(90 days)
Focus Technologies' HerpeSelect® 2 ELISA IgG test is intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-2 in human sera. In conjunction with the Focus HerpeSelect® I ELISA IgG, the test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive digenosis of HSV infection. The assay can be used manually or in conjunction with an automated system as outlined in the package insert. The user is responsible for assay performance characteristics when an automated system is used. The performance of this assay has not been established for use in a pediatric population, for neonatal screening, or for testing of immunocompromised patients.
In the HerpeSelect 2 ELISA IgG assay, the polystyrene microwells are coated with recombinant gG-2 antigen. Diluted serum samples and controls are incubated in the wells to allow specific antibody present in the samples to react with the antigen. Nonspecific reactants are removed by washing, and peroxidase-conjugated anti-human IgG is added and reacts with specific IgG. Excess conjugate is removed by washing. Enzyme substrate and chromogen are added, and the color is allowed to develop. After adding the Stop Reagent, the resultant color change is quantified by a spectrophotometric reading of optical density (OD). Sample optical density readings are compared with reference cut-off OD readings to determine results.
The provided document describes the performance characteristics of the Focus Technologies HerpeSelect® 2 ELISA IgG assay for detecting HSV-2 IgG antibodies. The acceptance criteria are not explicitly stated in a single section but are implied through the reported performance metrics against a Western blot (WB) reference method across various populations.
1. Table of Acceptance Criteria and Reported Device Performance
Since explicit "acceptance criteria" are not given in a dedicated table, the reported performance metrics against the reference Western blot (considered the gold standard for serostatus) are used to infer them. Performance is presented for different populations, implying that satisfactory results in these different contexts are within the "acceptance criteria" for the device's intended use.
| Characteristic | Acceptance Criteria (Implied by Reported Performance) | Reported Device Performance (HerpeSelect 2 ELISA IgG) |
|---|---|---|
| For Expectant Mothers (n=241) | ||
| Relative Sensitivity (vs. WB) | High (e.g., above 90%) | 100% (58/58) (95% CI: 93.8-100%) |
| Relative Specificity (vs. WB) | High (e.g., above 90%) | 96.1% (172/179) (95% CI: 92.1-98.4%) |
| For Sexually Active Adults (n=246) | ||
| Relative Sensitivity (vs. WB) | High (e.g., above 90%) | 96.1% (73/76) (95% CI: 88.9-99.2%) |
| Relative Specificity (vs. WB) | High (e.g., above 90%) | 97.0% (159/164) (95% CI: 93.0-99.0%) |
| For Culture Positives (n=63) | ||
| Relative Sensitivity (vs. culture) | High (e.g., above 90%) | 96.8% (61/63) (95% CI: 89.0-99.6%) |
| Relative Sensitivity (vs. WB) | High (e.g., above 90%) | 98.4% (61/62) (95% CI: 91.3-100%) |
| For Low Prevalence Population (n=81) | ||
| Relative Specificity (vs. WB) | High (e.g., above 90%) | 98.7% (77/78) (95% CI: 93.1-100%) |
| Relative Sensitivity (vs. WB) | High (e.g., above 90%) | 100% (2/2) (95% CI: 15.8-100%) |
| Type Specificity with HSV-1 WB Positives (n=287) | High (e.g., above 90%) | 96.5% (276/286) (95% CI: 93.7-98.3%) |
| Cross-reactivity with Taxonomically Related Viruses (n=27) | High agreement (e.g., above 90% negative agreement) | Total 90.9% (70/77) (95% CI: 82.2-96.3%) |
| Agreement between Manual and Automated Methods (n=257) | High (e.g., above 95% overall agreement) | 98.1% (252/257) (95% CI: 95.5-99.4%) |
| Inter-assay Reproducibility (automated) | Low CV (acceptable variability) | Samples had inter-assay CVs ranging from 0.9% to 25.2% |
2. Sample Sizes and Data Provenance for Test Set
- Sexually Active Adults: n = 246 (retrospective, archived, masked sera)
- Expectant Mothers: n = 241 (retrospective, archived, masked sera)
- Culture Positive Patients: n = 63 (sera from culture positive patients)
- Low Prevalence Population: n = 81 (college students claiming to lack sexual experience)
- Type Specificity (HSV-1 WB positives): n = 287 (from expectant mothers, sexually active adults, low prevalence persons, and HSV-1 culture positives)
- Cross-reactivity with Taxonomically Related Viruses: n = 27 (HSV sero-negative by other FDA cleared HSV ELISAs, and IFA IgG positive for CMV, EBV VCA, HHV6, VZV)
- CDC Panel: Undisclosed specific number of samples (panel consists of 37% positive and 63% negative samples).
