(186 days)
Alinity m SARS-CoV-2 is a real-time in vitro reverse transcription polymerase chain reaction (RT-PCR) assay for use with the automated Alinity m System for the qualitative detection of nucleic acid from SARS-CoV-2 from patients with signs and symptoms of COVID-19 in nasopharyngeal (NP) swab and anterior nasal swab (ANS) specimens.
Results are for the detection and identification of SARS-CoV-2 RNA. Alinity m SARS-CoV-2 assay is intended for use as an aid in the diagnosis of COVID-19 if used in comunction with other clinical, endemiologic, and laboratory findings. Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses.
Negative results do not preclude SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions. Negative results must be combined with clinical observations, patient history, and epidemiological information.
Alinity m SARS-CoV-2 is a real-time in vitro reverse transcription polymerase chain reaction (RT-PCR) assay for use with the automated Alinity m System for the qualitative detection of nucleic acid from SARS-CoV-2 in specimens collected from patients with signs and symptoms of COVID-19.
The steps of the Alinity m SARS-CoV-2 assay consist of sample preparation, RT-PCR assembly, amplification/detection, and result reporting. All stages of the Alinity m SARS-CoV-2 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 SARS-CoV-2 assay in parallel with other Alinity m assays on the same instrument.
The Alinity m SARS-CoV-2 assay requires two separate assay specific kits as follows:
- . Alinity m SARS-CoV-2 AMP Kit; 09N78-096 is comprised of 2 types of multi-well trays: Alinity m SARS-CoV-2 AMP TRAY 1 and Alinity m SARS-CoV-2 ACT TRAY 2. The intended storage condition for the Alinity m SARS-CoV-2 AMP Kit is -15°C to -25°C.
- Alinity m SARS-CoV-2 CTRL Kit: 09N78-086 consists of negative controls and . positive controls, each supplied as liguid in single-use tubes. The Alinity m SARS-CoV-2 controls are used for validity determination of the Alinity m SARS-CoV-2 assay on the automated Alinity m System. These controls are intended to be used with the Alinity m SARS-CoV-2 assay. The intended storage condition for the Alinity m SARS-CoV-2 Control Kit is -15°C to -25°C.
The Alinity m SARS-CoV-2 assay may utilize the following for collection and transport of anterior nasal swab specimens:
- Abbott Universal Collection Kit; 09N92-030 consists of one Transport Tube with a solid cap containing 1.65 mL Specimen Transport Buffer and one sterile Specimen Collection Swab. The Abbott Universal Collection Kit is intended for the collection and transport of anterior nasal swabs for testing with the Alinity m SARS-CoV-2 assay. The collected specimens are intended to be tested on the automated Alinity m System. The intended storage condition for the Abbott Universal Collection Kit is 15°C to 30°C.
- Abbott Universal Collection Kit II: 09N92-040 consists of one Transport Tube with . a pierceable cap containing 1.65 mL Specimen Transport Buffer, one sterile Specimen Collection Swab, and one absorbent pad. The Abbott Universal Collection Kit II is intended for the collection and transport of anterior nasal swabs for testing with the Alinity m SARS-CoV-2 assay. The collected specimens are intended to be tested on the automated Alinity m System; The intended storage condition for the Abbott Universal Collection Kit is 15℃ to 30℃.
SARS-CoV-2 RNA from specimens 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 nucleic acids are then combined with the liquid unit-dose activation reagent, liquid unit-dose amplification reagents, and Alinity m Vapor Barrier Solution, and transferred by the instrument to an amplification/detection module for reverse transcription, PCR amplification, and realtime fluorescence detection.
Assay controls are tested 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. Each Alinity m SARS-CoV-2 CTRL kit contains 12 vials (1.3 mL fill volume) of Negative Control and 12 vials (1.3 mL fill volume) of Positive Control.
The Alinity m SARS-CoV-2 amplification reagents include primers and probes that amplify and detect an exogenous internal control (containing an armored RNA sequence). Amplification and detection of the internal control demonstrates proper sample processing. The internal control is used to demonstrate assay validity.
Patient results are automatically reported on the Alinity m instrument. The Alinity m SARS-CoV-2 application parameters will be contained in an assay application specification file.
