, optimization, and verification using characterized samples (e.g., known positive/negative samples, spiked samples, reference strains) to establish assay parameters and thresholds. This is distinct from establishing ground truth for a machine learning training dataset.

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The Alinity m STI Assay is an in vitro polymerase chain reaction (PCR) assay for use with the automated Alinity m System for the direct, qualitative detection and differentiation of ribosomal RNA from Chlamydia trachomatis (CT), DNA from Neisseria gonorrhoeae (NG), ribosomal RNA from Trichomonas vaginalis (TV), and ribosomal RNA from Mycoplasma genitalium (MG), to aid in the diagnosis of disease(s) caused by infection from these organisms. The assay may be used to test the following specimens from symptomatic and asymptomatic individuals for the following analytes:

• . CT: vaginal swabs (clinician-collected and self-collected in a clinical setting). endocervical swabs, gynecological specimens in ThinPrep PreservCyt Solution, female urine, male urine, oropharyngeal swabs, and rectal swabs
• . NG: vaginal swabs (clinician-collected and self-collected in a clinical setting), endocervical swabs, gynecological specimens in ThinPrep PreservCyt Solution, female urine, male urine, oropharyngeal swabs, and rectal swabs
• . TV: vaginal swabs (clinician-collected and self-collected in a clinical setting). endocervical swabs, gynecological specimens in ThinPrep PreservCyt Solution, female urine, and male urine
• . MG: vaginal swabs (clinician-collected and self-collected in a clinical setting), endocervical swabs, and male urine

A vaginal swab (self-collected or clinician-collected) is the preferred specimen type for MG testing in females due to the higher clinical sensitivity compared to endocervical swabs. If endocervical swab specimens test negative, testing with a vaginal swab may be indicated if M. genitalium infection is suspected.

The Alinity m STI Assay utilizes real time PCR to amplify and detect Chlamydia trachomatis (CT) ribosomal RNA sequences, Neisseria gonorrhoeae (NG) genomic DNA sequences, Trichomonas vaginalis (TV) ribosomal RNA sequences, Mycoplasma genitalium (MG) ribosomal RNA sequences, and human genomic DNA sequences that have been extracted from endocervical swab specimens, vaginal swab specimens, oropharyngeal swab specimens, rectal swab specimens, male and female urine specimens, and gynecological specimens preserved in PreservCyt Solution. Endocervical swab, vaginal swab, oropharyngeal swab, rectal swab, and urine specimens are collected with the Alinity m multi-Collect Specimen Transport Kit. PreservCyt specimens are transferred to a transport tube for processing on the Alinity m System.

This device is similar to the predicate device originally cleared (K202977). It does not introduce any changes to the Alinity m STI Assay reagents, sample processing, assay procedure, and data reduction. This device is updating the previous FDA-cleared Intended Use (K202977) to include claims for the following specimens for the following analytes:

• CT: Gynecological specimens in ThinPrep PreservCyt Solution, female urine .
• NG: Female urine

Two studies were initiated to support these claims (refer to Section 1.7.2.) This supplemental data was used with data previously obtained from the Alinity m STI Assay clinical testing studies submitted in K202977.

The steps of the Alinity m STI Assay consist of sample preparation. RT-PCR assembly, amplification/detection, and result calculation and reporting. All stages of the Alinity m STI Assay procedure are executed automatically by the Alinity m System. No intermediate processing or transfer steps are performed by the user. The Alinity m System is designed to be a random-access analyzer that can perform the Alinity m STI Assay in parallel with other Alinity m assays on the same instrument.

The Alinity m STI Assay is an in vitro diagnostic device for the qualitative detection and differentiation of nucleic acids from Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), and Mycoplasma genitalium (MG) in various human specimen types. The device operates on the automated Alinity m System and utilizes real-time Polymerase Chain Reaction (PCR) technology. This submission primarily focuses on supporting expanded claims for specific analytes and specimen types: CT in gynecological specimens in ThinPrep PreservCyt Solution and female urine, and NG in female urine.

Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" for the clinical performance in terms of specific thresholds (e.g., minimum PPA/NPA). Instead, it presents the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) values with 95% Confidence Intervals (CI) as the primary performance metrics, demonstrating the device's accuracy against a Composite Comparator Algorithm (CCA).

Note: The table is constructed based on the "specimen-specific positive and negative agreement" data. The document does not provide specific acceptance thresholds, but the presented performance metrics are high, demonstrating the device's effectiveness.

2. Sample Size Used for the Test Set and Data Provenance:

• CT and NG in Female Urine:
  • Sample Size: A total of 2,798 female subjects were enrolled. 2,785 CT results and 2,784 NG results were used in the analysis after exclusions due to missing/indeterminate CCA results.
  • Data Provenance: The study was a multicenter clinical study conducted in the United States. Subjects provided urine specimens. The data includes both symptomatic and asymptomatic individuals.
• CT in PreservCyt Specimens:
  • Sample Size: 1,939 specimens from a multicenter clinical study were included in the analysis.
  • Data Provenance: The study was a multicenter clinical study conducted in the United States. Female subjects provided gynecological specimens collected in PreservCyt Solution.

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

The ground truth was established using a clinical comparator method, not individual experts.

• Ground Truth Method: A Composite Comparator Algorithm (CCA) was used.
• Details: For each subject, a CCA was determined for each analyte based on the combined results from commercially available nucleic acid amplification tests (NAATs).
  • For the female urine study (CT and NG), comparator assays included 3 commercially available NAATs. Specimens were initially tested with 2 NAATs. If they disagreed or a result was missing/indeterminate, a third tiebreaker NAAT was used.
  • For the PreservCyt study (CT), specimens were tested with up to 3 comparator NAATs. Similar to the urine study, specimens were initially tested with 2 NAATs, and a third was used as a tiebreaker if needed.
• Qualifications of Experts: The document does not mention the use of human experts or their qualifications for establishing ground truth. The ground truth is effectively an "expert panel of assays" (the comparator NAATs).

4. Adjudication Method for the Test Set:

• Method: A 2+1 adjudication method was employed for establishing the Composite Comparator Algorithm (CCA).
  • Description: Specimens were initially tested with two comparator NAATs.
  • If the two initial NAATs agreed (both positive or both negative), that result formed the CCA.
  • If the two initial NAATs disagreed, or if one result was missing or indeterminate, a third "tiebreaker" NAAT was used to resolve the discrepancy and establish the CCA.
  • A subject was categorized as "Positive" if at least 2 comparator assay results were positive and "Negative" if at least 2 comparator assay results were negative.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:

No, an MRMC comparative effectiveness study was not done. The Alinity m STI Assay is an in vitro diagnostic device (IVD) that provides a qualitative result directly. Its performance is compared against a composite reference standard (CCA) derived from other NAATs, not against human readers. Therefore, the concept of human readers improving with AI assistance is not applicable in this context.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:

Yes, a standalone performance study was done. The reported performance metrics (PPA and NPA) reflect the accuracy of the Alinity m STI Assay (algorithm and reagents performed on the automated Alinity m System) operating independently against the established ground truth (CCA). The device provides a direct, qualitative result without human interpretation of the algorithm's output for diagnosis.

7. The Type of Ground Truth Used:

The ground truth used was a Composite Comparator Algorithm (CCA), which is an expert consensus based on multiple FDA-cleared nucleic acid amplification tests (NAATs). These NAATs are considered the gold standard for detecting these pathogens. The CCA essentially serves as the "best available truth" when a true clinical outcome or pathological confirmation for all cases is not feasible or practical in a large-scale clinical trial.

8. The Sample Size for the Training Set:

The document does not explicitly describe a separate "training set" for the Alinity m STI Assay in the context of this 510(k) submission. This is typical for IVD devices, where the assay's design, reagent formulation, and analytical parameters are developed through internal R&D, rather than a machine learning training paradigm with a distinct training dataset for an "algorithm." The clinical studies mentioned (both the original K202977 studies and the supplemental studies) serve as validation/test sets to demonstrate the performance of the already developed assay.

