(197 days)
The i-STAT CK-MB test is an in vitro diagnostic test for the quantitative measurement of creatine kinase MB in whole blood or plasma samples. CK-MB measurements can be used as an aid in the diagnosis of myocardial infarction (MI).
The cartridge is to be used with the i-STAT 1 Analyzer bearing the (Immuno) symbol, but not with the i-STAT Portable Clinical Analyzer or the Philips Medical Systems (formerly Agilent Technologies) Blood Analysis Module (BAM). As part of the i-STAT System, the CK-MB test is to be used by trained health care professionals in accordance with a facility's policies and procedures.
The i-STAT Cardiac Troponin I (cTnl) test is an in vitro diagnostic test for the quantitative measurement of cardiac troponin I in whole blood or plasma. Measurements on cardiac troponin I are used as an aid in the diagnosis and treatment of patients with acute myocardial infarction and as an aid in the risk stratification of patients with acute coronary syndromes with respect to their relative risk of mortality.
The i-STAT CK-MB test is contained in a single-use test cartridge. In use, the user scans a bar code and then places approximately 16 uL of whole blood or plasma in the cartridge. After the cartridge is closed, it is inserted into the thermally controlled i-STAT 1 Analyzer, and all analytical steps are performed automatically. Patient and use information may be entered into the analyzer via a keypad during the automated analysis cycle.
As the analyzer performs several quality checks and controls the temperature of the sensors via resistive heating to the underside of the sensor chips, the substratelwash fluid is released into a conduit within the cartridge and a metered volume of the sample over the sensor chips. The enzyme-linked antibody conjugate dissolves into the sample and the sample incubates for a controlled time. The sample is then pushed into a waste chamber and the substrate/wash solution is brought over the sensors. The alkaline phosphatase captured on the CK-MB sensor cleaves the substrate present in the substrate/wash fluid, giving rise to an amperometric signal which is measured.
Here's an analysis of the provided text, focusing on the acceptance criteria and study information for the i-STAT CK-MB Test.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for substantial equivalence are not explicitly stated as numerical targets in the document. Instead, the general criteria are that the device should be "substantially equivalent" to the predicate device in terms of performance and safety. The reported device performance is compared to the predicate and to laboratory standards.
| Acceptance Criteria (Implied) | Reported Device Performance (i-STAT CK-MB Test) |
|---|---|
| Insensitivity to various hematocrit levels | Insensitive to hematocrit levels from 0 to 70 %PCV. |
| Not significantly influenced by other CK isoforms | Not significantly influenced by the presence of CK-BB at 100 ng/mL or CK-MM at 10,000 ng/mL. |
| Similar interference effects from common medications to predicate | Interference effects from common medications (especially those for cardiovascular conditions) were similar to the Triage Cardiac Panel CK-MB. |
| Acceptable Lower Limit of Detection (LLD) | LLD of 0.6 ng/mL (comparable to predicate's 1.0 ng/mL). |
| Adequate imprecision for various control levels | Level 1 control %CV: 11.9% at 5.9 ng/mL Level 2 control %CV: 10.4% at 25.8 ng/mL Level 3 control %CV: 10.0% at 90.1 ng/mL |
| Acceptable clinical correlation to predicate device (Abbott AxSYM) | All Samples (N=263):- Slope: 1.01- Intercept: -0.19- Correlation: 0.994Samples where [CK-MB] < 20.0 ng/mL (N=234):- Slope: 0.993- Intercept: -0.05- Correlation: 0.960 |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 263 patient samples for the overall comparison, and 234 samples for the subset where CK-MB < 20.0 ng/mL.
- Data Provenance: The study states "Studies conducted at clinical sites," suggesting a prospective collection for the purpose of the study. The origin (country/specific sites) is not explicitly mentioned, but it's likely U.S. clinical sites given the FDA submission. The data is described as "samples from patients who presented to the hospital with chest pain," indicating clinical relevance.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not provided in the document. For in vitro diagnostic devices like the i-STAT CK-MB test, "ground truth" is typically established by comparing the device's results to a recognized reference method (the predicate device, in this case, the Abbott AxSYM). No human expert interpretation of images or data, as might be seen in diagnostic imaging, is involved in establishing the "ground truth" for quantitative biochemical measurements.
