(59 days)
CR-E reagent, when used in conjunction with SYNCHRON® Systems, UniCel® DxC Systems and SYNCHRON® Systems AQUA CAL 1 and 2 and SYNCHRON CX® Calibrator Level 1 and 2, is intended for the quantitative determination of creatinine (CR-E) concentration in human serum, plasma or urine (urine is not available on the SYNCHRON CX® PRO Systems). Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
CR-E reagent is used to measure the creatinine concentration by an enzymatic method. This enzymatic creatinine method utilizes a multi-step approach ending with a photometric end-point reaction. The SYNCHRON Enzymatic Creatinine (CR-E) Reagent is designed for optimal performance on the SYNCHRON LX®, UniCel® DxC 600/800, and SYNCHRON CX® PRO Clinical Systems. The reagent kit contains two 200-test cartridges that are packaged separately from the associated calibrator.
The provided [K091742](https://510k.innolitics.com/device/K091742) document describes the SYNCHRON® Systems Enzymatic Creatinine (CR-E) Reagent. The acceptance criteria and the study that proves the device meets them are summarized below.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for slope, intercept, R-value, or %C.V. for its performance metrics. Instead, it presents the results of its performance studies (method comparison and precision studies) which are then compared to a legally marketed predicate device (SYNCHRON Systems Creatinine (CR-S) Reagent) to demonstrate substantial equivalence. For the purpose of this response, "reported device performance" refers to the values obtained in the studies.
| Performance Metric | Acceptance Criteria (Implied/Compared to Predicate) | Reported Device Performance (CR-E Reagent) |
|---|---|---|
| Method Comparison (Serum) | ||
| Slope (vs. Predicate) | Close to 1.0 (indicating proportionality) | CX7 PRO Platform: 0.997 |
| Intercept (vs. Predicate) | Close to 0.0 (indicating no systematic bias) | CX7 PRO Platform: -0.002 |
| R (Correlation Coefficient) | Close to 1.0 (indicating strong correlation) | CX7 PRO Platform: 1.000 |
| Slope (vs. Predicate) | Close to 1.0 (indicating proportionality) | DxC800 Platform: 0.991 |
| Intercept (vs. Predicate) | Close to 0.0 (indicating no systematic bias) | DxC800 Platform: 0.012 |
| R (Correlation Coefficient) | Close to 1.0 (indicating strong correlation) | DxC800 Platform: 1.000 |
| Method Comparison (Urine) | ||
| Slope (vs. Predicate) | Close to 1.0 (indicating proportionality) | DxC800 Platform: 0.988 |
| Intercept (vs. Predicate) | Close to 0.0 (indicating no systematic bias) | DxC800 Platform: -3.096 |
| R (Correlation Coefficient) | Close to 1.0 (indicating strong correlation) | DxC800 Platform: 0.998 |
| Precision (Within-Run & Total Imprecision) | ||
| %C.V. (Coefficient of Variation) | Low values, consistent with precise measurement for clinical use (compared to typical lab practice and predicate's performance) | CX7 PRO: Within-Run: 0.3% - 1.4% Total: 0.5% - 1.5% DxC800 (Serum): Within-Run: 0.3% - 2.1% Total: 0.7% - 2.5% DxC800 (Urine): Within-Run: 0.4% - 0.5% Total: 1.0% |
2. Sample Sizes Used for the Test Set and Data Provenance
-
Method Comparison Studies:
- Serum (CX7 PRO Platform): N = 78 samples
- Serum (DxC800 Platform): N = 80 samples
- Urine (DxC800 Platform): N = 66 samples
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given it is a premarket submission for a medical device to the FDA, it is highly likely these were prospective studies conducted to demonstrate equivalence for regulatory approval.
-
Precision Studies:
- CX7 PRO Platform: N = 80 for each of the 4 sample levels/pools (Level 1, Level 2, Level 3, Human Pool) for both within-run and total imprecision.
- DxC800 Platform (Serum): N = 80 for each of the 4 sample levels/pools for both within-run and total imprecision.
- DxC800 Platform (Urine): N = 80 for each of the 2 urine sample levels/pools for both within-run and total imprecision.
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It is implied these were prospective studies.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
The ground truth in this submission is established through comparison to a predicate device (SYNCHRON Systems Creatinine (CR-S) Reagent), which is a legally marketed device often used as a reference method in clinical laboratories. This is not a ground truth established by human experts, but rather by an accepted analytical method. Therefore, the concept of "experts" as in radiologists reading images is not applicable here.
