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.

Device Description

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:

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

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

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

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

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

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

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

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

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

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

AI/ML Overview

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

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

1. Table of Acceptance Criteria and Reported Device Performance

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

Acceptance Criteria Category	Specific Metric	Target (Implicit)	Reported Device Performance (Table 9 - Prospective Study)	Reported Device Performance (Table 11 - Retrospective Study)
Clinical Agreement (Total)	HSV-1 PPA	High (e.g., >95%)	97.6% (123/126) (95% CI: 93.2, 99.2)	100.0% (72/72) (95% CI: 94.9, 100.0)
	HSV-1 NPA	High (e.g., >95%)	98.9% (1119/1131) (95% CI: 98.2, 99.4)	96.2% (325/338) (95% CI: 93.5, 97.7)
	HSV-2 PPA	High (e.g., >95%)	99.2% (122/123) (95% CI: 95.5, 99.9)	98.7% (74/75) (95% CI: 92.8, 99.8)
	HSV-2 NPA	High (e.g., >95%)	99.2% (1125/1134) (95% CI: 98.5, 99.6)	95.8% (321/335) (95% CI: 93.1, 97.5)
	VZV PPA	High (e.g., >95%)	97.7% (43/44) (95% CI: 88.2, 99.6)	97.8% (44/45) (95% CI: 88.4, 99.6)
	VZV NPA	High (e.g., >95%)	99.8% (1211/1213) (95% CI: 99.4, 100.0)	98.4% (360/366) (95% CI: 96.5, 99.2)
Analytical Sensitivity	LoD (HSV-1)	Low (e.g., as defined)	5.90 TCID50/mL	N/A (Analytical study)
	LoD (HSV-2)	Low (e.g., as defined)	2.07 TCID50/mL	N/A (Analytical study)
	LoD (VZV)	Low (e.g., as defined)	0.055 TCID50/mL	N/A (Analytical study)
Analytical Specificity	Cross-Reactivity	No cross-reactivity	No cross-reactivity observed with 55 microorganisms	N/A (Analytical study)
	Interference	No interference	No interference observed with 55 microorganisms at 3X LoD	N/A (Analytical study)
Precision	Detection Rate (3X LoD / 5X LoD)	100%	100% for all analytes at 3X LoD (Table 6)	100% for all analytes at 5X LoD (Table 7)
	Carryover Contamination	0%	0.0% (0/360) (95% CI: 0.0%, 1.1%)	N/A (Analytical study)

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

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

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

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

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

4. Adjudication Method for the Test Set

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

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

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

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

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

7. The Type of Ground Truth Used

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

8. The Sample Size for the Training Set

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

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

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

Summary

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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).

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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

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Indications for Use

510(k) Number (if known) K233349

Device Name Alinity m HSV 1 & 2 / VZV

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

❌ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

Submitter

Applicants Name and Address:	Abbott Molecular Inc.1300 E. Touhy AveAbbott Molecular Inc.
Contact Person:	Stacy FergusonDirector Regulatory AffairsAbbott Molecular, Inc.1350 E. Touhy AvenueDes Plaines, IL 60018Phone: 224-206-4081
Date Prepared:	May 1, 2024

Device Information

Trade Name	Regulation Name	ProductCode	RegulationNumber	Class
Alinity m HSV 1 & 2 / VZV	Herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel.	PGI	21 CFR866.3309	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

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infections and should not be used as the sole basis for diagnosis, treatment or other management decisions.

Device Description

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

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 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.

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· 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

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 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

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Similarities and Differences to Predicate Device

