← Product Code [MXJ](/submissions/MI/subpart-d%E2%80%94serological-reagents/MXJ) · K220923 # Elecsys HSV-1 IgG (08948844160) (K220923) _Roche Diagnostics · MXJ · Oct 12, 2022 · Microbiology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/MXJ/K220923 ## Device Facts - **Applicant:** Roche Diagnostics - **Product Code:** [MXJ](/submissions/MI/subpart-d%E2%80%94serological-reagents/MXJ.md) - **Decision Date:** Oct 12, 2022 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 866.3305 - **Device Class:** Class 2 - **Review Panel:** Microbiology ## Indications for Use lmmunoassay for the in vitro qualitative determination of IgG class antibodies to HSV-1 in human serum and lithium-hepain plasma, K2-EDTA plasma, and K3-EDTA plasma. The test is intended for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-1 infection. The test results may not determine the state of active lesions or associated disease manifestations, particularly for primary infection. The predictive value of positive and negative results depends on the population's prevalence and the pretest likelihood of HSV-1. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers. This test is not FDA-cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates, immunocompromised patients, or for use at point-of-care facilities. ## Device Story In vitro diagnostic immunoassay for qualitative detection of HSV-1 IgG antibodies in human serum/plasma. Uses sandwich test principle with biotinylated recombinant HSV-1 antigens and ruthenium-labeled recombinant HSV-1 antigens. Operates on cobas e immunoassay analyzers via electrochemiluminescence (ECLIA). Software automatically calculates results by comparing sample signal to calibrated cutoff value. Used in clinical laboratories; results interpreted by physicians to aid in presumptive diagnosis of HSV-1 infection. Does not determine active lesion state or primary infection status. Benefits include standardized serological assessment for sexually active individuals and expectant mothers. ## Clinical Evidence No clinical data provided. Substantial equivalence supported by non-clinical bench testing demonstrating improved biotin tolerance and reduced streptavidin interference. ## Technological Characteristics Sandwich immunoassay using biotinylated and ruthenium-labeled recombinant HSV-1 antigens. Electrochemiluminescence (ECLIA) detection. Reagents include biotin-depleting agent and streptavidin interference reducing agent. Designed for use on cobas e immunoassay analyzers. ## Regulatory 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. ## Special Controls *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). ## Predicate Devices - Elecsys Hsv-1 Igg Immunoassay ([K120625](/device/K120625.md)) ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} FDA U.S. FOOD & DRUG ADMINISTRATION # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY ## I Background Information: A 510(k) Number K220923 B Applicant Roche Diagnostics C Proprietary and Established Names Elecsys HSV-1 IgG (08948844160) D Regulatory Information | Product Code(s) | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | MYF | Class II | 21 CFR 866.3305 - Herpes Simplex Virus Serological Assays | MI - Microbiology | ## II Submission/Device Overview: ### A Purpose for Submission: Market clearance for a previously cleared assay to detect antibodies to Herpes Simplex HSV-1 IgG in human serum and plasma that has been modified to: - remove analyzer not supported by Roche “Modular Analytics E170” - increase biotin tolerance - reduce streptarvidin interference ### B Measurand: Antibodies to Herpes Simplex Virus HSV-1 IgG ### C Type of Test: A qualitative antigen sandwich electrochemiluminescence immunoassay “ECLIA” Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} K220923 - Page 2 of 8 ## III Intended Use/Indications for Use: ### A Intended Use(s): Immunoassay for the in vitro qualitative determination of IgG class antibodies to HSV-1 in human serum and lithium heparin plasma, K2 EDTA plasma, and K3 EDTA plasma. The test is intended for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-1 infection. The test results may not determine the state of active lesions or associated disease manifestations, particularly for primary infection. The predictive value of positive and negative results depends on the population's prevalence and the pretest likelihood of HSV-1. The electrochemiluminescence immunoassay “ECLIA” is intended for use on cobas e immunoassay analyzers. This test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates, immunocompromised patients, or for use at point of care facilities. ### B Indication(s) for Use: Same as Intended use ### C Special Conditions for Use Statement(s): Rx - For Prescription Use Only ### D Special Instrument Requirements: For use with cobas e 411 ## IV Device/System Characteristics: ### A Device Description: The Elecsys HSV-1 IgG immunoassay makes use of a sandwich test principle using biotinylated