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510(k) Data Aggregation
(209 days)
LFZ
The ARCHITECT CMV IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of IgG antibodies to cytomegalovirus in human serum, serum separator, and plasma tubes (lithium heparin, lithium heparin separator, and tripotassium EDTA) on the ARCHITECT i System.
The ARCHITECT CMV IgG assay is to be used as an aid in the diagnosis of infection with cytomegalovirus and as an aid in the determination of serological status to cytomegalovirus in individuals including women of child-bearing age.
The ARCHITECT CMV IgG assay has not been cleared for use in screening blood, plasma, or tissue donors.
The ARCHITECT CMV IgG assay is a chemiluminescent microparticle immunoassay (CMIA) for the qualitative detection of IgG antibodies to cytomegalovirus. The reagent kit contains microparticles coated with CMV virus lysate, murine anti-human IgG acridinium-labeled conjugate, and assay diluent. The assay is performed on the ARCHITECT i System. The presence or absence of anti-CMV IgG is determined by comparing the chemiluminescent relative light unit (RLU) in the reaction to a cutoff RLU from an active calibration.
Here's an analysis of the acceptance criteria and study information for the ARCHITECT CMV IgG device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical targets in the document. However, based on the non-clinical and clinical performance summaries, we can infer performance goals for the device's accuracy and precision. The "Predicate Device" (ADVIA Centaur CMV IgG Assay, K181213) serves as a benchmark for substantial equivalence.
| Performance Metric | Acceptance Criteria (Inferred from Study Design & Predicate Equivalence) | Reported Device Performance (ARCHITECT CMV IgG) |
|---|---|---|
| Within-Laboratory Precision (Repeatability) | Low variability; %CV values typically +0.6 AU/mL) noted for Triglycerides at 2475 mg/dL on 4.0 AU/mL sample. | |
| Drugs/Other Substances: No significant interference observed for Acetaminophen, Ascorbic Acid, Beta Carotene, Biotin, Cidofovir, Diphenhydramine, Folic Acid, Foscarnet, Gangciclovir, Ibuprofen, Valganciclovir. | ||
| Analytical Specificity (Other Conditions) | Low rate of false positives/reactives with specimens from individuals with unrelated medical conditions. | 1 reactive result out of 187 specimens tested across various medical conditions (Toxoplasmosis (IgG) specimen was reactive). 1 equivocal parvovirus B19 (IgG) specimen. |
| CDC Panel Agreement (Positive) | High positive percent agreement, ideally >90% | 100% (91.59%, 100%) |
| CDC Panel Agreement (Negative) | High negative percent agreement, ideally >90% | 92.11% (78.62%, 98.34%) |
| CDC Panel Agreement (Overall) | High overall percent agreement, ideally >90% | 96.25% (89.43%, 99.22%) |
| Clinical Percent Agreement (Positive) - Routine Order | High positive percent agreement with comparator, ideally >90% | 97.7% (96.1%, 98.7%) |
| Clinical Percent Agreement (Negative) - Routine Order | High negative percent agreement with comparator, ideally >90% | 99.2% (97.3%, 99.8%) |
| Clinical Percent Agreement (Positive) - Pregnant Females | High positive percent agreement with comparator, ideally >90% | 99.0% (94.5%, 99.8%) |
| Clinical Percent Agreement (Negative) - Pregnant Females | High negative percent agreement with comparator, ideally >90% | 100.0% (96.4%, 100.0%) |
2. Sample Size Used for the Test Set and Data Provenance
- Within-Laboratory Precision (20-Day): 117-120 replicates per panel/control across 3 reagent lots/calibrator lot combinations.
- Analytical Specificity (Interference): Not explicitly stated, but each substance was tested at 3 analyte levels.
- Analytical Specificity (Other Conditions): 187 specimens.
- CDC Panel Agreement: 80 samples (either CMV IgG negative or CMV IgG positive). Data provenance is the Centers for Disease Control and Prevention (CDC). The document doesn't specify if this was retrospective or prospective, but the description "masked, characterized serum panel" suggests it was a curated, retrospective panel.
- Clinical Percent Agreement:
- Routine Order: 591 specimens collected in the US and 198 specimens collected outside of the US.
- Pregnant Females: 200 specimens collected in the US.
- Further Evaluation: 4 specimens (3 routine order, 1 pregnant female) with equivocal/grayzone results by the comparator assay.
- Data provenance for the clinical study is multi-site (Indianapolis Indiana, Lewisville Texas, and Palo Alto California) for the US samples, and unspecified international locations for the "outside of the US" routine order specimens. This was a clinical study (method comparison), suggesting prospective collection relative to the comparison against the investigational assay.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
There is no information provided about experts being used to establish a ground truth for the test set in the conventional sense (e.g., for image interpretation).
- For the CDC Panel Agreement, the CDC provided "their result interpretation for each sample," implying the CDC's own characterization (likely by reference methods/consensus) served as the ground truth. No specific number or qualifications of experts are given.
- For the Clinical Percent Agreement, the ground truth was established by a "current, FDA-cleared, commercially available anti-CMV IgG assay" (the comparator assay), essentially establishing a reference standard from an already approved diagnostic device. For 4 equivocal/grayzone samples, "consensus testing" with "2 additional current, FDA-cleared, commercially available anti-CMV IgG assays" was used. The document does not mention human experts establishing ground truth for these studies.
4. Adjudication Method for the Test Set
- CDC Panel Agreement: The results were compared directly to CDC's result interpretation. No explicit adjudication method is described beyond this direct comparison.
- Clinical Percent Agreement: The primary comparison was against a single comparator assay. For specific equivocal/grayzone cases (4 specimens), a form of adjudication was used where the result was "negative by consensus testing" or "negative based on the consensus result from the comparator assay and 2 additional current, FDA-cleared, commercially available anti-CMV IgG assays." This implies a form of multi-comparator consensus for ambiguous cases, but not necessarily human expert adjudication in the traditional sense.
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 device is an automated in vitro diagnostic (IVD) assay (chemiluminescent microparticle immunoassay), not an AI-powered diagnostic imaging device or tool that assists human readers. Therefore, the concepts of human readers, AI assistance, and effect size in improving human reader performance are not applicable.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
The device itself, the ARCHITECT CMV IgG assay on the ARCHITECT i System, is a standalone algorithm/device for qualitative detection. Its performance is evaluated entirely as an automated system without human interpretation in the loop influencing the direct output of IgG antibody detection. The "human-in-the-loop" would be the clinician interpreting the result provided by the device (e.g., Reactive, Nonreactive, Grayzone/Equivocal) in the context of a patient's overall clinical picture, but not in generating the result itself.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- CDC Panel Agreement: Ground truth was based on CDC's own "result interpretation" of their characterized serum panel. This likely represents a highly robust reference method or internal consensus.
- Clinical Percent Agreement: Ground truth was primarily established by a "current, FDA-cleared, commercially available anti-CMV IgG assay" (comparator assay). For a few ambiguous cases, consensus results from multiple FDA-cleared comparator assays were used. This is a form of reference method comparison.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI. As this is a traditional immunoassay, it undergoes development and validation using various biological samples. However, no specific number is provided for samples used during the development or optimization phases that could be analogized to a training set. The clinical study samples described are specifically for performance evaluation (test set).
9. How the Ground Truth for the Training Set Was Established
As no explicit training set is defined (because it's not an AI/ML device), this question is not applicable. The assay's parameters (e.g., cutoff values) would have been established during product development using a large set of characterized samples and optimized for performance, but this is a different process than establishing ground truth for an AI training set.
