Who is the manufacturer of Alinity m HSV 1 & 2 / VZV?

Abbott Molecular, Inc. filed the 510(k) submission for Alinity m HSV 1 & 2 / VZV (K233349).

What is the FDA product code for Alinity m HSV 1 & 2 / VZV?

PGI. It is classified under 21 CFR 866.3309 as a Class 2 device in the Microbiology panel.

What is the regulatory pathway for Alinity m HSV 1 & 2 / VZV?

510(k) clearance (submission type: Traditional).

What are the predicate devices for Alinity m HSV 1 & 2 / VZV?

Lyra Direct HSV 1 + 2/VZV Assay (K133448).

Who can help prepare an FDA 510(k) submission like Alinity m HSV 1 & 2 / VZV?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

Alinity m HSV 1 & 2 / VZV

K233349 · Abbott Molecular, Inc. · PGI · May 3, 2024 · Microbiology

Device Facts

Record ID	K233349
Device Name	Alinity m HSV 1 & 2 / VZV
Applicant	Abbott Molecular, Inc.
Product Code	PGI · Microbiology
Decision Date	May 3, 2024
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 866.3309
Device Class	Class 2
Attributes	Pediatric

Intended Use

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

Device Story

The Alinity m HSV 1 & 2 / VZV assay is an automated, in vitro real-time PCR test performed on the Alinity m System. It processes clinician-collected cutaneous or mucocutaneous lesion swabs to detect and differentiate HSV-1, HSV-2, and VZV DNA. The system performs all steps—sample preparation, PCR assembly, amplification, detection, and result calculation—automatically without user intervention. The device is intended for use in clinical laboratories by trained personnel. Results aid clinicians in diagnosing active infections; however, they are not intended as the sole basis for management decisions. The automated workflow reduces manual handling, minimizing potential for contamination and variability compared to manual methods.

Clinical Evidence

Clinical performance was established via prospective (N=1,258) and retrospective (N=411) studies comparing the Alinity m assay to a commercially available NAAT comparator. Prospective study results: HSV-1 PPA 97.6%, NPA 98.9%; HSV-2 PPA 99.2%, NPA 99.2%; VZV PPA 97.7%, NPA 99.8%. Retrospective study results: HSV-1 PPA 100.0%, NPA 96.2%; HSV-2 PPA 98.7%, NPA 95.8%; VZV PPA 97.8%, NPA 98.4%. Discordant samples were resolved using a second NAAT method.

Technological Characteristics

Real-time PCR assay; utilizes synthetic oligonucleotides, DNA polymerase, dNTPs, and exogenous internal control (plasmid DNA). Fully automated on Alinity m System. Reagents stored at -25°C to -15°C. Qualitative detection based on fluorescent signal cycle number (CN) thresholds.

Indications for Use

Indicated for symptomatic patients of all ages (pediatric to geriatric) suspected of active HSV-1, HSV-2, or VZV cutaneous or mucocutaneous infections. Not for use with CSF, CNS infection diagnosis, or prenatal screening.

Regulatory Classification

Identification

A herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel is a qualitative in vitro diagnostic device intended for the simultaneous detection and differentiation of different herpes viruses in cutaneous and mucocutaneous lesion samples from symptomatic patients suspected of Herpetic infections. Negative results do not preclude infection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use in cerebrospinal fluid samples.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed documentation for the device description, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology including primer design and selection. (2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (Limit of Detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, and cross contamination. (3) Premarket notification submissions must include detailed documentation of a clinical study using lesion samples in which Herpes Simplex Virus 1, Herpes Simplex Virus 2, or Varicella Zoster Virus DNA detection was requested. The study must compare the device performance to an appropriate well established reference method. (4) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling. (5) The device labeling must include a limitation statement that reads: “The device is not intended for use with cerebrospinal fluid or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS).” (6) Premarket notification submissions must include quality assurance protocols and a detailed documentation for device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software. (7) The risk management activities performed as part of the manufacturer's 21 CFR 820.10(c) design and development activities must document an appropriate end user device training program that will be offered as part of efforts to mitigate the risk of failure to correctly operate the instrument.

