Search Results

For the qualitative determination of total (IgG and IgM) antibodies to Treponema pallidum (TP) specific antigens in human serum and plasma using the VITROS 5600 Integrated System.

The presence of antibodies to Treponema pallidum (TP) specific antigens, in conjunction with non-treponemal laboratory tests and clinical findings may aid in the diagnosis of syphilis infection.

The VITROS Syphilis test is not intended for blood and tissue donor screening.

The VITROS Immunodiagnostic Products Syphilis test is performed using the VITROS Immunodiagnostic Products Syphilis Reagent Pack and VITROS Immunodiagnostic Products Syphilis Calibrator on the VITROS 5600 Integrated System.

An immunometric technique is used; this involves a two-stage reaction. In the first stage antibodies to Syphilis TP specific antigens present in the sample bind with biotinylated recombinant Syphilis TP antigens immobilized on streptavidin coated wells. Unbound sample is removed by washing. In the second stage conjugate reagent containing horseradish peroxidase (HRP)-labeled recombinant Syphilis TP antigens is added. The conjugate binds specifically to any antibody to Syphilis TP specific antigens captured on the well in the first stage. Unbound conjugate is removed by washing.

The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the system.

Here's a detailed breakdown of the acceptance criteria and the study proving the device meets these criteria, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the clinical performance results meeting high percentage agreements. While explicit numeric acceptance criteria (e.g., "PPA must be >X%") are not directly stated in a dedicated section, the sponsor presents the results and concludes substantial equivalence, indicating that these results were considered acceptable.

2. Sample size used for the test set and the data provenance

• Test Set Sample Size:
  • Prospective Specimens: 924 total specimens.
    • 615 subjects for routine syphilis testing (from 6 sites in the United States).
    • 47 pregnant women.
    • 262 HIV positive subjects.
  • Retrospective Specimens: 547 total specimens.
    • 243 samples from pregnant women.
    • 152 HIV positive samples.
    • 152 pre-selected positive samples.
  • Medically Diagnosed Individuals: 151 samples.
  • Apparently Healthy Individuals: 201 prospective specimens (from 3 sites in the United States).
  • Total Clinical Samples: 924 (prospective) + 547 (retrospective) + 201 (apparently healthy) = 1672 specimens for primary clinical evaluation. The medically diagnosed group is a subset likely included within the prospective/retrospective groups or as additional targeted samples.
• Data Provenance:
  • Country of Origin: United States (for prospective and apparently healthy specimens). Retrospective samples are "purchased," implying they may originate from various sources but were tested at sites.
  • Retrospective or Prospective: Both retrospective and prospective clinical studies were conducted.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document does not specify the number of experts or their qualifications for establishing the ground truth. Instead, the ground truth was established using a "composite testing algorithm."

4. Adjudication method for the test set

The adjudication method relied on a composite testing algorithm using:

• A treponemal electrochemiluminescence immunoassay (TP-ECLIA)
• A Rapid Plasma Reagin (RPR) non-treponemal assay
• A Treponema pallidum Particle Agglutination (TP-PA) Treponema-specific assay

Cases were categorized as "Positive for Syphilis" or "Negative for Syphilis" based on the results of these FDA-cleared comparator assays. The document describes specific combinations of results from these three assays that led to a final comparator result. For example, "Non-reactive TP-ECLIA + Non-reactive RPR" was deemed "Negative," while "Reactive TP-ECLIA + Reactive RPR (and N/A TP-PA)" was "Positive." Discordant results with the final comparator were further analyzed (e.g., 14 discordant prospective samples were found reactive by another FDA-cleared TP antibody test).

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, an MRMC comparative effectiveness study involving human readers and AI assistance was not conducted or reported. This device is an in vitro diagnostic test (IVD) for laboratory use, not an AI-powered image analysis or diagnostic aid for human readers.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

Yes, the studies presented are standalone performance evaluations of the VITROS Immunodiagnostic Products Syphilis test (an algorithm-driven instrument/reagent system) without human-in-the-loop performance being a variable in the reported clinical accuracy. The assay itself performs the determination.

7. The type of ground truth used

The ground truth used was a composite testing algorithm based on multiple FDA-cleared comparator assays (TP-ECLIA, RPR, and TP-PA). This is a form of clinical surrogate ground truth derived from established diagnostic tests, rather than direct pathology, biopsy, or long-term outcomes data, which are typically used for definitive diagnosis in some other medical fields.

8. The sample size for the training set

The document does not provide information on the sample size for a training set. This is because the device described is an immunoassay, a biochemical test, not a machine learning or AI algorithm that typically requires a separate training set. The reported studies evaluate the locked-down analytical and clinical performance of the manufactured diagnostic kit.

9. How the ground truth for the training set was established

Since there is no training set mentioned for an AI/machine learning algorithm, the concept of establishing ground truth for a training set is not applicable here. The assay's internal calibration and optimization would have been performed during product development, but this is distinct from "training" an AI model in the context of imaging or predictive analytics.

Ask a specific question about this device

For in vitro diagnostic use only.

For the quantitative measurement of human chorionic gonadotropin (hCG) and its ß-subunit in human serum and plasma (heparin and EDTA) using the VITROS 5600 Integrated System to aid in the early detection of pregnancy.

The VITROS Immunodiagnostic Products Total ß-hCG II Reagent Pack (test) is performed using the VITROS Immunodiagnostic Products Total β-hCG II Reagent Pack and VITROS Immunodiagnostic Products Total B-hCG II Calibrators on the VITROS 5600 Integrated System.

An immunometric immunoassay technique is used, which involves the reaction of human chorionic gonadotropin (hCG) present in the sample with a microwell coated with biotinylated Antibody (mouse monoclonal anti-ß-hCG) bound to streptavidin, and a Horseradish Peroxidase (HRP)-labelled antibody conjugate (mouse monoclonal anti-ß-hCG). Unbound materials are removed by washing.

The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent, is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the system. The amount of HRP conjugate bound is directly proportional to the concentration of hCG present in the sample.

VITROS Immunodiagnostic Products Total ß-hCG II Reagent Pack contains:
1 reagent pack containing:

• 100 coated wells (antibody, mouse monoclonal anti-ß-hCG, binds >600 mIU hCG/well)
• 14.4 mL assay reagent (buffer containing mouse serum, bovine serum albumin, bovine gamma globulin and . antimicrobial agent)
• 19.2 mL conjugate reagent (HRP-mouse monoclonal anti-β-hCG, binds ≥4005 mIU hCG/mL) in buffer with ● bovine serum albumin and antimicrobial agent.

VITROS Total ß-hCG II Calibrators contains:

• 3 sets of VITROS Total ß-hCG II Calibrators 1, 2 and 3, (freeze-dried, recombinant hCG in human plasma with antimicrobial agent, reconstitution volume 1.0 mL), nominal values 0; 3,000; 14,000 mIUmL (U/L)
• 24 calibrator bar code labels (8 for each calibrator)

Here's an analysis of the acceptance criteria and study information based on the provided text, structured according to your request:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly present a dedicated "acceptance criteria" table for all non-clinical tests. Instead, it describes each test (e.g., Precision, Detection Capability, Linearity) and then presents the results, implying that the results met internal acceptance criteria for substantial equivalence to the predicate device. Therefore, I will derive the "acceptance criteria" from the stated goals or industry guidelines mentioned for each test and then present the reported performance.

