Alinity m Resp-4-Plex
K241573 · Abbott Molecular, Inc. · QOF · Feb 14, 2025 · Microbiology
Device Facts
| Record ID | K241573 |
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| Device Name | Alinity m Resp-4-Plex |
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| Applicant | Abbott Molecular, Inc. |
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| Product Code | QOF · Microbiology |
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| Decision Date | Feb 14, 2025 |
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| Decision | SESE |
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| Submission Type | Traditional |
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| Regulation | 21 CFR 866.3981 |
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| Device Class | Class 2 |
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Intended Use
Alinity m Resp-4-Plex is a multiplexed real-time in vitro reverse transcription polymerase chain reaction (RT-PCR) assay for use with the automated Alinity m System for the qualitative detection and differentiation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), influenza A virus, influenza B virus and Respiratory Syncytial Virus (RSV) in nasopharyngeal swab specimens collected from patients with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza A, influenza B, and RSV can be similar. The Alinity m Resp-4-Plex assay is intended for use in the differential detection of SARS-CoV-2, influenza A, influenza B and/or RSV RNA and aids in the diagnosis of COVID-19, influenza and/or RSV infections if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza A, influenza B and RSV viral RNA are generally detectable in nasopharyngeal swab specimens during the acute phase of infection. This test is not intended to detect influenza C virus infections. Positive results are indication of the presence of the identified virus, but do not rule out bacterial infection or co-infection with other pathogens not detected by the test. The agent(s) detected by the Alinity m Resp-4-Plex assay may not be the definite cause of disease. Negative results do not preclude SARS-CoV-2, influenza A, influenza B, and/or RSV infections and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Device Story
Multiplexed RT-PCR assay for automated Alinity m System; detects SARS-CoV-2, influenza A, influenza B, and RSV RNA in nasopharyngeal swabs. System automates sample prep, PCR assembly, amplification, and detection. Uses magnetic microparticle technology for nucleic acid extraction; real-time PCR with analyte-specific fluorescent probes for simultaneous detection. Used in clinical laboratories; operated by trained personnel. Output provides qualitative results for each target; aids in differential diagnosis of respiratory infections. Results used alongside clinical/epidemiological data to guide patient management.
Clinical Evidence
Prospective multicenter study (n=2,753 for flu A/B; n=2,745 for RSV; n=826 for SARS-CoV-2) compared Alinity m Resp-4-Plex to composite comparators (FDA-cleared assays). Prospective PPA/NPA: flu A (100%/99.6%), flu B (N/A/100%), RSV (98%/99.7%), SARS-CoV-2 (95.3%/96%). Retrospective study (n=515) supplemented flu B data, showing 100% PPA and 98.5% NPA. Bench testing confirmed LoD, inclusivity, precision, and lack of interference/cross-reactivity.
Technological Characteristics
Multiplexed RT-PCR assay; utilizes magnetic microparticle-based nucleic acid extraction. Targets: SARS-CoV-2 (RdRp, N), flu A (Matrix), flu B (Nonstructural 1), RSV (Matrix). Real-time fluorescence detection. Automated on Alinity m System. Storage: -25°C to -15°C. Includes internal control for process validity.
Indications for Use
Indicated for qualitative detection and differentiation of SARS-CoV-2, influenza A, influenza B, and RSV in nasopharyngeal swab specimens from patients with signs/symptoms of respiratory tract infection. Aids in diagnosis of COVID-19, influenza, and RSV. Not for influenza C detection. Prescription use only.
Regulatory Classification
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.
Special Controls
*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.
Predicate Devices
- Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay (K222736)
Related Devices
- K242465 — Panther Fusion SARS-CoV-2/Flu A/B/RSV assay · Hologic, Inc. · Nov 15, 2024
Submission Summary (Full Text)
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February 14, 2025
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA acronym and name on the right. The Department of Health & Human Services logo is a stylized depiction of a human figure. The FDA acronym is in a blue square, and the words "U.S. FOOD & DRUG ADMINISTRATION" are in blue text to the right of the square.
