(207 days)
Not Found
No
The device description and performance studies focus on a homogeneous sandwich chemiluminescent immunoassay and standard analytical performance metrics. There is no mention of AI or ML in the text.
No.
This device is an in vitro diagnostic test for measuring procalcitonin levels, used as an aid in diagnosis, risk assessment, and decision-making on antibiotic therapy. It does not directly provide therapy or treatment.
Yes
The 'Intended Use / Indications for Use' section explicitly states that the assay "is an in vitro diagnostic test." It also describes its use as "an aid in" risk assessment and decision-making for antibiotic therapy, which are diagnostic purposes.
No
The device is an in vitro diagnostic test that measures procalcitonin in human samples using a chemistry system and reagents, which are physical components, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
The intended use statement explicitly states: "The Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay is an in vitro diagnostic test for the quantitative measurement of procalcitonin in human serum and plasma..."
This clearly identifies the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay is an in vitro diagnostic test for the quantitative measurement of procalcitonin in human serum and plasma (lithium heparin, K2EDTA, and K3EDTA) using the Dimension® EXL™ integrated chemistry system with LOCI® Module.
The Dimension EXL LOCI® BRAHMS PCT assay is intended for use in conjunction with other laboratory findings and clinical assessments, as an aid in:
· The risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock.
• Assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission using percentage change in PCT levels over time.
· Decision making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) - defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) - in an inpatient setting or an emergency department.
· Decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.
Product codes (comma separated list FDA assigned to the subject device)
PRI, PMT
Device Description
The Dimension EXL LOCI BRAHMS PCT assay is a homogeneous sandwich chemiluminescent immunoassay based on LOCI technology. The LOCI reagents include two synthetic bead reagents and one biotinylated anti-procalcitonin (anti-PCT) monoclonal antibody. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitizer dye. The second bead reagent (Chemibeads) is coated with two anti-PCT monoclonal antibodies and contains chemiluminescent dye. Sample is incubated with biotinylated antibody and Chemibeads to form bead-PCT-biotinylated antibody sandwiches. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the procalcitonin (PCT) concentration in the sample.
The Dimension EXL LOCI BRAHMS PCT assay is comprised of the following reagents:
Component: Biotinylated Antibody Well 1 (W1) and Well 2 (W2) Reagent 1 (R1); Volume: 1.0 mL; Ingredients: PCT Biotinylated Antibody-mouse monoclonal (3.5 µg/mL), bovine serum albumin, bovine gamma globulin, goat serum, mouse IgG, rat IgG, sodium azide (10% bias). Limitations statements for these substances are included in the Instructions For Use.
- Cross-Reactivity: Calcitonin (human, eel, salmon), Katacalcin (human), α-CGRP, and β-CGRP showed negligible cross-reactivity ( 50.00 ng/mL).
13.8 Sample Carryover
Study Type: Sample carryover study.
Sample Size: 11 separate runs, each with a pattern of high (1068.88 ng/mL PCT) and low (≤0.10 ng/mL PCT) samples.
Key Results: No sample carryover was observed (calculated to be 0.00 ng/mL).
13.9 Method Comparison
Study Type: Method comparison study designed in accordance with CLSI EP09c-ED3, comparing candidate device to predicate device.
Sample Size: 595 native human serum samples (0.05-1000.00 ng/mL).
Key Results:
- Measuring Interval (0.05-50.00 ng/mL, n=555):
- Lot FB1218: Slope = 1.07 (95% CI: 1.05-1.10), Intercept = -0.01 ng/mL, Correlation coefficient (r) = 0.958.
- Lot FC1218: Slope = 1.04 (95% CI: 1.02-1.07), Intercept = 0.00 ng/mL, Correlation coefficient (r) = 0.963.
- Concordance (Lot FB1218): Overall Agreements at various cut-offs: 0.10 ng/mL (96.9%), 0.25 ng/mL (96.2%), 0.50 ng/mL (95.9%), 2.00 ng/mL (97.5%).
- Concordance (Lot FC1218): Overall Agreements at various cut-offs: 0.10 ng/mL (96.4%), 0.25 ng/mL (96.4%), 0.50 ng/mL (96.4%), 2.00 ng/mL (97.5%).
- Extended Measuring Interval (0.05-1000.00 ng/mL, n=595):
- Lot FB1218: Slope = 1.08 (95% CI: 1.05-1.10), Intercept = -0.01 ng/mL, Correlation coefficient (r) = 0.988.
- Lot FC1218: Slope = 1.05 (95% CI: 1.04-1.07), Intercept = 0.00 ng/mL, Correlation coefficient (r) = 0.991.
- Concordance (Lot FB1218): Overall Agreements at various cut-offs: 0.10 ng/mL (97.1%), 0.25 ng/mL (96.5%), 0.50 ng/mL (96.1%), 2.00 ng/mL (97.6%).
- Concordance (Lot FC1218): Overall Agreements at various cut-offs: 0.10 ng/mL (96.6%), 0.25 ng/mL (96.6%), 0.50 ng/mL (96.6%), 2.00 ng/mL (97.6%).
13.10 Matrix Comparison
Study Type: Matrix comparison study conducted in accordance with CLSI EP09C-ED3.
Sample Size: 76 matched sets (Serum, Lithium Heparin plasma, Sodium Heparin plasma, K2EDTA plasma, and K3EDTA plasma, except RST with 75 matched sets).
Key Results: No significant difference was observed based on Passing-Bablok regression analysis, with correlation coefficients (r) ranging from 0.996 to 0.998.
14.1 Reference Interval
Study Type: Reference interval verification according to CLSI EP28-A3c.
Sample Size: 33 apparently healthy individuals.
Key Results: Verified reference interval is
§ 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis.
(a)
Identification. A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended.
(2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection.
(3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability.
(4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(i) Results must demonstrate adequate device performance relative to a well-accepted comparator.
(ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population.
(iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses.
(5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and gender distribution) similar to the Intended Use population.(6) As part of the risk management activities performed under 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (
e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA text logo on the right. The text logo has the FDA acronym in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.
August 26, 2022
Siemens Healthcare Diagnostics, Inc. Amy Tyler Regulatory Affairs Professional 500 GBC Drive, P.O. Box 6101 Mail Stop 514 Newark, Delaware 19714
Re: K220262
Trade/Device Name: Dimension EXL LOCI BRAHMS Procalcitonin (PCT) Regulation Number: 21 CFR 866.3215 Regulation Name: Device To Detect And Measure Non-Microbial Analyte(S) In Human Clinical Specimens To Aid In Assessment Of Patients With Suspected Sepsis Regulatory Class: Class II Product Code: PRI, PMT Dated: January 26, 2022 Received: January 31, 2022
Dear Amy Tyler:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
1
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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
for
Noel Gerald Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K220262
Device Name Dimension EXL LOCI BRAHMS Procalcitonin (PCT)
Indications for Use (Describe)
The Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay is an in vitro diagnostic test for the quantitative measurement of procalcitonin in human serum and plasma (lithium heparin, K2EDTA, and K3EDTA) using the Dimension® EXL™ integrated chemistry system with LOCI® Module.
The Dimension EXL LOCI® BRAHMS PCT assay is intended for use in conjunction with other laboratory findings and clinical assessments, as an aid in:
· The risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock.
• Assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission using percentage change in PCT levels over time.
· Decision making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) - defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) - in an inpatient setting or an emergency department.
· Decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92 and the Safe Medical Device Act of 1990.
The assigned 510(k) Number is: K220262
1. Date Updated
August 24, 2022
2. Applicant Information
| Contact: | Amy Tyler
Regulatory Affairs Professional |
|----------|----------------------------------------------------------------------------------------------------------------|
| Address: | Siemens Healthcare Diagnostics, Inc.
500 GBC Drive, P.O. Box 6101
Mail Stop 514
Newark, DE 19714, USA |
| Email: | amy.c.tyler@siemens-healthineers.com |
3. Regulatory Information
Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT)
| Trade Name: | Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) |
|---|---|
| Classification Name: | Procalcitonin Assay: Device to detect and measure non-microbial |
| analyte(s) in human clinical specimens to aid in assessment of patients | |
| with suspected sepsis. | |
| FDA Classification: | Class II |
| Review Panel: | Microbiology |
| Product Codes: | PRI, PMT |
| Regulation Numbers: | 21 CFR 866.3215 |
4. Predicate Device Information
Device Name: B·R·A·H·M·S PCT sensitive KRYPTOR 510(k) Number: DEN150009/K171338 Manufacturer: B·R·A·H·M·S GmbH (Thermo Fisher Scientific)
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5. Intended Use / Indications For Use
The Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay is an in vitro diagnostic test for the quantitative measurement of procalcitonin in human serum and plasma (lithium heparin, sodium heparin, K2EDTA, and K3EDTA) using the Dimension® EXL™ integrated chemistry system with LOCI® Module.
The Dimension EXL LOCI® BRAHMS PCT assay is intended for use in conjunction with other laboratory findings and clinical assessments, as an aid in:
- The risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission ● for progression to severe sepsis and septic shock.
- . Assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission using percentage change in PCT levels over time.
- . Decision making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) – defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) – in an inpatient setting or an emergency department.
- Decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.
6. Special Conditions for Use Statement
For Prescription Use Only
7. Warnings and Precautions for Test Interpretation
- The Dimension EXL LOCI BRAHMS PCT assay is not indicated to be used as a stand-alone diagnostic assay and should be used in conjunction with clinical signs and symptoms of infection and other diagnostic evidence.
- Decisions regarding antibiotic therapy should NOT be based solely on PCT concentrations.
- . PCT results should always be interpreted in the context of the clinical status of the patient and other laboratory results. Changes in PCT levels for the prediction of mortality, and overall mortality, are strongly dependent on many factors, including pre-existing patient risk factors and clinical course.
- The need to continue ICU care at Day 4 and other covariates, such as age and Sequential Organ Failure Assessment (SOFA) score, are also significant predictors of 28-day cumulative mortality risk.
- . PCT levels may not be elevated in patients infected by certain atypical pathogens, such as Chlamydophila pneumoniae and Mycoplasma pneumoniae.
- Certain patient characteristics, such as severity of renal failure or insufficiency, may influence PCT values and should be considered as potentially confounding clinical factors when interpreting PCT values.
- . The safety and performance of PCT-guided therapy for individuals younger than 18 years of age, pregnant women, immunocompromised individuals, or those on immunomodulatory agents, was not formally analyzed in the supportive clinical trials.
- Increased PCT levels may not always be related to systemic infection. These conditions include, but are not limited to:
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- Patients experiencing major trauma and/or recent surgical procedure, including O extracorporeal circulation or burns;
- Patients under treatment with OKT3 antibodies, OK-432, interleukins, TNF-alpha, and O other drugs stimulating the release of pro-inflammatory cytokines or resulting in anaphylaxis;
- Patients diagnosed with active medullary C-cell carcinoma, small cell lung carcinoma, or O bronchial carcinoid;
- Patients with acute or chronic viral hepatitis and/or decompensated severe liver O cirrhosis (Child-Pugh Class C);
- Patients with prolonged or severe cardiogenic shock, prolonged severe organ perfusion O anomalies, or after resuscitation from cardiac arrest;
- O Patients receiving peritoneal dialysis or hemodialysis treatment;
- O Patients with biliary pancreatitis, chemical pneumonitis, or heat stroke;
- Patients with invasive fungal infections (such as candidiasis and aspergillosis) or acute O attacks of plasmodium falciparum malaria; and
- Neonates during the first 2 days of life. O
8. Special Instrument Requirement
For use on the Dimension® EXL™ integrated chemistry system with LOCI® Module.
9. Test Principle and Device Description
The Dimension EXL LOCI BRAHMS PCT assay is a homogeneous sandwich chemiluminescent immunoassay based on LOCI technology. The LOCI reagents include two synthetic bead reagents and one biotinylated anti-procalcitonin (anti-PCT) monoclonal antibody. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitizer dye. The second bead reagent (Chemibeads) is coated with two anti-PCT monoclonal antibodies and contains chemiluminescent dye. Sample is incubated with biotinylated antibody and Chemibeads to form bead-PCT-biotinylated antibody sandwiches. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the procalcitonin (PCT) concentration in the sample.
| Component | Volume | Ingredients | ||
|---|---|---|---|---|
| Biotinylated Antibody | ||||
| Well 1 (W1) and Well 2 (W2) | ||||
| Reagent 1 (R1) | 1.0 mL | PCT Biotinylated Antibody-mouse monoclonal | ||
| (3.5 µg/mL), bovine serum albumin, bovine | ||||
| gamma globulin, goat serum, mouse IgG, rat | ||||
| IgG, sodium azide (50.00 ng/mL and 4 additional levels with concentrations near the lower medical decision levels were made with a second high pool targeted near 4.00 ng/mL). |
Regression analysis using first, second, and third order models was conducted to determine the linearity of the assay. Regression statistics (i.e., deviation from linearity for non-linear pools) at all levels tested demonstrated a ≤20% deviation (≤ 0.04 ng/mL for the lowest sample) from the predicted linear fit.
The study demonstrated a linear range of 0.03 to 55.05 ng/mL, which supports a measuring interval of 0.05 to 50.00 ng/mL for the Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay.
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13.5 Dilution Recovery
Dilution recovery (using manual dilution) was conducted according to CLSI EP34-ED1. Ten native serum specimens with concentrations determined to be greater than 50.00 ng/mL were diluted 1:20 with saline, which is the recommended diluent for this assay. Recoveries for all specimens ranged from 88 to 108% (mean % recovery was 98%). The following results were obtained:
| Sample | Dilution | PCT Mean Results ng/mL (µg/L) | % Recovery | |
|---|---|---|---|---|
| Expected | Observed | |||
| 1 | 1:20 | 411.3 (411.3) | 390.60 (390.60) | 95% |
| 2 | 1:20 | 300.3 (300.3) | 285.40 (285.40) | 95% |
| 3 | 1:20 | 394.4 (394.4) | 413.60 (413.60) | 105% |
| 4 | 1:20 | 646.2 (646.2) | 695.00 (695.00) | 108% |
| 5 | 1:20 | 203.2 (203.2) | 178.80 (178.80) | 88% |
| 6 | 1:20 | 65.23 (65.23) | 61.60 (61.60) | 94% |
| 7 | 1:20 | 72.43 (72.43) | 73.40 (73.40) | 101% |
| 8 | 1:20 | 216.9 (216.9) | 202.20 (202.20) | 93% |
| 9 | 1:20 | 124.1 (124.1) | 118.80 (118.80) | 96% |
| 10 | 1:20 | 143.1 (143.1) | 148.40 (148.40) | 104% |
Manual dilution of 1:20 increases the upper end of the analytical measuring interval which supports an extended measuring interval from 50.00 ng/mL (50.00 µg/L) to 1000.00 ng/mL (1000.00 µg/L).
