(182 days)
The LIAISON® VZV IgG HT assay uses chemiluminescent immunoassay (CLIA) technology for the in vitro qualitative detection of specific IgG antibodies to varicella-zoster virus (VZV) in human serum (with gel and without gel-SST), dipotassium EDTA (K2- EDTA), lithium heparin and sodium heparin plasma samples. This assay is intended as an aid in the determination of previous infection of varicella- zoster virus. The test must be performed on the LIAISON® XL Analyzer. The assay performance in detecting antibodies to VZV in individuals vaccinated with the FDA-licensed VZV vaccine is unknown. The user of this assay is responsible for establishing the performance characteristics with VZV vaccinated individuals.
The LIAISON® VZV IgG HT is an indirect chemiluminescence immunoassay (CLIA) for qualitative detection of specific IgG antibodies to varicella-zoster virus in human serum and plasma.
The LIAISON® Control VZV IgG HT are liquid ready-to-use controls based in human serum and plasma. The negative control is intended to provide an assay response characteristic of negative patient specimens and the positive control is intended to provide an assay response characteristic of positive patient specimens.
The assay and controls are designed for use with DiaSorin LIAISON® analyzer family
Here's an analysis of the provided text regarding the DiaSorin LIAISON® VZV IgG HT device, focusing on acceptance criteria and supporting study details:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for this device are primarily expressed as Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a predicate device, as well as satisfactory performance in interference, cross-reactivity, precision, and high-dose saturation studies.
| Acceptance Criterion | Requirement/Goal (Implied or Stated) | Reported Device Performance |
|---|---|---|
| Clinical Agreement (vs. Predicate): | ||
| Known Positive Specimens: PPA | High agreement, ideally >95% (common for diagnostic assays) | 99.2% (123/124); 95% CI (95.6%-99.9%) |
| Known Positive Specimens: NPA | High agreement (common for diagnostic assays) | 100% (1/1); 95% CI (20.7%-100%) |
| Known Negative Specimens: PPA | Low false positive rate, ideally <5% | 0.0% (0/6); 95% CI (0.0%-39.0%) - Indicates low false positives in known negatives |
| Known Negative Specimens: NPA | High agreement, ideally >95% | 97.9% (190/194); 95% CI (94.8%-99.2%) |
| Normal Lab Routine Specimens: PPA | High agreement, ideally >95% | 97.4% (556/571); 95% CI (95.7%-98.4%) |
| Normal Lab Routine Specimens: NPA | High agreement, ideally >95% | 98.2% (503/512); 95% CI (96.7%-99.1%) |
| Pregnant Women: PPA | High agreement, ideally >95% | 98.2% (108/110); 95% CI (93.6%-99.5%) |
| Pregnant Women: NPA | High agreement, ideally >95% | 96.0% (24/25); 95% CI (80.5%-99.3%) |
| Potential Interfering Substances: | No interference at specified concentrations for listed endogenous and exogenous substances | No interference observed for all listed substances at specified concentrations. |
| Potential Cross-Reactivity: | No false positives from antibodies to other common infectious agents or medical conditions | No reactive results for any of the 226 tested cross-reactive samples (0/226). |
| Precision (Within-Laboratory): | Acceptable variability (SD and CV%) for negative, near cut-off, low positive, and positive samples | CV% ranges from 1.8% to 23.5% (Total column). Lower for positive controls/samples, higher for negative controls. |
| Reproducibility (Multi-site): | Acceptable variability (SD and CV%) across different sites and days | CV% ranges from 3.2% to 13.0% (Reproducibility column). Lower for positive samples, higher for negative control. |
| High-dose saturation effect: | No misclassification or underestimation of high-titer samples | No sample misclassification and no high-dose saturation effect observed. |
| Analytical sensitivity: | Defined sensitivity at cutoff | 152.4 mIU/mL at cutoff level (1.0 S/CO) |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Total Clinical Agreement Study: 1544 clinical human serum samples (1543 used in analysis due to one sample with insufficient volume).
- Breakdown: 125 known positive, 200 known negative, 135 pregnant women, and 1084 routine lab specimens.
- Specific sub-studies:
- Interfering Substances: Not specified, but involved VZV IgG antibody negative, around the cut-off, low positive, and high positive samples.
- Cross-Reactivity: 226 samples from various conditions.
