(69 days)
System reagent for the quantitative determination of Creatine Kinase-MB isoenzyme in human serum and plasma on Olympus analyzers.
Measurements of Creatine Kinase are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.
In this Olympus procedure: The R1 reagent antibody binds to the M subunit of CK in the serum sample. The B subunit of the enzyme acts on the substrate present in the R2 reagent. CK reversibly catalyzes the transfer of a phosphate group from creatine phosphate to ADP to give creatine and ATP. The ATP is used to produce glucose-6-phosphate and ADP, catalyzed by hexokinase (HK) which requires magnesium ions for maximum activity. The glucose-6-phosphate is oxidized by the action of the enzyme G6P-DH with simultaneous reduction of the coenzyme NADP to give NADPH and 6-phosphogluconate. The rate of increase of absorbance at 340/660 nm due to the formation of NADPH is directly proportional to the activity of CK-MB in the sample.
Here's an analysis of the provided text regarding the Olympus CK-MB Reagent (OSR6x155), focusing on the acceptance criteria and the study proving its performance:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document compares the new Olympus CK-MB (OSR6x155) reagent with a predicate device (Olympus CK-MB OSR6x53). While explicit "acceptance criteria" for performance are not directly stated in the format of a threshold to be met, the comparison with the predicate device implies that performance similar to or better than the predicate is the acceptance standard.
| Performance Characteristic | Acceptance Criteria (Implied by Predicate) | Reported Device Performance (Olympus CK-MB OSR6x155) |
|---|---|---|
| Precision (Total CV%) | ||
| AU400/400e | ||
| Sample 1 | Predicate: 2.85% | 4.26% |
| Sample 2 | Predicate: 0.65% | 1.31% |
| Sample 3 | Predicate: 0.52% | 1.10% |
| AU600/640/640e | ||
| Sample 1 | Predicate: 9.12% | 5.05% |
| AU2700/5400 | ||
| Sample 1 | Predicate: 5.59% | 3.50% |
| Sample 2 | Predicate: 3.54% | 1.13% |
| Sample 3 | Predicate: 3.76% | 1.21% |
| Assay Range | 10 to 2000 U/L | 10 to 2000 U/L |
| Sensitivity | Predicate: ~0.08 mAbsorbance per 1 U/L | ~0.12 mAbsorbance per 1 U/L |
| Method Comparison (Linear Regression) | ||
| Intercept | Predicate: 2.700 | 2.207 |
| Slope | Predicate: 0.965 | 1.061 |
| R2 | Predicate: 1.000 | 1.000 |
| Range | Predicate: 2-1881 U/L | 12-1860 U/L |
| Interfering Substances (Bilirubin) | ||
| AU600/640/640e | Predicate: <3% up to 40 mg/dL | <10% up to 40 mg/dL |
| AU400/400e | Predicate: <3% up to 40 mg/dL | <10% up to 40 mg/dL |
| AU2700/5400 | Predicate: <10% up to 24 mg/dL | <6% up to 40 mg/dL |
| Interfering Substances (Lipemia) | ||
| AU600/640/640e | Predicate: <10% up to 200 mg/dL | <15% up to 900 mg/dL |
| AU400/400e | Predicate: <3% up to 1000 mg/dL | <10% up to 900 mg/dL |
| AU2700/5400 | Predicate: <6% up to 1000 mg/dL | <20% up to 900 mg/dL |
Summary of Acceptance Criteria and Performance:
- Precision: For AU400/400e, the new device shows higher CV% values (less precise) than the predicate for all samples. For AU600/640/640e and AU2700/5400, the new device generally shows lower (better) CV% values than the predicate. Without explicit thresholds, it's hard to say if the higher CVs on AU400/400e meet acceptance, but the improvements on other instruments are positive.
- Assay Range: The new device matches the predicate's assay range.
- Sensitivity: The new device shows a larger change in absorbance per U/L, suggesting potentially better sensitivity than the predicate.