13.6 Interference and Cross-Reactivity
Interference testing was conducted using EP07-ED3 for general guidance. Human serum pools at approximately 0.25 ng/mL and 2.00 ng/mL PCT were prepared by pooling native PCT. Each pool was divided into control and test pools were spiked with the potentially interfering substances and the control pools were spiked with an equivalent volume of diluent.
Percent interference (% bias) was calculated according to the following equation:
$$% \text{ Bias} = \frac{(\text{Observed Mean} - \text{Control Mean Concentration})}{\text{Control Mean concentration}} \times 100$$
Bias >10% is considered interference. Analyte results should not be corrected based on this bias.
The conversion factor from conventional units (ng/mL) to SI units (ug/L) is 1.00. Based on this, all results shown in ng/mL units would have the same values when displayed in µg/L units.
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Hemolysis, Icterus, and Lipemia (HIL)
The Dimension EXL LOCI BRAHMS PCT assay is designed to have ≤10% interference from hemoglobin, bilirubin, and lipemia. The following results were obtained:
| Substance | Substance Concentration | | PCT Analyte
Concentration
(ng/mL) | % Bias |
|----------------------------|-------------------------|------------|-----------------------------------------|--------|
| | Conventional Units | SI Units | | |
| Bilirubin, Conjugated | 40 mg/dL | 474 µmol/L | 0.24 | 0 |
| Bilirubin, Conjugated | 40 mg/dL | 474 µmol/L | 2.02 | 0 |
| Bilirubin, Unconjugated | 40 mg/dL | 684 µmol/L | 0.22 | 0 |
| Bilirubin, Unconjugated | 40 mg/dL | 684 µmol/L | 1.75 | 1 |
| Hemoglobin | 1000 mg/dL | 10 g/L | 0.20 | -5 |
| Hemoglobin | 1000 mg/dL | 10 g/L | 1.61 | -7 |
| Lipemia (from Intralipid®) | 2000 mg/dL | 20 g/L | 0.21 | 0 |
| Lipemia (from Intralipid®) | 2000 mg/dL | 20 g/L | 1.69 | 3 |
Non-Interfering Substances
The following substances do not interfere with the Dimension EXL LOCI BRAHMS PCT assay when present in serum, lithium heparin plasma, sodium heparin plasma, K2EDTA plasma, or K3EDTA plasma. Bias due to these substances was ≤10% at PCT analyte concentrations of 0.25 and 2.00 ng/mL.
| Substance | Substance Concentration | | PCT Analyte
Concentration
ng/mL | % Bias |
|----------------------------|-------------------------|--------------------------------------------|-----------------------------------------|--------|
| | Conventional Units | SI Units | | |
| Acetaminophen | 20 mg/dL | 1324 µmol/L | 0.25 | -4 |
| Acetaminophen | 20 mg/dL | 1324 µmol/L | 2.02 | 1 |
| Acetylsalicylic acid | 3 mg/dL | 166.5 µmol/L | 0.24 | 4 |
| Acetylsalicylic acid | 3 mg/dL | 166.5 µmol/L | 2.04 | 0 |
| Albumin | 6 g/dL | 60 g/L | 0.21 | -5 |
| Albumin | 6 g/dL | 60 g/L | 1.75 | -9 |
| Amoxicillin | 5.4 mg/dL | 147.96 µmol/L | 0.22 | 5 |
| Amoxicillin | 5.4 mg/dL | 147.96 µmol/L | 1.81 | 2 |
| Azithromycin | 1.15 mg/dL | 15.4 µmol/L | 0.22 | 0 |
| Substance | Substance Concentration | | PCT Analyte
Concentration
ng/mL | % Bias |
| | Conventional Units | SI Units | | |
| Azithromycin | 1.15 mg/dL | 15.4 µmol/L | 1.78 | -1 |
| Caffeine | 10.8 mg/dL | 556.2 µmol/L | 0.24 | 0 |
| Caffeine | 10.8 mg/dL | 556.2 µmol/L | 2.02 | 0 |
| Cefotaxime | 52.8 mg/dL | 1161.6 µmol/L | 0.25 | 0 |
| Cefotaxime | 52.8 mg/dL | 1161.6 µmol/L | 2.02 | 0 |
| Celecoxib | 0.88 mg/dL | 23 µmol/L | 0.22 | 0 |
| Celecoxib | 0.88 mg/dL | 23 µmol/L | 1.81 | -1 |
| Cetirizine HCl | 0.43 mg/dL | 11.1 µmol/L | 0.22 | 0 |
| Cetirizine HCl | 0.43 mg/dL | 11.1 µmol/L | 1.81 | -3 |
| Cholesterol | 400 mg/dL | 10.4 mmol/L | 0.22 | -5 |
| Cholesterol | 400 mg/dL | 10.4 mmol/L | 1.73 | -2 |
| Dextran 40 | 4500 mg/dL | 1125 µmol/L | 0.26 | -4 |
| Dextran 40 | 4500 mg/dL | 1125 µmol/L | 2.12 | -1 |
| Dextromethorphan | 0.00156 mg/dL | 0.057 µmol/L | 0.24 | 4 |
| Dextromethorphan | 0.00156 mg/dL | 0.057 µmol/L | 2.04 | -5 |
| Dobutamine | 0.121 mg/dL | 4 µmol/L | 0.22 | 5 |
| Dobutamine | 0.121 mg/dL | 4 µmol/L | 1.81 | -3 |
| Dopamine | 0.06 mg/dL | 3.9 µmol/L | 0.25 | 0 |
| Dopamine | 0.06 mg/dL | 3.9 µmol/L | 2.02 | 0 |
| Doxycycline | 1.8 mg/dL | 40.5 µmol/L | 0.22 | 0 |
| Doxycycline | 1.8 mg/dL | 40.5 µmol/L | 1.81 | -4 |
| EDTA | 0.099 mg/dL | 3.4 µmol/L | 0.22 | 5 |
| EDTA | 0.099 mg/dL | 3.4 µmol/L | 1.75 | 3 |
| Epinephrine | 0.18 mg/dL | 9.8 µmol/L | 0.25 | 0 |
| Epinephrine | 0.18 mg/dL | 9.8 µmol/L | 2.02 | 1 |
| Ethanol | 400 mg/dL | 86.8 mmol/L | 0.24 | 0 |
| Substance | Substance Concentration | | PCT Analyte
Concentration
ng/mL | % Bias |
| | Conventional Units | SI Units | | |
| Ethanol | 400 mg/dL | 86.8 mmol/L | 2.02 | -1 |
| Fentanyl | 0.03 mg/dL | 0.89 µmol/L | 0.24 | 0 |
| Fentanyl | 0.03 mg/dL | 0.89 µmol/L | 2.04 | -1 |
| Fluorescein | 0.01 mg/dL | 0.3 µmol/L | 0.22 | 0 |
