(424 days)
The B.R.A.H.M.S PCT sensitive KRYPTOR® is designed for automated detection of PCT (procalcitonin) in human serum or plasma (EDTA, heparin) samples by the immunofluorescent B·R·A·H·M·S PCT sensitive KRYPTOR® assay.
The B·R·A·H·M·S PCT sensitive KRYPTOR® is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock.
The B-R-A-H-M-S PCT sensitive KRYPTOR® assay is a homogeneous sandwich immunoassay for detection of PCT in human serum or plasma. The BrR.A.H.M.S KRYPTOR® analyzer is a fully automated system. The B·R·A·H·M·S KRYPTOR® analyzer is a closed system and can only operate utilizing special reagents provided by B.R.A.H.M.S Aktiengesellschaft. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE®) technology, which measures the signal that is emitted from an immunocomplex with time delay.
The basis of the TRACE® technology is a non-radiative energy transfer from a donor [a cage-like structure with a europium ion in the center (cryptate)] to an acceptor (XL 665). The proximity of donor (cryptate) and acceptor (XL 665) in a formed immunocomplex and the spectral overlap between donor emission and acceptor absorption spectra on the one hand intensifies the fluorescent signal and on the other hand extends the life span of the acceptor signal, allowing for the measurement of temporally delayed fluorescence.
After the sample to be measured has been excited with a nitrogen laser at 337 nm, the donor (cryptate) emits a long-life fluorescent signal in the milli-second range at 620 nm, while the acceptor (XL 665) generates a short-life signal in the range of nanoseconds at 665 nm. When both components are bound in an immunocomplex, both the signal amplification and the prolonged life span of the acceptor signal occur at 665 nm, and the life is in the microsecond range. This delayed acceptor signal is proportional to the concentration of the analyte to be measured.
The specific fluorescence which is proportional to the antigen concentration is obtained through a double selection: spectral (separation depending on wave-length) and temporal (time resolved measurement). This enables an exclusive measurement of the signal emitted by the immunological complex and the ratio between the two wave-lengths (665/620) allows a real-time correction of the variations in optic transmission from the medium.
Here's a summary of the acceptance criteria and the study details for the B·R·A·H·M·S PCT sensitive KRYPTOR® Test System, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Metric | Acceptance Criteria (Not explicitly stated as such, but inferred from reporting) | Reported Device Performance (B·R·A·H·M·S PCT sensitive KRYPTOR®) |
|---|---|---|---|
| Analytical Sensitivity | Limit of Detection (LOD) | Not explicitly stated as an AC; implied to be low. | 0.02 ng/ml |
| Functional Assay Sensitivity (FAS) | Lowest concentration with acceptable precision | Not explicitly stated as an AC; implied to be low. | 0.06 ng/ml |
| Precision | Total Precision (%CV) | Not explicitly stated as an AC; implied to be within acceptable clinical ranges. | 3.2 - 13.4 % CV |
| Within-Run Precision (%CV) | Not explicitly stated as an AC; implied to be within acceptable clinical ranges. | 1.0 - 13.6 % CV | |
| High Dose Hook Effect | Ability to detect high concentrations and allow dilution | Not explicitly stated as an AC; implied to handle high values. | Detects > 50 ng/ml up to 5000 ng/ml (with automatic re-assay after dilution) |
| Interference | No effect on performance from common interfering substances | Not explicitly stated as an AC; implied to demonstrate non-interference. | No effect found from bilirubin, hemoglobin, triglycerides, albumin, PCT-similar amino acid sequences, and common drugs for septic/COPD patients. |
| Method Comparison (vs. Predicate Device) | Correlation with predicate device (B·R·A·H·M·S PCT LIA) | "Nearly perfect correlation" (implied strong statistical correlation) | Passing-Bablock: y = 0.95x + 0.03, R-squared = 0.98 |
| Expected Values (Normal Subjects) | PCT concentration in healthy individuals | Not explicitly stated as an AC; implied to be low. | 2 ng/ml indicates high risk) implicitly relies on established clinical consensus criteria for severe sepsis and septic shock (American College of Chest Physicians/Society of Critical Care Medicine) as the clinical ground truth against which the PCT values are correlated to assess risk. |
8. Sample Size for the Training Set
- Not explicitly provided/applicable in the same way: For in vitro diagnostic assays, especially those based on established immunofluorescence technology like TRACE®, the concept of a "training set" for an algorithm in the machine learning sense is not directly applicable. The assay formulation, antibody selection, and calibration are developed through R&D, not typically "trained" on a large dataset in the way an AI algorithm would be. The document describes the device's components and underlying technology rather than a data-driven training process.
9. How the Ground Truth for the Training Set Was Established
- Not explicitly provided/applicable: As mentioned above, the assay's development isn't described in terms of a "training set" and "ground truth" in an AI/machine learning context. The "ground truth" in assay development is typically established through rigorous analytical verification and validation against known standards, spiked samples, and comparison with reference methods or clinically characterized samples during the research and development phases of the assay itself. The given document focuses on the validation of the finalized device.
§ 866.3210 Endotoxin assay.
(a)
Identification. An endotoxin assay is a device that uses serological techniques in whole blood. The device is intended for use in conjunction with other laboratory findings and clinical assessment of the patient to aid in the risk assessment of critically ill patients for progression to severe sepsis.(b)
Classification. Class II (special controls). The special control for this device is the FDA guidance entitled “Class II Special Controls Guidance Document: Endotoxin Assay.” See § 866.1(e) for the availability of this guidance document.