Abbott Molecular Inc Stacy Ferguson Director Regulatory Affairs 1300 E Touhy Ave Des Plaines, Illinois 60018
Re: K241573
Trade/Device Name: Alinity m Resp-4-Plex 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: QOF 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.
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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
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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, PhD. Deputy Branch Chief (Acting) Viral Respiratory and HPV Branch 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) K241573
Device Name
Alinity m Resp-4-Plex
Indications for Use (Describe)
Almity m Resp-4-Plex is a multiplexed real-time in vitro reverse transcription polymerase chain reaction (RT-PCR) assay for use with the automated Alinity m System for the qualitative detection and differentiation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), influenza A virus, influenza B virus and Respiratory Syncytial Virus (RSV) in nasopharyngeal swab specimens collected from patients with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza B, and RSV can be similar.
The Alinity m Resp-4-Plex assay is intended for use in the differential detection of SARS-CoV-2, influenza B and/or RSV RNA and aids in the diagnosis of COVID-19, influenza and/or RSV infections if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza B and RSV viral RNA are generally detectable in nasopharyngeal swab specimens during the acute phase of infection. This test is not intended to detect influenza C virus infections.
Positive results are indication of the identified virus, but do not rule out bacterial infection or co-infection with other pathogens not detected by the test. The agent(s) detected by the Alinity m Resp-4-Plex assay may not be the definite cause of disease.
Negative results do not preclude SARS-CoV-2, influenza B and/or RSV infections and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
| Type of Use (Select one or both, as applicable) | | | | |
|--------------------------------------------------|---------------------------------------------|--|--|--|
| X Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) | | | |
| CONTINUE ON A SEPARATE PAGE IF NEEDED. | | | | |
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## 510(k) Summary
| Table of Contents | | |
|-------------------|----------------------------------------------------------------|----|
| 1.0 | Submitter | 2 |
| 1.1 | Device Information | 3 |
| 1.2 | Predicate Device | 3 |
| 1.3 | Intended Use | 4 |
| 2.0 | Device Description | 5 |
| 3.0 | Similarities and Differences to the Predicate Device | 8 |
| 4.0 | Performance Data | 12 |
| 4.1 | Specific Performance Characteristics – Analytical Studies | 12 |
| 4.1.1 | Limit of Detection (Analytical Sensitivity) | |
| 4.1.2 | Inclusivity | |
| 4.1.3 | Precision | |
| 4.1.4 | Reproducibility | |
| 4.1.5 | Analytical Specificity: Potentially Interfering Substances | |
| 4.1.6 | Analytical Specificity: Potential Cross-Reactants | |
| 4.1.7 | On-Panel Cross-Reactivity | |
| 4.1.8 | Competitive Interference | |
| 4.1.9 | Carryover | |
| 4.2 | Clinical Performance | 28 |
| 4.2.1 | Performance with Clinical Specimens Prospective Clinical Study | |
| 4.2.2 | Retrospective Clinical Study | |
| 4.2.3 | Expected Values | |
| 5.0 | Conclusion Drawn from the Studies | 35 |
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## 510(k) Summary
This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirement of 21 CFR Section 807.92(c).
