(87 days)
Focus Technologies' HerpeSelect® 1 ELISA IgG test is intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-1 in human sera. In conjunction with the Focus HerpeSelect® 2 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.
In the HerpeSelect® I ELISA IgG IgG assay, the polystyrene microwells are coated with recombinant gG-1 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.
Here's an analysis of the provided text regarding the HerpeSelect® 1 ELISA IgG device, broken down by your requested criteria:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in terms of specific thresholds the device needed to meet for regulatory approval. Instead, it presents various "performance characteristics" studies. However, we can infer performance goals based on the reported results within the different populations. The primary comparative method used is the HSV-1 Western blot (WB).
| Metric / Population | Inferred Performance Goal (based on typical assay expectations) | Reported Device Performance (HerpeSelect® 1 ELISA IgG) |
|---|---|---|
| Sexually Active Adults | High Sensitivity and Specificity | Sensitivity: 91.2% (95% CI: 85.2-95.4%) |
| (compared to WB) | Specificity: 92.3% (95% CI: 85.4-96.6%) | |
| Expectant Mothers | Very High Sensitivity and Specificity | Sensitivity: 96.0% (95% CI: 92.0-98.4%) |
| (compared to WB) | Specificity: 95.2% (95% CI: 86.5-99.0%) | |
| Culture Positives | High Sensitivity (compared to Culture and WB) | Sensitivity (vs. Culture): 78.9% (95% CI: 62.7-90.4%) |
| Sensitivity (vs. WB): 81.1% (95% CI: 64.8-92.0%) | ||
| Low Prevalence Population | High Specificity (compared to WB) | Specificity: 98.2% (95% CI: 90.5-100%) |
| (for ruling out infection) | Sensitivity: 75.0% (95% CI: 53.3-90.2%) | |
| Type Specificity (HSV-2+) | High Type-specificity (low cross-reactivity with HSV-2) | Type-specificity: 91.1% (95% CI: 83.2-96.1%) |
| Cross-reactivity (Other Viruses) | 100% Negative Agreement | 100% Agreement (for CMV, EBV VCA, HHV6, VZV) |
| Agreement with CDC Panel | High overall agreement with characterized samples | 96.0% total agreement |
| 93.1% agreement with positive specimens | ||
| 100% agreement with negative specimens | ||
| Manual vs. Automated Methods | High agreement between methods | Overall Agreement: 97.6% (95% CI: 94.8-99.1%) |
| Negative Agreement: 98.1% (95% CI: 93.5-99.8%) | ||
| Positive Agreement: 97.8% (95% CI: 93.7-99.5%) |
2. Sample Size Used for the Test Set and Data Provenance
- Sexually Active Adults: n = 246 (archived, unselected sera)
- Expectant Mothers: n = 241 (archived, unselected sera)
- Culture Positives: n = 38 (sera from culture positive patients)
- Low Prevalence Population: n = 81 (sera from college students claiming to lack sexual experience)
- Type Specificity (HSV-2 Western blot positives / HSV-1 negatives): n = 90 (combined from expectant mothers, sexually active adults, low prevalence persons, and HSV-2 culture positives)
- Cross-reactivity (Taxonomically Related Viruses): n = 26 (HSV sero-negative by other FDA cleared ELISAs, IFA IgG positive for CMV, EBV VCA, HHV6, VZV)
- CDC Panel: Panel of unstated size (59% positive, 41% negative samples)
- Manual vs. Automated Methods Agreement: n = 248 (adult samples from US and 2 outside US, submitted for HSV testing)
Data Provenance:
- Most studies were conducted by an "outside investigator."
- The reference method for most studies (excluding cross-reactivity and agreement with CDC) was an HSV-1 Western blot from a Pacific Northwest university.
- The sera were "archived" and "masked" for several studies, indicating a retrospective design.
- The "outside investigator" for the manual vs. automated method comparison was part of a CLIA validation for a major clinical laboratory in Southern California.
- The CDC panel was obtained from the CDC.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
The document does not explicitly state the number of experts used or their qualifications for establishing the ground truth. The ground truth for most studies was established using a "HSV-1 Western blot from a Pacific Northwest university" or "culture" results. Western blot interpretation is typically done by trained laboratory personnel or experts in serology, but specific details on the number and qualifications are not provided here. For the CDC panel, it states the panel was "characterized," implying expert review and consensus, but again, no specifics are given.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method for the test set. It reports concordance with the reference methods (Western blot, culture, or CDC panel) and notes "equivocals" and "atypical Western blots" that were excluded from calculations, but it doesn't detail a process for resolving discrepancies.
