(154 days)
The LIAISON® HSV-1 Type Specific IgG assay is a chemiluminescent immunoassay (CLIA) to be used with the LIAISON® Analyzer for the qualitative determination of type specific IgG antibodies to Herpes Simplex Virus Type 1 (HSV-1) in human serum, The assay is indicated for testing sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-1 infection.
The LIAISON® HSV-1 Type Specific IgG assay has not been established for use in the pediatrics population, for neonatal screening, or for testing immunocompromised patients. The assay is neither FDA cleared nor approved for testing blood or plasma donors.
The LIAISON® Control HSV-1 (negative and positive) are intended for use as assayed quality control samples to monitor the performance of the LIAISON® HSV-1 Type Specific IgG assay.
The method for qualitative determination of specific IgG to HSV-1 is an indirect chemiluminescence immunoassay (CLIA). HSV-1 gG1recombinant antigen is used for coating magnetic particles (solid phase) and a mouse monoclonal antibody is linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation. HSV-1 antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with HSV-1 IgG already bound to the solid phase. After each incubation the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of HSV-1 IgG present in calibrators, samples or controls.
Here's a summary of the acceptance criteria and study details for the DiaSorin LIAISON® HSV-1 Type Specific IgG assay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to the predicate device and the desired performance characteristics for diagnostic assays. While explicit acceptance thresholds (e.g., "sensitivity must be > X%") are not stated, the study aims to demonstrate equivalent performance to the FDA-cleared predicate device across various populations.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (LIAISON® HSV-1 Type Specific IgG) |
|---|---|---|
| Sensitivity (Sexually Active Adults) | Equivalent to predicate (Focus Diagnostics HerpeSelect® 1 and 2 Immunoblot IgG) | 96.9% (95% CI: 94.3 - 98.6%) |
| Specificity (Sexually Active Adults) | Equivalent to predicate | 91.3% (95% CI: 86.9 - 94.6%) |
| Sensitivity (Expectant Mothers) | Equivalent to predicate | 98.7% (95% CI: 96.8 - 99.7%) |
| Specificity (Expectant Mothers) | Equivalent to predicate | 93.7% (95% CI: 90.0 - 96.3%) |
| Sensitivity (Low Prevalence Population) | Equivalent to predicate | 96.8% (95% CI: 90.1 - 99.4%) |
| Specificity (Low Prevalence Population) | Equivalent to predicate | 100.0% (95% CI: 94.9 - 100.0%) |
| Positive Agreement (CDC Panel) | High agreement with CDC characterized positive samples | 100% (52/52) |
| Negative Agreement (CDC Panel) | High agreement with CDC characterized negative samples | 93.75% (45/48) |
| Reproducibility (Overall %CV) | Low variability; acceptance implicitly based on typical assay CVs for similar tests (not explicitly stated here, but demonstrated by low reported %CVs across sites and runs) | Ranged from 10.1% to 14.9% across different samples |
2. Sample Size Used for the Test Set and Data Provenance
- Total Sample Size for Comparative Clinical Trials: 951 samples
- "At risk" samples (Sexually Active Adults): 401
- Expectant Mothers: 430
- Low Prevalence population: 120
- Data Provenance: Samples were collected in the Northeastern United States. The study was retrospective, using collected samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth was primarily established using an FDA-cleared Immunoblot (Focus Diagnostics HerpeSelect® 1 and 2 Immunoblot IgG) as the reference method. For samples that were "repeat Equivocal" on the predicate device, they were sent for Western Blot testing at a Reference Laboratory.
- No specific number of human experts for interpreting the Immunoblot or Western Blot is mentioned, nor are their qualifications. It's implied that these reference methods were performed and interpreted according to their standard operating procedures at designated facilities (a reference laboratory for Western Blot).
4. Adjudication Method for the Test Set
- The primary method of determining the true status of a sample (ground truth) was through an FDA-cleared Immunoblot.