| Fluorescein | 0.01 mg/dL | 0.3 µmol/L | 1.75 | 0 |
| Furosemide | 2 mg/dL | 60.4 µmol/L | 0.24 | -8 |
| Furosemide | 2 mg/dL | 60.4 µmol/L | 2.04 | -1 |
| HAMA | 22.8 mg/mL | 22.8 g/L | 0.27 | -7 |
| HAMA | 22.8 mg/mL | 22.8 g/L | 2.19 | -9 |
| Heparin | 330 U/dL | 3300 U/L | 0.25 | -4 |
| Heparin | 330 U/dL | 3300 U/L | 2.02 | 3 |
| Human Immunoglobulin (IgG) | 5 g/dL | 50 g/L | 0.23 | -9 |
| Human Immunoglobulin (IgG) | 5 g/dL | 50 g/L | 1.80 | -8 |
| Human serum albumin | 1 g/dL | 10 g/L | 0.22 | 5 |
| Human serum albumin | 1 g/dL | 10 g/L | 1.85 | -1 |
| Human serum gamma globulin | 2.5 g/dL | 25 g/L | 0.26 | -8 |
| Human serum gamma globulin | 2.5 g/dL | 25 g/L | 2.12 | -7 |
| Ibuprofen | 21.9 mg/dL | 1062.2 µmol/L | 0.24 | 4 |
| Ibuprofen | 21.9 mg/dL | 1062.2 µmol/L | 2.04 | -1 |
| Imipenem | 118 mg/dL | 3941.2 µmol/L | 0.22 | 5 |
| Imipenem | 118 mg/dL | 3941.2 µmol/L | 1.75 | 3 |
| Levofloxacin | 3.6 mg/dL | 99.7 µmol/L | 0.22 | 0 |
| Levofloxacin | 3.6 mg/dL | 99.7 µmol/L | 1.75 | -1 |
| Loratadine | 0.0087 mg/dL | 0.27 µmol/L | 0.22 | 5 |
| Loratadine | 0.0087 mg/dL | 0.27 µmol/L | 1.81 | -1 |
| Nicotine | 0.1 mg/dL | 6.2 µmol/L | 0.24 | -4 |
| Substance | Substance Concentration | | PCT Analyte
Concentration
ng/mL | % Bias |
| | Conventional Units | SI Units | | |
| Nicotine | 0.1 mg/dL | 6.2 µmol/L | 2.04 | -5 |
| Noradrenaline | 0.2 mg/dL | 11.8 µmol/L | 0.22 | 0 |
| Noradrenaline | 0.2 mg/dL | 11.8 µmol/L | 1.75 | -2 |
| Oxymetazoline HCl | 9 µg/dL | 0.3 µmol/L | 0.25 | 0 |
| Oxymetazoline HCl | 9 µg/dL | 0.3 µmol/L | 2.02 | 2 |
| Phenylephrine | 0.003 mg/dL | 0.179 µmol/L | 0.25 | 0 |
| Phenylephrine | 0.003 mg/dL | 0.179 µmol/L | 2.02 | 1 |
| Prednisolone | 0.12 mg/dL | 3.3 µmol/L | 0.22 | 5 |
| Prednisolone | 0.12 mg/dL | 3.3 µmol/L | 1.81 | -1 |
| Rheumatoid Factor | 500 IU/mL | 500 IU/mL | 0.21 | -5 |
| Rheumatoid Factor | 500 IU/mL | 500 IU/mL | 1.64 | 1 |
| Salmeterol | 6 µg/dL | 0.1 µmol/L | 0.24 | 4 |
| Salmeterol | 6 µg/dL | 0.1 µmol/L | 2.04 | -6 |
| Tiotropium | 2.16 mg/dL | 45.8 µmol/L | 0.24 | 0 |
| Tiotropium | 2.16 mg/dL | 45.8 µmol/L | 2.04 | -3 |
| Total Protein | 10.6 g/dL | 106 g/L | 0.22 | -9 |
| Total Protein | 10.6 g/dL | 106 g/L | 1.74 | -9 |
| Triglycerides | 1500 mg/dL | 16.9 mmol/L | 0.22 | -5 |
| Triglycerides | 1500 mg/dL | 16.9 mmol/L | 1.73 | -2 |
| Vancomycin | 12 mg/dL | 82.8 µmol/L | 0.25 | -4 |
| Vancomycin | 12 mg/dL | 82.8 µmol/L | 2.02 | 0 |
| Substance | Substance Concentration | | PCT Analyte
Concentration
(ng/mL) | % Bias |
| | Conventional Units | SI Units | | |
| Biotin (mega dose) | 3510 ng/mL | 14.356 µmol/L | 0.23 | -26 |
| Biotin (mega dose) | 3510 ng/mL | 14.356 µmol/L | 1.88 | -29 |
| Biotin | 1500 ng/mL | 6.135 µmol/L | 0.23 | -4 |
| Biotin | 1500 ng/mL | 6.135 µmol/L | 1.88 | -19 |
| Biotin | 1200 ng/mL | 4.908 µmol/L | 0.23 | 0 |
| Biotin | 1200 ng/mL | 4.908 µmol/L | 1.78 | -2 |
| Biotin | 600 ng/mL | 2.454 µmol/L | 0.23 | 4 |
| Biotin | 600 ng/mL | 2.454 µmol/L | 1.88 | 1 |
| Biotin | 300 ng/mL | 1.227 µmol/L | 0.23 | 0 |
| Biotin | 300 ng/mL | 1.227 µmol/L | 1.88 | -2 |
| Biotin | 150 ng/mL | 0.614 µmol/L | 0.23 | 0 |
| Biotin | 150 ng/mL | 0.614 µmol/L | 1.88 | -3 |
| Biotin | 99.6 ng/mL | 0.407 µmol/L | 0.23 | 0 |
| Biotin | 99.6 ng/mL | 0.407 µmol/L | 1.88 | -2 |
| Biotin | 80.4 ng/mL | 0.329 µmol/L | 0.23 | 0 |
| Biotin | 80.4 ng/mL | 0.329 µmol/L | 1.88 | -1 |
| Biotin | 39.6 ng/mL | 0.162 µmol/L | 0.23 | 4 |
| Biotin | 39.6 ng/mL | 0.162 µmol/L | 1.88 | -3 |
| Biotin | 30.0 ng/mL | 0.123 µmol/L | 0.23 | 4 |
| Biotin | 30.0 ng/mL | 0.123 µmol/L | 1.88 | -1 |
| Biotin | 20.4 ng/mL | 0.083 µmol/L | 0.23 | 0 |
| Biotin | 20.4 ng/mL | 0.083 µmol/L | 1.88 | -1 |
| Biotin | 9.6 ng/mL | 0.039 µmol/L | 0.23 | 4 |
| Biotin | 9.6 ng/mL | 0.039 µmol/L | 1.88 | 0 |
| Substance | Substance Concentration | | PCT Analyte | % Bias |
| | Conventional Units | SI Units | Concentration ng/mL | |
| HAMA 1 | 65.0 mg/mL | 65.0 g/L | 0.21 | -10 |
| HAMA 1 | 65.0 mg/mL | 65.0 g/L | 1.64 | -12 |
| HAMA 2 | 65.0 mg/mL | 65.0 g/L | 0.21 | -14 |
| HAMA 2 | 65.0 mg/mL | 65.0 g/L | 1.64 | -13 |
| HAMA 1 | 32.5 mg/mL | 32.5 g/L | 0.27 | -11 |
| HAMA 1 | 32.5 mg/mL | 32.5 g/L | 2.19 | -12 |
| HAMA 2 | 32.5 mg/mL | 32.5 g/L | 0.27 | -7 |
| HAMA 2 | 32.5 mg/mL | 32.5 g/L | 2.19 | -11 |
| HAMA 1 | 22.8 mg/mL | 22.8 g/L | 0.27 | -7 |
| HAMA 1 | 22.8 mg/mL | 22.8 g/L | 2.19 | -9 |
| HAMA 2 | 22.8 mg/mL | 22.8 g/L | 0.27 | -7 |
| HAMA 2 | 22.8 mg/mL | 22.8 g/L | 2.19 | -7 |
| HAMA 1 | 16.3 mg/mL | 16.3 g/L | 0.27 | -4 |
| HAMA 1 | 16.3 mg/mL | 16.3 g/L | 2.19 | -9 |
| HAMA 2 | 16.3 mg/mL | 16.3 g/L | 0.27 | -4 |
| HAMA 2 | 16.3 mg/mL | 16.3 g/L | 2.19 | -5 |
| HAMA 1 | 0.001 mg/mL | 0.001 g/L | 0.21 | 0 |