- Precision (Within-Lab): 7 samples (panel of coded samples) tested 240 times each.
- Reproducibility (Multi-site): 7 samples tested 90 times each across sites.
- High-dose saturation: 3 high-titer samples.
- Analytical sensitivity: Not a sample size of patient specimens, but derived from serial dilutions of WHO International Standard on 3 assay lots.
- Data Provenance: The general clinical samples were collected within the United States. The study was prospective in execution as it involved testing these samples with the new device and comparing them to a predicate, conducted at three independent external laboratories.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document does not explicitly state the number of experts used and their qualifications for establishing the ground truth of the test set.
4. Adjudication Method for the Test Set
The document does not explicitly state an adjudication method (like 2+1, 3+1). The "ground truth" for the clinical agreement study appears to be defined by the results of the FDA cleared predicate device (LIAISON® VZV IgG, K150375), which is referred to as the "comparator." It notes that "Specimens which were repeatedly equivocal by the predicate device were graded against the performance of the LIAISON® VZV IgG HT assay which does not have an equivocal zone." This implies a direct comparison to the predicate's results rather than an independent expert adjudication process for the clinical samples. For cross-reactivity, samples were "pre-screened with another commercially available VZV IgG assay" and then confirmed for the presence of potential cross-reactants using "US-marked assays."
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an automated in vitro diagnostic assay (CLIA technology) for qualitative detection of antibodies, not an imaging device requiring human reader interpretation or AI assistance in the human-in-the-loop context.
6. Standalone (Algorithm Only) Performance Study
Yes, the entire clinical performance evaluation described (Clinical Agreement, Interfering Substances, Cross-Reactivity, Precision, Reproducibility, High-dose saturation, Analytical Sensitivity) is essentially a standalone algorithm-only performance study. The LIAISON® VZV IgG HT assay is an automated system run on the LIAISON® XL Analyzer, meaning its performance is evaluated without human interpretation of results beyond reading the automated output.
7. Type of Ground Truth Used
The primary ground truth for the clinical agreement study was established by the FDA cleared predicate device (LIAISON® VZV IgG, K150375). For the "known positive" and "known negative" specimens, their status was pre-determined, likely by previous clinical diagnosis or established VZV serology results (though the exact method for this is not detailed beyond being "known"). For cross-reactivity studies, ground truth was based on positive results from "US-marked assays" for the specific cross-reacting agent.
8. Sample Size for the Training Set
The document does not specify a training set sample size. This is typical for in vitro diagnostic (IVD) assays like this one. While there is an "algorithm" (the CLIA technology and interpretation logic), it's not a machine learning model that undergoes a separate training phase with a distinct dataset in the way a medical imaging AI would. The "development" and "optimization" of such assays usually happen using internal samples and established chemical/biological principles, not a formalized, reported training set size like in AI/ML submissions.
9. How the Ground Truth for the Training Set Was Established
Since a formalized "training set" for a machine learning algorithm isn't explicitly mentioned or directly applicable in the typical sense for this type of IVD, the concept of establishing ground truth for it is also not directly addressed. The assay's performance characteristics are developed and validated based on its underlying chemical and biological reactions and internal testing, which ensures it correctly identifies VZV IgG antibodies.
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October 27, 2023
Image /page/0/Picture/1 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, which consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, with the word "ADMINISTRATION" underneath.
DiaSorin Inc. Kelly Olien Regulatory Affairs Specialist II 1952 Northwestern Avenue Stillwater. Minnesota 55082
Re: K231214
Trade/Device Name: LIAISON VZV IgG HT, LIAISON Control VZV IgG HT Regulation Number: 21 CFR 866.3900 Regulation Name: Varicella-zoster virus serological reagents Regulatory Class: Class II Product Code: LFY Dated: September 29, 2023 Received: September 29, 2023
Dear Kelly Olien:
We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
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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approvals in the device master record (21 CFR 820.181).
Your device is also subject to, among other requirements, the Quality System (QS) 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
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).
Sincerely,
Image /page/1/Picture/6 description: The image shows a digital signature. The signature is for Laura E. Ulitzky -S. The date of the signature is 2023.10.27, and the time is 12:17:29 -04'00'.
