The LIAISON® VZV IgG Assay uses chemiluminescence immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative detection of specific IgG antibodies to varicella-zoster virus in human serum. This assay can be used as an aid in the determination of previous infection of varicella-zoster virus.

Device Description

The method for the qualitative determination of specific IgG to varicella- zoster virus is an indirect chemiluminescence immunoassay (CLIA). All assay steps and incubations are performed by the LIAISON® Analyzer.

Varicella-zoster virus antigen is used for coating magnetic particles (solid phase) and a mouse monoclonal antibody to human IgG is linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, anti-VZV IgG antibodies, present in calibrators, samples or controls, bind to the solid phase. After each incubation, the unbound material is removed with a wash cycle. During the second incubation, the antibody conjugate reacts with anti-VZV IgG already bound to the solid phase. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is induced. The light signal, directly related to the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of anti-VZV IgG in calibrators, samples or controls.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the DiaSorin LIAISON® VZV IgG device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the clinical trial results. The device aims to demonstrate substantial equivalence to the predicate device.

Metric	Acceptance Criteria (Implied)	Reported Device Performance (General Samples)	Reported Device Performance (Pregnant Women)
Positive Agreement	High agreement with predicate device for positive samples	98.8% (97.7 - 99.5% 95% CI)	99.2% (98.2 - 99.7% 95% CI)
Negative Agreement	High agreement with predicate device for negative samples	84.4% (74.4 - 91.7% 95% CI)	64.1% (47.6 - 78.8% 95% CI)
Overall Reproducibility	Consistent results across runs, sites, and operators (low %CV)	See detailed tables below	See detailed tables below
Assay Precision	Consistent results over time on a single instrument (low %CV)	See detailed tables below	See detailed tables below

Reproducibility (3-site, 5-day study with 3 kit lots):

ID#	N	Mean Index (Overall %CV)
DiaSorin Neg Ctl	60	30.3 (18.6)
DiaSorin Pos Ctl	60	434 (14.4)
011006 (Cutoff Ctl)	60	246 (13.8)
BR Neg Ctl (100% serum)	60	<10 (8.24)
BR Pos Ctl (100% serum)	60	863 (12.6)
3314	60	60.2 (9.54)
3360	60	265 (12.9)
3385	60	242 (13.8)
3403	60	164 (9.14)
3492	60	276 (12.3)
3515	60	252 (14.5)
3554	60	291 (14.3)
Pos 5	60	1530 (19.0)
Pos 9	60	679 (12.2)

Assay Precision (single-site, 20-day study with 1 kit lot):

ID#	N	Mean Index (Overall %CV)
DiaSorin Neg Ctl	40	36.3 (20.05)
DiaSorin Pos Ctl	40	446 (20.07)
011006 (Cutoff Ctl)	40	271 (17.01)
BR Neg Ctl (100% serum)	40	<10 (12.62)
BR Pos Ctl (100% serum)	40	952 (19.25)
3314	40	60.8 (13.00)
3360	40	318 (16.85)
3385	40	292 (23.02)
3403	40	164 (14.80)
3492	40	330 (16.62)
3515	40	280 (14.79)
3554	40	286 (18.00)
Pos 5	40	1761 (19.79)
Pos 9	40	769 (16.50)

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

General Samples: 745 total samples.
- 33 equivocal results were excluded from agreement calculations (implied by the statement: "Specimens that were equivocal by both assays were not included in the percent agreement calculation").
- Resulting in 667 for positive agreement calculation and 77 for negative agreement calculation (after adjusting for equivocal results in the reference assay matched with positive/negative device results).
Pregnant Women Samples: 689 total samples.
- 11 equivocal results in the predicate assay and 3 equivocal results in the device were handled in agreement calculation.
- Resulting in 650 for positive agreement calculation and 39 for negative agreement calculation (after adjusting for equivocal results in the reference assay matched with positive/negative device results).
Reproducibility/Precision Samples:
- Reproducibility (3 sites): 9 coded frozen repository samples, plus 4 controls (DiaSorin Neg Ctl, DiaSorin Pos Ctl, Cutoff Ctl, BR Neg Ctl, BR Pos Ctl). Each sample/control tested 60 times (implied 3 sites * X runs * Y replicates per run, totaling 60).
- Precision (1 site): The same serum samples and controls as the reproducibility study. Each sample/control tested 40 times (quadruplicate over 20 working days).
Data Provenance: Prospectively-collected U.S. samples.

