The Focus Diagnostics Simplexa™ HSV 1 & 2 Direct is intended for use on the 3M Integrated Cycler instrument for the qualitative detection and differentiation of HSV-1 and HSV-2 DNA in cerebrospinal fluid (CSF) samples from patients suspected of herpes simplex virus (HSV) infections of the central nervous system (CNS). This test is intended as an aid in the diagnosis of HSV-1 and HSV-2 infections of the CNS.

Negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions.

The assay is not intended for use as a donor screening test. The assay is for professional use only.

The Simplexa™ HSV 1 & 2 Positive Control Pack is intended to be used as a control with the Simplexa™ HSV 1 & 2 Direct kit. This control is not intended for use with other assays or systems.

Device Description

The Simplexa™ HSV 1 & 2 Direct assay system is a real-time PCR that enables the direct amplification, detection and differentiation of HSV-1 and/or HSV-2 DNA from unprocessed CSF specimens without nucleic acid extraction. The system consists of the Simplexa™ HSV 1 & 2 Direct assay, the 3M Integrated Cycler (with 3M Integrated Cycler Studio Software), the Direct Amplification Disc and associated accessories.

In the Simplexa™ HSV 1 & 2 Direct assay, bi-functional fluorescent probe-primers are used together with corresponding reverse primers to amplify HSV-1, HSV-2 and internal control targets. Well conserved regions of the HSV-1 and HSV-2 DNA polymerase genes are targeted to identify HSV-1 and HSV-2 DNA respectively in the specimen. An internal control is used to detect PCR failure and/or inhibition.

AI/ML Overview

The provided text describes a 510(k) summary for the Simplexa™ HSV 1 & 2 Direct and Simplexa™ HSV 1 & 2 Positive Control Pack, which is a modification to a previously cleared device (K133621). The changes are specifically related to the Integrated Cycler Studio Software version 6.0.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. A table of acceptance criteria and the reported device performance

The document mentions that "Verification activities for the Integrated Cycler Studio software version 6.0 included development of verification test plans with defined acceptance criteria (design inputs), conducting and documenting verification testing and review of the verification results as they compared to the verification test plans predetermined acceptance criteria (design outputs)." It also states that "Integrated Cycler Studio software version 6.0 was validated in a similar fashion with the development of validation test plans with defined acceptance criteria (design inputs), conducting validation testing and review of the validation results as they compared to the validation test plans predetermined acceptance criteria (design outputs)."

However, the specific acceptance criteria (e.g., percentage agreement, sensitivity, specificity, or specific values for these metrics) for the software's performance with the assay, and the reported device performance against these criteria, are not explicitly detailed in the provided text. The text only states that "The results of verification and validation of Integrated Cycler Studio software version 6.0 show the results met the predetermined acceptance criteria." and "The results of assays ran with the Integrated Cycler Studio software version 6.0 demonstrate that the results obtained with the previously released versions of Integrated Cycler Studio software were equivalent to the results obtained using Integrated Cycler Studio software version 6.0."

Without the actual defined acceptance criteria and the quantitative or qualitative results against them, a detailed table cannot be created from this document.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document focuses on software changes and comparison to a predicate device. It indicates that "The results of assays ran with the Integrated Cycler Studio software version 6.0 demonstrate that the results obtained with the previously released versions of Integrated Cycler Studio software were equivalent to the results obtained using Integrated Cycler Studio software version 6.0." This suggests that a comparison study was performed, likely using existing assay data or running new assays with the modified software.

However, the sample size for any test set, the specific data provenance (country of origin), and whether the data was retrospective or prospective are not mentioned in the provided text.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not provided in the text. The device is an in vitro diagnostic for detecting HSV-1 and HSV-2 DNA. The "ground truth" for such devices is typically established through molecular reference methods or clinical diagnosis, not usually expert consensus in the same way as imaging analysis.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This information is not applicable or provided in the text. Adjudication methods are typically used in studies involving human interpretation (e.g., radiologists reviewing images), where disagreement among experts needs resolution. For a PCR-based diagnostic device, the assessment of results against a ground truth would follow established laboratory protocols for molecular diagnostics, not human adjudication.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

An MRMC study is not applicable here as the device is a direct molecular diagnostic test, not an AI-assisted human reader interpretation system. The device directly detects viral DNA.