| HAMA 1 | 0.001 mg/mL | 0.001 g/L | 1.64 | 4 |
| HAMA 2 | 0.001 mg/mL | 0.001 g/L | 0.21 | -5 |
| HAMA 2 | 0.001 mg/mL | 0.001 g/L | 1.64 | 2 |
| Substance | Substance Concentration | | PCT Analyte
Concentration
ng/mL | % Bias |
| | Conventional Units | SI Units | | |
| Biotin | 3510 ng/mL | 14.356 $ \u03bcmol/L $ | 0.23 | -26 |
| Biotin | 3510 ng/mL | 14.356 $ \u03bcmol/L $ | 1.88 | -29 |
| HAMA 1 | 32.5 mg/mL | 32.5 g/L | 0.27 | -11 |
| HAMA 1 | 32.5 mg/mL | 32.5 g/L | 2.19 | -12 |
| HAMA 2 | 32.5 mg/mL | 32.5 g/L | 0.27 | -7 |
| HAMA 2 | 32.5 mg/mL | 32.5 g/L | 2.19 | -11 |
| Total Protein | 15.0 g/dL | 150 g/L | 0.22 | -18 |
| Total Protein | 15.0 g/dL | 150 g/L | 1.74 | -18 |
15
16
17
Biotin Interference Testing
Biotin testing was performed by spiking a range of concentrations into serum pools with PCT analyte concentrations of 0.25 and 2.00 ng/mL. The results of this testing are shown in the following table.
18
19
HAMA Interference Testing
HAMA testing was performed at a range of concentrations to determine the level at which HAMA would cause >10% interference. Both HAMA 1 and HAMA 2 were tested in serum pools with PCT analyte concentrations of 0.25 and 2.00 ng/mL. The results of this testing are shown in the following table.
20
Interfering Substances
The following substances were observed to have >10% interference in serum pools with PCT analyte concentrations of 0.25 and 2.00 ng/mL. The Instructions For Use contains limitations statements for these substances at the concentrations listed in the following table.
Note: HAMA interference listed in the IFU does not differentiate between HAMA 1 and HAMA 2.
Cross-Reactivity
Potential cross-reactivity was evaluated using EP07-ED3 for general guidance. Human serum pools at approximately 0.25 ng/mL and 2.00 ng/mL PCT were prepared by pooling native PCT. Each pool was divided into control and test pools. The test pools were spiked with the potentially crossreacting substances and the control pools were spiked with an equivalent volume of diluent. Cross-reactivity was calculated using the following equation:
$$% \text{Cross} - \text{recativity} = 100 \frac{[\text{Test} - \text{Control}]}{[\text{Compound}]}$$
The results of this testing are shown in the following table.
| Cross-Reactant | Cross-Reactant test concentration | PCT Analyte | ||
|---|---|---|---|---|
| Conventional units | SI Units | Concentration ng/mL | % Cross-Reactivity | |
| Calcitonin (Human) | 8 ng/mL | 8 µg/L | 0.23 | 0.00% |
| Calcitonin (Human) | 8 ng/mL | 8 µg/L | 1.79 | -0.50% |
| Calcitonin (Eel) | 30 ng/mL | 30 µg/L | 0.23 | -0.03% |
| Calcitonin (Eel) | 30 ng/mL | 30 µg/L | 1.79 | -0.13% |
21
| | Cross-Reactant test concentration | | PCT Analyte
Concentration ng/mL | % Cross-Reactivity |
|---------------------|-----------------------------------|-----------|------------------------------------|--------------------|
| Cross-Reactant | Conventional units | SI Units | | |
| Calcitonin (Salmon) | 30 ng/mL | 30 µg/L | 0.24 | -0.03% |
| Calcitonin (Salmon) | 30 ng/mL | 30 µg/L | 1.78 | 0.07% |
| Katacalcin (Human) | 30 ng/mL | 30 µg/L | 0.23 | -0.03% |
| Katacalcin (Human) | 30 ng/mL | 30 µg/L | 1.79 | -0.20% |
| α-CGRP | 30 ng/mL | 30 µg/L | 0.23 | 0.00% |
| α-CGRP | 30 ng/mL | 30 µg/L | 1.79 | 0.00% |
| B-CGRP | 30 ng/mL | 30 µg/L | 0.23 | 0.00% |
| B-CGRP | 30 ng/mL | 30 µg/L | 1.79 | 0.00% |
13.7 Hook Effect
A study was performed to evaluate whether a hook effect occurs with the assay for PCT concentrations up to 2000.00 ng/mL. For patient specimens with PCT concentrations between 50.00 ng/mL and 2000.00 ng/mL the assay will report results as "Above Assay Range" (> 50.00 ng/mL).
13.8 Sample Carryover
Sample carryover was performed using eleven separate runs. Each run consisted of testing a pattern of high (1068.88 ng/mL PCT) and low (≤0.10 ng/mL PCT) analyte samples for a total of 21 tests per run. The high sample was prepared by spiking recombinant procalcitonin into a normal human serum sample and the low sample was a normal human serum sample containing ≤0.10 ng/ml PCT (no spiking or dilution occurred). The following test order was used for each run, with L corresponding to the low sample and H corresponding to the high sample: 11, L2, L3, H1, H2, L4, H3, H4, L5, L6, L7, L8, H5, H6, L9, H7, H8, L10, H9, H10, L11.
No sample carryover from high samples into low samples was observed when a pattern of high and low samples was tested (sample carryover was calculated to be 0.00 ng/mL).
22
13.9 Method Comparison
The method comparison study was designed in accordance with CLSI EP09c-ED3 to compare the performance of the Dimension EXL LOCI BRAHMS Procalcitonin (PCT) assay to that of the predicate device (B·R·A·H·M·S PCT sensitive KRYPTOR).