Laura Ulitzky Lead Biologist Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K231214
Device Name LIAISON VZV IgG HT, LIAISON Control VZV IgG HT
Indications for Use (Describe)
The LIAISON VZV IgG HT assay uses chemiluminescent immunoassay (CLIA) technology for the in vitro qualitative detection of specific IgG antibodies to varicella-zoster virus (VZV) in human serum (with gel and without gel-SST), dipotassium EDTA (K2- EDTA), lithium heparin and sodium heparin plasma samples. This assay is intended as an aid in the determination of previous infection of varicella-zoster virus. The test must be performed on the LIALSON XL Analyzer. The assay performance in detecting antibodies to VZV in individuals vaccinated with the FDA-licensed VZV vaccine is unknown. The user of this assay is responsible for establishing the performance characteristics with VZV vaccinated individuals.
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
| SUBMITTED BY: | Kelly OlienRegulatory Affairs Specialist IIDiaSorin Inc.1951 Northwestern AvenueP.O. Box 285Stillwater, MN 55082-0285Email: kelly.olien@diasorin.com |
|---|---|
| DATE PREPARED: | October 27, 2023 |
| NAME OF DEVICE:Trade Name: | LIAISON® VZV IgG HT,LIAISON® Control VZV IgG HT |
| Common Names/Description: | VZV IgG Assay and VZV IgG Controls |
| Classification: | Varicella-zoster virus Serological Reagents: 21 CFR866.3900; Class II (performance standards); Microbiology(83)Quality Control Material: 21 CFR 862.1660; Classreserved; Clinical Chemistry (75) |
| Product Code: | LFY |
| PREDICATE DEVICE: | LIAISON® VZV IgG, LIAISON® Control VZV IgG(K150375) |
DEVICE DESCRIPTION:
The LIAISON® VZV IgG HT is an indirect chemiluminescence immunoassay (CLIA) for qualitative detection of specific IgG antibodies to varicella-zoster virus in human serum and plasma.
The LIAISON® Control VZV IgG HT are liquid ready-to-use controls based in human serum and plasma. The negative control is intended to provide an assay response characteristic of negative patient specimens and the positive control is intended to provide an assay response characteristic of positive patient specimens.
The assay and controls are designed for use with DiaSorin LIAISON® analyzer family
INTENDED USE:
The LIAISON® VZV IgG HT assay uses chemiluminescent immunoassay (CLIA) technology for the in vitro qualitative detection of specific IgG antibodies to varicella-zoster virus (VZV) in human serum (with gel and without gel-SST), dipotassium EDTA (K2- EDTA), lithium heparin and sodium heparin plasma samples. This assay is intended as an aid in the determination of previous infection of varicella- zoster virus. The test must be performed on the LIAISON® XL Analyzer. The assay performance in detecting antibodies to VZV in individuals vaccinated with the FDA-licensed VZV vaccine is unknown. The user of this assay is responsible for establishing the performance characteristics with VZV vaccinated individuals.
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COMPARISON TO THE PREDICATE The following tables provide a summary of the similarities and differences between the FDA cleared LIAISON® VZV IgG, and the new device.
| Similarities | ||
|---|---|---|
| Characteristic | Predicate DeviceLIAISON® VZV IgGK150375 | New DeviceLIAISON® VZV IgG HTK231214 |
| Technology/Assay Principle | Chemiluminescent Immunoassay (CLIA) | Same |
| SampleHandling/AssayProcessing | Automated | Same |
| ManufacturingProcess | No Change | Same |
| Storage | Store at 2-8° C until ready to use | Same |
| Measured Analyte | IgG antibodies to Varicella-zoster virus | Same |
| Sample Volume | 20 μL | Same |
| Assay Procedure | Dispense calibrators, controls, or samples Dispense magnetic particles Dispense specimen diluent Incubate Wash Dispense conjugate Incubate Wash Dispense starter reagent Measure Light emitted (RLUs) | Same |
| MeasurementSystem | Photomultiplier (flash chemiluminescencereader) | Same |
| Calibrators | Included with kit | Same |
| Open Use/OnBoard Stability | Eight (8) weeks at 2-8°C or onboard theanalyzer | Same |
| CalibrationStability | Eight (8) weeks | Same |
| Controls | Provided Separately | Same |
| Sample Storage at2-8°C | Seven (7) days | Same |
| Serum StorageFreeze-ThawCycles | 5 freeze-thaw cycles | Same |
| Differences | ||
| Characteristic | Predicate DeviceLIAISON® VZV IgGK150375 | New DeviceLIAISON® VZV IgG HTK231214 |