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

Since a distinct "training set" in the machine learning sense is not described, the question of how its ground truth was established is not directly applicable. The Alinity m STI Assay's underlying technology (real-time PCR) and design would have been established and optimized based on known genetic sequences, analytical performance studies (e.g., analytical sensitivity, specificity), and prior knowledge of the target organisms, where ground truth sources for these developmental phases would likely include:

• Well-characterized isolates/strains: Known positive and negative biological samples.
• Synthetic nucleic acid targets: Designed to validate primer and probe performance.
• Spiked matrix samples: To assess analytical performance in relevant specimen types.

These developmental activities would precede the clinical validation studies that are the focus of this 510(k) submission.

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Alinity m EBV is an in vitro polymerase chain reaction (PCR) assay for the quantitation of Epstein-Barr Virus (EBV) DNA in human EDTA plasma on the automated Alinity m System.

Alinity m EBV is intended for use as an aid in the management of EBV in transplant patients undergoing monitoring of EBV, 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 EBV must be interpreted within the context of all relevant clinical and laboratory findings. Alinity m EBV is not cleared for use as a screening test for donors of blood products, or human cells, tissues, and cellular and tissue-based products (HCT/Ps) for EBV.

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

The steps of the Alinity m EBV assay consist of sample preparation, real-time PCR assembly, amplification/detection, result calculation, and reporting. All stages of the Alinity m EBV procedure are executed automatically by the Alinity m System. No intermediate processing or transfer steps are performed by the user. The Alinity m System is designed to be a random-access analyzer that can perform the Alinity m EBV assay in parallel with other Alinity m assays on the same instrument.

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

• . Alinity m EBV AMP Kit (List No. 09N43-095) consisting of multi-well amplification trays (AMP Trays) containing lyophilized, unit-dose PCR amplification/detection reagents and multi-well activation trays (ACT Trays) containing liquid, unit-dose activation reagents (MgCl2, TMAC, KCl, and ProClin). The intended storage condition for the Alinity m EBV AMP Kit is 2°C to 8°C.
• Alinity m EBV CTRL Kit (List No. 09N43-085) consisting of a negative control, a low positive control, and a high positive control, each supplied as liquid in single-use tubes. The intended storage condition for the Alinity m EBV CTRL Kit is —15°C to —25°C.
• . Alinity m EBV CAL Kit (List No. 09N43-075) consisting of two levels of calibrators (CAL A and CAL B), each supplied as liquid in single-use tubes. The intended storage condition for the Alinity m EBV CAL Kit is -15°C to -25°C.

EBV DNA from specimens 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 the liquid unit-dose Alinity m EBV activation reagent and lyophilized unit-dose Alinity m EBV 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 EBV targets.

An EBV calibration curve is required for the quantitation of EBV targets. Two levels of calibrators are processed through sample preparation and real-time PCR to generate the calibration curve. The concentration of EBV 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 remain satisfactory. During each control event, a negative control, a low-positive control, and a high-positive control are processed through sample preparation and real-time PCR procedures that are identical to those used for specimens.

At the beginning of the Alinity m EBV sample preparation process, a lyophilized unit -dose of Internal Control on the AMP Tray is rehydrated by the Alinity m System and delivered into each sample preparation reaction. The Internal Control 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 assay validity.

The Alinity m EBV amplification and detection reagents include primers and probes that amplify and detect dual targets in the EBV genome. Amplification and detection of the two EBV targets ensures sensitive detection of the viral genome even at low levels.

The Alinity m EBV assay also utilizes the following accessories:

• . Alinity m EBV Application Specification File, List No. 09N43-05A
• . 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 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
• . 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

Here's a summary of the acceptance criteria and study details for the Alinity m EBV AMP Kit, extracted from the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document describes performance characteristics but doesn't explicitly state "acceptance criteria" for each in a table. Instead, it presents the validated performance values. I've constructed a table based on the key performance metrics and their demonstrated values.