- Manual vs. Automated Method Agreement: n = 257 (adult samples submitted for HSV testing, 255 from US, 2 from outside US, retrospectively selected and manually tested by an external investigator as part of CLIA validation).
Data Provenance: The data primarily originated from a "Pacific Northwest university" for Western blot reference testing and a "major university located in the Northwestern United States" for discrepant analysis of cross-reactivity. One study on manual vs. automated method agreement involved a "major clinical laboratory located in Southern California" with samples predominantly from the US (255/257). The CDC panel information suggests samples from the US. The studies are described as using "masked, archived, and unselected sera" or "sequentially submitted" sera, indicating a retrospective data collection approach for most studies.
3. Number of Experts and Qualifications for Ground Truth
The document does not explicitly state the number of experts used to establish the ground truth for the test set or their specific qualifications (e.g., "radiologist with 10 years of experience"). However, it clearly states that the reference method for determining HSV-2 serostatus was an HSV-2 Western blot (WB) performed at a "Pacific Northwest university." For culture-positive patients, the reference methods included both culture (infection) and the HSV-2 Western blot. For cross-reactivity studies, a "type specific Western blot from a major university located in the Northwestern United States" was used for discrepant analysis.
For the "Agreement with CDC Panel," the ground truth was established by the CDC, implying a highly qualified and standardized reference.
The interpretation of Western blot results for HSV-2 would typically be performed by trained specialists in a reference laboratory, although their specific credentials are not detailed in this summary.
4. Adjudication Method for the Test Set
The document does not describe a formal adjudication method (like 2+1 or 3+1 consensus) for the initial Western blot interpretation or other reference methods. The Western blot results are presented as the established ground truth. Discrepant analysis between the HerpeSelect ELISA and other methods (e.g., other FDA cleared HSV ELISAs for cross-reactivity) was performed using a "type specific Western blot," suggesting this was the arbiter for discrepancies in those specific cases.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No multi-reader multi-case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance (or in this case, the automated ELISA) is described. The studies focus on the performance of the HerpeSelect 2 ELISA IgG assay (both manual and automated options) against a reference standard (Western blot or culture), not on the improvement of human readers with AI assistance.
6. Standalone Performance Study
Yes, standalone performance studies were done. The entire document describes the performance of the HerpeSelect® 2 ELISA IgG device (both the manual and the automated option) as a standalone diagnostic tool. Its sensitivity, specificity, agreement, and reproducibility were evaluated independently against established reference methods (Western blot, culture) or in comparison with its own manual method.
7. Type of Ground Truth Used
The primary type of ground truth used was expert reference method, specifically:
- HSV-2 Western blot (WB): Considered the gold standard for HSV-2 antibody detection. This was used across most population studies (expectant mothers, sexually active adults, low prevalence population, type specificity).
- Culture (infection): Used as a reference alongside Western blot for the "culture positives" study.
- CDC Panel: A characterized serum panel from the CDC, implying a highly validated ground truth.
- Previously FDA cleared HSV ELISAs and IFA IgG for taxonomically similar viruses: Used as initial screening/reference for the cross-reactivity study, with Western blot for discrepant analysis.
8. Sample Size for the Training Set
The document does not provide information about a "training set" for the HerpeSelect® 2 ELISA IgG assay. This assay is a diagnostic laboratory test, not an AI or machine learning algorithm that typically requires distinct training sets. The studies described are performance evaluations of the final, already developed assay.
9. How Ground Truth for the Training Set Was Established
As there is no mention of a "training set" for algorithm development in this context (the device is an ELISA assay rather than an AI/ML algorithm), the method for establishing ground truth for a training set is not applicable or described. The performance data presented refers to the test set or validation set of samples on which the device's accuracy was demonstrated.
