(237 days)
No
The summary describes a standard immunoassay based on electrochemiluminescence and antibody binding. There is no mention of AI, ML, or any computational methods beyond standard calibration curve generation and data analysis for performance characteristics.
No
The device is an immunoassay for the quantitative determination of specific determinants to aid in the detection of ovarian carcinoma and monitor the disease, meaning it is a diagnostic tool, not a therapeutic device.
Yes
The device aids in the detection of recurrent ovarian carcinoma and monitors patients for disease progress or response to therapy, which are diagnostic purposes.
No
The device is an immunoassay reagent and calibrator intended for use on a specific immunoassay analyzer (cobas e 411). It involves chemical reactions and physical components (reagents, microparticles) to determine analyte concentration, which is not a software-only function.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the Elecsys CA 125 II is an "immunoassay for the in vitro quantitative determination..." and is "indicated for use as an aid in the detection of recurrent ovarian carcinoma" and "in monitoring patients for disease progress or response to therapy." The term "in vitro" is a key indicator of an IVD, meaning it's used to test samples outside of the body.
- Device Description: The description details the assay principle, which involves testing human serum and plasma samples using specific antibodies and detection methods. This is consistent with the nature of an IVD.
- Performance Studies: The extensive performance studies described (precision, linearity, interference, method comparison, stability, etc.) are typical evaluations required for IVD devices to demonstrate their analytical and clinical performance.
- Predicate Device: The mention of a "predicate assay (K972162)" and "predicate CalSet (K102086)" further confirms its classification as an IVD, as predicate devices are used for comparison in regulatory submissions for new IVDs.
Therefore, based on the provided information, the Elecsys CA 125 II is clearly an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
Elecsys CA 125 II is an immunoassay for the in vitro quantitative determination of OC 125 reactive determinants in human serum, Li heparin, K2-EDTA, as well as Li-heparin plasma tubes containing separating gel on the cobas e 411 analyzer.
These determinants are associated with a high molecular weight glycoprotein in serum and plasma of women with primary epithelial invasive ovarian cancer (excluding those with cancer of low malignant potential).
This immunoassay is indicated for use as an aid in the detection of recurrent ovarian carcinoma. This immunoassay is further indicated for use in monitoring patients for disease progress or response to therapy.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 411 immunoassay analyzers.
Elecsys CA 125 II CalCheck: For use in the verification of the calibration established by the Elecsys CA 125 II reagent on the Elecsys and cobas e immunoassay analyzers.
Product codes (comma separated list FDA assigned to the subject device)
LTK, JJX
Device Description
The Elecsys CA 125 II assay employs a sandwich test principle using biotinylated monoclonal CA 125-specific antibody and a monoclonal CA 125-specific antibody labeled with a ruthenium complex to form a sandwich complex. The use of streptavidin-coated microparticles serves as the solid phase for the electrochemiluminescence detection.
Results are determined using a calibration curve that is generated specifically on each instrument by a 2 point calibration and a master curve (5-point-calibration) provided with the reagent bar code.
The CA 125 II application is identical to the predicate assay (K972162). This submission is being done to modernize the labeling by adding the LoB, LoD and LoQ data and to change the sample:reagent ratio from 40:60μL to 20:70μL. Additionally, based on internal stability data the calibration frequency has been extended from 4 to 8 weeks.
The Elecsys CA 125 II CalCheck is a lyophilized product consisting of equine serum in level 1 and human serum matrix for levels 2 and 3. During manufacture, the analyte is spiked into the matrix at the desired concentration levels.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Prescription Use (Part 21 CFR 801 Subpart D)
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
LoB of the Elecsys CA125 II assay has been determined according to CLSI EP17-A2. The distribution of values for five analyte-free human samples was determined with three reagent lots on two cobas e 411 analyzers with six runs distributed over a period of up to 5 days. The sample was measured in one-fold determination in each run. In summary, 30 measuring points were collected per instrument. for a total of 60 measured values.
LoD of the Elecsys CA125 II assay has been determined according to CLSI EP17-A2. The distribution of values for five human samples with low analyte concentration has been determined with three reagent lots on two cobas e 411 analyzers with six runs distributed over a period of up to 5 days. Samples were measured in one-fold determination in each run. In summary, 30 measuring points were collected per instrument, for a total of 60 measured values.
LoQ of the Elecsys CA125 II assay was determined according to CLSI Guideline EP17-A2. The distribution of values for three human sample pools each diluted to concentrations which covered the range between LoB and 2x LoQ has been determined with three reagent lot on two cobas e 411 analyzers with six runs distributed over three to five days. Each run was calibrated separately using a two point calibration. Samples were measured in one-fold determination in each run. In summary, a total of 54 measuring points were collected per instrument, for a total of 108 measured values.
Six dilution series were prepared from six different spiked human samples. The first three dilution series were performed with serum samples and the other three with plasma samples. Each dilution series included 15 dilutions. Each sample was measured 3-fold within one run and the measured concentrations were plotted against the expected sample concentration.