• 5.33 mIU/mL: 0.095 (1.80%)
• 15.46 mIU/mL: 0.181 (1.20%)
• 45.67 mIU/mL: 0.666 (1.50%)
• 297.34 mIU/mL: 4.970 (1.70%)
• 4708.50 mIU/mL: 82.29 (1.70%)
• 9651.00 mIU/mL: 286.71 (3.00%) |
  | Precision (Within Lab) | Evaluation consistent with CLSI document EP05-A3. (Specific %CV or SD targets not explicitly stated in this section, but implied by acceptable performance.) | Within Lab (SD/%CV):
• 5.33 mIU/mL: 0.281 (5.30%)
• 15.46 mIU/mL: 0.706 (4.60%)
• 45.67 mIU/mL: 1.560 (3.40%)
• 297.34 mIU/mL: 8.640 (2.90%)
• 4708.50 mIU/mL: 151.22 (3.20%)
• 9651.00 mIU/mL: 464.48 (4.80%)
  Further breakdown including Between Lot shows Total %CV up to 6.4% |
  | Detection Capability (LoB) | Evaluation consistent with CLSI document EP17-A2. Supporting the claimed LoB of 0.05 mIU/mL. | Representative LoB is 0.00 mIU/mL (IU/L), which supports the claimed LOB of 0.05 mIU/mL. |
  | Detection Capability (LoD) | Evaluation consistent with CLSI document EP17-A2. Supporting the claimed LoD of 0.70 mIU/mL. | Representative Limit of Detection (LoD) is 0.21 mIU/mL (IU/L), which supports the claimed LoD of 0.70 mIU/mL (IU/L). |
  | Detection Capability (LoQ) | Designed to be less than or equal to the claimed low end of the measuring range (2.39 mIU/mL) at 20% CV. Consistent with CLSI document EP17 (Total Error approach). | Representative LoQ using the Total Error approach was 2.32 mIU/mL (IU/L). Claimed LoQ verified at 2.39 mIU/mL (IU/L). |
  | Linearity | Established in accordance with CLSI guideline EP06 2nd edition. Results support linearity across the specified range. | Supported linearity from 1.51 mIU/mL (IU/L) to 15695 mIU/mL (IU/L). For Lot 2643, Slope was 0.991 (38.6 to 15695) and 1.025 (1.51 to 51.18); R2 was 0.996 and 0.999 respectively; % Recovery ranged from 92.2% to 112.7%. |
  | Measuring Range | The device is expected to have a measuring range on the VITROS 5600 system. | 2.39*-15,000 mIU/mL (IU/L). |
  | Matrix Comparison | Serum and plasma (Lithium-Heparin and K2-EDTA) specimen matrices determined to be equivalent. Results met acceptance criteria for comparison between serum and plasma spanning the expected measuring interval. | Weighted Deming Regression: Li-Hep Plasma (Slope 0.978, Corr. Coef r 0.999), K2-EDTA Plasma (Slope 0.978, Corr. Coef r 0.999). Serum and plasma (Li-Heparin and K2-EDTA) found suitable matrices. |
  | Analytical Specificity (Known Interferents) | Evaluated following CLSI EP07 and EP37. None found to cause a bias of >10% at specified hCG concentrations. | Over 30 common substances (e.g., Acetaminophen, Bilirubin, Biotin, Hemoglobin, Triglycerides) tested at high concentrations (e.g., Acetaminophen 15.6 mg/dL, Hemoglobin 1000 mg/dL, Triglycerides 1500 mg/dL) showed no bias >10% at hCG concentrations of 5.00, 50.00, and 10,000 mIU/mL. |
  | Analytical Specificity (Cross-Reactivity) | Evaluation for cross-reactivity with FSH, LH, and TSH in hCG negative samples and samples with ~25 mIU/mL hCG. | In hCG negative samples, FSH, LH, and TSH (at 400 mIU/mL and 200 mIU/mL respectively) were Not Detectable (ND). With a pool at ~25 mIU/mL hCG, % Cross Reactivity was: FSH (0.6%), LH (-0.3%), TSH (0.4%). |
  | Expected Values (Adult Reference Interval) | Validated following CLSI document EP28-A3c. Distribution of hCG values from normal healthy non-pregnant blood donors shows equivalency to the predicate device's expected values claim. | Original Claim: Total 290 samples, Mean 0.56, Min 0.00, Max 6.66, 2.5th Percentile 0.00, 97.5th Percentile 4.83.
  Updated Pack: Total 180 samples, Mean 0.47, Min 0.00, Max 5.61, 2.5th Percentile 0.00, 97.5th Percentile 3.73. Demonstrated equivalency. |
  | Method Comparison (Accuracy) | Evaluated consistent with CLSI guideline EP09c. Comparison with predicate device (VITROS Immunodiagnostic Products Total β-hCG II reagent pack, K063720). | n=135 samples. Slope 0.99 (95% CI: 0.977 to 0.995). Correlation Coefficient 0.998. Intercept -0.0215 (95% CI: -0.160 to 0.117). (Comparing VITROS Total ß-hCG II (GEM.1076A) against predicate VITROS Total B-hCG (GEM.1076)). Consistent with graphs indicating strong agreement. |

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Stability Studies:
  • Long-term: 3 Lots evaluated.
  • On-board: 3 Lots evaluated.
• Precision:
  • Single Lot Precision: 6 precision fluids. 2 replicates per run, 2 runs per day for 20 days. Total of 80 data points per fluid.
  • Additional Precision Analysis Summary: 6 samples (PP1-6).
  • Multiple System (Reproducibility) Study: 6 precision fluids (RP1-6). 5 replicates per run, 1 run per day for 5 days. Tested on 3 VITROS 5600 integrated systems.
• Detection Capability (LoB): 4 serums containing no measurable hCG. Study design: 2 replicates per run, 2 runs per day over 5 test days (20 reps per test fluid x 4 fluids = 80 replicates) x 3 lots = 240 total replicates.
• Detection Capability (LoD & LoQ): 5 LoD samples targeted at 1 to 5 times LoB. 4 LoQ fluids for Total Error method. All samples run using 3 reagent lots on one VITROS 5600 System. 6 replicates per run, 2 runs per day over 5 test days (60 reps per fluid x 5 fluids = 300 replicates) x 3 lots = 900 total replicates.
• Linearity: Two series: one across entire range (pools 1a to 10a) and one in lower range (pools 1b to 10b). 10 replicates of pools 1a/10 and 10a/10b, and 5 replicates of pools 2a/2b to 9a/9b. Run on one VITROS 5600 Integrated System.
• Matrix Comparison: 41 samples each for Lithium-Heparin Plasma and K2-EDTA Plasma.
• Analytical Specificity (Known Interferents): Not specifically quantified, but refers to "compounds tested" at three hCG concentrations.
• Analytical Specificity (Cross-Reactivity): hCG negative samples and hCG pools at approximately 25 mIU/mL were used for spiking test substances (FSH, LH, TSH).
• Expected Values (Adult Reference Interval):
  • Original Claim (from predicate): 290 total samples (98 normal male, 123 normal female, 69 post-menopausal).
  • Updated Pack Validation: 180 normal healthy non-pregnant blood donors (60 Normal Male, 60 Normal Female, 60 Post-Menopausal).
• Method Comparison: 135 human serum samples.

