(186 days)
Not Found
No
The document describes a standard RT-PCR assay and automated system for detecting SARS-CoV-2 RNA. There is no mention of AI or ML in the device description, intended use, or performance studies. The system automates the process but does not appear to use AI/ML for interpretation or decision-making beyond standard assay validity checks.
No
This device is an in vitro diagnostic (IVD) assay designed to detect SARS-CoV-2 RNA. Its intended use is to aid in the diagnosis of COVID-19, not to treat or therapeutically intervene.
Yes
The Intended Use / Indications for Use section states that the assay is "intended for use as an aid in the diagnosis of COVID-19".
No
The device is an in vitro diagnostic (IVD) assay that requires specific reagents, collection kits, and an automated hardware system (Alinity m System) to perform the test. While it utilizes software for control and reporting, it is not solely software.
Based on the provided text, the device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the Alinity m SARS-CoV-2 is a "real-time in vitro reverse transcription polymerase chain reaction (RT-PCR) assay". The term "in vitro" directly indicates that it is used outside of the body.
- Device Description: The description further reinforces this by detailing how the assay is performed on specimens collected from patients, involving sample preparation, amplification, and detection of nucleic acid. This process is characteristic of in vitro diagnostic tests.
- Purpose: The assay is intended for the qualitative detection of nucleic acid from SARS-CoV-2 to aid in the diagnosis of COVID-19, which is a typical function of an IVD.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
QQX
Device Description
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:
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
Alinity m Sample Prep Kit 2, List No. 09N12-001
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
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
Mentions image processing
Not Found
Mentions AI, DNN, or ML
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Input Imaging Modality
Not Found
Anatomical Site
Nasopharyngeal (NP) swab, anterior nasal swab (ANS)
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Qualified clinical laboratory personnel specifically instructed and trained in the techniques of real-time PCR and on the use of the Alinity m System.
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
Performance of the Alinity m SARS-CoV-2 assay was evaluated in 2 prospective clinical studies.
Study 1:
Sample size: 627 UVT NPS specimens from symptomatic subjects; 535 specimens had CC and were included in the analysis.
Data source: NPS specimens prospectively collected by HCP at 8 geographically distributed locations in the US from January to February 2021.
Annotation protocol: One NPS UVT specimen was collected from each subject for both Alinity m SARS-CoV-2 and comparator testing. Alinity m SARS-CoV-2 results compared to a composite comparator (CC) established using a minimum of two and up to three highly sensitive EUA SARS-CoV-2 molecular assays. 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.
Study 2:
Sample size: 792 ANS UCK specimens and 787 ANS UVT specimens from symptomatic subjects. 785 ANS UCK and 778 ANS UVT specimens had valid Alinity m SARS-CoV-2 results. Of these, 766 ANS UCK specimens and 759 ANS UVT specimens had CC and were included in the analysis. Analysis of paired UCK and UVT included 778 pairs.
Data source: Anterior NS specimens prospectively collected at 8 geographically distributed locations in the US from September 2021 to January 2022.
Annotation protocol: Each subject self-collected 2 anterior NS specimens, one in UCK and another in UVT under HCP supervision. Collection order alternated between two nostrils. ANS UCK specimens were tested only by Alinity m SARS-CoV-2, ANS UVT specimens used for both Alinity m SARS-CoV-2 and comparator testing. Alinity m SARS-CoV-2 results compared to a composite comparator (CC) established using a minimum of two and up to three highly sensitive EUA SARS-CoV-2 molecular assays. 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.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Studies:
- Limit of Detection (Analytical Sensitivity):
- NPS Clinical Matrix: LoD of 0.009 TCID50/mL [or 55 Genome Equivalents (GE)/mL] using cultured gamma-irradiated SARS-CoV-2 virus (USA-WA1/2020) in pooled SARS-CoV-2 negative clinical NP swab specimens collected in UTM.
- Sample Size: 21 replicates for each of 3 target levels (0.0180, 0.0090, 0.0045 TCID50/mL).
- Key results: 95.2% positive rate at 0.0180 TCID50/mL, 100.0% at 0.0090 TCID50/mL, 33.3% at 0.0045 TCID50/mL.
- Nasal Swab Clinical Matrix: LoD of 0.0180 TCID50/mL [or 109 GE/mL] using cultured gamma-irradiated SARS-CoV-2 virus (USA-WA1/2020) in pooled SARS-CoV-2 negative clinical nasal swab specimens collected in UTM.
- Sample Size: 21 replicates for each of 3 target levels (0.0180, 0.0090, 0.0045 TCID50/mL).
- Key results: 100.0% positive rate at 0.0180 TCID50/mL, 81.0% at 0.0090 TCID50/mL, 42.9% at 0.0045 TCID50/mL.
- Universal Collection Kit Swab Clinical Matrix: LoD of 55 GE/mL using cultured gamma-irradiated SARS-CoV-2 virus (USA-WA1/2020) in pooled SARS-CoV-2 negative clinical Universal Collection Kit (UCK) nasal swab specimens.
- Sample Size: 20 replicates for each of 3 target levels (109.0, 55.0, 27.0 GE/mL).
- Key results: 100.0% positive rate at 109 GE/mL and 55 GE/mL, 20.0% at 27 GE/mL.
- NPS Clinical Matrix: LoD of 0.009 TCID50/mL [or 55 Genome Equivalents (GE)/mL] using cultured gamma-irradiated SARS-CoV-2 virus (USA-WA1/2020) in pooled SARS-CoV-2 negative clinical NP swab specimens collected in UTM.
- Detection of SARS-CoV-2 in WHO International Standard:
- Study type: Analytical evaluation.
- Sample size: 24 replicates for each of 8 concentration levels.
- Key results: Decreasing positive rate with decreasing concentration, for example, 100% at 125 IU/mL, 87.5% at 75 IU/mL, 0% at 1 IU/mL.
- Precision:
- Study type: Within-laboratory precision study.
- Sample size: 120 replicates for each of 3 panel members (moderate positive, low positive, negative).
- Key results: Positive percent agreement of 99.2% for low positive and 100.0% for moderate positive. Negative percent agreement of 100.0%.
- Precision in Universal Collection Kits Sample Matrix:
- Study type: Within-laboratory precision study.
- Sample size: 90 replicates for each of 3 panel members.
- Key results: Positive percent agreement of 100.0% and negative percent agreement of 100.0%.
- Reproducibility:
- Study type: Multi-site reproducibility study (3 external clinical testing sites).
- Sample size: 120 replicates for each of 3 panel members.
- Key results: Positive percent agreement of 100.0% for both moderate positive and low positive. Negative percent agreement of 100.0%.
