(36 days)
The Stratus® CS Acute Care™ BhCG method is an in vitro diagnostic test for the quantitative measurement of the total beta subunit, vis, both the intact hCG dimer and the free B subunt, of the human chorionic gonadotropin hormone in heparimized plasma. BhCG is used for the carly detection of pregnancy. 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™ (fhCG Calibrator (fhCG CalPak) is an in vitro diagnostic product intended to be used for calibration of the Stratus@ ('S Acute Care™ fshCG method.
The Stratus® CS Acute Care™ (ShCG Dilution Pak (BhCG DilPak) is an in wirro diagnostic product intended to be used in conjunction with the Acute Care™ [ShCG TestPak for the measurement of samples with clevated levels of (BhCG).
The Stratus® CS Acute Care™ NT-proBNP method is an in vitro diagnostic test for the quantitative measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) in heparinized plasma. In individuals suspected of having congestive heart failure (CHF), measurements of NT-proBNP are used as an aid in the diagnosis and assessment of severity. The test is further indicated for the risk stratification of patients with acute coronary syndrome and heart failure. This method is for use by trained health care professionals in the clinical laboratory and point of eare (POC) settings.
The Stratus® CS Acute Care™ NT-proBNP Calibrator (pBNP CalPak) is an in virro diagnostic product intended to be used for calibration of the Stratus® CS Acute Care™ NT-proBNP (pBNP) method.
The Stratus® CS Acute Carc™ NT-proBNP Dilution Pak (pBNP DilPak) is an in virro diagnostic product intended to be used in conjunction with the Acute Care™ (pBNP TestPak for the measurement of samples with elevated levels of NT-proBNP .
The Stratus® CS Acute Care™ BhCG method is a solid phase, two-site sandwich fluorometric immunoassay based upon Radial Partition Immunoassay (RPIA) technology. In this procedure, dendrimer linked monoclonal filt G antibody is added to the center portion of a square piece of glass fiber paper in the BhCG TestPak. The dendrimer binds clectrostatically to the glass fibers and immobilizes the capture antibody to the paper. Sample is then added, whereupon fillCG reacts with the immobilized antibody. After a short incubation, a conjugate, consisting of enzyme-laheled (alkaline phosphatase) monoclonal antibody directed against a distinct antigenic site on the ßhCG molecule, is pipetted onto the reaction zone of the paper. During this scoond incubation period, the unbound, labeled antibody is radially eluted with a wash solution. By including substrate (4methylumbeliferyl phosphate) for the enzyme within the wash solution, initiation of enzyme activity occurs simultancously with the wash. The enzymatic rate of the bound fraction increases directly with the concentration of BhCG in the sample.
Utilization of two monoclonal antibodies which are specific for distinct antigenie sites on the B subunit of hCG allows the assay to measure the total fihCG in the sample, vis, both the intact hCG dimer and the free B subunit. Concentration 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™ NT-proBNP method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology. In this procedure, dendrimer linked polyclonal antibody is added to the center portion of a square piece of glass fiber paper in the pBNP TestPak. This antibody recognizes a distinct antigenic site on the NT-proBNP 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 polyclonal antibody directed against a second distinct antigenic site on the NT-proBNP molecule is pipetted onto the reaction zone of the paper. During this second incubation period, enzyme-labeled antibody reacts with the bound NT-proBNP, forming an antibody-antigen-labeled antibody sandwich. The unbound labeled antibody is later cluted 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 NT-proBNP 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.
This summary describes the acceptance criteria and performance of the Dade Behring Stratus® CS Acute Care™ BhCG and NT-proBNP assays, based on the provided 510(k) summary.
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state quantitative acceptance criteria in terms of specific thresholds for precision and accuracy. Instead, the acceptance criterion for both the BhCG and NT-proBNP assays is based on demonstrating substantial equivalence to their respective legally marketed predicate devices, especially regarding:
- Principle of operation and performance.
- Comparability of precision and accuracy data generated by "non-laboratory" (point-of-care, POC) personnel to "laboratory" personnel, supporting the addition of POC to the intended use.