| IntendedUse/Indications forUse | The Diasorin LIAISON® VZV IgG useschemiluminescence immunoassay (CLIA)technology on the LIAISON® Analyzerfamily for the qualitative detection ofspecific IgG antibodies to varicella-zostervirus (VZV) in human serum. This assaycan be used as an aid in the determinationof previous infection of varicella-zostervirus.The assay performance in detectingantibodies to VZV in individualsvaccinated with the FDA licensed VZVvaccine is unknown. The user of thisassay is responsible for establishing theperformance characteristics with VZVvaccinated individuals. | The LIAISON® VZV IgG HT assayuses chemiluminescent immunoassay(CLIA) technology for the in vitroqualitative detection of specific IgGantibodies to varicella-zoster virus(VZV) in human serum (with gel andwithout gel-SST), dipotassium EDTA(K2- EDTA), lithium heparin andsodium heparin plasma samples. Thisassay is intended as an aid in thedetermination of previous infection ofvaricella-zoster virus. The test must beperformed on the LIAISON XLAnalyzer. The assay performance indetecting antibodies to VZV inindividuals vaccinated with the FDA-licensed VZV vaccine is unknown.The user of this assay is responsiblefor establishing the performancecharacteristics with VZV vaccinatedindividuals. |
| Reagent IntegralConfiguration(1 compartmenteach reagent) | Magnetic particles Calibrator 1 Calibrator 2 Specimen Diluent Conjugate | Magnetic particles Calibrator Assay Buffer Conjugate |
| Raw materials | Antigen: Inactivated varicella-zoster virus lysate (ROD strain) Detector: Mouse monoclonalanti-human IgG conjugated toisoluminol derivative Capture: Magnetic microparticlescoated with varicella-zosterantigen | Antigen: purified VaricellaZoster Virus glycoprotein; Detector: same Capture: Magnetic particlescoated with varicella ZosterVirus glycoprotein |
| Sample Type | Human Serum | Human Serum and Plasma |
| Tests per Kit | 100 | 200 |
| Cut-Off | 150 Index value | 1.00 S/CO |
| Equivocal Zone | 135 - 165 Index Value | No equivocal zone |
| Reagent VolumeProvided | Magnetic particles (2.5 ml)Conjugate (23ml) | Magnetic particles (2.45 ml)Conjugate (28.5 ml) |
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| Calibration | Two point verification of stored mastercurve | Calibration by using fully qualitativeapproach with one calibrator |
|---|---|---|
| Unit of Measure | Index Value | Signal/Cut-off (S/CO) |
| Summary of Similarities and Differences for the controls | ||
|---|---|---|
| Characteristic | Predicate DeviceLIAISON® Control VZV IgGK150375 | New Device LIAISON®Control VZV IgG HTK231214 |
| Intended Use | The DiaSorin LIAISON® Control VZVIgG (negative and positive) is intendedfor use as assayed quality controlsamples to monitor the performance ofthe DiaSorin LIAISON® VZV IgGassay on the LIAISON® Analyzerfamily. The performance characteristicsof the LIAISON® VZV Control IgGhave not been established for any otherassay or instrument platforms differentfrom LIAISON® and LIAISON® XL. | The LIAISON® Control VZV IgGHT (negative and positive) isintended for use as assayed qualitycontrol to monitor the performanceand reliability of LIAISON® VZVIgG HT assay. The performancecharacteristics of LIAISON®Control VZV IgG HT have not beenestablished for any other assays orinstrument platforms different fromthe automated LIAISON® XLAnalyzer. |
| Negative Control | Human Serum/plasma non-reactive forVZV IgG antibodies, 0.2% ProClin. | Human serum non-reactive for VZV IgGantibodies, 0.2% ProClin™ 300 andpreservatives. |
| Positive Control | Human Serum/plasma reactive for VZV IgGantibodies, 0.2% ProClin. | Human serum / defibrinated plasmareactive for VZV IgG antibodies, 0.2%ProClin™ 300 and preservatives. |
| ReagentConfiguration | 2 vials each level (negative and positive)0.7 mL/vial, ready to use. | Same |
| Storage | Store at 2-8º C until ready to use | Same |
| Open Use Stability | Once opened controls are stable for eight(8) weeks when properly stored at 2-8°Cbetween uses. | Same |
SUMMARY OF PERFORMANCE DATA:
Non-clinical verification and validation testing conducted with the LIAISON® VZV IgG HT and LIAISON® Control VZV IgG HT demonstrate that the new devices met predetermined acceptance criteria. supporting equivalency of the new device to the cleared device. Evidence is demonstrated through the following studies:
Clinical Agreement
A multisite clinical agreement study was conducted to evaluate the clinical performance of the LIAISON VZV IgG HT test. One thousand five hundred and forty four (1544) clinical human serum samples were used for this study, including 125 known positive specimens, 200 known negative specimens, 135 pregnant women specimens and 1084 specimens sent to the laboratory for testing.