A total of 595 native human serum samples within the concentration range of 0.05-1000.00 ng/mL were tested with the Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay and the predicate device (B·R·A·H·M·S PCT sensitive KRYPTOR). Samples recovering >50.00 ng/mL were diluted manually with saline using a 1:20 dilution and tested.
Data analysis for method comparison was completed for both the measuring interval (n=555) and the extended measuring interval (n=595) for each Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay lot. Weighted Deming and Passing and Bablok regression statistics were calculated. Data was further analyzed for concordance (percent agreement) between the Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay and the predicate B·R·A·H·M·S PCT sensitive KRYPTOR at each Clinical cutoff / Medical Decision Level (MDL).
Method comparison statistics for weighted Deming regression and Passing and Bablok regression for the measuring interval (0.05-50.00 ng/mL (0.05-50.00 µg/L))
| Lot FB1218 | Lot FC1218 | |||
|---|---|---|---|---|
| Parameter | Weighted Deming Regression | Passing and Bablok Regression | Weighted Deming Regression | Passing and Bablok Regression |
| N | 555 | 555 | 555 | 555 |
| Slope | 1.07 | 1.07 | 1.04 | 1.04 |
| 95% Confidence Interval | 1.05 to 1.10 | 1.05 to 1.09 | 1.02 to 1.07 | 1.02 to 1.06 |
| Intercept (ng/mL) | -0.01 | -0.01 | 0.00 | -0.01 |
| 95% Confidence Interval | -0.02 to 0.00 | -0.02 to -0.01 | -0.01 to 0.00 | -0.01 to 0.00 |
| Correlation coefficient (r) | 0.958 | 0.958 | 0.963 | 0.963 |
| Sample range (ng/mL) | 0.02 to 49.03 | 0.02 to 49.03 | 0.02 to 49.03 | 0.02 to 49.03 |
23
Concordance data for Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) lot FB1218 (measuring interval, 0.05-50.00 ng/mL (0.05-50.00 µg/L)).
PCT Results at 0.10 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | ||||
|---|---|---|---|---|
| Dimension EXL LOCI BRAHMS PCT | >0.10 ng/mL | ≤0.10 ng/mL | Total | |
| >0.10 ng/mL | 489 | 6 | 495 | |
| ≤0.10 ng/mL | 11 | 49 | 60 | |
| Total | 500 | 55 | 555 | |
| Positive % Agreement | = 97.8 % ; | 95% Confidence Interval: | 96.5% | - 99.1% |
| Negative % Agreement | = 89.1 % ; | 95% Confidence Interval: | 80.9% | - 97.3% |
| Overall % Agreement | = 96.9 % ; | 95% Confidence Interval: | 95.5% | - 98.4% |
PCT Results at 0.25 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | |||
|---|---|---|---|
| Dimension EXL LOCI BRAHMS PCT | >0.25 ng/mL | ≤0.25 ng/mL | Total |
| >0.25 ng/mL | 401 | 11 | 412 |
| ≤0.25ng/mL | 10 | 133 | 143 |
| Total | 411 | 144 | 555 |
| Positive % Agreement | = 97.6% ; | 95% Confidence Interval: 96.1% - 99.1% | |
| Negative % Agreement | = 92.4% ; | 95% Confidence Interval: 88.0% - 96.7% | |
| Overall % Agreement | = 96.2% ; | 95% Confidence Interval: 94.6% - 97.8% |
PCT Results at 0.50 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | |||||
|---|---|---|---|---|---|
| Dimension EXL LOCI BRAHMS PCT | >0.50 ng/mL | ≤0.50 ng/mL | Total | ||
| >0.50 ng/mL | 294 | 11 | 305 | ||
| ≤0.50 ng/mL | 12 | 238 | 250 | ||
| Total | 306 | 249 | 555 | ||
| Positive % Agreement | = | 96.1%; | 95% Confidence Interval: | 93.9% | 98.3% |
| Negative % Agreement | = | 95.6%; | 95% Confidence Interval: | 93.0% | 98.1% |
| Overall % Agreement | = | 95.9%; | 95% Confidence Interval: | 94.2% | 97.5% |
PCT Results at 2.00 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | ||||
|---|---|---|---|---|
| >2.00 ng/mL | ≤2.00 ng/mL | Total | ||
| Dimension EXL LOCI BRAHMS PCT | >2.00 ng/mL | 188 | 9 | 197 |
| ≤2.00 ng/mL | 5 | 353 | 358 | |
| Total | 193 | 362 | 555 | |
| Positive % Agreement | = 97.4 % ; | 95% Confidence Interval: | 95.2% | - 99.7% |
| Negative % Agreement | = 97.5 % ; | 95% Confidence Interval: | 95.9% | - 99.1% |
| Overall % Agreement | = 97.5 % ; | 95% Confidence Interval: | 96.2% | - 98.8% |
24
Cross-Tabulation of concordance data for all samples (n=555) for Dimension ° EXL™ LOCI ° BRAHMS Procalcitonin versus Predicate for lot FB1218 (measuring interval)
| Dimension EXL LOCI
BRAHMS PCT
| (ng/mL) | ≤0.10 | >0.10 - ≤0.25 | >0.25 - ≤0.50 | >0.50 - ≤2.00 | >2.00 | Total |
|---|---|---|---|---|---|---|
| ≤0.10 | 49 | 11 | 0 | 0 | 0 | 60 |
| >0.10 - ≤0.25 | 6 | 67 | 10 | 0 | 0 | 83 |
| >0.25 - ≤0.50 | 0 | 10 | 85 | 12 | 0 | 107 |
| >0.50 - ≤2.00 | 0 | 1 | 10 | 92 | 5 | 108 |
| >2.00 | 0 | 0 | 0 | 9 | 188 | 197 |
| Total | 55 | 89 | 105 | 113 | 193 | 555 |
25
Concordance data for Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) lot FC1218 (measuring interval, 0.05-50.00 ng/mL (0.05-50.00 μg/L))
PCT Results at 0.10 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | |||||
|---|---|---|---|---|---|
| >0.10 ng/mL | ≤0.10 ng/mL | Total | |||
| Dimension EXL LOCI BRAHMS PCT | >0.10 ng/mL | 486 | 6 | 492 | |
| ≤0.10 ng/mL | 14 | 49 | 63 | ||
| Total | 500 | 55 | 555 | ||
| Positive % Agreement | = 97.2 % | ; 95% Confidence Interval: | 95.8% | - | 98.6% |
| Negative % Agreement | = 89.1 % | ; 95% Confidence Interval: | 80.9% | - | 97.3% |
| Overall % Agreement | = 96.4 % | ; 95% Confidence Interval: | 94.8% | - | 97.9% |
PCT Results at 0.25 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | |||||
|---|---|---|---|---|---|
| >0.25 ng/mL | ≤0.25 ng/mL | Total | |||
| Dimension EXL LOCI BRAHMS PCT | |||||