4. Adjudication Method for the Test Set
Not applicable. The ground truth is established by a predicate analytical method, not human interpretation that would require an adjudication method.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging interpretation where human readers (e.g., radiologists) evaluate cases. This submission concerns an in vitro diagnostic reagent for quantitative chemical analysis, which relies on instrument readings rather than human interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this entire study represents a standalone performance evaluation of the SYNCHRON® Systems Enzymatic Creatinine (CR-E) Reagent. The device (reagent used on automated analyzers) produces quantitative creatinine measurements directly, without human interpretation of results as part of its primary function. The data presented are direct outputs from the synchronized clinical systems.
7. The Type of Ground Truth Used
The type of ground truth used for the method comparison studies is comparison to a legally marketed predicate device's performance, specifically the SYNCHRON Systems Creatinine (CR-S) Reagent. This is implicitly considered a well-established and accepted method for creatinine determination. For precision, the ground truth is statistical assessment of reproducibility around the measured mean.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI. This product is a chemical reagent for an enzymatic assay, not an AI or machine learning algorithm that requires a separate training phase with a distinct dataset. Clinical chemistry assays often involve calibration, internal quality control, and validation studies but do not typically concept of a "training set" for an algorithm. The reported studies are for validation/testing of the device's performance.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" is not applicable to this type of device. The performance validation studies (method comparison and precision) demonstrate the accuracy and reliability of the CR-E reagent against a predicate method and statistical standards for precision.
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Summary of Safety & Effectiveness SYNCHRON® Systems Enzymatic Creatinine (CR-E) Reagent
1.0 Submitted By:
Marine Bovaiian Senior Regulatory Affairs Specialist Beckman Coulter, Inc. 200 S. Kraemer Blvd., W-110 Brea, California 92822-8000 Telephone: (714) 961-6536 FAX: (714) 961-4234
Date Submitted: 2.0
June 11, 2009
3.0 Device Name(s):
- 3.1 Proprietary Names SYNCHRON® Systems Enzymatic Creatinine (CR-E) Reagent
- 3.2 Classification Name Enzymatic Method Creatinine (21 CFR § 862.1225)
4.0 Predicate Device:
| Candidate(s) | Predicate | Manufacturer | DocketNumber |
|---|---|---|---|
| SYNCHRON SystemsEnzymatic Creatinine (CR-E)Reagent | SYNCHRON SystemsCreatinine (CR-S) Reagent | BeckmanCoulter, Inc | K071283 |
5.0 Description:
CR-E reagent is used to measure the creatinine concentration by an enzymatic method. This enzymatic creatinine method utilizes a multi-step approach ending with a photometric end-point reaction.
The SYNCHRON Enzymatic Creatinine (CR-E) Reagent is designed for optimal performance on the SYNCHRON LX®, UniCel® DxC 600/800, and SYNCHRON CX® PRO Clinical Systems. The reagent kit contains two 200-test cartridges that are packaged separately from the associated calibrator.
6.0 Intended Use:
CR-E reagent, when used in conjunction with SYNCHRON® Systems, UniCel® DxC Systems and SYNCHRON® Systems AQUA CAL 1 and 2 and SYNCHRON CX Calibrator Level 1 and 2, is intended for the quantitative determination of creatinine (CR-E) concentration in human serum, plasma or urine (urine is not available on the SYNCHRON CX® PRO Systems).
Clinical Significance:
Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
AUG 1 4 2009
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Comparison to Predicate(s): 7.0
The following table shows similarities and differences between the candidate Enzymatic Creatinine (CR-E) Reagent and the predicate identified in Section 4.0 of this summary.
| Similarities | ||
|---|---|---|
| SYNCHRONSystemsEnzymaticCreatinine(CR-E)Reagent | Intended Use | Same |
| Sample Types | Same for the LX/DxC Systems | |
| Instrument Platforms | Same | |
| Calibrator | Same | |
| Analytical range (Urine) | Same | |
| Differences | ||
| SYNCHRONSystemsEnzymaticCreatinine(CR-E)Reagent | Analytical range(Serum and Plasma) | CR-E Reagent: 0.2 - 25.0 mg/dL |
| CR-S Reagent: 0.3 - 25.0 mg/dL | ||
| Sample Types | CR-E Reagent: Plasma and Serum for CX Systems | |
| CR-S Reagent: Plasma, Serum and Urine for CXSystems | ||
| Sample volume | CR-E Reagent: 10 µl (Serum, Plasma and Urine)Urine sample is diluted by thesystem at ratio of 1:10. | |
| CR-S Reagent: 20 µl Serum and Plasma, 3 µl Urine | ||
| Reaction Type(Methodology) | CR-E Reagent: Enzymatic method | |
| CR-S Reagent: Modified rate Jaffe method | ||
| Calibration Frequency | CR-E Reagent: Every 14 days | |
| CR-S Reagent: Every 5 days on LX/DxC SystemsEvery 7 days on CX Systems | ||
| Detection Wavelength | CR-E Reagent: 560 nm (Primary Wavelength) | |
| CR-S Reagent: 520 nm (Primary Wavelength) |
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8.0 Summary of Performance Data:
The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to chemistry test systems already in commercial distribution. Equivalence is demonstrated through method comparison, stability, linearity, and imprecision experiments.
