DiaSys Procalcitonin FS; DiaSys TruCal Procalcitonin Calibrator Set; DiaSys TruLab Procalcitonin Bi-Level Controls
Device Facts
| Record ID | K242294 |
|---|---|
| Device Name | DiaSys Procalcitonin FS; DiaSys TruCal Procalcitonin Calibrator Set; DiaSys TruLab Procalcitonin Bi-Level Controls |
| Applicant | Diasys Diagnostic Systems GmbH |
| Product Code | PTF · Microbiology |
| Decision Date | May 9, 2025 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3215 |
| Device Class | Class 2 |
Indications for Use
DiaSys Procalcitonin FS assay is a particle enhanced immunoturbidimetric test intended for the quantitative in vitro determination of procalcitonin (PCT) in human serum and lithium heparin plasma on automated Abbott ARCHITECT c8000 analyzer. Measurement of PCT in conjunction with other laboratory findings and clinical assessments aids 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. The TruCal Procalcitonin Calibrator Set is intended for in vitro use for calibration of the DiaSys Procalcitonin FS assay. TruLab Procalcitonin Bi-Level Controls are an assayed quality control material for monitoring the performance of quantitative in vitro determination of Procalcitonin (PCT) for the DiaSys Procalcitonin FS assay. For in vitro diagnostic use only.
Device Story
Particle enhanced turbidimetric immunoassay (PETIA) for quantitative procalcitonin (PCT) measurement; utilizes Abbott Architect c8000 analyzer. Input: 10 µL human serum or lithium heparin plasma. Mechanism: PCT binds to anti-PCT polyclonal antibodies on 0.35 µm polystyrene particles; causes agglutination; turbidity measured photometrically at 660 nm. Output: PCT concentration (ng/mL). Used in clinical laboratory settings by trained personnel. Results interpreted alongside clinical assessments to aid risk stratification for severe sepsis/septic shock in ICU patients. Benefits include rapid, automated quantitative assessment of sepsis risk.
Clinical Evidence
Bench testing only. Method comparison study (N=210) against predicate device using Passing/Bablok regression (R=0.965). Agreement at 0.5 ng/mL cutoff: 98% negative, 100% positive. Agreement at 2.0 ng/mL cutoff: 100% negative, 94% positive. Analytical performance validated per CLSI guidelines (EP05-A3, EP06, EP07, EP09c, EP15-A3, EP17-A2).
Technological Characteristics
Particle enhanced immunoturbidimetric assay. Reagents: Tris-buffer, goat anti-human PCT antibodies on polystyrene particles. Analyzed on Abbott ARCHITECT c8000. Sample matrices: serum, lithium heparin plasma. Stability: 24 months. Calibration: 6-level set. Controls: Bi-level.
Indications for Use
Indicated for critically ill patients on their first day of ICU admission to aid in risk assessment for progression to severe sepsis and septic shock. Used with human serum and lithium heparin plasma.
Regulatory Classification
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.
Special Controls
A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis must comply with the following special controls:
*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 820.10(c) design and development, 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.
Predicate Devices
- VIDAS B.R.A.H.M.S. PCT ASSAY (K071146)
Related Devices
- K170652 — ARCHITECT B.R.A.H.M.S PCT, ARCHITECT B.R.A.H.M.S PCT Calibrators, ARCHITECT B.R.A.H.M.S PCT Controls · Fisher Diagnostics · Jun 1, 2017
- K162297 — Diazyme Procalcitonin (PCT) Assay, Diazyme Procalcitonin (PCT) Calibrator Set, Diazyme Procalcitonin (PCT) Control Set · Diazyme Laboratories · Apr 18, 2017
Submission Summary (Full Text)
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FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY ONLY
## I Background Information:
A 510(k) Number
K242294
B Applicant
DiaSys Diagnostic Systems GmbH
C Proprietary and Established Names
DiaSys Procalcitonin FS assay; DiaSys TruCal Procalcitonin Calibrator Set; DiaSys TruLab Procalcitonin Bi-Level Controls
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| PTF | Class II | 21 CFR 866.3215 - Device To Detect And Measure Non-Microbial Analyte(S) In Human Clinical Specimens To Aid In Assessment Of Patients With Suspected Sepsis | MI - Microbiology |
## II Submission/Device Overview:
A Purpose for Submission:
The purpose of this submission is to obtain a substantial equivalence determination for the DiaSys Procalcitonin FS, DiaSys TruCal Procalcitonin Calibrator Set, and DiaSys TruLab Procalcitonin Bi-Level Controls.
B Measurand:
Procalcitonin
C Type of Test:
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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A particle enhanced immunoturbidimetric test for procalcitonin
## III Intended Use/Indications for Use:
### A Intended Use(s):
See Indications for Use below.
### B Indication(s) for Use:
DiaSys Procalcitonin FS assay is a particle enhanced immunoturbidimetric test intended for the quantitative in vitro determination of procalcitonin (PCT) in human serum and lithium heparin plasma on automated Abbott ARCHITECT c8000 analyzer.
