(277 days)
Not Found
No
The device description details a standard immunoluminometric assay (ILMA) based on antibody binding and luminescence measurement. There is no mention of AI, ML, or any computational algorithms beyond basic signal processing and comparison to a standard curve.
No
The device is an immunoluminometric assay (ILMA) used to determine the concentration of PCT (procalcitonin) in human serum and plasma to aid in risk assessment for progression to severe sepsis and septic shock. It is a diagnostic tool, not a therapeutic one.
Yes
The device aids in the risk assessment of critically ill patients for progression to severe sepsis and septic shock by measuring PCT concentration, which is a diagnostic function.
No
The device is an immunoluminometric assay (ILMA) which is a laboratory test involving chemical reagents and a luminometer, indicating it is a hardware-based diagnostic device, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device is used to "determine the concentration of PCT (procalcitonin) in human serum and plasma." This involves testing biological samples (serum and plasma) in vitro (outside the body).
- Device Description: The description details an "immunoluminometric assay (ILMA)" which is a laboratory test method performed in vitro to measure a substance in a biological sample.
- Performance Studies: The performance studies describe analytical and clinical evaluations of the assay's ability to measure PCT in patient samples.
All of these points align with the definition of an In Vitro Diagnostic device, which is used to examine specimens derived from the human body to provide information for the diagnosis, prevention, or treatment of a disease or condition.
N/A
Intended Use / Indications for Use
The B.R.A.H.M.S PCT LIA is an immunoluminometric assay (ILMA) used to determine the concentration of PCT (procalcitonin) in human serum and plasma.
The B.R.A.H.M.S PCT LIA 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
B-R A-H-S PCT LIA is an immunoluminometric assay (ILMA) used to determine the concentration of Procalcitonin (PCT) in human serum and plasma. Two antigen-specific monoclonal antibodies that bind PCT (the antigen) at two different binding sites (the calcitonin and katacalcin segments) are added in excess. One of these antibodies is luminescence labeled (the tracer), and the other is fixed to the inner walls of the tube (coated tube system).
During the course of incubation, both antibodies react with PCT molecules in the sample to form "sandwich complexes". As result the luminescence labeled antibody is bound to the inner surface of the tube. Once the reaction is completed, the excess tracer is completely removed from the tube and discarded.
Then, the amount of residual tracer on the test-tube wall is quantified by measuring the luminescence signal using a suitable luminometer and the B·R·A·H·M·S Basiskit LIA reagents. The intensity of the luminescence signal (RLU) is directly proportional to the PCT concentration in the sample. After a standard curve has been established using standards with known antigen concentrations (calibrated against recombinant intact human PCT), the unknown PCT concentrations in patient serum or plasma samples can then be quantitated by comparison of test values with the curve.
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
The median age of the study population was 59 years (age range, 23-86 years) in Study 1. The mean ages in Study 2 were as follows: SIRS, 51 ± 18 years; sepsis, 51 ± 21 years; severe sepsis, 59 ± 18 years; and septic shock, 54 ± 15 years.
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 NCCLS testing, the analytical sensitivity was determined to be 0.1 ng/ml and the functional assay sensitivity (FAS) was determined to be 0.3 ng/ml. In addition, the total precision ranges from 5.3 - 16.6 % CV and the within run precision ranges from 2.4 - 10 % CV.
High Dose Hook Effect:
A High Dose Hook Effect occurs in immunometrical assay systems and yields erroneously low PCT results in cases of very high PCT concentrations (beyond 900 ng/ml after calibration). Therefore, if a PCT result above the highest standard is obtained, the samples should be diluted with the dilution serum (Zero serum) contained in the assay kit and the test be re-run in order to obtain the correct PCT concentration. PCT concentrations up to 4000 ng/ml do not have an effect on the assignment of the patient to the reference ranges described above.
Interference and Cross Reactivity:
Based on NCCLS testing, the following substances were evaluated in the B·R·A·H·M·S PCT LIA at the concentrations listed and were found not to affect test performance: Bilirubin (conjugated) 40 mg/dl, Triglyceride 634 mg/dl, Hemoglobin 500 mg/dl, Protein (Albumin) 1 g/dl, Imipenem 1.18 mg/ml, Cefotaxim 90 mg/dl, Vancomycin 3.5 mg/ml, Dopamine 13 mg/ml, Noradrenaline 2 µg/ml, Dobutamine 11.2 µg/ml, Heparin 8000 U/l, Furosemide 2 mg/dl, Calcitonin 8 ng/ml, Katacalcin 30 ng/ml, α-CGRP* 30 ng/ml, β-CGRP* 30 ng/ml, Calcitonin Salmon 30 µg/ml, Calcitonin Eel 30 µg/ml.