- For equivocal results on the predicate Immunoblot, samples were repeat tested. If still equivocal, they were sent for Western Blot testing. This effectively acts as an adjudication step for indeterminate results from the primary reference method.
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
- No MRMC comparative effectiveness study was done. This study evaluates a laboratory assay (immunoassay) and not an imaging or interpretive AI device that assists human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, a standalone study was done. The LIAISON® HSV-1 Type Specific IgG assay is an automated chemiluminescent immunoassay run on the LIAISON® Analyzer. Its performance (sensitivity, specificity, agreement) was determined directly by comparing its results to a reference method (Immunoblot/Western Blot) without human intervention in the interpretation of the LIAISON® device's raw output.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- The primary ground truth was established by an FDA-cleared Immunoblot.
- For equivocal cases from the Immunoblot, a Western Blot was used as the confirmatory ground truth. Both are laboratory-based diagnostic tests considered highly reliable for HSV-1 type-specific IgG detection.
- Additionally, a CDC panel of characterized serum samples was used to further evaluate agreement.
8. The Sample Size for the Training Set
- The document does not provide information regarding a distinct training set. This is a traditional in vitro diagnostic device, not typically a machine learning or AI-driven system that requires a separate "training set" in the same sense. The device's parameters would have been optimized during its development, likely using internal validation samples, but this information is not detailed in the 510(k) summary.
9. How the Ground Truth for the Training Set was Established
- As no specific training set for a machine learning model is described, the method for establishing its ground truth is not applicable or provided. For a traditional immunoassay, calibration and internal validation would involve characterized samples whose status is known through established reference methods, but specifics are not mentioned here.
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KOr1685
NOV 1 8 2008
DiaSorin LIAISON® HSV-1 Type Specific IgG Premarket Notification K081685
5.0 510(k) SUMMARY
Carol A. DePouw Regulatory Affairs Specialist DiaSorin Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285 Phone (651) 351-5850 Fax (651) 351-5669 Email: carol.depouw@diasorin.com
LIAISON®HSV-1 Type Specific IgG
LIAISON® Control HSV-1 IgG
NAME OF DEVICE Trade Name:
SUBMITTED BY:
Trade Name:
- Common Names/Descriptions: Immunoassay for the detection of specific IgG antibodies to Herpes Simplex Virus Type 1 (HSV-1) in human serum samples.
Classification Names:
Product Code:
PREDICATE DEVICES
Focus Diagnostics HerpeSelect® 1 and 2 Immunoblot IgG (K000238)
Herpes Simplex Virus Serological Reagents
DEVICE DESCRIPTION:
INTENDED USE:
The LIAISON® HSV-1 Type Specific IgG assay is a chemiluminescent immunoassay to be used with the LIAISON® Analyzer for the qualitative determination of type specific lgG antibodies to Herpes simplex virus Type 1 (HSV-1) in human serum. The assay is indicated for testing sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-1 infection.
MXJ, JJX
The LIAISON® HSV-1 Type Specific IgG assay has not been established for use in the pediatrics population, for neonatal screening, or for testing immunocompromised patients. The assay is neither FDA cleared nor approved for testing blood or plasma donors.
The LIAISON® Control HSV-1 (negative and positive) are intended for use as assayed quality control samples to monitor the performance of the LIAISON® HSV-1 Type Specific IqG assay.
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KIT DESCRIPTION:
The method for qualitative determination of specific IgG to HSV-1 is an indirect chemiluminescence immunoassay (CLIA). HSV-1 gG1recombinant antigen is used for coating magnetic particles (solid phase) and a mouse monoclonal antibody is linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation. HSV-1 antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with HSV-1 IgG already bound to the solid phase. After each incubation the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of HSV-1 IgG present in calibrators, samples or controls.
