(230 days)
Lumipulse G CA125II Immunoreaction Cartridges For in vitro diagnostic use. Lumipulse G CA125II is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative determination of CA125 in human serum and plasma (sodium heparin, lithium heparin, or dipotassium EDTA) on the LUMIPULSE G System. The assay is to be used as an aid in monitoring recurrence or progressive disease in patients with ovarian cancer. Serial testing for patient CA125 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer. Lumipulse G CA125II Calibrators Lumipulse G CA125II Calibrators are for use in the calibration of the LUMIPULSE G System for the quantitative measurement of CA125 in human serum or plasma (sodium heparin, or dipotassium EDTA). LUMIPULSE G1200 System LUMIPULSE G1200 is intended for in vitro diagnostics use, and is designed to perform automated chemiluminescence immunoassays of specimens using Lumipulse G reagents, conducting various processes such as dispensing, agitation and photometric measurement.
Lumipulse G CA125Il is an assay system, including a set of immunoassay reagents, for the quantitative measurement of CA125 in specimens based on CLEIA technology by a two-step sandwich immunoassay method on the LUMIPULSE G System. Lumipulse G CA125II Immunoreaction Cartridges consists of 3 x 14 tests. Each kit contains Antibody-Coated Particle Solution and Enzyme-Labeled Antibody Solution. Lumipulse G CA125II Calibrators Each calibrator kit contains one bottle each of Calibrators 1 and 2. The calibrator kit is packaged separately. LUMIPULSE G1200 System LUMIPULSE G1200 is intended for in vitro diagnostics use, and is designed to perform automated chemiluminescence immunoassays of specimens using Lumipulse G reagents, conducting various processes such as dispensing, agitation, and photometric measurement. The chemiluminescent enzvme immunoassay system is carried out using the ferrite particle coated with antigen or antibody and conjugate with alkaline phosphatase and the chemical luminescent substrate. The luminescence which is produced by the chemiluminescent enzyme immunoassay is measured by photometric detector.
The provided text describes the Lumipulse G CA125II Immunoreaction Cartridges, Lumipulse G CA125II Calibrators, and LUMIPULSE G1200 System, which are used for the quantitative determination of CA125 in human serum and plasma to aid in monitoring recurrence or progressive disease in patients with ovarian cancer.
Here's an analysis of the acceptance criteria and study data provided:
1. A table of acceptance criteria and the reported device performance
Unfortunately, the document does not explicitly state pre-defined "acceptance criteria" in a structured table. However, performance goals can be inferred from the study results and general clinical practice for such assays. The study's conclusion states that the assay "is substantially equivalent to the performance of the Siemens ADVIA Centaur CA 125II assay," implying that meeting the performance of the predicate device serves as an acceptance criterion.
Based on the provided performance characteristics, here's a reconstructed table with inferred performance goals and reported performance:
| Performance Characteristic | Inferred Performance Goal (Acceptance Criteria) | Reported Device Performance (Lumipulse G CA125II) |
|---|---|---|
| Precision (Within-laboratory Total %CV) | ≤ 10% (as stated in section 1.a) | ≤ 2.6% |
| Precision (Site-to-site Total %CV) | Not explicitly stated, but clinical acceptability implied by study. | ≤ 6.4% |
| Precision (Lot-to-lot Total %CV) | Not explicitly stated, but clinical acceptability implied by study. | ≤ 5.2% |
| Linearity/Reportable Range | Demonstrates linearity across the intended measurement range (2.5 to 1000 U/mL) | Demonstrated linearity from 2.5 to 1000 U/mL (R-squared: 0.9999 for Serum, 0.9996 for Plasma) |
| Recovery | 100 ± 15% (as stated in section on recovery) | 97% to 115% |
| High Dose Hook Effect | No high dose hook effect within the expected range of clinical samples. | No effect observed up to 200,000 U/mL. |
| Limit of Blank (LoB) | Not explicitly stated as acceptance criterion, but low value is desirable. | 0.1 U/mL |
| Limit of Detection (LoD) | ≤ 2.0 U/mL (as stated in detection limit section) | 0.5 U/mL |
| Limit of Quantitation (LoQ) | ≤ 2.0 U/mL (as stated in detection limit section) | 0.5 U/mL |
| Analytical Specificity (Interference) | Average interference ≤ 10% (as stated in section 1.e) | Average interference ≤ 10% for listed endogenous and therapeutic compounds |
| Method Comparison (Correlation with Predicate) | High correlation (r) and acceptable bias compared to predicate device. | For 102 samples: r=0.9745, Slope=1.13, Average Bias=25.6 U/mLFor 120 samples: r=0.9829, Slope=1.08, Average Bias=18.2 U/mL |
| Matrix Comparison (Slope vs. Control) | 95% CI for slope within 0.9 to 1.1, and correlation coefficients ≥ 0.9. | Slopes for each tube type had 95% CI entirely within 0.9 to 1.1; correlation coefficients ≥ 0.9. |
| Clinical Performance (Sensitivity in Monitoring) | Not explicitly stated a priori as acceptance criterion, but demonstrated effectiveness is key. | 67.3% (95% CI: 29.9-100.0) |
| Clinical Performance (Specificity in Monitoring) | Not explicitly stated a priori as acceptance criterion, but demonstrated effectiveness is key. | 76.0% (95% CI: 61.0-90.9) |
| Clinical Performance (Total Concordance in Monitoring) | Not explicitly stated a priori as acceptance criterion, but demonstrated effectiveness is key. | 74.4% (95% CI: 60.9-87.9) |
| Clinical Performance (AUC for progression diagnosis) | Statistically significantly better than no-association (0.5 AUC). | 0.728 (SE 0.047), highly statistically significant. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Precision/Reproducibility (Within-laboratory): 8 human serum-based samples (specimen pools) and 2 commercially available serum-based controls. Each sample tested in replicates of two at two separate times of the day for 20 days (n=80 for each sample).
