(79 days)
The Stratus® CS Acute Care™ CKMB method is an in vitro diagnostic test for the measurement of the MB isoenzyme of creatine kinase (ATP: Creatine N-Phosphostransferase, E.C. No 2.7.3.2) in heparinized plasma. Measurements of CKMB can be used in the diagnosis and treatment of myocardial infarction and progressive, Duchenne-type muscular dystrophy. This method is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings.
The Stratus® CS Acute Care™ CKMB Calibrator (CKMB CalPak) is an in vitro diagnostic product intended to be used for calibration of the Stratus® CS Acute Care™ CKMB method.
The Stratus® CS Acute Care™ CKMB Dilution Pak (CKMB DilPak) is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ CKMB TestPak for the measurement of samples with elevated levels of CKMB.
The Stratus® CS Acute Care™ Troponin I method (cTnl) is an in vitro diagnostic assay for the measurement of cardiac troponin I in heparinized plasma. Cardiac troponin I measurements can be used as an aid in the diagnosis of acute myocardial infarction (AMI). Cardiac troponin I can also be used as aid in the risk stratification of patients with acute coronary syndromes (ACS) with respect to their relative risk of mortality. This method is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings.
The Stratus® CS Acute Care™ Troponin I Calibrator (cTnI CalPak) is an in vitro diagnostic product intended to be used for calibration of the Stratus® CS Acute Care™ Troponin I method.
The Stratus® CS Acute Care™ Troponin I Dilution Pak (cTnI DilPak) is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ cTnI TestPak for the measurement of samples with elevated levels of cardiac Troponin I.
The Stratus® CS Acute Care™ Myoglobin method (MYO) is an in vitro diagnostic assay for the measurement of myoglobin in heparinized plasma. Measurements of myoglobin aid in the rapid diagnosis of renal or heart disease, e.g. myocardial infarction. This method is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings.
The Stratus® CS Acute Care™ Myoglobin Calibrator (MYO CalPak) is an in vitro diagnostic product intended to be used for calibration of the Stratus® CS Acute Care™ myoglobin method.
The Stratus® CS Acute Care™ Myoglobin Dilution Pak (MYO DilPak) is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ MYO TestPak for the measurement of samples with elevated Myoglobin levels.
The Stratus® CS Acute Care™ CKMB method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology. In this procedure, dendrimer linked monoclonal antibody is added to the center portion of a square piece of glass fiber paper in the CKMB TestPak. Sample is then added onto the paper where it reacts with the immobilized antibody. After a short incubation, a conjugate consisting of enzyme-labeled monoclonal antibody directed against a distinct antigenic site on the B subunit of the CKMB molecule is pipetted onto the reaction zone of the paper. During this second incubation period, enzyme-labeled antibody reacts with the bound CKMB, forming an antibody-antigen-labeled antibody sandwich. The unbound labeled antibody is later eluted from the field of view of the Stratus® CS analyzer by applying a substrate wash solution to the center of the reaction zone. By including substrate for the enzyme within the wash solution, initiation of enzyme activity occurs simultaneously with the wash. The enzymatic rate of the bound fraction increases directly with the concentration of CKMB in the sample. The reaction rate is measured by an optical system that monitors the reaction rate via front surface fluorescence. All data analysis functions are performed by the microprocessor within the analyzer.
The Stratus® CS Acute Care CKMB calibrator (CKMB CalPak) is a refrigerated liquid product containing human heart CKMB in a buffered bovine protein matrix with stabilizers and preservative. The kit consists of five CalPaks at a single calibrator level. Each CalPak contains calibrator reagent in three wells.
The Stratus® CS Acute Care CKMB Diluent (CKMB DilPak) is a refrigerated liquid product containing buffered human protein matrix with stabilizers and 0.2% sodium azide. The kit consists of 5 DilPaks with diluent in one well.
