(210 days)
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
| Acceptance Criteria | Reported Device Performance (VITROS 5600 System) |
|---|---|
| Precision/Reproducibility | |
| Repeatability (Within-run precision) | Mean AFP Conc. (IU/mL) |
| 2.92 | |
| 11.9 | |
| 77.0 | |
| 236 | |
| 395 | |
| Within-Lab Precision | Mean AFP Conc. (IU/mL) |
| 2.92 | |
| 11.9 | |
| 77.0 | |
| 236 | |
| 395 | |
| Linearity/Measuring Range | 0.800–500 IU/mL |
| Detection Limits | |
| Limit of Blank (LoB) | 0.229 IU/mL |
| Limit of Detection (LoD) | 0.476 IU/mL |
| Limit of Quantitation (LoQ) | 0.800 IU/mL (at 20% CV) |
| Analytical Specificity (Known Interferences) | No interference (bias >10%) found for a list of tested compounds at approximately 4.80 IU/mL and 19.2 IU/mL AFP concentrations. |
| Cross-Reactivity | No detectable cross-reactivity with human α-1-acid glycoprotein, α-1-antitrypsin, ceruloplasmin, chorionic gonadotrophin, IgG, placental lactogen, serum albumin, transferrin, and prolactin (concentration below measuring interval of 0.800 to 500 IU/mL). |
| Method Comparison with Predicate Device (Accuracy) | N=150 |
| Intercept 95% CI: -0.029 to 0.066 | |
| Dilution Recovery | Able to dilute samples up to 4000-fold manually and up to 1:400 automatically. |
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.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
June 15, 2022
Ortho Clinical Diagnostics Declan Hynes Senior Regulatory Affairs Manager Felindre Meadows Pencoed, Bridgend CF35 5PZ United Kingdom
Re: K213626
Trade/Device Name: VITROS Immunodiagnostic Products AFP Reagent Pack Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: LOJ Received: November 17, 2021
Dear Declan Hynes:
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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part
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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 (QS) 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 medical devices and radiation-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, Ph.D. Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K213626
Device Name
VITROS Immunodiagnostic Products AFP Reagent Pack
Indications for Use (Describe)
For the quantitative measurement of alpha-fetoprotein (AFP) concentrations in human serum using the VITRO 5600 Integrated system to aid in the management of patients with non-seminomatous testicular 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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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: K213626
- Ortho-Clinical Diagnostics, Inc. 1. Submitter 100 Indigo Creek Drive name, Rochester, NY 14626 address, P: (+44) 01656 778032; F: (585) 453-3113 contact Contact Person: Declan Hynes
- April 29th, 2022 2. Preparation Date
-
- Device Name: VITROS® Immunodiagnostic Products AFP Reagent Pack
-
- Predicate Device: VITROS Immunodiagnostic Products AFP Reagent Pack K983031, cleared 18 December 1998
-
- Proprietary and Established Name: VITROS® Immunodiagnostic Products AFP Reagent Pack
6. Regulatory Information:
| ProductCode | Class | Regulation Section | Panel |
|---|---|---|---|
| LOJ | II | 21 CFR 866.6010 Tumor-associated antigenimmunological test system. | Immunology (82) |
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7. Intended Use:
-
- 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.
- Intended use:
-
- Special conditions for use statement:
Rx Only, IVD only
- Special conditions for use statement:
-
- Special instrument requirements:
- VITROS 5600 System .
I. Device Description:
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) ●
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8. Substantial Equivalence Information:
Predicate device name:
VITROS Immunodiagnostic Products AFP Reagent Pack K983031,
cleared 18 December 1998
8.1 Comparison with predicate: Similarities:
| DeviceCharacteristic | Predicate Device | Modified Device |
|---|---|---|
| Intended Use | For the quantitative measurement ofalpha-fetoprotein (AFP)concentrations in human serum usingthe VITROS ECi/ECiQ and VITROS3600 Immunodiagnostic Systems andthe VITROS 5600/XT7600 IntegratedSystems to aid in the management ofpatients with non-seminomatoustesticular cancer. | For the quantitativemeasurement of alpha-fetoprotein (AFP)concentrations in humanserum using the VITROS5600 Integrated Systemto aid in the managementof patients with non-seminomatous testicularcancer |
| Antibody | Monoclonal anti-AFP and Sheepanti-AFP | Same |
| Sample Type | Serum | Same |
| Traceability | Calibrated against First InternationalReference Preparation 72/225. | Same |
| MeasuringRange | 0.800-500 IU/mL | Same |
| DetectionLimit | LOB: 0.229 IU/mLLOD: 0.476 IU/mL | LOB: SameLOD: Same IU/mLLOQ: 0.800 IU/mL |
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Differences:
| Basic Principle | Sandwich immunoassay | Sandwich immunoassay. Inthe modified AFP ReagentPack the sheep anti-AFPantibody has been removedfrom the Biotin Reagent andcoated directly onto thewell. The modification toallow the biotinylatedantibody capture conjugateto be pre- bound to the well,eliminates the risk of biotininterference. |
|---|---|---|
| ConversionFactor betweenUnits | X 1.04 IU/ml to ng/mL | X 1.21 IU/mL to ng/mL.Different, the adoption ofthe 1.21 conversion factorwill align the VITROS AFPReagent Pack to othervendors using the sameconversion factor. |
8.2. Standard/Guidance Document Referenced (if applicable):
CLSI. Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline. CLSI guideline EP25-A. Wayne, PA: Clinical and Laboratory Standards Institute, 2009.