Predicate Devices

Lyra Direct HSV 1 + 2/VZV Assay (K133448)

Related Devices

K232286 — Savanna HSV 1+2/VZV Assay, Savanna HSV 1+2/VZV Control Set, Savanna Instrument · Quidel Corporation · Dec 20, 2023
K140198 — IMDX HSV-1/2 FOR ABBOTT M2000 · Intelligent Medical Devices, Inc. · May 13, 2014

Submission Summary (Full Text)

{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, with the words "U.S. FOOD & DRUG" on one line and "ADMINISTRATION" on the line below. The FDA logo is in blue. Abbott Molecular Inc. Stacy Ferguson Director Regulatory Affairs 1300 E Touhy Ave, Des Plaines. IL 60018. # Re: K233349 Trade/Device Name: Alinity m HSV 1 & 2 / VZV Regulation Number: 21 CFR 866.3309 Regulation Name: Herpes Virus Nucleic Acid-Based Cutaneous And Mucocutaneous Lesion Panel Regulatory Class: Class II Product Code: PGI Dated: March 26, 2024 Received: March 26, 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/cdrb/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. 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). {1}------------------------------------------------ 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 (QS) 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. 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 mediation-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-regulatoryassistance/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). Sincerelv. Laura E. Ulitzky Digitally signed by Laura E. Date: 2024.05.03 13:24:17 -5 -04'00' Laura Ulitzky, Team Lead on behalf of: Ryan Karsner, MD Branch Chief Deputy Assistant Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological HealthEnclosure {2}------------------------------------------------ # Indications for Use 510(k) Number (if known) K233349 Device Name Alinity m HSV 1 & 2 / VZV #### Indications for Use (Describe) The Alinity m HSV 1 & 2 / VZV assay is an in vitro real-time polymerase chain reaction (PCR) assay for the qualitative detection and differentiation of Herpes Simplex Virus 1 (HSV-1), Herpes Simplex Virus 2 (HSV-2) and Varicella Zoster Virus (VZV) DNA from clinician-collected cutaneous or mucocutaneous lesion swab specimens from symptomatic patients suspected of active herpes simplex virus 2 and/or varicella-zoster infection. The Alinity m HSV 1 & 2 / VZV assay is intended to aid in the diagnosis of herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster active cutaneous or mucocutaneous infections. Negative results do not preclude herpes virus type 1, herpes simplex virus type 2 or varicella-zoster virus infections and should not be used as the sole basis for diagnosis, treatment or other management decisions. The Alinity m HSV 1 & 2 / VZV assay is not intended for use with cerebrospinal fluid (CSF) or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Alinity m HSV 1 & 2 / VZV assay is not intended for use in prenatal screening. Type of Use (Select one or both, as applicable) | <div> ❌ Prescription Use (Part 21 CFR 801 Subpart D) </div> | |-------------------------------------------------------------------------------------------------------------------------| | <div> ☐ Over-The-Counter Use (21 CFR 801 Subpart C) </div> | CONTINUE ON A SEPARATE PAGE IF NEEDED.This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {3}------------------------------------------------ ### 510(k) Summary ### Submitter | Applicants Name and Address: | Abbott Molecular Inc. 1300 E. Touhy Ave Abbott Molecular Inc. | |------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------| | Contact Person: | Stacy Ferguson Director Regulatory Affairs Abbott Molecular, Inc. 1350 E. Touhy Avenue Des Plaines, IL 60018 Phone: 224-206-4081 | | Date Prepared: | May 1, 2024 | #### Device Information | Trade Name | Regulation Name | Product Code | Regulation Number | Class | |---------------------------|---------------------------------------------------------------------------|-----------------|----------------------|-------| | Alinity m HSV 1 & 2 / VZV | Herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel. | PGI | 21 CFR 866.3309 | II | #### Predicate Device | Predicate Device | Product Code | 510(k) | Date Cleared | |---------------------------------|--------------|---------|--------------| | Lyra Direct HSV 1 + 2/VZV Assay | PGI | K133448 | May 13, 2014 | #### Intended Use The Alinity m HSV 1 & 2 / VZV assay is an in vitro real-time