(639 days)
The ARCHITECT HSV-1 IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of specific IgG antibodies to herpes simplex virus type 1 (HSV-1) in human serum (collected in serum and serum separator tubes) and plasma (collected in dipotassium EDTA, lithium heparin plasma separator tubes) on the ARCHITECT i System.
The ARCHITECT HSV-1 IgG assay is to be used for testing sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-1 infection. The test results may not determine the state of active lessociated disease manifestations, particularly for primary infection. The predictive value of a reactive or nonreactive result depends on the prevalence of HSV-1 infection in the population and the pre-test likelihood of HSV-1 infection.
NOTE: The performance of the ARCHITECT HSV-1 IgG assay has not been established for use in the pediatric population, for neonatal screening, or for testing immunosompromised or immunosuppressed patients. The assay has not been FDA cleared or approved for screening blood or plasma donors.
This assay is an automated, two-step immunoassay for the qualitative detection of specific IgG antibodies to HSV-1 in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology. Sample, HSV-1 specific recombinant gG1 antigen coated paramagnetic microparticles, and assay diluent are combined and incubated. The IgG antibodies to HSV-1 (HSV-1 IgG) present in the sample bind to the HSV-1 specific recombinant gG1 antigen coated microparticles. The mixture is washed. Anti-human IgG acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added. The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a relationship between the amount of HSV-1 IgG in the sample and the RLU detected by the system optics. The presence or absence of HSV-1 IgG in the sample is determined by comparing the chemiluminescent RLU in the reaction to the cutoff RLU determined from an active calibration.
Here's a breakdown of the acceptance criteria and the studies performed for the ARCHITECT HSV-1 IgG assay, based on the provided document:
Acceptance Criteria and Device Performance
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance | Comments / Study Reference |
|---|---|---|---|
| Tube Type Matrix Comparison | < 10% difference for reactive HSV-1 IgG samples when compared to serum (control). | Serum Separator: 86.5% < 10% diff (32/37) | "Tube Type Matrix Comparison" (Page 7) |
| Dipotassium EDTA: 75.7% < 10% diff (28/37) | |||
| Lithium Heparin: 83.8% < 10% diff (31/37) | |||
| Lithium Heparin Separator: 67.6% < 10% diff (25/37) | |||
| < 0.1 S/CO absolute difference for nonreactive HSV-1 IgG samples when compared to serum (control). | Serum Separator: 72.0% ≤ 0.1 S/CO (18/25) | "Tube Types Matrix Comparison Results" (Page 7) | |
| Dipotassium EDTA: 80.0% ≤ 0.1 S/CO (20/25) | |||
| Lithium Heparin: 72.0% ≤ 0.1 S/CO (18/25) | |||
| Lithium Heparin Separator: 76.0% ≤ 0.1 S/CO (19/25) | |||
| Precision (Within-Laboratory - 20 Day) | Within-laboratory (total) imprecision ≤ 0.07 S/CO for samples < 1.00 S/CO. | Negative Control: 0.009 S/CO | "Precision Results" (Page 8) |
| Within-laboratory (total) imprecision ≤ 7.5% CV for samples > 1.00 S/CO. | Positive Control: 2.65% CV Serum Panel 1: 3.08% CV Serum Panel 2: 2.97% CV Serum Panel 3: 2.58% CV Plasma Panel 1: 5.23% CV Plasma Panel 2: 2.54% CV Plasma Panel 3: 2.68% CV | "Precision Results" (Page 8) | |
| Analytical Specificity (Interference) - Endogenous Substances | < 10% absolute difference for reactive HSV-1 IgG samples. | Achieved for all listed substances at specified concentrations. | "Potentially Interfering Endogenous Substances" (Page 10) |
| < 0.10 S/CO absolute difference for negative HSV-1 IgG samples. | Achieved for all listed substances at specified concentrations. | "Potentially Interfering Endogenous Substances" (Page 10) | |
| Analytical Specificity (Interference) - Drugs | < 10% absolute difference for reactive HSV-1 IgG samples. | Achieved for all listed drugs at specified concentrations. | "Potentially Interfering Drugs" (Page 11) |
| < 0.10 S/CO absolute difference for negative HSV-1 IgG samples. | Achieved for all listed drugs at specified concentrations. | "Potentially Interfering Drugs" (Page 11) | |
| CDC Panel Agreement | Not explicitly stated but implied to be high agreement ("100% PPA" and "100% NPA"). | 100% Positive Percent Agreement (PPA) for reactive samples (46/46). 100% Negative Percent Agreement (NPA) for nonreactive samples (54/54). | "CDC Panel Agreement" (Page 13) |
| Clinical Agreement (Sexually Active Population) | Not explicitly stated but implied to be high sensitivity and specificity. | PPA: 94.46% (95% CI: 91.95% to 96.22%) NPA: 96.41% (95% CI: 92.38% to 98.34%) | "Clinical Agreement Study" (Page 14) |
| Clinical Agreement (Pregnant Population) | Not explicitly stated but implied to be high sensitivity and specificity. | PPA: 96.10% (95% CI: 92.49% to 98.01%) NPA: 100.00% (95% CI: 95.99% to 100.00%) | "Clinical Agreement Study" (Page 14) |
Study Details
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Tube Type Matrix Comparison: 62 sets of unique human serum samples, with each set including samples collected in serum, serum separator, dipotassium EDTA plasma, lithium heparin plasma, and lithium heparin plasma separator tubes.