The Alinity m SARS-CoV-2 assay also utilizes the following:
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. Alinity m SARS-CoV-2 Assay Application Specification File, List No. 09N78-05A
The Alinity m SARS-CoV-2 application specification file is intended for use with the Alinity m SARS-CoV-2 assay on the automated Alinity m System to allow for processing of assay controls and patient samples. -
Alinity m System and System Software, List No. 08N53-002 •
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Alinity m Sample Prep Kit 2, List No. 09N12-001
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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 Aliquot Tube, List No. 09N49-013
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Alinity m System Solutions, List No. 09N20 •
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. Alinity m Lysis Solution, List No. 09N20-001
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Alinity m Diluent Solution, List No. 09N20-003
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Alinity m Vapor Barrier Solution, List No. 09N20-004
The Alinity m SARS-CoV-2 assay is a real-time in vitro reverse transcription polymerase chain reaction (RT-PCR) assay designed for the qualitative detection of SARS-CoV-2 nucleic acid. The study evaluated its performance for in vitro diagnostic use.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for qualitative assays like this are typically based on positive percent agreement (PPA) and negative percent agreement (NPA) with a composite comparator. While explicit acceptance criteria values (e.g., minimum PPA/NPA) are not directly stated in the provided text, the reported device performance is presented. The study results aim to demonstrate performance comparable to a predicate device, supporting substantial equivalence.
| Performance Metric | Specimen Type (Collection Method) | Reported Device Performance (PPA / NPA) | 95% Confidence Interval |
|---|---|---|---|
| PPA | Nasopharyngeal Swab (HCP-collected) | 96.3% | (92.1, 98.3) |
| NPA | Nasopharyngeal Swab (HCP-collected) | 95.2% | (92.5, 96.9) |
| PPA | Anterior Nasal Swab (Self-Collected, UVT) | 100.0% | (96.2, 100.0) |
| NPA | Anterior Nasal Swab (Self-Collected, UVT) | 99.7% | (98.9, 99.9) |
| PPA | Anterior Nasal Swab (Self-Collected, UCK) | 97.9% | (92.7-99.4) |
| NPA | Anterior Nasal Swab (Self-Collected, UCK) | 97.9% | (96.5-98.8) |
2. Sample Sizes Used for the Test Set and Data Provenance
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Study 1 (Nasopharyngeal Swab):
- Sample Size: 535 specimens included in the analysis (from an initial 627 UVT NPS specimens tested).
- Data Provenance: Prospective clinical study, collected at 8 geographically distributed locations in the US from January to February 2021.
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Study 2 (Anterior Nasal Swab):
- Sample Size (ANS UCK): 766 specimens included in the analysis (from an initial 792 ANS UCK specimens available).
- Sample Size (ANS UVT): 759 specimens included in the analysis (from an initial 787 ANS UVT specimens available).
- Data Provenance: Prospective clinical study, collected at 8 geographically distributed locations in the US from September 2021 to January 2022.
The data is explicitly stated as prospective and collected from the US.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth for the clinical studies was established using a composite comparator (CC) derived from a minimum of two and up to three highly sensitive EUA SARS-CoV-2 molecular assays. The document does not specify the number or qualifications of experts involved in interpreting the results of these comparator assays or in establishing the final composite result. The ground truth relies on the performance of these other molecular assays.
4. Adjudication Method for the Test Set
The adjudication method for the composite comparator ground truth was:
- CC Positive: If a minimum of 2 comparator positive results were reported.
- CC Negative: If a minimum of 2 comparator negative results were reported.
- CC Indeterminate: If a CC could not be determined due to missing results from the comparator assays.
This method resembles a "2-out-of-X" or "majority vote" approach among the comparator assays.
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
This document describes a diagnostic assay (Alinity m SARS-CoV-2) for the detection of nucleic acid, not an AI-assisted diagnostic imaging device or a system involving human "readers." Therefore, a multi-reader multi-case (MRMC) comparative effectiveness study focusing on the improvement of human readers with AI assistance is not applicable and was not performed or reported in this context. The Alinity m System is an automated platform, and the assay's output is a "positive," "negative," or "not detected" result based on the instrument's analysis of the PCR reaction.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented evaluate the standalone performance of the Alinity m SARS-CoV-2 assay on the automated Alinity m System. The device is designed to perform all assay steps automatically (sample preparation, RT-PCR assembly, amplification/detection, and result reporting) without intermediate user intervention. The clinical performance data presented in Table 13 directly reflects this standalone, algorithm-only performance against the composite comparator.
7. The Type of Ground Truth Used
The ground truth used for the clinical studies was a composite comparator established using a minimum of two and up to three highly sensitive EUA SARS-CoV-2 molecular assays. This falls under the category of using established, high-performing diagnostic tests as a reference standard.
8. The Sample Size for the Training Set
The document describes performance data for the Alinity m SARS-CoV-2 assay but does not provide details about a specific training set size for the development of the assay's underlying algorithms or parameters. Molecular assays like RT-PCR involve established biochemical principles and reagents rather than general-purpose machine learning algorithms that typically require large, explicit training datasets for model development in the same way an imaging AI algorithm would. The development of such assays often involves extensive analytical verification and validation, including optimization of primer/probe designs and reaction conditions, rather than a "training set" in the common AI sense.
