(428 days)
ARCHITECT CEA (K990774)
No
The device description details a standard immunoassay kit and the analysis of results is based on reading values from a calibration curve, which is a traditional laboratory method, not AI/ML. There is no mention of AI, ML, or related terms in the document.
No.
This device is an in vitro diagnostic (IVD) device used for quantitative determination of a biomarker, not for treating a disease. It aids in monitoring disease progression, but does not provide therapy.
Yes
The device is intended for the quantitative determination of a biomarker (soluble cytokeratin 19 fragments) in human serum as an aid in monitoring disease progression and treatment for lung cancer patients. This function of measuring a specific marker in the body to gather information about a patient's health status, especially for monitoring disease, falls under the definition of a diagnostic device.
No
The device description clearly outlines a physical immunoassay kit involving reagents, microstrips, and a spectrophotometer, indicating it is a hardware-based diagnostic test, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "quantitative determination of soluble cytokeratin 19 fragments in human serum." This involves testing a biological sample (serum) outside of the body (in vitro).
- Device Description: The description details a "solid phase, non-competitive immunoassay" using antibodies and reagents to measure a substance in a sample. This is a typical method for in vitro diagnostic tests.
- Clinical Application: The assay is used "as an aid in monitoring disease progression during the course of disease and treatment in lung cancer patients." This indicates a medical purpose based on the results of the in vitro test.
- Performance Studies: The document includes details about a clinical study using patient samples to assess the performance of the assay in relation to disease progression. This is a requirement for demonstrating the clinical utility of an IVD.
- Key Metrics: The inclusion of metrics like Sensitivity, Specificity, PPV, and NPV are standard for evaluating the performance of diagnostic tests.
- Predicate Device: The mention of a "Predicate Device" (K990774 ARCHITECT CEA) is common in regulatory submissions for IVDs, indicating a comparison to a previously cleared device.
All of these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The CYFRA 21-1 EIA kit is intended for the quantitative determination of soluble cytokeratin 19 fragments in human serum. The assay is to be used as an aid in monitoring disease progression during the course of disease and treatment in lung cancer patients. Serial testing for patient CYFRA 21-1 assay values should be used in conjunction with other clinical methods used for monitoring lung cancer.
Product codes (comma separated list FDA assigned to the subject device)
OVK
Device Description
The CYFRA 21-1 EIA is a solid phase, non-competitive immunoassay based on two monoclonal antibodies (derived from mice) directed against two separate antigenic determinants of soluble fragments of cytokeratin 19. Calibrators, controls and patient samples are incubated together with biotinylated Anti-CYFRA 21-1 MAb and horseradish peroxidase (HRP) labeled Anti-CYFRA 21-1 MAb in streptavidin coated micro strips. After washing, buffered Substrate/Chromogen reagent (hydrogen peroxide and 3, 3', 5, 5' tetramethylbenzidine) is added to each well and the enzyme reaction is allowed to proceed. During the enzyme reaction a blue color will develop if antigen is present. The intensity of the color development is proportional to the amount of CYFRA 21-1 present in the samples.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
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Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Clinical and Hospital laboratories
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Performance Characteristics:
Precision: Two (2) sites tested two (2) CYFRA 21-1 EIA Kit lots for the precision study. For each lot, the two (2) sites repeated the assay for twenty (20) days, (twenty (20) days each lot), and performed two (2) runs per day with four (4) serum based panel samples tested as unknowns. One (1) site tested three (3) CYFRA 21-1 EIA Kit lots for the precision study. This site repeated the assay for thirty (30) days (ten (10) days each lot), performing two (2) runs per day with eight (8) serum based panel samples tested as unknowns. The total precision of the CYFRA 21-1 EIA was found to be less than 8.6 %.