- Data Provenance: Not explicitly stated, but the company is based in Barcelona, Spain and the clinical study was conducted in the US. The type of samples suggests they would be clinical specimens. (Retrospective/Prospective not specified for this specific study, but the clinical agreement study was prospective).
- Precision (20-Day): 80 replicates per sample type (Negative Control, Positive Control, 3 Serum Panels, 3 Plasma Panels). Total of 8 samples * 80 replicates = 640 tests per reagent/calibrator lot combination (3 combinations used).
- Data Provenance: Human serum and plasma panel samples. (Country/Retrospective/Prospective not specified for this specific study).
- Precision (12-Day): 96 replicates per sample type (2 Serum Panels, 2 Plasma Panels). Total of 4 samples * 96 replicates = 384 tests per lot combination (2 reagent lots).
- Data Provenance: Human serum and plasma panel samples. (Country/Retrospective/Prospective not specified for this specific study).
- Reproducibility: 90 replicates per sample type (Negative Control, Positive Control, 3 Serum Panels, 3 Plasma Panels) across 3 sites.
- Data Provenance: Human serum and plasma panel samples. (Country/Retrospective/Prospective not specified for this specific study).
- Interference (Endogenous & Drugs): Not a direct sample count, but 12 replicates for each negative and low reactive HSV-1 IgG sample for each substance tested.
- Data Provenance: HSV-1 IgG negative and low reactive samples. (Country/Retrospective/Prospective not specified for this specific study).
- Cross-Reactivity: Total of 244 specimens (sum of 'n' column in the table).
- Data Provenance: Specimens from individuals with antibodies to other microorganisms or medical conditions unrelated to HSV-1. Confirmed negative for HSV-1 IgG by a comparator immunoblot method. (Country/Retrospective/Prospective not specified for this specific study).
- CDC Panel Agreement: 100 aliquots (2 aliquots each of 50 serum samples).
- Data Provenance: Obtained from the Centers for Disease Control and Prevention (CDC). Serum samples with unknown HSV-1 status, implying they are real-world clinical samples. (Country would be USA, retrospective).
- Clinical Agreement Study: 915 specimens.
- Data Provenance: Collected prospectively within the US. Included sexually active individuals and pregnant females. Tested at 3 independent external laboratories.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Clinical Agreement Study: A "composite comparator method" was used, consisting of:
- A commercially available anti-HSV-1 IgG immunoblot method.
- A Western Blot reference confirmatory test (University of Washington, Seattle).
- The document does not specify the number of experts or their qualifications for establishing the ground truth using these comparator methods. It refers to the methods themselves as the ground truth.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Clinical Agreement Study: The "composite comparator method" suggests an adjudication process, where the immunoblot results were presumably confirmed or clarified by the Western Blot. However, the exact adjudication method (e.g., 2+1, 3+1) is not explicitly detailed. The document only states the combination of methods used to establish the comparator.
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
- This device is an automated, two-step chemiluminescent microparticle immunoassay (CMIA), not an AI-based imaging or diagnostic tool that involves human readers interpreting results. Therefore, an MRMC comparative effectiveness study comparing human readers with and without AI assistance is not applicable and was not performed.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
- Yes, the performance studies described (Precision, Interference, Cross-Reactivity, CDC Panel Agreement, and Clinical Agreement) all represent standalone performance of the ARCHITECT HSV-1 IgG assay. The device is fully automated and provides a qualitative result (reactive/nonreactive) based on the measured Relative Light Unit (RLU) compared to a cutoff. There is no human interpretation of the assay's output involved in its primary function.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- Tube Type Matrix Comparison, Precision, Interference: These studies used internal controls, spiked samples, or reference materials. The "ground truth" for these is defined by the expected values of these controls/samples.
