(83 days)
CO2E reagent, when used in conjunction with UniCel® DxC 600/800 System(s) and SYNCHRON® Systems AQUA CAL 1 and 3, is intended for the quantitative determination of Carbon Dioxide in human serum or plasma.
The SYNCHRON Enzymatic CO2 (CO2E) Reagent is intended for use in the quantitative determination of Carbon Dioxide concentration in human serum or plasma. The SYNCHRON Systems CO2E assay is an enzymatic method utilizing phosphoenolpyruvate carboxylase (PEPC) and a stabilized NADH analog in two coupled enzymatic reactions. In the first reaction. PEPC catalyzes the reaction between phosphoenolpyruvate and HCO3 to yield oxaloacetate and inorganic phosphate. In the second step, oxaloacetate is reduced by a stable NADH analog to malate in the presence of malate dehydrogenase (MDH). The resulting decrease in absorbance at 410 nm is spectrophotometrically measured and directly proportional to the CO2 concentration in the test sample via measurement of bicarbonate ions (HCO3). The SYNCHRON DxC Systems utilize a twolevel calibrator for the Carbon Dioxide assay.
The SYNCHRON Enzymatic CO2 (CO2E) Reagent is designed for optimal performance on the UniCel DxC SYNCHRON Clinical Systems (UniCel DxC 600/800 SYNCHRON and UniCel DxC 600i/660i/860i/860i/880i SYNCHRON Access Clinical Systems). The reagent kit contains two 300-test cartridges that are packaged separately from the associated calibrator.
Here's an analysis of the provided text regarding the acceptance criteria and study for the SYNCHRON® Systems Enzymatic CO2 (CO2E) Reagent:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a separate section with pass/fail thresholds. However, it presents performance data for method comparison and precision that are implicitly the metrics used to demonstrate substantial equivalence to the predicate device.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (SYNCHRON CO2E Reagent) |
|---|---|---|
| Method Comparison | To be substantially equivalent to the predicate (UniCel DxC 800 SYNCHRON Clinical System CO2 rate pH) | |
| Slope | Close to 1.0 | 0.974 |
| Intercept | Close to 0.0 | 0.514 |
| R (Correlation) | Close to 1.0 | 0.996 |
| Precision (Imprecision Study Results) | To demonstrate acceptable reproducibility for clinical use. | |
| Within-Run Imprecision | ||
| Level 1 (%CV) | Implicitly acceptable for clinical lab assays | 3.4% |
| Level 2 (%CV) | Implicitly acceptable for clinical lab assays | 1.9% |
| Total Imprecision | ||
| Level 1 (%CV) | Implicitly acceptable for clinical lab assays | 4.6% |
| Level 2 (%CV) | Implicitly acceptable for clinical lab assays | 2.5% |
2. Sample Size Used for the Test Set and Data Provenance:
- Method Comparison Test Set Sample Size: N = 143
- Precision Test Set Sample Size: 80 for each level (Level 1 and Level 2) for both Within-Run and Total Imprecision. This seems to be the number of data points, not necessarily unique patient samples, as precision studies often involve repeated measurements on the same samples.
- Data Provenance: The document does not specify the country of origin. It is a premarket notification for an in vitro diagnostic device, typically based on internal laboratory studies. The studies are prospective in the sense that they were conducted for the purpose of this FDA submission to evaluate the device's performance against the predicate.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
This information is not provided in the document. For in vitro diagnostic reagents like this, the "ground truth" for method comparison and precision studies is typically the measurement obtained by the predicate device (the UniCel DxC 800 SYNCHRON Clinical System CO2 rate pH in this case) and the inherent chemical/physical properties of the control materials. There are no human experts involved in establishing ground truth in the same way there would be for image interpretation.
4. Adjudication Method for the Test Set:
This information is not applicable for this type of in vitro diagnostic device study. Adjudication methods (like 2+1, 3+1) are typically used in studies involving human interpretation or subjective assessments, where discrepancies between multiple readers need to be resolved to establish ground truth. Here, the comparison is against an objective measurement from a predicate device.