### 1.0 Submitter
| Applicants Name and Address: | Abbott Molecular Inc.<br>1300 E. Touhy Ave Des Plaines, IL 60018 |
|------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Stacy Ferguson<br>Director Regulatory Affairs<br>Abbott Molecular, Inc.<br>1300 E. Touhy Avenue<br>Des Plaines, IL 60018<br>Phone: 224-361-7449 |
| Date Prepared: | February 12, 2025 |
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### 1.1 Device Information
| Device Trade Name | Regulation Name | Product<br>Code | Regulation<br>Number | Class |
|------------------------------------------------------|--------------------------------------------------------------------------------------------------------------|-----------------|----------------------|-------|
| Alinity m Resp-4-Plex | Multi-Target Respiratory Specimen<br>Nucleic Acid Test Including<br>Sars-Cov-2 And Other Microbial<br>Agents | QOF | 21 CFR 866.3981 | II |
| 1.2 Predicate Device | | | | |
| Predicate Device | | 510(k) | Date Cleared | |
| Hologic™ Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay | | K222736 | May 16, 2023 | |
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#### 1.3 Intended Use
Alinity m Resp-4-Plex is a multiplexed real-time in vitro reverse transcription polymerase chain reaction (RT-PCR) assay for use with the automated Alinity m System for the qualitative detection and differentiation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), influenza A virus, influenza B virus and Respiratory Syncytial Virus (RSV) in nasopharyngeal swab specimens collected from patients with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza A, influenza B, and RSV can be similar.
The Alinity m Resp-4-Plex assay is intended for use in the differential detection of SARS-CoV-2, influenza A, influenza B and/or RSV RNA and aids in the diagnosis of COVID-19, influenza and/or RSV infections if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza A, influenza B and RSV viral RNA are generally detectable in nasopharyngeal swab specimens during the acute phase of infection. This test is not intended to detect influenza C virus infections.
Positive results are indication of the presence of the identified virus, but do not rule out bacterial infection or co-infection with other pathogens not detected by the test. The agent(s) detected by the Alinity m Resp-4-Plex assay may not be the definite cause of disease.
Negative results do not preclude SARS-CoV-2, influenza B and/or RSV infections and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
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#### 2.0 Device Description
The Alinity m Resp-4-Plex assay requires two separate assay-specific kits as follows:
- Alinity m Resp-4-Plex AMP Kit; 09N79-095, consists of 2 types of multi-well . assay trays. The amplification trays (AMP TRAY 1) contain unit-dose liquid PCR amplification/detection reagents and unit-dose liquid Internal Control (IC) in separate wells. The activation trays (ACT TRAY 2) contain liquid unit-dose activation reagent. The intended storage condition for the Alinity m Resp-4-Plex AMP Kit is -25°C to -15°C.
- . Alinity m Resp-4-Plex CTRL Kit; 09N79-085, consists of negative controls and positive controls, each supplied as liguid in single-use tubes. The Alinity m Resp-4-Plex controls are used for validity determination of the Alinity m Resp-4-Plex on the automated Alinity m System. The intended storage condition for the Alinity m Resp-4-Plex CTRL Kit is -25°C to -15°C.
The Alinity m Resp-4-Plex assay utilizes real-time PCR to amplify and detect genomic RNA sequences of influenza A (flu A), influenza B (flu B), RSV, and/or SARS-CoV-2 from nasopharyngeal (NP) swab specimens. The Alinity m Resp-4-Plex detects assay analytes and internal control (IC) separately, using analyte specific probes. The assay targets 2 different genes within the SARS-CoV-2 genome. The fluorescently labeled probes do not generate a detectable signal unless they are specifically bound to the amplified product. All probes are labeled with analyte specific fluorophores, thus allowing for simultaneous detection and differentiation of amplified products of all 4 viruses and IC in a single reaction vessel.
The steps of the Alinity m Resp-4-Plex assay consist of sample preparation, PCR assembly, amplification/ detection, and result calculation and reporting. All steps of the Alinity m Resp-4-Plex assay procedure are executed automatically by the Alinity m System. The Alinity m System is designed to be a continuous random-access analyzer that can perform the Alinity m Resp-4-Plex assay in parallel with other Alinity m assays on the same instrument. One PCR reaction can detect 1 or more pathogens with the Alinity m Resp-4-Plex assay. Therefore, only 1 patient specimen aliquot is required for detection of the selected assay(s).
The Alinity m System performs automated sample preparation 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
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elution. The IC is introduced into each specimen at the beginning of the sample preparation process to demonstrate that the process was completed correctly for each specimen and control sample.