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

The device is inherently a "standalone" algorithm (PCR assay interpreted by software) in the sense that it performs the detection and differentiation of HSV DNA without a human interpreting the primary assay signal directly for diagnosis. The software (Integrated Cycler Studio) processes the raw data from the PCR reaction to deliver a qualitative result (presence/absence of HSV-1/HSV-2 DNA). The statement that "The results of assays ran with the Integrated Cycler Studio software version 6.0 demonstrate that the results obtained with the previously released versions of Integrated Cycler Studio software were equivalent to the results obtained using Integrated Cycler Studio software version 6.0" implies an assessment of the software's performance on its own.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

Given that this is a molecular diagnostic for HSV DNA, the ground truth would typically be established by a highly sensitive and specific reference molecular method (e.g., an FDA-cleared or a well-validated in-house laboratory developed test with stringent analytical performance characteristics, or potentially by clinical diagnosis combined with other laboratory findings). The specific method for establishing ground truth is not explicitly stated in the provided text.

8. The sample size for the training set

The document describes software version changes and verification/validation activities. There is no mention of a "training set" in the context of machine learning or AI. The software is designed to interpret PCR assay results.

9. How the ground truth for the training set was established

As there is no mention of a "training set" or AI/machine learning development, this question is not applicable based on the provided text.

Summary

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Image /page/0/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in bold, sans-serif font, with the word "Diagnostics" in a smaller font size underneath. A curved, swooping line is placed to the left of the word "FOCUS", adding a dynamic element to the design. The logo is in black and white.

JUL 0 1 2014

510(k) Summary

Simplexa™ HSV 1 & 2 Direct REF MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack |REF|MOL2160 Prepared Date: July 1, 2014 Page 1 of 4

Applicant	Focus Diagnostics, Inc.11331 Valley View StreetCypress, California 90630USA
Establishment Registration No.	2023365
Contact Person	Sharon Youngtel 562.240.6680fax 562.240.6529syoung@focusdx.com
Summary Date	July 1, 2014
Proprietary Name	Simplexa™ HSV 1 & 2 Direct and Simplexa™ HSV 1 & 2 PositiveControl Pack
Generic Name	HSV-1 & HSV-2 DNA detection
Classification	Class II
US Product Code	PGH - HSV-1 and HSV-2 CNS Nucleic-Acid based panel
Regulation Number	§21 CFR 866.3307
Predicate Device	K133621

INTENDED USE

The Focus Diagnostics Simplexa™ HSV 1 & 2 Direct is intended for use on the 3M Integrated Cycler instrument for the qualitative detection and differentiation of HSV-2 DNA in cerebrospinal fluid (CSF) samples from patients suspected of herpes simplex virus (HSV) infections of the central nervous system (CNS). This test is intended as an aid in the diagnosis of HSV-1 and HSV-2 infections of the CNS.

Negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions.

The assay is not intended for use as a donor screening test. The assay is for professional use only.

INTENDED USE

The Simplexa™ HSV 1 & 2 Positive Control Pack is intended to be used as a control with the Simplexa™ HSV 1 & 2 Direct kit. This control is not intended for use with other assays or systems.

DEVICE DESCRIPTION

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Image /page/1/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features the word "FOCUS" in bold, uppercase letters, with a curved line extending from the left side of the "F" and arching over the top of the word. Below "FOCUS" is the word "Diagnostics" in a smaller, non-bold font, underlined with a thin line.

K141458

510(k) Summary Simplexa™ HSV 1 & 2 Direct REF MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack |REF|MOL2160 Prepared Date: July 1, 2014 Page 2 of 4

Simplexa™ HSV 1 & 2 Direct REF MOL2150

Kit Description
Component Name	REF	EC SYMBOLON LABEL	Abbreviated Name	Cap Color	Number of Vials	Reactions per Vial/Kit	Volume per Vial
Simplexa™ HSV 1 & 2Direct Reaction Mix	MOL2151	REAG	. RM	Brown	24	1/24	50 $ μ $ L

Component Description

Kit Component	Contents
DNA polymerase, buffer, dNTPs, template DNA (Internal Control) dye-labeled fluorescent probe-primers specific for detection of HSV-1 and/or HSV-2 and for the DNA Internal Control.
	Target	ProbeFluorophore(Dye)	Excitation (nm)	Emission (nm)	Targeted Gene
Simplexa™ HSV 1 &2 Direct Reaction Mix(RM)	HSV-1	CFR610	590	610	HSV-1 DNApolymerase
	HSV-2	FAM	495	520	HSV-2 DNApolymerase
	DNA InternalControl	Q670	644	670	NA
Simplexa™ HSV 1 &2 Kit Barcode Card	Assay specific parameters.