4. Adjudication Method for the Test Set
This term is generally not applicable to the type of quantitative in vitro diagnostic study described. Adjudication methods (like 2+1, 3+1) are primarily used in studies involving human interpretation (e.g., radiology reads) to resolve discrepancies among experts. In this study, the comparison is directly between quantitative measurements from two different analytical devices.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study involves multiple human readers interpreting cases, often with and without AI assistance, to measure the impact of the AI on human performance. The current study focuses on the standalone performance of the i-STAT CK-MB device compared to a predicate device.
6. If a Standalone Study Was Done
Yes, a standalone study was done. The entire clinical and non-clinical performance summary describes the i-STAT CK-MB test's performance without human intervention in the analytical process. The i-STAT 1 Analyzer performs "all analytical steps... automatically" after the sample is inserted. Its results are then compared to the predicate device.
7. The Type of Ground Truth Used
The ground truth for the clinical comparison was the results obtained from the Abbott AxSYM CK-MB test. The document states, "Clinical sites compared the results of the i-STAT CK-MB test to those of the CK-MB test on the Triage Cardiac Panel for samples from patients who presented to the hospital with chest pain. Heparinized whole blood and plasma samples were analyzed on the i-STAT System while plasma samples were analyzed on the Abbott AxSYM." This indicates the Abbott AxSYM served as the comparative or reference method.
8. The Sample Size for the Training Set
The document does not specify a separate training set size. The studies described are for validation/testing of the device's performance. For diagnostic tests like this, the "training" (development) of the assay is an internal process by the manufacturer, but the specific volume of samples used for that internal development is not typically disclosed in a 510(k) summary focused on validation.
9. How the Ground Truth for the Training Set Was Established
Since no distinct "training set" with established ground truth is mentioned for the purpose of this submission, this information is not provided. The development of an immunoassay typically involves extensive internal R&D, calibration, and optimization using characterized materials and reference methods, but these details are not part of the 510(k) summary's scope.
{0}------------------------------------------------
DEC 15 2005
K 051433
510(k) Summary
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1900 and CFR 807.92.
The assigned 510(k) number is:
Summary prepared on: Sep 10, 2005
Submitted by:
i-STAT Corporation 104 Windsor Center Drive E. Windsor, NJ 08520 FAX: 609-443-9310 Phone: 609-443-9300
Contact:
Mike Zelin Vice-President, R&D i-STAT Corporation 104 Windsor Center Drive East Windsor, NJ 08520 Fax: 609-443-9310 Phone: 609-443-9300
Establishment Registration Number: 2245578
ldentification of Device: .
Device Name: CK-MB Test Proprietary/Trade Name: i-STAT® CK-MB Test Common Name: CK-MB, Creatine Kinase MB Isoenzymes Device Classification: II Requlation Number: 21 CFR§ 862.1215 Panel: Biosensor, Immunoassay, Cpk Or Isoenzymes Product Code: MYT
Identification of the Predicate Device:
Device Name: CK-MB test, Triage Cardiac Panel for use on the Triage Meter.
Intended Use of the Device:
The i-STAT CK-MB test is an in vitro diagnostic test for the quantitative measurement of creatine kinase MB in whole blood or plasma samples. CK-MB measurements can be used as an aid in the diagnosis of myocardial infarction (MI).
The cartridge is to be used with the i-STAT 1 Analyzer bearing the (Immuno) symbol, but not with the i-STAT Portable Clinical Analyzer or the Philips Medical Systems (formerly Agilent Technologies) Blood Analysis Module (BAM). As part of the i-STAT System, the CK-MB test is to be used by trained health care professionals in accordance with a facility's policies and procedures.
Description of the Device:
The i-STAT CK-MB test is contained in a single-use test cartridge. In use, the user scans a bar code and then places approximately 16 uL of whole blood or plasma in the cartridge. After the cartridge is closed, it is inserted into the thermally controlled i-STAT 1 Analyzer, and all analytical steps are performed automatically. Patient and use information may be entered into the analyzer via a keypad during the automated analysis cycle.
{1}------------------------------------------------
As the analyzer performs several quality checks and controls the temperature of the sensors via resistive heating to the underside of the sensor chips, the substratelwash fluid is released into a conduit within the cartridge and a metered volume of the sample over the sensor chips. The enzyme-linked antibody conjugate dissolves into the sample and the sample incubates for a controlled time. The sample is then pushed into a waste chamber and the substrate/wash solution is brought over the sensors. The alkaline phosphatase captured on the CK-MB sensor cleaves the substrate present in the substrate/wash fluid, giving rise to an amperometric signal which is measured.