Measurement of PCT in conjunction with other laboratory findings and clinical assessments aids 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.
The TruCal Procalcitonin Calibrator Set is intended for in vitro use for calibration of the DiaSys Procalcitonin FS assay.
TruLab Procalcitonin Bi-Level Controls are an assayed quality control material for monitoring the performance of quantitative in vitro determination of Procalcitonin (PCT) for the DiaSys Procalcitonin FS assay.
For in vitro diagnostic use only.
### C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
### D Special Instrument Requirements:
The DiaSys Procalcitonin FS assay is intended for use with the Abbott Architect c8000 analyzer.
## IV Device/System Characteristics:
### A Device Description:
The DiaSys Procalcitonin FS assay is a particle enhanced turbidimetric immunoassay (PETIA) test for in vitro quantitative determination of procalcitonin (PCT) levels in human serum and lithium heparin plasma on the Abbott Architect c8000 analyzer. Measurement of PCT in conjunction with other laboratory findings and clinical assessments aids in the risk assessment of critically ill patients on their first day of ICU admission for progressive to severe sepsis and septic shock.
A description of the reagent pack is provided below.
- DiaSys Procalcitonin FS [Reagent 1]: 0.1 mol/L Tris-buffer, pH 6.5
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- DiaSys Procalcitonin FS [Reagent 2]: Includes polystyrene beads coupled with anti-hPCT polyclonal antibodies, facilitating the specific and quantitative antibody-antigen reaction. Contains materials of bovine origin to colloidally stabilize the suspension and mitigate potential non-specific binding.
The DiaSys TruCal Procalcitonin Calibrator Set is provided in six levels, traceable to a commercial assay for use in the calibration of the DiaSys Procalcitonin FS assay.
The DiaSys TruLab Procalcitonin Bi-Level Controls, Levels 1 (low) and 2 (high) are intended for use as quality control for the DiaSys Procalcitonin FS assay.
DiaSys PCT Calibrators and Bi-Level Controls are ready-to-use, stable, aqueous solutions containing recombinant human full-length PCT and biological additives from bovine origin.
## B Principle of Operation:
Ten microliters of human serum or lithium heparin plasma can be used in the DiaSys Procalcitonin FS assay. PCT in the sample binds to the anti-PCT antibodies on the particles and causes agglutination. The degree of the turbidity caused by agglutination is optically measured at 660 nm by the automated photometric system and is proportional to the amount of PCT in the sample. DiaSys Procalcitonin FS Reagent specifies settings for an automated photometric analyzer, the Abbott Architect c8000.
The instrument pipettes the first reagent (R1) into the cuvette in the dedicated rotating tray, followed by the introduction of the sample. After mixing, the reaction undergoes incubation at 37 °C for approximately five minutes. The second reagent (R2) is pipetted into the same cuvette, mixed, and once again incubated at 37 °C for additional five minutes. The test utilizes anti-human PCT polyclonal antibodies (goat) covalently bound to 0.35 µm polystyrene particles. PCT in the sample binds to the anti-PCT antibodies on the particles and causes agglutination. The absorbance of each cuvette is continuously monitored in real-time during the ten minutes to derive the specific kinetics of each reaction.
## V Substantial Equivalence Information:
A Predicate Device Name(s):
VIDAS B.R.A.H.M.S. PCT ASSAY
B Predicate 510(k) Number(s):
K071146
C Comparison with Predicate(s):
| Device & Predicate Device(s): | K242294 | K071146 |
| --- | --- | --- |
| | DiaSys Diagnostic Systems GmbH | BIOMERIEUX, INC. |
| Device Trade Name | DiaSys Procalcitonin FS assay; DiaSys TruCal Procalcitonin | VIDAS B.R.A.H.M.S. PCT ASSAY |
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K242294 - Page 4 of 17
| | Calibrator set; DiaSys TruLab Procalcitonin Bi-level controls | |
| --- | --- | --- |
| **General Device Characteristic Similarities** | | |
| Intended Use/Indications For Use | DiaSys Procalcitonin FS assay is a particle enhanced immuno-turbidimetric test intended for the quantitative in vitro determination of procalcitonin (PCT) in human serum and lithium heparin plasma on automated Abbott ARCHITECT c8000 analyzer. Measurement of PCT in conjunction with other laboratory findings and clinical assessments aids 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.
The TruCal Procalcitonin Calibrator Set is intended for in vitro use for calibration of the DiaSys Procalcitonin FS assay.