The resulting purified RNA is combined with liquid unit-dose Alinity m Resp-4-Plex activation reagent and liquid unit-dose Alinity m Resp-4-Plex amplification/detection reagent and transferred into a reaction vessel. Alinity m Vapor Barrier Solution is then added to the reaction vessel which is then transferred to an amplification/detection unit for reverse transcription, PCR amplification, and real-time fluorescence detection.
A positive control and a negative control are tested at or above an established minimum frequency to help ensure that instrument and reagent performance remain satisfactory. During each control event, a negative control and positive control are processed through sample preparation and PCR procedures that are identical to those used for specimens.
The target sequences for the Alinity m Resp-4-Plex assay are:
- RdRp and N genes of the SARS-CoV-2 genome .
- the Matrix gene of the flu A genome .
- . the Nonstructural 1 gene of the flu B genome
- the Matrix gene of the RSV genome
Patient results are automatically reported on the Alinity m instrument. The Alinity m Resp-4-Plex application parameters will be contained in an assay application specification file.
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The Alinity m Resp-4-Plex assay also utilizes the following:
- Alinity m Resp-4-Plex Assay Application Specification File, List No. 09N79-03A . The Alinity m Resp-4-Plex application specification file is intended for use with the Alinity m Resp-4-Plex 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. 08N53-002ª
- . Alinity m Sample Prep Kit 2, List No. 09N12-001ª
- Alinity m Tubes and Caps, List No. 09N49ª
- Alinity m Transport Tubes Pierceable Capped, List No. 09N49-010 ●
- Alinity m Transport Tube, List No. 09N49-011
- . Alinity m Aliquot Tube, List No. 09N49-013
- . Alinity m System Solutions, List No. 09N20
- . Alinity m Lysis Solution, List No. 09N20-001ª
- Alinity m Diluent Solution, List No. 09N20-003ª
- . Alinity m Vapor Barrier Solution, List No. 09N20-004a
ಡ Items previously approved by FDA under PMA P190025.
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#### 3.0 Similarities and Differences to the Predicate Device
The legally marketed predicate device chosen for the current submission is the Hologic™ Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay (for use on the Panther Fusion system). The Alinity m Resp-4-Plex assay is substantially equivalent to the legally marketed predicate device, Hologic™ Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay (for use on the Panther Fusion system), intended for the qualitative detection and differentiation of SARS-CoV-2, flu A virus, flu B virus, and RSV. The primary similarities between Alinity m Resp-4-Plex assay and the predicate device are presented in Table 1. The primary differences between Alinity m Resp-4-Plex and the predicate device are shown in Table 2. Both the Alinity m Resp-4-Plex assay and the predicate have the same intended use. Any technological differences that exist between Alinity m Resp-4-Plex 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 Resp-4-Plex Assay and Nucleic Acid Amplification Tests Predicate Device | | |
|-----------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature | Current Submission | Predicate Device |
| Device Trade Name | Alinity m Resp-4-Plex | Hologic™ Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay<br>(K222736) |
| Intended Use | Alinity m Resp-4-Plex is a multiplexed real-time in vitro reverse<br>transcription polymerase chain reaction (RT-PCR) assay for use<br>with the automated Alinity m System for the qualitative detection<br>and differentiation of Severe Acute Respiratory Syndrome<br>Coronavirus 2 (SARS-CoV-2) influenza A virus, influenza B virus<br>and Respiratory Syncytial Virus (RSV), in nasopharyngeal swab<br>specimens collected from patients with signs and symptoms of<br>respiratory tract infection. Clinical signs and symptoms of<br>respiratory tract infection due to SARS-CoV-2, influenza A,<br>influenza B, and RSV can be similar.<br>The Alinity m Resp-4-Plex assay is intended for use in the<br>differential detection of SARS-CoV-2, influenza A, influenza B<br>and/or RSV RNA and aids in the diagnosis of COVID-19,<br>influenza and/or RSV infections if used in conjunction with other<br>clinical and epidemiological information, and laboratory findings.<br>SARS-CoV-2, influenza A, influenza B and RSV viral RNA are<br>generally detectable in nasopharyngeal swab specimens during the<br>acute phase of infection. This test is not intended to detect<br>influenza C virus infections.