Comparison to Technological Features of the Predicate Device:
The followig is a comparison of technological features of the i-STAT and Triage Cardiac Panel CK-MB methods:
| Characteristic | Triage CK-MB | i-STAT CK-MB |
|---|---|---|
| Assay methodology | Two-site ELISA | Two-site ELISA |
| Capture site | Heterogeneous | Heterogeneous |
| Capture antibodies | Monoclonal | Monoclonal |
| Enzyme label antibody | Polyclonal | Monoclonal |
| Enzyme label | Fluorescent dye | Alkaline phosphatase |
| Analysis sequence | Simultaneous capture/label | Simultaneous capture/label |
| Analysis time | 16 minutes | 5 minutes |
| Sample type | Whole blood or plasma | Whole blood or plasma |
| Enzyme detection | Fluorescent | Electrochemical |
Summary of Non-Clinical Performance in Support of Substantial Equivalence:
- Studies established that the i-STAT CK-MB test is insensitive to hematocrit levels from 0 to . 70 %PCV.
- . The CK-MB assay is not significantly influenced by the presence of CK-BB at 100 ng/mL or CK-MM at 10,000 ng/mL.
- Studies established that the interference effects from common medications, particularly those . commonly prescribed to patients with cardiovascular conditions, were similar to the effects for those drugs on CK-MB of the Triage Cardiac Panel.
- . Studies established that the lower limit of detection (LLD) for the i-STAT method is a comparable 0.6 ng/mL versus 1.0 ng/mL for the CK-MB of the Triage Cardiac Panel.
- . The imprecision of the i-STAT CK-MB test using plasma controls was established using inhouse and user studies. The Level 1 control %CV was 11.9% at 5.9 ng/mL, the Level 2 control %CV was 10.4% at 25.8 ng/mL and the Level 3 control %CV was 10.0% at 90.1 ng/mL. This includes within-lot, lot-to-lot, vial-to-vial, analyzer-to-analyzer and operator-tooperator components of the imprecision.
{2}------------------------------------------------
Summary of Clinical Test Performance is Support of Substantial Equivalence Claims: Studies conducted at clinical sites compared the results of the i-STAT CK-MB test to those of the CK-MB test on the Triage Cardiac Panel for samples from patients who presented to the hospital with chest pain. Heparinized whole blood and plasma samples were analyzed on the i-STAT System while plasma samples were analyzed on the Abbott AxSYM. The methods were compared using Deming regression analysis. The results are summarized in the table below:
and the first the became of the comment of the status
் பட்டி மாவட்டத்தில் அமைந்து வருகிறது துடுப்பது திருவுகள் பல்கலை மாவட்டத்தில் ப
| Definition | i-STAT whole bloodand plasma vs AbbottAxSYM plasma | ||
|---|---|---|---|
| Statistic | allsamples | sampleswhere [CK-MB] <20.0ng/mL | |
| N | The number of patientsamples included in the dataset | 263 | 234 |
| Mean | The average of thecomparative method resultover the sample population | 10.82 | 3.58 |
| Range | The range of comparativemethod results obtained overthe sample population | 0.04 - 224 | 0.04-15.05 |
| Sxx | The pooled estimate of thewithin-sample standarddeviation of the comparativemethod over the samplepopulation | 1.84 | 0.34 |
| Syy | The pooled estimate of thewithin-sample standarddeviation of the test methodover the sample population | 2.66 | 0.38 |
| Slope | The Deming slope of thecorrelation | 1.01 | 0.993 |
| Intercept | The Deming intercept of thecorrelation | -0.19 | -0.05 |
| Correlation | The correlation coefficientdetermined from regression | 0.994 | 0.960 |
| Sy.x | The standard error of theestimate of the regression ofthe regression of y (testmethod) on x (comparativemethod) calculated using theregular regression slope | 3.98 | 0.94 |
Conclusions:
Based on clinical and non-clinical data the i-STAT CK-MB test is insensitive to hematocrit level from 0 - 70 %PCV, is not significantly influenced by the presence of other CK isoforms, shows similar interference effects to common drugs as the CK-MB test on the Triage Cardiac Panel, and has a lower limit of detection (LLD) of 0.6 ng/mL than the CK-MB test on the Triage Cardiac Panel. Studies using plasma controls indicate adequate imprecision for low, mid-range, and high results. Clinical data indicates acceptable correlation to the predicate device.