TruLab Procalcitonin Bi-Level Controls are an assayed quality control material for monitoring the performance of quantitative in vitro determination of Procalcitonin (PCT) for the DiaSys | The VIDAS BRAHMS PCT is an automated test for use on the VIDAS instruments for the determination of human procalcitonin in human serum or plasma (lithium heparin) using the Enzyme-Linked Fluorescent Assay (ELFA) technique. The VIDAS BRAHMS PCT 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. |
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| | Procalcitonin FS assay. For in vitro diagnostic use only | |
| --- | --- | --- |
| Analyte Measured | Procalcitonin (PCT) | Same |
| Sample Type | Human serum or Plasma (LiHep) | Same |
| Method | Automated Assay | Same |
| General Device Characteristic Differences | | |
| Technology | Particle enhanced immunoturbidimetric method – for use on automated photometric system(s) | Immunoassay based on sandwich Enzyme-Linked Fluorescent Assay (ELFA) – for use on automated assay |
| Assay Duration | 10 min | 20 min |
| Measuring Range | 0.23 – 50 ng/mL | 0.05 – 200 ng/mL |
| Sample Volume | 10 μL | 200 μL |
| Limit of Blank | 0.081 ng/mL | 0.01 ng/mL |
| Limit of Quantitation | 0.23 ng/mL | 0.05 ng/mL |
| Hook Effect | No prozone effect up to 1000 ng/mL | No hook effect found up to concentrations of 2600 ng/ml |
| Calibrators | Six-level Calibrator | Two-level Calibrator |
VI Standards/Guidance Documents Referenced:
- CLSI EP05-A3. Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - Third Edition.
- CLSI EP06. Evaluation of the Linearity of Quantitative Measurement Procedures.
- CLSI EP07. Interference Testing in Clinical Chemistry.
- CLSI EP09c. Measurement Procedure Comparison and Bias Estimation Using Patient Samples
- CLSI EP15-A3. User Verification of Precision and Estimation of Bias; Approved Guideline - Third Edition
- CLSI EP17-A2. Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition
- CLSI EP25-A. Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline.
- ISO 17511:2020. In vitro diagnostic medical devices - Requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples
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# VII Performance Characteristics (if/when applicable):
# A Analytical Performance:
# 1. Precision/Reproducibility:
Within-run and within-laboratory precision of the DiaSys Procalcitonin FS assay were evaluated using the Abbott Architect c8000 analyzer. Studies were performed in accordance with CLSI guideline EP05-A3, "Evaluation of Precision Performance of Quantitative Measurement Methods". One reagent lot was evaluated. Within-run precision was evaluated using five serum and five plasma samples with PCT concentrations spanning the measuring range. Each sample was divided into 20 aliquots and PCT concentrations were measured. PCT measurements were used to calculate the sample mean, standard deviation, and coefficient of variation (CV). The acceptance criteria required the following $\% \mathrm{CV}$ for each PCT concentration range: $0.2 - 1.0\mathrm{ng / mL}\% \mathrm{CV}\leq 10\%$ , CV for $1.0 - 3.0\mathrm{ng / mL}\% \mathrm{CV}\leq 7\%$ $3.0 - 20\mathrm{ng / mL}\% \mathrm{CV}\leq 5\%$ , and $20 - 30\mathrm{ng / mL}\% \mathrm{CV}\leq 4\%$ . Results for serum and plasma are shown below in Table 1. All evaluation samples except the near-LoQ serum sample met the acceptance criteria. The near-LoQ sample is expected to have greater imprecision due to the proximity to the limit of quantitation and similar variability results were observed at the LoQ and from the near-LoQ sample. The precision at both medical decision points were within the acceptance criteria and the data are acceptable.
Table 1. Summary of DiaSys Procalcitonin FS assay within-run precision
| Sample Type | Evaluation Sample | Mean PCT [ng/mL] | SD [ng/mL] | %CV | Δ Max - Min [ng/mL] |
| --- | --- | --- | --- | --- | --- |
| Serum | Near LoQ | 0.252 | 0.0418 | 16.62 | 0.14 |
| | Lower decision limit | 0.555 | 0.0216 | 3.89 | 0.08 |
| | Higher decision limit | 2.02 | 0.0562 | 2.78 | 0.26 |
| | High [PCT] | 9.68 | 0.217 | 2.24 | 0.72 |
| | Very high [PCT] | 18.8 | 0.406 | 2.16 | 1.50 |
| Plasma | Near LoQ | 0.314 | 0.0251 | 8.00 | 0.08 |
| | Lower decision limit | 0.475 | 0.0330 | 6.94 | 0.13 |
| | Higher decision limit | 1.91 | 0.0559 | 2.93 | 0.22 |
| | High [PCT] | 9.85 | 0.191 | 1.94 | 0.87 |
| | Very high [PCT] | 18.0 | 0.352 | 1.96 | 1.33 |
To determine within-laboratory precision, a study was conducted over 20 days with 2 runs per day and 2 replicates per sample. Five serum and five plasma samples with PCT concentrations spanning the measuring range were measured on 20 consecutive days. For each sample the mean, standard deviation, and coefficient of variation were calculated. The acceptance criteria required the following $\% \mathrm{CV}$ for each sample type: $0.2 - 1.0\mathrm{ng / mL}\% \mathrm{CV}$ $\leq 13\%$ , CV for $1.0 - 3.0\mathrm{ng / mL}\% \mathrm{CV}\leq 10\%$ $3.0 - 20\mathrm{ng / mL}\% \mathrm{CV}\leq 8\%$ , and $20 - 30\mathrm{ng / mL}$ $\% \mathrm{CV}\leq 7\%$ . Results are displayed in Table 2. The data were considered acceptable.
