(639 days)
Not Found
No
The device description details a standard immunoassay technology (CMIA) and the performance studies focus on traditional analytical and clinical metrics. There is no mention of AI, ML, or related concepts in the provided text.
No
Explanation: This device is an in vitro diagnostic (IVD) assay designed to detect specific antibodies to HSV-1. It is used for diagnostic purposes to aid in the presumptive diagnosis of HSV-1 infection, not to treat or prevent a disease or condition.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay is "to be used... to aid in the presumptive diagnosis of HSV-1 infection." This directly indicates its role in identifying a medical condition.
No
The device is a chemiluminescent microparticle immunoassay (CMIA) which is a laboratory-based test involving physical reagents and an instrument (ARCHITECT i System) to perform the assay and measure results. This is a hardware-dependent system, not software-only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "qualitative detection of specific IgG antibodies to herpes simplex virus type 1 (HSV-1) in human serum... and plasma..." This is a test performed on biological samples taken from the human body to provide information about a person's health status.
- Device Description: The description details a laboratory-based assay using chemical reactions (chemiluminescent microparticle immunoassay) to analyze components within the sample (antibodies to HSV-1).
- Performance Studies: The document describes clinical studies evaluating the performance of the assay in detecting HSV-1 antibodies in human samples, including metrics like sensitivity and specificity.
- Predicate Device: The mention of a predicate device (K000238) which is an "Immunoblot IgG" for HSV-1 & HSV-2 differentiation further indicates that this device falls within the category of diagnostic tests.
All these points align with the definition of an In Vitro Diagnostic device, which is used to examine specimens derived from the human body to provide information for diagnostic purposes.
N/A
Intended Use / Indications for Use
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 lesions or associated 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 immunocompromised or immunosuppressed patients. The assay has not been FDA cleared or approved for screening blood or plasma donors.
Product codes (comma separated list FDA assigned to the subject device)
MXJ
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Sexually active adults or expectant mothers. Not established for use in pediatric population or for neonatal screening.
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
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.
A multi-center clinical study was conducted to evaluate the clinical performance of the ARCHITECT HSV-1 IgG assay. 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. Comparison was made against a composite comparator method comprised of a commercially available anti-HSV-1 IgG immunoblot method and a Western Blot reference confirmatory test (University of Washington, Seattle).
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Tube Type Matrix Comparison: 62 sets of unique serum samples evaluated. Less than 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).
Precision:
- Within-Laboratory Precision (20-Day): 80 replicates for each sample type (controls, serum panels, plasma panels). Acceptable precision if within-laboratory (total) imprecision was ≤ 0.07 S/CO for samples 1.00 S/CO. Results met criteria.
- Within-Laboratory Precision (12-Day): 96 replicates for each serum and plasma panel. Results indicate good precision.
Reproducibility: 90 replicates for each sample type across 3 testing sites. Results indicate good reproducibility.
Analytical Specificity (Interference): Samples tested with various endogenous substances and drugs. 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 specified concentrations.
Analytical Specificity (Potential Cross-Reactivity): Specimens from individuals with antibodies to other microorganisms or medical conditions unrelated to HSV-1 infection (n=8 to 14 per category). False positive rates observed for Anti-dsDNA Autoantibodies (25%), Human-Herpesvirus-8 IgG (20%), Human papillomavirus (HPV) IgG (10%), Rheumatoid Factor (RF) (10%), and Streptococcus (14%).
CDC Panel Agreement: 100 serum samples (50 unique, 2 aliquots each). 100% positive percent agreement (PPA) for reactive samples (46/46) and 100% negative percent agreement (NPA) for nonreactive samples (54/54).
Clinical Agreement Study: 915 specimens from sexually active individuals and pregnant females. - Sexually Active Population: PPA = 94.46% (426/451); 95% CI= 91.95% to 96.22%. NPA = 96.41% (161/167); 95% CI= 92.38% to 98.34%.