Method Comparison Summary (2 independent, controlled prospective studies):
-
Study 1: Müller B. et al., Crit. Care Med. 2000; 28(4): 977-983.
- Sample Size: 101 consecutive critically ill patients (55 men, 46 women) in a medical ICU in Switzerland. Median age 59 years (range, 23-86 years).
- Key Results with PCT 0.5: No infection or SIRS/Sepsis (34), Severe Shock/Septic Shock (31)
- Key Results with PCT 2.0: No infection or SIRS/Sepsis (10), Severe Shock/Septic Shock (31)
-
Study 2: Harbarth S. et al., Am. J. Resp. Crit. Care Med. 2001; 164: 396-402.
- Sample Size: 78 consecutive critically ill patients newly admitted to a medical and surgical ICU in Switzerland, including neutropenic and immunosuppressed patients, with suspected diagnosis of infection. Mean ages: SIRS, 51 ± 18 years; sepsis, 51 ± 21 years; severe sepsis, 59 ± 18 years; and septic shock, 54 ± 15 years (57 men, 21 women).
- Key Results with PCT 0.5: SIRS/Sepsis (24), Severe Shock/Septic Shock (46)
- Key Results with PCT 2.0: SIRS/Sepsis (13), Severe Shock/Septic Shock (45)
Interpretation of Results:
- PCT > 2 ng/ml: High risk for progression to severe sepsis and/or septic shock on the first day of ICU admission.
- PCT
§ 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 7
510(K) SUMMARY OF SAFETY AND EFFECTIVENESS
General Information
| Submitted by: | B·R·A·H·M·S Aktiengesellschaft
Neuendorfstrasse 25
D-16761 Hennigsdorf near Berlin
Germany |
|-----------------|-----------------------------------------------------------------------------------------------------|
| | Phone: +49 (0) 3302/883 0 |
| | Fax: +49 (0) 3302/883 100 |
| Contact Person: | Jonas Leichtner |
| | B·R·A·H·M·S Diagnostica, LLC |
| | 6353 Genoa Road |
| | Tracys Landing, MD 20779 USA |
| | Phone: (410) 286 0067 |
| | Fax: (410) 286 0068 |
| | Email: j.leichtner@brahms.de |
| Date Prepared: | December 22, 2004 |
Device Name
| Trade Name: | B·R·A·H·M·S PCT LIA |
|---|---|
| Common Name: | Endotoxin Activity Assay |
| Classification Name: | Assay, Endotoxin Activity, Chemiluminescent |
Predicate Device
| Manufacturer | Product Name | 510(k) No. |
|---|---|---|
| Spectral Diagnostics, Inc. | Endotoxin Activity Assay (Eaa) | |
| Device | K021885 |
Device Description
B-R A-H-S PCT LIA is an immunoluminometric assay (ILMA) used to determine the concentration of Procalcitonin (PCT) in human serum and plasma. Two antigen-specific monoclonal antibodies that bind PCT (the antigen) at two different binding sites (the calcitonin and katacalcin segments) are added in excess. One of these antibodies is luminescence labeled (the tracer), and the other is fixed to the inner walls of the tube (coated tube system).
1
During the course of incubation, both antibodies react with PCT molecules in the sample to form "sandwich complexes". As result the luminescence labeled antibody is bound to the inner surface of the tube. Once the reaction is completed, the excess tracer is completely removed from the tube and discarded.
Then, the amount of residual tracer on the test-tube wall is quantified by measuring the luminescence signal using a suitable luminometer and the B·R·A·H·M·S Basiskit LIA reagents. The intensity of the luminescence signal (RLU) is directly proportional to the PCT concentration in the sample. After a standard curve has been established using standards with known antigen concentrations (calibrated against recombinant intact human PCT), the unknown PCT concentrations in patient serum or plasma samples can then be quantitated by comparison of test values with the curve.