Data Provenance:

• The document states that human serum samples for method comparison were "obtained from certified vendors."
• Precision fluids mentioned as "pooling female serum samples."
• "Normal healthy non-pregnant blood donors" for expected values.
• "Neat serum samples containing low levels of endogenous hCG" for LoD samples.
• The overall context is non-clinical laboratory testing. No specific country of origin or retrospective/prospective status is explicitly stated for the patient samples used, though the tests themselves were conducted in a laboratory setting per CLSI guidelines. The stability studies and many precision studies seem to be prospective evaluations of the manufactured product. Patient samples, however, are often retrospectively collected from vendors in such studies unless specified.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This device is an in-vitro diagnostic (IVD) test for quantitative measurement of hCG. The "ground truth" for such devices is established through reference methods, traceability to international standards, and comparison with legally marketed predicate devices, rather than expert human interpretation of images or clinical outcomes.

• Traceability: The device's calibration is traceable to "in-house reference calibrators, which have been value-assigned with reference to the 4th International Standard (NIBSC 75/589)." This international standard serves as the "ground truth" for the quantitative measurement.
• Method Comparison: The predicate device (VITROS Immunodiagnostic Products Total β-hCG II, K063720) serves as the comparative "ground truth" for assessing equivalence of performance with patient samples.

Therefore, there were no human "experts" (like radiologists) establishing ground truth in the way described for image-based diagnostic AI. The "ground truth" is defined by established metrological standards and comparative testing against a cleared predicate.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. This is an IVD device for quantitative measurement based on chemical reactions and instrumental readings. There is no human interpretation or subjective assessment of results that would require an adjudication method among experts.

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

Not applicable. This is an IVD device, not an AI-assisted diagnostic tool that aids human readers in image interpretation or clinical decision-making. No MRMC study was conducted.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This device itself is a "standalone" analytical system in the context of laboratory testing. The VITROS Immunodiagnostic Products Total ß-hCG II Reagent Pack, used on the VITROS 5600 Integrated System, performs the quantitative measurement of hCG without immediate human intervention in the assay process itself. The "performance" sections (Precision, Detection Capability, Linearity, etc.) describe its standalone analytical performance.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth for this IVD device is primarily:

• International Reference Standards: Specifically, the 4th International Standard (NIBSC 75/589) for hCG, to which the device's calibration is traceable.
• Comparison to a Legally Marketed Predicate Device: The performance of the new device is compared to the predicate device (VITROS Immunodiagnostic Products Total β-hCG II Reagent Pack, K063720), which established its own accuracy and reliability.
• CLSI Guidelines: Various CLSI (Clinical and Laboratory Standards Institute) documents (e.g., EP05-A3 for Precision, EP17-A2 for Detection Capability, EP06 for Linearity, EP07/EP37 for Interferents, EP28-A3c for Reference Intervals, EP09c for Method Comparison) define the acceptable methodologies for establishing truth and performance in laboratory diagnostics.

8. The sample size for the training set

This document describes a non-AI IVD device. There is no "training set" in the machine learning sense. The device is a chemical reagent pack used on an analyzer. Its "training" equivalent relies on the design, manufacturing tolerances, and calibration traceable to international standards.

9. How the ground truth for the training set was established

Not applicable, as there is no "training set" in the context of an AI/ML algorithm. The "ground truth" for the device's fundamental function (accurate hCG measurement) is established through its traceability to international reference materials and validation against the predicate device, as detailed in point 7.

Ask a specific question about this device

VITROS Immunodiagnostic Products Intact PTH II Reagent Pack quantitatively measures intact parathyroid hormone (iPTH) in human serum and plasma (K2-EDTA, lithium heparin) using the automated VITROS 3600 Immunodiagnostic System.

Intact PTH is indicated to aid in the diagnosis of hyperparathyroidism, differential diagnosis of hypocalcemia or hypercalcemia and for intraoperative measurement of iPTH levels.

The VITROS Immunodiagnostic Products Intact PTH II assay is performed using the VITROS Intact PTH II Reagent Pack and the VITROS Intact PTH II Calibrators on the VITROS 3600 Immunodiagnostic System.

VITROS Intact PTH II Reagent Pack contains:

1 reagent pack containing:

• 100 coated wells (biotinylated anti-PTH antibody, 2ug/ml). ●
• 7.4 mL assay reagent as buffer with bovine gamma globulin, bovine serum albumin, and antimicrobial agent.
• 7.4 mL conjugate reagent (HRP-mouse monoclonal anti-PTH, 6 ug/mL) in buffer with bovine serum albumin and antimicrobial agent).

The provided text is a 510(k) premarket notification for Ortho-Clinical Diagnostics' VITROS Immunodiagnostic Products Intact PTH II Reagent Pack, a device for quantitatively measuring intact parathyroid hormone (iPTH). While it details various performance characteristics, it does not describe an AI/ML-based device and therefore does not contain information on acceptance criteria for such a device, nor an AI/ML specific study.

The document focuses on the analytical and clinical performance of an in vitro diagnostic (IVD) assay, comparing it to a predicate device (Roche Elecsys PTH assay). The studies described are typical for IVD assays: precision, linearity, detection limits, analytical specificity (interference and cross-reactivity), and method comparison against a commercially available PTH assay and a clinical study for intra-operative use.

Therefore, I cannot extract the requested information regarding AI/ML device acceptance criteria and study details from the provided text. The questions below are specifically tailored for AI/ML device evaluations.

However, I can provide the available information relevant to the IVD device's performance studies:

Based on the provided document, here is the information available for the VITROS Immunodiagnostic Products Intact PTH II Reagent Pack, noting that it is an IVD assay, not an AI/ML device:

1. A table of acceptance criteria and the reported device performance

The document does not formally present a table of "acceptance criteria" against which performance is measured in the same way an AI/ML device would demonstrate specified accuracy metrics. Instead, it presents various performance characteristics and states that results "met the acceptance criteria" for certain comparisons without detailing those criteria explicitly in a table.

However, key performance parameters and their reported values are listed below:

2. Sample size used for the test set and the data provenance

• Precision/Reproducibility: Patient pools tested with 80 observations (measurements) over 20 days for each concentration level. Data provenance not specified (country of origin, retrospective/prospective implied as prospective measurement in lab).
• Method Comparison: 206 patient (serum) samples. Data provenance not specified.
• Intra-operative Clinical Study: 32 subjects (sets of specimens) qualified for primary endpoints. Data provenance not specified (likely prospective for the study measurements, but subjects were undergoing surgery, so possibly a mix of retrospective patient selection and prospective sample collection).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

• This device is an IVD assay, not an imaging/AI device requiring expert interpretation for ground truth. Ground truth for an IVD is established by standardized reference methods or the performance of a predicate device/comparator assay.
• For the intra-operative clinical study, the "success" criterion for surgery (50% or greater drop in PTH level) is based on the result from the comparator assay (hospital's assay) and the investigational device, rather than expert judgment on the device's output.

4. Adjudication method for the test set

• Not applicable as this is an IVD assay measuring a biomarker concentration, not an AI/ML device relying on human interpretation or adjudication of output.

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

• Not applicable as this is an IVD assay, not an AI/ML imaging device.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

• The device is a standalone IVD assay. Its performance (precision, linearity, detection limits, analytical specificity, method comparison) is evaluated directly, without human interpretation of its output in the sense of an AI/ML diagnosis. The intra-operative study compares its quantitative results to another quantitative assay.