- Analytical Specificity: Potentially Interfering Substances:
- Study type: Interference study.
- Sample size: Not explicitly stated, but substances were tested in SARS-CoV-2 negative panel and positive panel (3X LoD).
- Key results: No interference in performance observed for tested substances at listed concentrations.
- Analytical Specificity: Potential Cross-reactivity and Microbial Interference:
- Study type: Cross-reactivity and microbial interference study.
- Sample size: Not explicitly stated, but microorganisms tested at 10^5 Units/mL for viruses/fungi and 10^8 Units/mL for bacteria.
- Key results: No cross-reactivity or interference observed for tested microorganisms at specified concentrations.
- Inclusivity:
- Study type: Inclusivity evaluation.
- Sample size: 5 replicates for each of 7 SARS-CoV-2 isolates.
- Key results: All replicates of all isolates detected at tested concentrations (100% positive rate). In silico analysis showed >99.999% of sequences in GISAID and NCBI databases predicted to be detected.
- Carryover:
- Study type: Carryover rate determination.
- Sample size: 361 replicates of negative samples processed from alternating positions with high positive samples.
- Key results: Overall carryover rate of 0.0% (95% CI: 0.0% to 1.1%).
Clinical Performance:
- Study 1 (NPS specimens):
- Study type: Prospective clinical study.
- Sample size: 535 NP swab specimens.
- Key results: PPA = 96.3% (92.1%, 98.3%), NPA = 95.2% (92.5%, 96.9%) compared to Composite Comparator.
- Study 2 (Anterior NS specimens - UVT and UCK):
- Study type: Prospective clinical study.
- Sample size: 759 Anterior Nasal Swab (UVT) specimens, 766 Anterior Nasal Swab (UCK) specimens.
- Key results:
- ANS (UVT): PPA = 100.0% (96.2%, 100.0%), NPA = 99.7% (98.9%, 99.9%) compared to Composite Comparator.
- ANS (UCK): PPA = 97.9% (92.7-99.4%), NPA = 97.9% (96.5-98.8%) compared to Composite Comparator.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Clinical Performance:
- Nasopharyngeal Swab (HCP-collected)
- PPA (%): 96.3 (92.1,98.3)
- NPA (%): 95.2 (92.5,96.9)
- Self-Collected Anterior Nasal Swab (UVT)
- PPA (%): 100.0 (96.2,100.0)
- NPA (%): 99.7 (98.9,99.9)
- Self-Collected Anterior Nasal Swab (UCK)
- PPA (%): 97.9 (92.7-99.4)
- NPA (%): 97.9 (96.5-98.8)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
December 6, 2024
Abbott Molecular Stacv Ferguson Director Regulatory Affairs 1300 E Touhy Ave Des Plaines, Illinois 60018
Re: K241580
Trade/Device Name: Alinity m SARS-CoV-2 Regulation Number: 21 CFR 866.3981 Regulation Name: 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 Regulatory Class: Class II Product Code: QQX
Dated: May 31, 2024 Received: June 3, 2024
Dear Stacy Ferguson:
We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
1
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatory
2
assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Anna M. Mielech -S
Anna Mielech, Ph.D. Deputy Branch Chief (Acting) Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K241580
Device Name Alinity m SARS-CoV-2
Indications for Use (Describe)
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.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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510(k) Summary
Table of Contents
Page
| Table of Contents | 1 |
|---|---|
| 1.0 510(k) Summary | 2 |
| 1.1 Submitter | 2 |
| 1.2 Device Information | 3 |
| 1.3 Predicate Device | 3 |
| 1.4 Indication(s) for Use | 3 |
| 1.5 Device Description | 4 |
| 1.6 Similarities and Differences to Predicate Devices | 7 |
| 1.7 Performance Data | 15 |
| 2.0 Conclusion Drawn from the Studies | 33 |
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1.0 510(k) Summary
This 510(k) summary is being submitted in accordance with the requirement of 21 CFR Section 807.92(c).
| 1.1 | Submitter | |
|---|---|---|
| Applicants Name and Address: | Abbott Molecular Inc. | |
| 1300 E. Touhy Ave | ||
| Des Plaines, IL 60018 | ||
| Contact Person: | Stacy Ferguson | |
| Director Regulatory Affairs | ||
| Abbott Molecular, Inc. | ||
| 1300 E. Touhy Avenue | ||
| Des Plaines, IL 60018 | ||
| Phone: 224-361-7449 | ||
| Fax: 224-361-7269 | ||
| Date Prepared: | December 4, 2024 |
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1.2 Device Information
| Trade Name | Regulation Name | Product Code | Regulation Number | Class |
|---|---|---|---|---|
| Alinity m SARS-CoV-2 | Respiratory Specimen Nucleic | |||
| Acid SARS-CoV-2 Test | QQX | 21 CFR 866.3981 | II |
1.3 Predicate Device
| Predicate Device | 510(k) | Date Cleared |
|---|---|---|
| Roche cobas® SARS-CoV-2 Qualitative for use on | ||
| the cobas 6800/8800 Systems | K213804 | October 22, 2022 |
1.4 Indication(s) for Use
1.4.1 Alinity m SARS-CoV-2 AMP Kit (List No. 09N78-096)
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 (ANS) swab 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 conjunction with other clinical, epidemiologic, 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 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.
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1.5 Device Description
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
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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.
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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:
-
. 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 •
-
Alinity m Sample Prep Kit 2, List No. 09N12-001
-
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
-
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
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1.6 Similarities and Differences to Predicate Devices
1.6.1 Alinity m SARS-CoV-2
The legally marketed predicate device chosen for the current submission is the Roche cobas SARS-CoV-2 Qualitative for use on the cobas 6800/8800 Systems assay. The Alinity m SARS-CoV-2 assay is substantially equivalent to the predicate device intended for the qualitative detection of SARS-CoV-2. The primary similarities between Alinity m SARS-CoV-2 assay and the predicate device are presented in Table 1. The primary differences between Alinity m SARS-CoV-2 and the predicate device are shown in Table 2. Both the Alinity m SARS-CoV-2 assay and the predicate have the same intended use. Any technological differences that exist between Alinity m SARS-CoV-2 assay and the predicate device do not raise new types of safety or effectiveness questions.