polymerase chain reaction (PCR) assay for the qualitative detection and differentiation of Herpes Simplex Virus 1 (HSV-1), Herpes Simplex Virus 2 (HSV-2) and Varicella Zoster Virus (VZV) DNA from clinician-collected cutaneous or mucocutaneous lesion swab specimens from symptomatic patients suspected of active herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster infection. The Alinity m HSV 1 & 2 / VZV assay is intended to aid in the diagnosis of herpes simplex virus 1, herpes simplex virus 2 and/or varicellazoster active cutaneous or mucocutaneous infections. Negative results do not preclude herpes simplex virus type 1, herpes simplex virus type 2 or varicella-zoster virus {4}------------------------------------------------ infections and should not be used as the sole basis for diagnosis, treatment or other management decisions. The Alinity m HSV 1 & 2 / VZV assay is not intended for use with cerebrospinal fluid (CSF) or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Alinity m HSV 1 & 2 / VZV assay is not intended for use in prenatal screening. #### Device Description The Alinity m HSV 1 & 2 / VZV assay is an in vitro real-time polymerase chain reaction (PCR) assay for the qualitative detection and differentiation of Herpes Simplex Virus 1 (HSV-1), Herpes Simplex Virus 2 (HSV-2) and Varicella Zoster Virus (VZV) DNA from clinician--collected cutaneous or mucocutaneous lesion swab specimens from symptomatic patients suspected of active herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster infection. This assay is intended for use with the automated Alinity m System. The steps of the Alinity m HSV 1 & 2 / VZV assay consist of sample preparation, PCR assembly, amplification/detection, and result calculation and reporting. The steps involved in all stages of the Alinity m HSV 1 & 2 / VZV assay procedure are executed automatically by the Alinity m System. No intermediate processing or transfer steps are performed by the user. The Alinity m System is designed to be a random access analyzer that can perform the Alinity m HSV 1 & 2 / VZV assay in parallel with other Alinity assays on the same instrument. The Alinity m HSV 1 & 2 / VZV assay requires two separate assay specific kits as follows: 1) The Alinity m HSV 1 & 2 / VZV AMP Kit (List No. 09N61-095) is comprised of 2 types of multi-well trays: TRAY 1: Alinity m HSV 1 & 2 / VZV AMP TRAY 1 TRAY 2: Alinity m HSV 1 & 2 / VZV ACT TRAY 2. TRAY 1 - Alinity m HSV 1 & 2 / VZV AMP is individually packed in a foil pouch and contains 48 unit-dose liquid amplification reagent wells and 48 unitdose liquid IC wells. One well of each is used per test. · Amplification reagent wells consist of synthetic oligonucleotides, DNA Polymerase, dNTPs, and 0.15% ProClin® 950 in a buffered solution with a reference dye. IC wells consist of plasmid DNA with unrelated IC sequences and poly dA:dT in a TE buffer containing 0.15% ProClin 950 as a preservative. TRAY 2 - Alinity m HSV 1 & 2 / VZV ACT is individually packed in a foil pouch and contains 48 unit-dose liquid activation reagent wells. One reagent well is used per test. {5}------------------------------------------------ · Activation reagent wells consist of magnesium chloride, potassium chloride, and tetramethylammonium chloride. Preservative: 0.15% ProClin 950. | Alinity m HSV 1 & 2 / VZV Assay Kit | | |--------------------------------------|----------------------| | Alinity m HSV 1 & 2 / VZV AMP Kit | Quantity 192 Tests | | Alinity m HSV 1 & 2 / VZV AMP TRAY 1 | 4 Trays/48 Test Each | | Alinity m HSV 1 & 2 / VZV ACT TRAY 2 | 4 Trays/48 Test Each | 2) The Alinity m HSV 1 & 2 / VZV CTRL Kit (09N61-085) consists of negative controls and positive controls, each supplied as liquid in single-use tubes. Alinity m HSV 1 & 2 / VZV Negative CTRL (List No. 9N61Z) consists of Negative Diluent / TE buffer (containing 0.085% Sodium Azide and 0.087% ProClin 950). Alinity m HSV 1 & 2 / VZV Positive CTRL (List No. 9N61W) consists of linearized plasmid DNA containing HSV-1, HSV-2 and VZV DNA sequences in Negative Diluent / TE buffer (containing 0.085% Sodium Azide and 0.087% ProClin 950). | Alinity m HSV 1 & 2 / VZV Control Kit | | |-----------------------------------------|-------------------| | Alinity m HSV 1 & 2 / VZV Negative CTRL | 12 Tube x 0.75 mL | | Alinity m HSV 1 & 2 / VZV Positive CTRL | 12 Tube x 0.75 mL | The Alinity m HSV 1 & 2 / VZV