7. The type of ground truth used

• Analytical Performance (Precision, Linearity, Detection Limits): Established through laboratory testing using controlled samples (e.g., patient pools, dilutions, blanks) according to CLSI (Clinical and Laboratory Standards Institute) protocols (EP05, EP06, EP17). The "ground truth" here is the expected value of the controlled sample or the known characteristics of the samples used.
• Analytical Specificity (Interference, Cross-Reactivity): Known concentrations of interferents or cross-reactants added to samples with known PTH concentrations. Ground truth is the unbiased PTH value.
• Method Comparison: Comparison against a "commercially available PTH assay" (presumably the predicate device, although it's not explicitly named as such in this section, it's implied by "comparative method") as the reference.
• Intra-operative Clinical Study: The "success" criterion (50% or greater drop in PTH) was determined by comparing the device's results to the results from the hospital's (comparator) assay for the same patient samples. The "ground truth" for surgical success was defined by this 50% drop as measured by the comparator, and the study assessed concordance.

8. The sample size for the training set

• Not applicable. This is an IVD assay, not an AI/ML algorithm that requires a "training set." The system is a reagent pack and instrument system, not a learned model.

9. How the ground truth for the training set was established

• Not applicable (no training set for an IVD assay).

Ask a specific question about this device

For In Vitro Diagnostic Use Only

For the quantitative measurement of carcinoembryonic antigen (CEA) concentration in human serum and plasma (EDTA or heparin) using the VITROS 5600 Integrated System, to aid in the prognosis and management of cancer patients in whom changing concentrations of CEA are observed.

The VITROS Immunodiagnostic Products CEA Reagent Pack (test) is performed using the VITROS CEA Reagent Pack and VITROS CEA Calibrators on the VITROS 5600 System.

An immunometric immunoassay technique is used, which involves the reaction of CEA present in the sample with a microwell coated with biotinylated Antibody (Mouse monoclonal anti-CEA) bound to Streptavidin, and a Horseradish Peroxidase (HRP)-labelled antibody conjugate (Mouse monoclonal anti- CEA). Unbound (HRP)-labeled anti-CEA antibody conjugate is removed by washing.

The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent, is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the system. The amount of HRP conjugate bound is directly proportional to the concentration of CEA present in the sample.

VITROS CEA Reagent Pack contains:
1 reagent pack containing:

• 100 coated wells (antibody, mouse monoclonal anti-CEA, binds ≥8ng CEA/well); ●
• 9.7 mL assay reagent (buffer containing bovine serum albumin, bovine gamma globulin and . antimicrobial agent).
• 9.7 mL conjugate reagent (HRP-mouse monoclonal anti-CEA, binds ≥123ng CEA/mL). ●

VITROS CEA Calibrator contains:

• 1 set of VITROS CEA Calibrators 1 and 2 (human CEA in bovine serum with ● antimicrobial agent, 2 mL); nominal values 3 and 250 ng/mL (us/L)
• 16 calibrator bar code labels (8 for each calibrator) ●

The provided document describes the safety and effectiveness information for the VITROS Immunodiagnostic Products CEA Reagent Pack (K231517), which is intended for the quantitative measurement of carcinoembryonic antigen (CEA) in human serum and plasma to aid in the prognosis and management of cancer patients. The document primarily focuses on nonclinical performance studies to demonstrate substantial equivalence to a predicate device.

Here's a breakdown of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a singular table alongside performance for all aspects. However, it implicitly defines acceptance by stating that certain studies were performed "consistent with CLSI document" guidelines and that "all results were acceptable" or "met the acceptance criteria." For linearity, it specifies "Allowable nonlinearity." For matrix comparison, it states "The results met the acceptance criteria."

Here's an attempt to synthesize the acceptance criteria and performance from the text for key analytical characteristics:

2. Sample Size Used for the Test Set and Data Provenance

• Precision:
  • 5600 System (Table 1): 4 precision fluids. 2 replicates per fluid, 2 occasions per day, for 20 days. Total 80 data points per fluid.
  • Additional Precision Analysis (Table 2): 4 precision fluids (PP1-PP4). 240 observations per sample (likely 2 replicates per run, multiple runs, over multiple days/lots as per CLSI guideline EP05-A3).
• Detection Capability (LoB): 4 endogenous fluids. 2 replicates per run, 2 runs per day, over 5 test days. Total 20 replicates per test fluid x 4 fluids = 80 replicates total for LoB. Tested on 3 lots, so 240 total replicates.
• Detection Capability (LoD & LoQ): 5 samples. 6 replicates per run, 2 runs per day, over 5 test days. Total 60 replicates per fluid x 5 fluids = 300 replicates total for LoD/LoQ. Tested on 3 lots, so 900 total replicates.
• Linearity: 13 levels, five replicates for each level.
• Matrix Comparison: Not specified precisely, but samples were "spanning the expected measuring interval."
• Analytical Specificity (Interferents): Not specified (e.g., number of replicates or distinct samples).
• High Dose Hook: Panel of ten fluids. Tested in singleton.
• Method Comparison (Accuracy): 110 human serum samples. Tested in singleton.

Data Provenance:
The document consistently refers to "human serum" or "patient samples." For the method comparison, it states "Human serum samples were obtained from certified vendors." For detection capability, it mentions "endogenous fluids" and "admixtures of serum samples containing endogenous CEA combined with CEA affinity stripped serum." For expected values, it refers to "healthy non-smokers (n=68)" and "healthy smokers (n=72)."
The country of origin is not specified but the submitter is Ortho-Clinical Diagnostics Inc. from the UK. The studies are nonclinical performance studies, often conducted in-house or by contract research organizations. These studies are prospective in nature, as they are designed experiments to evaluate specific performance characteristics.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts

Ground truth for these studies is analytically derived, not expert consensus interpretation. For in vitro diagnostic devices like the CEA assay, the "ground truth" for test sets in nonclinical studies typically refers to:

• Reference values assigned by highly accurate reference methods or known concentrations of analytes (e.g., spiked samples) for linearity, detection, and accuracy studies.
• The known physiological state of samples (e.g., healthy non-smokers, healthy smokers) for reference intervals.
• The known presence/absence and concentration of interferents for specificity studies.

Therefore, the concept of "experts establishing ground truth" in the sense of clinical interpretation (like radiologists for imaging) is not applicable here. The ground truth is established by the design of the analytical experiment and the reference materials/methods used.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are typically used in clinical studies where human interpretation of data (e.g., images) forms the ground truth, and discrepancies need to be resolved. This is not relevant for the analytical performance studies of a laboratory immunoassay described in this document.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. An MRMC study is relevant for devices involving human interpretation (e.g., medical imaging) to assess how the device impacts human reader performance. This document describes the analytical performance of an in vitro diagnostic immunoassay.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, this entire submission describes the standalone performance of the VITROS Immunodiagnostic Products CEA Reagent Pack and the VITROS 5600 Integrated System. The data presented are purely analytical measurements performed by the device, without human interpretive input or assistance being part of its core function.

7. The Type of Ground Truth Used

• Stability: Time points with known age of reagents/calibrators/samples.
• Precision: Control materials or patient samples where inherent variability is being measured. No "ground truth" in the sense of an absolute true value is typically assigned for precision, but rather the repeatability and reproducibility of the measurements around a mean.
• Detection Capability: Samples confirmed to contain no measurable CEA (for LoB) or samples with targeted, known low concentrations of CEA (for LoD and LoQ), often prepared by spiking.
• Linearity: Samples covering a wide range of concentrations, often prepared by dilution of a high-concentration sample with known low-concentration diluent, such that the "expected value" is calculable.
• Matrix Comparison: Patient samples (serum vs. various plasma types) where a comparison between matrices is the objective, not an absolute ground truth value.
• Analytical Specificity: Samples spiked with known concentrations of potential interfering substances, with the expectation that the CEA measurement should not be significantly biased.
• High Dose Hook: Samples with extremely high, known CEA concentrations to ensure the device correctly reports high values and doesn't "hook" and report falsely low.
• Method Comparison (Accuracy): Patient samples compared against a legally marketed predicate device (VITROS CEA assay K041322) on the same system. The predicate device's results serve as the comparative measure, assumed to be accurate for the purpose of demonstrating equivalence.
• Expected Values: Clinically healthy subjects (non-smokers and smokers) categorized by their CEA levels.