The dilution study for the Elecsys CA125 II assay was performed on the cobas e 411 using three human samples spiked to analyte concentrations above the measuring range and diluted automatically. These measurements were compared against manual dilutions. The samples were diluted with the Elecsys Diluent Universal. The diluted and undiluted samples were measured in triplicate. Testing was performed on two cobas e 411 analyzers.
The high dose hook effect of the Elecsys CA125 II assay was assessed on the cobas e 411 analyzer. Two samples were spiked with analyte to a concentration of 50000U/mL. For each sample a dilution series was performed using Diluent Universal (Id. Nr. 175912) resulting in 5 to 6 samples above the measuring range. Each dilution was tested in single determination.
The effect of the presence of human anti-mouse antibodies on the Elecsys CA125 II assay was assessed on the cobas e 411 analyzer. A specified HAMA serum and the related basic serum without interferent were spiked with the analyte to a concentration of 13.0 U/mL. These two samples were measured in duplicates.
The effect on quantitation of analyte in the presence of endogenous interfering substances using the Elecsys CA125 II was determined on the cobas e 411 analyzer for the following 5 interfering substances Intralipid, Biotin, Bilirubin, Rheumatic Factor and Hemolysis using three spiked human samples (one low, one medium, and one high) to prepare dilution series of 11 dilutions that were tested with one reagent lot.
16 common and 23 additional pharmaceutical compounds were spiked into each of two human samples containing CA125 (low and high concentration). The spiked samples (spiked with 10.7 U/mL and 313 U/mL CA125) were evaluated at drug concentrations defined as 5- fold daily dose and tested for interference by the Elecsys CA125 II assay on cobas e 411 analyzer. Testing was performed in 3-fold determination with one reagent lot in one run on one cobas e 411 analyzer.
The effect on quantitation of analyte in the presence of anticoagulants with the Elecsys CA125 II assay was determined by comparing values obtained from native samples (single donors) drawn into Serum, Li-Heparin, K2-EDTA-, K3-EDTA-plasma primary tubes and Li-Heparin Plasma Separation Tubes. 51 or 52 serum/plasma pairs per sample material were tested in duplicates with one reagent lot on one cobas e 411 analyzer.
The method comparison study was performed on the Elecsys 2010 analyzer using the Elecsys CA125 II assay (sample/reagent ratios as cleared under K972162) and the CA125 II Cal Set (K003969)(X) against the Elecsys CA 125 II assay with the new sample/reagent ratios and the Elecsys CA125 II CalSet (K003969) (Y). A total of 80 human serum samples (all native single donors) with CA125 values from 4.7 -2680U/mL (X) and 4.8 -2594U/mL (Y) were measured in order to cover the entire measuring range.
A method comparison was performed using the Elecsys CA125 II assay in combination with the Elecsys CA125 II CalSet (cleared under K003969) as predicate device and in combination with the new cleared Elecsys CA125 II CalSet II (K140112). The study was performed on the cobas e 411 analyzer using the Elecsys CA125 II assay with the CA125 II Cal Set(X) and the Elecsys CA 125II assay with the new Elecsys CA125 II CalSet II assay (Y). A total of 111 human serum samples (all native single donors) with CA125 values from 3.19–2621U/mL (X) and 4.05–2641U/mL (Y) were measured in order to cover the entire measuring range.
Study 1: Reagent stability after first opening for the Elecsys CA125 II assay was determined on a cobas e 411 analyzer by comparing the reagent stability for four kits of the same lot. All reagent kits were opened on day 0. One kit was placed on the analyzer and calibrated and reference values for the samples tested were determined. The other three kits were stored at 2 to 8°C. After 5, 9 and 13 weeks, one of the stored kits was placed on the analyzer and calibrated, and the original test samples were measured. Samples tested in duplicate include five human serum (HS) samples and two controls. The human serum samples used were native single donors.
Study 2: On-board reagent stability for the CA125 II assay was tested on one cobas e 411 immunoassay analyzer. A fresh kit was placed on the analyzer and calibrated. Reference values for the samples tested were determined. After measurement, the kit was closed and kept at 20℃ ± 3℃ for 6 weeks to simulate on-board conditions. Measurements were repeated every week for nine weeks (64 days). The kit was placed on the analyzer again utilizing the calibration curve from seven days earlier for determinations of stability, and the original test samples were measured. The recovery was compared to the measurements from day zero. Samples were tested with one reagent lot in one run per day on one cobas e 411 analyzer in duplicate. Samples tested included five human samples (pooled patient samples and single donor samples spiked with CA125) and two controls (PreciControl Tumormarker Level 1 and 2).
Study 3: Shelf life stability (real-time stability) of CA125 II assay material stored at 2 to 8°C. The stored assay reagents were tested at time point T=0 and at specified intervals over the shelf life of the device up to the planned shelf life plus one month. Testing was performed using PreciControl Tumor Marker 1 and 2 (stored at -20°C). For the 154355-Lot, data for the time-points at 0, 9, 15 and 19 months were tested in duplicates. For the second and third lot (production lots 157240 and 158725) data for the time point at 0, 7, 13 and 19 months were tested in duplicates. The average on-test recovery was calculated as percent recovery compared to the reference value (Assigned value for PreciControl Tumor Marker 1 and 2).