- Cross-Reactivity: Comparator method (immunoblot) confirmed negative for HSV-1 IgG.
- CDC Panel Agreement: The "unknown HSV-1 status" samples from the CDC would have their 'true' status determined by the CDC's reference methods, which serve as the ground truth.
- Clinical Agreement Study: A composite comparator method comprising a commercially available anti-HSV-1 IgG immunoblot method and a Western Blot reference confirmatory test (University of Washington, Seattle). This acts as the "expert consensus" or "reference method" ground truth for the clinical samples.
8. The sample size for the training set
- The document does not specify a training set size because this device is an immunoassay, not a machine learning or AI algorithm that typically requires a separate training set. Immunoassays are developed through analytical optimization and validation, rather than model training.
9. How the ground truth for the training set was established
- As this is an immunoassay and not an AI/ML algorithm, there isn't a "training set" in the conventional sense used for machine learning. The development process would involve optimizing reagents and assay parameters against known positive and negative controls and clinical samples, but these are part of the assay development and validation, not a distinct "training set" for an algorithm.
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Date: September 20, 2023
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Biokit, S.A. Angels Roma Regulatory Affairs & Design Quality Director Av. Can Montcau, 7 Llica d'Amunt, Barcelona 08186 Spain
Re: K213987
Trade/Device Name: ARCHITECT HSV-1 IgG, ARCHITECT HSV-1 IgG Calibrator, ARCHITECT HSV-1 IgG Controls Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes Simplex Virus Serological Assays Regulatory Class: Class II Product Code: MXJ Dated: April 5, 2023 Received: April 7, 2023
Dear Àngels Roma:
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. 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 located 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.
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
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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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 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,
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Digitally signed by Ryan C. Karsner -S Date: 2023.09.20 13:46:31 -04'00'
Ryan Karsner, MD. Deputy Assistant Director Hepatitis and General Viral Infections Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K213987
Device Name ARCHITECT HSV-1 IgG
Indications for Use (Describe)
The ARCHITECT HSV-1 IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of specific IgG antibodies to herpes simplex virus type 1 (HSV-1) in human serum (collected in serum and serum separator tubes) and plasma (collected in dipotassium EDTA, lithium heparin plasma separator tubes) on the ARCHITECT i System.
The ARCHITECT HSV-1 IgG assay is to be used for testing sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-1 infection. The test results may not determine the state of active lessociated disease manifestations, particularly for primary infection. The predictive value of a reactive or nonreactive result depends on the prevalence of HSV-1 infection in the population and the pre-test likelihood of HSV-1 infection.
NOTE: The performance of the ARCHITECT HSV-1 IgG assay has not been established for use in the pediatric population, for neonatal screening, or for testing immunosompromised or immunosuppressed patients. The assay has not been FDA cleared or approved for screening blood or plasma donors.
| 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
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
| 1. Submitter's Information | Biokit, S.A.Av. Can Montcau, 7Lliçà d'Amunt 08186Barcelona (Spain) |
|---|---|
| ---------------------------- | -------------------------------------------------------------------------------- |
| 2. Contact Person | Àngels Roma, Regulatory Affairs and Design QualityDirectorPhone: +34 93 860 90 00Email: aroma@werfen.com |
|---|---|
| ------------------- | ---------------------------------------------------------------------------------------------------------------------- |
| 3. Preparation Date | 2023-Sep-20 |
|---|---|
| --------------------- | ------------- |
| 4. Device Trade Name | ARCHITECT HSV-1 IgG |
|---|---|
| ---------------------- | --------------------- |
| Regulation Number | 21 CFR 866.3305 | |
|---|---|---|
| 5. RegulatoryInformation | Regulation Description | Herpes simplex virusserological assays. |
| Classification | Class II Special Controls | |
| Product Code | MXJ | |
| Classification Panel | Microbiology |
| 6. Predicate Device | K000238 (HSV-1 & HSV-2 Differentiation ImmunoblotIgG) |
|---|---|
| --------------------- | ----------------------------------------------------------- |