Table 2. Summary of DiaSys Procalcitonin FS assay within-laboratory precision
| Sample Type | Evaluation Sample | Mean PCT [ng/mL] | Within-laboratory (total precision) %CV | Between-run (within-day) %CV | Between-day (day-to-day) %CV | Repeatability (within-run) %CV |
| --- | --- | --- | --- | --- | --- | --- |
| Serum | Near LoQ | 0.252 | 0.0418 | 16.62 | 0.14 | 0.08 |
| | Lower decision limit | 0.555 | 0.0216 | 3.89 | 0.08 | 0.08 |
| | Higher decision limit | 2.02 | 0.0562 | 2.78 | 0.26 | 0.08 |
| | High [PCT] | 9.68 | 0.217 | 2.24 | 0.72 | 0.08 |
| | Very high [PCT] | 18.8 | 0.406 | 2.16 | 1.50 | 0.08 |
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| Serum | Near LoQ | 0.29 | 11.52 | - | 4.22 | 10.72 |
| --- | --- | --- | --- | --- | --- | --- |
| | Lower decision limit | 0.57 | 5.64 | 3.14 | - | 4.69 |
| | Higher decision limit | 2.23 | 2.34 | 0.29 | 1.25 | 1.95 |
| | Pathological | 10.46 | 1.93 | 0.56 | 1.04 | 1.52 |
| | Strongly Pathological | 20.75 | 2.00 | - | 0.76 | 1.85 |
| Plasma | Near LoQ | 0.32 | 12.65 | - | 4.07 | 11.98 |
| | Lower decision limit | 0.48 | 8.31 | - | - | 8.31 |
| | Higher decision limit | 1.81 | 3.24 | 1.08 | 1.77 | 2.49 |
| | Pathological | 9.43 | 2.61 | 1.49 | 1.70 | 1.30 |
| | Strongly Pathological | 17.93 | 2.12 | 1.28 | - | 1.69 |
2. Linearity:
Studies to determine the linearity of the DiaSys Procalcitonin FS assay on the Abbott Architect c8000 analyzer were based on CLSI EP06-Ed2, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The linearity study data was used to evaluate the percent recovery for spiked samples by evaluating known concentrations of procalcitonin in serum and plasma samples. Sample dilutions distributed evenly across the analytical measuring range were made by mixing one high sample and one low sample in varying ratios. Four replicates of each sample were measured. Mean sample measurements and target values were plotted and analyzed by linear regression. The acceptance criteria were as follows: recovery of sample concentration between 0.2 ng/mL up to 0.5 ng/mL within ± 0.1 ng/mL limits to regression line; recovery of sample concentration between 0.5 ng/mL up to 5 ng/mL within ± 20% limits to regression line; and recovery of sample concentration between 5 ng/mL up to at least 50 ng/mL within ± 10% limits to regression line.
Overall, the DiaSys Procalcitonin FS assay demonstrated acceptable linearity throughout the analytical measuring range of 0.233 ng/mL to 50 ng/mL.
3. Analytical Specificity/Interference:
The analytical specificity of the DiaSys Procalcitonin FS assay was determined using native human serum samples spiked with the potential cross reactant and based on recommendations contained in the guideline EP07 Interference testing in Clinical Chemistry, 3rd edition. Solutions of the potential cross reactant were added directly to the serum in no more than 5% (v/v) final concentration. Control samples were prepared in the same manner using the solvent, without the cross-reactant added. Six replicates of each sample were tested. The samples were tested on an Abbott Architect c8000 analyzer. The means of the measured PCT concentrations were graphed against the concentration of the potential cross reactant. Recovery within ± 15 % of initial value at PCT concentrations near 0.5 ng/mL and 2.0 ng/mL was verified for each cross-reactant concentration. See Table 3 below for the list and concentrations of each interferent evaluated. All tested interferents met the acceptance criteria at both PCT concentrations.