recombinant HSV-1-specific antigens and HSV-1-specific recombinant antigens labeled with a ruthenium complex. The Elecsys HSV-1 IgG immunoassay is intended for the qualitative determination of IgG class antibodies to HSV-1 in human serum and plasma to aid in the presumptive diagnosis of HSV-1 infection. It is intended for use on the cobas e immunoassay analyzers. Results are determined automatically by the software by comparing the electrochemiluminescence signal obtained from the reaction product of the sample with the signal of the cutoff value previously obtained by calibration. Interpretation of the results: The cutoff for the Elecsys HSV-1 IgG assay was initially established by measuring a total of 269 serum samples from two cohorts: sexually active adults and pregnant women. The distribution of positive and negative results were compared with the predicate assay, an FDA-cleared {2} immunoblot. The cutoff was set as noted below. The result of a sample is given in the form of a cutoff index (signal sample/cutoff). Results obtained with the Elecsys HSV-1 IgG assay are interpreted as follows: Non-reactive: < 1.0 COI Reactive: ≥ 1.0 COI Samples with a cutoff index < 1.0 are non-reactive in the Elecsys HSV-1 IgG assay. These samples are considered negative for HSV-1 IgG-specific antibodies and do not need further testing. Samples with a cutoff index ≥ 1.0 are considered reactive in the Elecsys HSV-1 IgG assay. The HSV-1 IgG results for a given specimen, as determined by assays from different manufacturers, can vary due to differences in reagents and assay methods. If control results are out of their specified range, no patient results should be reported. ## B Principle of Operation: Sandwich principle. Total duration of assay: 18 minutes. - 1st incubation: 20 μL of sample, biotinylated recombinant HSV-1-specific antigens, and HSV-1-specific recombinant antigens labeled with a ruthenium complex⁽ᵃ⁾ form a sandwich complex. - 2nd incubation: After addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin. - The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier. - Results are determined automatically by the software by comparing the electrochemiluminescence signal obtained from the reaction product of the sample with the signal of the cutoff value previously obtained by calibration. ## V Substantial Equivalence Information: ### A Predicate Device Name(s): Elecsys Hsv-1 Igg Immunoassay ### B Predicate 510(k) Number(s): K120625 ### C Comparison with Predicate(s): K220923 - Page 3 of 8 {3} Table 1 | Device & Predicate Device(s): | Elecsys HSV-1 IgG K220923 | Elecsys HSV-1 IgG K120625 | | --- | --- | --- | | | | | | Indications for Use | Immunoassay for the in vitro qualitative determination of IgG class antibodies to HSV-1 in human serum and lithium heparin plasma, K2 EDTA plasma, and K3 EDTA plasma. The test is intended for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-1 infection. The test results may not determine the state of active lesions or associated disease manifestations, particularly for primary infection. The predictive value of positive and negative results depends on the population's prevalence and the pretest likelihood of HSV-1. The electrochemiluminescence immunoassay “ECLIA” is intended for use on cobas e immunoassay analyzers. This test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates, immunocompromised patients, or for use at point of care facilities. | Immunoassay for the in vitro qualitative determination of IgG class antibodies to HSV-1 in human serum and lithium-heparin plasma, K2-EDTA plasma, and K3-EDTA plasma. The test is intended for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-1 infection. The predictive value of positive and negative results depends on the population's prevalence and the pretest likelihood of HSV-1. The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. This test is not FDA-cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates, immunocompromised patients, or for use at point-of-care facilities. | | Technology | Same | ECLIA | | Test format | Same | Sandwich | | Test type | Same | qualitative | | Application time | Same | 18 min | | Buffer Composition R2 | Same | 2-morpholino-ethane sulfonic acid | | | Same | Stabilizer: Bovine serum albumin | | | Same | Preservatives | K220923 - Page 4 of 8 {4} | | | N-Methylisothiazolone Oxy-PYRION | | --- | --- | --- | | Reporting of values | Same | COI and result message (non-reactive) < 1.0 COI = non-reactive ≥ 1.0 COI = reactive | | Calibrators | Same | HSV-1 Cal1 / HSV-1 Cal2 | | Control material | Same | PreciControl HSV | | Antigens used in R2 | Antigen Same | Ruthenium-complex labeled antigen (recombinant, E. coli) | | General Device Characteristic Differences | | | | Antibodies used in R2 | Anti-Biotin antibody specific for free, unconjugated biotin (“scavenger antibody“) in R2 | None | | Streptavidin interference reducing agent | SA Mutein Poly | None | | SA interference elimination | Yes, optimized | No | | Biotin tolerance | ≤ 1200 ng/mL | <70 ng/mL | | Instrument Platform | cobas e 411 | cobas e 411, e 601, e 602, Modular Analytics E 170 | VI Standards/Guidance Documents Referenced: - CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - 3rd Edition. - CLSI EP07-3rd edition: Interference Testing in Clinical Chemistry - CLSI EP09c 3rd edition: Measurement Procedure Comparison and Bias Estimation Using Patient Samples - Elecsys HSV-1 IgG, product code MXJ, follows Special Control "Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays" issued August 9, 2011. VII Performance Characteristics (if/when applicable): A Analytical Performance: A limited number of studies were conducted to verify the assay performance cleared under K120625 was not affected by the changes made to improve tolerance to elevated levels of biotin. K220923 - Page 5 of 8 {5} # 1. Precision/Reproducibility: # a. Repeatability and intermediate precision studies: Precision was determined on the cobas e 411 analyzer using Elecsys reagents and controls in a protocol (EP05-A3) of the CLSI (Clinical and Laboratory Standards Institute). Results were generated from 5 human serum samples (covering a range of negative, near cut-off, and positive values), and 2 controls assayed in 2 runs per day in duplicate each for 21 days $(n = 84)$ . The following results were obtained: Table 2. Repeatability and Intermediate precision | cobas e 411 analyzer | | | | | | | --- | --- | --- | --- | --- | --- | | | | Repeatability | | Intermediate precision | | | Sample | Mean COIa) | SDf) COI | CV % | SD COI | CV % | | HSe) 1 | 0.029 | 0.001 | 1.6 | 0.001 | 1.9 | | HS 2 | 12.4 | 0.168 | 1.4 | 0.239 | 1.9 | | HS 3 | 43.1 | 0.532 | 1.2 | 0.839 | 1.9 | | HS 4 | 1.07 | 0.011 | 1.0 | 0.018 | 1.7 | | HS 5 | 0.859 | 0.008 | 0.9 | 0.012 | 1.4 | | PCb) HSV_1 | 0.248 | 0.002 | 0.9 | 0.004 | 1.5 | | PC HSV_2 | 4.26 | 0.040 | 0.9 | 0.076 | 1.8 | a) $\mathrm{COI} =$ cutoff index b) SD = standard deviation c) HS = human serum d) PC = PreciControl # b. Reproducibility study: See K120625 # 2. Linearity: Not applicable; this is a qualitative assay. # 3. Analytical Specificity/Interference: Potential interference of the analyte in the presence of biotin using the updated Elecsys HSV-1 IgG assay was determined by testing three serum samples (negative, near cut-off, positive) on the cobas e 411 immunoassay analyzer. One aliquot of each sample was spiked with the interfering substance (biotin) and another aliquot was spiked with the same volume of the respective solvent (dilution pool). The interfering pool was then incrementally diluted into K220923 - Page 6 of 8 {6} the dilution pool. The recovery for each sample was calculated by comparison to the analyte concentration of the respective dilution pools. The results of the study support the following statement in the assay labeling: "Serum samples that contain biotin at a concentration of 1200 ng/mL demonstrate less than or equal to 10 % negative bias in COI values" For complete endogenous interference study results see K120625 4. Assay Reportable Range: See K120625 5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods): a. On-board Reagent Stability: The claimed on-board reagent stability study of 28-days reported in K120625 was confirmed for the updated Elecsys HSV-1 IgG assay. b. Lot Calibration Stability: The claimed lot calibration stability of 12 weeks reported in K120625 was confirmed for the updated Elecsys HSV-1 IgG assay. 6. Detection Limit: See K120625 7. Assay Cut-Off: See K120625 ## B Comparison Studies: 1. Method Comparison with Predicate Device: A method comparison study was conducted to confirm the updated assay shows equivalent performance compared to the originally cleared assay (K120625). The results obtained from 204 samples distributed across the span of the reportable range were measured internally with one reagent lot of the current assay and three different reagent lots of the updated assay in single determination. The study showed 100% agreement of the qualitative results, and regression analysis of the COI values demonstrated acceptable concordance between the assays. The results of the original method comparison study are found in K120625. 2. Matrix Comparison: K220923 - Page 7 of 8 {7} See K120625 ## C Clinical Studies: 1. Clinical Sensitivity: See K120625 2. Clinical Specificity: See K120625 3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Not applicable ## D Clinical Cut-Off: See K120625 ## E Expected Values/Reference Range: See K120625 ## VIII Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. ## IX Conclusion: The submitted information in this premarket notification K220923 is complete and supports a substantial equivalence decision. K220923 - Page 8 of 8 --- **Source:** [https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/MXJ/K220923](https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/MXJ/K220923) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com