PERFORMANCE DATA:
COMPARATIVE CLINICAL TRIALS:
Studies were conducted which compared the LIAISON® HSV-1 Type Specific IgG assay to an FDA cleared Immunoblot. The studies were conducted on 951 samples collected in the Northeastern United States. The samples were classified as "At risk" samples (n=401) from Sexually Active Adults (at risk for a Sexually Transmitted Disease), Expectant Mothers (n=430) and a Low Prevalence population (n=120) from patients seen at the clinic for anything other than an STD. The studies were conducted at two (2) independent external laboratories.
The sample populations were divided between site 1 and site 2 for LIAISON® HSV-1 testing. Site 1 tested a total of 460 samples (201 Sexually Active Adults. 199 Expectant Mothers and 60 Low Prevalence). Site 2 tested a total of 491 samples (200 Sexually Active Adults, 231 Expectant Mothers and 60 Low Prevalence). Site 3 tested a total of 951 samples (401 Sexually Active Adults, 430 Expectant Mothers and 120 Low Prevalence) with the FDA cleared Immunoblot.
Equivocal samples were repeat tested as per the Instructions for Use. Any repeat Equivocal samples on the predicate device were sent to a Reference Laboratory in the Pacific Northwest for Western Blot testing. The Western Blot results are included in the tables. All results are expressed as sensitivity and specificity with exact 95% Confidence Intervals.
Sexually Active Adults (401)
Four Hundred one (401) samples were obtained from Sexually Active Adults who were seen at STD clinics in the Northeastern US were tested with the LIAISON® HSV-1 Type Specific IgG assay and the HSV-1 predicate method Immunoblot. Results are summarized below.
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| LIAISON®HSV-1 TypeSpecific IgG | Predicate Device | Total | ||
|---|---|---|---|---|
| Positive | 222 | 1 | 12 | 235 |
| Equivocal | 0 | 0 | 2 | 2 |
| Negative | 7 | 0 | 157 | 164 |
| Total | 229 | 1* | 171 | 401 |
| Percent | 95% Confidence Intervals | |
|---|---|---|
| Sensitivity | 96.9% (222/229) | 94.3 - 98.6% |
| Specificity | 91.3% (157/172) | 86.9 - 94.6% |
- This sample was Indeterminate with Western Blot testing
Expectant Mother Population (430)
Four hundred thirty (430) samples collected from Expectant Mothers in the Northeastern US were tested with the LIAISON® HSV-1 Type Specific IgG assay and the HSV-1 predicate method Immunoblot. Results are summarized below.
| LIAISON®HSV-1 TypeSpecific IgG | Predicate Device | Total | ||
|---|---|---|---|---|
| Positive | Equivocal | Negative | ||
| Positive | 236 | 0 | 10 | 246 |
| Equivocal | 0 | 0 | 2 | 2 |
| Negative | 3 | 0 | 179 | 182 |
| Total | 239 | 0 | 191 | 430 |
| Percent | 95% Confidence Intervals | |
|---|---|---|
| Sensitivity | 98.7% (236/239) | 96.8 - 99.7% |
| Specificity | 93.7% (179/191) | 90.0 - 96.3% |
Low Prevalance Population (120)
One hundred twenty (120) "Low Prevalence" samples obtained from individuals who were seen at clinics (not for STD) in the Northeastern US were tested with the LIAISON® HSV-1 Type Specific IgG assay and the HSV-1 predicate method Immunoblot. Results are summarized below.
| LIAISON®HSV-1 TypeSpecific IgG | Predicate Device | Total | ||
|---|---|---|---|---|
| Positive | Equivocal | Negative | ||
| Positive | 60 | 0 | 0 | 60 |
| Equivocal | 1 | 0 | 0 | 1 |
| Negative | 1 | 0 | 58 | 59 |
| 62 | 0 | 58 | 120 |
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| Percent | 95% Confidence Intervals | |
|---|---|---|
| Sensitivity | 96.8% (60/62) | 90.1 - 99.4% |
| Specificity | 100.0% (58/58) | 94.9 - 100.0% |
CDC PANEL:
A serum panel was obtained from the Centers for Disease Control and Prevention and tested by the LIAISON® HSV-1 Type Specific IgG assay. The results are presented as a means of conveying further information on the performance of this assay with a characterized serum panel. This does not imply an endorsement of the assay by the CDC.
