CA 125 II ASSAY FOR THE BAYER ADVIA INTEGRATED MODULE SYSTEM

K022329 · Bayer Diagnostics Corp. · LTK · Nov 27, 2002 · Immunology

Device Facts

• Record ID: K022329
• Device Name: CA 125 II ASSAY FOR THE BAYER ADVIA INTEGRATED MODULE SYSTEM
• Applicant: Bayer Diagnostics Corp.
• Product Code: LTK · Immunology
• Decision Date: Nov 27, 2002
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.6010
• Device Class: Class 2

Indications for Use

This in vitro immunoassay is intended to quantitatively measure OC 125 reactive determinants associated with a high molecular weight glycoprotein in serum of women with primary epithelial invasive ovarian cancer using ADVIA IMS CA125 II Assay on a Bayer ADVIA® IMS™. CA 125 II Assay is indicated as an aid in the management (monitoring) of ovarian cancer patients when used in conjunction with other diagnostics procedures. The CA 125 II Assay is also indicated as a one-time test for use as an aid in the detection of residual ovarian carcinoma in patients who have undergone firstline therapy and would be considered diagnostic second-look procedures. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system. An assay value of greater than 35 UlmL is predictive of residual disease, provided that alrernate causes of elevated CA 125 II Assay values can be excluded. It is recommended that the assessment and treatment of patients with ovarian cancer and the use of this CA 125 II Assay be under the order of a physician trained and experienced in the management of gynecologic cancers.

Device Story

In vitro immunoassay for quantitative measurement of OC 125 reactive determinants in serum; used on Bayer ADVIA IMS system. Operates via immunoassay principle to detect high molecular weight glycoprotein associated with ovarian cancer. Used in clinical laboratory settings by trained technicians; results interpreted by physicians specializing in gynecologic oncology. Output provides numerical CA 125 II concentration (U/mL); values >35 U/mL suggest residual disease. Assists clinicians in monitoring disease progression or response to therapy (doubling values indicate progression; 50% decrease indicates response). Benefits patients by providing objective data for longitudinal management and post-therapy assessment.

Clinical Evidence

Bench testing only. Performance evaluated via correlation with predicate (N=45, R=0.994), linearity, parallelism, and interference studies (hemoglobin, lipids, bilirubin, drugs, vitamins). Sensitivity 94.7%, specificity 22.2%, PPV 72.0%, NPV 66.7%, concordance 71.4%. Analytical range 0.5-550 U/mL. No clinical prospective trials presented; longitudinal monitoring data provided as comparative examples.

Technological Characteristics

In vitro immunoassay; quantitative measurement of OC 125 reactive determinants. System: Bayer ADVIA IMS. Analytical range: 0.5-550 U/mL. Minimum detectable concentration: 0.5 U/mL. Connectivity: Integrated modular system. No specific materials or software algorithm architecture details provided.

Indications for Use

Indicated for women with primary epithelial invasive ovarian cancer to aid in disease management (monitoring) and as a one-time test to aid in detecting residual carcinoma post-first-line therapy for patients considered for second-look procedures. Not for screening or primary diagnosis.

Regulatory Classification

Identification

A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.

Special Controls

*Classification.* Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.

Predicate Devices

• Immuno 1 CA125 II Assay (T01-3560-51)

Submission Summary (Full Text)