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The Alinity m STI Assay is an in vitro polymerase chain reaction (PCR) assay for use with the automated Alinity m System for the direct, qualitative detection and differentiation of ribosomal RNA from Chlamydia trachomatis (CT), DNA from Neisseria gonorrhoeae (NG), ribosomal RNA from Trichomonas vaginalis (TV), and ribosomal RNA from Mycoplasma genitalium (MG), to aid in the diagnosis of disease(s) caused by infection from these organisms. The assay may be used to test the following specimens from symptomatic and asymptomatic individuals for the following analytes:

CT: vaginal swabs (clinician-collected and self-collected in a clinical setting), endocervical swabs, male urine, oropharyngeal swabs, and rectal swabs

NG: vaginal swabs (clinician-collected and self-collected in a clinical setting). endocervical swabs, gynecological specimens in ThinPrep PreservCyt Solution, male urine, oropharyngeal swabs, and rectal swabs

TV: vaginal swabs (clinician-collected and self-collected in a clinical setting), endocervical swabs, gynecological specimens in ThinPrep PreservCyt Solution, female urine, and male urine

MG: vaginal swabs (clinician-collected and self-collected in a clinical setting), endocervical swabs, and male urine

A vaginal swab (self-collected or clinician-collected) is the preferred specimen type for MG testing in females due to higher clinical sensitivity compared to endocervical swabs. If endocervical swab specimens test negative, testing with a vaginal swab may be indicated if M. genitalium infection is suspected.

The Alinity m STI Assay is a real time polymerase chain reaction (PCR) assay for the amplification and detection of Chlamydia trachomatis (CT) ribosomal RNA sequences, Neisseria gonorrhea (NG) genomic DNA sequences, Trichomonas vaginalis (TV) ribosomal RNA sequences, Mycoplasma genitalium (MG) ribosomal RNA sequences, and human genomic DNA sequences. The assay can be used with endocervical swab specimens, vaginal swab specimens, male and female urine specimens, gynecological specimens in ThinPrep® PreservCyt® Solution, oropharyngeal swab specimens, and rectal swab specimens. Endocervical swab, vaginal swab, oropharyngeal swab, rectal swab and urine specimens are collected with the Alinity m multi-Collect Specimen Collection Kit. PreservCyt Solution specimens are transferred to an Alinity m Transport Tube for processing on the Alinity m System.

The steps of the Alinity m STI Assay consist of sample preparation, RT-PCR assembly, amplification/detection, and result calculation and reporting. All stages of the Alinity m STI Assay procedure are executed automatically by the Alinity m System. No intermediate processing or transfer steps are performed by the user. The Alinity m System is designed to be a random-access analyzer that can perform the Alinity m STI Assay in parallel with other Alinity m assays on the same instrument.

The Alinity m STI Assay requires two separate assay specific kits as follows:

• . Alinity m STI AMP Kit, List No. 09N17-095 consisting of multi-well amplification plates containing lyophilized, unit-dose PCR amplification/detection reagents and multi-well activator plates containing liquid, unit-dose activation reagents (MgCl2, TMAC, and KCl). The intended storage condition for the Alinity m STI AMP Kit is 2℃ to 8℃.
• . Alinity m STI CTRL Kit, List No. 09N17-085 consisting of negative controls and positive controls, each supplied as liquid in single-use tubes. The intended storage condition for the Alinity m STI Control Kit is -15°C to -25°C.

Nucleic acids from specimens are extracted automatically on-board the Alinity m System using the Alinity m Sample Prep Kit 1, Alinity m Lysis Solution, Alinity m Ethanol 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 the liquid unit-dose activator reagent, lyophilized unit-dose Alinity m STI amplification reagents, and Alinity m Vapor Barrier Solution, and transferred by the instrument to an amplification/detection module for reverse transcription, PCR amplification, and real-time fluorescence detection.

Assay controls are tested at or above an established minimum frequency of every 24 hours to help ensure that instrument and reagent performance remain satisfactory. During each control event, a negative control and a positive control are processed through sample preparation and RT-PCR procedures that are identical to those used for specimens. Assay controls are used to demonstrate proper sample processing and assay validity. The controls do not indicate if bacterial cells have been adequately lysed.

The Alinity m STI amplification reagents include primers and a probe that amplify and detect the single copy human gene, ß-globin. Amplification and detection of the ß-globin gene demonstrates proper sample processing and adequate sample input. In addition, an exogenous internal control (containing an armored RNA sequence) is included in the lyophilized Alinity m STI amplification reagents to assess amplification efficiency and to confirm that no PCR inhibitors are present in the sample. The cellular control and internal control are both used to demonstrate assay validity.