- Precision (Site-to-site): Human serum-based samples (specimen pools) and 2 commercially available serum-based controls. Each sample tested in replicates of two at two separate times of the day at each of 3 external laboratory sites for 10 days (n=40 for each sample). The document does not specify the country of origin or whether the data was retrospective or prospective.
- Precision (Lot-to-lot): Human serum-based samples (specimen pools) and 2 commercially available serum-based controls. Each sample tested in replicates of two at two separate times of the day for each of 3 lots for 10 days (n=40 for each sample).
- Linearity/Assay Reportable Range: One human serum specimen pool and one K2 EDTA plasma specimen pool with high CA125 levels were diluted with low CA125 levels. Specific N for individual samples is not given, but the study method is described.
- Recovery: Not specified, but involved human serum and K2 EDTA plasma samples.
- Limit of Detection (LoD): Seven low-level specimens were tested over 3 days using two LUMIPULSE G1200 Systems and two Lumipulse G CA125II lots, resulting in 120 determinations for each panel.
- Analytical Specificity (Interference): Human serum and K2 EDTA plasma specimen pools supplemented with potentially interfering compounds.
- Method Comparison:
- 102 samples (range 15.5-822.2 U/mL) for direct comparison.
- 120 samples (range 15.5-1128.8 U/mL) including those requiring dilution.
The document does not specify the country of origin or whether the data was retrospective or prospective for these samples.
- Matrix Comparison: Not specified, but involved different tube types (SST, K2EDTA, Lithium Heparin, and Sodium Heparin) versus red top serum samples.
- Clinical Studies (Monitoring of Disease Status): 59 patients, with a total of 289 pairs of observations (average of 5.9 observations per patient). The data provenance (country, retrospective/prospective) is not specified.
- Expected values/Reference range:
- Healthy premenopausal women: N=120
- Healthy postmenopausal women: N=120
- Benign Gynecological Disease: N=260
- Other Benign Disease: N=40
- Congestive Heart Failure: N=40
- Hypertension: N=40
- Pregnant: N=40
- Ovarian Cancer: N=105
- Bladder Cancer: N=40
- Breast Cancer: N=40
- Endometrial Cancer: N=40
- GI Cancer: N=40
- Lung Cancer: N=40
The data provenance (country, retrospective/prospective) is not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
For the "Monitoring of Disease Status in Patients Diagnosed with Ovarian Cancer" study, the ground truth ("disease progression") was determined by comparing "changes in CA125 levels in serial serum samples from 59 patients compared to changes in disease status." The document states that "Serial testing for patient CA125 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer." However, it does not specify the number of experts or their qualifications who established the "disease status" ground truth (i.e., whether the disease had progressed or not, independently of the CA125 reading).
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The document does not describe an adjudication method for establishing the ground truth for the clinical study. It implies that "disease status" was determined by "other clinical methods," but how conflicts or uncertainties in those methods were resolved is not detailed.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This device is an automated in vitro diagnostic assay, not an AI-assisted diagnostic tool that would involve human readers interpreting results. Its purpose is to quantify CA125 levels, and the clinical study evaluates its performance in monitoring disease status based on changes in these quantitative values, not reader performance.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are effectively standalone performance evaluations of the Lumipulse G CA125II assay and the LUMIPULSE G1200 System. The precision, linearity, recovery, detection limits, analytical specificity, and method comparison studies evaluate the algorithm's (the assay's) performance in quantifying CA125 levels. The clinical monitoring study also evaluates the assay's ability to track disease status based on its quantitative output, independent of human interpretive reading of images or complex data (beyond simple interpretation of CA125 value changes).
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
For the clinical monitoring study, the ground truth for "disease progression" was based on "changes in disease status," which is referred to as being determined by "other clinical methods used for monitoring ovarian cancer." This suggests a composite clinical ground truth, likely involving a combination of imaging, clinical assessment, and potentially other biomarkers or pathology, but the specific details are not provided. It is not explicitly stated as pathology or expert consensus, but rather a broader "clinical methods."
8. The sample size for the training set
The document does not describe a "training set" in the context of machine learning. The studies described are performance validation studies for an in vitro diagnostic device, which typically involves analytical validation and clinical validation using a distinct set of samples. The assay itself is a Chemiluminescent Enzyme Immunoassay (CLEIA), a biochemical measurement system, not a machine learning algorithm that requires a separate training set.
9. How the ground truth for the training set was established
As there is no "training set" for a machine learning algorithm, this question is not applicable to the provided document. The ground truth for the reference calibrators for the assay itself is established via traceability to "Fujirebio Diagnostics maintained reference preparation" and correlation to "Fujirebio Diagnostics' CA125II RIA."
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the seal of the Department of Health and Human Services (HHS). The seal features the department's name in a circular arrangement around an emblem. The emblem consists of a stylized caduceus, a symbol often associated with medicine and healthcare, with three intertwined snakes and a staff.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
Fujirebio Diagnostics, Inc. Ms. Diana Dickson Director, Clinical and Regulatory Science 201 Great Valley Parkway Malvern, PA 19355
Re: K142895
Trade/Device Name: Lumipulse G CA125II Immunoreaction Cartridges Lumipulse G CA125II Calibrators Lumipulse G1200 System Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: II Product Code: LTK, JIT, JJE Dated: May 4, 2015 Received: May 5, 2015
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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
{1}------------------------------------------------
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Leonthena R. Carrington -S
Leonthena R. Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
Indications for Use
510(k) Number (if known) K142895
Device Name
Lumipulse G CA125II Immunoreaction Cartridges Lumipulse G CA125II Calibrators LUMIPULSE G1200 System
Indications for Use (Describe) Indications for Use (Describe) Lumipulse G CA125II Immunoreaction Cartridges For in vitro diagnostic use.