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| 7. Indications for Use / Intended Use | The ARCHITECT HSV-1 IgG assay is a chemiluminescentmicroparticle immunoassay (CMIA) used for the qualitativedetection of specific IgG antibodies to herpes simplex virustype 1 (HSV-1) in human serum (collected in serum andserum separator tubes) and plasma (collected in dipotassiumEDTA, lithium heparin, and lithium heparin plasma separatortubes) on the ARCHITECT i System.The ARCHITECT HSV-1 IgG assay is to be used for testingsexually active adults or expectant mothers to aid in thepresumptive diagnosis of HSV-1 infection. The test resultsmay not determine the state of active lesions or associateddisease manifestations, particularly for primary infection.The predictive value of a reactive or nonreactive resultdepends on the prevalence of HSV-1 infection in thepopulation and the pre-test likelihood of HSV-1 infection.NOTE: The performance of the ARCHITECT HSV-1 IgGassay has not been established for use in the pediatricpopulation, for neonatal screening, or for testingimmunocompromised or immunosuppressed patients. Theassay has not been FDA cleared or approved for screeningblood or plasma donors. |
|---|---|
| --------------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
| 8. Device Description | This assay is an automated, two-step immunoassay for the qualitative detection of specific IgG antibodies to HSV-1 in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology. Sample, HSV-1 specific recombinant gG1 antigen coated paramagnetic microparticles, and assay diluent are combined and incubated. The IgG antibodies to HSV-1 (HSV-1 IgG) present in the sample bind to the HSV-1 specific recombinant gG1 antigen coated microparticles. The mixture is washed. Anti-human IgG acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added. The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a relationship between the amount of HSV-1 IgG in the sample and the RLU detected by the system optics. The presence or absence of HSV-1 IgG in the sample is determined by comparing the chemiluminescent RLU in the reaction to the cutoff RLU determined from an active calibration. |
|---|---|
| ----------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
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| COMPARISON PREDICATE | ||
|---|---|---|
| Item | Predicate | New Device |
| Trade Names | HSV-1 & HSV-2 DifferentiationImmunoblot IgG | ARCHITECT HSV-1 IgG,ARCHITECT HSV-1 IgGCalibrator, ARCHITECT HSV-1IgG Controls |
| 510K no. | K000238 | K213987 |
| Manufacturer | MLR DiagnosticsCypress, CA 90630 -USA | Abbott Ireland Diagnostics DivisionFinisklin Business Park, Sligo,Ireland |
| Similarities | ||
| Intended use | MLR Diagnostics' HSV-1 &HSV-2 DifferentiationImmunoblot IgG test is intendedfor qualitatively detecting thepresence or absence of human IgGclass antibodies to HSV-1 andHSV-2 in human sera. The test isindicated for testing sexuallyactive adults or expectant mothersfor aiding in the presumptivediagnosis of HSV-1 and HSV-2infection. The predictive value ofa positive or negative resultdepends on the population'sprevalence and the pretestlikelihood of HSV- 1 and HSV-2infection. The performance of thisassay has not been established foruse in a pediatric population, forneonatal screening, for testing ofimmunocompromised patients, foruse by a point of care facility orfor use with automated equipment | The ARCHITECT HSV-1 IgG assayis a chemiluminescent microparticleimmunoassay (CMIA) used for thequalitative detection of specific IgGantibodies to herpes simplex virustype 1 (HSV-1) in human serum(collected in serum and serumseparator tubes) and plasma(collected in dipotassium EDTA,lithium heparin, and lithium heparinplasma separator tubes) on theARCHITECT i System.The ARCHITECT HSV-1 IgG assayis to be used for testing sexuallyactive adults or expectant mothers toaid in the presumptive diagnosis ofHSV-1 infection. The test resultsmay not determine the state of activelesions or associated diseasemanifestations, particularly forprimary infection. The predictivevalue of a reactive or nonreactiveresult depends on the prevalence ofHSV-1 infection in the populationand the pre-test likelihood of HSV-1infection.NOTE: The performance of theARCHITECT HSV-1 IgG assay hasnot been established for use in thepediatric population, for neonatalscreening, or for testingimmunocompromised or |
| immunosuppressed patients. Theassay has not been FDA cleared orapproved for screening blood orplasma donors. | ||
| Analyte | Human IgG class antibodies toHSV-1 and HSV-2 | IgG antibodies to HSV-1 |
| Regulation Section | 21 CFR 866.3305 | Same |
| Classification | Class II Special Controls | Same |
| Assay Type | Qualitative | Same |
| Differences | ||
| Product Code | LGC | MXJ |
| Technology | Nitrocellulose immunoblot | Chemiluminescent immunoassay |
| Sample type | Human serum | Human serum (collected in serum and serum separator tubes) andplasma (collected in dipotassium EDTA, lithium heparin, and lithium heparin separator tubes) |
| ResultInterpretation | Visually evaluate multiple bands | The cutoff is 1.00 S/CO.<1.00 S/CO = Nonreactive≥1.00 S/CO = Reactive |
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9. Performance Summary
Tube Type Matrix Comparison
A total of 62 sets of unique serum samples paired with samples collected in serum separator, dipotassium EDTA plasma, lithium heparin plasma, and lithium heparin plasma separator tubes were evaluated with the ARCHITECT HSV-1 IgG assay on the ARCHITECT i2000SR instrument to support equivalent performance using each of these specimen types.