The Alinity m STI Assay also utilizes the following accessories:

• . Alinity m STI Assay Application Specification File, List No. 09N17-03A
• . Alinity m System and System Software, List No. 08N53-002
• Alinity m Sample Prep Kit 1, List No. 09N18-001 .
• Alinity m multi-Collect Specimen Collection Kit, List No. 09N19-010 .
• . Alinity m Tubes and Caps, List No. 09N49:
  • 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 System Solutions, List No. 09N20: .
  • Alinity m Lysis Solution, List No. 09N20-001 .
  • Alinity m Ethanol Solution, List No. 09N20-002 .
  • Alinity m Diluent Solution, List No. 09N20-003
  • Alinity m Vapor Barrier Solution, List No. 09N20-004 •

The Abbott Alinity m STI Assay is an in vitro polymerase chain reaction (PCR) assay used with the automated Alinity m System for the direct, qualitative detection and differentiation of ribosomal RNA from Chlamydia trachomatis (CT), DNA from Neisseria gonorrhoeae (NG), ribosomal RNA from Trichomonas vaginalis (TV), and ribosomal RNA from Mycoplasma genitalium (MG), to aid in the diagnosis of sexually transmitted infections.

The acceptance criteria and the study results are detailed below:

1. Table of Acceptance Criteria and Reported Device Performance

The device performance is reported as Sensitivity (Positive Percent Agreement or PPA) and Specificity (Negative Percent Agreement or NPA). The document does not explicitly state pre-defined acceptance criteria (e.g., a specific threshold like "Sensitivity must be >= X%"). However, the reported performance values are the outcome of the clinical trials conducted to demonstrate the device's effectiveness.

Urogenital Specimens

Extragenital Specimens

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

• Urogenital Specimens: A total of 7,099 male and female subjects were enrolled for the urogenital clinical study. Specimens were collected across 33 geographically diverse sites in the United States, including STI clinics, primary care offices, and gynecology practices. This was a prospective study. Data provenance is United States, from prospective collection.
  • Number of results used in analysis for each analyte:
    • CT: 12,903
    • NG: 15,655
    • TV: 18,843
    • MG: 12,829
• Extragenital Specimens: A total of 2,373 male and female subjects were enrolled. Specimens were previously collected and archived. Data provenance is United States, from archived specimens (retrospective).
  • Number of results used in analysis for each analyte:
    • CT (oropharyngeal): 2,316
    • CT (rectal): 2,053
    • NG (oropharyngeal): 2,312
    • NG (rectal): 2,049

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

The document does not explicitly state the "number of experts" or their "qualifications" involved in establishing the ground truth. Instead, the ground truth was established using comparator assays, which are commercially available nucleic acid amplification tests (NAATs) and, in some cases, culture. The results from these comparator assays were combined to derive a Patient Infected Status (PIS) or Composite Comparator (CC).

4. Adjudication Method for the Test Set

• Urogenital Specimens (PIS):
  • CT or NG (Female): A minimum of 2 positive results (at least 1 from each comparator NAAT) for infection, or at least 1 comparator NAAT reported negative results for all sample types for not infected.
  • TV or MG (Female): First 2 swab comparator NAAT results both positive, or 2 of 3 swab comparator NAAT results positive (if 3rd NAAT was a tie-breaker) for infection. First 2 swab comparator NAAT results both negative, or 2 of 3 swab comparator NAAT results negative (if 3rd NAAT was a tie-breaker) for not infected.
  • CT, NG, TV, or MG (Male): A minimum of two comparator positive results for infection. If the comparator TV culture assay result was positive, the subject was categorized as infected for TV regardless of NAAT results. Two or more comparator NAAT results negative for not infected (for CT, NG, MG). For TV, negative culture AND one or more negative comparator NAATs for not infected.
• Extragenital Specimens (CC): A specimen was categorized as infected (for CT or NG) if a minimum of 2 comparator positive results were reported. It was categorized as not infected if a minimum of 2 comparator negative results was reported.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. The study compares the Alinity m STI Assay's performance against a composite ground truth derived from multiple established comparator assays, not directly evaluating human reader performance with and without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, this was a standalone performance study. The Alinity m STI Assay is an automated PCR assay, and its results are directly compared to the established ground truth without involving human interpretation or modifications of its output in the primary performance analysis.