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(197 days)
LFZ
The Elecsys CMV IgG assay is an in vitro qualitative test for the detection of IgG antibodies to CMV in human serum, lithium-heparin plasma, K2-EDTA plasma, and K3-EDTA plasma. The test is intended as an aid in the determination of the serological status to CMV in individuals in which a CMV IgG test was ordered, including pregnant women.
Performance characteristics have not been evaluated in immunocompromised or immunosuppressed individuals. This test is not intended for use in neonatal screening or for use at point of care facilities. This test is not intended for use in screening blood and plasma donors.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
Elecsys CMV IgG is a two-step sandwich immunoassay with streptavidin microparticles, biotinylated recombinant CMV-specific antigen labeled with a ruthenium complex and electrochemiluminescence detection. The results are determined using a calibration curve which is instrument-specifically generated by a 2-point calibration and a master curve provided via the reagent bar code. Results greater than or equal to 1.0 U/mL are considered reactive CMV IgG antibody. The test system contains the human serum-based calibrators intended for use with the system.
Elecsys PreciControl CMV lgG contains liquid control serum. The controls are used for monitoring the accuracy of the Elecsys CMV IgG immunoassay.
Note: The reagent and calibrators are packaged together in the Elecsys CMV lgG assay kit, while the associated is packaged separately.
Here's an analysis of the provided text regarding the Elecsys CMV IgG device, structured according to your requested information:
Elecsys CMV IgG Device Acceptance Criteria and Supporting Study
The provided 510(k) summary details the performance evaluation of the updated Elecsys CMV IgG assay.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state a quantitative "acceptance criteria" table with specific thresholds (e.g., "sensitivity ≥ X%", "specificity ≥ Y%"). Instead, it describes various studies conducted and concludes that "All performance specifications were met." and "The analytical studies demonstrate that the device is as safe, as effective, and performs as well as the legally marketed predicate device with improved biotin tolerance level up to 1200 ng/mL."
However, based on the studies described, we can infer performance aspects and reported outcomes:
| Study Type | Implicit Acceptance Criteria/Goal | Reported Device Performance |
|---|---|---|
| Precision | Demonstrate acceptable repeatability and intermediate imprecision. | Repeatability and Intermediate imprecision were calculated according to CLSI EP05-A3. (No specific values provided, but stated that "All performance specifications were met.") |
| Biotin Interference | Achieve improved biotin tolerance; ensure no significant interference below a certain concentration. | Maximum value with no interference observed was 2400 ng/mL. The method sheet will be set to 1200 ng/mL. (Improvements from ≤ 100 ng/mL to ≤ 1200 ng/mL compared to the predicate.) |
| Method Comparison to Predicate | Demonstrate substantial equivalence between the updated assay and the predicate (K131605). | Positive Agreement and Negative Agreement were calculated. "The resulting data support the equivalence of the current non-biotin and biotin-updated assay." (No specific agreement percentages provided, but equivalence was concluded.) |
| Stability | Maintain performance over time under specified conditions. | "The stability data supports Roche Diagnostic's claims as reported in the package labeling." (No specific duration or performance metrics provided, but claims were supported.) |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Study:
- Sample Size: "3 levels of controls and 5 human serum samples per run, 2 runs per day for 21 days." This totals (3 controls + 5 samples) * 2 runs * 21 days = 336 individual measurements (or 21 days of testing on 8 distinct samples).
- Data Provenance: The text states "human serum samples" and "native human serum pools" for interference studies, implying human origin. No specific country of origin is mentioned. The studies are described as internal performance evaluations, which are typically prospective for the device under development.
- Biotin Interference Study:
- Sample Size: "three serum samples (negative, positive close to cut-off, positive)" were used, each subjected to "11 dilution steps." This amounts to 3 samples * 11 dilutions = 33 individual sample preparations for testing.
- Data Provenance: "Native human serum pools" and "a single serum donor." No specific country of origin or retrospective/prospective nature is stated, but it's an analytical study, likely prospective.
- Method Comparison to Predicate:
- Sample Size: "A total of 280 samples."
- Data Provenance: Not specified, but likely human serum/plasma samples. The study is analytical and likely prospective.
General Note on Data Provenance: For all studies, the document does not specify the country of origin of the data or explicitly state if the studies were retrospective or prospective, though the nature of these analytical performance studies suggests they were conducted prospectively as part of the device development and validation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The device is an in vitro diagnostic (IVD) for the detection of IgG antibodies to CMV. The "ground truth" for such assays typically relies on established reference methods, a "gold standard" laboratory test result, or classification based on a patient's clinical status (e.g., infected vs. uninfected based on a battery of tests or clinical history).
The provided text does not mention the use of experts (like radiologists) to establish ground truth for any of the studies. For IVDs, "ground truth" is usually analytical (e.g., a sample spiked with a known concentration, or a sample with a confirmed status by a highly sensitive and specific reference method).
4. Adjudication Method for the Test Set
Since the studies described are analytical performance studies for an IVD, and not clinical studies involving interpretation by multiple human readers, there is no mention of an adjudication method like 2+1 or 3+1. Ground truth for these types of studies is typically established by the analytical reference method or preparation of known samples.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for imaging devices where human readers interpret results, sometimes with and without AI assistance, to assess the impact of AI on reader performance. The Elecsys CMV IgG is an automated immunoassay, not an imaging device requiring human interpretation of results in the same manner.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies described are essentially standalone performance evaluations of the device (Elecsys CMV IgG assay). As an automated immunoassay, the "algorithm" (the assay's chemical reactions and instrument's detection/calculation) provides a result directly. The studies like precision, biotin interference, and method comparison assess the performance of the assay itself without human intervention in the result determination process. The output is a quantitative (U/mL) or qualitative (reactive/non-reactive) result.
7. The Type of Ground Truth Used
The types of "ground truth" implicitly used in the analytical studies are:
- Known Sample Status/Concentration: For the precision study, controls and samples with a certain expected concentration or qualitative status were used.
- Known Biotin Concentration: For the biotin interference study, samples were "spiked with the interfering endogenous substance" (biotin) to known concentrations.
- Predicate Device Results: For the method comparison study, the results from the legally marketed predicate device (Elecsys CMV IgG K131605) served as a comparative "ground truth" to demonstrate equivalence.
The document does not mention pathology, expert consensus, or outcomes data as ground truth, which are more common for diagnostic imaging or clinical decision support AI devices.
8. The Sample Size for the Training Set
The Elecsys CMV IgG assay is an immunoassay, not a machine learning or AI algorithm in the contemporary sense that requires a "training set" for model development. The assay relies on established biochemical reactions (electrochemiluminescence immunoassay "ECLIA"), calibration curves, and reagent lot-specific master curves. Therefore, there is no "training set" in the context of typical AI/ML algorithm development.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" for an AI/ML algorithm, this question is not applicable to the Elecsys CMV IgG device as described. The assay's performance is driven by its chemical formulation, reagents, and instrument calibration, not by a learned model from a training dataset.
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(84 days)
LFZ
The ADVIA Centaur® CMV IgG (CMV IgG) assay is for in vitro diagnostic use in the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human pediatric and adult serum and plasma (dipotassium EDTA, lithium heparin) using the ADVIA Centaur XP system. The assay is used to determine CMV IgG serological status and as an aid in the diagnosis of CMV infection in individuals for whom a CMV IgG test was ordered, including pregnant women. The ADVIA Centaur CMV IgG assay is not intended for blood and tissue donor screening.
The ADVIA Centaur® CMV IgG) Quality Control material is for in vitro diagnostic use for monitoring the performance of the ADVIA Centaur CMV IgG (CMV IgG) assay on ADVIA Centaur systems.