Study 1: Sample stability at 2 to 8°C. Ten human samples for each sample type (Serum, K2-EDTA-plasma, K3-EDTA-plasma, Li-Heparin-plasma) were collected and stored at -80°C (reference). After the first measurement (reference value), the samples were tested after storage at 2 to 8°C after 6 days. Measurements were performed with three-fold determination on cobas e 411 analyzer. The median was used to calculate the percent recovery or absolute deviation to the reference value.
Study 2: Sample stability at room temperature. Ten human samples for each sample type (Serum, K2-EDTA-plasma, K3-EDTA-plasma, Li-Heparin-plasma) were collected and stored at -80°C (reference). After the first measurement (reference value), the samples were tested after 9 hours at room temperature. Measurements were performed with three-fold determination on cobas e 411 analyzer. The median was used to calculate the percent recovery or absolute deviation to the reference value.
Study 3: Sample stability at -20°C. Ten human samples for each sample type (Serum, K2-EDTA-plasma, K3-EDTA-plasma, Li-Heparin-plasma) were measured fresh (reference) and after storage at -20°C for 25 weeks. Measurements were performed with three-fold determination on cobas e 411 analyzer. The median was used to calculate the percent recovery or absolute deviation to the reference value.
Study 4: Sample stability through freeze/thaw cycles. Ten human samples for each sample type (Serum, K2-EDTA-plasma, K3-EDTA-plasma, Li-Heparin-plasma) were collected and stored at -80°C (reference). After the first measurement (reference value), the samples were tested after 4 freeze/thaw cycles. Measurements were performed with three-fold determination on cobas e 411 analyzer. The median was used to calculate the percent recovery or absolute deviation to the reference value.
Study 1: Lot calibration stability. The stability of lot calibration was determined by comparing the calibration for four kits of the same lot. On day 0, the first reagent kit was opened and calibrated, and samples were measured. The same samples were also measured with fresh opened kits of the same lot, using the same calibration established by the first kit, after 5 and 9 weeks on one cobas e 411. Four human serum samples (pooled patient samples spiked with CA125) and two controls were measured in duplicate with one reagent lot in one run per day.
Study 2: On-board calibration stability. On-board calibration stability for the ElecsysCA125 II assay was tested on one cobas e 411 analyzer. One reagent kit was opened and samples were measured on day 0. The same samples were then retested after 8 days with a new opened reagent bottle kept at 20±3°C (on-board condition) using the calibration from day 1. Recovery was calculated based on the initial values. Five human serum samples (pooled patient samples and single donor samples spiked with CA125 II) and two controls were tested in duplicate with one reagent lot on one cobas e 411 in one run per day.
A set of PreciControl Tumor Marker was evaluated in duplicate with one reagent lot on two cobas e 411 analyzers. Two runs were performed on each analyzer. The results were compared against the target ranges of the PreciControl Tumor Marker.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision: Precision of the Elecsys CA125 II assay was evaluated on the cobas e 411 immunoassay analyzer according to CLSI EP5-A2 guideline. Precision was determined for 4 serum samples at one site using one Elecsys reagent lot and controls; 2 runs per day in duplicate each for 20 days (n=80). Precision was determined at another site for the remaining 2 serum samples using the same protocol. The measurements were performed on the cobas e 411 analyzer, with one reagent lot, performing rackpack calibration according to the instructions for use. Key results are shown in the Key Metrics section.
Linearity: Linearity of the Elecsys CA125 II assay was assessed on the cobas e 411 immunoassay analyzer according to CLSI EP6-A. The measured concentrations were plotted against the expected sample concentration.
Method Comparison (sample/reagent ratio): A method comparison was performed to evaluate the change in the sample/reagent ratio. The sample to reagent ratio has changed from 40 uL of sample and 60 µL of R1 and R2 on the formulation cleared under K972162 to 20uL of sample and 70 uL of R1 and R2 with the new assay. The method comparison proves the safety and effectiveness of the sample to reagent volumes has not affected the performance of the assay. Key results are shown in the Key Metrics section.