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| Age Range | Gender | Positive Result | Negative Result | Total | ||
|---|---|---|---|---|---|---|
| n | % | n | % | |||
| 0-9 | F | 1 | 16.7% | 5 | 83.3% | 6 |
| M | 0 | 0.0% | 4 | 100.0% | 4 | |
| 10-19 | F | 18 | 20.7% | 69 | 79.3% | 87 |
| M | 4 | 18.2% | 18 | 81.8% | 22 | |
| 10-19 | N* | 1 | 33.3% | 2 | 66.7% | 3 |
| 10-19 | F | 223 | 37.0% | 380 | 63.0% | 603 |
| M | 17 | 24.6% | 52 | 75.4% | 69 | |
| 20-29 | N* | 4 | 44.4% | 5 | 55.6% | 9 |
| 20-29 | F | 275 | 70.3% | 116 | 29.7% | 391 |
| M | 34 | 70.8% | 14 | 29.2% | 48 | |
| 30-39 | N* | 1 | 25.0% | 3 | 75.0% | 4 |
| 30-39 | F | 88 | 73.9% | 31 | 26.1% | 119 |
| M | 22 | 71.0% | 9 | 29.0% | 31 | |
| 40-49 | N* | 2 | 100.0% | 0 | 0.0% | 2 |
| 40-49 | F | 50 | 76.9% | 15 | 23.1% | 65 |
| M | 25 | 65.8% | 13 | 34.2% | 38 | |
| 50-59 | N* | 2 | 100.0% | 0 | 0.0% | 2 |
| 50-59 | F | 19 | 86.4% | 3 | 13.6% | 22 |
| M | 12 | 92.3% | 1 | 7.7% | 13 | |
| 60-69 | F | 1 | 50.0% | 1 | 50.0% | 2 |
| M | 0 | 0.0% | 0 | 0.0% | 0 | |
| 70-79 | F | 1 | 50.0% | 1 | 50.0% | 2 |
| M | 0 | 0.0% | 0 | 0.0% | 0 | |
| 80-89 | F | 1 | 100.00% | 0 | 0.0% | 1 |
| M | 0 | 0.0% | 0 | 0.0% | 0 | |
| Total** (1543) | 801 | 51.91% | 742 | 48.1% | 1543 |
The demography of the population tested is listed below:
*N= Unknown
**one of the 1544 samples was excluded due to insufficient volume for testing on the candidate device
The samples were collected within the United States and tested at three independent external laboratories. Each sample, was tested with the LIAISON VZV IgG HT test and the comparator. The results for all populations are shown in the tables below.
The positive and negative percent agreements were calculated and presented below for normal laboratory routine (all), normal laboratory routine pediatric, and pregnant women. Specimens which were repeatedly equivocal by the predicate device were graded against the performance of the LIAISON® VZV IgG HT assay which does not have an equivocal zone.