Lumipulse G CA125II is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative determination of CA125 in human serum and plasma (sodium heparin, lithium heparin, or dipotassium EDTA) on the LUMIPULSE G System.
The assay is to be used as an aid in monitoring recurrence or progressive disease in patients with ovarian cancer. Serial testing for patient CA125 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer.
Lumipulse G CA125II Calibrators
Lumipulse G CA125II Calibrators are for use in the calibration of the LUMIPULSE G System for the quantitative measurement of CA125 in human serum or plasma (sodium heparin, or dipotassium EDTA).
LUMIPULSE G1200 System
LUMIPULSE G1200 is intended for in vitro diagnostics use, and is designed to perform automated chemiluminescence immunoassays of specimens using Lumipulse G reagents, conducting various processes such as dispensing, agitation and photometric measurement.
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) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
Image /page/3/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized blue and white graphic to the left of the company name. The company name is written in a bold, blue sans-serif font, with "Diagnostics, Inc." written in a smaller, black sans-serif font below.
Section 5 510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
A. 510(k) Number:
B. Purpose for Submission:
New device and instrument
C. Measurand:
CA125
D. Type of Test:
Quantitative assay, automated chemiluminescent enzyme immunoassay (CLEIA)
E. Applicant:
| Address: | Fujirebio Diagnostics, Inc.201 Great Valley ParkwayMalvern, PA 19355 |
|---|---|
| Contact person: | Diana Dickson(610) 240-3917dicksond@fdi.com |
Summary preparation date: May 15, 2015
F. Proprietary and Established Names:
Lumipulse G CA125II Immunoreaction Cartridges Lumipulse G CA125II Calibrators LUMIPULSEG1200 System
G. Regulatory Information:
-
- Regulation section: 21 CFR § 866.6010, Tumor-associated antigen immunological test system 21 CFR § 862.1150, Calibrator 21 CFR § 862.2160 Discrete photometric chemistry analyzer for clinical use
-
- Classification: Class II and Class I
3. Product code: LTK, Test, Epithelial Ovarian Tumor-Associated Antigen (CA125)
{4}------------------------------------------------
JIT, Calibrator, Secondary JJE, analyzer, chemistry (photometric, discrete), for clinical use
-
- Panel: 82, Immunology (Assay and instrument) 75, Chemistry (Calibrators)
H. Intended Use:
-
- Intended use(s): See indications for use below.
-
- Indication(s) for use:
Lumipulse G CA125II Immunoreaction Cartridges
For in vitro diagnostic use.
Lumipulse G CA125II is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative determination of CA125 in human serum and plasma (sodium heparin, lithium heparin, or dipotassium EDTA) on the LUMIPULSE G System.
The assay is to be used as an aid in monitoring recurrence or progressive disease in patients with ovarian cancer. Serial testing for patient CA125 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer.
Lumipulse G CA125II Calibrators
Lumipulse G CA125II Calibrators are for use in the calibration of the LUMIPULSE G System for the quantitative measurement of CA125 in human serum or plasma (sodium heparin, lithium heparin, or dipotassium EDTA).
LUMIPULSE G1200 System
LUMIPULSE G1200 is intended for in vitro diagnostics use, and is designed to perform automated chemiluminescence immunoassays of specimens using Lumipulse G reagents, conducting various processes such as dispensing, agitation and photometric measurement.
-
- Special conditions for use statement(s): Prescription use only
-
- Special instrument requirements: LUMIPULSE G1200 System
{5}------------------------------------------------
Image /page/5/Picture/1 description: The image is a logo for Fujirebio Diagnostics, Inc. The logo has a blue and green abstract design on the left, followed by the company name in blue, and the words "Diagnostics, Inc." in black below it. The logo is clean and professional, and the colors are calming and trustworthy.
-Device Description:
Lumipulse G CA125Il is an assay system, including a set of immunoassay reagents, for the quantitative measurement of CA125 in specimens based on CLEIA technology by a two-step sandwich immunoassay method on the LUMIPULSE G System.
Lumipulse G CA125II Immunoreaction Cartridges |REF| 234273
Lumipulse G CA125II Immunoreaction Cartridges consists of 3 x 14 tests. Each kit contains the following:
Antibody-Coated Particle Solution
(Liquid when used. 250 uL/Immunoreaction Cartridge)
Contains 150 ug/mL anti-CA125 monoclonal antibody (mouse)-coated particles, protein stabilizers (bovine and mouse) and chemical stabilizers in 0.15 M sodium chloride/Tris buffer. This solution contains gelatin and turns into gel at 15 °C or lower. Preservative: sodium azide.
Enzyme-Labeled Antibody Solution (Liquid, 350 µL/Immunoreaction Cartridge) Contains 0.25 µg/mL alkaline phosphatase (ALP: calf) labeled anti-CA125 monoclonal antibody (mouse), protein stabilizers (bovine, calf and mouse) and chemical stabilizers in 0.1 M sodium chloride/MES buffer. Preservative: sodium azide.
Lumipulse G CA125II Calibrators |CAL 234266
Each calibrator kit contains one bottle each of Calibrators 1 and 2. The calibrator kit is packaged separately.
CAL Liquid, 1 × 2 Concentrations
CAL 1| 0 U/mL CA125 calibrator (1 x 1.5 mL)
1000 U/mL CA125 calibrator (1 x 1.5 mL) CAL 2
Contains 0.15 M sodium chloride in Tris buffer with protein stabilizer (bovine). Preservative: sodium azide.
LUMIPULSE G1200 System
LUMIPULSE G1200 is intended for in vitro diagnostics use, and is designed to perform automated chemiluminescence immunoassays of specimens using Lumipulse G reagents, conducting various processes such as dispensing, agitation, and photometric measurement. The chemiluminescent enzvme immunoassay system is carried out using the ferrite particle coated with antigen or antibody and conjugate with alkaline phosphatase and the chemical luminescent substrate. The luminescence which is produced by the chemiluminescent enzyme immunoassay is measured by photometric detector.