Method Comparison (CalSet): A method comparison was performed using the Elecsys CA125 II assay in combination with the Elecsys CA125 II CalSet (cleared under K003969) as predicate device and in combination with the new cleared Elecsys CA125 II CalSet II (K140112). Key results are shown in the Key Metrics section.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Precision:
Elecsys CA 125 II (K972162) - Elecsys 2010
Intra-Assay:
3.3% CV @ 7.83 U/mL
2.1% CV @ 38.30 U/mL
2.1% CV @ 70.80 U/mL
1.9% CV @ 39.00 U/mL
1.4% CV @ 121.41 U/mL
Total:
4.2% CV @ 7.83 U/mL
3.1% CV @ 38.30 U/mL
2.5% CV @ 70.80 U/mL
2.5% CV @ 39.00 U/mL
2.7% CV @ 121.41 U/mL
Elecsys CA 125 II Assay - cobas e411 analyzers
Within-run (Repeatability):
3.1% CV @ 14.70 U/mL
3.0% CV @ 3.07 U/mL
2.6% CV @ 2399 U/mL
1.9% CV @ 34.95 U/mL
0.9% CV @ 120.7 U/mL
1.1% CV @ 329.6 U/mL
Total (Intermediate):
4.1% CV @ 14.70 U/mL
4.2% CV @ 3.07 U/mL
3.4% CV @ 2399 U/mL
3.0% CV @ 34.95 U/mL
1.3% CV @ 120.7 U/mL
1.3% CV @ 329.6 U/mL
LoB: 0.6 U/mL
LoD: 1.2 U/mL
LoQ: 2 U/mL
Lower Detection Limit (Functional Sensitivity): 0.6 U/mL (Predicate), N/A (Candidate)
Hook Effect:
Predicate: There is no high-dose hook effect at CA 125 concentrations up to 20,000 U/mL.
Candidate: There is no high-dose hook effect at CA 125 concentrations up to 50,000 U/mL.
Limitations (Assay unaffected by):
Predicate:
Hemoglobin
§ 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.
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Image /page/0/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 symbol with three curved lines forming its body and head. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the symbol.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
August 6, 2015
Roche Professional Diagnostics Linda McCammack Regulatory Program Manager 9115 Hague Road Indianapolis, IN 46250
Re: K143534
Trade/Device Name: Elecsys CA 125 II Assay Elecsys CA 125 II CalCheck Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: II Product Code: LTK, JJX Dated: July 6, 2015 Received: July 7, 2015
Dear Ms. McCammack:
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 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) K143534
Device Name Elecsys CA 125 II Assay
Indications for Use (Describe)
Elecsys CA 125 II is an immunoassay for the in vitro quantitative determination of OC 125 reactive determinants in human serum, Li heparin, K2-EDTA, as well as Li-heparin plasma tubes containing separating gel on the cobas e 411 analyzer.
These determinants are associated with a high molecular weight glycoprotein in serum and plasma of women with primary epithelial invasive ovarian cancer (excluding those with cancer of low malignant potential).
This immunoassay is indicated for use as an aid in the detection of recurrent ovarian carcinoma. This immunoassay is further indicated for use in monitoring patients for disease progress or response to therapy.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 411 immunoassay analyzers.
X 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
Indications for Use
510(k) Number (if known) K143534
Device Name Elecsys CA 125 II CalCheck
Indications for Use (Describe)
For use in the verification of the callbration established by the Elecsys CA 125 II reagent on the Elecsys and cobas e immunoassay analyzers.
Type of Use (Select one or both, as applicable)
X 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."
4
510(k) Summary for the Elecsys CA 125 II assay and Elecsys CA 125 II CalCheck
| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. |
|---|---|
| Submitter Name, Address, Contact | Roche Diagnostics |
| 9115 Hague Road | |
| P.O. Box 50416 | |
| Indianapolis, IN 46250-0415 | |
| Contact Person: Linda McCammack | |
| Phone: (317) 521-7144 Fax: (317) 521-2324 Email: linda.mccammack@roche.com | |
| Secondary Contact Person: Angelo Pereira | |
| Phone: (317) 521-3544 Fax: (317) 521-2324 Email: angelo.pereira@roche.com | |
| Date Updated: August 6, 2015 | |
| Purpose | In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification 510(k). |
The purpose of this premarket notification is to modernize the label for the Elecsys CA 125 II assay, which currently does not contain information on LoB, LoD or LoQ. In addition, we would like to include new data for precision on the cobas e instruments in our product labeling.
Information is also provided on a new Elecsys CA 125 II CalCheck product. |
5
510(k) Summary for Elecsys CA 125 II assay, continued
| Device Name | Proprietary name: | Elecsys CA 125 II Assay |
|---|---|---|
| Common name: | CA 125 II assay | |
| Classification name: | Test, Epithelial Ovarian Tumor Associated Antigen | |
| (Ca125) | ||
| Product Code: | LTK | |
| Predicate Device: | Elecsys CA 125 II (K972162) | |
| Device Name | Proprietary name: | Elecsys CA 125 II CalCheck |
| Common name: | CA 125 II CalCheck | |
| Classification name: | Single (specified) analyte controls (assayed and | |
| unassayed) | ||
| Product Code: | JJX | |
| Predicate Device: | Elecsys CA 125 II CalCheck 5 (K102086) | |
| Establishment | ||
| Registration | For the Elecsys CA 125 II assay and the CA 125 II CalCheck, the | |
| establishment registration number for Roche Diagnostics GmbH in | ||
| Mannheim, Germany, is 9610126 and for Penzberg, Germany, is 9610529. | ||
| The establishment registration number for Roche Diagnostics in the United | ||
| States is 1823260 | ||
| Device | ||
| Description | The CA 125 II assay employs a sandwich test principle using biotinylated | |
| monoclonal CA 125-specific antibody and a monoclonal CA 125-specific | ||
| antibody labeled with a ruthenium complex to form a sandwich complex. The | ||
| use of streptavidin-coated microparticles serves as the solid phase for the | ||
| electrochemiluminescence detection. | ||
| Results are determined using a calibration curve that is generated specifically | ||
| on each instrument by a 2 point calibration and a master curve (5-point- | ||
| calibration) provided with the reagent bar code. | ||
| The CA 125 II application is identical to the predicate assay (K972162). This | ||
| submission is being done to modernize the labeling by adding the LoB, LoD | ||
| and LoQ data and to change the sample:reagent ratio from 40:60μL to | ||
| 20:70μL. Additionally, based on internal stability data the calibration | ||
| frequency has been extended from 4 to 8 weeks. |
6
The Elecsys CA 125 II CalCheck is a lyophilized product consisting of equine Device serum in level 1 and human serum matrix for levels 2 and 3. During Description, manufacture, the analyte is spiked into the matrix at the desired concentration continued levels.