| Reagent | Quantity for 100 det. | Contents |
|---|---|---|
| A | 1 vial lyophilized | Tracer, luminescence labeled (acridinium derivate) |
| anti-PCT antibody (monoclonal, mouse), blue colored | ||
| solution, 29 ml after reconstitution with buffer B. | ||
| B | 1 x 29 ml vial | Buffer, for reconstituting tracer A, ready for use. |
| C | 2 x 50 tubes | Coated tubes (test tubes), coated with anti-PCT |
| antibody (monoclonal, mouse), ready for use. | ||
| G | 1 x 4 ml vial | Zero serum (human serum), for reconstituting the |
| standards resp. calibrators and controls, ready for use. | ||
| W | 2 x 11 ml vials | B·R·A·H·M·S Washing solution universal, concentrate, |
| 11 ml. | ||
| S1, S2/C1, | ||
| S3, S4/C2, | ||
| S5, S6 | 6 vials lyophilized | PCT standards (recombinant), reconstitute each with |
| 0.25 ml zero serum G before use. Concentration | ||
| ranges: 0.08 (def.); 0.3-0.7; 1.5-2.5; 16-24; 160- | ||
| 240; 400 - 600 ng/ml. Precise concentrations see | ||
| leaflet enclosed. | ||
| K1, K2 | 2 vials lyophilized | PCT controls 1 and 2, reconstitute each with 0.25 ml |
| zero serum G before use. Concentrations see leaflet | ||
| enclosed. |
The contents of the B.R.A.H.M.S.PCT LIA kit are:
Intended Use
The B.R.A.H.M.S PCT LIA is an immunoluminometric assay (ILMA) used to determine the concentration of PCT (procalcitonin) in human serum and plasma.
The B.R.A.H.M.S PCT LIA 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.
2
Technological Comparison
The B.R.A.H.M.S PCT LIA immunoassay kit is similar to the Spectral Diagnostics Endotoxin Activity Assay (K021885) in the indications for use regarding risk assessment of patients for progression to severe sepsis in conjunction with other clinical information. The B R A H M S PCT LIA test differs from the Spectral Diagnostics Endotoxin Activity Assay in assay principle, using solid phase, in performance and result in the B-R-A-H-M-S PCT LIA assay, two antigen-specific monoclonal antibodies bind PCT (the antigen) at two different binding sites (the calcitonin and katacalcin segments). The intensity of the luminescence signal (RLU) is directly proportional to the PCT concentration in the sample. The Spectral Diagnostics Endotoxin Activity Assay measures the endotoxin activity in whole blood by the priming of host neutrophil respiratory burst activity via complement opsonized LPS-IgM immune complexes. The luminol reaction in the presence of immune complexes emits light energy. This light energy is measured and recorded by a luminometer. The Relative Light Units (RLU) measured by the instrument are converted by calculation into an Endotoxin Activity (EA) value which is reported as a percentage proportion of the total possible activity (0-1.0).
Performance Summary
Precision and Reproducibility
Based on NCCLS testing, the analytical sensitivity was determined to be 0.1 ng/ml and the functional assay sensitivity (FAS) was determined to be 0.3 ng/ml. In addition, the total precision ranges from 5.3 - 16.6 % CV and the within run precision ranges from 2.4 - 10 % CV.
High Dose Hook Effect
A High Dose Hook Effect occurs in immunometrical assay systems and yields erroneously low PCT results in cases of very high PCT concentrations (beyond 900 ng/ml after calibration).
Therefore, if a PCT result above the highest standard is obtained, the samples should be diluted with the dilution serum (Zero serum) contained in the assay kit and the test be re-run in order to obtain the correct PCT concentration. should PCT concentrations up to 4000 ng/ml do not have an effect on the assignment of the patient to the reference ranges described above.
3
Interference and Cross Reactivity
Based on NCCLS testing, the following substances were evaluated in the B·R·A·H·M·S PCT LIA at the concentrations listed and were found not to affect test performance.
| Interfering Substance | Non-Interfering
Concentration |
|------------------------|----------------------------------|
| Bilirubin (conjugated) | 40 mg/dl |
| Triglyceride | 634 mg/dl |
| Hemoglobin | 500 mg/dl |
| Protein (Albumin) | 1 g/dl |
| Imipenem | 1.18 mg/ml |
| Cefotaxim | 90 mg/dl |
| Vancomycin | 3.5 mg/ml |
| Dopamine | 13 mg/dl |
| Noradrenaline | 2 µg/ml |
| Dobutamine | 11.2 µg/ml |
| Heparin | 8000 U/l |
| Furosemide | 2 mg/dl |
| Calcitonin | 8 ng/ml |
| Katacalcin | 30 ng/ml |
| a-CGRP* | 30 ng/ml |
| β-CGRP* | 30 ng/ml |
| Calcitonin Salmon | 30 µg/ml |
| Calcitonin Eel | 30 µg/ml |
*Calcitonin Gene Related Peptide
4
Method Comparison Summary
The clinical data for the B·R·A·H·M·S PCT LIA were obtained in two independent, controlled prospective studies performed in the ICUs of academic hospital settings
The data from the two studies is summarized in the following graph and tables. The 2x2 tables below show the PCT results for SIRS and Sepsis compared to Severe Sepsis and Septic Shock on the first day of ICU admission.