{6}------------------------------------------------
Image /page/6/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic on the left, consisting of blue and green shapes that resemble a water droplet or a stylized leaf. To the right of the graphic, the company name "FUJIREBIO" is written in bold, blue letters, with "Diagnostics, Inc." written in a smaller, dark gray font below it.
J. Substantial Equivalence Information:
-
- Predicate device name(s): Siemens ADVIA Centaur CA 125II
-
- Predicate 510(k) number(s): K020828
-
- Comparison with predicate:
{7}------------------------------------------------
Image /page/7/Picture/1 description: The image is a logo for Fujirebio Diagnostics, Inc. The logo consists of a blue and green abstract shape on the left, followed by the company name in blue, and the words "Diagnostics, Inc." in black below the company name. The abstract shape is made up of three curved shapes, one blue, one white, and one green.
| Similarities | |||||
|---|---|---|---|---|---|
| Lumipulse GCA125II Assay(Proposed Device) K142895 | Siemens ADVIA CentaurCA 125II Assay(Predicate Device) K020828 | ||||
| Device Type | In vitro diagnostic | In vitro diagnostic | |||
| Classification | Class II | Class II | |||
| CFR section | 866.6010 | 866.6010 | |||
| Product Code | LTK | LTK | |||
| Product Usage | Clinical and Hospital laboratories | Clinical and Hospital laboratories | |||
| Intended Use | Lumipulse G CA125II is aChemiluminescent EnzymeImmunoassay (CLEIA) for thequantitative determination of CA125 inhuman serum and plasma (sodiumheparin, lithium heparin, ordipotassium EDTA) on theLUMIPULSE G System.The assay is to be used as an aid inmonitoring recurrence or progressivedisease in patients with ovariancancer. Serial testing for patientCA125 assay values should be usedin conjunction with other clinicalmethods used for monitoring ovariancancer. | For in vitro diagnostic use in thequantitative, serial determination ofCA125 in human serum and to aid inthe management of patients withovarian carcinoma using the ADVIACentaur® and ADVIA Centaur XP®systems.The test is intended for use as an aidin monitoring patients previouslytreated for ovarian cancer. Serialtesting for CA 125 in the serum ofpatients who are clinically free ofdisease should be used in conjunctionwith other clinical methods used forthe early detection of cancerrecurrence. The test is also intendedfor use as an aid in the managementof ovarian cancer patients withmetastatic disease by monitoring theprogression or regression of diseasein response to treatment. It isrecommended that the ADVIACentaur CA 125 II assay be usedunder the order of a physician trainedand experienced in the managementof gynecological cancers. This assayis not intended for screening ordiagnosis of ovarian cancer or for useon any other system. | |||
| Interpretation of Results | Calibrator Curve | Calibrator Curve | |||
| Specimen CollectionMethod | Routine Phlebotomy Techniques | Routine Phlebotomy Techniques | |||
| Antibodies | M11 and OC125 (mousemonoclonal) | M11 and OC125 (mousemonoclonal) | |||
| Analvte | Human CA125 | Human CA125 |
{8}------------------------------------------------
Image /page/8/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized, abstract symbol in blue and green, resembling a water droplet or a stylized flower. To the right of the symbol, the word "FUJIREBIO" is written in a bold, sans-serif font, also in blue. Below "FUJIREBIO", the words "Diagnostics, Inc." are written in a smaller, lighter font.
| Differences | ||
|---|---|---|
| Lumipulse GCA125II Assay(Proposed Device) K142895 | Siemens ADVIA CentaurCA 125II Assay(Predicate Device) K020828 | |
| Instrument System | LUMIPULSE G1200 System | ADVIA Centaur® and ADVIACentaur XP® |
| Principle of Operation | Chemiluminscent EnzymeImmunoassay (CLEIA) | Chemiluminescent Immunoassay(CLIA) |
| Type of Specimen | Human Serum or Plasma (sodiumheparin, lithium heparin, ordipotassium EDTA) | Human Serum |
| Assay Range | 2.5 – 1000 U/mL | 2 - 600 U/mL |
| Calibrators | 2 Levels (0 and 1000 U/mL)Ready to Use-Liquid-Supplied as separate kit | 2 Levels (Low and High)-Lyophilized-Supplied as separate kit |
K. Standard/Guidance Document Referenced (if applicable):
- BS EN 13640:2002 Stability Testing of In Vitro Diagnostic Reagents ●
- ISO 17511:2003 Measurement of Quantities in Biological Samples Metrological ● Traceability of Values Assigned to Calibrator and Control Materials
- CLSI EP5-A2 Evaluation of Precision Performance of Quantitative Measurement Methods; . Approved Guideline - Second Edition
- CLSI EP7-A2 - Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition
- CLSI C28-A3c Defining, Establishing, and Verifying Reference Intervals in the Clinical . Laboratory: Approved Guideline-Third Edition
- . CLSI EP17-A2 - Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline Second Edition
- CLSI EP6-A - Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
- . CLSI EP9-A3 – Measurement Procedure Comparison and Bias Estimation Using Patient Samples; approved Guideline - Third Edition
- . FDA Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications, [510(k)], to FDA
- . Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable - Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff
- FDA Guidance Document Guidance for the Content of Premarket Submissions for . Software Contained in Medical Devices (May 11, 2005)
{9}------------------------------------------------
Image /page/9/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. On the left side of the logo is a graphic of a blue and green design. To the right of the graphic is the company name, "FUJIREBIO" in blue, with "Diagnostics, Inc." in black underneath.