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 devices where human readers (e.g., radiologists) interact with the device's output, and the goal is to evaluate the improvement in human performance with AI assistance. The SYNCHRON CO2E Reagent is an automated in vitro diagnostic assay where results are generated directly by the instrument, not interpreted by human readers in a diagnostic capacity that would warrant an MRMC study.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the data presented effectively represents the standalone performance of the SYNCHRON CO2E Reagent. The method comparison and precision studies evaluate the algorithm's (reagent's) ability to quantitatively determine Carbon Dioxide concentration independently, without direct human intervention in the result generation or interpretation to correct for algorithm errors. The results are compared directly to a "gold standard" (the predicate device) or evaluated for inherent reproducibility.
7. The Type of Ground Truth Used:
The ground truth used for the method comparison study is the measurements obtained from the predicate device, the UniCel DxC 800 SYNCHRON Clinical System CO2 rate pH. For precision studies, the ground truth is the expected value of the control materials and the ability of the device to consistently produce measurements close to that expected value. It is not expert consensus, pathology, or outcomes data in the usual sense.
8. The Sample Size for the Training Set:
The document does not specify a training set size. This is because the SYNCHRON CO2E Reagent is a chemical reagent and an enzymatic assay, not an AI/machine learning algorithm that typically requires a distinct training phase with a large dataset. The "development" of such a reagent involves chemical formulation, optimization, and characterization, not machine learning training.
9. How the Ground Truth for the Training Set was Established:
This question is not applicable as there is no mention of a "training set" in the context of an enzymatic reagent. The development process for such a reagent involves optimizing chemical compositions and reaction conditions rather than training an algorithm on a dataset with established ground truth.
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K09115-3
Summary of Safety & Effectiveness SYNCHRON® Systems Enzymatic CO2 (CO2E) Reagent
1.0 Submitted Bv:
Marine Boyajian 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
JUL 1 3 2009
Date Submitted: 2.0
April 16, 2009
3.0 Device Name(s):
- 3.1 Proprietary Names SYNCHRON® Systems Enzymatic CO2 (CO2E) Reagent
- 3.2 Classification Name Bicarbonate/carbon dioxide test system (21 CFR § 862.1160)
4.0 Predicate Device:
| Candidate(s) | Predicate | Manufacturer | DocketNumber |
|---|---|---|---|
| SYNCHRON SystemsEnzymatic CO2 (CO2E) Reagent | UniCel DxC 600/800SYNCHRON ClinicalSystems CO2 rate pH | BeckmanCoulter, Inc | K042291 |
5.0 Description:
The SYNCHRON Enzymatic CO2 (CO2E) Reagent is intended for use in the quantitative determination of Carbon Dioxide concentration in human serum or plasma. The SYNCHRON Systems CO2E assay is an enzymatic method utilizing phosphoenolpyruvate carboxylase (PEPC) and a stabilized NADH analog in two coupled enzymatic reactions. In the first reaction. PEPC catalyzes the reaction between phosphoenolpyruvate and HCO3 to yield oxaloacetate and inorganic phosphate. In the second step, oxaloacetate is reduced by a stable NADH analog to malate in the presence of malate dehydrogenase (MDH). The resulting decrease in absorbance at 410 nm is spectrophotometrically measured and directly proportional to the CO2 concentration in the test sample via measurement of bicarbonate ions (HCO3). The SYNCHRON DxC Systems utilize a twolevel calibrator for the Carbon Dioxide assay.
The SYNCHRON Enzymatic CO2 (CO2E) Reagent is designed for optimal performance on the UniCel DxC SYNCHRON Clinical Systems (UniCel DxC 600/800 SYNCHRON and UniCel DxC 600i/660i/860i/860i/880i SYNCHRON Access Clinical Systems). The reagent kit contains two 300-test cartridges that are packaged separately from the associated calibrator.
6.0 Intended Use:
CO2E reagent, when used in conjunction with UniCel® DxC 600/800 System(s) and SYNCHRON® Systems AQUA CAL 1 and 3, is intended for the quantitative determination of Carbon Dioxide in human serum or plasma.
Beckman Coulter. Inc., Section 510(k) Notification SYNCHRON® Systems Enzymatic CO2 (CO2E) Reagent SYN CO2E 510K Summary.doc
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Clinical Significance:
Carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.