7
510(k) Summary for Elecsys CA 125 II assay, continued
| Intended Use/
Indications
for Use | Elecsys CA 125 II Assay:
Immunoassay for the in vitro quantitative determination of OC 125 reactive
determinants in human serum, Li-heparin, K2-EDTA and K3-EDTA, as well
as Li-heparin plasma tubes containing separating gel on the cobas e 411
analyzer. |
|--------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | These determinants are associated with a high molecular weight glycoprotein
in serum and plasma of women with primary epithelial invasive ovarian
cancer (excluding those with cancer of low malignant potential). |
| | This immunoassay is indicated for use as an aid in the detection of residual or
recurrent ovarian carcinoma. This immunoassay is further indicated for use in
monitoring patients for disease progress or response to therapy. |
| | The electrochemiluminescence immunoassay “ECLIA” is intended for use on
the cobas e 411 immunoassay analyzers. |
| | Elecsys CA 125 II CalCheck: |
| | For use in the verification of the calibration established by the Elecsys CA
125 II reagent on the indicated Elecsys and cobas e immunoassay analyzers. |
| Substantial
Equivalence | The Elecsys CA 125 II assay is equivalent to Elecsys CA 125 II assay
(K972162). |
| | The Elecsys CA 125 II CalCheck is equivalent to the Elecsys CA 125 II
CalCheck 5 (K102086) |
| Substantial
Equivalence -
Comparison | The following table compares the Elecsys CA 125 II Assay with its predicate
device (K972162). |
8
510(k) Summary for Elecsys CA 125 II, continued
Comparison of Assays, Similarities and Differences Table 1
| Assay Comparison | ||
|---|---|---|
| Feature | Predicate Device: | |
| Roche Elecsys CA 125 II (K972162) | Candidate Device: | |
| Elecsys CA 125 II Assay | ||
| General Assay Features | ||
| Intended Use/ | ||
| Indications | ||
| for Use | Immunoassay for the in vitro quantitative | |
| determination of OC 125 reactive determinants in | ||
| human serum and plasma. These determinants are | ||
| associated with a high molecular weight | ||
| glycoprotein in serum and plasma of women with | ||
| primary epithelial invasive ovarian cancer | ||
| (excluding those with cancer of low malignant | ||
| potential). |
The Elecsys CA 125 II assay is indicated for use as
an aid in the detection of residual or recurrent
ovarian carcinoma in patients who have undergone
first-line therapy and would be considered for
second-look procedures. The Elecsys CA 125 II
assay is further indicated for serial measurement of
CA 125 to aid in the management of cancer
patients.
The electrochemiluminescence immunoassay
"ECLIA" is intended for use on Elecsys and cobas
e immunoassay analyzers. | Immunoassay for the in vitro
quantitative determination of
OC 125 reactive determinants
in human serum, Li-heparin,
K2-EDTA and K3-EDTA, as
well as Li-heparin plasma
tubes containing separating gel
on the cobas e 411 analyzer.
These determinants are
associated with a high
molecular weight glycoprotein
in serum and plasma of
women with primary epithelial
invasive ovarian cancer
(excluding those with cancer
of low malignant potential).
This immunoassay is indicated
for use as an aid in detection of
residual or recurrent ovarian
carcinoma. This immunoassay
is further indicated for use in
monitoring patients for disease
progress or response to
therapy.
The electrochemiluminescence
immunoassay "ECLIA" is
intended for use on the cobas e
411 immunoassay analyzers. |
| Assay
Protocol | The CA 125 II Assay employs a sandwich test
principle using biotinylated monoclonal CA 125-
specific antibody and a monoclonal CA 125-
specific antibody labeled with a ruthenium
complex to form a sandwich complex. The use of
streptavidin-coated microparticles serves as the
solid phase for the electrochemiluminescence
detection. | Same. |
| Assay Comparison | | |
| Feature | Predicate Device:
Elecsys CA 125 II (K972162) | Candidate Device:
Elecsys CA 125 II Assay |
| General Assay Features | | |
| Detection
Protocol | Electrochemiluminescent Assay | Same. |
| Applications | 18 minute application | Same. |
| Instrument
Platform | Elecsys 2010, cobas e 411, MODULAR Analytics
E170, cobas e 601 and cobas e 602 immunoassay
analyzers. | cobas e 411 analyzer |
| Sample:
Reagent
Ratio | 40:60 μL | 20:70 μL |
| Sample
Type | Human serum and plasma treated with Li-, Na-.