Linearity: The CYFRA 21-1 EIA assay mean dilution linearity is 100 plus or minus 20%. A study was conducted for the CYFRA 21-1 EIA Kit modeled after the CLSI quideline EP6-A. Serum samples with elevated CYFRA 21-1 values were diluted with CYFRA 21-1 Calibrator A (zero). The CYFRA 21-1 concentration was determined for each dilution and the percent (%) recovery was calculated. The nonlinearity calculated by weighted polynomial regression is less than or equal to 10% across the measurement range of 0.5 to 50.0 ng/mL.
Detection and Quantitation Limit: The Limit of Detection of the CYFRA 21-1 EIA Kit was determined to be 0.12 ng/mL. The CLSI quideline EP17-A (22) was used to design the LoD experiments. The limit of detection (LoD) corresponds to the upper limit of the 95% confidence interval and represents the lowest concentration of CYFRA 21-1 antigen that can be distinquished from zero. The Limit of Quantitation of the CYFRA 21-1 EIA Kit was determined to be 0.21 ng/mL. The limit of quantitation (LoQ) corresponds to the lowest amount of analyte in a sample that can be accurately quantitated with the highest allowable imprecision of 17.78%.
Interference: The CYFRA 21-1 EIA Kit mean assay specificity is 100 plus or minus 15%. Recovery studies were performed to compare sera containing the following compounds at the indicated concentrations with control sera. The CLSI guideline EP7-A was used to design the interference experiments. The following substances and concentrations were tested and found not to interfere with the test: Triglycerides (30 mg/mL), Billirubin (0.2 mg/mL), Hemoglobin (5 mg/mL), Total Protein (120 mg/mL), Carboplatin (500 microgram/mL), Cisplatin (165 microgram/mL), Dexamethasone (10 microgram/mL), Doxorubicin (1.16 microgram/mL), Leucovorin (2.68 microgram/mL), Methotrexate (45 microgram/mL), Paclitaxel (3.5 ng/mL).
Potentially interfering clinical conditions: The CYFRA 21-1 EIA assay was evaluated using specimens with HAMA and Rheumatoid Factor (RF) to further assess the assay specificity. Six specimens positive for HAMA and five specimens positive for RF were evaluated for % recovery with CYFRA 21-1 antigen spiked into each specimen at approximately 5 and 25 ng/mL. Mean % recovery for HAMA (6 specimens) was 98%, and for RF (5 specimens) was 101%.
MONITORING THE COURSE OF DISEASE IN PATIENTS DIAGNOSED WITH LUNG CANCER: The effectiveness of the CYFRA 21-1 EIA as an aid in monitoring the course of disease in lung cancer patients was determined through a retrospective clinical study. Changes in CYFRA 21-1 levels in serial serum samples collected from a tertiary cancer center were compared to changes in disease status. A study involving 100 patients was undertaken with a total of 314 observation pairs with an average number of 4.1 observations per patient. For the 100 lung cancer cases, 95 were classified as non-small cell lung cancer (NCSLC) and 5 were classified as small cell lung cancer (SCLC). 90 of the NSCLC were further classified as adenocarcinoma (68), squamous cell carcinoma (19), and large cell carcinoma (3). 79 of these the 100 lung cancer cases had staging information. In this study, only 5 patients had Stage I or II disease, the performance of CYFRA 21-1 has not been adequately assessed in this subpopulation. A positive change in CYFRA 21-1 was defined as a measurable increase in the value that was at least 50% greater than the previous value of the test. Observation pairs with both values below the normal reference range of 1.8 ng/mL were defined as no significant change. Forty-six percent (46%) or 39/85 of the patient samples with a positive change correlated with the disease progression while eighty-seven percent (87%) or 200/229 of the patient serial samples with no significant change in CYFRA 21-1 value correlated with no progression. The total concordance was seventy-six percent (76%) or 239/314.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Based on a >50% increase in CYFRA 21-1 concentration:
Sensitivity: 45.9%
Specificity: 87.3%
PPV: 57.4%
NPV: 81.3%
The following table shows the resulting sensitivities and specificities of the CYFRA 21-1 EIA at various percent changes in CYFRA 21-1 EIA concentrations, together with the positive values (PPV) and negative predictive values (NPV) for the population tested (85 sequential pairs from patients with disease progression and 229 sequential pairs from patients with no progression.):
| Percent Increase in CYFRA 21-1 Concentration (%) | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) |
|---|---|---|---|---|
| 30 | 52.9 | 84.3 | 55.6 | 82.8 |
| 40 | 48.2 | 85.6 | 55.4 | 81.7 |
| 50 | 45.9 | 87.3 | 57.4 | 81.3 |
| 60 | 44.7 | 88.2 | 58.5 | 81.1 |
| 70 | 43.5 | 89.5 | 60.7 | 81.0 |
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
ARCHITECT CEA (K990774)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
Premarket Notification (510(k)) CYFRA 21-1 EIA
Image /page/0/Picture/2 description: The image shows the logo for "FUJIREBIO Diagnostics, Inc.". The logo consists of a stylized graphic on the left, followed by the company name in bold, sans-serif font. The word "Diagnostics, Inc." is placed below "FUJIREBIO" in a smaller font size. The logo appears to be designed for brand recognition and corporate identity.
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: K100831.
Submitter Information
Address: .
Fuiirebio Diagnostics, Inc. 201 Great Valley Parkway Malvern, PA 19355
- Diana Dickson Contact person: (610) 240-3917 dicksond@fdi.com
Summary preparation date: May 26, 2011
Name of Device
| Trade/Proprietary Name: | CYFRA 21-1 EIA Kit |
|---|---|
| ------------------------- | -------------------- |
Common/Usual Name: CYFRA 21-1 EIA Test Kit
Regulation Number: 21 CFR 866.6010
Regulatory Class: Class II
Product Code: OVK
Predicate Device
ARCHITECT CEA (K990774)
Device Description
The CYFRA 21-1 EIA is a solid phase, non-competitive immunoassay based on two monoclonal antibodies (derived from mice) directed against two separate antigenic determinants of soluble fragments of cytokeratin 19. Calibrators, controls and patient samples are incubated together with biotinylated Anti-CYFRA 21-1 MAb and horseradish peroxidase (HRP) labeled Anti-CYFRA 21-1 MAb in streptavidin coated micro strips. After washing, buffered Substrate/Chromogen reagent (hydrogen peroxide and 3, 3', 5, 5' tetramethylbenzidine) is added to each well and the enzyme reaction is allowed to proceed. During the enzyme reaction a blue color will develop if antigen is present. The intensity of the color development is proportional to the amount of CYFRA 21-1 present in the samples.
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Image /page/1/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo consists of a stylized graphic to the left of the company name. The graphic is a three-part design with black, white, and striped sections. The text "FUJIREBIO Diagnostics, Inc." is to the right of the graphic.
The color intensity is determined in a microplate spectrophotometer at 620 nm (or optionally at 405 nm after addition of Stop Solution).
Calibration curves are constructed for each assay by plotting absorbance value versus the concentration for each calibrator. The CYFRA 21-1 concentrations of patient samples are then read from the calibration curve.
Reportable Range
The CYFRA 21-1 ElA measures concentrations between 0.5 and 50 ng/mL.
Intended Use
The CYFRA 21-1 EIA kit is intended for the quantitative determination of soluble cytokeratin 19 fragments in human serum. The assay is to be used as an aid in monitoring disease progression during the course of disease and treatment in lung cancer patients. Serial testing for patient CYFRA 21-1 assay values should be used in conjunction with other clinical methods used for monitoring lung cancer.
Statement of Substantial Equivalence
The CYFRA 21-1 EIA kit is intended for the quantitative determination of soluble cytokeratin 19 fragments in human serum.