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1 2002
Image /page/0/Picture/1 description: The image shows the logo for Focus Technologies. The word "FOCUS" is written in large, bold, sans-serif letters. Below the word "FOCUS" is the word "technologies" written in a smaller, sans-serif font. The two crescent moon shapes are placed in the middle of the word FOCUS, replacing the letter "O".
510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 1 of 9
021486
| Applicant | Focus Technologies, Inc.10703 Progress WayCypress, California 90630USA |
|---|---|
| EstablishmentRegistration No. | 2023365 |
| Contact Person | Michael J. Wagner, Esq.tel (714) 220-1900fax (714) 995-6921mwagner@focusanswers.com |
| Summary Date | July 23, 2002 |
| Proprietary Name | HerpeSelect®2 ELISA IgG (automated option) |
| Generic Name | HSV-2 ELISA IgG |
| Classification | Herpes Simplex Virus Serological Reagents21 CFR §866.3305Class III |
| Predicate Device | HerpeSelect®2 ELISA IgG (manual option) |
Device Description
In the HerpeSelect 2 ELISA IgG assay, the polystyrene microwells are coated with recombinant gG-2 antigen. Diluted serum samples and controls are incubated in the wells to allow specific antibody present in the samples to react with the antigen. Nonspecific reactants are removed by washing, and peroxidase-conjugated anti-human IgG is added and reacts with specific IgG. Excess conjugate is removed by washing. Enzyme substrate and chromogen are added, and the color is allowed to develop. After adding the Stop Reagent, the resultant color change is quantified by a spectrophotometric reading of optical density (OD). Sample optical density readings are compared with reference cut-off OD readings to determine results.
Intended Use
Focus Technologies' HerpeSelect® 2 ELISA IgG test is intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-2 in human sera. In conjunction with the Focus HerpeSelect® I ELISA IgG, the test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive digenosis of HSV infection. The assay can be used manually or in conjunction with an automated system as outlined in the package insert. The user is responsible for assay performance characteristics when an automated system is used. The performance of this assay has not been established for use in a pediatric population, for neonatal screening, or for testing of immunocompromised patients.
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Image /page/1/Picture/1 description: The image shows the logo for Focus Technologies. The logo consists of the word "FOCUS" in a bold, sans-serif font, with a stylized crescent moon shape incorporated into the "O". Below the word "FOCUS" is the word "technologies" in a smaller, sans-serif font with more spacing between the letters. The logo is black and white.
510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 2 of 9
EXPECTED VALUES
An outside investigator assessed the device with masked, archived and unselected sera from 1) sexually active adults over the age of 14 (n = 246), and 2) from expectant mothers (n = 241). The reference method was a HSV-2 Western blot from a Pacific Northwest university. The observed prevalences and the hypothetical predictive values for the two populations are shown in the tables below. The positive value will decrease proportionally to the prevalence of HSV infection as reflected in the table below. The calculations are based on HerpeSelect 2 ELISA IgG having
I) a hypothetical sensitivity of 96.1% & a hypothetical specificity of 97.0% (sexually active adults), and
- a hypothetical sensitivity of 100% and a hypothetical specificity of 96.1% (expectant mothers).
| Population | HSV-2Serostatus | Observed Prevalence | |
|---|---|---|---|
| WB | Focus ELISA | ||
| Sexually Active Adults * | neg | 68.5% | 67.2% |
| + | 31.5% | 32.4% | |
| Expectant Mothers † | neg | 75.6% | 72.3% |
| + | 24.4% | 27.3% |
Observed Prevalence with Sexually Active Adults & Expectant Mothers
- Excludes 5 atypical Western blots and 1 ELISA equivocal.
† Excludes 3 atypical Western blots and 1 ELISA equivocal.
| Prevalence vs. Hypothetical Predictive Values | ||||
|---|---|---|---|---|
| Prevalence | Sexually Active Adults | Expectant Mothers | ||
| PPV | NPV | PPV | NPV | |
| 50% | 97.0% | 97.0% | 96.2% | 96.1% |
| 40% | 95.5% | 98.0% | 94.5% | 97.4% |
| 30% | 93.2% | 98.7% | 91.7% | 98.3% |
| 25% | 91.4% | 99.0% | 89.5% | 98.7% |
| 20% | 88.9% | 99.2% | 86.5% | 99.0% |
| 15% | 85.0% | 99.5% | 81.9% | 99.3% |
| 10% | 78.1% | 99.7% | 74.0% | 99.6% |
| 5% | 62.8% | 99.8% | 57.4% | 99.8% |
Prevalence vs. Hynothetical Predictive Values
Note: Sexually active adult and expectant mother populations in different geographic areas may produce different frequency distributions from the table above. Each laboratory should establish frequency distributions for their specific patient populations.