NH4+-heparin, K2-EDTA, K3-EDTA, sodium
citrate plasma as well as Li-heparin plasma tubes
containing separating gel. When sodium citrate is
used, the results must be corrected by +10%. | Human serum and Li-
heparin, K2-EDTA and K3-
EDTA, as well as Li-heparin
plasma tubes containing
separating gel |
| Reagents | The sample is incubated with a biotinylated
monoclonal CA 125-specific antibody, and a
monoclonal CA 125 specific antibody labeled with
a ruthenium complex to form a sandwich complex.
Steptavidin-coated microparticles are added in the
second incubation. | Same. |
| Calibrator | Elecsys CA 125 II CalSet (K003969) | Elecsys CA 125 II CalSet II
(K140112) |
9
510(k) Summary for Elecsys CA 125 II, continued
Table 1, continued
10
Table 1, continued
| Assay Comparison | ||
|---|---|---|
| Feature | Predicate Device: | |
| Elecsys CA 125 II (K972162) | Candidate Device: | |
| Elecsys CA 125 II Assay | ||
| General Assay Features | ||
| Calibration | ||
| Interval | Calibration must be performed once per | |
| reagent lot using fresh reagent (i.e. not | ||
| more than 24 hours since the reagent kit | ||
| was registered on the analyzer). | ||
| Renewed calibration is recommended as | ||
| follows: | ||
| After 1 month (28 days) when | ||
| using the same reagent lot.After 7 days (when using the | ||
| same reagent kit on the | ||
| analyzer).As required: e.g. quality control | ||
| findings outside the specified | ||
| limits | Calibration must be performed once | |
| per reagent lot using fresh reagent (i.e. | ||
| not more than 24 hours since the | ||
| reagent kit was registered on the | ||
| analyzer). Renewed calibration is | ||
| recommended as follows: | ||
| After 8 weeks when using the | ||
| same reagent lotAfter 7 days (when using the | ||
| same reagent kit on the | ||
| analyzer)As required, e.g. quality | ||
| control findings outside the | ||
| defined limits. | ||
| Controls | Elecsys PreciControl Tumor Marker | |
| (K972235). | Same. | |
| Traceability/ | ||
| Standardiz- | ||
| ation | The method has been standardized | |
| against the Enzymun-Test CA 125 II | ||
| method. This in turn has been | ||
| standardized against the CA 125 II RIA | ||
| from Fujirebio Diagnostics. | Same. | |
| Reagent | ||
| Stability | Store at 2-8 °C. Store the reagent kit | |
| upright in order to ensure complete | ||
| availability of the microparticles during | ||
| automatic mixing prior to use. |
Stability:
Unopened at 2-8 °C—up to the stated
expiration date
After opening at 2-8 °C—12 weeks
On the analyzers—4 weeks | Store at 2-8 °C. Store the reagent kit
upright in order to ensure complete
availability of the microparticles
during automatic mixing prior to use.
Stability:
Unopened at 2-8 °C—up to the stated
expiration date
After opening at 2-8 °C—12 weeks
On the analyzers—6 weeks |
11
Table 1, continued
| Assay Comparison | ||
|---|---|---|
| Predicate Device: | Candidate Device: | |
| Feature | Elecsys CA 125 II (K972162) | Elecsys CA 125 II Assay |
| Labeled Performance Characteristics | ||
| Measuring | ||
| Range | 0.6 (LDL) - 5000 U/mL | 2 (LoQ) -3000 U/mL |
| Precision | Elecsys 2010 | cobas e411 analyzers |
| Intra-Assay | Within-run (Repeatability) | |
| 3.3% CV @ 7.83 U/mL | 3.1% CV @ 14.70 U/mL | |
| 2.1% CV @ 38.30 U/mL | 3.0% CV @ 3.07 U/mL | |
| 2.1% CV @ 70.80 U/mL | 2.6% CV @ 2399 U/mL | |
| 1.9% CV @ 39.00 U/mL | 1.9% CV @ 34.95 U/mL | |
| 1.4% CV @ 121.41 U/mL | 0.9% CV @ 120.7 U/mL | |
| 1.1% CV @ 329.6 U/mL | ||
| Total | Total (Intermediate) | |
| 4.2% CV @ 7.83 U/mL | 4.1% CV @ 14.70 U/mL | |
| 3.1% CV @ 38.30 U/mL | 4.2% CV @ 3.07 U/mL | |
| 2.5% CV @ 70.80 U/mL | 3.4% CV @ 2399 U/mL | |
| 2.5% CV @ 39.00 U/mL | 3.0% CV @ 34.95 U/mL | |
| 2.7% CV @ 121.41 U/mL | 1.3% CV @ 120.7U/mL | |
| 1.3% CV @ 329.6U/mL | ||
| LoB | Not Reported | 0.6 U/mL |
| LoD | Not Reported | 1.2 U/mL |
| LoQ | Not Reported | 2 U/mL |
| Lower | ||
| Detection | ||
| Limit | Functional Sensitivity: 0.6 U/mL | N/A |
12
Table 1, continued
| Assay Comparison | ||
|---|---|---|
| Feature | Predicate Device: | |
| Elecsys CA 125 II | Candidate Device: | |
| Elecsys CA 125 II Assay | ||
| Performance Characteristics | ||
| Hook Effect | There is no high-dose hook effect at CA | |
| 125 concentrations up to 20,000 U/mL. | There is no high-dose hook effect at | |