- Pregnant Population: PPA = 96.10% (197/205); 95% CI= 92.49% to 98.01%. NPA = 100.00% (92/92); 95% CI=95.99% to 100.00%.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
CDC Panel Agreement:
PPA = 100% (46/46)
NPA = 100% (54/54)
Clinical Performance of the ARCHITECT HSV-1 IgG Assay in the Sexually Active Population:
PPA = 94.46% (426/451); 95% CI= 91.95% to 96.22%
NPA = 96.41% (161/167); 95% CI= 92.38% to 98.34%
Clinical Performance of the ARCHITECT HSV-1 IgG Assay in the Pregnant Population:
PPA = 96.10% (197/205); 95% CI= 92.49% to 98.01%
NPA = 100.00% (92/92); 95% CI=95.99% to 100.00%
Potential Cross-Reactivity False Positive Rates:
Anti-dsDNA Autoantibodies: 25% (2/8)
Antinuclear Antibody (ANA): 0% (0/11)
Candida albicans: 0% (0/12)
Chlamydia trachomatis: 0% (0/12)
Cytomegalovirus (CMV) IgG: 0% (0/13)
Elevated IgG: 0% (0/10)
Elevated IgM: 0% (0/8)
Epstein-Barr virus (EBV) IgG: 0% (0/14)
Gardnerella vaginalis: 0% (0/10)
HAMA: 0% (0/8)
Hepatitis A virus (HAV) IgG: 0% (0/11)
Hepatitis B virus (HBV) IgG: 0% (0/12)
Hepatitis C virus (HCV) IgG: 0% (0/11)
HSV-2 IgG: 0% (0/13)
Human-Herpesvirus-6 IgG: 0% (0/14)
Human-Herpesvirus-8 IgG: 20% (1/5)
Human immunodeficiency virus IgG: 0% (0/12)
Human papillomavirus (HPV) IgG: 10% (1/10)
Monoclonal hyperimmunoglobulinemia: 0% (0/12)
Mycoplasma pneumoniae: 0% (0/5)
Neisseria gonorrhea: 0% (0/8)
Parvovirus B19 IgG: 0% (0/14)
Rheumatoid Factor (RF): 10% (1/10)
Rubella virus IgG: 0% (0/11)
Streptococcus: 14% (1/7)
Toxoplasma gondii: 0% (0/11)
Treponema pallidum: 0% (0/11)
Varicella-zoster virus (VZV) IgG: 0% (0/11)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
K000238 (HSV-1 & HSV-2 Differentiation Immunoblot IgG)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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).
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Date: September 20, 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 is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
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
1
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,
Image /page/1/Picture/6 description: The image shows the name "Ryan C. Karsner -S" in a large, bold font. The name is split into two lines, with "Ryan C." on the first line and "Karsner -S" on the second line. The text is black and is set against a white background. The letter "S" is slightly cut off.
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
2
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, 7
Lliçà d'Amunt 08186
Barcelona (Spain) |
| ---------------------------- | -------------------------------------------------------------------------------- |
|---|
| 2. Contact Person | Àngels Roma, Regulatory Affairs and Design Quality
Director
Phone: +34 93 860 90 00
Email: aroma@werfen.com |
| ------------------- | ---------------------------------------------------------------------------------------------------------------------- |
|---|
| 3. Preparation Date | 2023-Sep-20 |
|---|---|
| --------------------- | ------------- |
| 4. Device Trade Name | ARCHITECT HSV-1 IgG |
|---|---|
| ---------------------- | --------------------- |
| Regulation Number | 21 CFR 866.3305 | |
|---|---|---|
| 5. Regulatory | ||
| Information | Regulation Description | Herpes simplex virus |
| serological assays. | ||
| Classification | Class II Special Controls | |
| Product Code | MXJ | |
| Classification Panel | Microbiology |
| 6. Predicate Device | K000238 (HSV-1 & HSV-2 Differentiation Immunoblot
IgG) |
| --------------------- | ----------------------------------------------------------- |
|---|
4
| 7. Indications for Use / Intended Use | 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, and 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 lesions or associated
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
immunocompromised or immunosuppressed patients. The
assay has not been FDA cleared or approved for screening
blood 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 Differentiation | |
| Immunoblot IgG | ARCHITECT HSV-1 IgG, | |
| ARCHITECT HSV-1 IgG | ||
| Calibrator, ARCHITECT HSV-1 | ||