7. The Type of Ground Truth Used

The ground truth used was a Composite Comparator / Patient Infected Status (PIS/CC), derived from the combined results of multiple commercially available and clinically cleared comparator nucleic acid amplification tests (NAATs) and, for male TV, culture results.

8. The Sample Size for the Training Set

The document does not explicitly provide the sample size for the training set for the Alinity m STI Assay. The provided performance data (Sensitivity and Specificity tables) are from the validation (test) sets.

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

Since the document does not provide information about a separate training set, it is assumed that the analytical studies and the design of the assay would have utilized reference materials and potentially early clinical samples for optimization and establishment of analytical performance characteristics (like LoD, inclusivity, cross-reactivity). However, specific details on how ground truth was established for a training set are not available in this document. The clinical studies described are for validation/testing, with ground truth established by comparator assays as detailed in point 4.

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The Abbott RealTime CT/NG assay is an in vitro polymerase chain reaction (PCR) assay for the direct, qualitative detection of the plasmid DNA of Chlamydia trachomatis and the genomic DNA of Neisseria gonorthoeae. The assay may be used to test the following specimens from symptomatic individuals: female endocervical swab, clinician-collected vaginal swab, and patient-collected vaginal swab specimens; male urethral swab specimens; and female and male urine specimens. The assay may be used to test the following specimens from asymptomatic individuals: clinician-collected vaginal swab and patient-collected vaginal swab specimens; female and male urine specimens.

The Abbott multi-Collect Specimen Collection Kit is intended for the collection and transportation of male and female swab and urine specimens for the detection of Chlamydia trachomatis and Neisseria gonorrheae per instructions provided. Refer to the specimen collection procedure in the package insert for specimen collection instructions for specific sample types.

Self-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The Abbott multi-Collect Specimen Collection Kit is not intended for home use.

The Abbott multi-Collect Specimen Collection Kit can be used to collect either a swab or a urine specimen. Each Abbott multi -Collect Specimen Collection Kit contains:

• . One capped Transport Tube containing 1.2 mL Specimen Transport Buffer
• . One Individually Packaged Sterile Specimen Collection Swab
• . One disposable transfer pipette.

The Specimen Transport Buffer is used to stabilize DNA until sample preparation. The individually packaged sterile Specimen Collection Swab is used for swab sample collection and placed directly into the Transport Tube. The transfer pipette is used to add approximately 3 mL of urine to the Transport Tube. The Abbott multi -Collect Specimen Collection Kit is for single use only.

The Abbott multi-Collect Specimen Collection Kit Swab is approximately 14 cm in length with a polyester fiber tip. The swab shaft has a polystyrene solid core that is orange in color. The swab has a molded score completely around the shaft, between 7.86 cm and 7.89 cm from the swab tip, to provide a clean break-point. The polyesterfiber swab tip is approximately 1.3 cm in length and less than 3.28 mm in diameter.

This document describes the regulatory submission for a modification to the Abbott multi-Collect Specimen Collection Kit, specifically a change in the swab fiber component. The submission focuses on demonstrating that the new swab is substantially equivalent to the previously cleared swab and does not impact the performance of the Abbott RealTime CT/NG assay.

1. Table of Acceptance Criteria and Reported Device Performance

The submission doesn't explicitly state "acceptance criteria" in a numerical, threshold-based format. Instead, the studies demonstrate performance relative to the existing device and expected assay performance (e.g., detection rates approaching 100% for low positive samples). The goal of these studies is to confirm that the new swab material does not negatively impact the assay's performance.

