(56 days)
Elecsys HSV-2 IgG Immunoassay: The Roche Elecsys HSV-2 IgG immunoassay is a test for the in vitro qualitative determination of IgG class antibodies to HSV-2 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 presumptive diagnosis of HSV-2 infection. The predictive value of positive or negative results depends on the population's prevalence and the pretest likelihood of HSV-2. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the indicated 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 and immunocompromised patients or for use at point of care facilities.
Elecsys PreciControl HSV: The Elecsys PreciControl HSV is used for quality control of the Elecsys HSV-2 IgG immunoassay on the Elecsys and cobas e immunoassay analyzers.
(1) Elecsys HSV-2 IgG is a two-step sandwich immunoassay with streptavidin microparticles, biotinylated recombinant HSV-2-specific antigen labeled with a ruthenium complex and electrochemiluminescence detection. This assay is a qualitative test based on a cut-off formula dependent on the negative and positive calibrators. Cut-off index (COI) is based on the ratio of assay signal to cut-off signal (also abbreviated s/co). COI values greater than or equal to 1.0 are considered positive for the presence of anti-HSV-2 IgG antibody. Results are determined using a two-point calibration. The test system contains the human serum-based calibrators intended for use with the system.
(2) Elecsys PreciControl HSV contains lyophilized control serum based on human serum. The controls are used for monitoring the accuracy of the Elecsys HSV-2 IgG immunoassay.
The provided 510(k) summary describes the Elecsys HSV-2 IgG Immunoassay and Elecsys PreciControl HSV. The document focuses on establishing substantial equivalence to a predicate device, rather than defining explicit acceptance criteria and a detailed study proving the device meets those criteria in a typical clinical trial format for a novel device.
However, based on the information provided, we can infer performance characteristics and study details that serve a similar purpose for an IVD (In Vitro Diagnostic) device submission.
Here's the breakdown of the information requested:
1. Table of Acceptance Criteria (Inferred from Performance Data) and Reported Device Performance
For an IVD device, acceptance criteria are often defined by demonstrating performance comparable to a legally marketed predicate device, or by meeting certain analytical performance targets for sensitivity, specificity, and agreement. The document frequently compares the candidate device's performance to the predicate device and CDC panel.
| Acceptance Criteria (Inferred) | Reported Device Performance (Elecsys HSV-2 IgG Immunoassay) |
|---|---|
| Sensitivity/Positive Percent Agreement (PPA) | |
| Expectant Mother Cohort: High PPA (e.g., >95%) | 97.83% (95% CI: 88.47-99.94%) |
| Sexually Active Cohort: High PPA (e.g., >90%) | 93.63% (95% CI: 88.60-96.90%) |
| Low Prevalence Cohort: Agreement commensurate with prevalence | 75.00% (95% CI: 19.41-99.37%) |
| Specificity/Negative Percent Agreement (NPA) | |
| Expectant Mother Cohort: High NPA (e.g., >95%) | 98.73% (95% CI: 93.15-99.97%) |
| Sexually Active Cohort: High NPA (e.g., >95%) | 98.72% (95% CI: 96.75-99.65%) |
| Low Prevalence Cohort: High NPA (e.g., >95%) | 98.47% (95% CI: 95.59-99.68%) |
| Agreement with CDC Panel | 100% |
| Analytical Specificity (Cross-Reactivity) | 100% agreement with comparator assay for 311 HSV-2-negative specimens with various cross-reactants. |
| Precision | |
| Intra-assay: Low SD/CV | Low Control: SD 0.005 COI; High Control: CV 1.3% |
| Inter-assay: Low SD/CV | Low Control: SD 0.010 COI; High Control: CV 3.3% |
| Serum Samples: Low SD/CV | 0.8 COI: CV 1.2 - 1.6% (Intra-assay), CV 2.8 - 3.6% (Inter-assay) |
| Interference | Unaffected by icterus, hemolysis, lipemia, biotin, rheumatoid factor, and various pharmaceuticals (including Famciclovir, Acyclovir, Valacyclovir). |
2. Sample Size Used for the Test Set and Data Provenance
The document describes several cohorts used for performance evaluation:
- Expectant Mother Cohort: n = 125
- Sexually Active Cohort: n = 469
- Low Prevalence Cohort: n = 200
- Analytical Specificity Cohort: 311 HSV-2-negative specimens positive for various cross-reactants.
The data provenance (e.g., country of origin, retrospective/prospective) is not explicitly stated in the provided text. It is common for such clinical performance studies for IVDs to use a mix of retrospective and prospective samples collected from diverse populations, but this specific information is missing here.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document mentions "Agreement with CDC Panel" for which 100% agreement was demonstrated.
For the other performance metrics (Positive Percent Agreement, Negative Percent Agreement), the comparison is made against the Focus HerpeSelect 1 and 2 Immunoblot IgG (K000238), which serves as the comparator or "ground truth" for these studies, referred to as "Relative Sensitivities to Western Blot" and "Relative Specificity to Western Blot."
The document does not specify the number of experts or their qualifications used to establish the ground truth for the test set, other than the implicit expertise associated with a "CDC Panel" and the established nature of the predicate device (HerpeSelect 1 and 2 Immunoblot). The predicate device itself relies on qualitative band comparison, which typically involves trained laboratory personnel interpreting the results.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method (like 2+1, 3+1) for the interpretation of results in the test set. For IVD devices, especially those with quantitative or semi-quantitative outputs like a Cut-off Index (COI), the result interpretation is typically based on predefined thresholds and calculations rather than subjective expert consensus on each case. The "ground truth" often refers to the result obtained from a gold standard or predicate method.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
A MRMC comparative effectiveness study, which typically evaluates how much human readers improve with AI vs. without AI assistance, is not mentioned or implied. This device is an in vitro diagnostic immunoassay, meaning it directly measures biomarkers in a sample and produces a result (reactive/non-reactive). It's not an imaging or interpretation assistance device where human readers interact with AI output in a diagnostic workflow.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, the studies presented are effectively standalone performance studies. The Elecsys HSV-2 IgG Immunoassay operates as an automated system ("ECLIA" on Elecsys and cobas e immunoassay analyzers). The performance characteristics reported (PPA, NPA, analytical specificity, precision) reflect the device's inherent ability to correctly classify samples based on its internal algorithm and detection method. There is no human-in-the-loop component for result interpretation for a qualitative immunoassay. The device determines if a sample is reactive or non-reactive based on its COI value.
7. Type of Ground Truth Used
The primary ground truth used for performance evaluation appears to be:
- Predicate Device/Comparator Assay: The Focus HerpeSelect 1 and 2 Immunoblot IgG (K000238), described as "Relative Sensitivities to Western Blot" and "Relative Specificity to Western Blot." Western Blot is generally considered a highly specific and often used gold standard for HSV-2 serology.
- CDC Panel: A smaller reference panel from the CDC, against which the device showed 100% agreement.
8. Sample Size for the Training Set
The document does not specify a separate training set size. For IVD devices, especially those based on established immunoassay principles, the "training" (development and optimization) often happens during assay design, reagent formulation, and calibration curve development. The clinical performance data presented here would generally be considered external validation or test set performance, not a training set for an AI/machine learning algorithm.
9. How the Ground Truth for the Training Set Was Established
Since a distinct "training set" in the context of an AI/ML algorithm is not described, the method for establishing its ground truth is not applicable/not provided. The ground truth for the overall assay development and validation would have been established through a combination of well-characterized clinical samples and comparison to established gold standard methods or predicate devices, as seen with the predicate device and CDC panel used for the test set.
§ 862.1660 Quality control material (assayed and unassayed).
(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.