| CA 125 concentrations up to 50,000 | ||
| U/mL. | ||
| Limitations | The assay is unaffected by: | |
| Hemoglobin 15 U/mL) of the drug sample to the reference. |
21
| Evaluations
Summary,
continued | Exogenous Interference, continued
2) Anticoagulants
The effect on quantitation of analyte in the presence of anticoagulants with the Elecsys CA125 II assay was determined by comparing values obtained from native samples (single donors) drawn into Serum, Li-Heparin, K2-
EDTA-, K3-EDTA-plasma primary tubes and Li-Heparin Plasma Separation
Tubes. |
|--------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 51 or 52 serum/plasma pairs per sample material were tested in duplicates
with one reagent lot on one cobas e 411 analyzer. | |
Potential effects are assessed by Passing/Bablok regression analyses.
Method Comparison
A method comparison was performed to evaluate the change in the sample/reagent ratio. The sample to reagent ratio has changed from 40 uL of sample and 60 µL of R1 and R2 on the formulation cleared under K972162 to 20uL of sample and 70 uL of R1 and R2 with the new assay. The method comparison proves the safety and effectiveness of the sample to reagent volumes has not affected the performance of the assay.
The study was performed on the Elecsys 2010 analyzer using the Elecsys CA125 II assay (sample/reagent ratios as cleared under K972162) and the CA125 II Cal Set (K003969)(X) against the Elecsys CA 125 II assay with the new sample/reagent ratios and the Elecsys CA125 II CalSet (K003969) (Y). A total of 80 human serum samples (all native single donors) with CA125 values from 4.7 -2680U/mL (X) and 4.8 -2594U/mL (Y) were measured in order to cover the entire measuring range.
22
| Evaluations
Summary,
| continued | Method Comparison (CalSet) |
|---|---|
| A method comparison was performed using the Elecsys CA125 II assay in | |
| combination with the Elecsys CA125 II CalSet (cleared under K003969) as | |
| predicate device and in combination with the new cleared Elecsys CA125 II | |
| CalSet II (K140112). | |
| The Elecsys CA125 II Assay is standardized against the Enzymun-Test CA | |
| 125 II method. This in turn was standardized against the CA 125 II RIA from | |
| Fujirebio Diagnostics. | |
| The study was performed on the cobas e 411 analyzer using the Elecsys | |
| CA125 II assay with the CA125 II Cal Set(X) and the Elecsys CA 125II | |
| assay with the new Elecsys CA125 II CalSet II assay (Y) | |
| A total of 111 human serum samples (all native single donors) with CA125 | |
| values from 3.19–2621U/mL (X) and 4.05–2641U/mL (Y) were measured | |
| in order to cover the entire measuring range. |
23
| Evaluations
Summary,
continued | The reagent stability was performed in three different studies and they are:
Study 1: Reagent stability after first opening
Reagent stability after first opening for the Elecsys CA125 II assay was
determined on a cobas e 411 analyzer by comparing the reagent stability
for four kits of the same lot. All reagent kits were opened on day 0. One kit
was placed on the analyzer and calibrated and reference values for the
samples tested were determined. |
|--------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | The other three kits were stored at 2 to 8°C. After 5, 9 and 13 weeks, one
of the stored kits was placed on the analyzer and calibrated, and the
original test samples were measured. |
| | Samples tested in duplicate include five human serum (HS) samples and
two controls. The human serum samples used were native single donors. |
| | Study 2: On-board reagent stability
On-board reagent stability for the CA125 II assay was tested on one
cobas e 411 immunoassay analyzer. A fresh kit was placed on the analyzer. |
cobas e 411 immunoassay analyzer. A fresh kit was placed on the and calibrated. Reference values for the samples tested were determined. After measurement, the kit was closed and kept at 20℃ ± 3℃ for 6 weeks to simulate on-board conditions. Measurements were repeated every week for nine weeks (64 days). The kit was placed on the analyzer again utilizing the calibration curve from seven days earlier for determinations of stability, and the original test samples were measured. The recovery was compared to the measurements from day zero. Samples were tested with one reagent lot in one run per day on one cobas e 411 analyzer in duplicate.