CLSI. Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - Third Edition. CLSI document EP28-A3c. Wayne, PA: Clinical and Laboratory Standards Institute; 2010.
CLSI. Evaluation of Precision Performance of Quantitative Measurement Methods; Third Edition. CLSI guideline EP05-A3. Wayne, PA: Clinical and Laboratory Standards Institute, 2014.
CLSI. Evaluation of Linearity of Quantitative Measurement Procedures. 2nd ed. CLSI guideline EP06. Clinical and Laboratory Standards Institute, 2020.
CLSI. Interference Testing in Clinical Chemistry - Third Edition. CLSI guideline EP07-A3. Wayne, PA: Clinical and Laboratory Standards Institute, Clinical and Laboratory Standards Institute; 2018
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CLSI. Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Second Edition. CLSI guideline EP 17-A2. Wayne, PA: Clinical and Laboratory Standards Institute, 2012.
CLSI. Measurement Procedure Comparison and Bias Estimation Using Patient Samples. 3rd ed. CLSI guideline EP09c. Wayne, PA: Clinical and Laboratory Standards Institute: 2018.
CLSI. Supplemental Tables for Interference Testing in Clinical Chemistry. 1st ed. CLSI supplement EP37. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
8.3. Test Principles:
An immunometric immunoassay technique is used. AFP present in the sample reacts with a biotinylated antibody (sheep anti-AFP) bound to streptavidin on a microwell. Unbound sample is removed by washing. In a second incubation a horseradish peroxidase (HRP)labeled antibody conjugate (mouse monoclonal anti-AFP) binds to the immobilized AFP. 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 AFP present.
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9. Performance Characteristics (if/when applicable):
9.1. Analytical performance:
- a. Precision/Reproducibility:
Precision was evaluated with patient pools on the systems in the table below following the CLSI document EP05.
The data presented are a representation of test performance and are provided as a guideline.
| Units = IU/mL | |||||||
|---|---|---|---|---|---|---|---|
| System | MeanAFPConc. | Repeatability* | Within Lab** | No. ofObs. | No. ofDays | ||
| SD | %CV | SD | %CV | ||||
| 2.92 | 0.055 | 1.9% | 0.067 | 2.3% | 80 | 20 | |
| 11.9 | 0.20 | 1.6% | 0.33 | 2.8% | 80 | 20 | |
| 5600 | 77.0 | 1.51 | 2.0% | 2.12 | 2.8% | 80 | 20 |
| 236 | 7.5 | 3.2% | 9.7 | 4.1% | 80 | 20 | |
| 395 | 9.6 | 2.4% | 17.9 | 4.5% | 80 | 20 |
*Repeatability (formerly called within-run precision) was determined using two replicates per run.
** Within Lab precision was determined using a single reagent lot and a single ca libration.
b. Linearity/assay measuring range:
The linearity was established in accordance with the CLSI protocol EP06.
Linearity/Measuring Range
| VITROS System | Measuring (Reportable) Range |
|---|---|
| 5600 | 0.800–500 IU/mL |
d. Dilution Recovery
Serum samples with concentrations greater than the measuring range may be diluted up to 4000-fold (1 part sample with 3999 parts diluent) with the VITROS High Sample Diluent A. Dilutions of up to 1:400 (1 part sample with 399 parts diluent) may be performed automatically on the VITROS 5600 Integrated System, using the VITROS High Sample Diluent A Reagent Pack.
e. Traceability:
Calibration of the VITROS AFP test is traceable to in-house reference calibrators which have been calibrated against the First International Reference Preparation 72/225.
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f. Detection Limits:
The Limit of Detection (LoD) for the VITROS AFP test is 0.476 IU/mL (0.576 ng/mL), determined consistent with CLSI document EP17. The Limit of Quantitation (LoQ) for the VITROS AFP test was determined to be 0.800 IU/mL (0.968 ng/mL) at 20% CV. The Limit of Blank (LOB) is 0.229 IU/mL.
g. Analytical Specificity:
Known Interferences
The VITROS AFP test was screened for interfering substances at AFP concentrations of approximately 4.80 IU/mL (5.81 ng/mL) and 19.2 IU/mL (23.2 ng/mL) following CLSI EP07 and EP37. Of the compounds tested, none were found to cause a bias of >10%. Refer to "Specificity" for a list of compounds that did not show interference.