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| FDA Cleared VZV IgG comparator | |||||
|---|---|---|---|---|---|
| Positive | Equivocal | Negative | Total | ||
| LIAISONVZV IgGHT | Positive | 123 | 0 | 0 | 123 |
| Negative | 1 | 0 | 1 | 2 | |
| Total | 124 | 0 | 1 | 125 |
Clinical Performance- Known Positive Specimens (n=125)
Positive Percent Agreement (PPA): 99.2% (123/124); 95% CI (95.6%-99.9%) Negative Percent Agreement (NPA): 100% (1/1); 95% CI (20.7%-100%)
Clinical Performance- Known Negative Specimens (n=200)
| FDA Cleared VZV IgG comparator | |||||
|---|---|---|---|---|---|
| Positive | Equivocal | Negative | Total | ||
| LIAISONVZV IgGHT | Positive | 0 | 1 | 3 | 4 |
| LIAISONVZV IgGHT | Negative | 0 | 6 | 190 | 196 |
| LIAISONVZV IgGHT | Total | 0 | 7 | 193 | 200 |
Positive Percent Agreement (PPA): 0.0% (0/6); 95% CI (0.0%-39.0%) Negative Percent Agreement (NPA): 97.9% (190/194); 95% CI (94.8%-99.2%)
| Clinical performance- Normal Laboratory Routine Specimens (n=1083, ages 0-8) | |||||
|---|---|---|---|---|---|
| FDA Cleared VZV IgGcomparator | |||||
| Positive | Equivocal | Negative | Total | ||
| LIAISON | Positive | 556 | 4 | 5 | 565 |
5
9
ર૦૩
૨૦૪
218
1083
| Positive Percent Agreement (PPA): 97.4% (556/571); 95% CI (95.7%-98.4%) |
|---|
| Negative Percent Agreement (NPA): 98.2% (503/512); 95% CI (96.7%-99.1%) |
10
ર્સ્વ
Clinical Performance- Pregnant Women (n=135)
Negative
Total
VZV IgG
HT
| FDA Cleared VZV IgG comparator | |||||
|---|---|---|---|---|---|
| Positive | Equivocal | Negative | Total | ||
| LIAISONVZV IgGHT | Positive | 108 | 0 | 1 | 109 |
| Negative | 0 | 2 | 24 | 26 | |
| Total | 108 | 2 | 25 | 135 |
Positive Percent Agreement (PPA): 98.2% (108/110); 95% CI (93.6%-99.5%) Negative Percent Agreement (NPA): 96.0% (24/25); 95% CI (80.5%-99.3%)
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Potential Interfering substances
The LIAISON VZV IgG HT assay was evaluated for potential interference caused by endogenous and exogenous substances using VZV IgG antibody negative, around the cut-off, low positive, and high positive samples. Controlled studies of potentially interfering substances showed no interference to each substance listed below in the LIAISON® VZV IgG HT, at the indicated concentration.
| Substance | Concentrations tested |
|---|---|
| Endogenous Substances | |
| Unconjugated bilirubin | 40 mg/dL |
| Conjugated bilirubin | 40 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Triglycerides | 3000 mg/dL |
| Human Serum Albumin | 6000 mg/dL |
| Cholesterol | 400 mg/dL |
| Total IgG | 2000 mg/dL |
| Total IgM | 400 mg/dL |
| Total protein (high) | ≥ 120 g/L |
| Total protein (low) | ≤ 60 g/L |
| Human anti-mouse antibody (HAMA) | 820 ng/mL |
| Rheumatoid Factor (RF) | 2000 IU/mL |
| Exogenous Substances | |
| Biotin | 3500 ng/mL |
| Vitamin A | 800 µg/dL |
| Vitamin B12 | 2850 pg/mL |
| Vitamin C | 20 mg/dL |
| Vitamin D | 450 ng/mL |
| Vitamin E | 120 mg/L |
| Folic Acid | 160 ng/mL |
| Acetaminophen | 15.6 mg/dL |
| Ibuprofen | 21.9 mg/dL |
| Acetylsalicylic acid | 50 mg/dL |
| Naproxen | 36.0 mg/dL |
| Penicillin | 110 mg/dL |
| Streptomycin (sulphate) | 25.8 mg/dL |
| Erythromycin | 13.8 mg/dL |
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Potential Cross-Reactivity
The cross-reactivity study for the LIAISON® VZV IgG HT assay was designed to evaluate potential interference from antibodies to other viruses that may cause infectious diseases, as well as from other conditions. Samples for these studies were pre-screened with another commercially available VZV IgG assay. If found negative for VZV IgG antibodies, those specimens were used to study potential crossreactivity. After the presence of potential cross-reactants in the samples was confirmed using USmarked assays, samples were tested with the LIAISON® VZV IgG HT assay. None of the specimens tested reactive with the LIAISON® XL VZV IgG HT assay. There is no evidence of cross reactivity with the tested medical conditions.