Samples tested included five human samples (pooled patient samples and single donor samples spiked with CA125) and two controls (PreciControl Tumormarker Level 1 and 2).
24
| Evaluations
| Summary, | Reagent Stability, continued |
|---|---|
| continued | Study 3: Shelf life stability |
| In addition, real-time stability was used to determine CA125 II shelf-life | |
| stability. | |
| In the real-time stability study, the CA125 II assay material was stored at 2 | |
| to 8°C. The stored assay reagents were tested at time point T=0 and at | |
| specified intervals over the shelf life of the device up to the planned shelf | |
| life plus one month. Testing was performed using PreciControl Tumor | |
| Marker 1 and 2 (stored at -20°C). | |
| For the 154355-Lot, data for the time-points at 0, 9, 15 and 19 months | |
| were tested in duplicates. For the second and third lot (production lots | |
| 157240 and 158725) data for the time point at 0, 7, 13 and 19 months were | |
| tested in duplicates. | |
| The average on-test recovery was calculated as percent recovery compared | |
| to the reference value (Assigned value for PreciControl Tumor Marker 1 | |
| and 2). |
25
| Evaluations
Summary,
continued | The sample stability was performed with four different studies and they
are: |
|--------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Study 1: Sample stability at 2 to 8°C |
| | Ten human samples for each sample type (Serum, K2-EDTA-plasma, K3-
EDTA-plasma, Li-Heparin-plasma) were collected and stored at -80°C
(reference). |
| | After the first measurement (reference value), the samples were tested after
storage at 2 to 8°C after 6 days. |
| | Measurements were performed with three-fold determination on cobas e
411 analyzer. The median was used to calculate the percent recovery or
absolute deviation to the reference value. |
| | Study 2: Sample stability at room temperature |
| | Ten human samples for each sample type (Serum, K2-EDTA-plasma, K3-
EDTA-plasma, Li-Heparin-plasma) were collected and stored at -80°C
(reference). |
| | After the first measurement (reference value), the samples were tested after 9
hours at room temperature. |
| | Measurements were performed with three-fold determination on cobas e 411
analyzer. The median was used to calculate the percent recovery or absolute
deviation to the reference value. |
| | Continued on next page |
26
| Evaluations
Summary,
| continued | Sample Stability- continued |
|---|---|
| continued | Study 3: Sample stability at -20°C |
| Ten human samples for each sample type (Serum, K2-EDTA-plasma, K3-EDTA-plasma, Li-Heparin-plasma) were measured fresh (reference) and after storage at -20°C for 25 weeks. | |
| Measurements were performed with three-fold determination on cobas e 411 analyzer. The median was used to calculate the percent recovery or absolute deviation to the reference value. | |
| Study 4: Sample stability through freeze/thaw cycles | |
| Ten human samples for each sample type (Serum, K2-EDTA-plasma, K3-EDTA-plasma, Li-Heparin-plasma) were collected and stored at -80°C (reference). | |
| After the first measurement (reference value), the samples were tested after 4 freeze/thaw cycles. | |
| Measurements were performed with three-fold determination on cobas e 411 analyzer. The median was used to calculate the percent recovery or absolute deviation to the reference value. |
27
| Evaluations
Summary,
| continued | Calibration Stability was performed with two different studies and they are: |
|---|---|
| Study 1: Lot calibration stability: | |
| The stability of lot calibration was determined by comparing the calibration | |
| for four kits of the same lot. On day 0, the first reagent kit was opened and | |
| calibrated, and samples were measured. The same samples were also | |
| measured with fresh opened kits of the same lot, using the same calibration | |
| established by the first kit, after 5 and 9 weeks on one cobas e 411. | |
| Four human serum samples (pooled patient samples spiked with CA125) | |
| and two controls were measured in duplicate with one reagent lot in one | |
| run per day. | |
| Study 2: On-board calibration stability: | |
| On-board calibration stability for the ElecsysCA125 II assay was tested on | |
| one cobas e 411 analyzer. One reagent kit was opened and samples were | |
| measured on day 0. The same samples were then retested after 8 days with | |
| a new opened reagent bottle kept at 20±3°C (on-board condition) using | |
| the calibration from day 1. Recovery was calculated based on the initial | |
| values. | |
| Five human serum samples (pooled patient samples and single donor |
samples spiked with CA125 II) and two controls were tested in duplicate with one reagent lot on one cobas e 411 in one run per day.
28
| Evaluations Summary, continued | Recovey of Controls A set of PreciControl Tumor Marker was evaluated in duplicate with one reagent lot on two cobas e 411 analyzers. Two runs were performed on each analyzer. The results were compared against the target ranges of the PreciControl Tumor Marker. |
|---|---|
| The measuring range is defined to meet CLSI guideline EP17-A2 requirements. | |
| Performance Characteristics of CA 125 II CalCheck The Elecsys CA 125 II Calcheck was evaluated for value assignment and stability. | |
| Conclusion | Based on performance data described above the Elecsys CA 125 II assay and CA 125 II CalCheck devices were found to have safety and effectiveness profiles similar to the predicate devices. |