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Table 3. Interfering Substances Tested
| Potential Interferent | Tested Concentration |
| --- | --- |
| Ascorbic acid | 151 mg/dL |
| α-CGRP | 12 μg/mL |
| Azithromycin | 1.44 mg/dL |
| β-CGRP | 12 μg/mL |
| Bilirubin (conjugated) | 72.5 mg/dL |
| Bilirubin (unconjugated) | 71.4 mg/dL |
| Calcitonin | 10.8 ng/mL |
| Cefotaxime | 189 mg/dL |
| Cromolyn | 28.8 mg/L |
| Dobutamine | 27.3 μg/mL |
| Dopamine | 27.3 mg/dL |
| Doxycycline | 6.61 mg/dL |
| Enoxaparin | 24000 U/L |
| Ethanol | 720 mg/dL |
| Furosemide | 4.2 mg/dL |
| HAMA | 480 ng/dL |
| Hemolysis | 1200 mg/dL |
| Ibuprofen | 63.1 mg/dL |
| Imipenem | 2.52 mg/mL |
| Katacalcin | 6 ng/mL |
| | 1910 mg/dL |
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| Lipemia | |
| --- | --- |
| Noradrenalin | 4.2 µg/mL |
| Pantoprazole | 4.32 mg/dL |
| Rheumatoid factor | 1020 IU/mL |
| Salmeterol
Xinafoate | 104 ng/mL |
| Scopolamine-N-
butyl bromide | 72 mg/L |
| Total Protein | 139 g/mL |
| Vancomycin | 3.78 mg/mL |
4. **Assay Reportable Range:**
The analytical measuring interval is 0.23 – 50 ng/mL of PCT.
5. **Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):**
**Calibrators/Traceability**
The TruCal Procalcitonin Calibrators are a six-level calibrator set intended to calibrate the DiaSys Procalcitonin FS assay for the quantitative determination of procalcitonin levels in human serum and plasma using the Abbott Architect c8000 analyzer. The calibrators are provided at six PCT concentration levels – Level 0: 0.00 ng/mL, Level 1: 0.9 ng/mL ± 0.2 ng/mL, Level 2: 4,0 ng/mL ± 2.5 ng/mL, Level 3: 10 ng/mL ± 2.0 ng/mL, Level 4: 20 ng/mL ± 2.5 ng/mL, Level 5: 50 ± 5 ng/mL. The TruCal Procalcitonin Calibrators are intended for storage at 2 - 8°C and are stable for 12 months after opening or until the expiry date. Values assigned to the DiaSys internal master TruCal PCT calibrator for the DiaSys Procalcitonin FS assay are traceable to a commercially available test (VIDAS B.R.A.H.M.S. PCT, which is also the predicate assay).
**Sample Stability**
The *in vitro* stability of procalcitonin antigen in human serum and lithium heparin plasma using the DiaSys Procalcitonin FS assay was characterized at one internal site to determine sample handling and storage conditions. Fifteen human serum and 15 human plasma lithium heparin samples spanning the entire analytical range of the DiaSys Procalcitonin FS test were measured at pre-determined times using the Abbott Architect c8000 analyzer. Samples were stored at the specified storage conditions (-20°C, at 2-8°C, 20-25°C). At each time point, an aliquot of each sample was equilibrated to measurement temperature and measured. The percent recovery of each sample at each time point was
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calculated and compared to the concentration measured at time 0. Acceptance criteria specified sample measurements be within $\pm 15\%$ of the concentration at time zero. Sample stability results are shown in Tables 4, 5, and 6.
Table 4. DiaSys Procalcitonin FS assay -30°C to -15°C sample stability
| | | Freezer (-30°C to -15°C) | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | 3 days | 7 days | 10 days | 14 days | 15 days | 17 days | 18 days |
| Sample Type | Sample Number | Mean % Concentration Difference from T0 | | | | | | |
| Serum | 1 | 8.6 | 0.9 | 6.2 | 7.5 | 3.9 | 5.9 | -4.5 |
| | 2 | 4.3 | 0.3 | 9.7 | 1.5 | -4.6 | -3.0 | -4.2 |
| | 3 | -0.4 | 1.0 | 4.3 | -0.9 | -0.8 | 0.5 | -3.5 |
| | 4 | -4.4 | 0.0 | -0.4 | 0.6 | -0.9 | -0.7 | -2.9 |
| | 5 | -0.4 | -0.3 | -1.0 | -0.1 | -1.0 | -0.2 | -1.7 |
| | 6 | 0.2 | -1.1 | -1.6 | -1.1 | -1.3 | -0.3 | -1.5 |