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 ELISA (Enzyme-linked Immunosorbent Assay), which is a laboratory test for detecting antibodies. It's not an imaging or diagnostic device that involves human "readers" in the context of interpreting complex medical images like radiology or pathology. Therefore, an MRMC comparative effectiveness study comparing human reader performance with and without AI assistance is not applicable to this type of device and was not performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies evaluating "Relative Sensitivity and Relative Specificity" with various populations (sexually active adults, expectant mothers, culture positives, low prevalence, type specificity) demonstrate the standalone performance of the HerpeSelect® 1 ELISA IgG device. The results (optical density readings) are automatically compared to reference cut-off OD readings to determine results, implying an algorithmic determination. The device's performance is compared directly against the reference standard (Western blot or culture), indicating a standalone assessment.
The document also describes "Reproducibility Using an Automated Instrument" and "% Agreement between the Manual and Automated Methods," which further supports assessment of the device's automated, standalone capabilities.
7. The Type of Ground Truth Used
The primary type of ground truth used was:
- Reference Method: HSV-1 Western blot from a Pacific Northwest university.
- Culture: For the "Relative Sensitivity with Culture Positives" study.
- CDC Panel Characterization: For the "Agreement with CDC Panel" study, indicating a highly characterized set of samples.
- Other FDA cleared HSV ELISAs and IFA IgG positive for taxonomically similar viruses: For the "Cross-reactivity with Taxonomically Related Viruses" study.
8. The Sample Size for the Training Set
The document describes performance characteristics using various test sets (as detailed in point 2). It does not explicitly mention a "training set" or a separate process for training the device. For ELISA tests, the "training" equivalent would typically involve the development and validation of the assay's reagents and cut-off values using known positive and negative samples during the assay development phase. This document focuses on the validation of the finalized device.
9. How the Ground Truth for the Training Set was Established
Since an explicit "training set" is not detailed, the method for establishing its ground truth is also not provided. However, the general principle for establishing ground truth during the development of an ELISA (which constitutes the implicit "training" for the assay's cut-offs and performance characteristics) would typically involve:
- Well-characterized clinical samples: Samples from individuals with confirmed HSV-1 infection (via culture or strong clinical evidence) and confirmed non-infected individuals.
- Comparative methods: Using established gold standard tests like Western blot, PCR, or viral culture to classify these samples.
- Expert Consensus: Review by infectious disease specialists or laboratory experts to ensure accurate classification of reference samples.
The studies presented here are mainly for the validation of the device rather than its initial development or training.
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JUL 2 9 2002
Image /page/0/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) Summarv of Safety and Effectiveness HerpeSelect® 1 ELISA IgG Catalog No. EL0910G Prepared July 23, 2002 Page 1 of 9
| 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®1 ELISA IgG (automated option) |
| Generic Name | HSV-1 ELISA IgG |
| Classification | Herpes Simplex Virus Serological Reagents21 CFR §866.3305Class III |
| Predicate Device | HerpeSelect®1 ELISA IgG (manual option) |
Device Description
In the HerpeSelect® I ELISA IgG IgG assay, the polystyrene microwells are coated with recombinant gG-1 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® 1 ELISA IgG test is intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-1 in human sera. In conjunction with the Focus HerpeSelect® 2 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.
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510(k) Summary of Safety and Effectiveness HerpeSelect® 1 ELISA IgG Catalog No. EL0910G 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-1 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® 1 ELISA IgG having
-
a hypothetical sensitivity of 91.2% & a hypothetical specificity of 92.3% (sexually active adults), and
-
a hypothetical sensitivity of 96.0% and a hypothetical specificity of 95.2% (expectant mothers).
| Population | HSV-1Serostatus | Observed Prevalence | |
|---|---|---|---|
| WB | Focus ELISA | ||
| Sexually Active Adults * | neg | 42.9% | 41.2% |
| + | 55.9% | 56.7% | |
| Expectant Mothers † | neg | 25.7% | 22.4% |
| + | 73.9% | 75.5% |
Observed Prevalence with Sexually Active Adults & Expectant Mothers
- Excludes 3 atvpical Western blots and 2 ELISA equivocals.