| Condition | Number of tested samples | Assay Reactive results |
|---|---|---|
| CMV (anti-CMV positive) | 10 | 0 |
| Epstein-Bar Virus (anti-EBV positive) | 10 | 0 |
| Herpes Simplex Virus (anti-HSV 1 positive) | 10 | 0 |
| Herpes Simplex Virus (anti-HSV 2 positive) | 10 | 0 |
| Rubella (anti-Rubella positive) | 10 | 0 |
| Hepatitis C Virus (anti-HCV positive) | 10 | 0 |
| Human Immunodeficiency Virus (anti-HIV antibodies) | 10 | 0 |
| Hepatitis A Virus (anti-HAV positive) | 10 | 0 |
| Borrelia burgdorferi (anti-B. burgorferi antibodies) | 10 | 0 |
| Toxoplasma. gondii (anti-T. gondii antibodies) | 11 | 0 |
| Parvovirus B19 (anti-Parvovirus B19 positive) | 16 | 0 |
| Measles virus (anti-Measles antibodies) | 11 | 0 |
| Mumps virus (anti-Mumps antibodies) | 12 | 0 |
| Adenovirus (anti-Adenovirus antibodies) | 10 | 0 |
| Anti-Influenza A antibodies | 11 | 0 |
| Anti-Influenza B antibodies | 12 | 0 |
| Mycoplasma pneumonia (anti-M. pneumonia antibodies) | 10 | 0 |
| Respiratory syncytial virus (RSV) antibodies | 11 | 0 |
| Rheumatoid Factor (anti-Fc Immunoglobulin) | 10 | 0 |
| Human anti-mouse antibodies (HAMA) | 14 | 0 |
| Anti-nuclear antibodies (ANA) | 10 | 0 |
| Total | 226 | 0 |
Precision
Within Laboratory Precision with LIAISON® XL Analyzer: A twenty-day precision study was performed in accordance with CLSI document EPS-A3, using a coded panel of seven (7) samples prepared by either spiking or diluting samples as necessary to obtain negative, near to cut off, low positive and positive samples. Kit Controls set was also included in the study. The panel samples and kit controls were tested with the LIAISON® VZV IgG HT assay in two (2) replicates per run, two (2) runs per day for twenty (20) operating days on one LIAISON® XL Analyzer, on three (3) assay lots.
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| Sample ID | N | Mean(S/CO) | Repeatability | Between Run | Between Day | Between-Lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | CV% | SD | CV% | SD | CV% | SD | CV% | SD | CV% | |||
| Negative Control A | 240 | 0.0166 | 0.0012 | 7.3% | 0.0017 | 10.4% | 0.0021 | 13.0% | 0.0021 | 12.8% | 0.0034 | 20.7% |
| Negative Control B | 240 | 0.0150 | 0.0018 | 11.9% | 0.0014 | 9.6% | 0.0020 | 13.2% | 0.0023 | 15.3% | 0.0035 | 23.5% |
| Positive Control A | 240 | 3.73 | 0.069 | 1.8% | 0.076 | 2.0% | 0.211 | 5.7% | 0.206 | 5.5% | 0.285 | 7.6% |
| Positive Control B | 240 | 3.57 | 0.079 | 2.2% | 0.089 | 2.5% | 0.216 | 6.1% | 0.193 | 5.4% | 0.289 | 8.1% |
| Positive Control C | 240 | 3.49 | 0.070 | 2.0% | 0.078 | 2.2% | 0.199 | 5.7% | 0.210 | 6.0% | 0.279 | 8.0% |
| Sample 1 | 240 | 0.120 | 0.005 | 3.8% | 0.003 | 2.8% | 0.005 | 4.2% | 0.009 | 7.1% | 0.010 | 8.5% |
| Sample 2 | 240 | 0.669 | 0.021 | 3.1% | 0.023 | 3.4% | 0.029 | 4.4% | 0.027 | 4.0% | 0.047 | 7.0% |
| Sample 3 | 240 | 0.850 | 0.019 | 2.3% | 0.021 | 2.4% | 0.036 | 4.3% | 0.065 | 7.7% | 0.070 | 8.2% |
| Sample 4 | 240 | 1.26 | 0.030 | 2.4% | 0.021 | 1.7% | 0.055 | 4.4% | 0.037 | 2.9% | 0.072 | 5.7% |
| Sample 5 | 240 | 3.33 | 0.071 | 2.1% | 0.053 | 1.6% | 0.151 | 4.5% | 0.099 | 3.0% | 0.190 | 5.7% |
| Sample 6 | 240 | 6.84 | 0.13 | 1.8% | 0.17 | 2.5% | 0.26 | 3.9% | 0.20 | 3.0% | 0.37 | 5.4% |
| Sample 7 | 240 | 12.6 | 0.25 | 2.0% | 0.44 | 3.5% | 0.22 | 1.8% | 0.40 | 3.1% | 0.64 | 5.0% |
Reproducibility: A five-day precision study was performed. The coded panel used in the 5-day study was the same panel used in the 20-day study. The coded panel was tested at all three (3) sites, using six (6) replicates per run in one (1) run per day for five (5) operating days. The CLSI Document EP-05A3 was consulted in the preparation of the testing protocol. The means, standard deviation, and coefficient of variation (%CV) of the results were computed for each of the tested specimens across sites.