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

• Biocompatibility: The specific sample sizes for cytotoxicity, irritation, and sensitization tests are not provided in the summary.
• 90-Day Specimen Stability: Not explicitly stated, but involved testing "simulated high and low positive swab specimens."
• Sample Freeze-Thaw Stability: 90 CT analyte samples and 90 NG analyte samples (total 180 samples) were tested.
• LOD Confirmation: 234 samples were tested for both CT and NG.
• Reproducibility: 189 replicates were tested for each panel member. There were 4 panel members (3 concentrations + 1 negative) for each analyte (CT and NG). This suggests a total of 189 replicates/panel member * 4 panel members * 2 analytes = 1512 individual tests for quantification, or more accurately, 189 replicates per panel member across the different conditions. Seven replicates of each panel member were tested in each run, with nine runs performed across three m2000 instrument systems.
• Accelerated Stressed Swab Stability: Not explicitly stated, but involved "testing simulated low positive swab specimens containing a target concentration of 320 copies of CT and 320 copies of NG in each 400 uL sample preparation input volume."
• Provenance: All data appears to be retrospective experimental data generated in a laboratory setting using simulated specimens rather than prospective clinical samples. The country of origin of the data is not explicitly stated but is implicitly associated with Abbott Molecular Inc. in the USA.

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

No human experts were used to establish the "ground truth" in these studies. The studies are analytical performance studies, not clinical studies involving patient diagnoses. The "ground truth" (e.g., presence and concentration of CT/NG DNA) was established by spiking known concentrations of target analytes into simulated specimens in a laboratory setting.

4. Adjudication Method for the Test Set

Not applicable. As described above, the ground truth was established by precise laboratory spiking of analytes, not by expert consensus or clinical adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. This is not an MRMC study. The device is a specimen collection kit the performance of which is measured using an in vitro assay (Abbott RealTime CT/NG assay). There are no human readers or interpretation involved in the performance evaluation of the collection device itself. The studies focus on the analytical performance of the kit to collect and preserve DNA for subsequent automated testing.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, this is an algorithm-only (assay-only) performance evaluation. The "device" being evaluated is the Abbott multi-Collect Specimen Collection Kit, specifically its swab component. Its performance is assessed by how effectively it allows the Abbott RealTime CT/NG assay (an automated PCR assay) to detect targets. Therefore, the performance demonstrated is that of the collection kit in conjunction with the fully automated assay, without any human interpretation steps directly related to the collection kit's function.

7. The Type of Ground Truth Used

The ground truth used was based on known concentrations of spiked target analytes (DNA for Chlamydia trachomatis and Neisseria gonorrhoeae) in simulated laboratory specimens. This is a form of analytical truth or definitive measurement through controlled experimental design.

8. The Sample Size for the Training Set

These studies are analytical validation studies for a medical device modification (swab component), not a machine learning or AI model development. Therefore, there is no concept of a "training set" in the context of these studies. The experiments described are test/validation studies for the physical collection device.

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

Not applicable, as there was no training set for an AI model.

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The Vysis D7S486/CEP 7 FISH Probe Kit is a device intended for specimen characterization, and detects the LSI D7S486 probe target on chromosome 7q31 and the CEP 7 probe target on chromosome 7p11.1-q11.1 in bone marrow and peripheral blood specimens from patients with acute myeloid leukemia or myelodysplastic syndrome. The assay results are intended to be interpreted by a qualified pathologist or cytogeneticist. This device is not intended for high-risk uses such as selecting therapy, predicting therapeutic response or disease screening. The use of this device for diagnosis, prognosis, monitoring or risk assessment has not been established.

The Vysis D7S486/CEP 7 FISH Probe Kit is for specimen characterization and detects the LSI D7S486 (7q31) probe target on chromosome 7q31 and CEP 7 probe target chromosome 7p11.1-q11.1 in bone marrow and peripheral blood specimens.

DNA Probe Description

Vysis LSI D7S486 SpectrumOrange/ CEP 7 SpectrumGreen Probes:

The SpectrumOrange labeled LSI D7S486 probe is approximately 308 kb in length (chr7:115983468-115675366; February 2009 Assembly UCSC Human Genome Browser).

The SpectrumGreen labeled CEP 7 probe targets the D7Z1 alpha satellite sequence at the centromere of chromosome 7.