Other Limitations
- The results from this test should be used and interpreted only in the context of the overall clinical picture.
- . Heterophile, as well as human anti-animal antibodies (most common being human antimouse antibodies or HAMA) in serum or plasma of certain individuals are known to cause interference with immunoassays. The anti-animal antibodies may be present in blood samples from individuals regularly exposed to animals or who have received preparations of mouse monoclonal antibodies for diagnosis or therapy. Results inconsistent with clinical observations indicate the need for additional testing.
- For changes in tumor marker concentrations during therapy: ●
- Progressive disease is defined by an increase of at least 25%. Sampling should be O repeated within two to four weeks for additional evidence.
- Partial remission is defined as a decrease of at least 50% in the tumor marker o concentrations.
- . Different test methods cannot be used interchangeably. 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 to the physician must include the identity of the AFP test used.
- Certain drugs and clinical conditions are known to alter AFP concentrations in vivo. For . additional information, refer to one of the published summaries.
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Substances that do not Interfere
The substances listed in the table below were tested with the VITROS AFP test following CLSI EP07and EP37 and found not to cause bias > 10% at AFP concentrations of approximately 4.80 IU/mL (5.81 ng/mL) and 19.2 IU/mL (23.2 ng/mL) at the test concentrations shown.
| Substance | Concentration | |
|---|---|---|
| 5-Fluorouracil | 17 mg/dL | 1.31 mmol/L |
| Acetaminophen | 20 mg/dL | 1.32 mmol/L |
| N-Acetylcysteine | 15 mg/dL | 0.919 mmol/L |
| Acetylsalicylic acid | 50 mg/dL | 2.78 mmol/L |
| Actinomycin D | 50 mg/dL | 0.40 mmol/L |
| Alpha-tocopherol | 6.45 mg/dL | 0.150 mmol/L |
| Amoxicillin | 5.4 mg/dL | 0.148 mmol/L |
| Ascorbic acid | 300 mg/dL | 17 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 | 3510 ng/mL |
| Bleomycin sulfate | 300 mg/dL | N/A |
| Cefoxitin sodium | 695 mg/dL | 15.5 mmol/L |
| Cisplatin | 100 mg/dL | 3.33 mmol/L |
| Cholesterol, total | 400 mg/dL | 10.3 mmol/L |
| Codeine | 0.141 mg/dL | 4.72 µmol/L |
| Cholecalciferol | 19.2 µg/dL | 0.499 µmol/L |
| Cotinine | 0.24 mg/dL | 13.6 µmol/L |
| Cyclophosphamidemonohydrate | 25 mg/dL | 0.96 mmol/L |
| Dextran 40 | 2400 mg/dL | 0.600 mmol/L |
| Doxorubicin hydrochloride | 1 mg/dL | 17.2 µmol/L |
| Enoxaparin | 360 U/dL | N/A |
| Ethanol | 600 mg/dL | 130 mmol/L |
| Etoposide | 25 mg/dL | 0.43 mmol/L |
| Furosemide | 1.59 mg/dL | 48.0 µmol/L |
| HAMA (Human Anti-Mouse | 800 µg/L | 0.053 µmol/L |
| Substance | Concentration | Concentration |
| Antibodies) | ||
| Hemoglobin | 500 mg/dL | 77.6 $\mu$ mol/L |
| Hydralazine hydrochloride | 1.44 mg/dL | 73.2 $\mu$ mol/L |
| Hydrocodone (+) - bitartrate | 0.0072 mg/dL | 0.241 $\mu$ mol/L |
| Ibuprofen | 40 mg/dL | 1.94 mmol/L |
| Intralipid | 2000 mg/dL | 19.2 mmol/L |
| Levothyroxine | 0.0429 mg/dL | 0.552 $\mu$ mol/L |
| Loratadine | 0.0087 mg/dL | 0.227 $\mu$ mol/L |
| Methotrexate | 450 mg/dL | 9.90 mmol/L |
| Mitomycin C | 0.72 mg/dL | 21.5 $\mu$ mol/L |
| Morphine sulfate saltpentahydrate | 0.78 mg/dL | 10.3 $\mu$ mol/L |
| Naproxen | 36 mg/dL | 1.56 mmol/L |
| Omeprazole | 0.84 mg/dL | 24.3 $\mu$ mol/L |
| Phenytoin | 6 mg/dL | 0.238 $\mu$ mol/L |
| Prednisone | 0.01 mg/dL | 0.279 $\mu$ mol/L |
| Rheumatoid factor | 900 IU/mL | N/A |
| Sorafenib | 3 mg/dL | 64.5 $\mu$ mol/L |
| Theophylline | 6 mg/dL | 0.333 mmol/L |
| Total protein | 15 g/dL | 17.1 nmol/L |
| Triglycerides, total | 1500 mg/dL | 16.9 mmol/L |
| Vancomycin hydrochloride | 12.3 mg/dL | 82.8 $\mu$ mol/L |
| Vinblastine sulfate | 100 mg/dL | 1.23 mmol/L |
| Vincristine sulfate | 70 mg/dL | 0.85 mmol/L |
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Cross-Reactivity
The cross-reactivity of the VITROS AFP test was evaluated by adding the following substances to a sample containing no AFP.