L. Test Principle:
Lumipulse G CA125Il is an assay system, including a set of immunoassay reagents, for the quantitative measurement of CA125 in specimens based on CLEI/A technology by a two-step sandwich immunoassay method on the LUMIPULSE G System. CA125 in specimens specifically binds to anti-CA125 monoclonal antibody (mouse) on the particles, and antigenantibody immunocomplexes are formed. The particles are washed and rinsed to remove unbound materials. Alkaline phosphatase (ALP: calf)-labeled anti-CA125 monoclonal antibody (mouse) specifically binds to CA125 of the immunocomplexes on the particles, and additional immunocomplexes are formed. The particles are washed and rinsed to remove unbound materials. Substrate Solution is added and mixed with the particles. AMPPD contained in the Substrate Solution is dephosphorylated by the catalysis of ALP indirectly conjugated to particles. Luminescence (at a maximum wavelength of 477 nm) is generated by the cleavage reaction of dephosphorylated AMPPD. The luminescent signal reflects the amount of CA125.
M. Performance Characteristics (if/when applicable):
Data were generated using the LUMIPULSE G1200 System.
-
- Analytical performance:
- a. Precision/Reproducibility:
Lumipulse G CA125II is ≤10% total (within-laboratory) CV (coefficient of variation). Lumipulse G CA125Il demonstrated precision ≤2.6% total %CV in a study run according to the Clinical and Laboratory Standards Institute (CLSI) guideline EP5-A2. Eight human serum-based samples (specimen pools) and two commercially available serum-based controls were assayed in replicates of two at two separate times of the day for 20 days (n=80 for each sample) using one LUMIPULSE G1200 System. Data from this study are presented below.
| Sample | MeanConc.(U/mL)n=80 | Within-runSD(U/mL) | Within-run%CV | TotalSD(U/mL) | Total%CV |
|---|---|---|---|---|---|
| Serum 1 | 21.1 | 0.36 | 1.7 | 0.48 | 2.3 |
| Serum 2 | 37.5 | 0.54 | 1.4 | 0.60 | 1.6 |
| Serum 3 | 112.2 | 1.47 | 1.3 | 1.80 | 1.6 |
| Serum 4 | 254.8 | 3.74 | 1.5 | 3.96 | 1.6 |
| Serum 5 | 577.9 | 10.90 | 1.9 | 11.01 | 1.9 |
| Serum 6 | 10.9 | 0.21 | 1.9 | 0.26 | 2.4 |
| Serum 7 | 454.7 | 6.51 | 1.4 | 8.78 | 1.9 |
| Serum 8 | 798.6 | 13.04 | 1.6 | 13.74 | 1.7 |
| Control 1 | 20.2 | 0.47 | 2.3 | 0.52 | 2.6 |
| Control 2 | 292.5 | 4.23 | 1.4 | 6.60 | 2.3 |
Site to site: Lumipulse G CA125Il demonstrated precision ≤6.4% total %CV when tested at 3 external laboratory sites. The human serum-based samples (specimen pools) and two commercially available serum-based controls were assayed in replicates of two at two
{10}------------------------------------------------
Image /page/10/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic on the left, consisting of blue and white shapes with vertical lines. To the right of the graphic, the text "FUJIREBIO" is displayed in a bold, blue sans-serif font. Below "FUJIREBIO", the words "Diagnostics, Inc." are written in a smaller, black sans-serif font.
separate times of the day at each of the sites for 10 days (n=40 for each sample) using one LUMIPULSE G1200 System. Data from this study are summarized below.
| Sample | MeanConc.(U/mL)n=120 | Within-runSD(U/mL) | Within-run%CV | TotalSD(U/mL) | Total%CV |
|---|---|---|---|---|---|
| Serum 1 | 21.4 | 0.40 | 1.9 | 1.12 | 5.2 |
| Serum 2 | 38.0 | 0.62 | 1.6 | 1.81 | 4.8 |
| Serum 3 | 112.5 | 2.04 | 1.8 | 4.44 | 3.9 |
| Serum 4 | 254.8 | 3.27 | 1.3 | 9.08 | 3.6 |
| Serum 5 | 580.5 | 9.85 | 1.7 | 19.45 | 3.4 |
| Control 1 | 21.2 | 0.62 | 2.9 | 1.35 | 6.4 |
| Control 2 | 301.8 | 3.71 | 1.2 | 17.22 | 5.7 |
Lot-to-lot: Lumipulse G CA125Il demonstrated precision ≤5.2% total %CV when tested using 3 lots of Lumipulse G CA125II immunoreaction cartridges and calibrators. The human serum-based samples (specimen pools) and two commercially available serum-based controls were assayed in replicates of two at two separate times of the day for each of the lots for 10 days (n=40 for each sample) using one LUMIPULSE G1200 System. Data from this study are summarized below.
| Sample | MeanConc.(U/mL)n=120 | Within-runSD(U/mL) | Within-run%CV | TotalSD(U/mL) | Total%CV |
|---|---|---|---|---|---|
| Serum 1 | 22.1 | 0.43 | 1.9 | 1.12 | 5.1 |
| Serum 2 | 39.1 | 0.64 | 1.6 | 1.88 | 4.8 |
| Serum 3 | 118.4 | 1.53 | 1.3 | 6.13 | 5.2 |
| Serum 4 | 268.0 | 3.78 | 1.4 | 12.75 | 4.8 |
| Serum 5 | 599.3 | 10.75 | 1.8 | 22.45 | 3.7 |
| Control 1 | 21.1 | 0.52 | 2.5 | 1.01 | 4.8 |
| Control 2 | 305.0 | 4.06 | 1.3 | 14.61 | 4.8 |
b. Linearity/assay reportable range:
Lumipulse G CA125II demonstrated linearity on the LUMIPULSE G1200 system in a study consistent with CLSI quideline EP6-A. One human serum specimen pool and one K2 EDTA plasma specimen pool with high CA125 levels were diluted with one human serum specimen pool and one K2 EDTA plasma specimen pool with low CA125 levels throughout the range of the assay. The linearity was found in the range of 2.5 to 1000 U/mL. Lumipulse G CA125Il correlated with expected concentrations according to the linear regression formulas:
y= 0.9973(x)+ 1.5017; R-squared: 0.9999 Serum: y= 1.0147(x)+ 3.9653; R-squared: 0.9996 Plasma:
{11}------------------------------------------------
Image /page/11/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. On the left side of the logo is a blue and green abstract symbol. To the right of the symbol is the company name, "FUJIREBIO" in large blue letters. Below the company name is "Diagnostics, Inc." in smaller black letters.