Serum Method Comparison Summary
| Candidate | Platform | Slope | Intercept | R | N | Predicate Method |
|---|---|---|---|---|---|---|
| EnzymaticCreatinine(CR-E) Reagent | CX7 PRO | 0.997 | -0.002 | 1.000 | 78 | SYNCHRONSystems Creatinine(CR-S) Reagent |
| DxC800 | 0.991 | 0.012 | 1.000 | 80 |
Urine Method Comparison Summary
| Candidate | Platform | Slope | Intercept | R | N | Predicate Method |
|---|---|---|---|---|---|---|
| EnzymaticCreatinine(CR-E) Reagent | DxC800 | 0.988 | -3.096 | 0.998 | 66 | SYNCHRONSystems Creatinine(CR-S) Reagent |
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SYNCHRON Systems Enzymatic Creatinine (CR-E) Reagent Precision Study Results
| Sample | Mean(mg/dL) | S.D. | %C.V. | N |
|---|---|---|---|---|
| Within-Run Imprecision | ||||
| Level 1 | 0.62 | 0.01 | 1.4 | 80 |
| Level 2 | 4.16 | 0.02 | 0.5 | 80 |
| Level 3 | 7.69 | 0.02 | 0.3 | 80 |
| Human Pool | 1.50 | 0.02 | 1.0 | 80 |
| Total Imprecision | ||||
| Level 1 | 0.62 | 0.01 | 1.5 | 80 |
| Level 2 | 4.16 | 0.02 | 0.6 | 80 |
| Level 3 | 7.69 | 0.04 | 0.5 | 80 |
| Human Pool | 1.50 | 0.02 | 1.0 | 80 |
Precision Study Results on SYNCHRON CX7 PRO Clinical System
Precision Study Results on UniCel DxC 800 SYNCHRON Clinical System
F
| Sample | Mean(mg/dL) | S.D. | %C.V. | N | |
|---|---|---|---|---|---|
| Within-Run Imprecision | |||||
| Serum | Level 1 | 0.64 | 0.01 | 2.1 | 80 |
| Level 2 | 4.09 | 0.01 | 0.3 | 80 | |
| Level 3 | 7.56 | 0.03 | 0.3 | 80 | |
| Human Pool | 1.50 | 0.01 | 0.7 | 80 | |
| Urine | Level 1 | 66.45 | 0.31 | 0.5 | 80 |
| Level 2 | 146.61 | 0.60 | 0.4 | 80 | |
| Total Imprecision | |||||
| Serum | Level 1 | 0.64 | 0.02 | 2.5 | 80 |
| Level 2 | 4.09 | 0.03 | 0.7 | 80 | |
| Level 3 | 7.56 | 0.06 | 0.8 | 80 | |
| Human Pool | 1.50 | 0.01 | 0.9 | 80 | |
| Urine | Level 1 | 66.45 | 0.68 | 1.0 | 80 |
| Level 2 | 146.61 | 1.47 | 1.0 | 80 |
This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.
. `
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Image /page/4/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three tail feathers, representing the three levels of government: federal, state, and local. The eagle is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993
Beckman Coulter, Inc. c/o Ms. Marine Boyajian Senior Regulatory Affairs Specialist 200 S Kraemer Blvd., M/S W-110 Brea, CA 92822
AUG 1 4 2009
Re: K091742
Trade Name: Synchron Systems Enzymatic Creatinine (CR-E) Reagent Regulation Number: 21 CFR §862.1225 Regulation Name: Creatinine Test System Regulatory Class: Class II Product Codes: JFY Dated: June 11, 2009 Received: June 16, 2009
Dear Ms. Boyajian:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.goy/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
G.C.H.
Courtney C. Harper, Ph.D. Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indication for Use
510(k) Number (if known):
091742
Device Name: SYNCHRON® Systems Enzymatic Creatinine (CR-E) Reagent
Indication For Use:
CR-E reagent, when used in conjunction with SYNCHRON® Systems, UniCel® DxC Systems and SYNCHRON® Systems AQUA CAL 1 and 2 and SYNCHRON CX® Calibrator Level 1 and 2, is intended for the quantitative determination of creatinine (CR-E) soncentration in human serum,
plasma or urine (urine is not available on the SYNCHRON CX PRO Systems).
Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
Prescription Use _ _ X (21 CFR Part 801 Subpart D)
Over the
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
And/Or
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Carol C. Benam
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K091742
Page 1 of 1
§ 862.1225 Creatinine test system.
(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.