Device andPredicate	New DeviceK233349	Predicate DeviceK133448
Device TradeNumber	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 isan in vitro real-time polymerase chainreaction (PCR) assay for the qualitativedetection and differentiation of HerpesSimplex Virus 1 (HSV-1), Herpes SimplexVirus 2 (HSV-2), and Varicella ZosterVirus (VZV) DNA from clinician-collected cutaneous or mucocutaneouslesion swab specimens from symptomaticpatients suspected of active herpes simplexvirus 1, herpes simplex virus 2 and/orvaricella-zoster virus infection. The Alinitym HSV 1 & 2 / VZV assay is intended toaid in the diagnosis of herpes simplex virus1, herpes simplex virus 2 and/or varicella-zoster virus active cutaneous ormucocutaneous infections. Negativeresults do not preclude herpes simplexvirus type 1, herpes simplex virus type 2 orvaricella-zoster virus infections and shouldnot be used as the sole basis for diagnosis,treatment or other management decisions.The Alinity m HSV 1 & 2 / VZV assay isnot intended for use with cerebrospinalfluid (CSF) or to aid in the diagnosis ofHSV or VZV infections of the centralnervous system (CNS). The Alinity mHSV 1 & 2 / VZV assay is not intended foruse in prenatal screening.	The Lyra Direct HSV 1 + 2/VZV Assay isan in vitro multiplex Real-Time PCR testfor qualitative detection and differentiationof herpes simplex virus type 1, herpessimplex virus type 2, and varicella-zostervirus DNA isolated and purified fromcutaneous or mucocutaneous lesionsamples obtained from symptomaticpatients suspected of active herpes simplexvirus 1, herpes simplex virus 2 and/orvaricella-zoster infection. The Lyra DirectHSV 1 + 2/VZV Assay is intended to aidin the diagnosis of herpes simplex virus 1,herpes simplex virus 2 and varicella-zostervirus active cutaneous or mucocutaneousinfections. Negative results do notpreclude herpes simplex virus 1, herpessimplex virus 2 and varicella-zoster virusinfections and should not be used as thesole basis for diagnosis, treatment or othermanagement decisions. The Lyra DirectHSV 1 + 2/VZV Assay is not intended foruse with cerebrospinal fluid or to aid in thediagnosis of HSV or VZV infections of thecentral nervous system (CNS). The LyraDirect HSV 1 + 2/VZV Assay is notintended for use in prenatal screening. Thedevice is not intended for point-of-careuse.
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
AmplificationTechnology	Real-Time Polymerase Chain Reaction(PCR)	Same
AutomatedAnalysis	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 executedautomatically by the Alinity m System.No intermediate processing or transfersteps are performed by the user.	Assay processing steps are executedmanually until placed on instrument forsignal evaluation:• Life Technologies QuantStudio Dx• Applied Biosystems 7500 Fast Dx• Cepheid SmartCycler II System
SamplePreparationInstrumentComponents	Automated liquid handling and roboticmanipulation platform.Automated process for sample processingusing an internal control (IC)	Mechanical lysis and addition of ProcessBuffer. Manual process for sampleprocessing using the processing control(PRC)
Reagent KitStorage(Unopened) untilexpiration date	-25°C to -15°C	2°C to 8°C

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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

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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.

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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.

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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

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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.

PanelNumber	High Analyte	HSV-1Positivity	HSV-2Positivity	VZVPositivity
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%).

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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.

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Table 6. Precision
--------------------

				Within-RunComponent			Between-RunComponent	Between-DayComponent		Within-Laboratoryc		Between-Instrument/Lot/OperatorComponent		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.

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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.

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Table 7. Reproducibility

					Within-Run/DayComponent		Between-Run/DayComponent		Between-LotComponent		Between-Site/InstrumentComponent		Totalc
Analyte	PanelDescription	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.

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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.

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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.

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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 (%) with 95% CI	NPA (%) with 95% CI
HSV-1	Cutaneous	641	36	0	600	5	100.0 (36/36) (90.4, 100.0)	99.2 (600/605) (98.1, 99.6)
	Mucocutaneous	613	87	2	517	7	97.8 (87/89) (92.2, 99.4)	98.7 (517/524) (97.3, 99.4)
	Uncategorizeda	3	0	1	2	0	0.0 (0/1) (0.0, 79.3)	100.0 (2/2) (34.2, 100.0)
	Total	1257	123	3b	1119	12c	97.6 (123/126) (93.2, 99.2)	98.9 (1119/1131) (98.2, 99.4)
HSV-2	Cutaneous	641	61	1	575	4	98.4 (61/62) (91.4, 99.7)	99.3 (575/579) (98.2, 99.7)
	Mucocutaneous	613	60	0	548	5	100.0 (60/60) (94.0, 100.0)	99.1 (548/553) (97.9, 99.6)
	Uncategorizeda	3	1	0	2	0	100.0 (1/1) (20.7, 100.0)	100.0 (2/2) (34.2, 100.0)
	Total	1257	122	1d	1125	9e	99.2 (122/123) (95.5, 99.9)	99.2 (1125/1134) (98.5, 99.6)
VZV	Cutaneous	641	38	0	601	2	100.0 (38/38) (90.8, 100.0)	99.7 (601/603) (98.8, 99.9)
	Mucocutaneous	613	5	1	607	0	83.3 (5/6) (43.6, 97.0)	100.0 (607/607) (99.4, 100.0)
	Uncategorizeda	3	0	0	3	0	-	100.0 (3/3) (43.9, 100.0)
	Total	1257	43	1f	1211	2g	97.7 (43/44) (88.2, 99.6)	99.8 (1211/1213) (99.4, 100.0)

a The lesion type for these swabs could not be determined.

b 3 out of 3 NAAT 1+/Alinity m HSV-1 negative results were negative by NAAT 2.

c 2 out of 12 NAAT 1-/Alinity m HSV-1 positives were positive by NAAT 2.

d 1 out of 1 NAAT 1+/Alinity m HSV-2 negative results were negative by NAAT 2.

e 3 out of 9 NAAT 1-/Alinity m HSV-2 positives were positive by NAAT 2.

t 1 out of 1 NAAT 1+/Alinity m VZV negative results were negative by NAAT 2.

0 out of 2 NAAT 1-/Alinity m VZV positives were positive by NAAT 2. පර

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Retrospective Study

The retrospective study was conducted using archived, leftover lesion swab specimens from routine clinical testing, collected from male and female individuals of all ages, including pediatric and geriatric populations. All lesion swab specimens were previously collected in BD UVT, COPAN UTM, or Remel M4RT collection media per standard of care. One lesion swab specimen was obtained from each individual.