PERFORMANCE CHARACTERISTICS
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Image /page/2/Picture/1 description: The image shows the logo for Focus Technologies. The logo is in black and white and features the word "FOCUS" in large, bold letters. Below the word "FOCUS" is the word "technologies" in a smaller, sans-serif font. The two crescent shapes are nested inside the letter O.
510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 3 of 9
Relative Sensitivity and Relative Specificity with Expectant Mothers †
An outside investigator assessed the device's relative sensitivity and relative specificity with sera from expectant mothers (n = 241). The sera were sequentially submitted to the laboratory, archived, and masked. The reference method was a HSV-2 Western blot (WB) from a Pacific Northwest university. Of 3 atypical Western blots, HerpeSelect® 2 ELISA IgG (EL) was 1 equivocal and 2 negatives. Of 58 Western blot positives, HerpeSelect® 2 ELISA IgG was 58 positive. Of 180 Western blot negatives, HerpeSelect® 2 ELISA IgG was 172 negatives, 7 positives, and 1 equivocal.
| Characteristic | % (EL/WB)* | 95% CI |
|---|---|---|
| Sensitivity relative to Western blot | 100% (58/58) | 93.8-100% |
| Specificity relative to Western blot | 96.1% (172/179) | 92.1-98.4% |
Relative Sensitivity and Relative Specificity with Expectant Mothers (n = 241) †
- Excludes three atypical Western blots and one ELISA equivocal
- The word "relative" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease. Assay performed by manual method.
Relative Sensitivity and Relative Specificity with Sexually Active Adults †
An outside investigator assessed the device's relative sensitivity and relative specificity with sera from sexually active adults over the age of 14 (n = 246). The sera were sequentially submitted to the laboratory, archived, and masked. The reference method was a HSV-2 Western blot from a Pacific Northwest university. Of 5 atypical Western blots, HerpeSelect® 2 ELISA IgG was 2 equivocal, 2 negative and 1 positive. Of 76 Western blot positives, HerpeSelect® 2 ELISA IgG was 73 positive. Of 165 Western blot negatives, HerpeSelect® 2 ELISA IgG was 159 negative, 5 positive, and 1 equivocal.
Relative Sensitivity and Relative Specificity with Sexually Active Adults (n = 246) †
| Characteristic | % (EL/WB)* | 95% CI |
|---|---|---|
| Sensitivity relative to Western blot | 96.1% (73/76) | 88.9-99.2% |
| Specificity relative to Western blot | 97.0% (159/164) | 93.0-99.0% |
-
Excludes five atypical Western blots and one ELISA equivocal
-
The word "relative" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease. Assay performed by manual method.
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Image /page/3/Picture/1 description: The image shows the logo for Focus Technologies. The logo is black and white and features the word "FOCUS" in large, bold letters. Below the word "FOCUS" is the word "technologies" in smaller letters. The two crescent moon shapes are used to create the letter O in the word FOCUS.
510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 4 of 9
Relative Sensitivity with Culture Positives +
An outside investigator assessed the device's relative sensitivity using sera from culture positive patients (n = 63). Reference methods included culture (infection) and a HSV-2 Western blot (antibody) from a Pacific Northwest university. Of 5 atypical Western blots, HerpeSelect®2 ELISA IgG was 2 equivocal, 2 negative and 1 positive. Of 63 culture positives, HerpeSelect® 2 ELISA IgG was 61 positive and 2 negative, and Western blot was 62 positive and 1 negative. Of 62 Western blot positives, HerpeSelect® 2 ELISA IgG was 61 positive and 1 negative.
| Characteristic | % (EL/WB orCulture) | 95% CI |
|---|---|---|
| Sensitivity relative to culture | 96.8% (61/63)* | 89.0-99.6% |
| Sensitivity relative to Western blot | 98.4% (61/62)* | 91.3-100% |
*Of the 2 ELISA negatives, one was WB positive and the other WB negative.