The assay is to be used as an aid in monitoring disease progression during the course of disease and treatment in lung cancer patients. Serial testing for patient CYFRA 21-1 assay values should be used in conjunction with other clinical methods used for monitoring lung cancer.
As there is no FDA cleared or approved device for the CYFRA 21-1 EIA Kit, substantial equivalence for the CYFRA 21-1 EIA test kit was determined by comparing the performance characteristics obtained with the CYFRA 21-1 EIA to the package insert claims in the ARCHITECT CEA assay.
The requlatory submission will be prepared pursuant to Title 21CFR § 866.6010(b) which states Tumor Markers must comply with the following special controls;
-
- Guidance document entitled "Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA".
-
- Voluntary assay performance standards issued by the Clinical Laboratory Standards Institute (CLSI), formally NCCLS.
A comparison of the features of the CYFRA 21-1 EIA Kit and the ARCHITECT CEA assay are as follows:
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Image /page/2/Picture/1 description: The image contains the logo for "FUJIREBIO Diagnostics, Inc.". The logo consists of a stylized graphic on the left, followed by the company name in bold, sans-serif font. The word "Diagnostics, Inc." is written in a smaller font size below the company name.
| Similarities | ||
|---|---|---|
| CYFRA 21-1 EIA Kit | ||
| (Proposed Device) | ARCHITECT CEA | |
| (Predicate Device) | ||
| K990774 | ||
| Device Type | In vitro diagnostic | In vitro diagnostic |
| Classification | Class II | Class II |
| Regulation Number | 21 CFR 866.6010 | 21 CFR 866.6010 |
| Product Usage | Clinical and Hospital laboratories | Clinical and Hospital laboratories |
| Specimen Collection | ||
| Method | Routine Phlebotomy Techniques | Routine Phlebotomy Techniques |
| Interpretation of Results | Standard Curve | Standard Curve |
| Differences | ||
|---|---|---|
| CYFRA 21-1 EIA Kit | ||
| (Proposed Device) | ARCHITECT CEA | |
| (Predicate Device) | ||
| K042731 | ||
| Product Code | To be determined | DHX |
| Type of Specimen | Human Serum Only | Human Serum or Plasma |
| Antigen Detected | CYFRA 21-1 | CEA |
| Calibrators | Supplied with Kit | Supplied as separate Kit |
| Controls | Supplied with Kit | Supplied as separate Kit |
| Principle of Operation | Manual | |
| Enzymatic Immunoassay (EIA) | Automated | |
| Chemiluminescent Microparticle | ||
| Immunoassay (CMIA) | ||
| Intended Use | Aid in monitoring disease | |
| progression during the course of | ||
| disease and treatment in lung | ||
| cancer patients. | Aid in the prognosis and | |
| management of cancer patients in | ||
| whom changing concentrations of | ||
| CEA are observed. |
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Image /page/3/Figure/1 description: The image shows the logo for FUJIREBIO Diagnostics, Inc. The logo consists of a stylized graphic on the left, followed by the text "FUJIREBIO" in bold, uppercase letters. Below the company name, the text "Diagnostics, Inc." is printed in a smaller, regular font. The graphic appears to be an abstract design, possibly representing a molecule or a stylized flower.
Performance Characteristics
Precision:
Two (2) sites tested two (2) CYFRA 21-1 EIA Kit lots for the precision study. For each lot, the two (2) sites repeated the assay for twenty (20) days, (twenty (20) days each lot), and performed two (2) runs per day with four (4) serum based panel samples tested as unknowns. One (1) site tested three (3) CYFRA 21-1 EIA Kit lots for the precision study. This site repeated the assay for thirty (30) days (ten (10) days each lot), performing two (2) runs per day with eight (8) serum based panel samples tested as unknowns. The total precision of the CYFRA 21-1 EIA was found to be Total (with Stage Information) | 79 |
| Unknown | 17 |
| Unstaged | 4 |
| Total Lung Cancer Cases | 100 |
A positive change in CYFRA 21-1 was defined as a measurable increase in the value that was at least 50% greater than the previous value of the test. Observation pairs with both values below the normal reference range of 1.8 ng/mL were defined as no significant change. This level of change takes into account the variability of the assay and the biological variability.