-
Study 1: Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit Müller B. et al., Crit. Care Med. 2000; 28(4): 977-983.
101 consecutive critically ill patients of representative population of Patients: unselected, well-defined patients in a medical ICU in the Switzerland. The median age of the study population was 59 years (age range, 23-86 years). There were 55 men and 46 women in this study. -
Study 2: Diagnostic Value of Procalcitonin, Interleukin-6 and Interleukin-8 in Critically III Patients admitted with suspected Sepsis Harbarth S. et al., Am. J. Resp. Crit. Care Med. 2001; 164: 396-402.
-
78 consecutive critically ill patients newly admitted to a medical and surgical Patients: ICU in the Switzerland, including also neutropenic and immunosuppressed patients, with suspected diagnosis of infection. Patients had to fulfill at least 2 criteria of SIRS. Source of infection was the respiratory tract, intra-abdominal space and bloodstream infection. The mean ages were as follows: SIRS, 51 ± 18 years; sepsis, 51 ± 21 years; severe sepsis, 59 ± 18 years; and septic shock, 54 ± 15 years. There were 57 men and 21 women in this study.
| PCT Result
Study 1 | No infection or
SIRS/Sepsis | Severe Shock/
Septic Shock | Totals |
|-----------------------|--------------------------------|-------------------------------|--------|
| PCT 0.5 | 34 | 31 | 65 |
| Totals | 70 | 31 | 101 |
| PCT Result
Study 2 | SIRS/Sepsis | Severe Shock/
Septic Shock | Totals |
| PCT 0.5 | 24 | 46 | 70 |
| Totals | 32 | 46 | 78 |
PCT by no infection or SIRS, Sepsis versus Severe Sepsis or Septic Shock Cut Off 0.5 ng/ml
5
| PCT Result
Study 1 | No infection or
SIRS/Sepsis | Severe Shock/
Septic Shock | Totals |
|-----------------------|--------------------------------|-------------------------------|--------|
| PCT 2.0 | 10 | 31 | 41 |
| Totals | 70 | 31 | 101 |
| PCT Result
Study 2 | SIRS/Sepsis | Severe Shock/
Septic Shock | Totals |
| PCT 2.0 | 13 | 45 | 58 |
| Totals | 32 | 46 | 78 |
PCT by no infection or SIRS, Sepsis versus Severe Sepsis or Septic Shock Cut Off 2.0 ng/ml
The 4 box and whisker diagrams below summarize the individual PCT results of the 4 subgroups of patients on the first day of ICU admission.
Image /page/5/Figure/6 description: This image is a box plot comparing PCT levels in different disease conditions. The y-axis represents PCT levels in ng/ml on a logarithmic scale, ranging from 0.01 to 500. The x-axis shows the disease conditions: no infection or SIRS (n=66), Sepsis (n=36), Severe Sepsis (n=36), and Septic Shock (n=41). The plot shows an increase in PCT levels with increasing severity of the disease condition.
Summary of 2 studies: PCT by disease condition on the 1st day of admission
6
Interpretation of Results
The data from the two studies supports 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.
PCT Trade/Device Name: B.R.A.H.M.S PCT LIA Regulation Number: 21 CFR 866.3610 Regulation Name: Endotoxin Assay Regulatory Class: Class II Product Code: NTM Dated: December 1, 2004 Received: December 1, 2004
Dear Mr. Leichtner:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the 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 devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing 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 can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
8
Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification 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, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International 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.
Sale, a For
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
9
INDICATIONS FOR USE
K040887 510(k) Number (if known):
B·R·A·H·M·S PCT LIA Device Name:
B.R.A.H.M.S Aktiengesellschaft Sponsor Name:
Indications for Use:
The B.R.A.H.M.S.PCT LIA is an immunoluminometric assay (ILMA) used to determine the concentration of PCT (procalcitonin) in human serum and plasma.
The B.R.A.H.M.S PCT LIA 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.
Prescription Use X (21 CFR 801 Subpart D)
And/Or
Over-The-Counter Use | (21 CFR 807 Subpart C)
Do Not Write Below This Line – Continue on Another Page if Needed
Concurrence of CDRH, Office of Device Evaluation (ODE)
Luddi V. Poole
ision Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K040887