| Sample ID | N | Mean(S/CO) | Repeatability | Between Day | Between Site | Reproducibility | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | CV% | SD | CV% | SD | CV% | SD | CV% | |||
| Negative Control | 90 | 0.017 | 0.002 | 9.1% | 0.001 | 7.6% | 0.001 | 7.3% | 0.002 | 13.0% |
| Positive Control | 90 | 3.55 | 0.115 | 3.2% | 0.135 | 3.8% | 0.121 | 3.4% | 0.201 | 5.7% |
| Sample 1 | 90 | 0.108 | 0.007 | 6.7% | 0.010 | 9.4% | 0.000 | 0.4% | 0.011 | 10.4% |
| Sample 2 | 90 | 0.638 | 0.029 | 4.6% | 0.042 | 6.6% | 0.019 | 3.0% | 0.050 | 7.8% |
| Sample 3 | 90 | 0.783 | 0.041 | 5.2% | 0.054 | 6.9% | 0.019 | 2.4% | 0.064 | 8.1% |
| Sample 4 | 90 | 1.18 | 0.047 | 4.0% | 0.079 | 6.7% | 0.063 | 5.4% | 0.104 | 8.8% |
| Sample 5 | 90 | 3.31 | 0.143 | 4.3% | 0.176 | 5.3% | 0.172 | 5.2% | 0.267 | 8.1% |
| Sample 6 | 90 | 6.95 | 0.279 | 4.0% | 0.187 | 2.7% | 0.240 | 3.5% | 0.388 | 5.6% |
| Sample 7 | 90 | 13.2 | 0.446 | 3.4% | 0.427 | 3.2% | 0.509 | 3.9% | 0.756 | 5.7% |
High-dose saturation effect
Whenever samples containing extremely high antibody concentrations are tested, the saturation effect can mimic concentrations lower than the real ones. However, a well-optimized two-step method excludes grossly underestimated results because the analytical signals remain consistently high (saturation curve).
Analysis of the saturation effect was evaluated by diluting three high-titer samples positive for VZV IgG. All samples resulted in concentration values above the assay range that would be expected with high-titler sera, indicating no sample misclassification and with no high-dose saturation effect observed.
Analytical sensitivity
In order to determine sensitivity of LIAISON® VZV IgG HT assay, the IgG to varicella-zoster virus concentration which corresponds to the measured signal of the cutoff value (1.0 S/CO) was read off the curves of serial dilutions of WHO 1ª International Standard for varicella zoster immunoglobulin, 1987 code W1044, in human negative serum. The data was analyzed by regression analysis, considering the best fit. Three lots of the LIAISON VZV IgG HT assay were used. The analytical sensitivity at the cutoff is the higher
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concentration among the 3 lots. The analytical sensitivity of LIAISON® VZV IgG HT assay at cutoff level is 152.4 mIU/mL.
CONCLUSION:
As summarized, the DiaSorin LIAISON® VZV IgG HT and LIAISON® Control VZV IgG HT, are substantially equivalent to the originally cleared devices. The device do not constitute new intended/indications for use, or changes to the fundamental scientific technology. Performance testing of the device demonstrates that the device functions as intended, meeting the requirements of design specifications. The device is as safe and effective as the predicate and does not raise new questions of safety and efficacy.
§ 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).