A weighted Deming regression analysis was performed in the whole assay range and around the cut-off, separately.
The following tube types are acceptable for use with the ARCHITECT HSV-1 IgG assay:
- Serum (serum and serum separator) .
- . Plasma (dipotassium EDTA, lithium heparin, and lithium heparin separator)
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werfer
On average, the tube types evaluated showed less than a 10% difference for reactive HSV-1 IgG samples and less than 0.1 S/CO absolute difference for nonreactive HSV-1 IgG samples when compared to the control tube type (serum). The distribution of the percent differences per tube type for reactive samples is listed in the following table.
| Distribution of Absolute % Differences | ||||
|---|---|---|---|---|
| Tube Type | < 10% | >10% to ≤20% | >20% to ≤30% | |
| Serum Separator | 86.5% (32/37) | 8.1% (3/37) | 5.4% (2/37) | |
| Dipotassium EDTA | 75.7% (28/37) | 16.2% (6/37) | 8.1% (3/37) | |
| Lithium heparin | 83.8% (31/37) | 5.4% (2/37) | 10.8% (4/37) | |
| Lithium heparin separator | 67.6% (25/37) | 21.6% (8/37) | 10.8% (4/37) |
Tube Types Matrix Comparison Results
The distribution of the absolute differences (S/CO) per tube type for nonreactive samples is listed in the following table.
| Tube Type | Distribution of Absolute Differences (S/CO) | ||
|---|---|---|---|
| ≤ 0.1 S/CO | >0.1 to ≤0.2 S/CO | >0.2 to ≤0.3 S/CO | |
| Serum Separator | 72.0% (18/25) | 20.0% (5/25) | 8.0% (2/25) |
| Dipotassium EDTA | 80.0% (20/25) | 8.0% (2/25) | 12.0% (3/25) |
| Lithium heparin | 72.0% (18/25) | 20.0% (5/25) | 8.0% (2/25) |
| Lithium heparin separator | 76.0% (19/25) | 8.0% (2/25) | 16.0% (4/25) |
Study results support the use of the above-mentioned blood collection tubes with the ARCHITECT HSV-1 IgG assay for serum and plasma.
Precision
Within-Laboratory Precision (20-Day)
A within-laboratory precision study was performed according to CLSI EP05-A3. Testing was conducted using 3 lots of the ARCHITECT HSV-1 IgG reagents, 3 lots of the ARCHITECT HSV-1 IgG Calibrator, 1 lot of the ARCHITECT HSV-1 IgG Controls, and 1 ARCHITECT i2000SR instrument. Two controls, 3 human serum panel samples, and 3 human plasma panel samples were tested in a minimum of 2 replicates at 2 separate times per day on 20 days on 3 reagent lot/calibrator lot combinations, where a unique reagent lot and a unique calibrator lot were paired.
The precision of the ARCHITECT HSV-1 IgG assay was considered acceptable if the withinlaboratory (total) imprecision (within-run, between-run, and between-day) was less than or equal to 0.07 S/CO for samples less than 1.00 S/CO and less than or equal to 7.5 %CV for samples greater than 1.00 S/CO.
The performance of 1 representative lot of the ARCHITECT HSV-1 IgG reagents is shown in the following table.
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| Precision Results | ||||||
|---|---|---|---|---|---|---|
| Mean | Within-Run (Repeatability) | Within-Laboratorya | ||||
| Sample | n | (S/CO) | SD | %CV | SD | %CV |
| Negative Control | 80 | 0.32 | 0.008 | N/A | 0.009 | N/A |
| Positive Control | 80 | 3.11 | 0.082 | 2.63 | 0.082 | 2.65 |
| Serum Panel 1 | 80 | 1.12 | 0.030 | 2.69 | 0.035 | 3.08 |
| Serum Panel 2 | 80 | 1.59 | 0.043 | 2.68 | 0.047 | 2.97 |
| Serum Panel 3 | 80 | 2.54 | 0.063 | 2.48 | 0.065 | 2.58 |
| Plasma Panel 1 | 80 | 1.14 | 0.057 | 5.00 | 0.059 | 5.23 |
| Plasma Panel 2 | 80 | 1.58 | 0.035 | 2.19 | 0.040 | 2.54 |
| Plasma Panel 3 | 80 | 2.92 | 0.065 | 2.23 | 0.078 | 2.68 |
N/A = Not applicable
4Includes within-run, between-run, and between-day variability.