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Bayer Diagnostics Group

K022329/S1

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SSE

| 510(K) SUMMARY OF SAFETY AND EFFECTIVENESS | | |
| --- | --- | --- |
| 1. Applicant/Laboratory Information | | |
| A | Name | Bayer Business Group Diagnostics |
| B | Mailing address | 511 Benedict Avenue, Tarrytown, NY 10591 |
| C | Phone number | 914-631-8000 |
| D | Fax number | 914-524-2132 |
| E | E-mail/internet address | http://www.bayerdiag.com |
| F | Contact | Kenneth T. Edds, Ph.D., Regulatory Affairs Manager |
| 2. Regulatory Information | | |
| A | Class | II (assay), I (calibrator) |
| B | Product code | 82 LTK (assay), 75 JIT (calibrator) |
| C | Classification Names | Tumor-associated Antigen Immunological test system §866.6010 Calibrator §862.1150 |
| D | Common name | Tumor-associated antigen immunological test system |
| E | Proprietary name | CA 125 II Assay for the Bayer ADVIA Integrated Module System |
| 3. Intended Use(s)/Indication Statement | | |
| The BAYER ADVIA IMS CA 125 II Assay is an in vitro diagnostic device intended to quantitatively measure OC 125 reactive determinants associated with a high molecular weight' glycoprotein in serum of women with primary epithelial invasive ovarian cancer. The CA 125 II Assay is indicated as an aid in the management (monitoring) of ovarian cancer patients when used in conjunction with other diagnostic procedures. The CA 125 II Assay is also indicated as a onetime test for use as an aid in the detection of residual ovarian carcinoma in patients who have undergone first-line therapy and would be considered diagnostic second-look procedures. An assay value of greater than 35 U mL is predictive of residual disease, provided that alternate causes of elevated CA 125 II Assay values can be excluded. It is recommended that the assessment and treatment of patients with ovarian cancer and the use of this CA 125 II Assay be under the order of a physician trained and experienced in the management of gynecologic cancers. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system. | | |
| 4. Substantial Equivalence Information | | |
| A | Predicate device | Bayer Immuno 1 CA 125 II Test |
| B | K number | K983715 |
| C | Comparison with predicate | • Correlation (Y = ADVIA IMS, X = Immuno 1) [N=45] • Regression equation = 1.074 (X) - 3.94 = y • Syx (U/mL) = 13.74 • R = 0.994 • Sample Range (U/mL) = 5.1 - 509.2 |
| 5. Procedure | | |
| The ADVIA® IMS CA125 II Assay is an in vitro heterogeneous sandwich immunoassay using magnetic separation. Reagent 1 (R1) contains a monoclonal antibody to OC 125 labeled with FITC and Reagent 2 (R2) contains a monoclonal antibody to OC 125 conjugated to the enzyme alkaline phosphatase (ALP). The sandwich complex formed by the analyte and the antibody conjugates is captured by the magnetic particles so that the CA 125 11 concentration in the sample can be measured in terms of enzyme activity. The substrate used for this assay is a dioxetane phosphate derivative, which is dephosphorylated by ALP resulting in photon emission. A photomultiplier tube measures luminescence. The dose response curve is proportional to the analyte concentration in sample. | | |
| 6. Reagents | | |
| A | Material | • M11 Antibody Conjugate (R1) (Source: Mouse) • Alkaline Phosphate-labeled antibody (R2) • Monoclonal ImmunoMagnetic Particle (mIMP™) • Serum • OC 125 determinants [Calibrators] (Source: Mouse) |
| B | Amount | As shipped Concentrations: R1 = 1.5 mg/L; monoclonal OC 125 ALP conjugate = 25.0 mg/L; Sodium Azide = 0.095 % (in each reagent prep), Other (Buffer, surfactant, preservative) Post Assay Concentrations: R1 = 0.08 mg/L; monoclonal OC 125 ALP conjugate = 1.28 mg/L; Sodium Azide = 0.01 %, Other (Buffer, surfactant, preservative) |