CMV IgG Assay Kit (100-Tests) consists of 1 ReadyPack containing ADVIA Centaur CMV IgG Lite Reagent and Solid Phase reagent, and 1 ReadyPack ancillary reagent pack that contains ADVIA Centaur CMV IgG Diluent, and a set of Calibrators (1 vial each of Low and High, with fill volume of 2 mL each). The reagents and calibrators are packaged together in the ADVIA Centaur CMV IgG Assay kit, while the associated ADVIA Centaur CMV IgG Quality Control is packaged separately.
The ADVIA Centaur CMV IgG assay is a fully automated, 2-step sandwich immunoassay using indirect chemiluminometric technology.
Here's a breakdown of the acceptance criteria and study information for the ADVIA Centaur CMV IgG assay, based on the provided FDA 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally inferred from the "Assay Cut-off" section, where the cutoff value was set to achieve a certain agreement with a comparator device. The performance is then demonstrated in the clinical studies.
| Acceptance Criteria Category | Specific Acceptance Criteria (Inferred) | Reported Device Performance (Combined Population) |
|---|---|---|
| Agreement with Comparator | ≥ 95% Positive Agreemen | 99.6% (1037/1041) |
| ≥ 95% Negative Agreemen | 96.8% (637/658) | |
| Precision (Within-Lab) | Not explicitly stated as acceptance criteria, but demonstrated by low %CV values. | Ranges from NA (for very low mean values) up to 3.9% CV for positive control. |
| Reproducibility | Not explicitly stated as acceptance criteria, but demonstrated by low %CV values across sites. | Ranges from NA (for very low mean values) up to 7.0% CV for a high positive serum pool. |
| No Interference | No change in clinical interpretation at specified interferent concentrations. | No change in clinical interpretation throughout the assay range. |
| Cross-Reactivity | Agreement with comparator assay (no significant false positives/negatives due to cross-reactants). | Generally good agreement with comparator, minimal discrepancies identified for equivocal samples. |
| Matrix Equivalence | Good correlation (high 'r' value, slope near 1, intercept near 0) for different plasma types compared to serum. | Correlation Coefficient (r) = 0.99 (Dipotassium EDTA plasma vs. Serum), 0.96 (Lithium heparin plasma vs. Serum). Slopes were 1.01. |
| CDC Panel Agreement | Not explicitly stated as acceptance criteria, but 100% agreement indicates strong performance. | 100% agreement with CDC serological status (39 positive, 41 negative). |
2. Sample Sizes Used for the Test Set and Data Provenance
- Initial Cut-off Study: 389 remnant clinical samples (negative: 196, positive: 186, equivocal: remainder - exact number not specified but implied to be few).
- Method Comparison (Primary Test Set): A total of 1842 samples
- Prospective Study: 1699 specimens
- 684 general population subjects
- 348 pregnant subjects
- 229 pediatric subjects (2-21 years old)
- 44 HIV-positive subjects
- 394 transplant-patient subjects
- Provenance: 6 collection sites in the United States.
- Retrospective Study: 143 HIV-positive specimens
- Provenance: 1 site (implied to be in the US, given the overall context of the submission).
- Prospective Study: 1699 specimens
- CDC Panel: 80 previously characterized serum samples.
- Provenance: Centers for Disease Control (CDC).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not explicitly provided in the document. The ground truth for the comparison studies was established by a "comparator CMV IgG assay" (bioMerieux VIDAS CMV IgG (CMVG) Assay, K920661). For equivocal samples, additional testing was done on "2 other CMV IgG comparator assays" to achieve a "two out of three consensus result."
There is no mention of human experts (e.g., radiologists, pathologists) establishing ground truth for the primary clinical studies. The ground truth for the CDC panel samples was "previously characterized" by the CDC, implying expert determination at some point in the past, but details are absent.
4. Adjudication Method for the Test Set
- For the primary method comparison, the comparator CMV IgG assay served as the reference.
- For samples that tested equivocal on the comparator assay, an adjudication method of "two out of three consensus result" was used, comparing the initial comparator result with results from two other CMV IgG comparator assays.
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 is not applicable. The device is an in-vitro diagnostic (IVD) assay for detecting antibodies, not an AI-assisted diagnostic imaging or pathology device that involves human readers interpreting cases. Therefore, no MRMC study or effect size for AI assistance is provided or expected.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this is a standalone device. The ADVIA Centaur CMV IgG assay is a fully automated immunoassay that generates a qualitative result (reactive or non-reactive) based on an Index value. Its performance is evaluated entirely without human interpretation of raw assay data. The results are reported directly by the system.
7. The Type of Ground Truth Used
The primary ground truth for the clinical studies was established by a comparator CMV IgG assay. This is a surrogate ground truth based on the performance of an already legally marketed and accepted diagnostic test. For equivocal samples, an expert consensus of other comparator assays (two out of three consensus) was used. For the CDC panel, the ground truth was previously characterized serological status provided by the CDC.
8. The Sample Size for the Training Set
The document does not explicitly describe a separate training set for the device in the context of machine learning or AI. The term "training set" is typically used in the development of AI algorithms. This device is an immunoassay, and its development would involve optimization and calibration rather than distinct "training" in the AI sense.
However, the "Assay Cut-off" section describes a study performed to determine the cutoff value:
- A comparison study involving 389 remnant clinical samples was used to determine the placement of the cutoff value. While not a "training set" in the AI sense, these samples were used to establish a critical decision-making parameter for the assay.
9. How the Ground Truth for the Training Set Was Established
As discussed above, there isn't a "training set" in the AI context. For the 389 samples used to establish the cut-off value:
- The ground truth for these samples was established by a comparator CMV IgG assay. The aim was to set the cutoff such that the new device's results agreed with the comparator.
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(88 days)
LFZ
Immunoassay for the in vitro qualitative detection of IgM antibodies to CMV in human serum, lithium-heparin plasma, K2-EDTA plasma, and K3-EDTA plasma. The test is intended as an aid in the diagnosis of recent or current CMV infection in individuals for which a CMV IgM test was ordered, including pregnant women.
Performance characteristics have not been evaluated in immunocompromised or immunosuppressed individuals. This test is not intended for use in neonatal screening or for use at point of care facilities. This test is not intended for use in screening blood and plasma donors.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
Elecsys CMV IgM is a qualitative assay for the detection of IgM antibodies to CMV in human serum and plasma for use on the cobas e 801 immunoassay analyzer. The cobas e 801 immunoassay analyzer is a fully automated, software controlled analyzer system for in vitro determination of analytes in human body fluids. It is part of the cobas 8000 modular analyzer series cleared under K100853. It uses electrochemiluminescent technology for signal generation and measurement.
The document describes the Elecsys CMV IgM assay on the cobas e 801 analyzer, which is a qualitative immunoassay for the detection of IgM antibodies to CMV. The submission (K163569) seeks to demonstrate substantial equivalence to a predicate device, the Elecsys CMV IgM on the cobas e 601 (K142133).