In summary, the ground truth is primarily based on analytical reference materials, known spiked concentrations, and comparative measurements against a predicate device, all within the domain of quantitative laboratory measurements.

8. The Sample Size for the Training Set

This document describes nonclinical performance testing for an in vitro diagnostic device, not a machine learning or AI algorithm in the typical sense that would involve a "training set." The device is a chemical reagent pack used on an automated immunoassay system. While there were certainly development and validation phases during the device's creation (which might involve analogous processes to "training"), the document provided does not detail a "training set" in the context of an AI/ML algorithm. The studies described are validation studies of the finalized product.

9. How the Ground Truth for the Training Set Was Established

As noted in point 8, the concept of a "training set" with established ground truth as typically understood for AI/ML is not applicable to this kind of device and its regulatory submission. The document focuses on demonstrating the analytical performance of a developed immunoassay kit.

Ask a specific question about this device

For in vitro diagnostic use only.

For the quantitative measurement of 1116-NS-19-9 defined antigen in human serum and plasma (EDTA or heparin), using the VITROS 5600 Integrated System. The VITROS CA 19-9 test is to be used to aid in the management of patients diagnosed with cancers of the exocrine pancreas. The VITROS CA 19-9 test can be used to monitor the disease status in patients with confirmed pancreatic cancer who show measurable CA 19-9 values over the course of their disease. Serial CA 19-9 test results should be used in conjunction with all other available clinical and laboratory data before a medical decision is determined.

The VITROS Immunodiagnostic Products CA 19-9 assay (test) is performed using the VITROS Immunodiagnostic Products CA 19-9TM Reagent Pack and VITROS CA 19-9 Calibrators on the VITROS 5600 System.

An immunometric immunoassay technique is used, which involves the simultaneous reaction of 1116-NS-19-9 defined antigen present in the sample with a microwell coated with biotinylated Antibody (Mouse monoclonal anti-1116-NS-19-9 defined antigen) bound to Streptavidin. In a second incubation a Horseradish Peroxidase (HRP)- labelled antibody conjugate (Mouse monoclonal anti-1116-NS-19-9 defined antigen) binds to the immobilized 1116-NS-19-9 defined antigen. Unbound materials are removed by washing.

The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent, is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the system. The amount of conjugate bound is directly proportional to the concentration of 1116-NS-19-9 defined antigen present in the sample.

VITROS Immunodiagnostic Products CA 19-9™ Reagent Pack contains:
1 reagent pack containing:

• 100 coated wells (antibody, mouse monoclonal anti-1116-NS-19-9 defined antigen, binds >49 U 1116-NS-19-9 defined antigen/well)
• 13.4 mL assay reagent (buffer containing bovine gamma globulin and antimicrobial agent)
• 20.0 mL conjugate reagent (HRP-mouse monoclonal anti-1116-NS-19-9 defined antigen, binds ≥326 U 1116-NS-19-9 defined antigen/mL) in buffer with bovine serum albumin, bovine gamma globulin and antimicrobial agent.

VITROS CA 19-9 Calibrator contains:

• 1, 2, and 3 (OC 1116-NS-19-9 defined antigen in buffer with bovine serum albumin and antimicrobial agent, 1.75 mL); nominal values 15; 60 and 700 U 1116-NS-19-9 defined antigen/mL
• 24 calibrator bar code labels (8 for each calibrator)

This document describes the non-clinical performance studies conducted for the VITROS CA 19-9 assay to demonstrate its safety and effectiveness. The information focuses on analytical performance characteristics rather than clinical diagnostic accuracy studies involving human experts for ground truth, which are typically found in studies for AI/ML-based medical devices or imaging diagnostics.

Since this device is an in-vitro diagnostic (IVD) assay for measuring a tumor-associated antigen (CA 19-9) in human serum and plasma, the "acceptance criteria" and "study that proves the device meets the acceptance criteria" are primarily based on established analytical performance parameters, not on human-expert-validated diagnostic accuracy. Therefore, several points from your request (e.g., number of experts, adjudication methods, MRMC studies, human-in-the-loop performance) are not directly applicable or reported in this type of submission.

Here's the breakdown of the acceptance criteria and study information provided:

1. Table of Acceptance Criteria and Reported Device Performance

The document presents validation studies against established guidelines (e.g., CLSI documents) and compares the modified device's performance to its predicate. The nature of these acceptance criteria is based on quantitative analytical performance characteristics.

2. Sample Sizes Used for the Test Set and Data Provenance

The "test set" here refers to the samples used in the analytical validation studies. These are not human-interpreted images or clinical datasets in the AI/ML sense but rather biological samples.

• Stability Studies: Four runs on each of 3 lots at monthly intervals for long-term; 3 lots up to 12 weeks for on-board stability. Number of samples not explicitly stated but implies sufficient runs to validate stability claims.
• Precision: 6 precision fluids; 2 replicates, 2 runs/day for 20 days (total 80 data points per fluid).
• Detection Capability (LoB): 4 endogenous fluids with no CA19-9; 2 replicates, 2 runs/day for 5 test days (20 reps/fluid) x 4 fluids = 80 replicates x 3 lots = 240 total replicates.
• Detection Capability (LoD/LoQ): 5 samples; 6 replicates, 2 runs/day for 5 test days (60 reps/fluid) x 5 fluids = 300 replicates x 3 lots = 900 total replicates.
• Linearity: 16 levels in the test panel; 5 replicates of each level run on 3 reagent lots over 2 days.
• Matrix Comparison: 41 specimens for Li-Hep vs. Serum and 41 specimens for EDTA vs. Serum.
• Analytical Specificity (Interferences): Tested at CA 19-9 concentrations of ~5.0 U/mL and ~50.0 U/mL. Specific sample numbers for this testing are not given but are implied to be within CLSI guidelines.
• Expected Values (Reference Interval): 60 normal blood donors.
• Method Comparison: 118 patient serum samples.

Data Provenance: The document does not explicitly state the country of origin for the samples or if they were retrospectively or prospectively collected. The studies appear to be laboratory-based analytical validation studies.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This concept is not applicable to this type of IVD analytical device validation. The "ground truth" for the performance of a CA 19-9 assay is established by the known concentration of the analyte in control samples, reference materials, or by comparison to a well-validated predicate method, not by human expert interpretation of images or clinical outcomes.

4. Adjudication Method for the Test Set

This concept is not applicable to this type of IVD analytical device validation. Adjudication is typically used for reconciling disagreements among human experts in diagnostic imaging interpretation or clinical decision-making.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size

An MRMC study is not applicable to this device. This type of study assesses how human readers' diagnostic accuracy changes with or without AI assistance, which is for AI/ML-based diagnostic devices (e.g., imaging AI). This device is a quantitative immunoassay.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

This concept is not applicable in the context of an IVD assay. The "algorithm" is the biochemical reaction and the instrument's measurement system. The device's "standalone" performance is what these non-clinical analytical studies demonstrate. The results are quantitative measurements of the CA 19-9 antigen, not classifications or detections that would then be presented to a human for interpretation.