| >0.25 ng/mL | 402 | 11 | 413 | ||
| ≤0.25ng/mL | 9 | 133 | 142 | ||
| Total | 411 | 144 | 555 | ||
| Positive % Agreement | = | 97.8 % ; | 95% Confidence Interval: | 96.4 % | 99.2 % |
| Negative % Agreement | = | 92.4 % ; | 95% Confidence Interval: | 88.0 % | 96.7 % |
| Overall % Agreement | = | 96.4 % ; | 95% Confidence Interval: | 94.8 % | 97.9 % |
PCT Results at 0.50 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | ||||
|---|---|---|---|---|
| Dimension EXL LOCI BRAHMS PCT | >0.50 ng/mL | ≤0.50 ng/mL | Total | |
| >0.50 ng/mL | 295 | 9 | 304 | |
| ≤0.50 ng/mL | 11 | 240 | 251 | |
| Total | 306 | 249 | 555 | |
| Positive % Agreement | = 96.4 % ; | 95% Confidence Interval: | 94.3 % | 98.5 % |
| Negative % Agreement | = 96.4 % ; | 95% Confidence Interval: | 94.1 % | 98.7 % |
| Overall % Agreement | = 96.4 % ; | 95% Confidence Interval: | 94.8 % | 97.9 % |
PCT Results at 2.00 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | ||||||
|---|---|---|---|---|---|---|
| >2.00 ng/mL | ≤2.00 ng/mL | Total | ||||
| Dimension EXL LOCI BRAHMS PCT | >2.00 ng/mL | 189 | 10 | 199 | ||
| ≤2.00 ng/mL | 4 | 352 | 356 | |||
| Total | 193 | 362 | 555 | |||
| Positive % Agreement | = | 97.9 % ; | 95% Confidence Interval: | 95.9% | - | 99.9% |
| Negative % Agreement | = | 97.2 % ; | 95% Confidence Interval: | 95.5% | - | 98.9% |
| Overall % Agreement | = | 97.5 % ; | 95% Confidence Interval: | 96.2% | - | 98.8% |
26
Cross-Tabulation of concordance data for all samples (n=555) for Dimension " EXL™ LOCI" BRAHMS Procalcitonin versus Predicate for lot FC1218 (measuring interval)
| Dimension EXL LOCI
BRAHMS PCT
| (ng/mL) | B·R·A·H·M·S PCT sensitive KRYPTOR (ng/mL) | |||||
|---|---|---|---|---|---|---|
| ≤0.10 | >0.10 - ≤0.25 | >0.25 - ≤0.50 | >0.50 - ≤2.00 | >2.00 | Total | |
| ≤0.10 | 49 | 14 | 0 | 0 | 0 | 63 |
| >0.10 - ≤0.25 | 6 | 64 | 9 | 0 | 0 | 79 |
| >0.25 - ≤0.50 | 0 | 10 | 88 | 11 | 0 | 109 |
| >0.50 - ≤2.00 | 0 | 1 | 8 | 92 | 4 | 105 |
| >2.00 | 0 | 0 | 0 | 10 | 189 | 199 |
| Total | 55 | 89 | 105 | 113 | 193 | 555 |
Method comparison statistics for weighted Deming regression and Passing and Bablok regression for the extended measuring interval (0.05-1000.00 ng/mL (0.05-1000.00 μg/L))
| Parameter | Lot FB1218 | Lot FC1218 | ||
|---|---|---|---|---|
| Weighted Deming Regression* | Passing and Bablok Regression* | Weighted Deming Regression | Passing and Bablok Regression | |
| N | 595 | 595 | 595 | 595 |
| Slope | 1.08 | 1.07 | 1.05 | 1.05 |
| 95% Confidence Interval | 1.05 to 1.10 | 1.05 to 1.09 | 1.02 to 1.07 | 1.04 to 1.07 |
| Intercept (ng/mL) | -0.01 | -0.01 | 0.00 | -0.01 |
| 95% Confidence Interval | -0.02 to 0.00 | -0.02 to -0.01 | -0.01 to 0.00 | -0.02 to 0.00 |
| Correlation coefficient (r) | 0.988 | 0.988 | 0.991 | 0.991 |
| Sample range (ng/mL) | 0.02 to 691.00 | 0.02 to 691.00 | 0.02 to 691.00 | 0.02 to 691.00 |
*Data shown in IFU
27
Concordance data for Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) lot FB1218 (extended measuring interval, 0.05-1000.00 ng/mL (0.05-1000.00 μg/L))
PCT Results at 0.10 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | ||||
|---|---|---|---|---|
| >0.10 ng/mL | ≤0.10 ng/mL | Total | ||
| Dimension EXL LOCI BRAHMS PCT | >0.10 ng/mL | 529 | 6 | 535 |
| ≤0.10 ng/mL | 11 | 49 | 60 | |
| Total | 540 | 55 | 595 | |
| Positive % Agreement | = 98.0% ; | 95% Confidence Interval: | 96.8% | 99.2% |
| Negative % Agreement | = 89.1% ; | 95% Confidence Interval: | 80.9% | 97.3% |
| Overall % Agreement | = 97.1% ; | 95% Confidence Interval: | 95.8% | 98.5% |
PCT Results at 0.25 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | |||||
|---|---|---|---|---|---|
| >0.25 ng/mL | ≤0.25 ng/mL | Total | |||
| Dimension EXL LOCI BRAHMS PCT | >0.25 ng/mL | 441 | 11 | 452 | |
| ≤0.25ng/mL | 10 | 133 | 143 | ||
| Total | 451 | 144 | 595 | ||
| Positive % Agreement | = 97.8% | ; | 95% Confidence Interval: | 96.4% | 99.1% |
| Negative % Agreement | = 92.4% | ; | 95% Confidence Interval: | 88.0% | 96.7% |
| Overall % Agreement | = 96.5% | ; | 95% Confidence Interval: | 95.0% | 98.0% |
PCT Results at 0.50 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | ||||||
|---|---|---|---|---|---|---|
| >0.50 ng/mL | ≤0.50 ng/mL | Total | ||||
| Dimension EXL LOCI BRAHMS PCT | >0.50 ng/mL | 334 | 11 | 345 | ||
| ≤0.50 ng/mL | 12 | 238 | 250 | |||
| Total | 346 | 249 | 595 | |||
| Positive % Agreement | = 96.5% | ; | 95% Confidence Interval: | 94.6% | - | 98.5% |
| Negative % Agreement | = 95.6% | ; | 95% Confidence Interval: | 93.0% | - | 98.1% |
| Overall % Agreement | = 96.1% | ; | 95% Confidence Interval: | 94.6% | - | 97.7% |
PCT Results at 2.00 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | |||||||
|---|---|---|---|---|---|---|---|
| >2.00 ng/mL | ≤2.00 ng/mL | Total | |||||
| Dimension EXL LOCI BRAHMS PCT | >2.00 ng/mL | 228 | 9 | 237 | |||
| ≤2.00 ng/mL | 5 | 353 | 358 | ||||
| Total | 233 | 362 | 595 | ||||
| Positive % Agreement | = 97.9% | ; | 95% Confidence Interval: | 96.0% | - | 99.7% | |
| Negative % Agreement | = 97.5% | ; | 95% Confidence Interval: | 95.9% | - | 99.1% | |
| Overall % Agreement | = 97.6% | ; | 95% Confidence Interval: | 96.4% | - | 98.9% |
28
Cross-Tabulation of concordance data for all samples (n=595) for Dimension® EXL™ LOCI® BRAHMS Procalcitonin versus Predicate for lot FB1218 (extended measuring interval)