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| Table 1. Similarities Between Alinity m SARS-CoV-2 Assay and Predicate Device | ||
|---|---|---|
| Feature | Current Submission | Predicate Device |
| Device Trade Name | Alinity m SARS-CoV-2 Assay (K241580) | Roche cobas® SARS-CoV-2 Qualitative for use on the cobas |
| 6800/8800 Systems (K213804) | ||
| Regulation Number | ||
| and Product Code | 21 CFR 866.3981; QQX | 21 CFR 866.3981; QQX |
| Device Class | II | II |
| Technology/Detection | Real-Time Reverse Transcription- Polymerase Chain | |
| Reaction (RT-PCR) | Real-Time Reverse Transcription- Polymerase Chain Reaction | |
| (RT-PCR) | ||
| Intended Use/ | ||
| Indications For Use | 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 (ANS) swab | ||
| 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 conjunction with other | ||
| clinical, epidemiologic, 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. | cobas SARS-CoV-2 Qualitative for use on the cobas 6800/8800 | |
| Systems is a real- time RT-PCR test intended for the qualitative | ||
| detection of nucleic acids from SARS- CoV-2 in nasal and | ||
| nasopharyngeal specimens collected from symptomatic | ||
| individuals suspected of COVID-19 by their healthcare provider. | ||
| Results are for the detection of SARS-CoV-2 RNA. 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 pathogens. | ||
| Negative results do not preclude SARS-CoV-2 infection and | ||
| should not be used as the sole basis for patient management | ||
| decisions. Results are meant to be used in conjunction with clinical | ||
| observations, patient history, recent exposures and epidemiological | ||
| information, and laboratory data, in accordance with the guidelines | ||
| provided by the relevant public health authorities. cobas SARS- | ||
| Table 1. Similarities Between Alinity m SARS-CoV-2 Assay and Predicate Device | ||
| Feature | Current Submission | Predicate Device |
| Device Trade Name | Alinity m SARS-CoV-2 Assay (K241580) | Roche cobas® SARS-CoV-2 Qualitative for use on the cobas |
| 6800/8800 Systems (K213804) | ||
| 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. | CoV-2 is intended for use by qualified clinical laboratory personnel | |
| specifically instructed and trained in the techniques of real-time | ||
| PCR and on the use of the cobas 6800/8800 Systems. | ||
| Conditions for use | For prescription use | For prescription use |
| Assay Type | Qualitative | Qualitative |
| Specimen Types | Nasopharyngeal swab Anterior Nasal swab | Nasopharyngeal swab Nasal swab |
| Assay Targets | SARS-CoV-2 RNA | SARS-CoV-2 RNA |
| Assay Steps | All steps of the Alinity SARS-CoV-2 assay procedure | |
| are executed automatically by the Alinity m System. | ||
| No intermediate processing or transfer steps are | ||
| performed by the user. | All steps of the cobas® SARS-CoV-2 qualitative assay procedure | |
| are executed automatically by the cobas® 6800/8800 Systems. No | ||
| intermediate processing or transfer steps are performed by the | ||
| user. | ||
| Principles of the | ||
| Procedure | 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 | cobas® SARS-CoV-2 is based on fully automated sample | |
| preparation (nucleic acid extraction and purification) followed by | ||
| PCR amplification and detection. The cobas® 6800/8800 Systems | ||
| consist of the sample supply module, the transfer module, the | ||
| processing module, and the analytic module. Automated data | ||
| Table 1. Similarities Between Alinity m SARS-CoV-2 Assay and Predicate Device | ||
| Feature | Current Submission | Predicate Device |
| Device Trade Name | Alinity m SARS-CoV-2 Assay (K241580) | Roche cobas® SARS-CoV-2 Qualitative for use on the cobas |
| 6800/8800 Systems (K213804) | ||
| nucleic acid from SARS-CoV-2 in NP swab and | ||
| ANS specimens. | ||
| 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. | management is performed by the cobas® 6800/8800 software, | |
| which assigns test results for all tests. Results can be reviewed | ||
| directly on the system screen, and printed as a report. | ||
| Nucleic acid from patient samples and added internal control RNA | ||
| (RNA IC) molecules are simultaneously extracted. Nucleic acid is | ||
| released by addition of proteinase and lysis reagent to the sample. | ||
| The released nucleic acid binds to the silica surface of the added | ||
| magnetic glass particles. Unbound substances and impurities, such | ||
| as denatured protein, cellular debris and potential PCR inhibitors, | ||
| are removed with subsequent wash steps and purified nucleic acid | ||
| is eluted from the magnetic glass particles with elution buffer at | ||
| elevated temperature. External controls (positive and negative) are | ||
| processed in the same way with each cobas® SARS-CoV- 2 run. | ||
| SARS-CoV-2 RNA from specimens are 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 | Selective amplification of target nucleic acid from the sample is | |
| achieved by the use of target-specific forward and reverse primers | ||
| for ORF1 a/b non-structural region that is unique to SARS-CoV-2. | ||
| Additionally, a conserved region in the structural protein envelope | ||
| E-gene were chosen for pan-Sarbecovirus detection. The pan- | ||
| Sarbecovirus detection sets will also detect SARS-CoV-2 virus. | ||
| Selective amplification of RNA Internal Control is achieved by | ||
| the use of non- competitive sequence specific forward and reverse | ||
| primers which have no homology with the coronavirus genome. A | ||
| thermostable DNA polymerase enzyme is used for amplification. | ||
| Table 1. Similarities Between Alinity m SARS-CoV-2 Assay and Predicate Device | ||
| Feature | Current Submission | Predicate Device |
| Device Trade Name | Alinity m SARS-CoV-2 Assay (K241580) | Roche cobas® SARS-CoV-2 Qualitative for use on the cobas |
| 6800/8800 Systems (K213804) | ||
| 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. | The cobas® SARS-CoV-2 master mix contains detection probes | |
| which are specific for the coronavirus type SARS-CoV-2, | ||
| members of the Sarbecovirus subgenus, and the RNA Internal | ||
| Control nucleic acid. The coronavirus and RNA Internal Control | ||
| detection probes are each labeled with unique fluorescent dyes that | ||
| act as a reporter. Each probe also has a second dye which acts as a | ||
| quencher. When not bound to the target sequence, the fluorescent | ||
| signals of the intact probes are suppressed by the quencher dye. | ||
| During the PCR amplification step, hybridization of the probes to | ||
| the specific single-stranded DNA template results in cleavage of | ||
| the probe by the 5' to 3' exonuclease activity of the DNA | ||
| polymerase resulting in separation of the reporter and quencher | ||
| dyes and the generation of a fluorescent signal. With each PCR | ||
| cycle, increasing amounts of cleaved probes are generated and the | ||
| cumulative signal of the reporter dye increases concomitantly. | ||
| Each reporter dye is measured at defined wavelengths, which | ||