Here's an breakdown of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly present a "table of acceptance criteria" with corresponding performance values in every section, but rather states "All results met predefined acceptance criteria" for various performance characteristics. I will compile the relevant performance data points that were provided.
| Performance Characteristic | Acceptance Criteria (Implicit: "met predefined criteria") | Reported Device Performance (Elecsys CMV IgM on cobas e 801) |
|---|---|---|
| Precision | Implicit: Predefined precision limits satisfied. | Repeatability (CV) |
- HSP 1: 1.2%
- HSP 2: 1.3%
- HSP 3: 1.6%
- HSP 4: 1.0%
- HSP 5: 1.0%
- PC CMV IgM 1: 0.9%
- PC CMV IgM 2: 1.9% |
| | | Intermediate Precision (CV) - HSP 1: 2.8%
- HSP 2: 1.8%
- HSP 3: 1.8%
- HSP 4: 1.4%
- HSP 5: 1.8%
- PC CMV IgM 1: 2.6%
- PC CMV IgM 2: 2.2% |
| Analytical Sensitivity | Implicit: LoD below cut-off. | Limit of Blank (LoB): 0.243 COI
Limit of Detection (LoD): 0.276 COI (well below cut-off of 0.7 COI) |
| High Dose Hook Effect | Implicit: No high-dose hook effect observed. | "All results met the predefined acceptance criteria demonstrating no high dose hook effect for the Elecsys CMV IgM assay." |
| Endogenous Interferences | Implicit: No significant interference from tested substances. | No interference from: - Hemoglobin up to 500 mg/dL
- Intralipid up to 1500 mg/dL
- Bilirubin up to 20 mg/dL
- Biotin up to 100 ng/mL
- Rheumatoid factor up to 899 IU/mL |
| Exogenous Interferences (Anticoagulants) | Implicit: Acceptable sample types. | Serum, serum with separating gel, Li-heparin plasma, K2EDTA plasma, K3EDTA plasma are acceptable. |
| Exogenous Interferences (Drugs) | Implicit: No significant interference from tested drugs. | No interference from 18 common drugs, Ganciclovir, and Valganciclovir. |
| Method Comparison (Platform Equivalence) | Implicit: High positive and negative agreement. | Negative Percent Agreement (NPA): 100% (142/142)
Positive Percent Agreement (PPA): 100% (73/73)
Agreement rate for Indeterminate: 75% (6/8) |
2. Sample Size Used for the Test Set and Data Provenance
The document focuses on the technical performance of the device and its equivalence to a predicate. It does not clearly define a "test set" in the context of clinical cohorts but rather describes samples used for various analytical performance studies.
- Precision Study: 84 runs for repeatability and intermediate precision for each of the 7 samples (HSP 1-5, PC CMV IgM 1-2). The samples are referred to as "serum samples." Provenance is not specified (e.g., country of origin, retrospective/prospective).
- Method Comparison (Between Analyzer Platforms): 142 negative plasma samples, 73 positive plasma samples, and 8 indeterminate plasma samples. This totals 223 plasma samples. Provenance (e.g., country, retrospective/prospective) is not specified.
- Interference Studies: Number of samples not explicitly stated; typically involves spiking substances into a limited number of samples.
- Analytical Sensitivity (LoB/LoD): Number of runs/replicates used for determination is not specified, but the methodology (CLSI EP17-A2) implies a structured approach.
Data Provenance: The document generally lacks explicit details on the country of origin for the samples used in these performance studies or whether they were retrospective or prospective. It refers to "in-house studies" and "external clinical studies" for cutoff validation, but specifics are missing from this summary.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This device is an in vitro diagnostic immunoassay, not an imaging device. Therefore, the concept of "experts" (like radiologists) establishing ground truth for a "test set" in the traditional sense of image interpretation is not directly applicable.
For this type of device:
- The "ground truth" for the test samples (e.g., positive, negative, indeterminate) would typically be established by known clinical status (e.g., confirmed CMV infection or absence of infection based on various clinical and laboratory parameters, potentially using a "gold standard" or reference assay).
- The document implies that the "cutoff was established with in-house studies by characterizing samples using several commercially available CMV IgG and CMV IgM assays" and "validation of the assay cutoff was performed by external clinical studies." This suggests the ground truth (or referent status) for the samples was determined by established laboratory methods, not expert consensus on qualitative interpretation.
No specific number or qualification of "experts" is mentioned for establishing the ground truth of the performance study samples.
4. Adjudication Method for the Test Set
Since this is an immunoassay and "ground truth" is established by laboratory methods rather than subjective expert interpretation, the concept of an "adjudication method" (like 2+1 or 3+1) is not applicable here. The results are quantitative (COI values) and then categorized based on predefined cut-offs.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. This type of study is specifically designed for evaluating diagnostic aids (like AI algorithms in imaging) that assist human readers. The Elecsys CMV IgM assay is a standalone laboratory diagnostic test.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) was Done
Yes, the performance data presented (precision, sensitivity, interference, method comparison) represents the standalone performance of the Elecsys CMV IgM assay on the cobas e 801 analyzer. This device does not have a human-in-the-loop component for its primary diagnostic function.
7. The Type of Ground Truth Used
The ground truth used for establishing performance characteristics and assay cut-offs appears to be:
- For Method Comparison: The results from the predicate device (Elecsys CMV IgM on cobas e 601) and potentially other established/commercial CMV IgM assays. The document states "Positive and negative agreement of the results between the two platforms were calculated."
- For Assay Cut-off: "in-house studies by characterizing samples using several commercially available CMV IgG and CMV IgM assays." Additionally, "Validation of the assay cutoff was performed by external clinical studies on the Elecsys 2010." This implies a combination of reference assay results and potentially clinical outcomes/established disease status for the samples used in those studies.
It's not explicitly stated as "pathology" or "outcomes data" in this summary, but rather defined by comparison to other commercial assays and clinical studies.
8. The Sample Size for the Training Set
This document describes the validation of a commercial in vitro diagnostic assay, not an AI/machine learning algorithm that requires a "training set" in the same way. The principles for developing diagnostic assays involve extensive research and development phases where reagents, protocols, and cutoffs are refined. The "training" in this context refers to the development and optimization studies that led to the final assay characteristics.
The specific sample sizes for these development/optimization phases are not provided in this 510(k) summary, as the summary focuses on the final analytical and comparative performance data for the substantial equivalence determination.
9. How the Ground Truth for the Training Set Was Established
Again, applying the term "training set" directly to a traditional immunoassay is not precise. However, for the establishment of the assay cut-off (which is analogous to setting decision boundaries in an algorithm), the summary states:
- "The cutoff was established with in-house studies by characterizing samples using several commercially available CMV IgG and CMV IgM assays."
- "Validation of the assay cutoff was performed by external clinical studies on the Elecsys 2010."
This indicates that the "ground truth" for determining the assay cut-offs was established through a combination of results from other established commercial CMV assays and samples from clinical studies, which would have had their CMV status determined by other means (e.g., patient history, other diagnostic tests, or clinical follow-up). The exact "how" for these broader clinical studies is referenced as being included in the predicate device's K-submission (K142133).
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The LIAISON® CMV IgG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer family* for the qualitative determination of IgG antibodies to human cytomegalovirus (hCMV) in human serum. It is intended to be used as an aid in the determination of serological status to CMV.
The DiaSorin LIAISON® CMV IgG Serum Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® CMV IgG assay on the LIAISON® Analyzer family *. The performance characteristics of the LIAISON® CMV IgG controls have not been established for any other assay or instrument platforms different from the LIAISON® and LIAISON® XL.
*(LIAISON® and LIAISON® XL).
The LIAISON® CMV IgG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer family* for the qualitative determination of IgG antibodies to human cytomegalovirus (hCMV) in human serum.
The LIAISON® CMV IgG Serum Control Set (negative and positive) consists of liquid ready-touse controls in human serum/defibrinated plasma. The negative control is intended to provide an assay response characteristic of negative patient specimens and the positive control is intended to provide an assay response characteristic of positive patient specimens.
