(424 days)
Not Found
No
The description focuses on the immunoassay technology and automated system for detecting PCT, with no mention of AI or ML algorithms for data analysis or interpretation.
No.
The device is used for diagnostic purposes by detecting PCT (procalcitonin) to aid in the risk assessment of critically ill patients developing severe sepsis and septic shock, not for treatment.
Yes
Explanation: The device is designed for automated detection of PCT in human samples to aid in the risk assessment of critically ill patients for progression to severe sepsis and septic shock, which is a diagnostic purpose.
No
The device description clearly outlines a physical analyzer (B·R·A·H·M·S KRYPTOR® analyzer) that performs a laboratory assay using specific reagents and a laser-based measurement principle. This involves significant hardware components and is not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device is designed for the "automated detection of PCT (procalcitonin) in human serum or plasma... samples." This involves testing samples taken from the human body in vitro (outside the body).
- Purpose: The device is intended "to aid in the risk assessment of critically ill patients... for progression to severe sepsis and septic shock." This is a diagnostic purpose, providing information to help clinicians make decisions about patient care.
- Device Description: The description details an "assay" and an "analyzer" that perform measurements on biological samples using chemical and physical principles (immunofluorescence, TRACE technology). This is characteristic of an IVD.
- Performance Studies: The document includes performance studies like "Precision and Reproducibility," "Interference and Cross Reactivity," and "Method Comparison Summary," which are standard evaluations for IVD devices to demonstrate their analytical performance.
- Predicate Device: The mention of a "Predicate Device" (K040887; B·R·A·H·M·S PCT LIA) is common in regulatory submissions for IVDs, where a new device is compared to a previously cleared device.
All these elements strongly indicate that the B.R.A.H.M.S PCT sensitive KRYPTOR® is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
NTM
Device Description
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.
The contents of the B.R.A.H.M.S.PCT sensitive KRYPTOR® assay are:
Reagent: Cryptate Conjugate, 1 bottle lyophilized, Content: Cryptate conjugate, cryptate labeled, anti-PCT antibody (polyclonal, sheep), 3.2 ml after reconstitution with KRYPTOR® Solution 1 and KRYPTOR® Solution 2
Reagent: XL665 Conjugate, 1 bottle lyophilized, Content: XL665 conjugate, XL665 labeled, anti-PCT antibody (monoclonal, mouse), 3.95 ml after reconstitution with KRYPTOR® Solution 1 and KRYPTOR® Solution 2
Reagent: Diluent, 1 bottle, Content: Defibrinated human plasma, for diluting samples above 50 ng/ml, ready to use
Controls, Calibrator, and Consumables are provided separate from the reagent unit.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Critically ill patients on their first day of ICU admission.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision and Reproducibility:
Based on CLSI testing, the analytical sensitivity was determined to be 0.02 ng/ml and the functional assay sensitivity (FAS) was determined to be 0.06 ng/ml. In addition, the total precision ranges from 3.2 - 13.4 % CV and the within run precision ranges from 1.0 - 13.6 % CV.
High Dose Hook Effect:
The B.R.A.H.M.S PCT sensitive KRYPTOR® assay is homogenous, and does not require separation or washing steps. It is thus possible to obtain data without interrupting the immunological reaction. High concentration samples (> 50 ng/ml) are detected in the first few seconds of incubation and may be diluted by the appropriate dilution factor, then re-assayed automatically. This process allows for sample measurements greater than 50 ng/ml up to 5000 ng/ml.
Interference and Cross Reactivity:
Based on CLSI testing, the substances evaluated with the B.R.A.H.M.S PCT sensitive KRYPTOR® assay were found not to affect the test performance at concentrations reasonably and consistently found in clinical situations. The substances included the following:
- bilirubin,
- hemoglobin,
- triglycerides,
- albumin,
- substances that share amino acid sequences with procalcitonin,
- drugs which are typically used for septic patients in intensive care units, and
- drugs which may be commonly used in subjects at greater risk of developing community acquired pneumonia than the general population, such as in asthma and/or COPD patients.