- Excludes 1 atypical Western blot and 1 ELISA equivocal.
| Prevalence | Sexually Active Adults | Expectant Mothers | ||
|---|---|---|---|---|
| PPV | NPV | PPV | NPV | |
| 50% | 92.2% | 92.3% | 95.2% | 95.2% |
| 40% | 88.8% | 94.7% | 93.0% | 96.7% |
| 30% | 83.5% | 96.5% | 89.6% | 97.9% |
| 25% | 79.8% | 97.3% | 87.0% | 98.3% |
| 20% | 74.8% | 98.0% | 83.3% | 98.8% |
| 15% | 67.6% | 98.5% | 77.9% | 99.1% |
| 10% | 56.8% | 99.1% | 69.0% | 99.4% |
| 5% | 38.4% | 99.6% | 51.3% | 99.7% |
Prevalence vs. Hypothetical 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.
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Image /page/2/Picture/1 description: The image shows the logo for Focus Technologies. The word "FOCUS" is written in large, bold, sans-serif font, with two crescent moon shapes forming the letter "O". Below the word "FOCUS", the word "technologies" is written in a smaller, sans-serif font, with each letter spaced out.
510(k) Summary of Safety and Effectiveness HerpeSelect® 1 ELISA IgG Catalog No. EL0910G Prepared July 23, 2002 Page 3 of 9
PERFORMANCE CHARACTERISTICS
Relative Sensitivity and Relative Specificity with Expectant Mothers +
An outside investigator assessed the device's 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-1 Western blot (WB) from a Pacific Northwest university. Of 178 WB positives, HerpeSelect® 1 ELISA IgG (EL) was 170 positive, 7 negative and one equivocal. Of 62 Western blot negatives, HerpeSelect® 1 ELISA IgG was 59 negatives, and 3 positives. The one atypical Western blot was HerpeSelect® 1 ELISA IgG negative.
| Relative Sensitivity and Relative Specificity with Expectant Mothers (n=241) 1 |
|---|
| -------------------------------------------------------------------------------- |
| Characteristic | % (EL/WB)* | 95% CI |
|---|---|---|
| Sensitivity relative to Western blot | 96.0% (170/177) | 92.0-98.4% |
| Specificity relative to Western blot | 95.2% (59/62) | 86.5-99.0% |
- Excludes one atypical Western blot 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 the 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-1 Western blot from a Pacific Northwest university. Of 138 Western blot positives, HerpeSelect® 1 ELISA IgG was 125 positive, 12 negatives, and one equivocal. Of 105 Western blot Western blots, HerpeSelect® 1 ELISA IgG was one negative and two positives.
Relative Sensitivity and Relative Specificity with Sexually Active Adults (n = 246) +
| Characteristic | % (EL/WB)* | 95% CI |
|---|---|---|
| Sensitivity relative to Western blot | 91.2% (125/137) | 85.2-95.4% |
| Specificity relative to Western blot | 92.3% (96/104) | 85.4-96.6% |
- Excludes three atypical Western blots and two ELISA equivocals.
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 the manual method.
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Relative Sensitivity with Culture Positives †
An outside investigator assessed the device's relative sensitivity using sera from culture positive patients (n = 38). Reference methods included culture (infection) and a HSV-1 Western blot (antibody) from a Pacific Northwest university. Of 38 culture positives: 1) Western blot was 37 positive and one negative; and 2) HerpeSelece 1 ELISA IgG was 30 positive and eight negative. Of the 37 Western blot positives, HerpeSelect® 1 ELISA IgG was 30 positive and seven negatives.
| Characteristic | % (EL/WB orCulture) | 95% CI |
|---|---|---|
| Sensitivity relative to culture | 78.9% (30/38) | 62.7-90.4% |
| Sensitivity relative to Western Blot | 81.1% (30/37) | 64.8-92.0% |
Relative Sensitivity with Culture Positives (n = 38) +
- 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 the 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 59% positive and 41% negative samples. The Focus Technologies HerpeSelect® 1 ELISA IgG demonstrated 96.0% total agreement with the CDC results. Of the results obtained by Focus Technologies, there was 93.1% agreement with the positive specimens and 100% agreement with the negative specimens.