Forty-six percent (46%) or 39/85 of the patient samples with a positive change correlated with the disease progression while eighty-seven percent (87%) or 200/229 of the patient serial samples with no significant change in CYFRA 21-1 value correlated with no progression. The total concordance was seventy-six percent (76%) or 239/314. The following table presents the data in a 2 x 2 format.
| Change in Disease State per Sequential Pair | |||
|---|---|---|---|
| Increase in CYFRA | |||
| 21-1 concentration | Progression | No Progression | Total |
| >50% | 39 | 29 | 68 |
| ≤50% | 46 | 200 | 246 |
| Total | 85 | 229 | 314 |
Clinicians may wish to use other percent changes in CYFRA 21-1 concentration to reflect their preferences in the trade-off between sensitivity and specificity. The following table shows the resulting sensitivities and specificities of the CYFRA 21-1 EIA at various percent changes in CYFRA 21-1 EIA concentrations, together with the positive values (PPV) and negative predictive values (NPV) for the population tested (85 sequential pairs from patients with disease progression and 229 sequential pairs from patients with no progression.)
- . Sensitivity is represented as the proportion of patients with disease progression that had elevated CYFRA 21-1
- Specificity is represented as the proportion of patients without disease progression that . had no elevation in CYFRA 21-1
- PPV is represented as the proportion of patients with elevated CYFRA 21-1 that had . disease progression
- NPV is represented as the proportion of patients with no elevation in CYFRA 21-1 that . did not have disease progression
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Image /page/6/Picture/1 description: The image shows the logo for FUJIREBIO Diagnostics, Inc. The logo consists of a stylized graphic on the left, followed by the company name in bold, sans-serif font. The word "Diagnostics, Inc." is placed below the company name in a smaller font size.
| Percent Increase in
CYFRA 21-1
Concentration (%) | Sensitivity
(%) | Specificity
(%) | PPV
(%) | NPV
(%) |
|--------------------------------------------------------|--------------------|--------------------|------------|------------|
| 30 | 52.9 | 84.3 | 55.6 | 82.8 |
| 40 | 48.2 | 85.6 | 55.4 | 81.7 |
| 50 | 45.9 | 87.3 | 57.4 | 81.3 |
| 60 | 44.7 | 88.2 | 58.5 | 81.1 |
| 70 | 43.5 | 89.5 | 60.7 | 81.0 |
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Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines representing its body and wings. The logo is surrounded by text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.
Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-G609 Silver Spring, MD 20993-0002
Fujirebio Diagnostics, Inc. c/o Ms. Diana Dickson Regulatory Affairs Manager 201 Great Valley Parkway Malvern, PA 19355
MAY 2 6 2011
Re: K100831
Trade/Device Name: CYFRA 21-1 EIA Kit Regulation Number: 21 CFR §866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: Class II Product Codes: OVK Dated: May 18, 2011 Received: May 19, 2011
Dear Ms. Dickson:
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. 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.
If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice
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Page 2 - Ms. Diana Dickson
requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Maria Chan
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use Form
510(k) Number (if known): K100831
Device Name: _CYFRA 21-1 EIA
Indications for Use:
The CYFRA 21-1 EIA kit is intended for the quantitative determination of soluble cytokeratin 19 fragments in human serum. The assay is to be used as an aid in monitoring disease progression during the course of disease and treatment in lung cancer patients. Serial testing for patient CYFRA 21-1 assay values should be used in conjunction with other clinical methods used for monitoring lung cancer.
Prescription Use _____________________________________________________________________________________________________________________________________________________________
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Deena Philip
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K100831
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