- Method Comparison: The R2 value of 1.000 for the new device is excellent, indicating strong linearity and agreement with the predicate. The slope and intercept are also very close, demonstrating substantial equivalence in performance. The range is comparable although slightly different.
- Interfering Substances: The performance varies. For bilirubin, the new device sometimes shows a higher percentage interference but often allows for higher concentrations of bilirubin (e.g., 40 mg/dL vs 24 mg/dL on AU2700/5400). For lipemia, the new device generally shows a higher percentage of interference but also allows for much higher concentrations of intralipid (e.g., 900 mg/dL vs 200 mg/dL on AU600/640/640e). These differences would need to be evaluated against specific clinical requirements for acceptable interference.
2. Sample Size Used for the Test Set and Data Provenance
The document provides specific data points for precision (using 3 samples per instrument type, but the number of replicates for each sample is not specified). For method comparison, a range of 12-1860 U/L is given, implying a comparison against samples across this range, but the exact number of individual samples is not stated.
Data Provenance: The document does not explicitly state the country of origin or whether the data is retrospective or prospective. Given that it's a submission by "Olympus Life and Material Science Europa GmbH" from Ireland, it's likely the testing was conducted in Europe. The context suggests a prospective laboratory study to generate performance data for the new reagent.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This section is not applicable to this type of device. This document describes an in vitro diagnostic (IVD) reagent for quantitative determination of a biomarker (CK-MB). The "ground truth" or reference method for such devices is typically an established laboratory method (e.g., the predicate device or a recognized standard method like the IFCC or Szasz method mentioned). The accuracy is determined by analytical performance against these methods or known concentrations, not by expert consensus on visual assessment or clinical interpretation.
4. Adjudication Method for the Test Set
This section is not applicable to this type of device. Adjudication refers to processes like multiple reviewers resolving discrepancies, which is common in image interpretation or clinical decision-making. For an IVD reagent, performance is objectively measured against analytical standards.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
This section is not applicable to this type of device. MRMC studies are typically for medical imaging or interpretation devices where human readers are involved. This device is an automated laboratory reagent.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
This is essentially what the performance data presented represents. The "device" (reagent) is used on automated Olympus analyzers to produce quantitative results. The performance characteristics (precision, sensitivity, method comparison, interference) are measurements of the reagent's analytical performance on these instruments, without human interpretation influencing the numerical result.
7. The Type of Ground Truth Used
The ground truth for evaluating the Olympus CK-MB Reagent (OSR6x155) is based on:
- Comparison to a legally marketed predicate device: Olympus OSR6X53 CK-MB method (K971817). The performance of the new reagent is directly compared side-by-side with this predicate.
- Theoretical extinction coefficients: The calibration of the new device is based on the theoretical extinction coefficient for NADPH, while the predicate used NADP. This indicates a reliance on established chemical principles for quantification.
- Modification of established methods: The new procedure is described as a "modification of the IFCC method," which is a widely recognized standard for CK measurements. The predicate was a modification of the Szasz method, another established method. This implies that the 'ground truth' is tied to these established analytical methodologies.
8. The Sample Size for the Training Set
The document does not provide information about a "training set." For an IVD reagent, development typically involves optimizing the chemical formulation and reaction conditions. While there's an R&D phase where different formulations are tested, there isn't a "training set" in the sense of machine learning algorithms. The performance characteristics presented are from verification and validation testing, not a dataset used to "train" the reagent.
9. How the Ground Truth for the Training Set was Established
As there is no "training set" for this type of device in the context of machine learning, this question is not applicable. The "ground truth" for the development of such reagents would involve rigorous chemical and analytical testing against known standards and established reference methods to ensure accurate and reliable measurements.