{3}------------------------------------------------
ldentification of Device:
Proprietary/Trade Name: i-STAT® cTnl Test Name: Immunoassay Method, Troponin Subunit Device Classification: II Regulation Number: 21 CFR§ 862.1215 Product Code: MMI
and and the many of the seat of the seat of the section the section the section to the
1:00 pm 1 personal
Supplie 1121
...
Conclusions:
Based on comparative data the i-STAT Tn1 test can be run on both heparanized and nonheparanized whole blood samples as contrasted with the original restriction to heparanized whole blood samples (along with plasma samples) as per the current indications for use statement.
{4}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or feathers. The bird is positioned above the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA", which is arranged in a circular fashion around the bird symbol.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
DEC 15 2005
Ms. Sue Kent Manager, Clinical Affairs i-STAT Corporation 104 Windsor Center Drive East Windsor, NJ 08520
Re: K051433
Trade/Device Name: i-STAT CK-MB test i-STAT Cardiac Troponin I test Regulation Number: 21 CFR 862.1215 Regulation Name: 21 OFF 00211241128211241111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111 Regulatory Class: Class II Product Code: MYT, MMI Dated: November 26, 2005 Received: November 29, 2005
Dear Mr. Zelin:
We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your becaren or (x) fee 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 conniered phorts to May 20, 1978, are excordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). alle Costicule 700 (710) that to nov requent to the general controls provisions of the Act. The I ou may, merelory, mans of the Act include requirements for annual registration, listing of general controls provincity 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 it may be subject to sach dadnedial dema Regulations (CFR), Parts 800 to 895. In addition, FDA ean be found in Ther announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean I Teast of advised that I Dris issuance or our device complies with other requirements of the Act mall 1 DA has made a determinations administered by other Federal agencies. You must of any it cacal statutes and regaranents, including, but not limited to: registration and listing (21 comply with an the Prec 201 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
{5}------------------------------------------------
Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) I his icher witi anow you to ogin finding of substantial equivalence of your device to a legally premation notification - The stassification 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, If you desire specific information advertising of your device, please contact the Office of In of questions on the promie Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Tegulation other general information on your responsibilities under the Act from the I ou inay other general mormansional and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Alberto Guts
Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
{6}------------------------------------------------
Indications for Use
K051433 (previously K031739) 510(k) Number (if known):
i-STAT Cardiac Troponin I test Device Name:
Indications For Use:
The i-STAT Cardiac Troponin I (cTnl) test is an in vitro diagnostic test for the The FSTAT Oardiae Troponin I in whole blood or plasma.
quantitative measurement of cardiac troponin I in whole blood ond tractm quantitative measurement of ourchas in the diagnosis and treatment of Measurements on cardiac troponial Fare accums and as and as a catients with acute myocardial infaretion and as a see a their relative risk of mortality.
Prescription Use
X
(Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________ (21 CFR 801 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)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Jivision Sign-Off
Livision Sign-Off
Page 1 of ____________________________________________________________________________________________________________________________________________________________________
Office of In Vitro Diagnostic Device Evaluation and Safety
10(k)_ Ko 51433 ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
{7}------------------------------------------------
Indications for Use
510(k) Number (if known): K051433
i-STAT CK-MB test Device Name:
Indications For Use:
The i-STAT CKMB test is an in vitro diagnostic test for the quantitative measurement of The F-STAT CKMB test is an in vitto diagnoons too. Ios. CK-MB measurements
creatinine kinase MB mass in whole blood or plasma samples. CK-MB measurements creatinine Kiflase MD mass in whole blood or pracma out procardial infarction (MI).
can be used as an aid in the diagnosis and treatment of myocardial infarction (MI).
Prescription Use (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________ (21 CFR 801 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)
Page 1 of ____________________________________________________________________________________________________________________________________________________________________
22
- Ision Sign-Off
Office of In Vit-o Diagnostic Device Waluation and Safety
Kas1433
§ 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.