7.0 Comparison to Predicate(s):
The following table shows similarities and differences between the predicates identified in Section 4.0 of this summary.
| Similarities | ||
|---|---|---|
| SYNCHRONSystemsEnzymaticCO2 (CO2E)Reagent | Intended Use | Same |
| Sample Types | Same | |
| Analytical Sensitivity | Same | |
| Calibrator | Same | |
| Differences | ||
| SYNCHRONSystemsEnzymaticCO2 (CO2E)Reagent | Analytical range | CO2E Reagent: 5.0 - 45.0 mmol/LCO2 ISE Reagent: 5.0 - 50.0 mmol/L |
| Sample volume | CO2E Reagent: 6 μlCO2 ISE Reagent: 40 μl | |
| Reaction Type(Methodology) | CO2E Reagent: enzymatic methodCO2 ISE Reagent: pH rate change method | |
| Instrument Platforms | CO2E Reagent: UniCel DxC 600/800 SystemsCO2 ISE Reagent: SYNCHRON LX and UniCel DxC 600/800 Systems | |
| Calibration Frequency | CO2E Reagent: every 72 hoursCO2 ISE Reagent: every 24 hours |
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.
| Candidate | Platform | Slope | Intercept | R | N | Predicate Method |
|---|---|---|---|---|---|---|
| SYNCHRONSystemsEnzymatic CO2(CO2E) Reagent | UniCelDxC | 0.974 | 0.514 | 0.996 | 143 | UniCel DxC 800SYNCHRON ClinicalSystem CO2 rate pH |
SYNCHRON Systems Enzymatic CO2 (CO2E) Reagent Precision Study Results
| Sample | Mean(mmol/L) | S.D.(mmol/L) | %C.V. | N |
|---|---|---|---|---|
| Within-Run Imprecision | ||||
| Level 1 | 11.50 | 0.39 | 3.4 | 80 |
| Level 2 | 27.50 | 0.52 | 1.9 | 80 |
| Total Imprecision | ||||
| Level 1 | 11.50 | 0.53 | 4.6 | 80 |
| Level 2 | 27.50 | 0.68 | 2.5 | 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.
Beckman Coulter, Inc., Section 510(k) Notification SYNCHRON® Systems Enzymatic CO2 (CO2E) Reagent SYN CO2E 510K_Summary.doc
Page 2 of 2
April 16, 2009
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| See OMB Statement on Reverse. Form Approved: OMB No. 0910-0616, Expiration Date: 06-30-2008 |
|---|
| --------------------------------------------------------------------------------------------- |
See OMB Statement on Reverse. Form Approved: OMB No. 0910-0616, Expiration Date: 06-30-2008
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Certification of Compliance, under 42 U.S.C. § 282(j)(5)(B), with
Requirements of ClinicalTrials.gov Data Bank (42 U.S.C. § 282(j))
(For submission with an application/submission, including amendments, supplements, and resubmissions, under §§ 505, 515, 520(m), or 510(k) of the
Federal Food, Drug, and Cosmetic Act or § 351 of the Public Health Service Act.)
| 1. NAME OF SPONSOR/APPLICANT/SUBMITTER | Marine Boyajian / Beckman Coulter, Inc. / Chemistry Systems Business Center |
|---|---|
| 2. DATE OF THE APPLICATION/SUBMISSIONWHICH THIS CERTIFICATION ACCOMPANIES | 04/17/2009 |
| 3. ADDRESS (Number, Street, State, and ZIP Code) | 200 S. Kraemer Blvd.M/S W-110Brea, CA 92821US |
| 4. TELEPHONE AND FAX NUMBER(Include Area Code) | (Tel.) (714) 961 - 6536(Fax) (714) 961 - 4234 |
PRODUCT INFORMATION
| 5. FOR DRUGS/BIOLOGICS: Include Any/All Available Established, Proprietary and/or Chemical/Biochemical/Blood/Cellular/Gene Therapy Product Name(s)FOR DEVICES: Include Any/All Common or Usual Name(s), Classification, Trade or Proprietary or Model Name(s) and/or Model Number(s)(Attach extra pages as necessary) | SYNCHRON Systems Enzymatic CO2 (CO2E) Reagent |
|---|---|
| ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ----------------------------------------------- |
APPLICATION / SUBMISSION INFORMATION
| 6. TYPE OF APPLICATION/SUBMISSION WHICH THIS CERTIFICATION ACCOMPANIES | |
|---|---|
| IND NDA ANDA BLA PMA HDE 510(k) PDP Other | |
| 7. INCLUDE IND/NDA/ANDA/BLA/PMA/HDE/510(k)/PDP/OTHER NUMBER (If number previously assigned) | |
| 8. SERIAL NUMBER ASSIGNED TO APPLICATION/SUBMISSION WHICH THIS CERTIFICATION ACCOMPANIES |
CERTIFICATION STATEMENT / INFORMATION
| 9. CHECK ONLY ONE OF THE FOLLOWING BOXES (See instructions for additional information and explanation) | |
|---|---|