Simplexa™ HSV 1 & 2 Positive Control Pack REF MOL2160

Product Description

Component Name	REF	Description	Cap Color	Number of Vials	Reactions per Vial/Kit	Volume per Vial
Simplexa™ HSV 1 & 2 Direct Positive Control	MOL2161	Inactivated HSV-1 Virus, Inactivated HSV-2 Virus	Red	10	1/10	100 μL

MATERIALS SUPPLIED SEPARATLY

Direct Amplification Disc Kit (REF MOL1455) 1.

a. Direct Amplification Discs for use on the 3M Integrated Cycler.

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Image /page/2/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features the word "FOCUS" in bold, uppercase letters. Below "FOCUS" is the word "Diagnostics" in a smaller font size, underlined with a thin line. To the left of the word "FOCUS" is a curved, black shape that resembles a check mark.

K141458

510(K) Simplexa™ HSV 1 & 2 Direct REF|MOL2150
Simplexa™ HSV 1 & 2 Positive Control Pack [RE] MOL2150
Simplexa™ HSV 1 & 2 Positive Control Pack [REF]MOL2160 Prepared Date: July 1, 2014 Page 3 of 4

COMPARISON TO PREDICATE

Similarities

Feature	Predicate K133621	Modified Device K141458
Intended Use	The Focus Diagnostics Simplexa™HSV 1 & 2 Direct is intended for useon the 3M Integrated Cyclerinstrument for the qualitativedetection and differentiation of HSV-1 and HSV-2 DNA in cerebrospinalfluid (CSF) samples from patientssuspected of Herpes Simplex Virus(HSV) infections of the centralnervous system (CNS). This test isintended as an aid in the diagnosis ofHSV-1 and HSV-2 infections of theCNS.Negative results do not precludeHSV-1 or HSV-2 infection and shouldnot be used as the sole basis fortreatment or other patientmanagement decisions.The assay is not intended for use asa donor screening test. The assay isfor professional use only.The Positive Control is intended tobe used as a control with theSimplexa™ HSV 1 & 2 Direct. Thiscontrol is not intended for use withother assays or systems.	Same
Technology	The Simplexa™ HSV 1 & 2 Directassay system is a real-time PCR thatenables the direct amplification,detection and differentiation of HSV-1 and/or HSV-2 DNA fromunprocessed CSF specimens withoutnucleic acid extraction.	Same
Analyte	HSV-1 & HSV-2 DNA.	Same
Assay Type	Qualitative.	Same

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Image /page/3/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in large, bold, sans-serif font, with the word "Diagnostics" in a smaller font size underneath. A curved, swooping shape is positioned to the left of the word "FOCUS", adding a dynamic element to the design. The overall design is simple, clean, and professional.

510(k) Summary Simplexa™ HSV 1 & 2 Direct REF MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack |REF| MOL2160 Prepared Date: July 1, 2014 Page 4 of 4

Differences

	Predicate	Modified Device
Integrated Cycler Studio Software	Integrated Cycler Studio Softwareversion 5.0 or higher.	Integrated Cycler Studio Softwareversion 6.0 or higher.Software changes were made torestrict manual modification of thespectral matrix and to resolveanomalies.