assay is to be run on the Alinity m System which is a fully integrated, sample to result automated system that performs real-time PCR test using the Alinity m HSV 1 & 2 / VZV AMP Kit along with the Alinity m HSV 1 & 2 / VZV CTRL Kit. {6}------------------------------------------------ # Similarities and Differences to Predicate Device | Device and Predicate | New Device K233349 | Predicate Device K133448 | |---------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Device Trade Number | Alinity m HSV 1 & 2 / VZV Assay | Lyra Direct HSV 1 + 2/VZV Assay | | Similarities | | | | Intended Use | The Alinity m HSV 1 & 2 / VZV assay is an in vitro real-time polymerase chain reaction (PCR) assay for the qualitative detection and differentiation of Herpes Simplex Virus 1 (HSV-1), Herpes Simplex Virus 2 (HSV-2), and Varicella Zoster Virus (VZV) DNA from clinician- collected cutaneous or mucocutaneous lesion swab specimens from symptomatic patients suspected of active herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster virus infection. The Alinity m HSV 1 & 2 / VZV assay is intended to aid in the diagnosis of herpes simplex virus 1, herpes simplex virus 2 and/or varicella- zoster virus active cutaneous or mucocutaneous infections. Negative results do not preclude herpes simplex virus type 1, herpes simplex virus type 2 or varicella-zoster virus infections and should not be used as the sole basis for diagnosis, treatment or other management decisions. The Alinity m HSV 1 & 2 / VZV assay is not intended for use with cerebrospinal fluid (CSF) or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Alinity m HSV 1 & 2 / VZV assay is not intended for use in prenatal screening. | The Lyra Direct HSV 1 + 2/VZV Assay is an in vitro multiplex Real-Time PCR test for qualitative detection and differentiation of herpes simplex virus type 1, herpes simplex virus type 2, and varicella-zoster virus DNA isolated and purified from cutaneous or mucocutaneous lesion samples obtained from symptomatic patients suspected of active herpes simplex virus 1, herpes simplex virus 2 and/or varicella-zoster infection. The Lyra Direct HSV 1 + 2/VZV Assay is intended to aid in the diagnosis of herpes simplex virus 1, herpes simplex virus 2 and varicella-zoster virus active cutaneous or mucocutaneous infections. Negative results do not preclude herpes simplex virus 1, herpes simplex virus 2 and varicella-zoster virus infections and should not be used as the sole basis for diagnosis, treatment or other management decisions. The Lyra Direct HSV 1 + 2/VZV Assay is not intended for use with cerebrospinal fluid or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS). The Lyra Direct HSV 1 + 2/VZV Assay is not intended for use in prenatal screening. The device is not intended for point-of-care use. | | Assay Type | Qualitative | Same | | Assay Targets | Viral DNA from HSV-1, HSV-2, and VZV | Same | | Specimen Types | Cutaneous and Mucocutaneous (Lesion and Lesion swab specimens) | Same | | Amplification Technology | Real-Time Polymerase Chain Reaction (PCR) | Same | | Automated Analysis | Yes | Same | | Assay Controls | Negative Control Positive Control | Same | | Differences | | | | Assay Steps | All steps of the Alinity m HSV 1 & 2 / VZV assay procedure are executed automatically by the Alinity m System. No intermediate processing or transfer steps are performed by the user. | Assay processing steps are executed manually until placed on instrument for signal evaluation: • Life Technologies QuantStudio Dx • Applied Biosystems 7500 Fast Dx • Cepheid SmartCycler II System | | Sample Preparation Instrument Components | Automated liquid handling and robotic manipulation platform. Automated process for sample processing using an internal control (IC) | Mechanical lysis and addition of Process Buffer. Manual process for sample processing using the processing control (PRC) | | Reagent Kit Storage (Unopened) until expiration date | -25°C to -15°C | 2°C to 8°C | {7}------------------------------------------------ # Performance Data The following performance data were provided in support of the substantial equivalence determination. # Analytical Studies ## Analytical Sensitivity/Limit of Detection (LoD) The limit of detection (LoD) for Alinity m HSV 1 & 2 / VZV assay for each analyte were determined by quantified (TCID50/mL) cultures of HSV-1 (Maclntyre), HSV-2 (MS) or