| IgG Controls | ||
| 510K no. | K000238 | K213987 |
| Manufacturer | MLR Diagnostics | |
| Cypress, CA 90630 -USA | Abbott Ireland Diagnostics Division | |
| Finisklin Business Park, Sligo, | ||
| Ireland | ||
| Similarities | ||
| Intended use | MLR Diagnostics' HSV-1 & | |
| HSV-2 Differentiation | ||
| Immunoblot IgG test is intended | ||
| for qualitatively detecting the | ||
| presence or absence of human IgG | ||
| class antibodies to HSV-1 and | ||
| HSV-2 in human sera. The test is | ||
| indicated for testing sexually | ||
| active adults or expectant mothers | ||
| for aiding in the presumptive | ||
| diagnosis of HSV-1 and HSV-2 | ||
| infection. The predictive value of | ||
| a positive or negative result | ||
| depends on the population's | ||
| prevalence and the pretest | ||
| likelihood of HSV- 1 and HSV-2 | ||
| infection. The performance of this | ||
| assay has not been established for | ||
| use in a pediatric population, for | ||
| neonatal screening, for testing of | ||
| immunocompromised patients, for | ||
| use by a point of care facility or | ||
| for use with automated equipment | 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, and 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 | ||
| lesions or associated 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 | ||
| immunocompromised or | ||
| immunosuppressed patients. The | ||
| assay has not been FDA cleared or | ||
| approved for screening blood or | ||
| plasma donors. | ||
| Analyte | Human IgG class antibodies to | |
| HSV-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) and |
| plasma (collected in dipotassium EDTA, lithium heparin, and lithium heparin separator tubes) | ||
| Result | ||
| Interpretation | Visually evaluate multiple bands | The cutoff is 1.00 S/CO. |
| 10% to ≤20% | >20% to ≤30% | |
| Serum Separator | 86.5% (32/37) | 8.1% (3/37) |
| Dipotassium EDTA | 75.7% (28/37) | 16.2% (6/37) |
| Lithium heparin | 83.8% (31/37) | 5.4% (2/37) |
| Lithium heparin separator | 67.6% (25/37) | 21.6% (8/37) |
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 |
| Negative
Control | 90 | 0.35 | 0.01 | N/A | 0.00 | N/A | 0.00 | N/A | 0.01 | N/A | 0.02 | N/A |
| Positive
Control | 90 | 3.28 | 0.09 | 2.8 | 0.01 | 0.2 | 0.03 | 0.8 | 0.07 | 2.1 | 0.12 | 3.7 |
| Serum
Panel 1 | 90 | 1.10 | 0.04 | 3.3 | 0.01 | 1.2 | 0.00 | 0.0 | 0.04 | 3.7 | 0.06 | 5.1 |
| Serum
Panel 2 | 90 | 1.63 | 0.04 | 2.6 | 0.00 | 0.0 | 0.00 | 0.0 | 0.04 | 2.4 | 0.06 | 3.6 |
| Serum
Panel 3 | 90 | 2.46 | 0.07 | 2.8 | 0.00 | 0.0 | 0.00 | 0.0 | 0.07 | 2.7 | 0.10 | 3.9 |
| Plasma
Panel 1 | 90 | 1.10 | 0.03 | 3.0 | 0.01 | 0.9 | 0.00 | 0.0 | 0.03 | 3.0 | 0.05 | 4.3 |
| Plasma
Panel 2 | 90 | 1.55 | 0.06 | 3.8 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 0.06 | 3.8 |
| Plasma
Panel 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 Endogenous
Substance | Potential Interferent Concentration
Default 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-dsDNA | ||||
| Autoantibodies | 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 immunodeficiency | ||||
| virus IgG | 12 | 0 | 12 | 0 |
| Human papillomavirus | ||||
| (HPV) IgG | 10 | 1 | 9 | 10 |
| Monoclonal | ||||
| hyperimmunoglobulinemia | 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 | ||
| ARCHITECT | ||||
| HSV-1 IgG | Reactive | 426 | 0 | 6 |
| Nonreactive | 25 | 0 | 161 | |
| Total | 451 | 0 | 167 | |
| PPA= 94.46% | ||||
| (426/451); | ||||
| 95% CI= 91.95% to | ||||
| 96.22% | NPA=96.41% | |||
| (161/167); | ||||
| 95% CI= 92.38% to | ||||
| 98.34% |
Clinical Performance of the ARCHITECT HSV-1 IgG Assay in the Pregnant Population
| Composite Comparator Assay | ||||
|---|---|---|---|---|
| Positive | Equivocal | Negative | ||
| Reactive | 197 | 0 | 0 | |
| ARCHITECT | ||||
| HSV-1 IgG | Nonreactive | 8 | 0 | 92 |
| Total | 205 | 0 | 92 | |
| PPA= 96.10% | ||||
| (197/205); | ||||
| 95% CI= 92.49% to | ||||
| 98.01% | NPA= 100.00% | |||
| (92/92); | ||||
| 95% CI=95.99% to | ||||
| 100.00% |
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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.