SUMMARY OF DESIGN CONTROL ACTIVITIES

Design controls in accordance with $21 CFR 820.30 were conducted to modify the device. Verification activities for the Integrated Cycler Studio software version 6.0 included development of verification test plans with defined acceptance criteria (design inputs), conducting and documenting verification testing and review of the verification results as they compared to the verification test plans predetermined acceptance criteria (design outputs). Integrated Cycler Studio software version 6.0 was validated in a similar fashion with the development of validation test plans with defined acceptance criteria (design inputs), conducting validation testing and review of the validation results as they compared to the validation test plans predetermined acceptance criteria (design outputs). The results of verification and validation of Integrated Cycler Studio software version 6.0 show the results met the predetermined acceptance criteria. The results of assays ran with the Integrated Cycler Studio software version 6.0 demonstrate that the results obtained with the previously released versions of Integrated Cycler Studio software were equivalent to the results obtained using Integrated Cycler Studio software version 6.0.

The changes made to the Integrated Cycler Studio software version 6.0 were assessed using risk management. Risk management involved analysis of the characteristics of Integrated Cycler Studio software version 6.0, the characteristics of the process that might create a hazard with the Integrated Cycler Studio software version 6.0, and the possible hazards associated with the use of the Integrated Cycler Studio software version 6.0. The risk management process consisted of risk analysis, risk evaluation, risk benefit and evaluation of residual risk acceptability. A thorough review was performed to ensure identified from all hazardous situations were considered to assess if previously estimated risks were affected. After risk control measures were applied, any residual risk(s) were evaluated. Acceptability of overall residual risk took into consideration whether anticipated medical benefits outweighed the overall residual risks of a product placed on the market for its intended use.

A declaration of conformity to design controls in accordance to §21 CFR 820.30 is included in the K141458 Simplexa™ HSV 1 & 2 Direct REF MOL2150 and Simplexa™ HSV 1 & 2 Positive Control Pack [REF] MOL2160 Special 510(k) submission. The declaration of conformity was signed by the individuals responsible for the activities.

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Image /page/4/Picture/0 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter of the circle. Inside the circle is an emblem that appears to be a stylized representation of an eagle or bird.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 1, 2014

FOCUS DIAGNOSTICS SHARON YOUNG 11331 VALLEY VIEW STREET CYPRESS, CA 90630

Re: K141458 Trade/Device Name: Simplexa™ HSV 1 & 2 Direct and Simplexa™ HSV 1 & 2 Positive Control Pack Regulation Number: 21 CFR 866.3307 Regulation Name: Herpes simplex virus nucleic acid-based assay for central nervous system infections Regulatory Class: II Product Code: PGH Dated: May 29, 2014 Received: June 2, 2014

Dear Ms. Young:

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 (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. 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 }] (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.

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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2-Ms. Young

If vou desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled. * Misbranding by reference to premarket notification* (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/delault.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely vours.

Stephen J. Lovell -S

Sally A. Hojvat. M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K141458

Device Name Simplexa™ HSV 1 & 2 Direct Simplexa™ HSV 1 & 2 Positive Control Pack

Indications for Use (Describe)

Simplexa™ HSV 1 & 2 Direct (MOL2150)

Negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions.

The assay is not intended for use as a donor screening test. The assay is for professional use only.

SimplexaTM HSV 1 & 2 Positive Control Pack (MOL2160)

The Simplexa™ HSV 1 & 2 Positive Control Pack is intended to be used as a control with the Simplexa™ HSV 1 & 2 Direct kit. This control is not intended for use with other assays or systems.

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)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Stephen J. Lovell -S 2014.07.01 14:37:03 -04'00' Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

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Regulation Number and Section

§ 866.3307 Herpes simplex virus nucleic acid-based assay for central nervous system infections.

(a)
Identification. A herpes simplex virus nucleic acid-based assay for central nervous system infections is a qualitative in vitro diagnostic device intended for the detection and differentiation of HSV-1 and HSV-2 in cerebrospinal fluid (CSF) samples from patients suspected of Herpes Simplex Virus (HSV) infections of the central nervous system (CNS). This test is intended as an aid in the diagnosis of HSV-1 and HSV-2 infections of the CNS. Negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) 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.
(ii) Detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (limit of detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carryover, and cross contamination. Documentation must include reagent and sample stability recommendations.
(iii) Detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to the results of two polymerase chain reaction methods followed by bidirectional sequencing.
(iv) Documentation of 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.
(v) Quality assurance protocols and detailed documentation for device software, including standalone software applications and hardware-based devices that incorporate software.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed explanation of the interpretation of results and acceptance criteria.
(ii) A limiting statement indicating that negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions.