(216 days)
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
| Acceptance Criteria Category | Specific Acceptance Criteria (Implied/Stated) | Reported Device Performance |
|---|---|---|
| Precision | % CV for various CA 125 concentrations (implied to be within acceptable clinical limits) | For Sample 1 (9.09 U/mL): Total SD=0.21, %CV=2.4 |
| For Sample 2 (29.5 U/mL): Total SD=0.55, %CV=1.9 | ||
| For Sample 3 (105 U/mL): Total SD=2.04, %CV=1.9 | ||
| For Sample 4 (268 U/mL): Total SD=4.70, %CV=1.8 | ||
| For Sample 5 (401 U/mL): Total SD=7.35, %CV=1.8 | ||
| For Sample 6 (767 U/mL): Total SD=11.74, %CV=1.5 | ||
| Detection Capability | Limit of Detection (LoD) $\ge$ 5.5 U/mL, Limit of Quantitation (LoQ) $\le$ 5.5 U/mL at 20% CV (designed) | LoD: 5.5 U/mL |
| LoQ (observed): 0.8 U/mL at 20% CV | ||
| Claimed LoQ: 5.5 U/mL | ||
| Linearity | Linear over the measuring range (e.g., 80.0% to 101% recovery, R$^2$ close to 1) | Linearity Range: 3.6 to 1288 U/mL |
| % Recovery: 80.0% to 101% | ||
| Slope: 0.992 (95% CI: 0.985 to 0.999) | ||
| Intercept: -0.932 (95% CI: -1.075 to -0.788) | ||
| R$^2$: 1.000 | ||
| Matrix Comparison | Serum and plasma (Li-Hep, EDTA) deemed equivalent (implied by "Pass" status based on Deming regression results) | Li-Hep vs. Serum: Slope=0.984, Intercept=0.160, Correlation=1.000 (Pass) |
| EDTA vs. Serum: Slope=0.990, Intercept=0.162, Correlation=1.000 (Pass) | ||
| Analytical Specificity (Interference) | Observed bias $\ge$ 10% for specific interferents should be identified. Substances not interfering should have bias < 10%. | Interfering Substances (Bias $\ge$ 10%): Hemoglobin (1000 mg/dL yielded 12.6% bias at 10.0 U/mL CA 125), Rheumatoid Factor (1043 U/mL yielded 28.3% bias at 11.4 U/mL CA 125). Total Protein (15.8 g/dL yielded 11.3% bias at 10.0 U/mL CA 125). |
| Non-Interfering Substances: A long list of substances showed <10% bias. | ||
| Expected Values (Reference Interval) | No more than 10% of healthy donors fall outside the current reference interval ($ \le $ 35 U/mL) | Overall (60 donors): 1 female out of 60 fell outside ($ > $ 35 U/mL) for Lot 9991 on VITROS 5600. (1/60 = 1.67% < 10%). |
| Method Comparison | Strong correlation and agreement between the new device and the predicate device (Passing Bablok regression parameters close to ideal, e.g., slope ~1, intercept ~0, high correlation coefficient). | VITROS 5600 vs. Comparative Method: Slope=1.018 (95% CI: 1.009 to 1.027), Intercept=-0.449 (95% CI: -1.444 to -0.166), Correlation Coefficient=0.999 |
| Dilution Recovery/Imprecision | Product requirements met (implied by statement) | "The dilution recovery and dilution imprecision product requirements were met..." |
Study Details
-
Sample Size Used for the Test Set and Data Provenance:
- Precision: Not explicitly stated for the "test set" in the context of device approval but uses multiple runs, days, and lots for calculation. Each sample shown in the precision table represents multiple determinations over different runs, days, and reagent lots.
- Detection Capability: Not explicitly stated, but consistent with CLSI EP17-A2.
- Linearity: 4 replicates from each level of a linearity panel (2 through 15 levels) were collected using three reagent lots. Data for one lot (9991) is presented.
- Matrix Comparison: n=49 for both Li-Hep and EDTA comparisons.
- Analytical Specificity: Not explicitly stated, but tested at two CA 125 concentrations (10.0 U/mL and 50.0 U/mL) with various interferent concentrations.
- Expected Values (Reference Interval): 60 healthy female and male blood donors.
- Method Comparison: n=146 patient serum samples.
- Data Provenance: Not explicitly stated, but typical for such studies performed by manufacturers. Generally, such studies are prospective, and data would be collected from various clinical sites. No country of origin is specified.
-
Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts:
- This device is an in-vitro diagnostic (IVD) assay measuring a quantitative biomarker (CA 125 II antigen concentration). The "ground truth" for these types of devices is based on well-defined analytical methods, reference materials, and established predicate devices. No human experts or consensus panels are typically used to establish ground truth for this type of quantitative IVD device. The "ground truth" here is the actual concentration of the analyte, often determined by a reference method or assigned value of a calibrator.
-
Adjudication Method for the Test Set:
- Not applicable as this is an analytical performance study for a quantitative IVD, not a diagnostic imaging or clinical decision-making study that would involve expert interpretation requiring adjudication.
-
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 was not done. This device is a lab-based immunoassay, not an AI-powered diagnostic imaging tool or a system involving human readers in its direct use.
-
If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the entire submission describes standalone performance. This is an automated immunoassay system (VITROS 5600 Integrated System) that produces a quantitative result. Its performance is entirely "algorithm only" or "device only" in the sense that once a sample is loaded, the measurement is automated without human interpretation of the direct signal to derive the CA 125 concentration. Human interpretation comes into play when a clinician uses the result in conjunction with other clinical findings.
-
The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for the analytical performance studies (precision, linearity, detection, etc.) is the known concentration of the analyte in control materials, calibrators, or spiked samples, or comparison to a legally marketed predicate device (for method comparison).
- For the method comparison study, the "ground truth" is established by the predicate device's measurement (VITROS CA 125 II (GEM.1125A)).
-
The Sample Size for the Training Set:
- Not applicable in the context of an immunoassay using a specific reagent pack and established analytical reactions. This is not a machine learning or AI model that requires a "training set" in the conventional sense. The "training" of the device is its initial calibration and quality control setup based on manufacturer-defined calibrators and controls.
-
How the Ground Truth for the Training Set Was Established:
- Not applicable. The "ground truth" for the device's operational setup (calibration) is established by in-house reference calibrators that have been value-assigned to correlate to another commercially available test. These calibrators have known, assigned concentrations of the OC 125 defined antigen.
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December 12, 2022
Ortho Clinical Diagnostics Rebecca Lewis Senior Regulatory Affairs Associate Felindre Meadows Pencoed, Bridgend CF35 5PZ United Kingdom
Re: K221355
Trade/Device Name: VITROS Immunodiagnostic Products CA 125 II Reagent Pack Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: LTK Dated: April 27, 2022 Received: May 10, 2022
Dear Rebecca Lewis:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
{1}------------------------------------------------
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ying Mao -S
Ying Mao, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Ouality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K221355
Device Name
VITROS Immunodiagnostic Products CA 125 II Reagent Pack
Indications for Use (Describe)
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.
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The assigned 510(k) number is: K221355.
Submitter's Information
Ortho-Clinical Diagnostics Inc.
Felindre Meadows,
Pencoed,
UK CF35 5PZ Phone: +44 07971 427649
Fax: (585) 453-3368 Contact Person: Rebecca Lewis
Preparation Date
December 12, 2022
Device Proprietary Name(s)
VITROS® Immunodiagnostic Products CA 125 II Reagent Pack
Common Name(s) VITROS CA125 Reagent Pack
Classification Names
| Product Code | Class | Regulation Section | Panel |
|---|---|---|---|
| LTK | II | 21 CFR 866.6010Tumor-associated antigen immunological testsystem | Immunology |
Predicate Device(s)
| Predicate Device | FDA 510(k) Number |
|---|---|
| VITROS Immunodiagnostic Products CA 125 II Reagent Pack | K983875 |
Device Description
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
{4}------------------------------------------------
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.
VITROS CA 125 II Reagent Pack contains:
1 reagent pack containing:
- 100 coated wells (antibody, mouse monoclonal anti-OC 125 defined antigen, binds >32.5 U OC 125 ● defined antigen/well)
- 9.4 mL assay reagent (buffer containing bovine serum albumin, bovine gamma globulin and antimicrobial agent)
- 9.4 mL conjugate reagent (HRP-mouse monoclonal anti-OC 125 defined antigen, binds ≥542 U OC ● 125 defined antigen/mL) in buffer with bovine serum albumin, bovine gamma globulin and antimicrobial agent.
VITROS CA 125 II Calibrator contains:
- 1 set of VITROS CA 125 II Calibrators 1, 2, and 3 (OC 125 defined antigen in buffer with bovine ● serum albumin and antimicrobial agent, 1.75 mL); nominal values 24.0; 130 and 875 U OC 125 defined antigen/mL
- 24 calibrator bar code labels (8 for each calibrator)
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Intended Use Statement(s):
Rx ONLY
For in vitro diagnostic use only.
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.
Comparison to Predicate Devices
The following tables provide a summary of the key features of the new device assessed against the predicate.
| DeviceCharacteristic | Predicate DeviceVITROS Immunodiagnostic ProductsCA 125 II Reagent Pack, K983875, cleared14 May 1999 | Modified DeviceVITROS ImmunodiagnosticProducts CA 125 II Reagent Pack |
|---|---|---|
| Intended Use | Rx ONLYFor in vitro diagnostic use only. | Rx ONLYFor in vitro diagnostic use only. |
| For the quantitative measurement of OC 125defined antigen concentration in human serumand plasma (EDTA or heparin) using theVITROS 5600 Integrated System. TheVITROS CA 125 II assay is to be used as anaid in monitoring response to therapy forpatients with epithelial ovarian cancer. Serialtesting for patient CA 125 assay concentrationsshould be used in conjunction with otherclinical methods used for monitoring ovariancancer. | For the quantitative measurement of OC 125defined antigen concentration in human serumand plasma (EDTA or heparin) using theVITROS 5600 Integrated System. The VITROSCA 125 II assay is to be used as an aid inmonitoring response to therapy for patients withepithelial ovarian cancer. Serial testing forpatient CA 125 assay concentrations should beused in conjunction with other clinical methodsused for monitoring ovarian cancer. | |
| Assay Principle | Immunometric. | Same. |
| Antibody | Mouse Monoclonal anti-OC 125 antigen. | Same. |
| Sample Type | Serum and Plasma. | Same. |
| Sample Volume | 25 μL. | Same. |
| Traceability | Calibration of the VITROS CA 125 II test istraceable to in-house reference calibratorswhich have been value assigned to correlateto another commercially available test. | Same. |
| Measuring Range | 5.5-1000 (U/mL) | Same. |
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| Detect on Limit | LOB: 2.9 (U/mL)LOD: 5.5 (U/mL) | LOB: Same.LOD: Same.LOQ: 5.5 (U/mL) |
|---|---|---|
| Calibrator Levels | 3. | Same. |
| Instrumentation | VITROS 5600 Integrated System | Same. |
Nonclinical Performance
Several nonclinical tests were performed.
Precision
Precision was evaluated consistent with CLSI document EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline—Third Edition.
The data presented are a representation of test performance and are provided as a guideline. Variables such as sample handling and storage, reagent handling and storage, laboratory environment, and system maintenance can affect reproducibility of test results.
| Sample | Mean | Within-Run(Repeatability) | Between-Run | Within-Day | Between-Day | Between-Lot | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV | ||
| 1 | 9.09 | 0.09 | 1.0 | 0.08 | 0.9 | 0.15 | 1.6 | 0.18 | 1.9 | 0.00 | 0.0 | 0.21 | 2.4 |
| 2 | 29.5 | 0.24 | 0.8 | 0.25 | 0.8 | 0.39 | 1.3 | 0.43 | 1.4 | 0.06 | 0.2 | 0.55 | 1.9 |
| 3 | 105 | 1.04 | 1.0 | 0.87 | 0.8 | 1.56 | 1.5 | 1.30 | 1.2 | 0.79 | 0.8 | 2.04 | 1.9 |
| 4 | 268 | 2.06 | 0.8 | 2.85 | 1.1 | 3.86 | 1.4 | 2.81 | 1.1 | 1.33 | 0.5 | 4.70 | 1.8 |
| 5 | 401 | 3.02 | 0.8 | 4.92 | 1.2 | 6.28 | 1.6 | 4.30 | 1.1 | 1.50 | 0.4 | 7.35 | 1.8 |
| 6 | 767 | 6.90 | 0.9 | 5.92 | 0.8 | 9.91 | 1.3 | 6.25 | 0.8 | 4.02 | 0.5 | 11.74 | 1.5 |
Detection Capability
Detection studies for the VITROS CA 125 II Reagent were evaluated consistent with CLSI document EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition.
The Limit of Detection (LoD) for the VITROS CA 125 II test is 5.5 U/mL, determined consistent with CLSI document EP17. The Limit of Quantitation (LoQ) for the VITROS CA
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125 II test was designed to be less than or equal to 5.5 U/mL at 20% CV. The observed LoQ at 20% CV was determined to be 0.8 U/mL, consistent with CLSI document EP17. The claimed LoQ is set at 5.5 U/mL.
Linearitv
Linearity studies were performed according to CLSI document Evaluation of Linearity of Quantitative Measurement Procedures. 2nd ed. CLSI guideline EP06. Linearity testing fluids covering the measuring range were prepared from mixtures of low and high pools. Four replicates were collected from each level in the panel using three reagent lots of VITROS Immunodiagnostics Products CA125 II Reagent were tested on the VITROS 5600 Integrated System. Data for one lot. 9991 is presented. The VITROS CA 125 II Reagent was linear over the measuring range for the VITROS 5600 Integrated System for all reagent lots tested. The regression analysis and results of the study that established the linearity interval are shown in the Tables below.
| VITROS SystemName | VITROS SystemNumber | ReagentLot | LinearityPanelLevels used | LLLI(IU/mL) | ULLI(IU/mL) |
|---|---|---|---|---|---|
| VITROS 5600 | 56000118(PM118) | 9991 | 2through15 | 3.6 | 1288 |
| Slope | Intercept | ||||||
|---|---|---|---|---|---|---|---|
| Lot | DilutionRange | % Recovery | Estimate | 95% CI | Estimate | 95% CI | R2 |
| 9991 | 3.6 to 1288 | 80.0% to 101% | 0.992 | 0.985 to0.999 | -0.932 | -1.075 to -0.788 | 1.000 |
Matrix Comparison
Serum and plasma (Li-Hep and EDTA) specimen matrices was determined to be equivalent. The results met the acceptance criteria for the comparison between serum and plasma (Li-Hep and EDTA) specimens spanning the expected measuring interval. Based on the analysis serum and plasma (Li-Hep and EDTA) are suitable specimen matrices for use with the VITROS CA 125 II assay.
Specimens Recommended
-
Serum and Plasma
Specimens Not Recommended. -
Do not use turbid specimens. Turbidity in specimens may affect test results. ●
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| VITROS 5600 System | ||
|---|---|---|
| Ordinary Deming | Li-Hep | EDTA |
| Slope | 0.984 | 0.990 |
| 95% CI (Slope) | 0.980 to 0.988 | 0.984 to 0.995 |
| Intercept | 0.160 | 0.162 |
| 95% CI (Intercept) | -0.019 to 0.338 | -0.100 to 0.424 |
| CorrelationCoefficient (r) | 1.000 | 1.000 |
| n | 49 | 49 |
| Pass/Fail Status | Pass | Pass |
Analytical Specificity
Known Interferences
The VITROS CA 125 II assay was screened for interfering substances at CA 125 II concentrations of approximately 10.0 U/mL and 50.0 U/mL following EP07 3rd ed - Interference Testing in Clinical Chemistry and EP37 1st ed - Supplemental Tables for Interference Testing in Clinical Chemistry. Commonly encountered substances were tested. The substances listed in the table demonstrated observed bias of ≥ 10% when tested at the concentrations shown.
For substances that were tested and did not interfere, refer to "Substances that do not Interfere."
| Interferent | Interferent Concentration | AnalyteConc.*(U/mL) | Bias %** | |
|---|---|---|---|---|
| Hemoglobin | 1000 mg/dL | 0.155 mmol/L | 10.0 | 12.6 |
| 750 mg/dL | 0.116 mmol/L | 45.9 | 4.8 | |
| 9.6 | 7.8 | |||
| RheumatoidFactor | 1043 U/mL | N/A | 11.4 | 28.3 |
| 1063 U/mL | 49.7 | 3.2 | ||
| 975 U/mL | 30.6 | 8.3 | ||
| 267 U/mL | 9.6 | 8.2 | ||
| Total Protein | 15.8 g/dL | N/A | 10.0 | 11.3 |
| 16.3 g/dL | 48.4 | -0.4 | ||
| 11.5 g/dL | 9.5 | 5.6 |
- Average test concentration of replicate determinations using 3 different lots of reagent, on the VITROS 5600 Integrated System.
** Estimate of the average difference observed.
These results are representative. It is possible that other interfering substances may be encountered in the patient population. The degree of interference at concentrations other than those listed might not be predictable.
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VITROS CA 125 II Reagent Traditional 510(k)
Substances that do not Interfere
The substances listed in the table below were tested with the VITROS CA 125 II test following CLSI EP07and EP37 and found not to cause bias > 10% at CA 125 II concentrations of approximately 10 U/mL and 50 U/mL at the test concentrations shown.
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| Substance | Concentration | |
|---|---|---|
| Acetaminophen | 20.0 mg/dL | 1.32 mmol/L |
| N-Acetylcysteine | 15.0 mg/dL | 0.919 mmol/L |
| Acetylsalicylic acid | 50 mg/dL | 2.78 mmol/L |
| Alpha-tocopherol | 6.45 mg/dL | 0.150 mmol/L |
| Amoxicillin | 5.40 mg/dL | 0.148 mmol/L |
| Ascorbic acid | 300 mg/dL | 17.0 mmol/L |
| Bevacizumab | 24.0 mg/dL | 0.002 mmol/L |
| Bilirubin, conjugated | 40 mg/dL | 0.475 mmol/L |
| Bilirubin, unconjugated | 40 mg/dL | 0.684 mmol/L |
| Biotin | 0.351 mg/dL | 0.014 mmol/L |
| Carboplatin | 15.0 mg/dL | 0.404 mmol/L |
| Cefoxitin sodium | 695 mg/dL | 15.5 mmol/L |
| Chlorpromazine | 1.0 mg/dL | 0.028 mmol/L |
| Cholecalciferol (D3) | 19.2 µg/dL | 0.499 µmol/L |
| Cholesterol, total | 400 mg/dL | 10.3 mmol/L |
| Cisplatin | 100 mg/dL | 3.33 mmol/L |
| Codeine | 0.141 mg/dL | 0.005 mmol/L |
| Cotinine | 0.24 mg/dL | 0.014 mmol/L |
| Coumadin | 1.4 mg/dL | 0.042 mmol/L |
| Cyclophosphamide | 54.9 mg/dL | 1.97 mmol/L |
| Dexamethasone | 135 µg/dL | 0.003 mmol/L |
| Dextran 40 | 2400 mg/dL | 0.600 mmol/L |
| Dextromethorphan | 0.00156 mg/dL | 0.057 µmol/L |
| Dimenhydrinate | 1.0 mg/dL | 0.021 mmol/L |
| Diphenhydramine | 1.0 mg/dL | 0.039 mmol/L |
| Docetaxel | 1.326 mg/dL | 0.015 mmol/L |
| Doxorubicin hydrochloride | 75 µg/dL | 0.001 mmol/L |
| Enoxaparin - Low molecular weightHeparin | 360 U/dL | N/A |
| Ethanol | 600 mg/dL | 130 mmol/L |
| Etoposide | 6.0 mg/dL | 0.102 mmol/L |
| 5-Fluorouracil | 9.76 mg/dL | 0.750 mmol/L |
| Furosemide | 1.59 mg/dL | 0.048 mmol/L |
| Gemcitabine | 7.0 mg/dL | 0.234 mmol/L |
| HAMA (Human Anti-Mouse Antibodies) | 800 µg/L | 0.053 µmol/L |
| Hydralazine | 1.44 mg/dL | 0.073 mmol/L |
| Hydrocodone | 0.0072 mg/dL | 0.160 µmol/L |
| Ibuprofen | 70.0 mg/dL | 3.39 mmol/L |
| Leucovorin | 15.0 mg/dL | 0.293 mmol/L |
| Levothyroxine | 0.0429 mg/dL | 0.552 µmol/L |
| Loratadine | 0.0087 mg/dL | 0.227 µmol/L |
| Methotrexate | 454 mg/dL | 9.99 mmol/L |
| Metoclopramide | 1.0 mg/dL | 0.030 mmol/L |
| Mitomycin C | 300 µg/L | 0.009 mmol/L |
| Morphine | 0.780 mg/dL | 0.010 mmol/L |
| Naproxen | 36.0 mg/dL | 1.56 mmol/L |
| Olaparib | 1.71 mg/dL | 0.039 mmol/L |
| Omeprazole | 0.840 mg/dL | 0.024 mmol/L |
| Paclitaxel | 1.0 mg/dL | 0.012 mmol/L |
| Phenytoin | 6.00 mg/dL | 0.238 mmol/L |
| Salicylic acid | 2.86 mg/dL | 0.207 mmol/L |
| Theophylline | 6.0 mg/dL | 0.333 mmol/L |
| Topotecan | 0.0019 mg/dL | 0.045 µmol/L |
| Triglycerides, total | 1500 mg/dL | 16.9 mmol/L |
| Vancomycin hydrochloride | 12.3 mg/dL | 0.083 mmol/L |
| Vinblastine | 0.0084 mg/dL | 0.092 µmol/L |
| Vinorelbine | 0.19 mg/dL | 0.002 mmol/L |
Ortho-Clinical Diagnostics, Inc.
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Other Limitations
- The results from this or any other diagnostic test should be used and interpreted only in the context of ● the overall clinical picture.
- Heterophilic antibodies in the serum or plasma of certain individuals may cause interference with . immunoassays. These antibodies may be present in blood samples from individuals regularly exposed to animals or who have been treated with animal serum products. Results which are inconsistent with
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clinical observations indicate the need for additional testing.
- . Individuals receiving mouse immunoglobulin by parenteral routes may produce anti-mouse antibodies. Serum from such individuals may produce erroneous results.
- . The VITROS CA 125 II has no high dose hook effect up to 340,000 U/mL.
- The VITROS CA 125 II test is not recommended as a screening procedure to detect cancer in the general population.
- . Different test methods cannot be used interchangeably. OC 125 defined antigen in a given patient sample determined with different tests and from different manufacturers can vary due to differences in test methods and reagent specificity. A change to the test used during serial monitoring of a patient should be accompanied by additional sequential testing to confirm baseline concentrations. The results reported by the laboratory to the physician must include the identity of the CA 125 II test used.
- . CA 125 test concentrations are elevated in 1-2% of healthy individuals and may be elevated in diseases other than ovarian carcinoma, including both benign and malignant disorders. CA 125 test concentrations greater than or equal to 35 U/mL may be found in patients with non-malignant conditions, such as pericarditis, cirrhosis, severe hepatic necrosis, endometriosis (Stages II-IV), first trimester pregnancy, and ovarian cysts or in patients with non-ovarian malignancies, such as uterine carcinoma, hepatoma, pancreatic adenocarcinoma, and lung cancer.
- . A CA 125 test concentration below 35 U/mL does not indicate the absence of residual ovarian cancer because patients with histopathologic evidence of ovarian carcinoma may have CA 125 test concentrations within the range of healthy individuals. Clinical decisions should not be based on a VITROS CA 125 II test concentration below 35 U/mL.
- The test should not be performed until at least three weeks after the completion of primary chemotherapy and at least two months after abdominal surgery. This is recommended because it is not clear what effect, if any, these procedures may have on the CA 125 test concentration.
- For changes in tumor marker concentrations during therapy: ●
- . Progressive disease is defined by an increase of at least 25%. Sampling should be repeated within two to four weeks for additional evidence.
- Partial remission is defined as a decrease of at least 50% in the tumor marker concentrations.
- Certain drugs are known to alter CA 125 concentrations in vivo. Please consult one of the published ● summaries for details.
Dilution
The dilution recovery and dilution imprecision product requirements were met for the VITROS Immunodiagnostic Products CA 125 II Reagent Pack. Serum or plasma (EDTA or heparin) samples with concentrations greater than the measuring range may be automatically diluted on the system up to 20-fold (1 part sample with 19 parts diluent) by the VITROS 5600 Integrated System with the VITROS High Sample Diluent B Reagent Pack prior to test. Refer to the VITROS High Sample Diluent B Reagent Pack instructions for use.
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Expected Values
Adult Reference Interval
The adult reference interval was validated following CLSI document EP28-A3c Defining. Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - Third Edition.
| Unit (U/L) |
|---|
| $≤$ 35 U/mL |
The number of test results from 60 healthy female and male blood donors that fell outside the current reference interval claim of >35 U/mL are shown in Table 1, for each reagent lot and instrument combination. As no more than 10% of the test results were outside the current limit, the reference interval claim of the current VITROS CA 125 II will be transferred to the updated VITROS CA 125 II Reagent Pack.
Table 1: Test results outside the current reference interval claim of VITROS CA 125 II Reagent Pack
| System | Reagent Lot | Gender | No. of testresults >35U/mL |
|---|---|---|---|
| VITROS5600 | 9991 | Female | 1 |
| Male | 0 |
Traceability of Calibration
Calibration of the VITROS CA 125 II test is traceable to in-house reference calibrators which have been value assigned to correlate to another commercially available test.
Method Comparison
Accuracy was evaluated consistent with CLSI documents Measurement Procedure Comparison and Bias Estimation Using Patient Samples. 3rd ed. CLSI guideline EP09c; and Evaluation of Total Analytical Error for Quantitative medical laboratory Measurement Procedures. 2nd ed. CLSI guideline EP21.
Accuracy was evaluated consistent with CLSI document EP09. The plot and table show the results of a method comparison study using patient serum samples analyzed on the VITROS 5600 Integrated System compared with those analyzed using the VITROS CA 125 reagent pack. The relationship between the 2 methods was determined by Passing Bablok regression.
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Image /page/14/Figure/1 description: The image is a scatter plot titled "Conventional Units". The x-axis is labeled "Comparative Method: VITROS CA 125 II (GEM.1125A) (U/mL)", and the y-axis is labeled "VITROS CA 125 II (GEM.1125B) (U/mL)". The plot shows a strong positive correlation between the two variables, with data points clustered around a red line. The x and y axis range from 0 to 1000.
| VITROS System | n | Slope(95% CI) | CorrelationCoefficient | Conventional Units (U/mL) | |
|---|---|---|---|---|---|
| Range ofSamples | Intercept(95% CI) | ||||
| 5600 vs. Comparative Method | 146 | 1.018 (1.009to 1.027) | 0.999 | 5.74-1000 | -0.449 (-1.444to -0.166) |
Conclusion
The conclusions drawn from the nonclinical tests (discussed above) demonstrate the VITROS Immunodiagnostic Products CA 125 II Reagent pack is as safe, effective, and performs as well as the cleared predicate device. The information submitted in the premarket notification is complete and supports a substantial equivalence decision.
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
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.(b)
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.