Method Comparison Summary:
A correlation study was performed in accordance with CLSI guideline EP9-A, "Method Comparison and Bias Estimation Using Patient Samples" between the B-R-A-H-M-S PCT sensitive KRYPTOR® assay and the B.R.A.H.M.S.PCT LIA assay. There were 184 samples from three (3) sites, which had B·R·A·H·M·S PCT LIA measurements of 0.3 ng/ml (the functional assay sensitivity of B·R·A·H·M·S PCT LIA) or higher and/or B.R.A.H.M.S. PCT sensitive KRYPTOR® measurements of 0.06 ng/ml (the functional assay sensitivity of B·R·A·H·M·S PCT sensitive KRYPTOR®) or higher. Passing-Bablock analysis shows a nearly perfect correlation of the B·R·A·H·M·S PCT sensitive KRYPTOR® assay and B.R.A.H.M:S PCT LIA assay, as demonstrated in the correlation graph. The equation of the regression line is y = 0.95x + 0.03, and the R-squared value is 0.98.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Analytical sensitivity: 0.02 ng/ml
Functional assay sensitivity (FAS): 0.06 ng/ml
Total precision: 3.2 - 13.4 % CV
Within run precision: 1.0 - 13.6 % CV
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
510(k) Premarket Notification
Page 1 of 6
510(k) SUMMARY
General Information
MAR 3 1 2008
| Submitted by: | B·R·A·H·M·S Aktiengesellschaft
Neuendorfstrasse 25
D-16761 Henningsdorf near Berlin
Germany |
|-----------------|------------------------------------------------------------------------------------------------------|
| Contact Person: | Jonas Leichtner
B·R·A·H·M·S USA, Inc.
2568A Riva Road, Suite 207
Annapolis, MD 21401 |
Phone: (410) 897 9960 Fax: (410) 972 2452 Email: j.leichtner@brahms-usa.com
| Date Prepared: | February 14, 2008 |
|---|---|
| ---------------- | ------------------- |
Device Name
| Trade Name: | B·R·A·H·M·S PCT sensitive KRYPTOR® Test System |
|---|---|
| Common Name: | Inflammatory Response Marker |
| Classification Name: | Antigen, Inflammatory Response Marker, Sepsis, |
| 21 CFR 866.3210 |
Predicate Device
| Manufacturer | Product Name | 510(k) No. |
|---|---|---|
| B·R·A·H·M·S Aktiengesellschaft | B·R·A·H·M·S PCT LIA | K040887 |
Device Description
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.
1
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.
| Reagent | Quantity for 50
determinations | Content |
|-----------------------|-----------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Cryptate
Conjugate | 1 bottle
lyophilized | Cryptate conjugate, cryptate labeled,
anti-PCT antibody (polyclonal, sheep),
3.2 ml after reconstitution with
KRYPTOR® Solution 1 and
KRYPTOR® Solution 2 |
| XL665
Conjugate | 1 bottle
lyophilized | XL665 conjugate, XL665 labeled,
anti-PCT antibody (monoclonal,
mouse), 3.95 ml after reconstitution
with KRYPTOR® Solution 1 and
KRYPTOR® Solution 2 |
| Diluent | 1 bottle | Defibrinated human plasma, for
diluting samples above 50 ng/ml,
ready to use |
The contents of the B.R.A.H.M.S.PCT sensitive KRYPTOR® assay are:
Controls, Calibrator, and Consumables are provided separate from the reagent unit.
2
510(k) Premarket Notification
Intended Use
The B·R·A·M·S PCT sensitive KRYPTOR® is an immunofluorescent assay used to determine the concentration of PCT (procalcitonin) in human serum and plasma. 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.