Within-Laboratory Precision (12-Day)
An additional within-laboratory precision study was conducted using samples with higher analyte levels, using 2 lots of the ARCHITECT HSV-1 IgG reagents, 1 lot of the ARCHITECT HSV-1 IgG Calibrator, and 1 instrument. Two human serum panels and 2 human plasma panels were tested in replicates of 2 at 2 separate times per day on 12 different days.
| Sample | n | Mean(S/CO) | Within-Run(Repeatability) | Between-Lot | Within-Laboratorya | |||
|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | |||
| Serum Panel 4 | 96 | 7.99 | 0.299 | 3.7 | 0.040 | 0.5 | 0.325 | 4.1 |
| Serum Panel 5 | 96 | 15.27 | 0.606 | 4.0 | 0.169 | 1.1 | 0.754 | 4.9 |
| Plasma Panel 4 | 96 | 7.68 | 0.333 | 4.3 | 0.220 | 2.9 | 0.406 | 5.3 |
| Plasma Panel 5 | 96 | 19.17 | 0.758 | 4.0 | 0.109 | 0.6 | 0.913 | 4.8 |
4Includes within-run, between-run, between-day, and between-lot variability.
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Reproducibility
A reproducibility study was performed based on guidance from CLSI EP05-A3. Testing was conducted at each of 3 testing sites using 1 lot of the ARCHITECT HSV-1 IgG reagents, 1 lot of the ARCHITECT HSV-1 IgG Calibrator, 1 lot of the ARCHITECT HSV-1 IgG Controls, and 1 instrument. Two controls, 3 human serum panel samples, and 3 human plasma panel samples were tested in 3 replicates at 2 separate times per day on 5 different days.
| Repeatability | Between-Run | Between-Day | Between-Site/Instrument | Reproducibilityª | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample | n | Mean(S/CO) | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| NegativeControl | 90 | 0.35 | 0.01 | N/A | 0.00 | N/A | 0.00 | N/A | 0.01 | N/A | 0.02 | N/A |
| PositiveControl | 90 | 3.28 | 0.09 | 2.8 | 0.01 | 0.2 | 0.03 | 0.8 | 0.07 | 2.1 | 0.12 | 3.7 |
| SerumPanel 1 | 90 | 1.10 | 0.04 | 3.3 | 0.01 | 1.2 | 0.00 | 0.0 | 0.04 | 3.7 | 0.06 | 5.1 |
| SerumPanel 2 | 90 | 1.63 | 0.04 | 2.6 | 0.00 | 0.0 | 0.00 | 0.0 | 0.04 | 2.4 | 0.06 | 3.6 |
| SerumPanel 3 | 90 | 2.46 | 0.07 | 2.8 | 0.00 | 0.0 | 0.00 | 0.0 | 0.07 | 2.7 | 0.10 | 3.9 |
| PlasmaPanel 1 | 90 | 1.10 | 0.03 | 3.0 | 0.01 | 0.9 | 0.00 | 0.0 | 0.03 | 3.0 | 0.05 | 4.3 |
| PlasmaPanel 2 | 90 | 1.55 | 0.06 | 3.8 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 0.06 | 3.8 |
| PlasmaPanel 3 | 90 | 2.83 | 0.08 | 2.8 | 0.03 | 0.9 | 0.00 | 0.0 | 0.11 | 3.9 | 0.14 | 4.9 |
Reproducibility Results
ªIncludes repeatability (within-run), between-run, between-day, and between-instrument/site variability.
Analytical Specificity
Interference
Potentially Interfering Endogenous Substances and Potentially Interfering Drugs
The ARCHITECT HSV-1 IgG assay was evaluated for potential interference of endogenous and exogenous (drugs) substances using HSV-1 IgG negative and low reactive samples. Studies were
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performed based on guidance from CLSI EP07, 3rd ed. Each substance was tested at 2 levels of the analyte, nonreactive and reactive (target ranges: 0.60 to 0.85 S/CO and 1.20 to 2.00 S/CO, respectively) using 12 replicates for each negative and low reactive HSV-1 IgG sample.