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, the concept of a "training set" and its "ground truth" in the context of this specific molecular diagnostic assay is not directly applicable or detailed in the provided summary as it would be for an AI/ML-based device. The assay's analytical characteristics (e.g., Limit of Detection, Inclusivity, Cross-reactivity) are established through controlled laboratory experiments using quantified viral material and known biological samples, which serve to define the assay's performance characteristics rather than "train" an algorithm with a labeled dataset.
§ 866.3981 Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test.
(a)
Identification. A device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test is an in vitro diagnostic device intended for the detection and identification of SARS-CoV-2 and other microbial agents when in a multi-target test in human clinical respiratory specimens from patients suspected of respiratory infection who are at risk for exposure or who may have been exposed to these agents. The device is intended to aid in the diagnosis of respiratory infection in conjunction with other clinical, epidemiologic, and laboratory data or other risk factors.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: Analytes and targets the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens;
(ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies including the following, as applicable: Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, precision, reproducibility, and clinical studies;
(iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;
(iv) A warning statement that viral culture should not be attempted in cases of positive results for SARS-CoV-2 and/or any similar microbial agents unless a facility with an appropriate level of laboratory biosafety (
e.g., BSL 3 and BSL 3+, etc.) is available to receive and culture specimens; and(v) A prominent statement that device performance has not been established for specimens collected from individuals not identified in the intended use population (
e.g., when applicable, that device performance has not been established in individuals without signs or symptoms of respiratory infection).(vi) Limiting statements that indicate that:
(A) A negative test result does not preclude the possibility of infection;
(B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;
(C) There is a risk of incorrect results due to the presence of nucleic acid sequence variants in the targeted pathogens;
(D) That positive and negative predictive values are highly dependent on prevalence;
(E) Accurate results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and
(F) When applicable (
e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer-reviewed literature), that the clinical performance may be affected by testing a specific clinical subpopulation or for a specific claimed specimen type.(4) Design verification and validation must include:
(i) Detailed documentation, including performance results, from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, as appropriate, additional characterized clinical samples. The clinical study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained using a comparator that FDA has determined is appropriate. Detailed documentation must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses.
(ii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel respiratory pathogen isolates or strains (
e.g., regular review of published literature and periodic in silico analysis of target sequences to detect possible mismatches). All results of this protocol, including any findings, must be documented and must include any additional data analysis that is requested by FDA in response to any performance concerns identified under this section or identified by FDA during routine evaluation. Additionally, if requested by FDA, these evaluations must be submitted to FDA for FDA review within 48 hours of the request. Results that are reasonably interpreted to support the conclusion that novel respiratory pathogen strains or isolates impact the stated expected performance of the device must be sent to FDA immediately.(iii) A detailed description of the identity, phylogenetic relationship, and other recognized characterization of the respiratory pathogen(s) that the device is designed to detect. In addition, detailed documentation describing how to interpret the device results and other measures that might be needed for a laboratory diagnosis of respiratory infection.
(iv) A detailed device description, including device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device (
e.g., saturation level of hybridization and maximum amplification and detection cycle number, etc.), internal and external controls, and computational path from collected raw data to reported result (e.g., how collected raw signals are converted into a reported signal and result), as applicable.(v) A detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review.
(vi) For devices intended for the detection and identification of microbial agents for which an FDA recommended reference panel is available, design verification and validation must include the performance results of an analytical study testing the FDA recommended reference panel of characterized samples. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens, the design verification and validation must include a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. An evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(5) When applicable, performance results of the analytical study testing the FDA recommended reference panel described in paragraph (b)(4)(vi) of this section must be included in the device's labeling under § 809.10(b) of this chapter.
(6) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens in addition to detection of SARS-CoV-2 and similar microbial agents, the required labeling under § 809.10(b) of this chapter must include the following:
(i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation.
(ii) Where applicable, a warning statement that reads if infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to State or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
(iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required followup actions or retesting in the case of an unusual or unexpected device result.
(iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated (
i.e., H1-2009 and H3), this result requires notification of appropriate local, State, or Federal public health authorities to determine necessary measures for verification and to further determine whether the specimen represents a novel strain of Influenza A.(7) If one of the actions listed at section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain:
(i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those influenza viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate.
(ii) Within 60 days from the date that FDA notifies manufacturers that characterized influenza viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by:
(A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or
(B) In a section of the device's label or in other labeling that accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's website, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the website containing this information and must allow unrestricted viewing access.