Reported Device Performance:
| Feature/Metric | BhCG TestPak, CalPak, DilPak Performance (vs. K003696 Predicate) | NT-proBNP TestPak, CalPak, DilPak Performance (vs. K043476 Predicate) |
|---|---|---|
| Substantial Equivalence | Demonstrated in principle of operation and performance. | Demonstrated in principle of operation and performance. |
| Formulation/Design Changes | None reported; identical to predicate. | None reported; identical to predicate. |
| Manufacturing Processes | Same as predicate. | Same as predicate. |
| Labeling Changes | Reflects new intended use (POC), supporting data, and new name. | Reflects new intended use (POC), supporting data, and new name. |
| Precision & Accuracy | Data generated by "non-laboratory" personnel is comparable to "laboratory" personnel. | Data generated by "non-laboratory" personnel is comparable to "laboratory" personnel. |
| Intended Use Expansion | Inclusion of Point-of-Care (POC) settings. | Inclusion of Point-of-Care (POC) settings. |
2. Sample Size for the Test Set and Data Provenance:
- Sample Size: The document does not specify the exact number of samples used in the "method comparison and precision analyses." It only states that these analyses were performed at three different locations.
- Data Provenance: The studies were conducted at three different locations:
- One clinical laboratory (LAB)
- One Emergency Department (ED)
- One Cardiac Care Unit (CCU)
The document indicates the data was generated through "method comparison and precision analyses," which are typically considered prospective data collection. The countries of origin are not specified but implied to be within the scope of the manufacturer's (Dade Behring Inc., Newark, DE, USA) operations.
3. Number of Experts and their Qualifications for Ground Truth:
- The document mentions "non-laboratory" personnel (ED or CCU operators) and "laboratory" personnel who generated the precision and accuracy data.
- It does not specify the number of individual "experts" used to establish ground truth or their specific qualifications (e.g., years of experience, specific medical board certifications). The ground truth for these assays would typically be the reference method results from a clinical laboratory or another established method.
4. Adjudication Method for the Test Set:
- The document does not describe an adjudication method for establishing ground truth, such as 2+1 or 3+1 consensus. The evaluation focuses on the device's performance (precision, accuracy, method comparison) against established laboratory methods, rather than expert consensus on diagnostic images or clinical assessments.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, an MRMC comparative effectiveness study was not done in the context of this 510(k) submission. This type of study is more common for diagnostic imaging AI systems where human readers interpret cases with and without AI assistance. This submission is for an in-vitro diagnostic assay for quantitative measurement, which doesn't involve human 'readers' interpreting 'cases' in the same way. The evaluation focused on the comparability of results generated by different types of operators (lab vs. non-lab) using the device, not on human cognitive performance with and without AI.
6. Standalone (Algorithm Only) Performance:
- This is an in-vitro diagnostic (IVD) device, specifically an immunoassay for quantitative measurement of biomarkers. The "device" itself (Stratus® CS analyzer and TestPaks) performs the measurement and analysis. Therefore, the performance described is already the standalone performance of the algorithm/device system without human-in-the-loop decision-making in the same manner as an AI imaging algorithm might require. Human operators perform the test and interpret the numerical result, but the measurement is device-driven.
7. Type of Ground Truth Used:
- The ground truth for evaluating the device's performance would have been established by reference laboratory methods for the BhCG and NT-proBNP analytes. The "method comparison" arm of the study indicates that results from the new device were compared against results from other established methods, typically the predicate device or a gold standard laboratory method.
- For the purpose of comparing "non-laboratory" personnel results to "laboratory" personnel results, the ground truth for performance metrics (precision and accuracy) would be derived from the known concentrations of control materials or the established values from the predicate device/reference method when run by trained laboratory professionals.
8. Sample Size for the Training Set:
- The document does not mention a separate "training set" or its sample size. This is consistent with the nature of the device. This 510(k) submission is for modifications to existing (predicate) IVD assays to expand their intended use to point-of-care settings. These are immunoassay-based systems, not machine learning algorithms that require a distinct training phase. The "development" of the assay itself would have involved extensive analytical validation, but this specific submission focuses on demonstrating equivalency for the expanded use.
9. How Ground Truth for the Training Set Was Established:
- As there is no distinct "training set" in the context of this 510(k) submission for an immunoassay, the establishment of ground truth for a training set is not applicable. The device's performance is validated against established analytical methods and clinical correlations, where "ground truth" refers to the accurate measurement of the analyte by a highly reliable method or the clinical outcome/diagnosis being correlated.
§ 862.1155 Human chorionic gonadotropin (HCG) test system.
(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.