The panel consisted of 52% positive and 48% negative samples. The LIAISON® HSV-1 Type Specific IgG assay demonstrated 100% positive agreement with the CDC positive results (52/52) and 93.75% negative agreement with the CDC negative results (45/48). There were three false positive results obtained with the Liaison HSV-1 Type specific assay.
Conclusion: The LIAISON® HSV-1 Type Specific IgG showed equivalent performance to the FDA cleared comparison method.
The results demonstrate that the LIAISON® HSV-1 Type Specific IgG assay can be used with the LIAISON® Analyzer for the qualitative determination of specific IgG antibodies to Herpes Simplex Virus Type 1 in human serum samples.
EXPECTED VALUES:
The prevalence may vary depending upon geographical location, age, gender, type of test employed, specimen collection and handling procedures as well as clinical history of the patient.
The observed and the hypothetical predictive values for the sexually active adults, expectant mothers, and low prevalence populations are shown below. The positive predictive value (PPV) will decrease proportionally to the prevalence of HSV-1 infection as reflected in the table. The calculations are based on LIAISON® HSV-1 positive and negative agreements of 96.9% and 91.3%, respectively, in a sexually active adult population, 98.7% and 93.7%, respectively, in an expectant mothers population, and 96.8% and 100%, respectively, in a low prevalence population.
| Population | Sero-Status | Observed Prevalence | |
|---|---|---|---|
| LIAISON | Predicate | ||
| Sexually Active Adultsa | HSV-1 Negative | 41.0% (164/400) | 42.8% (171/400) |
| HSV-1 Positive | 58.5% (234/400) | 57.3% (229/400) | |
| Expectant Mothersb | HSV-1 Negative | 42.5% (182/428) | 44.2% (189/428) |
| HSV-1 Positive | 57.5% (246/428) | 55.8% (239/428) | |
| Low Prevalencec | HSV-1 Negative | 49.6% (59/119) | 48.7% (58/119) |
| HSV-1 Positive | 50.4% (60/119) | 51.3% (61/119) |
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- a Excludes 1 Indeterminate by Predicate
- 6 Excludes 2 Equivocal by LIAISON
° Excludes 1 Equivocal by LIAISON
| Prevalence | Sexually Active Adults | Expectant Mothers | Low Prevalence | |||
|---|---|---|---|---|---|---|
| PPV | NPV | PPV | NPV | PPV | NPV | |
| 80% | 97.8% | 88.0% | 98.4% | 94.7% | 100% | 88.7% |
| 70% | 96.3% | 92.7% | 97.3% | 96.9% | 100% | 93.1% |
| 60% | 94.4% | 95.2% | 95.9% | 98.0% | 100% | 95.4% |
| 50% | 91.8% | 96.7% | 94.0% | 98.6% | 100% | 96.9% |
| 40% | 88.1% | 97.8% | 91.3% | 99.1% | 100% | 97.9% |
| 30% | 82.7% | 98.6% | 87.0% | 99.4% | 100% | 98.6% |
| 20% | 73.6% | 99.2% | 79.7% | 99.7% | 100% | 99.2% |
| 10% | 55.3% | 99.6% | 63.5% | 99.8% | 100% | 99.6% |
HSV-1 Prevalence vs. Hypothetical Predictive Values
REPRODUCIBILITY:
A reproducibility/precision study was conducted at two external laboratories and at DiaSorin Inc. This study included 3 LIAISON® HSV-1 Type Specific IgG Specific IgG Reagent Integral kit lots and 3 LIAISON® Analyzers. Each site used a different lot of the LIAISON® HSV-1 Type Specific IgG for the study.