- The word "relative" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease. Assay performed by manual method.
Agreement with CDC Panel +
The following information is from a serum panel obtained from the CDC and tested by Focus Technologies. The results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. This does not imply an endorsement of the assay by the CDC. The panel consists of 37% positive and 63% negative samples. The HerpeSelect® 2 ELISA IgG demonstrated 100% total agreement with the Of the results obtained by Focus Technologies, there was 100% agreement with the positive CDC results. specimens and 100% agreement with the negative specimens.
- Assay performed by manual method.
Relative Specificity with a Low Prevalence Population *
An outside investigator assessed the device's relative specificity using sera from a population of college students claiming to lack sexual experience (n = 81), and having a published HSV-2 antibody prevalence of 2% (4/186) ** The laboratory reference method was a HSV-2 Western blot from a Pacific Northwest university. One atypical Western blot was an HerpeSelect® 2 ELISA IgG negative. Of 78 Western blot negatives, HerpeSelect® 2 ELISA IgG was 77 negative and 1 positive. Of 2 Western blot negatives, HerpeSelect® 2 ELISA IgG was 2 positive.
| Characteristic | % (EL/WB)* | 95% CI |
|---|---|---|
| Specificity relative to Western blot† | 98.7% (77/78) | 93.1-100% |
| Sensitivity relative to Western blot† | 100% (2/2) | 15.8-100% |
Relative Specificity with a Low Prevalence Population (n = 81) +
- Excludes one atypical Western blot.
** Corey, L. A. Wald, New Developments in the Biology of Genital Herpes, in Clinical Management of Herpes Viruses, p.46.
+ The word "relative" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease. Assay performed by manual method.
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Image /page/4/Picture/1 description: The image shows the logo for Focus Technologies. The logo is black and white and features the word "FOCUS" in large, bold letters. Below the word "FOCUS" is the word "technologies" in smaller letters. The two crescent moon shapes are used in place of the letter "O" in the word "FOCUS".
510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 5 of 9
Type Specificity with HSV-1 Western Blot Positives †
An outside investigator assessed the device's type specificity using HSV-1 Western blot positive and HSV-2 Western Blot negative sera from the above described populations (n = 287): expectant mothers, sexually active adults, low prevalence persons, and HSV-1 culture positives. Of 287 HSV-1 Western blot positive and HSV-2 Western blot negative samples, HerpeSelect® 2 ELISA IgG was 276 negatives, 1 equivocal and 10 positives.
| Characteristic | % (EL/WB)* | 95% CI |
|---|---|---|
| Type-specificity relative to Western blot | 96.5% (276/286) | 93.7-98.3% |
| Type cross-reactivity relative to Western blot | 3.5% (10/286) | 1.7-6.3% |
| Type Specificity with HSV-1 Western Blot Positives (n = 287) † | |||
|---|---|---|---|
- Excludes one equivocal ELISA result.
- The word "relative" refers to comparing this assay's results with those of a similar assay. No attempt was made to correlate the assay results to disease presence or absence. No judgment can be made on the similar assay's accuracy in predicting disease. Assay performed by manual method. Assay performed by manual method.
Cross-reactivity with Taxonomically Related Viruses *
Focus Technologies assessed the device's cross-reactivity using sera (n = 27) from 1) HSV sero-negative by another manufacturer's FDA cleared HSV ELISAs, and 2) IFA IgG positive for taxonomically similar viruses including CMV, EBV VCA, HHV6 and VZV. Discrepants between the FDA cleared HSV ELISAs and the HerpeSelect" 2 ELISA IgG were analyzed using a type specific Western blot from a major university located in the Northwestern United States.
| Cross-reactivity with Taxonomically Related Viruses (n = 27) † | ||
|---|---|---|
| IFA IgG Pos | % AgreementNegative* | 95% CI |
| CMV | 91.7% (11/12) | 61.5-99.8% |
| EBV VCA | 90.9% (20/22) | 70.8-98.9% |
| HHV6 | 90.9% (20/22) | 70.8-98.9% |
| VZV | 90.5% (19/21) | 69.6-98.8% |
| Total | 90.9% (70/77) | 82.2-96.3% |
Cross-reactivity with Taxonomically Related Viruses (n
- Excludes 3 Western blot positives, and one discrepant that was not analyzed with the Western blot because of insufficient volume
- Assay performed by manual method.