VZV (Ellen) viral strains diluted into pooled negative clinical swab specimens. The LoD of each analyte is presented below in Table 1. | Table 1. Limit of Detection | | | |-----------------------------|-----------|-----------------| | Analyte | Strain | LoD (TCID50/mL) | | HSV-1 | MacIntyre | 5.90 | | HSV-2 | MS | 2.07 | | VZV | Ellen | 0.055 | {8}------------------------------------------------ # Inclusivity The inclusivity for the Alinity m HSV 1 & 2 / VZV assay was determined by testing 5 HSV-1 strains / isolates, 3 HSV-2 strains / isolates and 5 VZV strains / isolates. The strains whose reported units of measure were in TCID50/mL, were diluted to a concentration ≤ 3X LoD. For strains where concentration in TCID50/mL was not available, a dilution series based on copies/mL was prepared and tested. The dilution series consisted of at least one concentration that resulted in positive results 100% of the time, and at least one concentration that resulted in positive results <100% of the time. The Alinity m HSV 1 & 2 / VZV assay detected all strains listed in Table 2 at a level of 3X LoD. | Table 2. Inclusivity | | | | |----------------------|----------------|-----------------|--------------------| | Analyte | Strain | Concentration | Inclusive (Yes/No) | | HSV-1 | MacIntyre | 17.7 TCID50/mL | Yes | | | HF | 17.7 TCID50/mL | Yes | | | F | 17.7 TCID50/mL | Yes | | | KOS | 300 copies/mLa | Yes | | | Vero 2 Isolate | 17.7 TCID50/mL | Yes | | HSV-2 | MS | 6.21 TCID50/mL | Yes | | | G | 6.21 TCID50/mL | Yes | | | Vero 2 Isolate | 6.21 TCID50/mL | Yes | | VZV | Ellen | 0.093 TCID50/mL | Yes | | | 82 | 100 copies/mLa | Yes | | | Oka | 0.093 TCID50/mL | Yes | | | Webster | 0.093 TCID50/mL | Yes | | | AV92-3:L | 0.093 TCID50/mL | Yes | # Tahla 2 Inclusivity Lowest level that has 100% detection. {9}------------------------------------------------ ## Analytical Specificity- Cross Reactivity and Microbial Interference A total of 55 potential cross-reacting microorganisms (viruses, bacteria, and fungi) that are commonly encountered in lesion swab specimens were tested with Alinity m HSV 1 & 2 / VZV assay to assess analytical specificity. The microorganisms were tested at 105 Units/mL for viruses and fungi, and 106 Units/mL for bacteria or the highest titer available. No cross-reactivity was observed with the 55 microorganisms tested with the Alinity m HSV 1 & 2 / VZV assay. In addition, no interference was observed with 55 microorganisms when tested in the presence of each analyte at 3x LoD levels e.g., HSV-1, HSV-2 or VZV. | Table 3. Cross-Reacting and Interfering Microorganisms Tested | | |---------------------------------------------------------------|------------------------------| | Acinetobacter calcoaceticus | Herpes Virus 6A strain GS | | Acinetobacter Iwoffii | Herpes Virus 6B strain Z29 | | Actinomyces israelii | HIV-1 | | Adenovirus type 1 | HPV 16 | | Adenovirus type 7 | HPV 18 | | Bacteroides fragilis | Kingella kingae | | BK virus | Klebsiella pneumoniae | | Bordetella pertussis | Listeria monocytogenes | | Campylobacter jejuni | Mobiluncus mulieris | | Candida albicans | Moraxella catarrhalis | | Chlamydophila pneumoniae | Mycobacterium tuberculosisa | | Chlamydia trachomatis serovar D | Neisseria gonorrhoeae | | Chlamydia trachomatis serovar I | Neisseria meningitidis | | Clostridioides difficile | Proteus mirabilis | | Clostridium perfringens | Proteus vulgaris | | Cryptococcus neoformans | Pseudomonas aeruginosa | | Cutibacterium acnes | Staphylococcus aureus | | Cytomegalovirus | Staphylococcus epidermidis | | Enterobacter cloacae | Staphylococcus saprophyticus | | Enterococcus faecalis | Streptococcus agalactiae | | Enterococcus faecium | Streptococcus mitis | | Epstein-Barr virus | Streptococcus mutans | | Escherichia coli | Streptococcus pneumoniae | | Fusobacterium nucleatum | Streptococcus pyogenes | | Haemophilus ducreyi | Streptococcus salivarius | | Haemophilus influenzae | Treponema pallidum | | Hepatitis B virus | Toxoplasma gondii | | Hepatitis C virus | | ª Mycobacterium tuberculosis genomic DNA was used as target. {10}------------------------------------------------ # Interfering Substances The performance of the Alinity m HSV 1 & 2 / VZV assay was evaluated with potentially interfering endogenous and exogenous substances that may be present in cutaneous or mucocutaneous lesion specimens. A panel composed