The Stratus® CS Acute Care™ Troponin I method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology. In this procedure, dendrimer linked monoclonal antibody is added to the center portion of a square piece of glass fiber paper in the c TnI TestPak. This antibody recognizes a distinct antigenic site on the cardiac troponin I molecule. Sample is then added onto the paper where it reacts with the immobilized antibody. After a short incubation, a conjugate consisting of enzyme-labeled monoclonal antibody directed against a second distinct antigenic site on the cardiac troponin I molecule is pipetted onto the reaction zone of the paper. During this second incubation period, enzyme-labeled antibody reacts with the bound cardiac troponin I, forming an antibody-antigen-labeled antibody sandwich. The unbound labeled antibody is later eluted from the field of view of the Stratus® CS analyzer by applying a substrate wash solution to the center of the reaction zone. By including substrate for the enzyme within the wash solution, initiation of enzyme activity occurs simultaneously with the wash. The enzymatic rate of the bound fraction increases directly with the concentration of cardiac troponin I in the sample. The reaction rate can then be measured by an optical system that monitors the reaction rate via front surface fluorescence. All data analysis functions are performed by the microprocessor within the analyzer.
The Stratus® CS Acute Care Troponin I calibrator (cTnI CalPak) is a frozen liquid product containing native, human troponin complex, in a human serum base with less than 0.1% sodium azide. The kit consists of five CalPaks at a single calibrator level. Each CalPak contains calibrator reagent in three wells.
The Stratus® CS Acute Care Troponin I Diluent (cTnI DilPak) is a refrigerated liquid product containing a buffered human protein matrix with stabilizers and less than 0.1% sodium azide. The kit consists of 5 DilPaks with diluent in one well.
The Stratus® CS Acute Care™ MYO method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology. In this procedure, dendrimer linked monoclonal myoglobin antibody is added to the center portion of a square piece of glass fiber paper in the MYO TestPak. This antibody recognizes a distinct antigenic site on the myoglobin molecule. Sample is then added onto the paper where it reacts with the immobilized antibody. After a short incubation, a conjugate consisting of enzyme-labeled monoclonal antibody directed against a second distinct antigenic site on the myoglobin molecule is pipetted onto the reaction zone of the paper. During this second incubation period, enzyme-labeled antibody reacts with the bound myoglobin, forming an antibody-antigen-labeled antibody sandwich. The unbound labeled antibody is later eluted from the field of view of the Stratus® CS analyzer by applying a substrate wash solution to the center of the reaction zone. By including substrate for the enzyme within the wash solution, initiation of enzyme activity occurs simultaneously with the wash. The enzymatic rate of the bound fraction increases directly with the concentration of myoglobin in the sample. The reaction rate can then be measured by an optical system that monitors the reaction rate via front surface fluorescence. All data analysis functions are performed by the microprocessor within the analyzer.
The Stratus® CS Acute Care MYO calibrator (MYO CalPak) is a refrigerated liquid product containing human heart myoglobin in a bovine albumin matrix with stabilizers and less than 0.1 % sodium azide. The kit consists of five CalPaks at a single calibrator level. Each CalPak contains calibrator reagent in three wells.
The Stratus® CS Acute Care MYO Diluent (MYO DilPak) is a refrigerated liquid product containing a buffered bovine protein matrix with stabilizers and 0.2 % sodium azide. The kit consists of 5 DilPaks with diluent in one well.
The provided text describes a 510(k) premarket notification for Dade Behring's Stratus® CS Acute Care™ assays (CKMB, Troponin I, and Myoglobin), along with their associated calibrators and diluents. The core of this submission is to achieve substantial equivalence for these products to allow their use in Point-of-Care (POC) settings in addition to the clinical laboratory.
Here's an analysis of the acceptance criteria and study information, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly state quantitative acceptance criteria (e.g., specific thresholds for precision or accuracy). Instead, it relies on demonstrating substantial equivalence to predicate devices and showing that performance in "non-laboratory" (POC) settings is comparable to that in "laboratory" settings.
The key performance metric reported, implicitly serving as the acceptance criterion, is the comparability of precision and accuracy data generated by "non-laboratory" personnel (POC) to that generated by "laboratory" personnel.