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Image /page/5/Picture/0 description: The image shows the logo for Focus Technologies. The logo consists of the word "FOCUS" in large, bold, sans-serif letters, with a crescent moon shape replacing the letter "O". Below the word "FOCUS" is the word "technologies" in a smaller, sans-serif font. The logo is black and white.
Intra-assay & Inter-assay Reproducibility †
An internal investigator assessed the device's intra-assay reproducibility by assaying seven samples in duplicate, twice a day, for twenty days, for a total of forty runs. Two sets of samples were masked duplicates.
Inter-lot Reproducibility †
An internal investigator assessed the device's inter-lot reproducibility. Five samples were run on three separate days with three separate lots. For one lot, the samples were run in duplicate with the other two lots. Each of the three lots had a different lot of Antigen Wells.
Inter-laboratory Reproducibility †
An internal investigator and two off-site laboratories assessed the device's inter-laboratory reproducibility. Each of the three laboratories ran seven samples in triplicate on three different days. Three points were excluded because an incorrect sample (instead of sample 27) was run one day.
| Sample | Inter- & Intra-assay | Inter-lot | Inter-Laboratory | |||||
|---|---|---|---|---|---|---|---|---|
| IndexMean | Intra-assay%CV | Inter-assay%CV | IndexMean | Index%CV | IndexMean | %CV ofLabMeans | Mean ofLab%CVs | |
| 21* | 0.2 | 20.5 | 15.9 | 0.3 | 52.4 | 0.2 | 19.6 | 17.3 |
| 26* | 0.2 | 12.2 | 12.4 | NA | NA | 0.3 | 33.1 | 20.7 |
| 22** | 1.2 | 6.3 | 6.2 | 1.2 | 5.1 | 1.2 | 3.9 | 7.8 |
| 27** | 1.2 | 5.2 | 6.3 | NA | NA | 1.1 | 14.1 | 8.8 |
| 23 | 1.8 | 4.7 | 5.5 | 1.8 | 5.4 | 1.7 | 5.2 | 7. |
| 24 | 3.4 | 3.2 | 7.9 | 3.2 | 16.7 | 2.8 | 11.0 | 10.8 |
| 25 | 8.2 | 3.0 | 6.9 | 8.0 | 7.4 | 6.8 | 18.6 | 4.5 |
Reproducibility †
- #21 & #26 are same material.
** #22 & #27 are same material.
ート Assay performed by manual method.
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Image /page/6/Picture/1 description: The image shows the logo for Focus Technologies. The logo is in black and white and features the word "FOCUS" in large, bold letters. Below the word "FOCUS" is the word "technologies" in smaller, lowercase letters. The two crescent moon shapes are used in place of the letter "O" in the word "FOCUS".
510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 7 of 9
% Agreement between the Manual and Automated Methods (n = 257)
An internal and an external investigator compared % agreement between the HerpeSelect automated ws. the manual method as part of a CLIA validation for a major clinical laboratory located in Southern California. The external investigator sequentially selected and manually tested 257 sample was from an adult, and was submitted for HSV testing. 255 samples were from the US, and two samples from outside the US. Of the 257 samples, the manual method detected 175 negatives, 3 equivocals, and 79 positives. Of the 175 negatives by the manual method, the automated method agreed with 99.4% (174/175). Of the 3 equivocals by the manual method, the automated method agreed with 0% (0/3). Of the 79 positives by the manual method, the automated method agreed with 98.7% (78/79). Overall, the two methods agreed 98.1% (252/257). Of the five discrepants, two resolved in favor of the automated method, and the other three did not resolve.
| Interpretation* | % Agreement | 95% CI |
|---|---|---|
| Negative | 99.4% (174/175) | 96.4-100% |
| Equivocal | 0.0% (0/3) | 0.0-70.8% |
| Positive | 98.7% (78/79) | 93.1-100% |
| Overall | 98.1% (252/257) | 95.5-99.4% |
% Agreement between Manual and Automated Methods
- Interpretation by manual method.