7. The Type of Ground Truth Used

• Analyte Concentration: For precision, detection capability, linearity, known interferences, and dilution, the "ground truth" is based on the known or reference concentrations of CA 19-9 in control materials, spiked samples, or reference standards.
• Comparative Method: For method comparison, the "ground truth" is established by the results from the legally marketed predicate device (VITROS CA 19-9 assay, K052889).
• Normal Population Reference: For expected values, the "truth" is established by determining the range of values observed in a healthy, "normal" population.

8. The Sample Size for the Training Set

This document does not describe a "training set" in the context of machine learning. For an IVD assay, the development process involves reagent formulation, instrument calibration, and optimization using iterative testing and refinement, not a distinct "training set" of data in the AI/ML sense. The studies described are validation activities for the final device.

9. How the Ground Truth for the Training Set was Established

As there is no "training set" in the AI/ML sense for this IVD, this question is not applicable. The "ground truth" for developing and calibrating an IVD like this would be established through highly controlled laboratory preparations of samples with known concentrations of the target analyte, often traceable to international standards if available. Calibration itself establishes the relationship between the measured signal and the concentration of the analyte.

Ask a specific question about this device

For in vitro diagnostic and laboratory professional use.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator is a chemiluminescent immunoassay intended for the qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma (K2-EDTA and K3-EDTA) samples collected on or after 15 days post-symptom onset using the VITROS ECi/ECiO/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator

For use in the calibration of the VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems for the in vitro qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is a qualitative chemiluminescent immunoassay performed on the VITROS Systems (VITROS ECi/ECiO Immunodiagnostic System, VITROS 3600 Immunodiagnostic System, VITROS 5600 Integrated System and VITROS XT 7600 Integrated System) providing fully automated random-access testing.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls on the VITROS Systems.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack is supplied as ready to use and contains:

• 100 wells coated with 100ng/well of recombinant SARS-CoV-2 spike antigen derived from human cells.
• 18.0 mL assay reagent (buffer with bovine protein stabilizers and antimicrobial agent)
• 20.4 mL conjugate reagent [anti-human IgG (murine monoclonal) conjugated to horseradish peroxidase, 5ng/mL] in buffer with bovine protein stabilizers and antimicrobial agent.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator contains:

• 2 vials of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 1gG Calibrator 0 (anti-SARS-CoV-2 IgG in anti-SARS-CoV-2 IgG negative human serum with antimicrobial agent, 1 mL)
• Lot calibration card
• Protocol card
• 8 calibrator bar code labels

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls contain:

• 3 sets of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls 1 and 2 (defibrinated human plasma with anti-microbial agent, 2 mL). Control 1 is non-reactive and Control 2 is reactive

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is designed for use on the VITROS Systems. The VITROS Systems use the following ancillary reagents (general purpose reagents):

• VITROS Immunodiagnostic Products Signal Reagent
• VITROS Immunodiagnostic Products Universal Wash Reagent

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

Device: VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack, VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator (Chemiluminescent Immunoassay)

Purpose: Qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma, intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

1. Table of Acceptance Criteria and Reported Device Performance

The document describes the performance of the device rather than explicitly stating pre-defined acceptance criteria in a dedicated table. However, we can infer the implicit acceptance criteria from the observed results and the FDA's decision to grant the De Novo request.

Ask a specific question about this device

For in vitro diagnostic and laboratory professional use.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator is a chemiluminescent immunoassay intended for the qualitative detection of total antibodies to SARS-CoV-2 in human serum and plasma (K-EDTA. K-EDTA and lithium heparin) samples collected on or after 15 days post-symptom onset using the VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

For use in the calibration of the VITROS ECi/ECiO/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems for the in vitro qualitative detection of total antibodies to SARS-CoV-2 in human serum and plasma.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is a qualitative chemiluminescent immunoassay performed on the VITROS Systems (VITROS ECi/ECiQ Immunodiagnostic System, VITROS 3600 Immunodiagnostic System, VITROS 5600 Integrated System and VITROS XT 7600 Integrated System) providing fully automated random-access testing.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls on the VITROS Systems.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack is supplied as ready to use and contains:

• . 100 coated wells (streptavidin, bacterial; binds ≥3 ng biotin per well; biotin recombinant SARS-CoV-2 antigen 0.1 ug/mL)
• 6.0 mL assay reagent (buffer with bovine protein stabilizers and antimicrobial agent) .
• . 16.2 mL conjugate reagent (HRP-recombinant SARS-CoV-2 antigen) in buffer with bovine protein stabilizers and antimicrobial agent

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator contains:

• . 2 vials of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator (anti-SARS-CoV-2 in anti-SARS-CoV-2 negative human plasma with antimicrobial agent, 1 mL)
• . Lot calibration card
• . Protocol card
• . 8 calibrator bar code labels

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls contain:

• . 3 sets of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls 1 and 2 (defibrinated human plasma with anti-microbial agent, 2 mL). Control 1 is non-reactive and Control 2 is reactive.
  The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is designed for use on the VITROS Systems. The VITROS Systems use the following ancillary reagents (general purpose reagents):
• . VITROS Immunodiagnostic Products Signal Reagent
• VITROS Immunodiagnostic Products Universal Wash Reagent .

The document describes the evaluation of the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator, a chemiluminescent immunoassay intended for qualitative detection of total antibodies to SARS-CoV-2.

Here's an analysis of the acceptance criteria and the study proving the device meets them:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" for the clinical performance in a single, clear table with pass/fail thresholds. However, the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) are the key clinical performance metrics presented. The FDA's decision to grant De Novo status implies that the reported performance met their internal criteria for safety and effectiveness for its intended use.

Here's a summary of the reported clinical performance:

Note: The PPA for samples collected early (0-7 days and 8-14 days post-symptom onset) is considerably lower (e.g., 36.00% to 44.00% for 0-7 days), reflecting the time required for antibody development. The indication for use specifies "samples collected on or after 15 days post-symptom onset," making the PPA for ≥15 days the most relevant for the primary intended use.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Test Set Sample Size:

  • PPA (Clinical Sensitivity Equivalent): 296 samples from individuals with prior SARS-CoV-2 positive RT-PCR results were initially acquired. However, the "Number of Subjects Tested" varies slightly per analyzer, typically around 282-286 for individual system reporting, and 237-239 for the ≥15 days post-symptom onset group which is the most relevant for the device's claims.
  • NPA (Clinical Specificity Equivalent): 513 presumed SARS-CoV-2 negative samples collected prior to the COVID-19 pandemic. The "Presumed Negative" count also varies slightly per analyzer, typically around 505-511.

• Data Provenance:

  • Country of Origin: All samples were collected within the United States.
  • Retrospective or Prospective: The samples were collected retrospectively. Population 1 (positive samples) was collected between April 2020 and April 2021. Population 2 (negative samples) was collected prior to December 2019.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This is an in vitro diagnostic device for antibody detection, not an imaging AI system. Therefore, the "ground truth" for the clinical study was established by RT-PCR test results for SARS-CoV-2 infection (for positive samples) and collection of samples prior to the COVID-19 pandemic (for negative samples). There is no mention of human experts (e.g., pathologists or radiologists) adjudicating the ground truth for this type of test.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable for this type of in vitro diagnostic test where RT-PCR is the comparator and pre-pandemic samples define the negative group. Discrepancy resolution with expert radiologists would be relevant for imaging-based AI studies, not serology tests.