The controls are designed for use with DiaSorin LIAISON® CMV IgG assay on the LIAISON® Analyzer family.
Here's a summary of the acceptance criteria and study information for the LIAISON® CMV IgG and LIAISON® CMV IgG Serum Control Set, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state numerical acceptance criteria or specific numerical reported device performance values for the LIAISON® CMV IgG assay (which remains unchanged from the predicate device). However, it focuses on the performance of the LIAISON® CMV IgG Serum Control Set. The acceptance criteria for the controls are described qualitatively:
| Acceptance Criteria Category | Specific Criteria (from text) | Reported Device Performance (from text) |
|---|---|---|
| LIAISON® CMV IgG Serum Control Set | ||
| Commutability | Commutability between samples and controls (matrix effect) | Meets predetermined acceptance criteria, supporting equivalency. |
| Precision Equivalence | Precision equivalence between samples and controls | Meets predetermined acceptance criteria, supporting equivalency. |
| 20-Day Precision | (Implicit: acceptable precision over 20 days) | Meets predetermined acceptance criteria, supporting equivalency. |
| Control Value Assignment | (Implicit: accurate assignment of control values) | Meets predetermined acceptance criteria, supporting equivalency. |
| Control Range Definition | (Implicit: appropriate definition of control ranges) | Meets predetermined acceptance criteria, supporting equivalency. |
| Shelf-Life Stability | Shelf-life of 12 months at (2-8°C) | Real-time stability testing supports this claim. |
| Open Use Stability | Eight (8) weeks open use stability when stored at 2-8°C between uses | Real-time stability testing supports this claim. |
2. Sample Size and Data Provenance
- Test Set Sample Size: The document does not specify the exact sample sizes used for the "Test Set" in the context of commutability, precision, control value assignment, or control range definition. It mentions "samples and controls" for precision equivalence. For stability testing, it states "Real time stability testing," implying a duration-based study rather than a fixed sample count of individual specimens.
- Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be internal to the manufacturer (DiaSorin Inc.). The document implies these are non-clinical verification and validation studies. It does not clarify if the data is retrospective or prospective, but real-time stability testing would be prospective.
3. Number of Experts and Qualifications for Ground Truth
This information is not provided in the document. The device is an immunoassay for detecting antibodies, which typically relies on laboratory-defined cut-offs and established reference methods for "ground truth", rather than expert interpretation of images or clinical cases.
4. Adjudication Method for the Test Set
This information is not provided as it's not relevant for an immunoassay that doesn't involve subjective interpretation or a panel of experts.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
A MRMC comparative effectiveness study was not done, as this type of study is relevant for imaging devices or algorithms that involve human interpretation and reader variability. The LIAISON® CMV IgG is an automated immunoassay.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
The LIAISON® CMV IgG assay is a standalone algorithm/device for its performance. It measures IgG antibodies to hCMV in human serum automatically. The controls are also designed to monitor this automated performance. The study described focuses on the performance characteristics of the controls and their impact on the assay itself, rather than comparing its performance with or without human intervention for result interpretation.
7. Type of Ground Truth Used
The ground truth for immunoassay performance is typically established by:
- Reference methods/panels (e.g., CDC reference panels).
- Clinically characterized samples (e.g., samples from known CMV-positive and CMV-negative individuals).
- Comparison to a legally marketed predicate device (as in this 510(k), where the assay's performance is stated as "No Change" from the cleared predicate, K040290).
The document states that the studies demonstrate the modified device (Control Set) meets "predetermined acceptance criteria, supporting equivalency of the modified device to the cleared device." This strongly implies the ground truth for establishing acceptance and equivalency relies on the established performance characteristics and values of the predicate device and/or defined laboratory standards.
8. Sample Size for the Training Set
The document does not specify a training set sample size, as this filing is for a modification to an already cleared device (the control set for an existing assay). The primary focus is on validating the new control set, not on developing or training a new algorithm from scratch.
9. How the Ground Truth for the Training Set Was Established
As no training set is explicitly mentioned for a new algorithm development, this information is not applicable in the context of this 510(k) submission for a control set modification. For the original assay (K040290), ground truth would have been established using methods mentioned in point 7.
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(1) Immunoassay for the in vitro qualitative detection of IgM antibodies to CMV in human serum, lithium-heparin plasma, K2-EDTA plasma, and K3-EDTA plasma. The test is intended as an aid in the diagnosis of recent or current CMV infection in individuals for which a CMV IgM test was ordered, including pregnant women. Performance characteristics have not been evaluated in immunocompromised or immunosuppressed individuals. This test is not intended for use in neonatal screening or for use at point of care facilities. This assay is not intended for use in screening blood and plasma donors.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys immunoassay analyzers.
(2) PreciControl CMV IgM is used for quality control of the Elecsys CMV IgM immunoassay on the Elecsys and cobas e immunoassay analyzers.
(1) Elecsys CMV IgM is a u-capture immunoassay with streptavidin microparticles, biotinylated recombinant CMV-specific antigen labeled with a ruthenium complex and electrochemiluminescence detection. The results are determined using a calibration curve which is instrument-specifically generated by a 2-point calibration and a master curve provided via the reagent bar code. The test system contains the human serum-based calibrators intended for use with the system.
The CMV IgM assay begins with an automatic 1:20 predilution of sample with Elecsys Diluent Universal and the addition of biotinylated monoclonal anti-h-IgM-specific antibodies.
During the second incubation, CMV-specific recombinant antigen labeled with a ruthenium complex and streptavidin-coated microparticles are added. Anti-CMV IgM antibodies present in the sample react with the ruthenium-labeled CMV-specific recombinant antigen. 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 induces chemiluminescent emission which is measured by a photomultiplier.
The analyzer automatically calculates the cutoff based on the measurement of Cal 1 and Cal2. The result of the samples is given either as reactive or non-reactive as well as in the form of a cutoff index (signal samples/cutoff). Samples with a cutoff index (COI)
Here's a breakdown of the acceptance criteria and the study details for the Elecsys CMV IgM Immunoassay, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document primarily focuses on demonstrating that the device met its predefined acceptance criteria rather than explicitly listing the criteria in a single table with performance. However, I can construct a table summarizing the performance metrics and their implicit acceptance criteria from the "Analytical Performance Data" and "Clinical Performance Data" sections.