Lumipulse G CA125Il recovery on the LUMIPULSE G1200 System is 100 ± 15%, ranging from 97% to 115%. A study was performed where known concentrations of OC125 defined antigen were added to human serum and K2 EDTA plasma samples with low endogenous CA125 levels. The concentration of CA125 was determined using the Lumipulse G CA125II and the resulting percent recovery was calculated.
| Sample | TargetCA125Levels(U/mL) | MeasuredConc.U/mL(n=3) | ExpectedConc.(U/mL) | %Recovery |
|---|---|---|---|---|
| Serum 1 | 100 | 102.7 | 103.2 | 100 |
| 300 | 304.6 | 296.1 | 103 | |
| 500 | 500.9 | 502.9 | 100 | |
| 700 | 710.2 | 697.2 | 102 | |
| 950 | 1087.2 | 945.1 | 115 | |
| Serum 2 | 100 | 121.9 | 119.9 | 102 |
| 300 | 318.3 | 312.8 | 102 | |
| 500 | 506.8 | 519.6 | 98 | |
| 700 | 704.9 | 713.9 | 99 | |
| 950 | 981.6 | 961.8 | 102 | |
| Serum 3 | 100 | 104.6 | 103.7 | 101 |
| 300 | 301.3 | 296.6 | 102 | |
| 500 | 490.1 | 503.4 | 97 | |
| 700 | 679.9 | 697.7 | 97 | |
| 950 | 952.4 | 945.6 | 101 | |
| Plasma 1 | 100 | 103.9 | 101.9 | 102 |
| 300 | 293.6 | 294.8 | 100 | |
| 500 | 492.8 | 501.6 | 98 | |
| 700 | 680.0 | 695.9 | 98 | |
| 950 | 944.4 | 943.8 | 100 | |
| Plasma 2 | 100 | 105.5 | 110.0 | 96 |
| 300 | 307.7 | 302.9 | 102 | |
| 500 | 507.9 | 509.7 | 100 | |
| 700 | 719.5 | 704.0 | 102 | |
| 950 | 973.8 | 951.9 | 102 | |
| Plasma 3 | 100 | 106.5 | 105.2 | 101 |
| 300 | 291.2 | 298.1 | 98 | |
| 500 | 503.5 | 504.9 | 100 | |
| 700 | 684.2 | 699.2 | 98 | |
| 950 | 922.3 | 947.1 | 97 |
High dose hook is a phenomenon whereby very high level specimens may read within the dynamic range of the assay. For Lumipulse G CA125II, no high dose hook effect was observed for samples containing up to 200,000 U/mL of OC125 defined antigen on the LUMIPULSE G1200 system. However, values above 20,000 U/mL should be interpreted with caution because reading may be inaccurate above this concentration.
{12}------------------------------------------------
Image /page/12/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo consists of a blue and white abstract symbol on the left, followed by the company name in blue, bold letters. Below the company name, the words "Diagnostics, Inc." are written in a smaller, black font.
Traceability, Stability, Expected values (controls, calibrators, or methods): C.
Lumipulse G CA125II Calibrators are for use in the calibration of the LUMIPULSE G System when used for the quantitative measurement of CA125 in serum or plasma (dipotassium EDTA, lithium heparin, and sodium heparin). 2 Bottles (1.5 mL each) are supplied for the Lumipulse G CA125Il Calibrators. Preservatives: Sodium Azide. The calibrators are at the following concentrations:
| Calibrator | Concentration(U/mL) |
|---|---|
| CAL 1 | 0 |
| CAL 2 | 1000 |
There is currently no known internationally recognized consensus reference method or reference material for standardization. Lumipulse G CA125Il values are expressed as U/mL. This value is related to a Fujirebio Diagnostics maintained reference preparation. Calibration of the Lumipulse G CA125II is traceable to in-house reference calibrators, whose values have been assigned to correlate to Fujirebio Diagnostics' CA125II RIA.
The real time stability (including open use) has been demonstrated on the LUMIPULSE G1200 system for 10 months. The instrument cartridge and calibrators were found to be stable under simulated transport conditions. Shelf life assignment for the Lumipulse G CA125II Immunoreaction Cartridges and Calibrators is 10 months at 2-10°C.
- d. Detection limit:
The Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ) of LUMIPULSE G CA125Il on the LUMIPULSE G1200 system is ≤2.0 U/mL.
1) LoB and LoD
The LoB for Lumipulse G CA125II was 0.1 U/mL.
The LoD for Lumipulse G CA125Il on the LUMIPULSE G1200 system was 0.5 U/mL, determined consistent with the CLSI guideline EP17-A. Seven low level specimens were tested over 3 days using two LUMIPULSE G1200 Systems and two Lumipulse G CA125II lots giving 120 determinations for each panel.
2) LoQ
The LoQ for Lumipulse G CA125Il on the LUMIPULSE G1200 system was 0.5 U/mL, determined consistent with the guidelines in the CLSI guideline EP17-A. Since the percent total error in all cases is less than 30%, LoQ equals LoD.
e. Analytical specificity:
The Lumipulse G CA125II on the LUMIPULSE G1200 system demonstrated an average interference of ≤ 10% (for each compound) in a study consistent with the quidelines in the CLSI quideline EP7-A2. Human serum and K2 EDTA plasma specimen pools were supplemented with potentially interfering compounds. The following compounds were tested and found not to interfere with the test.