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

Not applicable. This is an in vitro diagnostic (IVD) device for laboratory use, not an AI-assisted diagnostic tool for human readers (e.g., radiologists interpreting images). Its performance is evaluated as a standalone laboratory test.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, the clinical performance (PPA and NPA) presented for the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is its standalone performance as an automated laboratory assay. There is no human-in-the-loop component for the interpretation or usage of the result beyond the laboratory professional's decision to report the qualitative positive/negative result.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

• For Positive Samples (PPA): Ground truth was established by prior SARS-CoV-2 positive RT-PCR test results. The document states, "...using a comparator that FDA determined is appropriate (RT-PCR test)."
• For Negative Samples (NPA): Ground truth was established by collection date prior to the widespread outbreak of COVID-19 (i.e., prior to December 2019), deeming them "presumed SARS-CoV-2 negative samples."

8. The sample size for the training set

This document describes the validation of a commercial in vitro diagnostic (IVD) product, not an AI/machine learning model where a distinct 'training set' of patient data in the typical AI sense would be used to train the algorithm. The "training" of this device involves the development and optimization of the chemical reagents, assay parameters, and cutoff values performed internally by the manufacturer (Ortho-Clinical Diagnostics).

The closest equivalent to a "training" activity described in the context of setting the device's operational parameters is the Assay Cut-Off determination study (page 12-13). This study used:

• "a collection of negative samples collected prior to the COVID-19 pandemic"
• "samples collected from individuals with a prior SARS-CoV-2 RT-PCR positive result."

The specific numbers of these samples for the cutoff determination are not explicitly stated, but are implied to be part of the broader pool of samples available to the manufacturer during development. The ROC curve analysis was performed on these samples to optimize sensitivity and specificity at the S/C = 1.00 cutoff.

9. How the ground truth for the training set was established

As noted in point 8, this isn't an AI model with a conventional training set. For the "samples" used in the Assay Cut-Off determination (analogous to internal optimization/training data):

• Negative Ground Truth: Established by "negative samples collected prior to the COVID-19 pandemic."
• Positive Ground Truth: Established by "samples collected from individuals with a prior SARS-CoV-2 RT-PCR positive result."

This implies a similar method to the clinical validation set for establishing true positive and true negative status, but performed during the device development phase to define the S/C cutoff.

Ask a specific question about this device

For the quantitative measurement of OC 125 defined antigen concentration in human serum and plasma (EDTA or heparin) using the VITROS 5600 Integrated System. The VITROS CA 125 II assay is to be used as an aid in monitoring response to therapy for patients with epithelial ovarian cancer. Serial testing for patient CA 125 assay concentrations should be used in conjunction with other clinical methods used for monitoring ovarian cancer.

The VITROS Immunodiagnostic Products CA 125 II Reagent Pack (test) is performed using the VITROS CA 125 II Reagent Pack and VITROS CA 125 II Calibrators on the VITROS 5600 System. An immunometric immunoassay technique is used, which involves the reaction of OC 125 present in the sample with a microwell coated with biotinylated Antibody (Mouse monoclonal anti-OC 125) bound to Streptavidin, and a Horseradish Peroxidase (HRP)-labelled antibody conjugate (Mouse monoclonal anti- OC 125). Unbound (HRP)-labeled anti-OC 125 antibody conjugate is removed by washing. The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent, is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the system. The amount of conjugate bound is directly proportional to the concentration of OC 125 present in the sample.

Here's an analysis of the provided text, outlining the acceptance criteria and study details for the VITROS Immunodiagnostic Products CA 125 II Reagent Pack:

This document is a 510(k) summary for a medical device ([K221355](https://510k.innolitics.com/search/K221355)) and primarily focuses on demonstrating substantial equivalence to a predicate device. As such, it reports on various analytical performance studies rather than user studies or comparative effectiveness studies involving human readers or AI.

Acceptance Criteria and Reported Device Performance

Ask a specific question about this device

For the quantitative measurement of alpha-fetoprotein (AFP) concentrations in human serum using the VITROS 5600 Integrated system to aid in the management of patients with non-seminomatous testicular cancer.

The VITROS Immunodiagnostic Products AFP Reagent Pack is performed using the VITROS Immunodiagnostic Products AFP Reagent Pack and the VITROS AFP Calibrators on the VITROS 5600 System. VITROS Immunodiagnostic Products AFP Reagent Pack contains: 1 reagent pack containing: 100 coated wells (antibody, sheep anti-AFP, binds>25 IU AFP/well); 20.6 mL conjugate reagent (HRP-mouse monoclonal anti-AFP, binds ≥156 IU AFP/ mL) in buffer with bovine serum and antimicrobial agent; 15.8 mL assay reagent (buffer containing bovine serum albumin and antimicrobial agent). VITROS Immunodiagnostic Products AFP Calibrator contains: 1 set of VITROS AFP Calibrators 1, 2 and 3 (human cord serum/plasma derived AFP in human plasma with antimicrobial agent, 2 mL); nominal values 2; 22 and 220 IU/mL (1st International Reference Preparation 72/225) (2.42; 26.6 and 266 ng/mL); Lot calibration card; Protocol card; 24 calibrator bar code labels (8 for each calibrator).

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for the VITROS Immunodiagnostic Products AFP Reagent Pack:

Device Name: VITROS® Immunodiagnostic Products AFP Reagent Pack
Intended Use: For the quantitative measurement of alpha-fetoprotein (AFP) concentrations in human serum using the VITROS 5600 Integrated system to aid in the management of patients with non-seminomatous testicular cancer.

1. Acceptance Criteria and Reported Device Performance

2. Sample Size Used for the Test Set and Data Provenance

• Precision/Reproducibility: Patient pools were used.
  • For each mean AFP concentration value, 80 observations were made over 20 days.
  • Provenance: Not explicitly stated (e.g., country of origin). The use of "patient pools" implies human samples, likely retrospective, created by combining individual patient samples.
• Linearity: Not specified as a separate "test set" with a specific sample size, but established using the CLSI protocol EP06, which involves creating dilution series.
• Detection Limits (LoB, LoD, LoQ): Not specified as a distinct "test set" sample size. Determined consistent with CLSI document EP17.
• Analytical Specificity/Known Interferences: Not specified as a distinct "test set" sample size. Tested at two AFP concentrations (4.80 IU/mL and 19.2 IU/mL) with various interfering substances.
• Cross-Reactivity: Not specified as a distinct "test set" sample size. Evaluated by adding specific substances to an AFP-free sample.
• Method Comparison with Predicate Device:
  • Sample Size: 150 patient serum samples.
  • Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). The samples were "patient (serum) samples."

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

This device is an in vitro diagnostic (IVD) immunoassay for quantitative measurement of alpha-fetoprotein. The "ground truth" for such devices is typically established through reference methods and certified reference materials traceable to international standards, rather than expert consensus on individual cases.

• Traceability: Calibration is traceable to in-house reference calibrators, which are calibrated against the First International Reference Preparation 72/225. This indicates a high-level, international standard for AFP measurement, providing the "ground truth" reference for the assays.
• There were no experts used in the sense of clinical specialists establishing a diagnosis or outcome for the test data, as the study focuses on the analytical performance of the assay.