Technological Comparison
The B.R.A.H.M.S.PCT sensitive KRYPTOR® and the B.R.A.H.M.S.PCT LIA have similar indications for use, are quantitative assays, and are used to determine the concentration of PCT in human serum and plasma The devices utilize different technologies and instruments to obtain the results. TRACE® technology (immunofluorescence) is used with the B.R.A.H.M.S KRYPTOR® analyzer and chemiluminescence is used with a luminometer for B.R.A.H.M.S.PCT LIA. Each device uses 2 antibodies, one of which is the same for both devices. The monoclonal antibody used in both devices binds to Katacalcin. For the second antibody, the B-R-A-H-S PCT sensitive KRYPTOR® uses a polyclonal antibody, which is directed against Calcitonin. The B-R-A-H-M-S PCT LIA uses a monoclonal antibody directed against Calcitonin instead of a polyclonal antibody. Although the antibodies directed against Calcitonin come from different origin they bind to the same epitopes. Therefore they will bind to the same PCT molecule.
Performance Summary
Precision and Reproducibility
Based on CLSI testing, the analytical sensitivity was determined to be 0.02 ng/ml and the functional assay sensitivity (FAS) was determined to be 0.06 ng/ml. In addition, the total precision ranges from 3.2 - 13.4 % CV and the within run precision ranges from 1.0 - 13.6 % CV.
High Dose Hook Effect
The B.R.A.H.M.S PCT sensitive KRYPTOR® assay is homogenous, and does not require separation or washing steps. It is thus possible to obtain data without interrupting the immunological reaction. High concentration samples (> 50 ng/ml) are detected in the first few seconds of incubation and may be diluted by the appropriate dilution factor, then re-assayed automatically. This process allows for sample measurements greater than 50 ng/ml up to 5000 ng/ml.
3
Interference and Cross Reactivity
Based on CLSI testing, the substances evaluated with the B.R.A.H.M.S PCT sensitive KRYPTOR® assay were found not to affect the test performance at concentrations reasonably and consistently found in clinical situations. The substances included the following
- bilirubin, .
- hemoglobin, .
- triglycerides, .
- albumin, .
- substances that share amino acid sequences with procalcitonin, ●
- drugs which are typically used for septic patients in intensive care units, and .
- drugs which may be commonly used in subjects at greater risk of developing . community acquired pneumonia than the general population, such as in asthma and/or COPD patients.
Method Comparison Summary
The B·R·A·H·M·S PCT sensitive KRYPTOR® and the B·R·A·H·M·S PCT LIA both detect procalcitonin (PCT) in human serum or plasma. A correlation study was performed in accordance with CLSI guideline EP9-A, "Method Comparison and Bias Estimation Using Patient Samples" between the B-R-A-H-M-S PCT sensitive KRYPTOR® assay and the B.R.A.H.M.S.PCT LIA assay. There were 184 samples from three (3) sites, which had B·R·A·H·M·S PCT LIA measurements of 0.3 ng/ml (the functional assay sensitivity of B·R·A·H·M·S PCT LIA) or higher and/or B.R.A.H.M.S. PCT sensitive KRYPTOR® measurements of 0.06 ng/ml (the functional assay sensitivity of B·R·A·H·M·S PCT sensitive KRYPTOR®) or higher. Passing-Bablock analysis shows a nearly perfect correlation of the B·R·A·H·M·S PCT sensitive KRYPTOR® assay and B.R.A.H.M:S PCT LIA assay, as demonstrated in the correlation graph below.
4
Image /page/4/Figure/3 description: This image is a scatter plot comparing two different methods of measuring PCT. The x-axis represents the B-R-A-H-M-S PCT LIA method, while the y-axis represents the B-R-A-H-M-S PCT sensitive KRYPTOR method. The plot shows a strong positive correlation between the two methods, with most of the data points clustered around a regression line. The equation of the regression line is y = 0.95x + 0.03, and the R-squared value is 0.98.
Interpretation of Results
The B·R·A·H·M·S PCT sensitive KRYPTOR® is intended 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.
SIRS, Sepsis, Severe Sepsis, and Septic Shock were categorized according to the criteria of the consensus conference of the American College of Chest Physicians/Society of Critical Care Medicine.
PCT should always be interpreted in the clinical context of the patient. Therefore, clinicians should use the PCT results in conjunction with other laboratory findings and clinical signs of the patient.
Data support the following interpretative risk assessment criteria:
PCT > 2 ng/ml
PCT levels above 2.0 ng/ml on the first day of ICU admission represent a high risk for progression to severe sepsis and/or septic shock.