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

The ground truth was established by a "comparison assay" (Diamedix Is-VZV IgG Test System, K981867), which is another immunoassay. No human experts are mentioned as establishing the ground truth for the clinical agreement studies. For the reproducibility and precision studies, a coded panel of samples was used, but the initial "truth" of these samples (negative, low positive, moderate to high positive) is not attributed to experts.

4. Adjudication Method for the Test Set

No explicit adjudication method (like 2+1 or 3+1) is mentioned. The comparison was directly between the LIAISON® VZV IgG assay and the predicate VZV IgG ELISA. Equivocal results were handled by excluding them from percent agreement calculations or by considering them as non-agreements when the reference assay was equivocal and the LIAISON® result was positive/negative.

5. Multi-reader Multi-case (MRMC) Comparative Effectiveness Study

No multi-reader, multi-case (MRMC) comparative effectiveness study was done. This study focuses on the performance of an automated immunoassay device, not on human reader performance with or without AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, the studies presented are all standalone. The DiaSorin LIAISON® VZV IgG is an automated chemiluminescence immunoassay (CLIA) system. Its performance is measured directly against a predicate immunoassay (clinical agreement) and its own internal consistency (reproducibility and precision). There is no human-in-the-loop component described for these performance evaluations.

7. Type of Ground Truth Used

The "ground truth" for the clinical agreement studies was established by a predicate immunoassay (VZV IgG ELISA). For reproducibility and precision, it was based on known control materials and coded repository samples with established characteristics (negative, low-positive, high-positive).

8. Sample Size for the Training Set

The document does not provide information on the sample size used for the training set of the DiaSorin LIAISON® VZV IgG assay. The provided data is for the validation/test phase of the device.

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

The document does not provide information on how the ground truth for the training set (if any was used for algorithm development) was established. The information focuses on the validation of the device.

Summary

{0}------------------------------------------------

K061820

FEB 2 6 2007

SUBMITTED BY:

5.0 510(k) SUMMARY

Mari Meyer Requlatory Affairs Specialist DiaSorin Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285 Phone (651) 351-5635 Fax (651) 351-5669 E-mail: mari meyer@diasorin.com

NAME OF DEVICE:

Trade Name:

Common Names/Descriptions:

DiaSorin LIAISON® VZV IgG

Immunoassay for the detection of specific IgG antibodies to varicella-zoster virus (VZV IgG).

Classification Names:

Product Code:

PREDICATE DEVICE:

Varicella-zoster virus Serological Reagents

LFY

Diamedix Is-VZV IgG Test System, K981867

DEVICE DESCRIPTION:

INTENDED USE: The DiaSorin LIAISON® VZV IgG uses chemiluminescence immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative detection of specific IgG antibodies to varicellazoster virus (VZV) in human serum. This assay can be used as an aid in the determination of previous infection of varicella-zoster virus.

KIT DESCRIPTION: The method for the qualitative determination of specific IgG to varicella- zoster virus is an indirect chemiluminescence immunoassay (CLIA). All assay steps and incubations are performed by the LIAISON® Analyzer.

PERFORMANCE DATA:

COMPARATIVE CLINICAL TRIALS: The clinical trials were conducted at two external U.S. laboratories and at DiaSorin. Testing was performed on prospectively-collected U.S. samples as defined below. The samples were tested by LIAISON® VZV IgG and a comparison assay, at the trial sites per the manufacturers' instructions for use.