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510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 8 of 9
Reproducibility Using an Automated Instrument
An internal investigator assessed the device's inter-assay reproducibility with an automated instrument. Ten samples were tested in triplicate on three different days. The manual and automated methods agreed 98.9% (89/90). One point from Sample 3 was an outlier (162 standard deviations from the mean).
| Sample | Mean Index | Intra-assay%CV | Inter-assay%CV |
|---|---|---|---|
| 6 | 0.06 | 27.2 | 20.8 |
| 3 (without outlier)* | 0.45 | 8.8 | 4.6 |
| 8 | 0.10 | 28.3 | 25.2 |
| 3 (with outlier)* | 1.18 | 51.4 | 105.4 |
| 10 | 1.39 | 6.0 | 5.5 |
| 9 | 1.87 | 4.8 | 2.5 |
| 5 | 5.23 | 2.8 | 0.9 |
| 1 | 6.38 | 1.3 | 3.5 |
| 4 | 7.14 | 3.0 | 3.3 |
| 7 | 7.97 | 6.4 | 10.8 |
| 2 | 8.21 | 0.8 | 4.6 |
*One point from Sample 3 was an outlier (162 standard deviations from the mean).
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Image /page/8/Picture/1 description: The image shows the logo for Focus Technologies. The word "FOCUS" is written in large, bold, black letters. Below the word "FOCUS" is the word "technologies" written in a smaller, thinner font. The two crescent moon shapes are used to create the letter "O" in the word "FOCUS".
510(k) Summary of Safety and Effectiveness HerpeSelect®2 ELISA IgG Catalog No. EL0920G Prepared July 23, 2002 Page 9 of 9
Stability after Opening Reagents
An internal investigator assessed stability after the reagents had been opened and used with an automated instrument. The kit was used in the inter-assay reproducibility study (above), re-closed, stored at 2-8C for at least 30 days, and then used again to re-test the same samples. There was 100% agreement with the index when the reagents were opened.
| Sample | Index whenOpened | After at Least30 Days (Run 1) | After at Least30 Days (Run 2) |
|---|---|---|---|
| 6 | 0.06 | 0.06 | 0.07 |
| 3 (without outlier) | 0.45* | 0.43 | 0.48 |
| 8 | 0.10 | 0.14 | 0.10 |
| 10 | 1.39 | 1.60 | 1.76 |
| 9 | 1.87 | 2.03 | 2.11 |
| 5 | 5.23 | 5.13 | 5.10 |
| 1 | 6.38 | 6.79 | 6.57 |
| 4 | 7.14 | 7.67 | 7.26 |
| 7 | 7.97 | 8.16 | 8.29 |
| 2 | 8.21 | 8.38 | 8.35 |
Stability after Opening Reagent
*One point from Sample 3 was an outlier, it was 162 SDs from the mean. The values without the outlier are used here.
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Image /page/9/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with three lines representing its wings. The eagle is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA", which is arranged in a circular fashion around the left side of the logo.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
AUG 0 1 2002
Michael J. Wagner, Esq. Senior Regulatory Affairs Specialist Focus Technologies, Inc. 10703 Progress Way Cypress, CA 90630
Re: K021486 Trade/Device Name: HerpeSelect ™ 2 ELISA IgG Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes Simplex Virus Serological Reagents Regulatory Class: Class III Product Code: MXJ Dated: May 2, 2002 Received: May 3, 2002
Dear Mr. Wagner:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and ' additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device. please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrb/dsma/dsmamain.html".
Sincerely yours,
Steven Butman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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510(k) Number (if known): K021486
Device Name:
HerpeSelect® 2 ELISA IgG
Indications for Use:
Focus Technologies' HerpeSelect® 2 ELISA IgG test is intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-2 in human sera. In conjunction with the Focus HerpeSelect® 1 ELISA IgG, the test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of HSV infection. The assay can be used manually or in conjunction with an automated system as outlined in the package insert. The user is responsible for assay performance characteristics when an automated system is used. The performance of this assay has not been established for use in a pediatric population, for neonatal screening, or for testing of immunocompromised patients.
(PLEASE DO NOT WRITE BELOW THIS LINE CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE)
Woody Duboer
0(k) Number
For PRESCRIPTION USE_X
(Optional Format 3-10-98)
§ 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).