| | 7 | 0.6 | -0.6 | -1.5 | -0.6 | -1.3 | -1.0 | -2.1 |
| | 8 | 0.4 | -1.4 | -2.1 | -1.2 | -1.6 | -1.1 | -1.8 |
| | 9 | -0.2 | -1.2 | -2.4 | -2.0 | -2.2 | -1.1 | -2.9 |
| | 10 | -0.1 | -1.2 | -2.9 | -1.9 | -1.9 | -1.6 | -2.8 |
| | 11 | 0.8 | -0.8 | -3.2 | -1.9 | -1.9 | -1.6 | -3.0 |
| | 12 | 0.3 | -1.6 | -3.3 | -2.6 | -2.9 | -2.0 | -3.5 |
| | 13 | 0.6 | -0.8 | -3.9 | -2.5 | -2.2 | -1.8 | -3.4 |
| | 14 | 1.3 | 0.0 | -3.6 | -1.2 | -1.4 | -0.4 | -3.5 |
| | 15 | 1.4 | -0.2 | -3.9 | -2.1 | -1.1 | -1.1 | -4.4 |
| Plasma Lithium Heparin | 1 | -0.2 | -7.8 | 2.9 | 2.5 | -0.7 | -2.0 | -8.0 |
| | 2 | 7.4 | 5.8 | 3.7 | 7.2 | -7.9 | 0.3 | 5.5 |
| | 3 | 2.6 | -4.6 | -4.4 | 1.7 | -0.7 | 0.6 | 1.4 |
| | 4 | 5.4 | 3.9 | 2.7 | 3.2 | 8.0 | 7.3 | 6.9 |
| | 5 | -0.6 | -1.9 | -0.8 | -1.0 | -2.0 | -1.4 | -0.8 |
| | 6 | -0.4 | -1.8 | -1.9 | -0.7 | -1.1 | -1.3 | -1.2 |
| | 7 | -0.1 | -0.7 | -1.3 | -0.6 | -0.5 | 0.0 | -0.8 |
| | 8 | 0.6 | -0.6 | -2.1 | -0.3 | -0.2 | -0.1 | -0.8 |
| | 9 | -0.1 | -1.0 | -2.2 | -0.8 | -0.9 | -1.0 | -2.1 |
| | 10 | -0.1 | -1.8 | -3.3 | -0.9 | -1.2 | -2.1 | -2.5 |
| | 11 | 0.2 | -1.7 | -3.9 | -0.9 | -0.9 | -0.1 | -1.9 |
| | 12 | 0.2 | -1.4 | -3.9 | -1.0 | -1.5 | -1.5 | -2.2 |
| | 13 | -1.3 | -2.3 | -4.3 | -1.2 | -2.0 | -2.3 | -2.4 |
| | 14 | 0.3 | -1.9 | -4.9 | -2.0 | -1.5 | -2.3 | -4.3 |
| | 15 | 1.6 | -1.1 | -4.9 | -2.4 | -2.0 | -1.5 | -3.1 |
Table 5. DiaSys Procalcitonin FS assay ${2}^{ \circ }\mathrm{C}$ to ${8}^{ \circ }\mathrm{C}$ sample stability
| | | Refrigerated (2°C to 8°C) | | | |
| --- | --- | --- | --- | --- | --- |
| | | 3 days | 5 days | 6 days | 7 days |
| Sample Type | Sample Number | Mean % Concentration Difference from T0 | | | |
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Table 6. DiaSys Procalcitonin FS assay ${20}^{ \circ }\mathrm{C}$ to ${25}^{ \circ }\mathrm{C}$ sample stability
| | | Room Temperature (20°C to 25°C) | | |
| --- | --- | --- | --- | --- |
| | | 24 h | 30 h | 48 h |
| Sample Type | Sample Number | Mean % Concentration Difference from T0 | | |
| | 1 | -9.3 | -4.7 | -3.9 |
| | 2 | -11.7 | -6.6 | -5.2 |
| | 3 | 6.3 | -0.2 | 3.7 |
| | 4 | -0.6 | -0.3 | -1.7 |
| | 5 | -0.6 | -2.2 | -2.1 |
| | 6 | -1.1 | -2.1 | -2.3 |
| | 7 | -0.8 | -1.9 | -2.0 |
| | | | | |
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| Serum | 8 | -1.1 | -2.3 | -1.9 |
| --- | --- | --- | --- | --- |
| | 9 | -0.3 | -1.8 | -1.7 |
| | 10 | -1.1 | -2.1 | -2.2 |
| | 11 | -1.9 | -2.6 | -4.0 |
| | 12 | -1.6 | -2.7 | -3.1 |
| | 13 | -1.5 | -3.2 | -4.4 |
| | 14 | -1.2 | -2.3 | -3.5 |
| | 15 | -1.9 | -4.2 | -2.7 |
| Plasma Lithium Heparin | 1 | -6.1 | -3.5 | -10.0 |
| | 2 | -3.6 | 2.5 | -9.4 |
| | 3 | 1.2 | -1.2 | -9.6 |
| | 4 | -2.4 | -5.1 | -7.0 |
| | 5 | -3.6 | -4.5 | -6.0 |
| | 6 | -2.5 | -4.6 | -6.5 |
| | 7 | -4.1 | -6.0 | -8.4 |
| | 8 | -3.3 | -6.4 | -8.2 |
| | 9 | -3.7 | -6.0 | -4.6 |
| | 10 | -2.5 | -5.5 | -4.4 |
| | 11 | -5.0 | -6.5 | -6.0 |
| | 12 | -2.4 | -5.5 | -4.4 |
| | 13 | -3.1 | -6.3 | -5.6 |
| | 14 | -2.0 | -5.5 | -4.3 |
| | 15 | -3.8 | -5.8 | -5.3 |
Freeze-thaw stability of human serum and plasma lithium heparin samples used the same sample distribution as noted for the sample storage stability study. Fifteen human samples (either serum or plasma lithium heparin) covering the analytical range of the DiaSys Procalcitonin FS assay were measured using the Abbott Architect c8000 analyzer, at time 0, then after one freeze/thaw cycle, and again after a second freeze thaw cycle. Both serum and plasma samples were tested. All samples tested after two freeze/thaw cycles met the acceptance criteria of within $15\%$ of the PCT concentration of fresh samples (Table 7).