Less than 10% absolute difference for reactive HSV-1 IgG samples and less than 0.10 S/CO absolute difference for negative HSV-1 IgG samples were observed at the following concentrations of potentially interfering substances.
| Potentially Interfering EndogenousSubstance | Potential Interferent ConcentrationDefault Units | Alternate Units |
|---|---|---|
| Bilirubin (Conjugated) | 40 mg/dL | 475 µmol/L |
| Bilirubin (Unconjugated) | 40 mg/dL | 684 µmol/L |
| Hemoglobin | 1000 mg/dL | 10 g/L |
| Triglycerides | 1500 mg/dL | 16.94 mmol/L |
| Total Protein | 15 g/dL | 150 g/L |
| Serum Albumin | 6 g/dL | 60 g/L |
| Total Cholesterol | 400 mg/dL | 10.3 mmol/L |
Potentially Interfering Endogenous Substances
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Potentially Interfering Drugs
| Potentially Interfering Drug | Potential Interferent Concentration | |
|---|---|---|
| Default Units | Alternate Units | |
| Acetaminophen | 15.6 mg/dL | 1030 µmol/L |
| Acetylsalicylic acid | 3.00 mg/dL | 167 µmol/L |
| Acyclovir | 6.6 mg/dL | 293 µmol/L |
| Ampicillin | 7.5 mg/dL | 215 µmol/L |
| Ascorbic acid | 5.25 mg/dL | 298 µmol/L |
| Biotin | 4250 ng/mL | 17.3 µmol/L |
| Calcium dobesilate | 6.00 mg/dL | 144 µmol/L |
| Cefoxitin | 660 mg/dL | 15 500 µmol/L |
| Cyclosporine | 0.180 mg/dL | 1.50 µmol/L |
| Doxycycline | 1.80 mg/dL | 40.5 µmol/L |
| Famvir | 0.25 mg/L | 0.778 µmol/L |
| Ibuprofen | 21.9 mg/dL | 1060 µmol/L |
| Levodopa | 0.750 mg/dL | 38.0 µmol/L |
| Methyldopa | 2.25 mg/dL | 107 µmol/L |
| Metronidazole | 12.3 mg/dL | 719 µmol/L |
| N-Acetylcysteine | 15.0 mg/dL | 920 µmol/L |
| Phenylbutazone | 32.1 mg/dL | 1040 µmol/L |
| Rifampicin | 4.8 mg/dL | 58.3 µmol/L |
| Sodium heparin | 330 units/dL | N/A |
| Theophylline | 6.00 mg/dL | 333 µmol/L |
| Valacyclovir | 3 mg/L | 8.314 µmol/L |
Potential Cross-Reactivity
The ARCHITECT HSV-1 IgG assay was evaluated for potential cross-reactivity using specimens from individuals containing antibodies to other microorganisms or with medical conditions unrelated to HSV-1 infection. Specimens confirmed negative for HSV-1 IgG by a comparator method (immunoblot) were evaluated with the ARCHITECT HSV-1 IgG assay.
The data are summarized in the following table.
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Cross Reactivity Study Performance Results
| Category | n | ARCHITECT HSV-1 IgG | False Positive Rate | |
|---|---|---|---|---|
| Reactive | Nonreactive | (%) | ||
| Anti-dsDNAAutoantibodies | 8 | 2 | 6 | 25 |
| Antinuclear Antibody(ANA) | 11 | 0 | 11 | 0 |
| Candida albicans | 12 | 0 | 12 | 0 |
| Chlamydia trachomatis | 12 | 0 | 12 | 0 |
| Cytomegalovirus (CMV)IgG | 13 | 0 | 13 | 0 |
| Elevated IgG | 10 | 0 | 10 | 0 |
| Elevated IgM | 8 | 0 | 8 | 0 |
| Epstein-Barr virus (EBV)IgG | 14 | 0 | 14 | 0 |
| Gardnerella vaginalis | 10 | 0 | 10 | 0 |
| HAMA | 8 | 0 | 8 | 0 |
| Hepatitis A virus (HAV)IgG | 11 | 0 | 11 | 0 |
| Hepatitis B virus (HBV)IgG | 12 | 0 | 12 | 0 |
| Hepatitis C virus (HCV)IgG | 11 | 0 | 11 | 0 |
| HSV-2 IgG | 13 | 0 | 13 | 0 |
| Human-Herpesvirus-6 IgG | 14 | 0 | 14 | 0 |
| Human-Herpesvirus-8 IgG | 5 | 1 | 4 | 20 |
| Category | n | ARCHITECT HSV-1 IgG | False Positive Rate | |
| Reactive | Nonreactive | (%) | ||
| Human immunodeficiencyvirus IgG | 12 | 0 | 12 | 0 |
| Human papillomavirus(HPV) IgG | 10 | 1 | 9 | 10 |
| Monoclonalhyperimmunoglobulinemia | 12 | 0 | 12 | 0 |
| Mycoplasma pneumoniae | 5 | 0 | 5 | 0 |
| Neisseria gonorrhea | 8 | 0 | 8 | 0 |
| Parvovirus B19 IgG | 14 | 0 | 14 | 0 |