{13}------------------------------------------------
Image /page/13/Picture/1 description: The image is a logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic on the left, consisting of blue and white shapes. To the right of the graphic, the word "FUJIREBIO" is written in large, blue, sans-serif font. Below "FUJIREBIO", the words "Diagnostics, Inc." are written in a smaller, black, sans-serif font.
| Endogenous | TestConcentration |
|---|---|
| Interferences | |
| Free Bilirubin (unconjugated) | 60 mg/dL |
| Conjugated Bilirubin | 60 mg/dL |
| Triglycerides (Intralipid 20%Emulsion) | 3000 mg/dL |
| Hemoglobin | 500 mg/dL |
| Human Serum Albumin | 12 g/dL |
| Immunoglobulin G (IgG) | 5 g/dL |
| Biotin | 19.7 mg/dL |
| Human Anti-Mouse Antibodies(HAMA) | 1,000 ng/mL |
| Rheumatoid Factor (RF) | 1,000 IU/mL |
| Therapeutic drug | TestConcentration |
| Interferences | |
| Carboplatin | 600 µg/mL |
| Cisplatin | 180 µg/mL |
| Clotrimazole | 0.3 µg/mL |
| Cyclophosphamide | 800 µg/mL |
| Dexamethansone | 20 µg/mL |
| Doxorubicin | 120 µg/mL |
| Erlotinib | 150 µg/mL |
| Etoposide | 10 µg/mL |
| 5-Fluorouracil | 900 µg/mL |
| Gemcitabine | 100 µg/mL |
| Leucovorin | 750 µg/mL |
| Magestrol Acetate | 10 µg/mL |
| Melphalan | 15 µg/mL |
| Methotrexate | 450 µg/mL |
| Paclitaxel | 3.5 ng/mL |
| Tamoxifen | 60 µg/mL |
-
f. Assay cut-off:
See Clinical Cutoff in M (4) below -
- Comparison studies:
- a. Method Comparison
Lumipulse G CA125Il method comparison study was performed on the LUMIPULSE G1200 system using specimens consistent with CLSI guideline EP9-A3 using the weighted Deming regression method to compare Lumipulse G CA125II to ADVIA Centaur CA 125II. The ADVIA Centaur CA 12511 has a different measuring range than the Lumipulse G CA125II therefore the results limited to the measurement range of both devices (102 samples). The samples tested ranged from 15.5-822.2 U/mL. The data are summarized in the following table.
{14}------------------------------------------------
Image /page/14/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a blue abstract symbol on the left, followed by the company name in blue text. The word "FUJIREBIO" is in a larger, bolder font, and "Diagnostics, Inc." is in a smaller font below it.
| Lumipulse G CA125II vs. ADVIA Centaur CA 125II | ||||
|---|---|---|---|---|
| n | CorrelationCoefficient(r) | Intercept(95% CI) | Slope(95% CI) | AverageBias (U/mL) |
| 102 | 0.9745 | -0.87-6.32 – 4.58 | 1.131.06 – 1.12 | 25.6 |
The data summarized in the following table include results from a study with specimens above the measurement range of both devices requiring dilution (120 samples). The samples tested ranged from 15.5-1128.8 U/mL.
| n | CorrelationCoefficient(r) | Intercept(95% CI) | Slope(95% CI) | AverageBias (U/mL) |
|---|---|---|---|---|
| 120 | 0.9829 | 1.55-2.89 – 5.99 | 1.081.03 - 1.13 | 18.2 |
b. Matrix Comparison
The Lumipulse G CA125II matrix comparison study was performed on the LUMIPULSE G1200 system to evaluate the difference across tube types (SST, K2EDTA, Lithium Heparin, and Sodium Heparin) versus the means of the control samples (Red top serum) analyzed per CLSI guideline EP9-A3. The slope for each tube type when compared to the control had 95% confidence intervals that lay entirely within the range 0.9 to 1.1 and the correlation coefficients were ≥ 0.9.
Clinical studies: 3.
- a. Clinical sensitivity:
See 3(c) below
- b. Clinical specificity:
See 3(c) below
{15}------------------------------------------------
Image /page/15/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic on the left, consisting of blue and white shapes. To the right of the graphic, the word "FUJIREBIO" is written in a bold, blue sans-serif font. Below "FUJIREBIO", the words "Diagnostics, Inc." are written in a smaller, black sans-serif font.
Other clinical supportive data (when a. and b. are not applicable): C.
Monitoring of Disease status in Patients Diagnosed with Ovarian Cancer
The effectiveness of Lumipulse G CA125II on the LUMIPULSE G1200 system as an aid in monitoring of disease status in ovarian cancer patients was determined by assessing changes in CA125 levels in serial serum samples from 59 patients compared to changes in disease status. A study involving a total of 289 pairs of observations was undertaken with an average number of 5.9 observations per patient. A positive change in CA125 was defined as an increase in the value that was at least 20% greater than the previous value of the test. This level of change takes into account the variability of the assay. Sixty-seven percent (67%) or 35/52 of the patient samples with a positive change correlated with the disease progression while seventy-six percent (76%) or 180/237 of the patient serial samples with no significant change in CA125 value correlated with no progression. The total concordance was seventy-four percent (74% or 215/289).
| Performance Measurement | SE | Lower95% CI | Upper95% CI | |
|---|---|---|---|---|
| Sensitivity | 67.3 | 18.70 | 29.9 | 100.0 |
| Specificity | 76.0 | 7.45 | 61.0 | 90.9 |
| Total Concordance | 74.4 | 6.74 | 60.9 | 87.9 |
| PPV | 38.0 | 10.57 | 16.9 | 59.2 |
| NPV | 91.4 | 8.96 | 73.4 | 100.0 |
Lumipulse G CA125II Performance Measurements (%):
SE = Standard Error
CI = Confidence Interval
The following table presents the data in a 2 x 2 format.
| Change in Disease State per Sequential Pair | |||||
|---|---|---|---|---|---|
| Change inCA125Concentration | Noprogression | Progression | Total | ||
| ≤ 20% | 180 | 17 | 197 | ||
| > 20% | 57 | 35 | 92 | ||
| Total | 237 | 52 | 289 |
A ROC curve for the diagnosis of progression from the ratio of successive CA125Il readings is shown below.