| Study/Test Area | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision (Repeatability) | CV (%) UCL95% values to be within acceptable limits (specific limits not explicitly stated, but implied by passing results). | All repeatability CVs ranged from 0.9% to 2.0% for controls and 1.0% to 1.8% for human serum samples. All met pre-defined acceptance criteria. |
| Precision (Intermediate) | CV (%) UCL95% values to be within acceptable limits. | All intermediate precision CVs ranged from 2.9% to 5.3% for controls and 2.0% to 4.4% for human serum samples. All met pre-defined acceptance criteria. |
| Reagent Stability (Unopened) | Stable for 15 months at 2-8°C. | Stable for up to 18 months at 2-8°C, supporting the 15-month claim. |
| Reagent Stability (Opened) | Stable for 12 weeks at 2-8°C. | Stable for up to 13 weeks at 2-8°C, supporting the 12-week claim. |
| On-Board Reagent Stability | Stable for 2 weeks at 20°C ± 3°C. | Stable for 34 days at 20°C ± 3°C, supporting the 2-week claim. |
| On-Board/Refrigerated R. Stability | Stable for 6 weeks when stored alternately in refrigerator and on analyzer. | Met acceptance criteria for 6 weeks. |
| Sample Stability (2-8°C) | Stable for 4 weeks at 2-8°C. | Stable for up to 35 days (5 weeks) at 2-8°C, supporting the 4-week claim. |
| Sample Stability (20-25°C) | Stable for 7 days at 20-25°C. | Stable for up to 10 days at 20-25°C, supporting the 7-day claim. |
| Sample Stability (-20°C) | Stable for 3 months at -20°C. | Stable for approximately 4 months (119 days) at -20°C, supporting the 3-month claim. |
| Sample Stability (Freeze/Thaw) | Stable through 5 freeze/thaw cycles. | Stable through 5 freeze/thaw cycles, with samples aliquoted for 6 cycles. |
| Calibration Stability (Lot) | Stable for 28 days. | Met acceptance criteria for 28 days. |
| Calibration Stability (On-Board) | Stable for 8 days (on the Elecsys 2010 analyzer). | Met acceptance criteria for 8 days. |
| Calibrator Stability (2-8°C) | Stable for 8 weeks at 2-8°C. | Met acceptance criteria for 8 weeks (tested for 10 weeks). |
| Open Vial Calibrator Stability | Stable for 5 hours. | Met acceptance criteria for 5 hours. |
| Control Stability (2-8°C) | Stable for 8 weeks at 2-8°C. | Met acceptance criteria for 8 weeks. |
| Control Open Vial Stability | Stable for 5 hours. | Met acceptance criteria for 5 hours. |
| Control Shelf-Life Stability | Stable for 15 months. | Met acceptance criteria for 15 months (tested during and beyond 18 months). |
| High Dose Hook Effect | No hook effect up to a specified high concentration. | No high dose hook effect observed up to 32.9 COI. |
| Endogenous & Drug Interferences | For COI 90% against comparator. No interference from 20 pharmaceutical compounds. | Hemoglobin: |
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Elecsys CMV IgG:
The Elecsys CMV IgG immunoassay is a test for the in vitro semi-quantitative determination of IgG class antibodies to CMV in human serum, lithium-heparin plasma, K2 -EDTA plasma, and K3 -EDTA plasma. The test is intended for adults, including expectant mothers, as an aid in presumptive diagnosis of CMV infection. Results with this assay are used to indicate past infection with CMV.
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 CMV IgG:
Elecsys PreciControl CMV IgG is used for quality control of the Elecsys CMV IgG immunoassay on the Elecsys and cobas e immunoassay analyzers.
(1) Elecsys CMV IgG is a two-step sandwich immunoassay with streptavidin microparticles, biotinylated recombinant CMV-specific antigen labeled with a ruthenium complex and electrochemiluminescence detection. The results are determined using a calibration curve which is instrument-specifically generated by a 2-point calibration and a master curve provided via the reagent bar code. Results greater than or equal to 1.0 U/mL are considered reactive CMV IgG antibody. The test system contains the human serum-based calibrators intended for use with the system.
(2) Elecsys PreciControl CMV IgG contains liquid control serum based on human serum. The controls are used for monitoring the accuracy of the Elecsys CMV IgG immunoassay.
Note: The reagent and calibrators are packaged together in the Elecsys CMV IgG assay kit, while the associated PreciControl is packaged separately.
The Elecsys CMV IgG Test System was evaluated through a clinical trial to demonstrate its performance characteristics.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Elecsys CMV IgG Immunoassay are not explicitly stated as numerical targets in the provided text. Instead, the study reports the "Percent Agreement" values (often referred to as sensitivity and specificity for agreement studies) against a reference method (the predicate device, Diamedix Is-CMV IgG).
| Performance Metric | Acceptance Criteria (Not explicitly stated in document. Based on typical agreement expectations for such assays, good agreement with a predicate is generally sought, e.g., >90%) | Reported Device Performance (Elecsys CMV IgG) | Predicate Device Performance (Diamedix Is-CMV IgG) |
|---|---|---|---|
| Routine Cohort (n=500) | |||
| Positive Percent Agreement (95% CI) | N/A (implied high agreement) | 100% (98.7-100%) | See "Relative Sensitivities" below |
| Negative Percent Agreement (95% CI) | N/A (implied high agreement) | 90.1% (85.3-93.7%) | See "Relative Specificities" below |
| Expectant Mother Cohort (n=98) | |||
| Positive Percent Agreement (95% CI) | N/A (implied high agreement) | 100% (95.4-100%) | Not explicitly provided for this cohort |
| Negative Percent Agreement (95% CI) | N/A (implied high agreement) | 73.7% (48.8-90.9%) | Not explicitly provided for this cohort |
| CMV IgM Positive Cohort (n=119) | |||
| Positive Percent Agreement (95% CI) | N/A (implied high agreement) | 96.6% (91.6-99.1%) | Not explicitly provided for this cohort |
| Negative Percent Agreement (95% CI) | N/A (implied high agreement) | 100% (2.5-100%) | Not explicitly provided for this cohort |
| Predicate Device (Diamedix Is-CMV IgG) relative to EIA (Manual) | |||
| Relative Sensitivities (Site 1, n=195) | N/A | - | 99.3% (96.3-100.0%) |
| Relative Sensitivities (Site 2, n=168) | N/A | - | 96.6% (91.5-99.1%) |
| Relative Sensitivities (Site 3, n=205) | N/A | - | 100.0% (97.6-100.0%) |
| Relative Specificities (Site 1, n=195) | N/A | - | 97.9% (88.9-99.9%) |
| Relative Specificities (Site 2, n=168) | N/A | - | 100.0% (93.0-100.0%) |
| Relative Specificities (Site 3, n=205) | N/A | - | 94.3% (84.3-98.8%) |
| Predicate Device (Diamedix Is-CMV IgG) relative to EIA (Automated) | |||
| Relative Sensitivities (Site 3, n=201) | N/A | - | 100.0% (97.6-100.0%) |
| Relative Specificities (Site 3, n=201) | N/A | - | 87.7% (75.2-95.4%) |
2. Sample Size and Data Provenance
The study included several cohorts for performance evaluation:
- Routine Cohort: n=500
- Expectant Mother Cohort: n=98
- CMV IgM Positive Cohort: n=119
- Cross-Reactivity Cohort: 249 samples positive for various cross-reactants.
The document does not specify the country of origin for the data or whether it was retrospective or prospective.
3. Number of Experts and Qualifications for Ground Truth
The document does not mention the use of human experts or their qualifications for establishing ground truth for the clinical trial comparing the Elecsys CMV IgG immunoassay with the predicate device. The performance is assessed based on agreement with the predicate device results.
4. Adjudication Method
No adjudication method is mentioned in the provided text, as the comparison is made directly against the predicate device's results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study involving human readers with and without AI assistance was performed, as this device is an in vitro diagnostic immunoassay, not an AI software intended for human interpretation assistance.
6. Standalone Performance (Algorithm Only)
Yes, a standalone study was performed. The Elecsys CMV IgG Immunoassay's performance metrics (Positive Percent Agreement, Negative Percent Agreement) were directly evaluated against the predicate device's results in various clinical cohorts, representing its standalone performance. Additional analytical performance characteristics like precision, LoB/LoD, hook effect, and cross-reactivity were also evaluated for the Elecsys CMV IgG assay itself.
7. Type of Ground Truth Used
The ground truth for the clinical performance evaluation appears to be established by the results of the predicate device, the Diamedix Is-CMV IgG Test System (K981163). The study reports "Percent Agreement" with this predicate device. For the cross-reactivity study, the ground truth was the known positive status for specific cross-reactants.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of an algorithm or machine learning model for the Elecsys CMV IgG Immunoassay. This device is an immunoassay, and its development likely involves laboratory optimization and validation studies, rather than machine learning training sets. Therefore, a sample size for a training set is not applicable or provided.