4. Adjudication Method for the Test Set

Not applicable. As an IVD device measuring a biomarker concentration, the "judgement" is determined by the analytical results against established reference materials and comparison to a predicate device, not by multi-expert review of clinical cases.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not done. This type of study is typically relevant for interpretative diagnostic devices (e.g., imaging AI) where human readers make a diagnosis or assessment, and the AI assists or replaces that human interpretation. For a quantitative immunoassay like this AFP reagent pack, the performance is assessed analytically and by method comparison, not by reader performance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, the studies presented are standalone performance evaluations of the VITROS Immunodiagnostic Products AFP Reagent Pack and the VITROS 5600 Integrated system. The reported precision, linearity, detection limits, analytical specificity, cross-reactivity, and method comparison are all characteristics of the assay system itself, without human intervention in the result generation or interpretation beyond the standard operation of the instrument.

7. Type of Ground Truth Used

The ground truth for the analytical performance of this immunoassay is based on:

• Reference Materials and International Standards: Calibration is traceable to the First International Reference Preparation 72/225. This is a highly characterized and internationally recognized standard for AFP.
• Predicate Device Comparison: For accuracy, the device's performance was compared against a legally marketed predicate device (VITROS Immunodiagnostic Products AFP Reagent Pack K983031), which itself would have been validated against reference standards.

8. Sample Size for the Training Set

The document does not specify a "training set" in the context of a machine learning or AI algorithm. This device is a traditional immunoassay, not an AI/ML-based diagnostic. Therefore, the concept of a "training set" for an algorithm is not applicable here. Performance characteristics are established through analytical validation studies using various types of samples (patient pools, spiked samples, etc.).

9. How the Ground Truth for the Training Set Was Established

As noted in point 8, the concept of a "training set" is not applicable for this traditional immunoassay device. The analytical "ground truth" is established using traceable reference materials and comparison to a predicate device, as described in point 7.

Ask a specific question about this device

Rx ONLY

For in vitro diagnostic use only.

For the quantitative measurement of CK-MB in human serum and plasma (EDTA or heparin) using the VITROS 3600 Immunodiagnostic System.

Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

The VITROS Immunodiagnostic Products CK-MB assay is performed using the VITROS CK-MB Reagent Pack and the VITROS CK-MB Calibrators on the VITROS Systems.

The current VITROS Immunodiagnostic Products CK-MB assay is susceptible to interference from biotin. Ortho has made a modification to the manufacturing process to allow the biotinylated antibody capture conjugate to be pre-bound to the well, thus mitigating the risk of biotin interference.
The modified product utilizes all the same antibodies and raw materials with the exception of the addition of 0.7% Tween 20 and an increase in EDTA concentration from 0.001M to 0.030M, both of these modifications are to improve serum/plasma agreement which required a conversion factor in the previously cleared product.

An immunometric immunoassay technique is used, which involves the reaction of CK-MB present in the sample with a microwell coated with biotinylated Antibody (Mouse monoclonal anti-CK-BB bound to Streptavidin), and a Horseradish Peroxidase (HRP)-labeled antibody conjugate (Mouse monoclonal anti-CK-MB). Unbound (HRP)-labeled anti-CK-MB antibody conjugate is removed by washing.

The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent, is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the system. The amount of CK-MB conjugate bound is directly proportional to the concentration of CK-MB present in the sample.

The provided document describes the 510(k) premarket notification for the VITROS Immunodiagnostic Products CK-MB Reagent Pack. This is an in vitro diagnostic device, not an AI/ML-based medical device. Therefore, many of the requested criteria related to AI/ML device testing (e.g., number of experts for ground truth, adjudication methods, MRMC studies, sample sizes for training sets) are not applicable to this document.

The document focuses on demonstrating the substantial equivalence of a modified CK-MB assay to a legally marketed predicate device, primarily through non-clinical performance studies.

Here's an analysis based on the provided text, addressing the applicable criteria for an in vitro diagnostic device:

1. Table of Acceptance Criteria and Reported Device Performance

For an in vitro diagnostic device like this, acceptance criteria typically revolve around analytical performance characteristics such as precision, linearity, detection limits, and method comparison to a predicate. The document doesn't explicitly state "acceptance criteria" as a pass/fail threshold, but rather presents the results of various validation studies.

• Cefoxitin (at 521 mg/dL): -27.7% bias at 3.00 ng/mL CK-MB
• Dextran 40 (at 2400 mg/dL): -15.0% bias at 3.00 ng/mL CK-MB; -44.9% bias at 50.0 ng/mL CK-MB |
  | Cross-Reactivity | Minimal or no cross-reactivity with structurally similar substances. | CK-BB (50 µg/dL): Not Detectable
  CK-MM (4 mg/dL): Not Detectable |
  | Method Comparison to Predicate Device (Accuracy) | Strong correlation and minimal bias compared to the predicate device, with slope close to 1 and intercept close to 0. | System (3600 vs. Comparative Method):
• n: 149 patient samples
• Slope: 0.99 (95% CI: 0.9812 to 0.9950)
• Correlation Coefficient: 0.999
• Intercept: 0.112 ng/mL (95% CI: 0.05080 to 0.1723) |
  | High Dose Hook Effect | No significant hook effect within relevant supraphysiological concentrations. | No high dose hook effect up to 44,200 ng/mL (µg/L). |

2. Sample Sizes Used for the Test Set and Data Provenance

• Precision:
  • Sample Size: 80 observations (likely meaning replicates across runs and days, as per CLSI EP05 methodology) for each of 4 patient pools.
  • Data Provenance: Not explicitly stated, but typically from internal lab testing.
• Limit of Detection/Quantitation: Not explicitly stated, but derived from experiments consistent with CLSI document EP17.
• Analytical Specificity (Interference) & Cross-Reactivity: Not explicitly stated, but involves testing at specific concentrations of CK-MB and interferents.
• Method Comparison to Predicate Device:
  • Sample Size: 149 patient (serum) samples.
  • Data Provenance: Not explicitly stated regarding country of origin, but described as "patient (serum) samples," implying collected clinical samples. The study is an analytical/non-clinical study, not a clinical trial, so it's prospective in the sense of testing the new device on these samples.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts

• Not Applicable. This is an in vitro diagnostic device measuring a biomarker concentration. The "ground truth" for method comparison is the measurement obtained by the predicate device and the analytical properties of the reference materials. Expertise is in laboratory medicine and analytical chemistry, not interpretation of images for diagnosis by human experts.

4. Adjudication Method for the Test Set

• Not Applicable. As above, no human expert adjudication is involved in establishing the "ground truth" for quantitative assay validation.

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

• Not Applicable. This is not an AI/ML device, nor does it involve human readers interpreting images.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

• Not Applicable. While the device operates standalone (human performs the test, the system provides a result), the concept of an "algorithm only" performance study typically refers to AI/ML models. For an IVD, the "standalone performance" is exactly what is described in the precision, linearity, and detection limit sections.

7. The Type of Ground Truth Used

• For precision, linearity, and detection limits: Analyte concentrations of reference materials or patient pools. The "truth" is established by highly controlled laboratory methods.
• For method comparison: Results obtained from the legally marketed predicate device (VITROS Immunodiagnostic CK-MB Reagent Pack, K993068). The predicate serves as the "true" or gold standard against which the modified device is compared. This is a common "ground truth" for demonstrating substantial equivalence for IVDs. While not explicitly stated, these predicate measurements would have been established through a similar robust validation process.

8. The Sample Size for the Training Set

• Not Applicable. This is not an AI/ML device, so there is no "training set" in the sense of machine learning. The device's performance characteristics are inherent to its chemical and biological components and manufacturing process, validated through the non-clinical studies detailed.

9. How the Ground Truth for the Training Set Was Established

• Not Applicable. As there is no training set for an AI/ML model, this question is not relevant. The device development involved standard IVD R&D and manufacturing, not machine learning training.

Ask a specific question about this device