| A. I certify that the requirements of 42 U.S.C. § 282(j), Section 402(j) of the Public Health Service Act, enacted by 121 Stat. 823, Public Law110-85, do not apply because the application/submission which this certification accompanies does not reference any clinical trial. | |
| B. I certify that the requirements of 42 U.S.C. § 282(j), Section 402(j) of the Public Health Service Act, enacted by 121 Stat. 823, Public Law110-85, do not apply to any clinical trial referenced in the application/submission which this certification accompanies. | |
| C. I certify that the requirements of 42 U.S.C. § 282(j), Section 402(j) of the Public Health Service Act, enacted by 121 Stat. 823, Public Law110-85, apply to one or more of the clinical trials referenced in the application/submission which this certification accompanies and thatthose requirements have been met. |
| 10. IF YOU CHECKED BOX C, IN NUMBER 9, PROVIDE THE NATIONAL CLINICAL TRIAL (NCT) NUMBER(S) FOR ANY "APPLICABLE CLINICAL TRIAL(S)."UNDER 42 U.S.C. § 282(j)(1)(A)(i), SECTION 402(j)(1)(A)(i) OF THE PUBLIC HEALTH SERVICE ACT, REFERENCED IN THE APPLICATION/SUBMISSION WHICH THIS CERTIFICATION ACCOMPANIES (Attach extra pages as necessary) | |
|---|---|
| NCT Number(s): |
The undersigned declares, to the best of her/his knowledge, that this is an accurate, true, and complete submission of information. I understand that the
failure to submit the certification required by 42 U.S.C. § 282(j)(5)(B), section 402(j)(5)(B) of the Public Health Service Act and the knowing submission
of a false certification under such section are prohibited acts under 21 U.S.C. § 331, section 301 of the Federal Food, Drug, and Cosmetic Act.
Warning: A willfully and knowingly false statement is a criminal offense, U.S. Code, title 18, section 1001.
| 11. SIGNATURE OF SPONSOR/APPLICANT/SUBMITTER OR ANAUTHORIZED REPRESENTATIVE (Sign) | 12. NAME AND TITLE OF THE PERON WHO SIGNED IN NO. 11 | |
|---|---|---|
| (Name) Marine Boyajian | ||
| (Title) Senior Regulatory Affairs Specialist | ||
| 13. ADDRESS (Number, Street, State, and ZIP Code) (of person identifiedin No. 11 and 12) | 14. TELEPHONE AND FAX NUMBER(Include Area Code) | 15. DATE OFCERTIFICATION |
| 200 S. Kraemer Blvd.M/S W-110Brea, CA 92821US | (Tel.) (714) 961 - 6536(Fax) (714) 961 - 4234 | 04/17/2009 |
FDA-3674 (1/08) (FRONT)
PSC Graphics: (301) 443-1090 EF ... . ... ...
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Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird symbol with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the bird symbol.
DEPARTMENT OF HEALTH & HUMAN SERVICES
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 South Kraemer Blvd., M/S W-110 Brea, CA 92822-8000
JUL 1 8 2009
Re: K091153
Trade name: Synchron® Systems Enzymatic CO2 (CO2E) Reagent Regulation Number: 21 CFR 862.1160 Regulation Name: Bicarbonate/carbon dioxide Test System Regulatory Class: Class II Product Code: KHS Dated: April 20, 2009 Received: April 22, 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.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely vours.
g.c.
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): んつ91153
Device Name: SYNCHRON® Systems Enzymatic CO2 (CO2E) Reagent
Indication For Use:
CO2E reagent, when used in conjunction with UniCel® DxC 800 System and SYNCHRON® Systems AQUA CAL 1 and 3, is intended for the quantitative determination of Carbon Dioxide in human serum or plasma.
Clinical Significance
Carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance
Prescription Use X (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)
Carol C. Benson
Revision Sign Off
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K091153
Page 1 of 1
§ 862.1160 Bicarbonate/carbon dioxide test system.
(a)
Identification. A bicarbonate/carbon dioxide test system is a device intended to measure bicarbonate/carbon dioxide in plasma, serum, and whole blood. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.(b)
Classification. Class II.