| enables simultaneous detection and discrimination of the amplified | ||
| coronavirus target and the RNA Internal Control. The master mix | ||
| includes deoxyuridine triphosphate (dUTP), instead of | ||
| deoxythimidine triphosphate (dTTP), which is incorporated into | ||
| the newly synthesized DNA (amplicon). Any contaminating | ||
| amplicons from previous PCR runs are destroyed by the AmpErase | ||
| enzyme [uracil-N-glycosylase], which is included in the PCR mix, | ||
| when heated in the first thermal cycling step. However, newly | ||
| Table 1. Similarities Between Alinity m SARS-CoV-2 Assay and Predicate Device | ||
| Feature | Current Submission | Predicate Device |
| Device Trade Name | Alinity m SARS-CoV-2 Assay (K241580) | Roche cobas® SARS-CoV-2 Qualitative for use on the cobas 6800/8800 Systems (K213804) |
| formed amplicons are not destroyed since the AmpErase enzyme is inactivated once exposed to temperatures above 55°C. | ||
| Instrumentation | ||
| System Components | Alinity m System: | |
| High-throughput, fully integrated laboratory automation system which utilize real-time PCR technology | cobas® 6800/8800 Systems: | |
| High-throughput, fully integrated laboratory automation systems which utilize real- time PCR technology | ||
| Sample Preparation | ||
| Instrument | ||
| Components | Automated liquid handling and robotic manipulation platform. | Automated liquid handling and robotic manipulation platform |
| Amplification and | ||
| Detection | ||
| Instrument | ||
| Components | The Amp-Detect units of the Alinity m System are comprised of PCR thermal cycler/fluorescence reader modules that automate the steps for real-time PCR. | The Analytic Modules of the cobas® 6800/8800 Systems are used for amplification and detection of nucleic acid using real-time PCR, which is carried out by employing fluorescence spectroscopy. |
| Sample Extraction | ||
| Technology | Non-specific nucleic acid capture with magnetic microparticles Magnetic microparticles are washed to remove unbound sample components including potential inhibitors. The bound nucleic acids are eluted and transferred to the lyophilized master mix. | Nucleic acid capture with magnetic glass particles Magnetic glass particles are washed to remove unbound substances and impurities, such as denatured protein, cellular debris and potential PCR inhibitors. The purified nucleic acids are eluted from the glass particles with elution buffer. |
| Table 1. Similarities Between Alinity m SARS-CoV-2 Assay and Predicate Device | ||
| Feature | Current Submission | Predicate Device |
| Device Trade Name | Alinity m SARS-CoV-2 Assay (K241580) | Roche cobas® SARS-CoV-2 Qualitative for use on the cobas |
| 6800/8800 Systems (K213804) | ||
| An internal control (IC) is taken through the entire | ||
| sample preparation and real-time PCR procedure | ||
| along with the specimens, calibrators, and controls to | ||
| demonstrate proper sample processing and IC | ||
| validity. | An internal control (ie, DNA-QS) is taken through the sample | |
| preparation procedure along with the specimens for monitoring the | ||
| sample preparation and PCR amplification process. | ||
| Amplification Controls | Assay specific IC. The IC primer/probe set amplifies | |
| and detects an exogenous RNA sequence unrelated to | ||
| the SARS-CoV-2 target sequences | Selective amplification of RNA Internal Control is achieved by the | |
| use of non- competitive sequence specific forward and reverse | ||
| primers which have no homology with the coronavirus genome. | ||
| Detection Procedure | Optical detection of stimulated fluorescence. | Optical detection of stimulated fluorescence. |
| The fluorescence reader monitors real-time | ||
| fluorescence during every PCR amplification cycle. | The Analytic Module monitors real-time fluorescence during | |
| every PCR amplification cycle. | ||
| Detection Chemistry | Fluorescence labeled, single stranded, target- | |
| specific probes. Detection of the DNA amplicon is achieved | ||
| using nucleic acid (DNA:DNA) hybridization. Probes labeled with different | ||
| fluorophores allowing SARS-CoV-2 to | ||
| be distinguished from the IC amplicons. | Paired reporter and quencher fluorescence labeled probes | |
| (TaqMan Technology) using fluorescence resonance energy | ||
| transfer (FRET) | ||
| Assay Controls | Internal Control (IC) Negative Control Positive Control | Sample processing Control (IC) Negative control Positive control |
| Table 2. Differences Between Alinity m SARS-CoV-2 Assay and Predicate Device | ||
| Feature | Current Submission | Predicate Device |
| Alinity m SARS-CoV-2 Assay (K241580) | Roche cobas® SARS-CoV-2 Qualitative (K213804) | |
| Specimen Collection and Transport | Nasopharyngeal samples must be collected in viral transport media. Nasal specimens must be collected in viral transport medium, universal transport media, or Abbott Universal Collection Kit, or Abbott Universal Collection Kit II. | Nasopharyngeal swab and nasal swab, specimens collected in viral transport medium or universal transport media. |
| Nasal swab specimens may also be collected in cobas® PCR Media Uni Swab Sample Kit, cobas® PCR Media Dual Swab Sample Kit, cobas® PCR Media Kit (and 100 tube PCR Media Kit), or 0.9% Physiological Saline. | ||
| Results Reporting | Not Detected, Negative xx.xx CN, Positive | Target 1 and Target 2 Positive, Detected Target 1 Positive and Target 2 Negative, Detected Target 1 Negative and Target 2 Positive, Presumptive Positive Target 1 and 2 Negative, Not Detected |
| Instrument System | Alinity m System | Cobas 6800/8800 Systems |
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1.7 Performance Data
The following performance data were provided in support of the substantial equivalence determination.
1.7.1 Specific Performance Characteristics - Analytical Studies
1.7.1.1 Limit of Detection (Analytical Sensitivity) Using Cultured Gamma-Irradiated Virus in Nasopharyngeal Swab Clinical Matrix
LoD in clinical Nasopharyngeal (NP) swab matrix was evaluated by testing dilutions of cultured gamma-irradiated SARS-CoV-2 virus (USA-WA1/2020; BEI Catalog NR-52287, Lot 70033322) prepared in pooled SARS-CoV-2 negative clinical NP swab specimens collected in UTM. The initial LoD was determined by testing 3 target levels at 0.0180, 0.0090, and 0.0045 TCIDs/mL, each in replicates of 4. LoD was confirmed by testing the 3 target levels, each in replicates of 21. The results are summarized in Table 3. The LoD for NP swab specimens was determined to be 0.009 TCIDsomL [or 55 Genome Equivalents (GE)/mL].
| Concentration | Number of Replicates | |||
|---|---|---|---|---|
| TCID50/mLa | GEb/mL | Valid | Positive | Positive Rate (%) |
| 0.0180 | 109 | 21 | 20 | 95.2 |
| 0.0090 | 55 | 21 | 21 | 100.0 |
| 0.0045 | 27 | 21 | 7 | 33.3 |
Table 3. Limit of Detection Using Cultured Gamma-Irradiated SARS-CoV-2 Virus in
a TCID50/mL = Median Tissue Culture Infectious Dose/mL.
b Based on the information provided in the Certificate of Analysis from the vendor, I TCIDs; is equal to 6,071 genome equivalents (GE) by ddPCR.