9. How the Ground Truth for the Training Set was Established
As noted in point 8, the concept of a "training set" and associated ground truth establishment is not typically applicable to the development of an immunoassay like the Elecsys CMV IgG Test System. The document describes standard laboratory validation procedures and clinical performance evaluation against a predicate device.
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The LIAISON® CMV IgG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative determination of IgG antibodies to human cytomegalovirus (hCMV) in human serum. It is intended to be used as an aid in the determination of serological status to CMV.
The LIAISON® CMV IgM assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative determination of IgM antibodies to human cytomegalovirus (hCMV) in human serum. It is intended to be used as an aid in the diagnosis of acute CMV infection.
The method for qualititative determination of specific IgG to hCMV is an indirect chemiluminescence immunoassay (CLIA). All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the LIAISON® Chemiluminescence Analyzer. The principal components of the test are magnetic particles (solid phase) coated with hCMV antigen and a conjugate of mouse monoclonal antibody to human IqG linked to an isoluminol derivative (isoluminol-antibody conjugate).
The method for qualititative determination of specific IgM to hCMV is an indirect chemiluminescence immunoassay (CLIA). All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the LIAISON® Chemiluminescence Analyzer. The principal components of the test are magnetic particles (solid phase) coated with hCMV antigen, a buffer of goat IgG to human IgG and a conjugate of mouse monoclonal antibody to human IgM linked to an isoluminol derivative (isoluminolantibody conjugate).
Here's a breakdown of the acceptance criteria and study information for both the LIAISON® CMV IgG and LIAISON® CMV IgM assays, based on the provided text:
LIAISON® CMV IgG Assay
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to a predicate device (DiaSorin CMV IgG ELISA Kit K955361) and a general expectation of high agreement. Specific numerical targets for acceptance criteria are not explicitly stated as "acceptance criteria" but rather as "percent agreement" for different sample types.
| Category | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Prospective Samples | High overall agreement with predicate assay. | Overall Agreement: 98.13% (314/320) |
| High positive agreement with predicate assay. | Positive Agreement: 100.0% (178/178) | |
| High negative agreement with predicate assay. | Negative Agreement: 96.45% (136/141) | |
| Pregnancy Samples | High overall agreement with predicate assay. | Overall Agreement: 99.01% (200/202) |
| High positive agreement with predicate assay. | Positive Agreement: 99.43% (175/176) | |
| High negative agreement with predicate assay. | Negative Agreement: 96.15% (25/26) | |
| Retrospective Samples | High overall agreement with known positive samples. | Overall Agreement: 100.0% (100/100) |
| High positive agreement with known positive samples. | Positive Agreement: 100.0% (100/100) | |
| Reproducibility | Acceptable within-run, between-run, and between-site precision. | Overall %CV values ranged from 7.68% to 22.07%. |
| Interference | No significant interference from common interfering substances. | No effects from hemolysis, lipemia, icterus (within tested limits). |
| Cross-Reactivity | No significant cross-reactivity with related infectious agents. | 0/46 samples showed positive results (with caveats). |
2. Sample Size and Data Provenance for Test Set
-
Sample Sizes:
- Prospective Samples: 320 samples
- Pregnancy Samples: 202 samples
- Retrospective Samples (Suspected Acute CMV Infection): 100 samples
- Reproducibility Panel: 9 frozen repository serum samples (tested 90 times each, 3 replicates per run for 10 runs across 4 sites).
- Interference Studies: Not explicitly stated for specific sample count, but "controlled studies" were performed.
- Cross-Reactivity Panel: 46 samples (from various conditions/organisms).
-
Data Provenance:
- Country of Origin: The clinical trials were conducted at two external US laboratories and at DiaSorin.
- Retrospective or Prospective: Both retrospective (repository) and prospective samples were used.
3. Number of Experts and Qualifications for Ground Truth
- Number of Experts: Not specified.
- Qualifications of Experts: Not specified. The ground truth was established by comparison to a "comparison assay" (DiaSorin CMV IgG ELISA Kit). It's implied that the reference method itself effectively serves as the "expert" for establishing the ground truth.
4. Adjudication Method for Test Set
- Adjudication Method: Not applicable/not specified. The study compared the new device's results directly against a predicate device (DiaSorin CMV IgG ELISA Kit). There's no indication of an expert adjudication process beyond the results of the predicate assay.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- MRMC Study Done: No. This is an in-vitro diagnostic device (immunoassay), not an imaging or interpretation device that would typically involve human "readers." The performance is measured directly by the assay's output.
6. Standalone Performance (Algorithm Only)
- Standalone Performance Done: Yes. The performance metrics presented (percent agreement, reproducibility, interference, cross-reactivity) are all "standalone" in the sense that they describe the device's performance without human interpretation or intervention in the final result determination, other than following the manufacturer's instructions for use. The device directly produces qualitative (Negative, Equivocal, Positive) or quantitative (U/mL) results.
7. Type of Ground Truth Used
- Ground Truth Type: Comparison to a predicate device (DiaSorin CMV IgG ELISA Kit). For the retrospective samples, it refers to "Suspected Acute CMV Infection," implying clinical diagnosis or established serological status.
8. Sample Size for Training Set
- Training Set Sample Size: Not specified. The document describes clinical performance data using test sets, but typically for immunoassay development, specific training set sizes are not disclosed in the same manner as for AI/ML algorithms. The development involved antigen selection and optimization, which indirectly uses data to establish assay parameters.
9. How Ground Truth for Training Set Was Established
- Ground Truth Establishment for Training Set: Not specified in the provided text. For an immunoassay, the "training" aspect would involve optimizing reagent concentrations, incubation times, and cutoff values using a panel of known positive and negative samples, which would have their ground truth established through clinical diagnosis, confirmed infection, or other reference methods (like another established ELISA).
LIAISON® CMV IgM Assay
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to a predicate device (Diamedix Is-CMV IgM Capture ELISA Kit K001767) and a general expectation of high agreement. Specific numerical targets for acceptance criteria are not explicitly stated as "acceptance criteria" but rather as "percent agreement" for different sample types.
| Category | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Prospective Samples | High overall agreement with predicate assay. | Overall Agreement: 90.79% (1361/1499) |
| High positive agreement with predicate assay. | Positive Agreement: 90.70% (39/43) | |
| High negative agreement with predicate assay. | Negative Agreement: 93.23% (1322/1418) | |
| Pregnancy Samples | High overall agreement with predicate assay. | Overall Agreement: 98.50% (197/200) |
| High negative agreement with predicate assay. | Negative Agreement: 98.50% (197/200) | |
| Positive agreement not applicable due to 0 positives. | Positive Agreement: N/A | |
| Retrospective Samples | High overall agreement with known positive samples. | Overall Agreement: 97.0% (97/100) |
| High positive agreement with known positive samples. | Positive Agreement: 100.0% (97/97) | |
| Reproducibility | Acceptable within-run, between-run, and between-site precision. | Overall %CV values ranged from 10.97% to 26.59%. |
| Interference | No significant interference from common interfering substances. | No effects from hemolysis, lipemia, icterus (within tested limits). |
| Cross-Reactivity | No significant cross-reactivity with related infectious agents. | 2/67 samples showed positive results (with caveats). |
2. Sample Size and Data Provenance for Test Set
-
Sample Sizes:
- Prospective Samples: 1499 samples (U.S. 610; European 889)
- Pregnancy Samples: 200 samples
- Retrospective Samples (Suspected Acute CMV Infection): 100 samples
- Reproducibility Panel: 9 frozen repository serum samples (tested 90 times each, 3 replicates per run for 10 runs across 4 sites).