<br>Positive results are indication of the presence of the identified<br>virus, but do not rule out bacterial infection or co-infection with<br>other pathogens not detected by the test. The agent(s) detected by<br>the Alinity m Resp-4-Plex assay may not be the definite cause of<br>disease.<br>Negative results do not preclude SARS-CoV-2, influenza A,<br>influenza B, and/or RSV infections and should not be used as the<br>sole basis for diagnosis, treatment or other patient management<br>decisions. | The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is a fully<br>automated multiplexed real-time polymerase chain reaction (RT-<br>PCR) in vitro diagnostic test intended for the qualitative detection and<br>differentiation of severe acute respiratory syndrome coronavirus 2<br>(SARS-CoV-2), influenza A virus (Flu A), influenza B virus (Flu B),<br>and respiratory syncytial virus (RSV). Nucleic acids are isolated and<br>purified from nasopharyngeal (NP) specimens obtained from<br>individuals exhibiting signs and symptoms of a respiratory tract<br>infection. Clinical signs and symptoms of respiratory viral infection<br>due to SARS-CoV-2, influenza, and RSV can be similar. This assay is<br>intended to aid in the differential diagnosis of SARS-CoV-2, Flu A,<br>Flu B, and RSV infections in humans and is not intended to detect<br>influenza C virus infections.<br>Nucleic acids from the viral organisms identified by this test are<br>generally detectable in NP specimens during the acute phase of<br>infection. The detection and identification of specific viral nucleic<br>acids from individuals exhibiting signs and symptoms of respiratory<br>tract infection are indicative of the presence of the identified virus<br>and aids in diagnosis if used in conjunction with other clinical and<br>epidemiological information, and laboratory findings. The results of<br>this test should not be used as the sole basis for diagnosis, treatment,<br>or other patient management decisions.<br>Positive results do not rule out coinfection with other organisms. The<br>organism(s) detected by the Panther Fusion SARS-CoV-2/ Flu<br>A/B/RSV assay may not be the definite cause of disease.<br>Negative results do not preclude SARS-CoV-2, influenza A virus,<br>influenza B virus, or RSV infections. This assay is designed for use<br>on the Panther Fusion system. |
| | Table 1. Similarities Between Alinity m Resp-4-Plex Assay and Nucleic Acid Amplification Tests Predicate Device | |
| Feature | Current Submission | Predicate Device |
| Device Trade Name | Alinity m Resp-4-Plex | Hologic™ Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay<br>(K222736) |
| Conditions for Use | For prescription use<br>For in vitro diagnostic use only | Same |
| Organisms Detected | influenza A (flu A) influenza B (flu B) Respiratory Syncytial Virus (RSV) SARS-CoV-2 | Same |
| Platform | All steps of this qualitative assay procedure are<br>executed automatically by the Alinity m System.<br>Uses Alinity m System for all steps including nucleic<br>acid extraction, amplification, detection, and result<br>processing.<br>No intermediate processing or transfer steps are<br>performed by the user. | All steps of this qualitative assay procedure are executed automatically by<br>the Panther Fusion System. Uses Panther Fusion System for all steps<br>including nucleic acid extraction, amplification, detection, and result<br>processing.<br>No intermediate processing or transfer steps are performed by the user. |
| Specimen Types | Nasopharyngeal (NP) swab specimens | Same |
| Assay Controls | Negative Control Positive Control Internal Control (IC) | Same |
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| Table 2. Differences Between Alinity m Resp-4-Plex Assay and Nucleic Acid Amplification Tests Predicate Device | | |
|----------------------------------------------------------------------------------------------------------------|----------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature | Current Submission | Predicate Device |
| Device Trade Name | Alinity m Resp-4-Plex | Hologic™ Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay (K222736) |
| Specimen Collection<br>and Transport | • BDTM UVT<br>• Copan UTM® | • Same<br>• Same<br>• Remel MicroTest M4RT, M5, or M6 formulations<br>• Hardy Diagnostics Viral Transport Medium<br>• Hologic RespDirect Collection Kit |
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#### 4.0 Performance Data
The following performance data were provided in support of the substantial equivalence determination.