Specimens that were equivocal by both assays were not included in the percent agreement calculation. Positive or negative results from the LIAISON® VZV IgG assay were considered as non-agreements in the calculation of percent positive agreement and percent negative agreement when the corresponding reference assay result was equivocal,

Section 5

Page 5 - 1

{1}------------------------------------------------

DiaSorin LIAISON® VZV IgG Premarket Notification

Compares number of samples positive on both assays to sum of all positive samples on the reference assay + samples equivocal on the reference assay and negative on the LIAISON® VZV IgG. Compared number of samples negative on both assay to sum of all negative samples on the reference assay + samples equivocal on the reference assay and positive on the LIAISON® VZV IgG

	DiaSorinLIAISON® VZV IgG	VZV IgG ELISA
		Positive	Equivocal	Negative	Total
	Positive	659	7	4	670
	Equivocal	1	1	1	3
	Negative	3	4	65	72
	Total	663	12	70	745
		Percent Agreement	Exact 95% confidence interval
Positive		98.8%(659/667)	97.7 - 99.5%
Negative		84.4%(65/77)	74.4 - 91.7%

Prospective samples: Subjects Sent to the Laboratory for varicella-zoster virus testing

Prospective Samples: Pregnant Women

LIAISON® VZV IgG Results	VZV IgG ELISA Results
	Positive	Equivocal	Negative	Total
Positive	645	11	3	659
Equivocal	3	0	0	3
Negative	2	0	25	27
Total	650	11	28	689
Percent Agreement
Positive	99.2%	(645/650)	98.2 - 99.7%
Negative	64.1%	(25/39)	47.6 - 78.8%

REPRODUCIBILITY: Reproducibility studies were performed at 3 sites in a five-day protocol outlined in CLSI document, EP15-A2. The study included 3 different LIAISON® VZV IgG kit lots. Each site used a different lot of the LIAISON® VZV IgG Assay for the study. A coded panel comprised of 9 frozen repository samples, prepared representing negative levels, low positive analyte levels, and moderate to high positive levels, was used in this study. The study also included the U.A.ISON® VZV IgG controls (Neg Ctl and Pos Ctl) which are marketed in Europe, an internal serum borderline control (011006) and a commercially marketed serum ToRCH Negative and Positive Control (BR Neg Ctl and BR Pos Ctl). Results expressed as an Index value are summarized in the following table.

ﮨﯿﮟ

{2}------------------------------------------------

DiaSorin LIAISON® VZV IgG Premarket Notification

. . .

		Mean	Within-run	Within-run	Between-run	Between-run	Between-site	Between-site	Overall	Overall
ID#	N	Index	sd	%CV	sd	%CV	sd	%CV	sd	%CV
DiaSorin Neg Ctl	60	30.3	2.97	9.0	4.52	7.87	3.88	12.8	5.64	18.6
DiaSorin Pos Ctl	60	434	42.6	9.81	48.9	9.21	40.3	9.29	62.4	14.4
011006 (Cutoff Ctl)	60	246	22.8	9.44	26.4	10.2	13.6	5.54	33.9	13.8
BR Neg Ctl(100% serum)	60	<10	15.0	5.53	18.0	6.15	4.0	1.62	23.0	8.24
BR Pos Ctl(100% serum)	60	863	86.4	10.2	70.6	8.05	27.8	3.22	108	12.6
3314	60	60.2	3.81	6.54	3.74	5.42	1.04	4.01	5.75	9.54
3360	60	265	19.5	7.35	29.3	7.59	6.88	9.75	34.2	12.9
3385	60	242	22.0	8.98	26.1	7.63	4.67	9.63	33.5	13.8
3403	60	164	8.23	4.86	13.1	5.73	0.73	6.96	14.9	9.14
3492	60	276	24.8	9.08	24.4	7.62	7.89	6.08	33.9	12.3
3515	60	252	27.4	10.6	24.9	8.42	7.12	6.25	36.5	14.5
3554	60	291	26.0	8.68	28.6	7.94	14.0	5.83	41.5	14.3
Pos 5	60	1530	227	14.6	184	10.2	138	7.02	291	19.0
Pos 9	60	679	60.6	9.06	57.1	7.79	38.8	1.20	82.7	12.2

BR Neg Ctl Index was below the reading range of the assay therefore; the precision calculations are based on signal (RLU) for this sample.