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510(k) Summary
510(k) Summary
in summary of the 510(k) safety and effectiveness information is being submitted in acc
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
| 1. | Submitter name, address, contact | Olympus Life andMaterial ScienceEuropa GmbHLismeehan,O'Callaghan's MillsCo. Clare, Ireland | JUN - 4 |
|---|---|---|---|
| U.S. Telephone:U.S. Fax:Telephone: | 469-230-0959972-317-7861011-353-65-683-1100 | ||
| Contact Person: | Stephanie G. Schwartz | ||
| Date Prepared: | March 25, 2007 | ||
| 2. | Device name | Proprietary Name: | Olympus CK-MB Reagent (OSR6x155) |
| Common Name: | CK-MB Reagent | ||
| Classification Name: | Colorimetric Method, CPK or Isoenzymestest system. | ||
| 3. | Predicate device | Reagent: | Olympus OSR6X53 CK-MB methodSubmitted (K971817) |
| 4. | Device description | In this Olympus procedure:The R1 reagent antibody binds to the M subunit of CK in the serum sample. The B subunit of the enzyme acts on the substrate present in the R2 reagent. CK reversibly catalyzes the transfer of a phosphate group from creatine phosphate to ADP to give creatine and ATP. The ATP is used to produce glucose-6-phosphate and ADP, catalyzed by hexokinase (HK) which requires magnesium ions for maximum activity. The glucose-6-phosphate is oxidized by the action of the enzyme G6P-DH with simultaneous reduction of the coenzyme NADP to give NADPH and 6-phosphogluconate. The rate of increase of absorbance at 340/660 nm due to the formation of NADPH is directly proportional to the activity of CK-MB in the sample. | |
| 5. | Intended use | System reagent for the quantitative determination of CreatineKinase-MB isoenzyme in human serum and plasma on Olympusanalyzers. |
2007
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510(k) Summary
The assigned 510(k) number is: 5070835
- ნ.
The following Tables compare the new Olympus CK-MB (OSR6x155) reagent with the current Olympus CK-MB (OSR6x53) reagent.
| Similarities | ||
|---|---|---|
| Item | Olympus CK-MB (OSR6x155) reagent | Predicate System |
| Intended Use | System reagent for the quantitative determination of Creatine Kinase-MB isoenzyme in human serum and plasma on Olympus analyzers. | System reagent for the quantitative determination of Creatine Kinase-MB isoenzyme in human serum and plasma on Olympus analyzers. |
| Instrument required | Olympus AU400/400°, 600/640/640° and 2700/5400 | Same |
| Measurement | Quantitative | Same |
| Specimen Type | Serum and heparinized plasma | Same |
| Assay Methodology | Isoenzymes | Same |
| Antibody | Antibody to CK-M subunit | Same |
| Calibration | Procedure is based upon a theoretical extinction coefficient. | Same |
| Expected Values | 1 - 10 U/L | Same |
| Differences | ||
| Item | Olympus CK-MB (OSR6x155) reagent | Predicate System |
| Traceability | This Olympus CK procedure is amodification of the IFCC method | This Olympus CK procedure is amodification of the Szasz method |
| Reagent storage form | LiquidOn -board storage | ReconstitutedOn -board storage |
| Reagent Handling | R1: Mix R1-2 into R1-1 before placingon instrument.R2 Ready for use | R1: Dissolve the contents of one R1 Lyocompletely with the contents of one bottleof R1 Buffer.R2: Dissolve the contents of one R2 Lyocompletely with the contents of one bottleof R2 Buffer |
| Reagent On Board Stability | Opened reagents are stable for 30days when stored in the refrigeratedcompartment of the analyzer. | Reconstituted reagents are stable for 5days when stored in the refrigeratedcompartment of the analyzer. |
| Antibody | Polyclonal anti CK-M goat antibody | Polyclonal anti CK-M sheep antibody |