### Specific Performance Characteristics – Analytical Studies 4.1
#### 4.1.1 Limit of Detection (Analytical Sensitivity)
Limit of Detection (LoD) studies determine the lowest concentration of Influenza A (flu A), Influenza B (flu B), RSV, and SARS-CoV-2 at which greater than or equal to 95% of replicates test positive.
The LoD was determined by testing 10 cultured viruses, including 5 flu A strains (H1N1 and H3N2 subtypes), 2 flu B strains (Victoria and Yamagata lineages), 2 RSV strains (RSV A and RSV B), and 1 SARS-CoV-2 strain diluted in pooled negative NP clinical specimens collected in viral transport media.
For each virus, the preliminary LoD was determined by testing a minimum of 3 levels, each in a minimum of 3 replicates. The final LoD was confirmed by testing a minimum of 3 panel members with target concentrations bracketing the preliminary LoD, each panel member in a minimum of 20 replicates. For each strain, LoD was defined as the lowest concentration at which greater than or equal to 95% of all replicates tested positive rate greater or equal to 95%), as summarized in Table 3.
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| Table 3. Limit of Detection | | | |
|-----------------------------|------------------------------------------------------------------------------|------------------------|-----------------|
| Virus | Strain (Source) | LoD | Mean CN at LoDa |
| Influenza A | A/H1N1/Brisbane/59/2007<br>(Cat No 0810244CF, Lot 323919) | 0.002 TCID50/mL | 36.29 |
| | A/H1N1/ Michigan/45/2015<br>(Cat No 0810538CF, Lot 326537) | 0.004 TCID50/mL | 35.75 |
| | A/H3N2/Switzerland/9715293/13<br>(Cat No 0810511CF, Lot 322440) | 0.015 TCID50/mL | 35.71 |
| | A/H3N2/Wisconsin/04/2018<br>(Cat No FR-1692, Lot 70030518) | 0.06 TCID50/mL | 35.15 |
| | A/H3N2/ Darwin/9/21<br>(Cat No 0810650CF, Lot 331100) | 0.004 TCID50/mL | 36.02 |
| Influenza B | B/Victoria lineage/Brisbane/33/08<br>(Cat No 0810253CF, Lot 316752) | 0.02 TCID50/mL | 36.23 |
| | B/Yamagata<br>lineage/Massachusetts/2/12<br>(Cat No 0810239CF, Lot 324519) | 0.05 TCID50/mL | 36.13 |
| RSV | RSVA/Long/MD/56<br>(Cat No VR-26PQ, Lot 70024412) | 0.3 TCID50/mL | 34.92 |
| | RSVB/West Virginia/14617/85<br>(Cat No VR-1400, Lot 70013461) | 0.1 TCID50/mL | 35.62 |
| SARS-CoV-2 | Isolate USA-WA1/2020, gamma<br>irradiated<br>(Cat No NR-52287, Lot 70048202) | 30 Genome<br>Copies/mL | 35.93 |
a Mean cycle number (CN) was calculated for all valid replicates with a positive result in the confirmation of LoD testing. TCID50/mL = Median Tissue Culture Infectious Dose/mL.