| Dimension EXL LOCI
BRAHMS PCT
| (ng/mL) | B·R·A·H·M·S PCT sensitive KRYPTOR (ng/mL) | |||||
|---|---|---|---|---|---|---|
| ≤0.10 | >0.10 - ≤0.25 | >0.25 - ≤0.50 | >0.50 - ≤2.00 | >2.00 | Total | |
| ≤0.10 | 49 | 11 | 0 | 0 | 0 | 60 |
| >0.10 - ≤0.25 | 6 | 67 | 10 | 0 | 0 | 83 |
| >0.25 -≤0.50 | 0 | 10 | 85 | 12 | 0 | 107 |
| >0.50 - ≤2.00 | 0 | 1 | 10 | 92 | 5 | 108 |
| >2.00 | 0 | 0 | 0 | 9 | 228 | 237 |
| Total | 55 | 89 | 105 | 113 | 233 | 595 |
29
Concordance data for Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) lot FC1218 (extended measuring interval, 0.05-1000.00 ng/mL (0.05-1000.00 μg/L))
PCT Results at 0.10 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | ||||
|---|---|---|---|---|
| >0.10 ng/mL | ≤0.10 ng/mL | Total | ||
| Dimension EXL LOCI BRAHMS PCT | >0.10 ng/mL | 526 | 6 | 532 |
| ≤0.10 ng/mL | 14 | 49 | 63 | |
| Total | 540 | 55 | 595 | |
| Positive % Agreement | = 97.4% ; | 95% Confidence Interval: | 96.1% | 98.7% |
| Negative % Agreement | = 89.1% ; | 95% Confidence Interval: | 80.9% | 97.3% |
| Overall % Agreement | = 96.6% ; | 95% Confidence Interval: | 95.2% | 98.1% |
PCT Results at 0.25 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | ||||||
|---|---|---|---|---|---|---|
| >0.25 ng/mL | ≤0.25 ng/mL | Total | ||||
| Dimension EXL LOCI BRAHMS PCT | >0.25 ng/mL | 442 | 11 | 453 | ||
| ≤0.25ng/mL | 9 | 133 | 142 | |||
| Total | 451 | 144 | 595 | |||
| Positive % Agreement | = | 98.0% | ; 95% Confidence Interval: | 96.7% | - | 99.3% |
| Negative % Agreement | = | 92.4% | ; 95% Confidence Interval: | 88.0% | - | 96.7% |
| Overall % Agreement | = | 96.6% | ; 95% Confidence Interval: | 95.2% | - | 98.1% |
PCT Results at 0.50 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | ||||||
|---|---|---|---|---|---|---|
| >0.50 ng/mL | ≤0.50 ng/mL | Total | ||||
| Dimension EXL LOCI BRAHMS PCT | >0.50 ng/mL | 335 | 9 | 344 | ||
| ≤0.50 ng/mL | 11 | 240 | 251 | |||
| Total | 346 | 249 | 595 | |||
| Positive % Agreement | = 96.8% ; | 95% Confidence Interval: | 95.0% | - | 98.7% | |
| Negative % Agreement | = 96.4% ; | 95% Confidence Interval: | 94.1% | - | 98.7% | |
| Overall % Agreement | = 96.6% ; | 95% Confidence Interval: | 95.2% | - | 98.1% |
PCT Results at 2.00 ng/mL Cut-Off
| B·R·A·H·M·S PCT sensitive KRYPTOR | ||||||||
|---|---|---|---|---|---|---|---|---|
| >2.00 ng/mL | ≤2.00 ng/mL | Total | ||||||
| Dimension EXL LOCI BRAHMS PCT | >2.00 ng/mL | 229 | 10 | 239 | ||||
| ≤2.00 ng/mL | 4 | 352 | 356 | |||||
| Total | 233 | 362 | 595 | |||||
| Positive % Agreement | = 98.3% ; | 95% Confidence Interval: | 96.6% | - | 100.0% | |||
| Negative % Agreement | = 97.2% ; | 95% Confidence Interval: | 95.5% | - | 98.9% | |||
| Overall % Agreement | = 97.6% ; | 95% Confidence Interval: | 96.4% | - | 98.9% |
30
Cross-Tabulation of concordance data for all samples (n=595) for Dimension EXL™ LOCI BRAHMS Procalcitonin versus Predicate for lot FC1218 (extended measuring interval)
| Dimension EXL LOCI
BRAHMS PCT
| (ng/mL) | B-R-A-H-M-S PCT sensitive KRYPTOR (ng/mL) | |||||
|---|---|---|---|---|---|---|
| ≤0.10 | >0.10 - ≤0.25 | >0.25 - ≤0.50 | >0.50 - ≤2.00 | >2.00 | Total | |
| ≤0.10 | 49 | 14 | 0 | 0 | 0 | 63 |
| >0.10 - ≤0.25 | 6 | 64 | 9 | 0 | 0 | 79 |
| >0.25 - ≤0.50 | 0 | 10 | 88 | 11 | 0 | 109 |
| >0.50 - ≤2.00 | 0 | 1 | 8 | 92 | 4 | 105 |
| >2.00 | 0 | 0 | 0 | 10 | 229 | 239 |
| Total | 55 | 89 | 105 | 113 | 233 | 595 |
13.10 Matrix Comparison
The matrix comparison study was conducted in accordance with CLSI EP09C-ED3 to evaluate the comparison between serum and plasma samples. A total of 76 matched sets (Serum, Lithium Heparin plasma, Sodium Heparin plasma, K2EDTA plasma, and K3EDTA plasma) spanning the assay range were evaluated, except for RST (rapid serum tubes) where 75 matched sets were evaluated. SST (serum separator tube) and RST were both included in this study. The SST was used as the control tube for comparison with all other tubes. Matched samples were spiked with equal amounts of recombinant procalcitonin (PCT) in order to span the assay range. No significant difference was observed based on Passing-Bablok regression analysis. Results are shown in the following table.
| Specimen
Type (x) | Comparison
Specimen Type
(y) | N | Sample range
(ng/mL) | Regression Equation | Correlation
Coefficient (r) |
|----------------------|------------------------------------|----|-------------------------|------------------------|--------------------------------|
| Serum (SST) | Serum (RST) | 75 | 0.05-46.59 | y = 1.00x + 0.00 ng/mL | 0.998 |
| Serum (SST) | Lithium
Heparin | 76 | 0.05-46.59 | y = 0.99x + 0.00 ng/mL | 0.997 |
| Serum (SST) | Sodium
Heparin | 76 | 0.05-46.59 | y = 0.98x + 0.01 ng/mL | 0.998 |
| Serum (SST) | K2EDTA | 76 | 0.05-46.59 | y = 0.99x + 0.00 ng/mL | 0.996 |
| Serum (SST) | K3EDTA | 76 | 0.05-46.59 | y = 1.00x + 0.01 ng/mL | 0.996 |
31
14. Clinical Study
Not applicable
14.1 Reference Interval
The reference Interval for the B·R·A·H·M·S PCT sensitive KRYPTOR assay was verified for serum and plasma specimens from 33 apparently healthy individuals with the Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay according to CLSI EP28-A3c. The reference interval claim in the Instructions For Use is