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1.7.1.2 Limit of Detection (Analytical Sensitivity) Using Cultured Gamma-Irradiated Virus in Nasal Swab Clinical Matrix
LoD in clinical nasal swab matrix was evaluated by testing dilutions of cultured gammairradiated SARS-CoV-2 virus (USA-WA1/2020; BEI Catalog NR-52287, Lot 70033322) prepared in pooled SARS-CoV-2 negative clinical nasal swab specimens collected in UTM. The initial LoD was determined by testing 3 target levels at 0.0180, 0.0090, and 0.0045 TCIDs/mL, each in replicates of 3. LoD was confirmed by testing the 3 target levels, each in replicates of 21. The results are summarized in Table 4. The LoD of 0.0180 TCIDs/mL [or 109 GE/mL] was determined for nasal swab specimens.
Table 4. Limit of Detection Using Cultured Gamma-Irradiated SARS-CoV-2 Virus in Nasal Swab Clinical Matrix
| Concentration | Number Of Replicates | |||
|---|---|---|---|---|
| TCID50/mL | GEᵃ/mL | Valid | Positive | Positive Rate (%) |
| 0.0180 | 109 | 21 | 21 | 100.0 |
| 0.0090 | 55 | 21 | 17 | 81.0 |
| 0.0045 | 27 | 21 | 9 | 42.9 |
a Based on the information provided in the Certificate of Analysis from the vendor, I TCIDso is equal to 6,071 genome equivalents (GE) by ddPCR.
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1.7.1.3 Limit of Detection Using Cultured Gamma-Irradiated Virus in Universal Collection Kit Swab Clinical Matrix
LoD in clinical nasal swab matrix was evaluated by testing dilutions of cultured gammairradiated SARS-CoV-2 virus (USA-WA1/2020; BEI Catalog NR-52287, Lot 70039068) prepared in pooled SARS-CoV-2 negative clinical Universal Collection Kit (UCK) nasal swab specimens. The initial LoD was determined by testing 4 target levels at 109.0. 55.0. 27.0, and 13.5 GE/mL, each in replicates of 3. LoD was confirmed by testing 3 target levels (109.0, 55.0, and 27.0 GE/mL), each in replicates of 20. The results are summarized in Table 5. The LoD of 55 GE/mL was determined for UCK swab specimens.
| Concentration | Number Of Replicates | ||
|---|---|---|---|
| GEa/mL | Valid | Positive | Positive Rate (%) |
| 109 | 20 | 20 | 100.0 |
| 55 | 20 | 20 | 100.0 |
| 27 | 20 | 4 | 20.0 |
Table 5. Limit of Detection Using Cultured Gamma-Irradiated SARS-CoV-2 Virus in Nasal Swab Matrix
a Based on the information provided in the Certificate of Analysis from the vendor, 1 TCD2g is equal to 273 genome equivalents (GE) by ddPCR.
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1.7.1.4 Detection of SARS-CoV-2 in WHO International Standard
Detection of SARS-CoV-2 by Alinity m SARS-CoV-2 was evaluated by testing World Health Organization (WHO) 1st International Standard for SARS-CoV-2 (NIBSC code: 20/146) at 8 concentration levels (125, 100, 75, 50, 25, 10, 5, and 1 IU/mL), prepared in simulated nasal matrix (SNM). Each concentration level was tested in a total of 24 replicates. The results are summarized in Table 6.
| Concentration | Number of Replicates | Positive Rate (%) | |
|---|---|---|---|
| IU/mL | Valid | Positive | |
| 125 | 24 | 24 | 100.0 |
| 100 | 24 | 24 | 100.0 |
| 75 | 24 | 21 | 87.5 |
| 50 | 24 | 20 | 83.3 |
| 25 | 24 | 16 | 66.7 |
| 10 | 24 | 7 | 29.2 |
| 5 | 24 | 1 | 4.2 |
| 1 | 24 | 0 | 0.0 |
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1.7.1.5 Precision
Alinity m SARS-CoV-2 assay within-laboratory precision was evaluated using a 3member panel composed of 2 positive panel members and 1 negative panel member in simulated nasal matrix (SNM). The 2 positive panels consisted of one moderate positive panel member containing gamma irradiated SARS-CoV-2 virus at approximately 5X LoD and one low positive panel at approximately 2X LoD. Negative SNM was used as a negative panel member. The SARS-CoV-2 positive panel members were prepared by diluting cultured gamma-irradiated SARS-CoV-2 virus (USA-WA1/2020; BEI Catalog No. NR-52287, Lot 70033322) in SNM. Each panel member was tested in 4 replicates in a run, 2 runs each day for 5 days, on 3 Alinity m Systems with 3 Alinity m SARS-CoV-2 AMP Kit lots by 3 operators, for a total of 120 replicates for each panel member. The results, representative of the precision of Alinity m SARS-CoV-2, are summarized in Table 7. The positive percent agreement was 99.2% for low positive and 100.0% for moderate positive. The negative percent agreement was 100.0%.
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Table 7. Precision
| | | | | | Within-Run
Component | | Between-Run
Component | | Between-Day
Component | | Within-
Laboratoryc | | Between-
Instrument/
Lot/Operator
Componentd | | Totale | |
|----------------------------------|-----|-----|--------------------|------------|-------------------------|------|--------------------------|------|--------------------------|------|------------------------|------|-------------------------------------------------------|------|--------|------|
| Panel
Member | Na | Nb | Agreement
(n/N) | Mean
CN | SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV |
| Moderate
Positive
(5x LoD) | 120 | 120 | 100.0% | 34.49 | 0.808 | 2.3 | 0.000 | 0.0 | 0.368 | 1.1 | 0.888 | 2.6 | 0.000 | 0.0 | 0.888 | 2.6 |
| Low
Positive
(2x LoD) | 119 | 118 | 99.2% | 36.15 | 0.966 | 2.7 | 0.000 | 0.0 | 0.311 | 0.9 | 1.015 | 2.8 | 0.181 | 0.5 | 1.031 | 2.9 |
| Negative | 119 | 119 | 100.0% | - | - | - | - | - | - | - | - | - | - | - | - | - |
ª Total number of valid replicates.
Replicats with positive result interpretation for positive result interpretation for negative parel. Number of replicates used in the Mean and SD calculation for the positi panel members.