- Interference Studies: Not explicitly stated for specific sample count, but "controlled studies" were performed.
- Cross-Reactivity Panel: 67 samples (from various conditions/organisms).
-
Data Provenance:
- Country of Origin: Clinical trials were conducted at two external US laboratories and at DiaSorin. Prospective samples included both U.S. and European origin.
- Retrospective or Prospective: Both retrospective (repository) and prospective samples were used.
3. Number of Experts and Qualifications for Ground Truth
- Number of Experts: Not specified.
- Qualifications of Experts: Not specified. The ground truth was established by comparison to a "comparison assay" (Diamedix Is-CMV IgM Capture ELISA Kit). It's implied that the reference method itself effectively serves as the "expert" for establishing the ground truth.
4. Adjudication Method for Test Set
- Adjudication Method: Not applicable/not specified. The study compared the new device's results directly against a predicate device (Diamedix Is-CMV IgM Capture ELISA Kit). There's no indication of an expert adjudication process beyond the results of the predicate assay.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- MRMC Study Done: No. This is an in-vitro diagnostic device (immunoassay), not an imaging or interpretation device that would typically involve human "readers." The performance is measured directly by the assay's output.
6. Standalone Performance (Algorithm Only)
- Standalone Performance Done: Yes. The performance metrics presented (percent agreement, reproducibility, interference, cross-reactivity) are all "standalone" in the sense that they describe the device's performance without human interpretation or intervention in the final result determination, other than following the manufacturer's instructions for use. The device directly produces qualitative (Negative, Equivocal, Positive) or quantitative (AU/mL) results.
7. Type of Ground Truth Used
- Ground Truth Type: Comparison to a predicate device (Diamedix Is-CMV IgM Capture ELISA Kit). For the retrospective samples, it refers to "Suspected Acute CMV Infection," implying clinical diagnosis or established serological status.
8. Sample Size for Training Set
- Training Set Sample Size: Not specified. The document describes clinical performance data using test sets, but typically for immunoassay development, specific training set sizes are not disclosed in the same manner as for AI/ML algorithms. The development involved antigen selection and optimization, which indirectly uses data to establish assay parameters.
9. How Ground Truth for Training Set Was Established
- Ground Truth Establishment for Training Set: Not specified in the provided text. For an immunoassay, the "training" aspect would involve optimizing reagent concentrations, incubation times, and cutoff values using a panel of known positive and negative samples, which would have their ground truth established through clinical diagnosis, confirmed infection, or other reference methods (like another established ELISA).
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For in vitro use with the IMMULITE® 2000 Automated Analyzer - for the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human serum as an aid in the determination of serological status to CMV. This kit is not cleared for use in testing (i.e. screening) blood or plasma donors.
IMMULITE® 2000 CMV IgG is a clinical use device intended for use with the IMMULITE® 2000 Automated Immunoassay Analyzer. IMMULITE® 2000 CMV IgG is a chemiluminescent immunoassay. The sold phase, a polystyrene bead enclosed within an IMMULITE Test Unit/IMMULITE 2000 Reaction Tube is coated with partially purified CMV antigen. One-in-twenty one prediluted patient sample for IMMULITE/instrument-diluted patient sample for IMMULITE 2000 and a protein-based buffer are simultaneously introduced into the Test Unit (IMMULITE)/Reaction Tube (IMMULITE 2000), and incubated for approximately 30 minutes at 37℃ with intermittent agitation. During this time, CMV-specific IgG in the sample binds to the CMV antigen-coated bead. Unbound serum is then removed by a centrifugal wash. In both procedures, an alkaline phosphatase-labeled anti-human IgG antibody is introduced, and the Test Unit/Reaction Tube is incubated for another 30-minute cycle. The unbound enzyme conjugate is removed by a centrifugal wash. Substrate is then added, and the Test Unit/Reaction Tube is incubated for a further 10 minutes (IMMULITE)/5 minutes (IMMULITE 2000). In both procedures, the chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex - and thus also the photon output, as measured by the luminometer - is related to the presence of CMV IgG in the sample. A qualitative result is then obtained by comparing the patient result to an established cutoff.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" as a separate, pre-defined set of targets. Instead, it presents a "Performance Equivalence - Method Comparison" study with the implicit understanding that high agreement, relative sensitivity, and relative specificity with the predicate device are the metrics for demonstrating equivalence.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (IMMULITE® 2000 CMV IgG vs. IMMULITE® CMV IgG) |
|---|---|---|
| Agreement | High agreement (e.g., >95%) | 99.6% |
| Relative Sensitivity | High sensitivity (e.g., >95%) | 100% |
| Relative Specificity | High specificity (e.g., >95%) | 100% |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 229 samples.
- Data Provenance: The document does not specify the country of origin for the samples or whether they were retrospective or prospective.
3. Number of Experts Used to Establish Ground Truth and Qualifications
The document does not mention the use of experts to establish ground truth for this comparison study. The comparison is between two devices, implying that the ground truth for this study is essentially the performance of the predicate device (IMMULITE® CMV IgG).
4. Adjudication Method for the Test Set
No adjudication method is described. The comparison is a direct method comparison between two assays.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
An MRMC study was not conducted. This is a comparison between two automated immunoassay devices, not a study involving human readers with and without AI assistance.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, this study is a standalone performance assessment of the new IMMULITE® 2000 CMV IgG device against a predicate device (IMMULITE® CMV IgG). Both are automated immunoassay systems, operating without human interpretation in the results generation process depicted here.
7. The Type of Ground Truth Used
The "ground truth" for this performance equivalence study is the performance of the predicate device, IMMULITE® CMV IgG. The study aims to demonstrate that the new device performs equivalently to an already cleared device.
8. The Sample Size for the Training Set
The document does not provide information about a separate training set for the IMMULITE® 2000 CMV IgG device. This submission is for a new iteration of an immunoassay, and the focus is on demonstrating equivalence to a previous version rather than presenting a de novo algorithm training process.
9. How the Ground Truth for the Training Set was Established
As no training set is described, there's no information on how its ground truth would have been established. It's likely that the original IMMULITE® CMV IgG (the predicate device) would have undergone its own validation studies where ground truth for determining CMV IgG status was established through methods like clinical diagnosis, seroconversion panels, or other established laboratory methods for infectious disease diagnosis.
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(180 days)
LFZ
- For the qualitative detection of IgM antibodies to CMV in human serum by enzyme immunoassay, to aid in the diagnosis of CMV infection.
- A positive result is presumptive for the detection of anti-CMV antibodies and presumptive for the diagnosis of acute or recent CMV infection.
- Useful for the above indications, with specimens obtained from women of childbearing age.
- For manual use, or for use with the HyPrep System Plus semi-automated fluid handler.
Not Found
I am sorry, but the provided text does not contain any information about acceptance criteria or a study that proves the device meets specific acceptance criteria. The document is an FDA 510(k) clearance letter for the SeraQuest CMV IgM device, which primarily concerns the substantial equivalence determination to a legally marketed predicate device.
The document discusses:
- The FDA's review and determination of substantial equivalence for the SeraQuest CMV IgM device.
- Regulatory classifications and general controls applicable to the device.
- CLIA complexity categorization.
- Contact information for various FDA offices.
- The intended uses (indications for use) of the device.
There is no mention of specific performance metrics, acceptance criteria, study design, sample sizes, expert qualifications, ground truth establishment, or any comparative effectiveness studies as requested in your prompt.
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