| Test Substance | Concentration | % Cross-reactivity |
|---|---|---|
| Human α-1-acid glycoprotein | 200 mg/dL | ND* |
| Human α-1-antitrypsin | 500 mg/dL | ND* |
| Human ceruloplasmin | 250 mg/dL | ND* |
| Human chorionic gonadotrophin | 1,000,000 mIU/mL | ND* |
| Human IgG | 6.00 g/dL | ND* |
| Human placental lactogen | 2000 µg/dL | ND* |
| Human serum albumin | 6000 mg/dL | ND* |
| Human transferrin | 2500 mg/dL | ND* |
| Prolactin | 50,000 mIU/L | ND* |
*Not Detectable. Concentration was below the measuring interval of the test, 0.800 to 500 IU/mL (0.968 – 605 ng/mL)
h. Assay cut-off:
Not applicable.
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i. Comparison studies:
a. Method comparison with predicate device:
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 using the candidate VITROS Immunodiagnostic Products AFP Reagent Pack compared with those analyzed using the cleared predicate VITROS Immunodiagnostic Products AFP Reagent Pack. The relationship between the 2 methods was determined by Weighted Deming regression
Image /page/13/Figure/3 description: This image is a scatter plot comparing two methods of measuring VITROS AFP. The x-axis represents the comparative method, VITROS AFP (GEM.1101) in IU/mL, while the y-axis represents the modified product, VITROS AFP (GEM.1101A) in IU/mL. The plot shows a strong positive correlation between the two methods, with data points clustered closely around a red line. The data ranges from 0 to 500 IU/mL.
| MethodComparison | N | Intercept | Intercept95%ConfidenceInterval | Slope | Slope 95%ConfidenceInterval | CorrelationCoefficient | SampleRangeIU/mL |
|---|---|---|---|---|---|---|---|
| VITROS 5600vsComparativeMethod | 150 | 0.019 | -0.029 to0.066 | 0.99 | 0.986 to0.999 | 0.999 | 0.935-438 |
j. Matrix comparison:
Specimens Recommended
- . Serum
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k. Conversion Factor Change
A study published in Clinica Chimica Acta 96 (1979) 59-65) established the correspondence between the international unit defining activity of the WHO standard ( I.U.) and the mass units as 1 I.U.= 1.21 ng of AFP (CI=1.02-1.43). The standard preparation has been investigated in two collaborative studies using several Reagent Pack methods, such as radioimmunoassay, single radial immunodiffusion and immunoelectrophoresis.1-2 Six laboratories estimated that one IU approximately equals 1.21 (1.02 - 1.43) nanograms of AFP1 .
For the Predicate VITROS AFP Reagent Pack AFP concentrations are quoted in IU/mL or ng/mL. Conversion between units is made using the formula: result in ng/mL= result in IU/mLx1.04.
Efforts to harmonize this conversion factor between manufacturers are ongoing and the National Cancer Institute is using the 1.21 conversion factor. The adoption of the 1.21 conversion factor aligns the modified VITROS AFP Reagent Pack to the other manufacturers already using the 1.21 conversion factor.
Unit Conversion for the predicate VITROS AFP Reagent Pack
| Alternate |
|---|
| ng/mL (IU/mL $\times$ 1.04*) |
Unit Conversion for the modified VITROS AFP Reagent Pack
| Alternate |
|---|
| ng/mL (IU/mL× 1.21*) |
Customer communications will be issued with full details of any identified risks and mitigations.
Specimens Not Recommended
Do not use turbid specimens. Turbidity in specimens may affect test results.
-
- Clinical studies:
- a. Clinical Sensitivity:
- Not applicable.
- b. Clinical Specificity: Not applicable.
- c. Other clinical supportive data:
- Not applicable.
-
- Clinical cut-off:
Not applicable.
-
- Expected values/Reference range:
Same as K983031
- Expected values/Reference range:
{15}------------------------------------------------
N. Proposed Labeling:
The labeling is sufficient, and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this 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.