& Within-laboratory includes Within-Run, Between-Run, and Between-Day Components.
4 Alinity m System, Alinity m SARS-CoV-2 AMP Kit lot, and Operator are confounding effect is represented by InstrumentLot/Operator.
e Total includes Within-Run, Between-Run, Between-Day, and Between-Instrument/Lot/Operator Components.
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1.7.1.6 Precision in Universal Collection Kits Sample Matrix
Alinity m SARS-CoV-2 assay within-laboratory precision was evaluated using a 3member panel composed of 2 positive panel members and 1 negative panel member in simulated Universal Collection Kits sample matrix. The 2 positive panels consisted of one moderate positive panel member containing gamma irradiated SARS-CoV-2 virus at approximately 5X LoD and one low positive panel at approximately 2X LoD. Negative SNM was used as a negative panel member. The SARS-CoV-2 positive panel members were prepared by diluting cultured gamma-irradiated SARS-CoV-2 virus (USA-WA1/2020; BEI Catalog No. NR-52287, Lot 70039068) in simulated Universal Collection Kit sample matrix. Each panel member was tested in 3 replicates in a run, 2 runs each day for 5 days, on 3 Alinity m Systems with 3 Alinity m SARS-CoV-2 AMP Kit lots by 3 operators, for a total of 90 replicates for each panel member. The results, representative of the precision of Alinity m SARS-CoV-2, are summarized in Table 8.
The positive percent agreement was 100.0% and the negative percent agreement was 100.0%.
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Table 8. Precision in Simulated Universal Collection Kits Sample Matrix
| | | | | | Within-Run
Component | | Between-Run
Component | | Between-Day
Component | | Within-
Laboratoryc | | Between-
Instrument/
Lot/Operator
Componentd | | Totale | |
|----------------------------------|----|----|--------------------|------------|-------------------------|------|--------------------------|------|--------------------------|------|------------------------|------|-------------------------------------------------------|------|--------|------|
| Panel
Member | Na | Nb | Agreement
(n/N) | Mean
CN | SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV |
| Moderate
Positive (5x
LoD) | 90 | 90 | 100.0% | 33.85 | 0.525 | 1.6 | 0.000 | 0.0 | 0.000 | 0.0 | 0.525 | 1.6 | 0.128 | 0.4 | 0.541 | 1.6 |
| Low
Positive
(2x
LoD) | 90 | 90 | 100.0% | 35.38 | 0.681 | 1.9 | 0.000 | 0.0 | 0.000 | 0.0 | 0.681 | 1.9 | 0.085 | 0.2 | 0.686 | 1.9 |
| Negative | 90 | 90 | 100.0% | - | - | - | - | - | - | - | - | - | - | - | - | - |
ª Total number of valid replicates.
" Replicats with positive result interpretation for positive result interpretation for negative parel. Number of replicates used in the Mean and SD calculation for the positi panel members.
& Within-laboratory includes Within-Run, Between-Run, and Between-Day Components.
4 Alinity m System, Alinity m SARS-CoV-2 AMP Kit lot, and Operator are confounding effect is represented by InstrumentLot/Operator.
6 Total includes Within-Run, Between-Run, Between-Day, and Between-Instrument/Lot/Operator Components.
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1.7.1.7 Reproducibility
Reproducibility of the Alinity m SARS-CoV-2 assay was evaluated at 3 external clinical testing sites by testing a 3-member panel prepared with SNM. The 2 positive panels consisted of one moderate positive panel member containing gamma irradiated SARS-CoV-2 virus (USA-WA1/2020; BEI Catalog NR-52287, Lot 70033322) at approximately 5X LoD and one low positive panel at approximately 2X LoD. Negative SNM was used as a negative panel member. A total of 3 Alinity m SARS-CoV-2 AMP Kit lots were used. Each of the 3 external sites tested 2 Alinity m SARS-CoV-2 AMP Kit lots, on 5 non-consecutive days for each lot. Four replicates of each panel member were tested on each of 5 days. Each of the 3 external sites used different lots of Alinity m SARS-CoV-2 CTRL Kits and Alinity m Sample Prep Kit 2. The reproducibility results are summarized in Table 9.
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Table 9. Reproducibility
| Panel
Member | Na | Nb | Agreement
(n/N) | Mean
CN | Within-Run
Component | | Between-Run
Component | | Between-Day
Component | | Within-
Laboratoryc | | Between-
Site/Instrument
Component | | Totald | |
|----------------------------------|-----|-----|--------------------|------------|-------------------------|-----|--------------------------|-----|--------------------------|-----|------------------------|-----|------------------------------------------|-----|--------|-----|
| Moderate
Positive
(5x LoD) | 120 | 120 | 100.0% | 34.27 | 0.62 | 1.8 | 0.00 | 0.0 | 0.54 | 1.6 | 0.535 | 1.6 | 0.00 | 0.0 | 0.82 | 2.4 |
| Low Positive
(2x LoD) | 119 | 119 | 100.0% | 35.78 | 0.74 | 2.1 | 0.38 | 1.1 | 0.28 | 0.8 | 0.681 | 1.9 | 0.17 | 0.5 | 0.89 | 2.5 |
| Negative | 119 | 119 | 100.0% | - | - | - | - | - | - | - | - | - | - | - | - | - |
a Total number of valid replicates.
- Replicates with positive result interpretation for positive result interpretation for negative parel. Number of replicates used in the Mean and SD calculation for the positive panel members.
° Within-laboratory includes Within-Run, Between-Run, and Between-Day Components.
d Total includes Within-Run, Between-Run, Between-Day, and Between-Instrument Components.
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Analytical Specificity: Potentially Interfering Substances 1.7.1.8
The effects of potentially interfering substances that may be encountered in respiratory specimens on Alinity m SARS-CoV-2 performance were evaluated by testing both SARS-CoV-2 negative panel and SARS-CoV-2 positive panel (targeted to 3X LoD) in the presence of the substances (Table 10). No interference in the performance of Alinity m SARS-CoV-2 was observed for the tested substances at concentrations listed in Table 10.