A coded panel comprised of 8 frozen "engineered" serum samples was prepared by DiaSorin Inc. and provided to the sites. The coded panel samples were prepared using neat positive serum or by blending positive and negative serum samples to achieve high negative, equivocal, low positive and high positive results. The LIAISON® Control HSV-1 set were also included in the 5 day study. All panel members were divided into aliquots and stored frozen prior to testing. The CLSI document EP15-A2 was consulted in the preparation of the testing protocol.
The coded panel was tested at all three sites, using four replicates per run in two runs per day with different operators performing each run during five operating days. The mean, standard deviation, and coefficient of variation (%CV) of the results were computed for each of the tested specimens for each of the sites and across sites,
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| SampleID | N | MeanIndex | Withinrun%CV | Betweenrun%CV | Total(by site)%CV | Betweensite%CV | OverallSD | Overall%CV |
|---|---|---|---|---|---|---|---|---|
| NC | 120 | 0.15 | 4.3 | 5.3 | 7.0 | 14.4 | 0.02 | 14.9 |
| PC | 120 | 2.31 | 3.6 | 5.6 | 6.2 | 11.2 | 0.28 | 12.0 |
| HSV1A | 120 | 1.92 | 5.2 | 7.5 | 8.3 | 10.6 | 0.25 | 12.9 |
| HSV1B | 120 | 1.29 | 2.6 | 5.7 | 5.9 | 13.5 | 0.18 | 13.8 |
| HSV1C | 120 | 1.09 | 2.4 | 4.7 | 5.1 | 12,5 | 0.14 | 12.7 |
| HSV1D | 120 | 63.8 | 3.8 | 4.7 | 6.4 | 8.4 | 6.43 | 10.1 |
| HSV1E | 120 | 0.85 | 2.7 | 4.8 | 5.2 | 10.8 | 0.10 | 11.3 |
| HSV1F | 120 | 0.88 | 2.8 | 5.7 | 6.1 | 11.6 | 0.11 | 12.3 |
| HSV1G | 120 | 1.20 | 4.1 | 6.6 | 7.9 | 12.8 | 0.17 | 14.4 |
| HSV1H | 120 | 1.35 | 3.4 | 5.8 | 6.7 | 13.6 | 0.19 | 14.3 |
CONCLUSION:
The material submitted in this premarket notification is complete and supports a substantial equivalence decision. The labeling is sufficient and it satisfies the requirements of 21CFR 809.10
:
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Carol DePouw Regulatory Affairs Specialist Diasorin Inc. 1951 Northwestern Avenue P. O. Box 285 Stillwater, MN 55082-0285
NOV 1 8 2008
NOV 1 8 2008
Re: K081685
Trade/Device Name: LIAISON® HSV-1 Type Specific IgG Assay Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes Simplex Virus serological reagents Regulatory Class: Class II Product Code: MXJ, JJX Dated: October 9, 2008 Received: October 10, 2008
Dear Ms. DePouw:
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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 --
This letter will allow you to begin marketing your device as described in your Section 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), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or ' (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Sally attayna
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indication for Use
510(k) Number (if known); K081685
Device Name:
Indications For Use:
LIAISON® HSV-1 Type Specific IgG and LIAISON® Control HSV-1 IgG
The LIAISON® HSV-1 Type Specific IgG assay is a chemiluminescent immunoassay (CLIA) to be used with the LIAISON® Analyzer for the qualitative determination of type specific IgG antibodies to Herpes Simplex Virus Type 1 (HSV-1) in human serum, The assay is indicated for testing sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-1 infection.
The LIAISON® HSV-1 Type Specific IgG assay has not been established for use in the pediatrics population, for neonatal screening, or for testing immunocompromised patients. The assay is neither FDA cleared nor approved for testing blood or plasma donors.
The LIAISON® Control HSV-1 (negative and positive) are intended for use as assayed quality control samples to monitor the performance of the LIAISON® HSV-1 Type Specific IgG assay.
Prescription Use X (21 CFR Part 801 Subpart D)
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
And/Or
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (QVD)
Uhe Schif
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K081685
§ 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).