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Bayer Diagnostics Group

K022329/S1

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SSE

7. Performance Characteristics

| A | Standard Curve | A typical standard curve is shown below: RPM 0 100 200 300 400 500 Concentration | | | |
| --- | --- | --- | --- | --- | --- |
| B | Imprecision | ADVIA IMS IMMUNO I | | | |
| | | Level (U/mL) | Total CV (%) | Level (U/mL) | Total CV (%) |
| | | 26.8 | 3 | 30.2 | 2.4 |
| | | 74.1 | 1.9 | 80.6 | 2.5 |
| | | 109.8 | 2.5 | 200.2 | 2.6 |
| D | Sensitivity | 94.7 % | | | |
| E | Specificity | 22.2 % | | | |
| F | PPV | 72.0 % | | | |
| G | NPV | 66.7 % | | | |
| H | Concordance | 71.4 % | | | |
| I | Accuracy | Linearity: Linearity was evaluated by diluting a high CA 125 II serum sample with a serum pool containing low CA 125 II level. Recovery was acceptable ranging from 96.7% to 106.2%, meeting specifications and in concordance with the Immuno I (predicate). Parallelism: Parallelism was evaluated by diluting a high CA 125 II serum sample with a high CA 125 II level, with Immuno I Sample Diluent B. Recovery was acceptable ranging from 95.6% to 109.7% in concordance with the Immuno I (predicate). Interfering Substances: Separate low serum pools were spiked with the following materials: Triglycerides (1000 mg/dL), hemoglobin (1000 mg/dL), bilirubin (25 mg/dL), albumin (6.5 g/dL), immunoglobulin (6.0 g/dL), over the counter medications, vitamins, caffeine, and drug pools (two times lethal dose). In all cases the observed recovery bias was found of no clinical significance. | | | |
| | | Interfering Substance | Interfering Substance Concentration μg/mL (* = mg/dL) | CA 125 Concentration (U/mL) | Effect (% Change) |
| | | Hemoglobin | 1000 * | 19.9 | -2.3 |
| | | Lipids (Triglycerides) | 1000 * | 18.5 | 0.9 |
| | | Bilirubin | 25 * | 22.5 | -2.6 |
| | | IgG | 6000 * | 35.1 | -4.0 |
| | | Albumin | 6500 * | 22.2 | 4.3 |
| | | Acetaminophen | 200 | 30.9 | -0.5 |
| | | Aspirin | 500 | 23.8 | -2.2 |
| | | Ibuprofen | 400 | 23.8 | -0.8 |
| | | Caffeine | 100 | 24.5 | 1.2 |
| | | Vitamin A | 10 (U/mL) | 21.6 | 0.1 |
| | | Vitamin B1 | 3 | 23.4 | -1.2 |
| | | Vitamin B2 | 3.4 | 21.6 | -1.3 |
| | | Vitamin B6 | 4 | 20.6 | -0.4 |
| | | Vitamin B12 | 12 (ng/mL) | 21.6 | 9.5 |

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Bayer Diagnostics Group
K022329/S1
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SSE

| | | Vitamin C | 30 | 24.5 | 1.4 |
| --- | --- | --- | --- | --- | --- |
| | | Vitamin D_{2} | 0.8 (U/mL) | 20.6 | 3.7 |
| | | Vitamin E | 0.06 (U/mL) | 20.6 | 2.5 |
| | | Folic Acid | 0.8 | 21.6 | 7.0 |
| | | Niacin | 40 | 21.6 | 4.4 |
| | | Vincristine Sulfate | 13.5 * | 20.6 | 4.1 |
| | | Vinblastine | 5.11 * | 20.6 | 4.1 |
| | | Mitomycin C | 73 * | 21.6 | 0.9 |
| | | Tamoxifen – Free | 60 * | 20.6 | 4.1 |
| | | Tamoxifen – Citrate | 60 * | 20.6 | 4.1 |
| | | Etoposide | 415 * | 22.5 | 4.1 |
| | | 5-Fluorouracil | 1600 * | 21.6 | 3.5 |
| | | Cyclophosphamide Monohydrate | 800* | 21.6 | 0.9 |
| | | Doxorubicin HCl | 51.8 * | 21.6 | 0.9 |
| | | Diethylstiberol | 23 * | 20.6 | 4.1 |
| | | Methotrexate | 450 * | 22.5 | 5.6 |
| | | Cis-Platinum | 173 * | 20.6 | 4.1 |
| | | Lupron | 15 * | 25.9 | -5.8 |
| | | Megesterol Acetate | 243 * | 21.6 | 0.9 |
| | | Hook Effect: On the ADVIA IMS the concentration of up to 80,000 U/mL did not produce a signal lower than the highest calibrator rate (level 6). | | | |
| | | J | Cut-off | 32.0 U/Ml | |
| | | K | Analytical Range | 0.5 - 550 U/mL | |
| L | Minimum Detectable Concentration | ADVIA IMS = 0.5 U/mL
Immuno 1 = 0.9 U/mL | | | |
| M | Clinical Results | Longitudinal Samples: Two examples of serial patient monitoring studies using Bayer ADVIA IMS assay results in comparison to results obtained for another marketed device are shown in the following figures: | | | |
| N | Conclusion | Performance of the ADVIA IMS CA 125 II Assay on a Bayer ADVIA® IMS™ is equivalent to the performance of the CA 125 II on the predicate device (Immuno I) and is within proposed specifications. No safety and effectiveness issues have been raised. | | | |