Table 7. DiaSys Procalcitonin FS assay Freeze-Thaw sample stability
| | | Freeze-Thaw Cycles | |
| --- | --- | --- | --- |
| | | 1 | 2 |
| Sample Type | Sample Number | Mean % Concentration Difference from Fresh | |
| | 1 | 5.0 | 4.5 |
| | 2 | 3.2 | 9.5 |
| | 3 | -1.9 | -1.3 |
| | 4 | -2.2 | -0.9 |
| | 5 | -0.5 | 0.4 |
| | 6 | -0.3 | 0.9 |
| | 7 | -1.7 | -0.7 |
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| Serum | 8 | -1.3 | 1.1 |
| --- | --- | --- | --- |
| | 9 | -0.3 | 0.6 |
| | 10 | -0.6 | 0.6 |
| | 11 | -2.3 | 0.2 |
| | 12 | -1.9 | 1.1 |
| | 13 | 1.3 | 1.8 |
| | 14 | -2.7 | 0.3 |
| | 15 | 1.9 | 3.3 |
| Plasma Lithium Heparin | 1 | 5.6 | 5.4 |
| | 2 | -0.4 | -2.9 |
| | 3 | 0.8 | 5.7 |
| | 4 | -3.2 | 0.3 |
| | 5 | 0.1 | 1.2 |
| | 6 | -0.4 | 1.3 |
| | 7 | -0.1 | 0.1 |
| | 8 | -0.2 | 0.7 |
| | 9 | -3.2 | -1.1 |
| | 10 | -0.6 | 0.7 |
| | 11 | -0.7 | -0.3 |
| | 12 | -5.4 | -2.7 |
| | 13 | -1.3 | -2.2 |
| | 14 | 1.8 | 0.0 |
| | 15 | -2.1 | -1.2 |
Cumulatively, these data support the claimed sample stability in the DiaSys Procalcitonin FS assay instructions for use.
# 6. Limit of Blank (LoB), Quantitation (LoQ), and Detection (LoD):
Studies were performed to determine the LoB, LoQ, and LoD for the DiaSys Procalcitonin FS assay consistent with recommendations in CLSI EP17-A2 (Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition).
# LoB
For estimation of LoB, one Abbott Architect c8000 analyzer was used in the study design with two reagent lots and one calibrator lot. TruCal PCT Level 0 Calibrators corresponding to lyophilized HEPES buffer with protein (bovine), $\leq 0.1\%$ sodium azide, and $0.1\%$ ProClin300. Four Level 0 Calibrators were measured five times per day over three days per reagent lot resulting in 120 determinations in total (60 determinations per reagent lot). The LoB was determined using the $95\%$ non-parametric percentile for both reagent lots and the higher of the two concentrations was selected as the LoB. The LoB estimate of the DiaSys Procalcitonin FS assay is $0.081\mathrm{ng / mL}$ and met the acceptance criteria of $\leq 0.2\mathrm{ng / mL}$ .
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# LoQ
To estimate the LoQ, nine human serum and nine plasma samples with different values were assayed on 20 consecutive days. On each day two replicates were measured non-consecutively. For each sample mean (per run and per day), standard deviation and coefficient of variation (%CV) were calculated. The higher of the two LoQ determinations (serum) was claimed as the LoQ. The lowest sample concentration that met the accuracy goal of %CV ≤ 20% was 0.233 ng/mL. The claimed LoQ concentration of 0.233 ng/mL met the acceptance criteria of LoQ ≤ 0.5 ng/mL; %CV ≤ 20%. The LoQ is equivalent to the limit of detection for the DiaSys Procalcitonin FS assay.
# LoD
The dataset used to estimate the LoQ was used to determine the LoD. The LoD was determined by fitting the precision profile model between within-lab standard deviation (SD) and concentration. The SD was multiplied by the 95th percentile of the standard normal distribution and added to the LoB to calculate the LoD per CLSI EP17-A2. The maximum observed LoD is taken as the reported value for the measurement procedure. The LoD estimate of the DiaSys Procalcitonin FS assay is 0.233 ng/mL and equivalent to the LoQ.