| Rheumatoid Factor (RF) | 10 | 1 | 9 | 10 |
| Rubella virus IgG | 11 | 0 | 11 | 0 |
| Streptococcus | 7 | 1 | 6 | 14 |
| Toxoplasma gondii | 11 | 0 | 11 | 0 |
| Treponema pallidum | 11 | 0 | 11 | 0 |
| Varicella-zoster virus(VZV) IgG | 11 | 0 | 11 | 0 |
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CDC Panel Agreement
The CDC Performance Panel was obtained from the Centers for Disease Control and Prevention (CDC) and tested using the ARCHITECT HSV-1 IgG assay. The panel consisted of 2 aliquots each of 50 serum samples with unknown HSV-1 status for a total of 100. The results were submitted to the CDC for data evaluation and do not imply endorsement of the assay by the CDC.
The ARCHITECT HSV-1 IgG assay demonstrated 100% positive percent agreement (PPA) for reactive samples (46/46) and 100% negative percent agreement (NPA) for nonreactive samples (54/54) when evaluating the CDC panel.
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Clinical Agreement Study
A multi-center clinical study was conducted to evaluate the clinical performance of the ARCHITECT HSV-1 IgG assay. Sensitivity and specificity were estimated using PPA and NPA as determined by comparing the performance of the ARCHITECT HSV-1 IgG assay to a composite comparator method comprised of a commercially available anti-HSV-1 IgG immunoblot method (comparator assay) and a Western Blot reference confirmatory test (University of Washington, Seattle).
A total of 915 specimens, which included sexually active individuals and pregnant females, were collected prospectively within the US and tested at 3 independent external laboratories.
The PPA and NPA results are summarized in the following tables.
Clinical Performance of the ARCHITECT HSV-1 IgG Assay in the Sexually Active Population
| Composite Comparator Assay | ||||
|---|---|---|---|---|
| Positive | Equivocal | Negative | ||
| ARCHITECTHSV-1 IgG | Reactive | 426 | 0 | 6 |
| Nonreactive | 25 | 0 | 161 | |
| Total | 451 | 0 | 167 | |
| PPA= 94.46%(426/451);95% CI= 91.95% to96.22% | NPA=96.41%(161/167);95% CI= 92.38% to98.34% |
Clinical Performance of the ARCHITECT HSV-1 IgG Assay in the Pregnant Population
| Composite Comparator Assay | ||||
|---|---|---|---|---|
| Positive | Equivocal | Negative | ||
| Reactive | 197 | 0 | 0 | |
| ARCHITECTHSV-1 IgG | Nonreactive | 8 | 0 | 92 |
| Total | 205 | 0 | 92 | |
| PPA= 96.10%(197/205);95% CI= 92.49% to98.01% | NPA= 100.00%(92/92);95% CI=95.99% to100.00% |
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10.Stability
The stability studies data support the following storage conditions for the ARCHITECT HSV-1 IgG assay:
| Stability Study | Claims |
|---|---|
| Reagent On-Board | Up to 30 days |
| Reagent Unopened Shelf Life | 12 months at 2-8°C |
| Reagent In-Use/Opened | 12 months at 2-8°C |
| Calibrator Unopened Shelf-Life | 12 months at 2-8°C |
| Calibrator In-Use/Opened | 12 months at 2-8°C |
| Controls Unopened Shelf Life | 12 months at 2-8°C |
| Controls In-Use/Opened | 12 months at 2-8°C |
11.Conclusion
The analytical and clinical study results demonstrate that the ARCHITECT HSV-1 IgG is substantially equivalent to the predicate device, HSV-1 & HSV-2 Differentiation Immunoblot IgG (FDA cleared under K000238), and that the assay is safe and effective for its labeled intended use.
§ 866.3305 Herpes simplex virus serological assays.
(a)
Identification. Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome.(b)
Classification. Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e).