of 24 substances listed in Table 4 was tested in the absence or presence of HSV-1, HSV-2, or VZV (MacIntyre strain, MS strain, Ellen strain, respectively) at 3x LOD in the Alinity m HSV 1 & 2 / VZV assay. There was no evidence of interference (false positive or false negative results) caused by the substances tested at the concentrations shown below in Table 4. | Table 4. Interfering Substances Tested | | |---------------------------------------------|--------------| | Substance | Test Level | | Blood (human) | 5% v/v | | Leukocytes | 106 cells/mL | | Mucin | 0.3% v/v | | Urine | 5% v/v | | Feces | 0.1% w/v | | Human Serum Albumin | 1% w/v | | Saliva | 4% v/v | | Seminal Fluid | 5% v/v | | K-Y Jelly (Personal Lubricant) | 2.5% w/v | | Vaginal Contraceptive Gel | 2.5% w/v | | Monistat (Miconazole Nitrate Vaginal Cream) | 3% w/v | | Preparation H (Hemorrhoidal Ointment) | 2.5% w/v | | Abreva (Cold Sore Cream) | 2.5% w/v | | Acyclovir | 2.5% w/v | | Vagisil (Anti-Itch Cream) | 0.25% w/v | | Vagicaine (Anti-Itch Cream) | 2.5% w/v | | Feminine Wash (Douche) | 2.5% w/v | | Denavir (Anti-retro viral cream) | 2.5% w/v | | Feminine Deodorant Spray | 2.5% w/v | | Lip Balm | 3% w/v | | Summer's Eve (Body Powder) | 2.5% w/v | | Toothpaste | 2.5% w/v | | Casein protein | 0.7% w/v | | Mouthwash | 3% v/v | {11}------------------------------------------------ # Competitive Interference A competitive interference study was conducted to challenge the performance of the Alinity m HSV 1 & 2 / VZV assay. Each sample was prepared with 2 of the analytes (HSV-1, HSV-2 or VZV) at 3X LoD and the third analyte at 1000X LoD in negative simulated matrix. The three Panel Members (PM) evaluated were: - PM 1: HSV-1 and HSV-2 at 3X LoD and VZV at 1000X LoD . - PM 2: HSV-1 and VZV at 3X LoD and HSV-2 at 1000X LoD - . PM 3: HSV-2 and VZV at 3X LoD and HSV-1 at 1000X LoD Across panel members, all replicates at the low concentration were detected for each of the 3 analytes. None of the analyte targets present at the high concentration interfered with the detection of the other 2 analyte targets at low levels. Results are presented in the Table 5. | Panel Number | High Analyte | HSV-1 Positivity | HSV-2 Positivity | VZV Positivity | |-----------------|------------------------------------------------|---------------------|---------------------|-------------------| | PM 1 | HSV- 1 & 2 at 3X LoD and VZV at 1000X LoD | 100.0% (24/24) | 100.0% (24/24) | 100.0% (24/24) | | PM 2 | HSV-1 and VZV at 3X LoD and HSV-2 at 1000X LoD | 100.0% (23/23) | 100.0% (23/23) | 100.0% (23/23) | | PM 3 | HSV-2 and VZV at 3X LoD and HSV-1 at 1000X LoD | 100.0% (24/24) | 100.0% (24/24) | 100.0% (24/24) | # Carryover Contamination The carryover rate for Alinity m HSV 1 & 2 / VZV assay was determined by testing 360 alternating replicates of negative and high-positive samples. High positive samples consisted of HSV-2 DNA targeted to a CN value of 10.00. The testing was performed across 3 different Alinity m Systems. All negative samples reported negative interpretations, resulting in an overall carryover rate of 0.0% (0/360, 95% C1: 0.0%, 1.1%). {12}------------------------------------------------ #### Within-Laboratory Precision Alinity m HSV 1 & 2 / VZV assay within-laboratory Precision was evaluated by testing a 4 member precision panel consisting of 4 target levels (Moderate Positive, Low Positive, Sub-LoD, and Negative). Each positive panel member was prepared by spiking HSV-1, HSV-2, and VZV stocks into simulated negative matrix to achieve the targeted level at Moderate Positive (3X LoD), Low Positive (1X to 2X LoD), sub-LoD (<1X LoD). Each panel member was tested with 3 replicates in a run, 2 runs on each of 5 days, on 3 Alinity m Systems operated by 3 operators (one operator per system), using 3 Alinity m HSV 1 & 2 / VZV AMP Kit lots (one lot per system) for a total of 90 replicates of each panel member. The results for HSV-1, HSV-2, and VZV are described in Table 6. For the negative panel member, no HSV-1, HSV-2, or VZV was detected in any replicate. {13}------------------------------------------------ | Table 6. Precision | |--------------------| |--------------------| | | | | | Within-Run Component | | | Between-Run Component | Between-Day Component | | Within- Laboratoryc | | Between-Instrument/ Lot/Operator Component | | Totald | | |---------|-------------------|---------------------------|-----------|-------------------------|------|-------|--------------------------|--------------------------|------|------------------------|------|--------------------------------------------------|------|--------|------| | Analyte | Panel Description | Rate of Detection (nª/Nb) | Mean (CN) | SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV | | HSV-1 | 3X LoD | 100.0% (90/90) | 26.31 | 0.233 | 0.9 | 0.000 | 0.0 | 0.000 | 0.0 | 0.233 | 0.9 | 0.178 | 0.7 | 0.293 | 1.1 | | HSV-1 | 1X - 2X LoD | 100.0% (90/90) | 26.82 | 0.181 | 0.7 | 0.060 | 0.2 | 0.089 | 0.3 | 0.210 | 0.8 | 0.245 | 0.9 | 0.323 | 1.2 | | HSV-1 | <1X LoD | 78.9% (71/90) | 30.26 | 0.418 | 1.4 | 0.095 | 0.3 | 0.000 | 0.0 | 0.428 | 1.4 | 0.125 | 0.4 | 0.446 | 1.5 | | HSV-2 | 3X LoD | 100.0% (90/90) | 29.03 | 0.265 | 0.9 | 0.000 | 0.0 | 0.024 | 0.1 | 0.266 | 0.9 | 0.233 | 0.8 | 0.354 | 1.2 | | HSV-2 | 1X - 2X LoD | 100.0% (90/90) | 29.60 | 0.270 | 0.9 | 0.156 | 0.5 | 0.000 | 0.0 | 0.311 | 1.1 | 0.243 | 0.8 | 0.395 | 1.3 | | HSV-2 | <1X LoD | 90.0% (81/90) | 32.07 | 0.474 | 1.5 | 0.219 | 0.7 | 0.000 | 0.0 | 0.522 | 1.6 | 0.063 | 0.2 | 0.526 | 1.6 | | VZV | 3X LoD | 100.0% (90/90) | 27.38 | 0.257 | 0.9 | 0.118 | 0.4 | 0.000 | 0.0 | 0.283 | 1.0 | 0.104 | 0.4 | 0.301 | 1.1 | | VZV | 1X - 2X LoD | 100.0% (90/90) | 28.77 | 0.305 | 1.1 | 0.204 | 0.7 | 0.000 | 0.0 | 0.367 | 1.3 | 0.125 | 0.4 | 0.388 | 1.3 | | VZV | <1X LoD | 88.9% (80/90) | 31.92 | 0.586 | 1.8 | 0.353 | 1.1 | 0.000 | 0.0 | 0.684 | 2.1 | 0.315 | 1.0 | 0.753 | 2.4 | ª Number of replicates with positive results used in the Mean and SD calculation. b Total Number of replicates. ° Within-Laboratory includes Within-Run, Between-Run and Between-Day Components. d Total includes Within-Run, Between-Run, Between-Day, and Between-Instrument/Lot/Operator Components. {14}------------------------------------------------ #### Reproducibility Study Reproducibility performance of the Alinity m HSV 1 & 2 / VZV assay was evaluated by testing a 4-member reproducibility panel consisting of 4 target levels (Positive, Low Positive, High Negative, and Negative). Each positive panel members were prepared by spiking HSV-1, HSV-2 and VZV stocks into simulated negative matrix to achieve the targeted level at 5X LoD (Positive), 1X to 2X LoD (Low Positive), sub-LoD (High Negative), and Negative panel member. A total of 3 Alinity m HSV 1 & 2 / VZV AMP Kit lots were used. Each of 3 external sites tested 2 Alinity m HSV 1 & 2 / VZV AMP Kit lots, on 5 non-consecutive days for each lot. Six replicates of each panel member were tested on each of 5 days. Each of the 3 external sites used different lots of Alinity m HSV 1 & 2 / VZV CTRL Kits and Alinity m Sample Prep Kit 2. The reproducibility results for HSV-1, HSV-2 and VZV are summarized in Table 7. {15}------------------------------------------------ # Table 7. Reproducibility | | | | | | Within-Run/Day Component | | Between-Run/Day Component | | Between-Lot Component | | Between-Site/Instrument Component | | Totalc | | |---------|----------------------|------------------------------|--------------|-------|-----------------------------|-------|------------------------------|-------|--------------------------|-------|--------------------------------------|-------|--------|--| | Analyte | Panel Description | Rate of Detection (na/Nb) | Mean (CN) | SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV | | | HSV-1 | 5X LoD | 100.0% (180/180) | 27.21 | 0.322 | 1.2 | 0.140 | 0.5 | 0.097 | 0.4 | 0.000 | 0.0 | 0.364 | 1.3 | | | HSV-1 | 1X-2X LoD | 98.9% (178/180) | 28.96 | 0.413 | 1.4 | 0.000 | 0.0 | 0.041 | 0.1 | 0.066 | 0.2 | 0.421 | 1.5 | | | HSV-1 | <1X LoD | 49.4% (89/180) | 30.52 | 0.406 | 1.3 | 0.000 | 0.0 | 0.000 | 0.0 | 0.037 | 0.1 | 0.408 | 1.3 | | | HSV-2 | 5X LoD | 100.0% (180/180) | 29.53 | 0.311 | 1.1 | 0.142 | 0.5 | 0.054 | 0.2 | 0.105 | 0.4 | 0.362 | 1.2 | | | HSV-2 | 1X-2X LoD | 100.0% (180/180) | 30.56 | 0.391 | 1.3 | 0.102 | 0.3 | 0.192 | 0.6 | 0.084 | 0.3 | 0.455 | 1.5 | | | HSV-2 | <1X LoD | 35.6% (64/180) | 32.38 | 0.421 | 1.3 | 0.000 | 0.0 | 0.115 | 0.4 | 0.000 | 0.0 | 0.437 | 1.3 | | | VZV | 5X LoD | 100.0% (180/180) | 27.38 | 0.409 | 1.5 | 0.154 | 0.6 | 0.000 | 0.0 | 0.184 | 0.7 | 0.474 | 1.7 | | | VZV | 1X-2X LoD | 100.0% (180/180) | 29.22 | 0.438 | 1.5 | 0.152 | 0.5 | 0.057 | 0.2 | 0.133 | 0.5 | 0.486 | 1.7 | | | VZV | <1X LoD | 62.2% (112/180) | 