The area under the AUC curve is 0.728 with SE 0.047; this is highly statistically significantly better than the no-association AUC of 0.5.
{16}------------------------------------------------
Image /page/16/Picture/1 description: The image is a logo for Fujirebio Diagnostics, Inc. The logo consists of a stylized graphic on the left and the company name on the right. The graphic is a blue and green design with a white teardrop shape in the center. The company name is written in blue, with "Diagnostics, Inc." written in a smaller, black font below the company name.
Image /page/16/Figure/2 description: This image is a plot of sensitivity versus false positives. The plot shows a curve that starts at the origin and increases to the upper right corner. The area under the curve (AUC) is 0.728, and the standard error (SE) is 0.047. The x-axis is labeled "False positives" and ranges from 0.0 to 1.0, while the y-axis is labeled "Sensitivity" and ranges from 0.0 to 1.0.
Progression
4. Clinical cut-off:
There is no conventional cut-off for this assay; however, CA125 is significantly elevated if it is at least 20% higher than the previous assay.
{17}------------------------------------------------
Image /page/17/Picture/1 description: The image shows the logo for Fujirebio Diagnostics, Inc. The logo consists of a stylized graphic on the left and the company name on the right. The graphic is a blue and white design with curved lines and a water droplet shape. The company name is written in blue and black, with "FUJIREBIO" in a larger, bolder font and "Diagnostics, Inc." in a smaller font below it.
5. Expected values/Reference range:
The distribution of CA125 levels determined on the LUMIPULSE G1200 system in healthy premenopausal women and healthy postmenopausal women is shown in the table below:
| AllHealthy Subjects | PremenopausalHealthy Subjects | PostmenopausalHealthy Subjects | |
|---|---|---|---|
| N | 240 | 120 | 120 |
| Mean | 12.2 | 13.6 | 10.7 |
| (SD) | (9.3) | (12.0) | (5.0) |
| Median | 10.4 | 11.7 | 9.6 |
| Range(min, max) | 2.9, 123.9 | 3.7, 123.9 | 2.9, 30.2 |
| ReferenceInterval(2.5th percentile,97.5th percentile) | 4.4, 30.2 | 4.4, 33.8 | 3.7, 24.2 |
| Proportionbelow97.5th Percentile | 97.5% | 95.8% | 100.0% |
All Lumipulse G CA125Il concentrations are presented as U/mL.
In this study 99.2% of the healthy female subjects had a CA125 assay value at or below 35.0 U/mL.
The distribution of CA125 levels determined on the LUMIPULSE G1200 system in benign conditions is shown in the table below:
| BenignGynecologicalDisease | OtherBenignDisease | CongestiveHeart Failure | Hypertension | Pregnant | |
|---|---|---|---|---|---|
| N | 260 | 40 | 40 | 40 | 40 |
| Mean | 42.0 | 30.5 | 26.3 | 31.2 | 23.8 |
| (SD) | (291.1) | (80.0) | (25.3) | (49.8) | (13.1) |
| Median | 14.9 | 11.4 | 18.9 | 16.9 | 17.0 |
| Range (min, max) | 4.3, 4677.0 | 4.5, 493.2 | 5.3, 145.9 | 5.2, 238.4 | 9.2, 54.7 |
| Reference Interval(2.5th percentile,97.5th percentile) | 5.0, 143.1 | 4.5, 485.0 | 5.3, 144.0 | 5.2, 238.2 | 9.2, 54.6 |
| Proportion below97.5th Percentile | 86.5% | 92.5% | 75.0% | 80.0% | 72.5% |
All Lumipulse G CA125Il concentrations are presented as U/mL.
{18}------------------------------------------------
Image /page/18/Picture/1 description: The image shows the logo for Fujirebio Diagnostics, Inc. On the left side of the logo is an abstract design in blue and green. The right side of the logo has the company name in blue, with "Diagnostics, Inc." in a smaller font size and in black.
The distribution of CA125 levels determined in malignancy conditions is shown in the table below:
| OvarianCancer | BladderCancer | BreastCancer | Endo-metrialCancer | GI Cancer | LungCancer | |
|---|---|---|---|---|---|---|
| N | 105 | 40 | 40 | 40 | 40 | 40 |
| Mean | 360.8 | 19.7 | 96.0 | 50.2 | 45.5 | 124.5 |
| (SD) | (768.3) | (14.4) | (417.5) | (131.3) | (152.3) | (242.5) |
| Median | 84.7 | 13.4 | 16.4 | 19.4 | 13.7 | 42.5 |
| Range (min, max) | 5.7, 3923.5 | 4.1, 69.0 | 5.8, 2660.0 | 5.9, 835.5 | 7.3, 976.8 | 8.4, 957.9 |
| Reference Interval(2.5th percentile,97.5th percentile) | 7.1, 3495.5 | 4.1, 68.4 | 5.8, 2597.9 | 5.9, 818.6 | 7.3, 955.1 | 8.4, 957.4 |
| Proportionbelow97.5th Percentile | 35.2% | 77.5% | 67.5% | 72.5% | 77.5% | 40.0% |
All Lumipulse G CA125Il concentrations are presented as U/mL.
It is recommended that each laboratory establish its own reference value for the population of interest for Lumipulse G CA125II on the LUMIPULSE G1200.
N. Proposed Labeling:
The labeling satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion
The results of these analytical) and clinical studies demonstrate that the Lumipulse G CA125Il assay is substantially equivalent to the performance of the Siemens ADVIA Centaur CA 125II assay.
§ 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.