- Assay performed by the 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-1 antibody prevalence of 26.9% (50/186).13 The laboratory reference method was a HSV-1 Western blot from a Pacific Northwest university. Of 57 Western blot negatives, HerpeSelect® 1 ELISA IgG was 55 negatives, 1 positive and 1 equivocal. Of 24 Western blot positives, HerpeSelect® 1 ELISA IgG was 18 positive and 6 negatives.
| Characteristic | % (EL/WB)* | 95% CI |
|---|---|---|
| Specificity relative to Western blot | 98.2% (55/56) | 90.5-100% |
| Sensitivity relative to Western blot | 75.0% (18/24) | 53.3-90.2% |
Relative Specificity with a Low Prevalence Population (n = 81) *
-
Excludes 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 the 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 letter "O" in the word "FOCUS" is replaced with a crescent moon shape.
510(k) Summary of Safety and Effectiveness HerpeSelect® 1 ELISA IgG Catalog No. EL0910G Prepared July 23, 2002 Page 5 of 9
Type Specificity with HSV-2 Western Blot Positives †
An outside investigator assessed the device's type specificity using HSV-2 Western blot positive and HSV-1 Western Blot negative sera from the above described populations (n = 90): expectant mothers, sexually active adults, low prevalence persons, and HSV-2 culture positives. Of 90 HSV-2 Western blot positive and HSV-1 Western blot negative samples, HerpeSelect® 1 ELISA IgG was 82 negatives, and eight positives.
| Characteristic | % (EL/WB) | 95% CI |
|---|---|---|
| Type-specificity relative to WB | 91.1% (82/90) | 83.2-96.1% |
| Type cross-reactivity relative to WB | 8.9% (8/90) | 3.9-16.8% |
Type Specificity with HSV-2 Western Blot Positives (n = 90)
- 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 the manual method.
Cross-reactivity with Taxonomically Related Viruses †
Focus assessed the device's cross-reactivity using sera (n = 26) that were 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® 1 ELISA IgG were analyzed using a type specific Western blot from a major university located in the Northwestern United States. Excluding one HerpeSelect® 1 ELISA IgG equivocal that was not analyzed with the Western blot because of insufficient volume.
| IFA IgG Pos | % Focus EL Neg | 95% CI |
|---|---|---|
| CMV | 100% (12/12) | 73.5-100% |
| EBV VCA | 100% (24/24) | 85.5-100% |
| HHV6 | 100% (24/24) | 85.5-100% |
| VZV | 100% (23/23) | 85.2-100% |
| Total | 100% (83/83) | 95.7-100% |
| Cross-reactivity with Taxonomically Related Viruses | ||
|---|---|---|
| -- | ----------------------------------------------------- | -- |
- Assay performed by the manual method.
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Intra-assay and 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. Seven samples were run on in duplicate and in parallel with three separate lots. Each of the three lots had at least 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.
| Sample | Inter- & Intra-assay | Inter-lot | Inter-Laboratory | |||||
|---|---|---|---|---|---|---|---|---|
| IndexMean | Intra-assay%CV | Inter-assay%CV | IndexMean | Index%CV | IndexMean | Mean ofLab%CVs | %CV ofLabMeans | |
| 11* | 0.1 | 40.0 | 50.4 | 0.1 | 26.8 | 0.2 | 6.6 | 70.9 |
| 16* | 0.1 | 0.0 | 11.6 | 0.1 | 20.2 | 0.2 | 23.6 | 63.1 |
| 12** | 1.6 | 3.8 | 7.0 | 1.5 | 8.2 | 1.4 | 13.5 | 7.0 |
| 17** | 1.6 | 40.0 | 5.4 | 1.4 | 2.9 | 1.5 | 13.0 | 4.3 |
| 13 | 2.7 | 3.6 | 4.9 | 2.5 | 11.1 | 2.4 | 10.8 | 5.7 |
| 14 | 3.1 | 3.9 | 6.5 | 2.6 | 9.4 | 2.7 | 10.7 | 7.5 |
| 15 | 12.0 | 2.2 | 5.6 | 10.9 | 25.1 | 14.2 | 24.3 | 64.6 |
- #11 & #16 are masked duplicates.
** #12 & #17 are masked duplicates.
† Assay performed by the manual method
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Image /page/6/Picture/1 description: The image shows the logo for Focus Technologies. The logo consists of the word "FOCUS" in bold, sans-serif font, with two crescent moon shapes forming the letter "O". Below the word "FOCUS" is the word "technologies" in a smaller, sans-serif font. The logo is black and white.