| Calibration | Calibration of this CK-MB procedure isbased upon the theoretical extinctioncoefficient for NADPH, which has a molarabsorptivity of 6300 at340/660 nm | Calibration of this CK-MB procedure isbased upon the theoretical extinctioncoefficient for NADP, which has a molarabsorptivity of 4960 at340/380 nm |
| Performance Characteristics | ||||
|---|---|---|---|---|
| Item | Olympus CK-MB (OSR6x155) reagent | Predicate System | ||
| Precision | AU400/400°Sample123 | AU400/400°Sample123 | ||
| Total CV%4.261.311.10 | Total CV%2.850.650.52 | |||
| AU600/640/640°Sample1 | AU600/640/640°Sample1 | |||
| Total CV%5.05 | Total CV%9.12 |
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510(k) Summary
The assigned 510(k) Summan ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
| 2 | 1.15 | 2 | 1.62 | ||
|---|---|---|---|---|---|
| 3 | 0.90 | 3 | 0.73 | ||
| AU2700/5400SampleTotal CV% | AU2700/5400SampleTotal CV% | ||||
| 1 | 3.50 | 1 | 5.59 | ||
| 2 | 1.13 | 2 | 3.54 | ||
| 3 | 1.21 | 3 | 3.76 | ||
| Assay Range | 10 to 2000 U/L | 10 to 2000 U/L | |||
| Sensitivity | Typical change in absorbance perminute for 1 U/L of CK-MB isapproximately 0.12 mAbsorbance | Typical change in absorbance perminute for 1 U/L of CK-MB isapproximately 0.08 mAbsorbance | |||
| Method Comparison (LinearRegression) | Intercept | 2.207 | Intercept | 2.700 | |
| Slope | 1.061 | Slope | 0.965 | ||
| R2 | 1.000 | R2 | 1.000 | ||
| Range | 12-1860 U/L | Range | 2-1881 U/L | ||
| Interfering Substances | AU600/640/640eBilirubin: Interference less than 10%up to 40 mg/dL BilirubinLipemia: Interference less than 15% upto 900 mg/dL Intralipid | AU600/640/640eBilirubin: Interference less than 3% upto 40 mg/dL BilirubinLipemia: Interference less than 10% upto 200 mg/dL Intralipid | |||
| AU400/400eBilirubin: Interference less than 10%up to 40 mg/dL BilirubinLipemia: Interference less than 10% upto 900 mg/dL Intralipid | AU400/400eBilirubin: Interference less than 3% upto 40 mg/dL BilirubinLipemia: Interference less than 3% upto 1000 mg/dL Intralipid | ||||
| AU2700/5400Bilirubin: Interference less than 6% upto 40 mg/dL BilirubinLipemia: Interference less than 20% upto 900 mg/dL Intralipid | AU2700/5400Bilirubin: Interference less than 10%up to 24 mg/dL BilirubinLipemia: Interference less than 6% upto 1000 mg/dL Intralipid |
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/3/Picture/1 description: The image shows the logo for the United States Department of Health and Human Services. The logo features a stylized eagle with three tail feathers, representing the department's commitment to health, human services, and well-being. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle symbol.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Olympus Life & Material Science Europa GMBH (Irish Branch) c/o Ms. Stephanie Schwartz Regulatory Affairs/Quality Assurance Manager Lismeehan, O'Callaghan's Mills, CO. Clare, Ireland
JUN - 4 2007
Re: K070835 Trade/Device Name: Olympus CK-MB Reagent Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: JHY Dated: March 24, 2007 Received: March 27, 2007
Dear Ms. Schwartz:
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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.
· Sincerely yours,
Jean M. Cooper, M.S., D.V.M.
Sean M. Cooper, M.S., D.V.M. 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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Indications for Use
510(k) Number (if known): K070835
Device Name:
Olympus CK-MB Reagent
Indications For Use:
System reagent for the quantitative determination of Creatine Kinase-MB isoenzyme in human serum and heparinized plasma on OLYMPUS analyzers
Measurements of Creatine Kinase are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.
Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k)
708
Page 1 of
§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.
(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.