The assay precision performance was established at DiaSorin following a protocol outlined in CLS1 document, EP5-A2. The same serum samples and controls described in the five-day study were tested in quadruplicate over 20 working days on one LIAISON® instrument and one kit lot.

Results

The results, expressed as an Index value, are summarized in the following table as sample global mean Index; mean %CV's computed for within run, between run, and total.

{3}------------------------------------------------

DiaSorin LIAISON® VZV IgG Premarket Notification

....

ID#	N	mean(Index)	withinrunsd	withinrun%CV	betweenrunsd	betweenrun%CV	overallsd	overall%CV
DiaSorin Neg Ctl	40	36.3	3.0	8.53	6.86	18.90	7.20	20.05
DiaSorin Pos Ctl	40	446	19.4	4.41	86.70	19.48	88.62	20.07
011006 (Cutoff Ctl)	40	271	18.3	6.78	43.45	16.06	45.62	17.01
BR Neg Ctl(100% serum Ctl)	40	<10	10.8	4.14	31.12	12.07	32.39	12.62
BR Pos Ctl(100% serum Ctl)	40	952	64.0	7.07	174.41	18.32	182.54	19.25
3314	40	60.8	2.9	4.94	7.46	12.28	7.86	13.00
3360	40	318	17.6	5.45	52.09	16.39	53.23	16.85
3385	40	292	6.9	2.40	66.92	22.94	66.39	23.02
3403	40	164	8.5	5.04	23.78	14.53	24.18	14.80
3492	40	330	22.0	6.83	50.39	15.27	54.36	16.62
3515	40	280	10.2	3.62	40.86	14.60	41.14	14.79
3554	40	286	21.1	7.10	48.00	16.77	51.07	18.00
Pos 5	40	1761	97.2	5.56	337.11	19.37	344.93	19.79
Pos 9	40	769	26.2	3.38	127.97	16.64	126.33	16.50

BR Neg Ctl Index was below the reading range of the assay therefore; the precision calculations are based on signal (RLU) for this sample.

CONCLUSION

The submitted material in this premarket notification is complete and supports a substantial equivalence decision. The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

{4}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is a staff with two snakes coiled around it. The caduceus is encircled by the text "U.S. Department of Health & Human Services" in a circular arrangement.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Mari Meyer Regulatory Affairs Specialist DiaSorin Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285

FEB 2 6 2007

Re: K061820

Trade/Device Name: LIAISON® VZV IgG Regulation Number: 21 CFR 866.3900 Regulation Name: Varicella-Zoster virus Serological Reagents Regulatory Class: Class II Product Code: LFY Dated: February 13, 2007 Received: February 16, 2007

Dear Ms. Meyer:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

{5}------------------------------------------------

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sally, anton

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

Enclosure

{6}------------------------------------------------

4.0 INDICATIONS FOR USE

510(k) Number (if known):

Device Name:

LIAISON® VZV IgG

K041820

Indications For Use:

Prescription Use _ × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use _ (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Soyland
Division Sign-Off

Page 4 - 1

Office of In Vitro Diagnostic Device Evaluation and Safety

700(k) K061820

Section 4

Regulation Number and Section

§ 866.3900 Varicella-zoster virus serological reagents.

(a)
Identification. Varicella-zoster virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to varicella-zoster in serum. The identification aids in the diagnosis of diseases caused by varicella-zoster viruses and provides epidemiological information on these diseases. Varicella (chicken pox) is a mild, highly infectious disease, chiefly of children. Zoster (shingles) is the recurrent form of the disease, occurring in adults who were previously infected with varicella-zoster viruses. Zoster is the response (characterized by a rash) of the partially immune host to a reactivation of varicella viruses present in latent form in the patient's body.(b)
Classification. Class II (performance standards).