| Substance | Active Ingredient(s) | Tested Concentration |
|---|---|---|
| Analgesic Ointment - Vicks® VapoRub™ | Camphor-synthetic, eucalyptus oil and | |
| menthol ointment | 1% (w/v) | |
| Antibacterial, Systemic (Tobramycin) | Tobramycin | 4 µg/mL |
| Antibiotic, Nasal Ointment - Bactroban® | Mupirocin | 5 mg/mL |
| Anti-Viral Drug - Relenza™ | Zanamivir | 5 mg/mL |
| Anti-Viral Drug - Tamiflu® | Oseltamivir | 3.3 mg/mL |
| Anti-Viral Drug - Veklury® | Remdesivir | 27.0 μM |
| Blood (human)a | N/A | 10% (v/v) |
| Chloroseptic Sore Throat Spray | Phenol | 5% (v/v) |
| Corticosteroid - Dexamethasone | Dexamethasone | 0.2 mg/mL |
| Cough Syrup (Wal-Tussin) | Dextromethorphan and guaifenesin | 5% (v/v) |
| FluMistcb | Live intranasal influenza virus | 10% (v/v) |
| Human Genomic DNA | N/A | 0.02 mg/mL |
| Leukocytes | Leukocytes | 1.1E6 cells/mL |
| Liposomal-NUMB250 Spray | Lidocaine and Phenylephrine | 2.68 mg/mL |
| Mucin - Bovine | Purified bovine mucin protein | 5 mg/mL |
| Mucin - Porcinec | Purified porcine mucin protein | 5 mg/mL |
| Nasal Corticosteroid - Budesonide | Budesonide | 2% (v/v) |
| Nasal Corticosteroid - Flunisolide | Flunisolide | 2% (v/v) |
Table 10. Potentially Interfering Endogenous and Exogenous Substances
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| Nasal Corticosteroid - Mometasone | Mometasone | 2% (v/v) |
|---|---|---|
| Nasal Corticosteroid - QVAR® | Beclomethasone | 2% (v/v) |
| Nasal Corticosteroid - Triamcinolone | Triamcinolone | 2% (v/v) |
| Nasal Corticosteroid - Flonase® Sensimist™ | Fluticasone Furoate | 10% (v/v) |
| Nasal Decongestant - Phenylephrine | Phenylephrine | 2% (v/v) |
| Nasal Gel /Homeopathic Allergy | ||
| Relief Medicine - Zicam® | Galphimia glauca, | |
| Histaminum hydrochloricum, | ||
| Luffa operculata, Sulfur | 10% (v/v) | |
| Nasal Spray-Afrin® | Oxymetazoline | 15% (v/v) |
| Nicotine Product | Nicotine | 0.05 mg/ml |
| Oral rinse- Listerine® Cool Mint® | Ethanol, essential oil | 10% (v/v) |
| Saline nasal mist | Sodium chloride | 2% (v/v) |
| Saliva (Human) | N/A | 10% (v/v) |
| Throat Lozenges, Oral Anesthetic and Analgesic - | ||
| Cepacol® | Benzocaine, Menthol | 5 mg/mL |
| Throat Lozenge - Cold Eeze® | Zincuum Gluconicum | 2.5% (w/v) |
| Tobacco product | Nicotine | 0.1% (w/v) |
| Toothpaste | Fluoride | 1% (w/v) |
| Vaseline® | Petroleum Jelly | 1% (w/v) |
Table 10. Potentially Interfering Endogenous and Exogenous Substances
ª One replicate was valid and not detected. Per protocol, the sample was retested in triplicate and all retest samples were valid and detected.
bFluMist was not tested for negative panel due to material availability.
^ One replicate was a "no test" (instrument error) and per protocol, the sample was retested in triplicate and all retest samples were valid and detected.
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1.7.1.9 Analytical Specificity: Potential Cross-reactivity and Microbial Interference
A panel of potential cross-reacting microorganisms (viruses, bacteria, and fungi) that are phylogenetically related to the analyte of the assay or that are commonly found in respiratory tract and pooled human nasal wash were tested with Alinity m SARS-CoV-2 to assess cross-reactivity and microbial interference. The microorganisms, except where noted otherwise in Table 11, were tested at 105 Units/mL for viruses and fungi and 100 Units/mL for bacteria, where these concentrations were available. The unit of measure was specific to each microorganism. Bacteria and fungi were tested as whole microorganisms. Viruses were tested as viral particles, viral lysate, or viral RNA.
To assess potential cross-reactivity, each microorganism was tested in SARS-CoV-2 negative samples. No cross-reactivity was observed in the presence of the tested microorganisms (Table 11) at the concentrations tested.
To assess potential microbial interference, microorganisms were added to positive samples containing SARS-CoV-2 targeted to 3X LoD. No interference in the performance of Alinity m SARS-CoV-2 was observed for the tested microorganisms (Table 11) at the concentrations tested.
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Table 11. Potential Cross-Reactants
| Bacteria | Viruses | ||
|---|---|---|---|
| Bordetella pertussis | Neisseria elongata | Adenovirus Type 5b | MERS-coronavirusd |
| Chlamydia pneumoniae | Neisseria meningitidis | Bocavirus DNA | Mumps Virus |
| Chlamydophila psittaci | Pseudomonas aeruginosa | Cytomegalovirus (CMV)b | Parainfluenza virus 1b |
| Corynebacterium diphtheriae | Staphylococcus epidermis | Enterovirus EV68b | Parainfluenza virus 2b |
| Coxiella burnetti | Staphylococcus aureus | Epstein-Barr Virus (EBV)b | Parainfluenza virus 3b |
| Escherichia coli | Streptococcus pneumoniae | Human coronavirus 229Ec | Parainfluenza virus 4b |
| Haemophilus influenzae | Streptococcus salivarius | Human coronavirus HKU1d | Parechovirus Type 3b |
| Lactobacillus gasseri | Streptococcus pyogenes | Human coronavirus NL63c | Respiratory syncytial virus Type Ac |
| Lactobacillus (plantarum 17-5) | Fungi | Human coronavirus OC43b | Respiratory syncytial virus Type Bc |
| Legionella pneumophila | Aspergillus fumigatus | Human Metapneumovirus (hMPV) | Rhinovirusc |
| Legionella longbeachae, Long Beach 4 | Candida albicans | Influenza A (H1N1)c | SARS-coronavirusd |
| Moraxella catarrhalis | Pneumocystis jirovecii (PJP) (2% and 100%)a | Influenza A (H3N2)c | |
| Mycoplasma pneumoniae | Other | Influenza Bc | |
| Mycobacterium tuberculosis | Pooled Human Nasal Wash (10%) | Measlesb |
ª The concentration provided by the vendor is expressed in Ct Range, 23 to 25. This sample was tested neat (100%) and as a 50-fold dilution (2%).
b Viral lysate
© Viral particles
d Viral RNA
Alinity m SARS-CoV-2 K241580
December 2024
Page 28 of 33
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1.7.1.10 Inclusivity
The inclusivity of Alinity m SARS-CoV-2 assay for the detection of SARS-CoV-2 was evaluated by testing 7 isolates of SARS-CoV-2 from 6 different geographical regions. SARS-CoV-2 isolates tested in this study were different from the inactivated virus tested in the Limit of Detection studies. Each individual virus isolate (inactivated virus or purified RNA) was tested in negative NP swab matrix in 5 replicates. The Alinity m SARS-CoV-2 assay detected all replicates of all isolates at the concentrations tested (Refer to Table 12). Additional in silico analysis of the RdRp and N primer/probe sets for homology with SARS-CoV-2 genomic sequences was performed and showed that more than 99.999% of the sequences available in the GISAID as of October 11, 2023 and NCBI as of October 10, 2023 databases are predicted to be detected by the Alinity m SARS-CoV-2 assay.
| Table 12. Inclusivity | ||
|---|---|---|
| SARS-CoV-2 Isolate | Concentrationa | Positive Rate |
| (Number Positive/Total Valid) | ||
| USA-AZ1/2020 | 165 GE/mL | 100% (5/5) |
| USA-CA3/2020 | 165 GE/mL | 100% (5/5) |
| Hong Kong/VM20001061/2020 | 165 GE/mL | 100% (5/5) |
| USA-IL1/2020 | 165 GE/mL | 100% (5/5) |
| Italy-INMI1 | 165 GE/mL | 100% (5/5) |
| USA/CA_CDC_5574/2020 | ||
| (B.1.1.7) | 0.027 TCID50/mL | 100% (5/5) |
| hCoV-19/South Africa/KRISP- | ||
| K005325/2020 (B.1.351) | 0.027 TCID50/mL | 100% (5/5) |
| | | | | Table 12. Inclusivity
- |
|--|--|--|--|----------------------------|
|--|--|--|--|----------------------------|
a GE/mL = Genome Equivalent/mL or TCIDsy/mL = Median Tissue Culture Infectious Dose/mL.
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1.7.1.11 Carryover
The carryover rate for Alinity m SARS-CoV-2 was determined by analyzing 361 replicates of negative samples processed from alternating positions with high positive samples containing SARS-CoV-2 target at 2.000.000.000 Copies/mL, across a total of 15 runs. SARS-CoV-2 RNA was not detected in any of the negative samples, resulting in an overall carryover rate of 0.0% (95% CI: 0.0% to 1.1%).
1.7.2 Clinical Performance
The performance of the Alinity m SARS-CoV-2 assay was evaluated in 2 prospective clinical studies that tested prospective clinical specimens collected in viral transport media (UVT or UTM) and in Abbott Universal Collection Kit (UCK) from individuals presenting with signs and symptoms of a respiratory tract infection and/or COVID-19. Study 1 tested nasopharyngeal swab (NPS) specimens, collected by a healthcare provider (HCP), in UVT. Study 2 tested anterior self-collected anterior nasal swab (ANS) specimens by the subject under HCP supervision, in the UCK and UVT.
In both studies, the Alinity m SARS-CoV-2 results were compared to a composite comparator (CC) established using a minimum of two and up to three highly sensitive EUA SARS-CoV-2 molecular assays. 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 as CC indeterminate if a CC could not be determined due to missing results from the comparator assays.
1.7.2.1 Studv 1
NPS specimens were prospectively collected by the HCP at 8 geographically distributed locations in the US from January to February 2021. One NPS UVT specimen was collected from each subject for both Alinity m SARS-CoV-2 and comparator testing. A
35
total of 627 UVT NPS specimens from symptomatic subjects were tested by Alinity m SARS-CoV-2.
Valid Alinity m SARS-CoV-2 results were obtained for 611 specimens, of which 535 specimens had CC and were included in the analysis, while 76 specimens did not have CC.
1.7.2.2 Study 2
Anterior NS specimens were prospectively collected at 8 geographically distributed locations in the US from September 2021 to January 2022. Each subject self-collected 2 anterior NS specimens, one in UCK and another in UVT under HCP supervision, where the collection order (first specimen collected in UVT or UCK) alternated between two nostrils. ANS UCK specimens were tested by Alinity m SARS-CoV-2 only, whereas ANS UVT specimens were used for both Alinity m SARS-CoV-2 and comparator testing. A total of 792 ANS UCK specimens and 787 ANS UVT specimens from symptomatic subjects were available for testing by Alinity m SARS-CoV-2, of which 785 ANS UCK and 778 ANS UVT specimens had valid Alinity m SARS-CoV-2 results. Of the 785 ANS UCK specimens with valid results, 766 specimens had CC and were included in the analysis, while 19 specimens did not have CC. Of the 778 NS UVT specimens with valid results, 759 specimens had CC and were included in the analysis, while 19 specimens did not have CC. The analysis of the Alinity m SARS-CoV-2 results for the paired UCK and UVT specimens included 778 pairs.
For specimens in UVT, Alinity m SARS-CoV-2 yielded a positive percent agreement (PPA) with CC of 96.3% for NPS, and 100.0% for self-collected (under HCP supervision) ANS specimens; and a negative percent agreement (NPA) with CC of 95.2% for NPS, and 99.7% for ANS specimens. For the self-collected (under HCP supervision) ANS specimens in UCK, Alinity m SARS-CoV-2 yielded a PPA of 97.9% and an NPA of 97.9% when compared to CC. (Table 13).
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| Table 13. Clinical Performance of the Alinity m SARS-CoV-2 Assay Versus Composite Comparator | |||||||
|---|---|---|---|---|---|---|---|
| Specimen Typea | N | TP | FN | TN | FP | PPA (%) | |
| (95% CI) | NPA (%) | ||||||
| (95% CI) | |||||||
| Nasopharyngeal Swab | |||||||
| HCP-collected | 535 | 154 | 6 | 357 | 18 | 96.3 (92.1,98.3) | 95.2 (92.5,96.9) |
| Self-Collectedb | |||||||
| Anterior Nasal Swab | |||||||
| (UVT) | 759 | 96 | 0 | 661 | 2 | 100.0 (96.2,100.0) | 99.7 (98.9,99.9) |
| Anterior Nasal Swab | |||||||
| (UCK) | 766 | 94 | 2 | 656 | 14 | 97.9 (92.7-99.4) | 97.9 (96.5-98.8) |
TP = true positive; FN = false negative; TN = true negative; FP = false positive
ª HCP-collected nasopharyngeal swab data were from study 1. HCP-collected nasal swab data were from study 3.
b Nasal swab specimens self-collected on-site with healthcare provider instructions.
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2.0 Conclusion Drawn from the Studies
The analytical and clinical study results demonstrate that the Alinity m SARS-CoV-2 assay on the Alinity m System performs comparably to the predicate device in detecting SARS-CoV-2 and supports a substantial equivalence decision.