The swab specimens included in the study were categorized as cutaneous (eg, skin lesion), mucocutaneous (eg, anorectal, vaginal/cervical, and oral lesion), and uncategorized (lesion type could not be determined or categorized). A total of 411 specimens were included in the clinical performance analysis that had results for at least one of the analytes (410 results for HSV-1, 410 results for HSV-2, and 411 results for VZV).

Table 10. Retrospective 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	8 (8)	17 (17)	25 (25)
	6 to 21 Years	9 (9)	9 (9)	18 (18)
	22 to 59 Years	60 (60)	25 (25)	85 (85)
	≥ 60 Years	9 (9)	10 (10)	19 (19)
	Total	86 (86)	61 (61)	147 (147)
Mucocutaneous	≤ 5 Years	31 (31)	28 (28)	59 (59)
	6 to 21 Years	18 (18)	13 (13)	31 (31)
	22 to 59 Years	78 (78)	33 (33)	111 (111)
	≥ 60 Years	20 (20)	13 (13)	33 (33)
	Total	147 (147)	87 (87)	234 (234)
Uncategorized	≤ 5 Years	5 (5)	4 (4)	9 (9)
	6 to 21 Years	2 (2)	1 (1)	3 (3)
	22 to 59 Years	8 (8)	8 (8)	16 (16)
	≥ 60 Years	0 (0)	2 (2)	2 (2)
	Total	15 (15)	15 (15)	30 (30)
Total	Total	248 (248)	163 (163)	411 (411)

The gender and age demographics for each lesion type are listed in Table 10.

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The retrospective clinical agreement of Alinity m HSV 1 & 2 / VZV assay compared to the comparator method is summarized in Table 11. For HSV-1, positive percent agreement (PPA) was 100.0% and negative percent agreement (NPA) was 96.2%. For HSV-2, PPA was 98.7% and NPA was 95.8%. For VZV, PPA was 97.8% and NPA was 98.4%. Clinical performance by the lesion type is also shown in Table 11.

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Table 11. Clinical Agreement by Analyte and Lesion Type - Retrospective Study
Analyte	Sample Type	N	NAAT 1 +Alinity +	NAAT 1 +Alinity -	NAAT 1 -Alinity -	NAAT 1 -Alinity +	PPA (%) with 95% CI	NPA (%) with 95% CI
HSV-1	Cutaneous	147	16	0	124	7	100.0 (16/16) (80.6, 100.0)	94.7 (124/131) (89.4, 97.4)
	Mucocutaneous	234	51	0	178	5	100.0 (51/51) (93.0, 100.0)	97.3 (178/183) (93.8, 98.8)
	Uncategorizedª	29	5	0	23	1	100.0 (5/5) (56.6, 100.0)	95.8 (23/24) (79.8, 99.3)
	Total	410	72	0	325	13b	100.0 (72/72) (94.9, 100.0)	96.2 (325/338) (93.5, 97.7)
HSV-2	Cutaneous	147	23	1	115	8	95.8 (23/24) (79.8, 99.3)	93.5 (115/123) (87.7, 96.7)
	Mucocutaneous	234	44	0	186	4	100.0 (44/44) (92.0, 100.0)	97.9 (186/190) (94.7, 99.2)
	Uncategorizedª	29	7	0	20	2	100.0 (7/7) (64.6, 100.0)	90.9 (20/22) (72.2, 97.5)
	Total	410	74	1c	321	14d	98.7 (74/75) (92.8, 99.8)	95.8 (321/335) (93.1, 97.5)
VZV	Cutaneous	147	20	0	125	2	100.0 (20/20) (83.9, 100.0)	98.4 (125/127) (94.4, 99.6)
	Mucocutaneous	234	17	0	214	3	100.0 (17/17) (81.6, 100.0)	98.6 (214/217) (96.0, 99.5)
	Uncategorizedª	30	7	1	21	1	87.5 (7/8) (52.9, 97.8)	95.5 (21/22) (78.2, 99.2)
	Total	411	44	1e	360	6f	97.8 (44/45) (88.4, 99.6)	98.4 (360/366) (96.5, 99.2)

The lesion type for these swabs could not be determined or categorized. a

b 0 out of 13 NAAT 1-/Alinity m HSV-1 positives were positive by NAAT 2.

с 1 out of 1 NAAT 1+/Alinity m HSV-2 negative results were negative by NAAT 2.

d 0 out of 14 NAAT 1-/Alinity m HSV-2 positives were positive by NAAT 2.

e 1 out of 1 NAAT 1+/Alinity m VZV negative results were negative by NAAT 2.

f 0 out of 6 NAAT 1-/Alinity m VZV positives were positive by NAAT 2.

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Conclusions Drawn from the Studies

The analytical and clinical study results demonstrate that the Alinity m HSV 1 & 2 / VZV assay on the Alinity m System performs comparably to the predicate device in detecting HSV 1 & 2 / VZV and supports a substantial equivalence decision.

Regulation Number and Section

§ 866.3309 Herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel.

(a)
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.(b)
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 820.30 design controls 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.