# 7. Assay Cut-Off:
The DiaSys Procalcitonin FS assay 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. The interpretation of PCT results are as follows:
Table 8. Result Interpretation
| PCT concentration | Result Interpretation |
| --- | --- |
| < 0.5 ng/mL | Low risk of severe sepsis and/or septic shock. |
| ≥ 2.0 ng/mL | High risk of severe sepsis and/or septic shock. |
PCT concentrations between 0.5 and 2.0 ng/mL should be interpreted with consideration of the patient's history.
# B Comparison Studies:
1. Method Comparison with Predicate Device:
A method comparison study was completed to compare the DiaSys Procalcitonin FS assay on the Abbott Architect c8000 analyzer to the predicate (B.R.A.H.M.S PCT assay on the VIDAS analyzer). Method comparison samples were residual serum samples from patients with a physician's order for procalcitonin testing on their first day of Intensive Care Unit (ICU) admission. Procalcitonin concentrations measured by the predicate device and the DiaSys Procalcitonin FS assay were analyzed by Passing/Bablok linear regression (Table 9 and Figure 1). These data were used to establish positive and negative agreement at clinical decision points (0.5 ng/mL and 2.0 ng/mL) (Tables 10, 11, and 12).
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A total of 210 native serum samples were measured in duplicate with each method. Results of the regression analysis are described below.
Figure 1: Passing/Bablok Regression plots of DiaSys Procalcitonin FS assay versus Predicate
Table 9. Regression Analysis of DiaSys Procalcitonin FS Assay versus Predicate
| N | DiaSys Procalcitonin FS Assay Range Of Observations (ng/mL) | B.R.A.H.M.S PCT assay Range Of Observations (ng/mL) | Intercept (ng/mL) [95% CI] | Slope [95% CI] | Correlation Coefficient (R) |
| --- | --- | --- | --- | --- | --- |
| 210 | 0.00 - 48.5 | 0.05 – 40.3 | 0.0140 [-0.008 – 0.047] | 0.939 [0.904 – 0.990] | 0.965 |
Table 10. Observed Agreement between DiaSys Procalcitonin FS assay and Predicate at ${0.5}\mathrm{\;{ng}}/\mathrm{{mL}}$ Cut-off
| DiaSys PCT Results | VIDAS PCT Results | | Samples |
| --- | --- | --- | --- |
| | PCT ≤ 0.5 ng/mL | PCT > 0.5 ng/mL | |
| PCT ≤ 0.5 ng/mL | 97 | 0 | 97 |
| PCT > 0.5 ng/mL | 2 | 111 | 113 |
| | 99 | 111 | 210 |
Table 11. Observed Agreement between DiaSys Procalcitonin FS assay and Predicate at ${2.0}\mathrm{\;{ng}}/\mathrm{{mL}}$ Cut-off
| DiaSys PCT Results | VIDAS PCT Results | | Samples |
| --- | --- | --- | --- |
| | PCT ≤ 2.0 ng/mL | PCT > 2.0 ng/mL | |
| PCT ≤ 2.0 ng/mL | 143 | 4 | 147 |
| PCT > 2.0 ng/mL | 0 | 63 | 63 |
| | 143 | 67 | 210 |
Table 12. Performance of DiaSys Procalcitonin FS assay Compared to Predicate Results
| Cutoff (> vs. ≤) | Negative Percent Agreement (95% CI) | Positive Percent Agreement (95% CI) |
| --- | --- | --- |
| 0.5 ng/mL | 98% (92.9% to 99.4%) | 100% (96.7% to 100%) |
| 2.0 ng/mL | 100% (97.4% to 100%) | 94% (85.6% to 97.7%) |
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These data support substantial equivalence of the DiaSys Procalcitonin FS assay to the predicate device.
## 2. Matrix Comparison:
A matrix comparison study was performed using human serum and lithium heparin plasma. Native patient samples were used to generate matched sets of serum and lithium heparin plasma. Samples spanned the analytical measuring range and were measured in duplicate for each matrix. Procalcitonin concentrations in serum matrix (x-axis) were compared against procalcitonin concentrations in lithium heparin plasma matrix (y-axis) by Passing/Bablok linear regression.
The observed linear fit for serum vs. lithium heparin plasma had an estimated slope of 0.999 with a 95% confidence interval (CI) of 0.976 to 1.02. Data from the regression analysis successfully demonstrate no significant performance differences between the evaluated sample matrices.
## C Clinical Studies:
1. Clinical Sensitivity:
Not applicable.
2. Clinical Specificity:
Not applicable.
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable.
## D Clinical Cut-Off:
Measurement of PCT in conjunction with other laboratory findings and clinical assessments aids 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. The established cut-offs for PCT are described below:
Table 13. Clinical Cut-offs
| PCT concentration | Result Interpretation |
| --- | --- |
| < 0.5 ng/mL | Low risk of severe sepsis and/or septic shock. |
| ≥ 2.0 ng/mL | High risk of severe sepsis and/or septic shock. |
PCT concentrations between 0.5 and 2.0 ng/mL should be interpreted with consideration of the patient's history.
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VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.
IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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