The Vysis D7S486/CEP 7 FISH Probe Kit (List No. 04N78-020) consists of a mixture of two DNA FISH probes and four general reagents sufficient to process 20 assays.

• . Vysis LSI D7S486 SpectrumOrange/ CEP 7 SpectrumGreen Probes
• . Vysis LSI/WCP Hybridization Buffer
• . DAPI II Counterstain
• NP-40 .
• . 20X SSC

The Vysis D7S486/CEP 7 FISH Probe Kit is designed for specimen characterization, specifically detecting the LSI D7S486 probe target on chromosome 7q31 and the CEP 7 probe target on chromosome 7p11.1-q11.1 in bone marrow and peripheral blood specimens from patients with acute myeloid leukemia or myelodysplastic syndrome.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Analytical Specificity: 4 male and 1 female karyotypically normal specimen slides.
• Analytical Sensitivity and Verification of Upper Reference Limit: 25 bone marrow and 25 peripheral blood specimens. These were from either karyotypically normal individuals or patients lacking monosomy 7 and loss of 7q. The provenance is not explicitly stated (e.g., country of origin, retrospective/prospective).
• Reproducibility (Site-to-Site & Lot-to-Lot): The panel members for the reproducibility studies were prepared by mixing positive cells with normal cells. The exact number of individual patient samples from which these positive and normal cells originated is not specified. The study used 2 high-positive, 2 low-positive, and 2 negative panel members for each specimen type (bone marrow and peripheral blood). The data provenance is not specified as retrospective or prospective, nor is the country of origin explicitly mentioned.

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

• Analytical Specificity: 1 technologist for evaluating metaphase chromosomes.
• Analytical Sensitivity and Verification of Upper Reference Limit: 2 technologists for evaluating interphase nuclei.
• Reproducibility: The ground truth for the reproducibility studies (negative, low positive, high positive categories) was established by mixing positive cells with normal cells to achieve desired levels of positivity, implying a predefined "known status" based on these mixtures. The expertise used to determine the initial "positive cells" or "normal cells" is not detailed.

The qualifications of these technologists/experts are not explicitly stated (e.g., years of experience, specific certifications like "radiologist with 10 years of experience").

4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set

For Analytical Sensitivity and Verification of Upper Reference Limit, the document states that each technologist evaluated 100 nuclei per specimen, implying independent scoring. There is no mention of an adjudication method (like 2+1 or 3+1) if scores differed between the two technologists, nor is an adjudication method specified for other tests.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance?

No MRMC comparative effectiveness study was done. This device is a FISH probe kit, not an AI-assisted diagnostic tool. Therefore, there is no discussion of human reader improvement with or without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done?

This is a laboratory diagnostic kit (FISH probe) that requires human interpretation (a qualified pathologist or cytogeneticist). Therefore, a standalone algorithm-only performance assessment is not applicable and was not performed. The performance studies evaluate the kit's analytical characteristics.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

• Analytical Specificity: Karyotypically normal specimens were used, with the "correct locus" pre-defined based on known chromosomal locations.
• Analytical Sensitivity and Verification of Upper Reference Limit: Karyotypically normal individuals or patients lacking the specific abnormalities (monosomy 7 and loss of 7q) were used. The expected typical signal pattern (2R2G) served as the ground truth for normalcy. The "atypical" patterns (1R1G, 1R2G) were defined based on the biological expectation of monosomy 7 or 7q deletion.
• Reproducibility: The ground truth for the panel members was established by preparing mixtures of positive and normal cells to achieve predefined "negative," "low positive," and "high positive" statuses. The origin of the "positive cells" would implicitly be from samples with confirmed deletion 7q or monosomy 7, likely established through standard cytogenetic or FISH methods.

8. The Sample Size for the Training Set

This document describes a diagnostic kit and its analytical validation. It does not refer to a machine learning or AI algorithm development pipeline, so there is no specific mention of a "training set" in the context of algorithm development. The studies performed are for analytical validation.

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

As there is no mention of a "training set" for an algorithm, this question is not applicable. The kit is based on established FISH technology, and its performance is validated through analytical studies.

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