32.21 | 0.577 | 1.8 | 0.000 | 0.0 | 0.000 | 0.0 | 0.097 | 0.3 | 0.585 | 1.8 | | Number of replicates with positive results used in the Mean and SD calculation. ಪ b Total Number of replicates. c Total includes Within-Run/Day, Between-Run/Day, Between-Lot, and Between-Site/Instrument Components. {16}------------------------------------------------ #### Clinical Performance Evaluation Performance characteristics of the Alinity m HSV 1 & 2 / VZV assay were established in prospective and retrospective clinical studies conducted in the United States. ## Prospective Study The multicenter, prospective clinical study was conducted using swab specimens from lesions (including cutaneous and mucocutaneous) of symptomatic individuals suspected of HSV-1, HSV-2. and/or VZV infection at geographically diverse locations in the US. All lesion swab specimens were prospectively collected in BD UVT, COPAN UTM, or Remel M4RT collection media. The subjects were male and female individuals of all ages, including pediatric and geriatric populations. The swab specimens included in the study were categorized as cutaneous (e.g., skin lesion), mucocutaneous (e.g., anorectal, vaginal/cervical, and oral lesion), and uncategorized (lesion type could not be determined). A total of 1,258 results were included in the clinical performance analysis for each analyte (1,257 results for HSV-1, 1,257 results for HSV-2, and 1,257 results for VZV). | Table 8. Prospective Study - Age and Gender Distribution by Lesion Type | | | | | |-------------------------------------------------------------------------|----------------|--------------------------------|------------------------------|-------------------| | | | Number of Specimens | | | | Lesion Type | Age | Female Subjects (# Lesions) | Male Subjects (# Lesions) | Total (# Lesions) | | Cutaneous | ≤ 5 Years | 10 (11) | 15 (16) | 25 (27) | | | 6 to 21 Years | 24 (28) | 27 (28) | 51 (56) | | | 22 to 59 Years | 176 (195) | 163 (183) | 339 (378) | | | ≥ 60 Years | 82 (95) | 78 (86) | 160 (181) | | | Total | 292 (329) | 283 (313) | 575 (642) | | Mucocutaneous | ≤ 5 Years | 13 (20) | 14 (29) | 27 (49) | | | 6 to 21 Years | 33 (34) | 12 (13) | 45 (47) | | | 22 to 59 Years | 219 (240) | 120 (170) | 339 (410) | | | ≥ 60 Years | 62 (80) | 21 (27) | 83 (107) | | | Total | 327 (374) | 167 (239) | 494 (613) | | Uncategorized | ≤ 5 Years | 0 (0) | 0 (0) | 0 (0) | | | 6 to 21 Years | 0 (0) | 0 (0) | 0 (0) | | | 22 to 59 Years | 0 (0) | 0 (0) | 0 (0) | | | ≥ 60 Years | 3 (3) | 0 (0) | 3 (3) | | | Total | 3 (3) | 0 (0) | 3 (3) | | Total | Total | 622 (706) | 450 (552) | 1072 (1258a) | The gender and age demographics for each lesion type are listed in Table 8. 30ne specimen did not have a result for HSV-1 and HSV-2 but did have a result for VZV; another specimen did not have result for VZV but did have result for HSV-1 and HSV-2; therefore, a total of 1,257 results were included for each analyte. {17}------------------------------------------------ The Alinity m HSV 1 & 2 / VZV assay results for each analyte were directly compared to commercially available NAAT comparator method (NAAT 1). For specimens with discordant results between Alinity m and the comparator method, testing with a second commercially available RT-PCR comparator method was performed (NAAT 2). Results of testing on discordant samples were not included in the analysis of device performance and are considered for information purposes only. The prospective clinical agreement of Alinity m HSV 1 & 2 / VZV assay compared to a commercially available NAAT comparator method is summarized in Table 9. Overall, for HSV-1, positive percent agreement (PPA) was 97.6% and negative percent agreement (NPA) was 98.9%. For HSV-2, PPA was 99.2% and NPA was 99.2%. For VZV, PPA was 97.7% and NPA was 99.8%. Clinical performance by the lesion type is also shown in Table 9. {18}------------------------------------------------ | Table 9. Clinical Agreement by Analyte and Lesion Type - Prospective Study | | | | | | | | | |----------------------------------------------------------------------------|----------------|------|-----------------------|-----------------------|-----------------------|-----------------------|-----------------------------|--------------------------------| | Analyte | Sample Type | N | NAAT 1 + Alinity + | NAAT 1 + Alinity - | NAAT 1 - Alinity - | NAAT 1 - Alinity + | PPA…