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#### 4.1.2 Inclusivity
In addition to strains tested in LoD study, the inclusivity of Alinity m Resp-4-Plex assay for the detection of flu A, flu B, RSV, and SARS-CoV-2 was also evaluated by testing 16 strains of flu A virus (including H1N1, H3N2, and H5N15), 9 strains of flu B virus (including Victoria and Yamagata lineages), 6 strains of RSV (including RSV A and B), and 9 strains of SARS-CoV-2 (including A, B, BA.1 and B.1.1.7 lineages) in pooled negative clinical NP swab matrix. Each individual virus isolate or strain (cultured virus or viral RNA) was tested in replicates of 5 at the level equal to or lower than 3 × LoD (Table 4). For strains with reported units of measure different than units listed in LoD study, dilution series were prepared and tested. The lowest concentration tested that resulted in 100% positive results is included in Table 4.
| Table 4. Inclusivity | | | | |
|----------------------|-----------------------------------------------------------------------|--------------------|------------|--------------------------|
| Virus | Strain/Isolate | Catalog<br>Numbera | Lot Number | Concentration<br>Testedb |
| Influenza A | A/H1N1/Brisbane/<br>02/2018 | 0810585CFHI | 325433 | 0.006<br>TCID50/mL |
| | A/H1N1/Fort Monmouth/1/1947 | VR-1754 | 59523491 | 1.67E+00<br>CEID50/mL |
| | A/H1N1/California/<br>07/2009 | VR-1894 | 70014833 | 3.33E+00<br>CEID50/mL |
| | A/H1N1/Puerto Rico/8/1934 | NR-348 | 70013122 | 3.33E+00<br>CEID50/mL |
| | A/H1N1/New Jersey/8/1976 | VR-897 | 58810588 | 1.00E+01<br>CEID50/mL |
| | A/H1N1/Wisconsin/<br>588/2019 – Candidate Vaccine<br>Virus | N/A | 3026054333 | 1.37E-06 HA |
| | A/H1N1/Guangdong-<br>Maonan/1536/2019 – Candidate<br>Vaccine Virus | N/A | 3001293900 | 8.53E-06 HA |
| | A/H1N1/Victoria/2570/2019 –<br>Candidate Vaccine Virus | N/A | 3000827519 | 5.12E-05 HA |
| | A/H3N2/Tasmania/503/2020 –<br>Candidate Vaccine Virus | N/A | 3000824430 | 2.37E-07 GP |
| | A/H3N2/Hong Kong/45/2019 –<br>Candidate Vaccine Virus | N/A | 3001584404 | 2.56E-06 GP |
| Virus | Strain/Isolate | Catalog<br>Numbera | Lot Number | Concentration<br>Testedb |
| | A/H3N2/Hong Kong/2671/2019<br>- Candidate Vaccine Virus | N/A | 3001292400 | 4.27E-05 GP |
| | A/H3N2/Singapore/<br>INFIMH-16-0019/2016 | 0810574CF | 327298 | 0.045<br>TCID50/mL |
| | A/H3N2/Brisbane/10/2007 | 0810138CF | 324694 | 0.045<br>TCID50/mL |
| | A/H3N2/Perth/16/2009 | 0810251CF | 313219 | 0.045<br>TCID50/mL |
| | A/H3N2/Delaware/01/2021 | FR-1748 | 70048306 | 3.64E-01<br>FFU/mL |
| | A/H5N1/Vietnam/1203/2004 | NR-12145 | VNV1F014A | 9.00E-05<br>µg/mL |
| Influenza B | B/Victoria<br>lineage/Brisbane/60/2008 | 0810254CF | 325527 | 0.06<br>TCID50/mL |
| | B/Victoria<br>lineage/Colorado/6/2017 | 0810573CF | 325651 | 0.02<br>TCID50/mL |
| | B/Victoria<br>lineage/Alabama/2/2017 | 0810572CF | 325540 | 0.02<br>TCID50/mL |
| | B/Victoria<br>lineage/Malaysia/2506/2004 | 0810258CF | 327609 | 0.006<br>TCID50/mL |
| | B/Victoria<br>lineage/Washington/02/2019 –<br>Candidate Vaccine Virus | N/A | 3026019537 | 1.42E-06 HA |
| | B/Yamagata<br>lineage/Phuket…