| Metric/Criteria | Acceptance Criteria (Implicit) | Reported Device Performance (Implicit) |
|---|---|---|
| Precision | Precision data generated by "non-laboratory" personnel should be comparable to precision data generated by "laboratory" personnel. | Precision data generated by "non-laboratory" personnel is comparable to precision data generated by "laboratory" personnel, supporting the addition of point of care to the intended use for CKMB, cTnI, and Myoglobin assays. |
| Accuracy | Accuracy data generated by "non-laboratory" personnel should be comparable to accuracy data generated by "laboratory" personnel. | Accuracy data generated by "non-laboratory" personnel is comparable to accuracy data generated by "laboratory" personnel, supporting the addition of point of care to the intended use for CKMB, cTnI, and Myoglobin assays. |
| Substantial Equivalence | The Stratus® CS Acute Care™ products (TestPaks, CalPaks, DilPaks for CKMB, cTnI, and MYO) are substantially equivalent in principle of operation and performance to their respective predicate devices. No formulation or design changes were made. | The Stratus® CS Acute Care™ products were determined to be substantially equivalent to their predicate devices. The products are identical, use the same manufacturing processes, and labeling changes only reflect new intended use and minor format changes. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Sample Size for Test Set: The document explicitly states: "Method comparison and precision analysis were performed at three different locations (clinical laboratory (LAB), Emergency Department (ED) and Cardiac Care Unit (CCU) within each of two hospitals (2))."
- It does not provide a specific number of samples or patients included in these method comparison and precision analyses. It only mentions where the testing was conducted.
- Data Provenance: The locations are described as "three different locations (clinical laboratory (LAB), Emergency Department (ED) and Cardiac Care Unit (CCU) within each of two hospitals (2))". This suggests a prospective study design as data was generated at these sites for the purpose of the submission. The country of origin is not explicitly stated, but given the submitter's address (Newark, DE, USA), it's highly likely the study was conducted in the USA.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- The document does not mention the use of experts to establish ground truth in the context of diagnostic interpretation for the test set. This type of submission is for in vitro diagnostic (IVD) assays, where the "ground truth" for evaluating performance is typically established by reference methods or clinical diagnosis (e.g., confirmed myocardial infarction) against which the assay results are compared.
- The text focuses on the performance of the assay itself (precision, accuracy) when operated by different personnel. It states: "This data and a summary of information on the operators and their training, from either the ED or CCU, i.e. "non-lab" operators, is also included in the original 510(k)'s." This implies the operators were "trained health care professionals" (as per the intended use), but not necessarily "experts" establishing ground truth in a diagnostic sense for the comparative study.
4. Adjudication Method for the Test Set
- No adjudication method is described in the provided text. The study focuses on comparing quantitative assay results between different operational settings (lab vs. POC) rather than on diagnostic interpretations that would require adjudication.
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 more common for imaging devices or algorithms that directly assist human interpretation in making a diagnosis where multiple readers evaluate cases.
- This submission is for an in vitro diagnostic (IVD) assay that measures biomarkers. The comparison is between the assay's performance (precision and accuracy) when operated by "laboratory" personnel versus "non-laboratory" personnel, not improving human readers' diagnostic accuracy with AI assistance.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
- This question is not directly applicable as the device is an in vitro diagnostic assay (a chemical test), not an AI algorithm. Its performance is inherent to the assay and analyzer, regardless of the operator, though operator technique can influence results.
- The study did evaluate the assay's performance in a standalone manner, meaning the assay itself produced results, and these results were then assessed for precision and accuracy when executed by different types of operators (laboratory vs. "non-lab" or POC). There isn't an "algorithm-only" concept here in the sense of AI.
7. The Type of Ground Truth Used
- For precision, the ground truth is the reproducibility of the assay itself, ideally measured against itself or reference materials.
- For accuracy, the ground truth would typically be established by reference methods for CKMB, Troponin I, and Myoglobin, or clinical diagnosis of the conditions they aid in diagnosing (e.g., acute myocardial infarction).
- However, the text strongly emphasizes substantial equivalence to existing predicate devices. This means the "ground truth" for the new intended use (POC) largely hinges on demonstrating that the results produced by the new method (in POC settings) are comparable to those produced by the predicate devices (which are already accepted) and the same device in traditional lab settings.
8. The Sample Size for the Training Set
- The text does not mention a training set sample size. This is expected because the submission is for an IVD assay, not an AI or machine learning model that typically requires a distinct training phase. The assays' underlying chemistry and calibration are established through development, not a "training set" in the AI sense.
9. How the Ground Truth for the Training Set Was Established
- As there is no "training set" in the context of an AI model, this question is not applicable. The development and initial validation of these assays would have followed standard IVD development procedures, establishing analytical performance characteristics (like linearity, limits of detection, interference, etc.) using reference materials and clinical samples. The current submission is primarily about demonstrating equivalent performance for an extended intended use (POC).
§ 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.