510(k) Summary of Safety and Effectiveness HerpeSelect® 1 ELISA IgG Catalog No. EL0910G Prepared July 23, 2002 Page 7 of 9
% Agreement between the Manual and Automated Methods
An internal and an external investigator compared % agreement between the HerpeSelect automated method vs. 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 248 sample was from an adult, and was submitted for HSV testing. 246 samples were from the US, and two samples from outside the US. Of the 248 samples, the manual method detected 108 negatives, 3 equivocals, and 137 positives. Of the 108 negatives by the manual method, the automated method agreed with 98.1% (106/108). Of the 3 equivocals by the manual method, the automated method agreed with 66.7% (2/3). Of the 137 positives by the manual method, the automated method agreed with 97.8% (134/137). Overall, the two methods agreed 97.6% (242/248). Of the five discrepants, three resolved in favor of the automated method, and the other two did not resolve.
| Interpretation* | % Agreement | 95% CI |
|---|---|---|
| Negative | 98.1% (106/108) | 93.5-99.8% |
| Equivocal | 66.7% (2/3) | 9.4-99.2% |
| Positive | 97.8% (134/137) | 93.7-99.5% |
| Overall | 97.6% (242/248) | 94.8-99.1% |
% Agreement between the Manual and Automated Methods
- Interpretation by manual method.
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510(k) Summary of Safety and Effectiveness HerpeSelect® 1 ELISA IgG Catalog No. EL0910G 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 |
|---|---|---|---|
| 2 | 0.2 | 7.8 | 17.5 |
| 7 | 0.3 | 9.8 | 3.1 |
| 8 | 0.4 | 6.7 | 6.1 |
| 10 | 1.2 | 4.4 | 6.2 |
| 9 | 2.0 | 7.6 | 7.0 |
| 4 | 3.0 | 15.7 | 3.9 |
| 5 | 3.9 | 6.8 | 6.1 |
| 3 | 5.3 | 14.0 | 2.2 |
| 1 | 5.6 | 13.5 | 1.4 |
| 6 | 7.6 | 5.0 | 8.0 |
Reproducibility Using an Automated Instrument
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Image /page/8/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 letters. The two letter O's in the word FOCUS are replaced with a crescent moon shape.
510(k) Summary of Safety and Effectiveness HerpeSelect® 1 ELISA IgG Catalog No. EL0910G Prepared July 23, 2002 Page 9 of 9
Stability after Opening Reagents
An internal investigator assessed stability after the reagents had been opened. The kit was used in the interassay/intra-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. The index for when the reagents were opened and the two runs after at least 30 days are provided below. There was 96.7% agreement with the index when the reagents were opened.
| Sample | Index whenOpened | After at Least30 Days (Run 1) | After at Least30 Days (Run 2) |
|---|---|---|---|
| 2 | 0.2 | 0.2 | 0.2 |
| 7 | 0.3 | 0.3 | 0.4 |
| 8 | 0.4 | 0.3 | 0.5 |
| 10 | 1.2 | 1.1 | 1.6 |
| 9 | 2.0 | 1.8 | 2.4 |
| 4 | 3.0 | 2.8 | 3.4 |
| 5 | 3.9 | 3.4 | 4.5 |
| 3 | 5.3 | 4.7 | 5.9 |
| 1 | 5.6 | 5.3 | 6.4 |
| 6 | 7.6 | 6.7 | 7.8 |
Stability after Opening Reagents
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DEPARTMENT OF HEALTH & HUMAN SERVICES
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUL 2 9 2002
Michael J. Wagner, Esq. Senior Regulatory Affairs Specialist Focus Technologies, Inc. 10703 Progress Way Cypress. CA 90630
K021429 Re:
Trade/Device Name: HerpeSelect TM 1 ELISA IgG Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes Simplex Virus Serological Reagents Regulatory Class: Class III Exempt 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, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in 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 1 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/dsmaldsmamain.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):K021429
Device Name:
HerpeSelect® 1 ELISA IgG
Indications for Use:
Focus Technologies' HerpeSelect® 1 ELISA IgG test is intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-1 in human sera. In conjunction with the Focus HerpeSelect® 2 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 Dubois
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).