The Access PCT assay is a paramagnetic, chemiluminescent immunoassay for in vitro quantitative determination of procalcitonin (PCT) levels in human serum and plasma (lithium heparin and EDTA) using the Access Immunoassay Systems. 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 to severe sepsis and septic shock.

The Access PCT Calibrators are intended to calibrate the Access PCT assay for the quantitative determination of procalcitonin levels in human serum and plasma (lithium heparin and EDTA) using the Access Immunoassay Systems.

Device Description

The Access PCT assay is a paramagnetic, chemiluminescent immunoassay for in vitro quantitative determination of procalcitonin (PCT) levels in human serum and plasma using the Access Immunoassay Systems. 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.

R1a: Dynabeads* paramagnetic particles coated with mouse anti-human ● Procalcitonin monoclonal antibody in a TRIS buffer with surfactant, protein (bovine), ≤ 0.1% sodium azide, and 0.1% ProClin**300
R1b: 0.10 N Sodium Hvdroxide ●
R1c: MOPS Buffer with surfactant and protein (bovine, murine). ≤ 0.1% . sodium azide, and 0.1% ProClin 300
R1d: Rat anti-Procalcitonin recombinant alkaline phosphatase conjugate in a ● MOPS buffer with surfactant and protein (bovine, murine, recombinant), ≤ 0.1% sodium azide, and 0.1% ProClin 300

AI/ML Overview

This document describes the acceptance criteria and study results for the Beckman Coulter Access PCT assay, which measures procalcitonin (PCT) levels in human serum and plasma to aid in the risk assessment of critically ill patients for severe sepsis and septic shock.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria	Reported Device Performance
Method Comparison	Slope = 0.90 ± 0.10 relative to predicate (VIDAS® B·R·A·H·M·S PCT®)	Slope = 0.96 (95% CI: 0.94 to 0.99)
	Correlation Coefficient (r) ≥ 0.95	r = 0.99
Imprecision	Total imprecision ≤ 8.0% CV at concentrations ≥ 0.150 ng/mL; SD ≤ 0.012 ng/mL at concentrations < 0.150 ng/mL	Met or exceeded criteria (Exact reported values not specified for all points, but stated to meet criteria).
	Within-run imprecision ≤ 6.0% CV at concentrations ≥ 0.150 ng/mL; SD ≤ 0.009 ng/mL at concentrations < 0.150 ng/mL	Met or exceeded criteria (Exact reported values not specified for all points, but stated to meet criteria).
High-dose Hook Effect	No hook effect up to a specified high concentration.	No hook effect up to 5,000 ng/mL.
Linearity	Linear across the assay range.	Demonstrated to be linear (0.05 ng/mL to approximately 100 ng/mL).
Dilution Recovery	Overall average recovery of 100 ± 10%; individual sample dose recovery within ± 15% when diluted 10-fold.	Demonstrated to dilute recover across the range (0.05 ng/mL to approximately 100 ng/mL) in serum, lithium heparin plasma, and EDTA plasma samples, for concentrations up to 1,000 ng/mL. Overall average recovery 100 ± 10%, individual sample dose recovery within ± 15%.
Limit of Blank (LoB)	≤ 0.005 ng/mL	≤ 0.005 ng/mL
Limit of Detection (LoD)	≤ 0.01 ng/mL	≤ 0.01 ng/mL
Limit of Quantitation (LoQ)	≤ 0.02 ng/mL (based on 20% within-laboratory imprecision)	≤ 0.02 ng/mL
Total Error (at clinical cutoffs)	≤ 9.4% at 0.5 ng/mL and 2.0 ng/mL (Weighted Deming) / ≤ 11.3% at 0.5 ng/mL and 2.0 ng/mL (Passing Bablok)	At 0.5 ng/mL: Bias (%) 0.6%, CV (%) 4.5%, Total Error (%) 9.4% (Weighted Deming) / Bias (%) -0.6%, CV (%) 4.5%, Total Error (%) 9.4% (Passing Bablok) At 2.0 ng/mL: Bias (%) 0.7%, CV (%) 4.2%, Total Error (%) 8.9% (Weighted Deming) / Bias (%) -3.1%, CV (%) 4.2%, Total Error (%) 11.3% (Passing Bablok)
Analytical Specificity	Change in concentration between diluent control and test samples within ± 10% for potential cross-reactants.	No significant cross-reactivity for human calcitonin, human katacalcin, human alpha CGRP, and human beta CGRP (within ± 10% change).
Interfering Substances	Change in concentration between diluent control and test sample within ± 10% for potential interferents.	None of the tested substances were found to cause significant interference (within ± 10% change).
Expected Reference Intervals	Consistent with commonly used reference intervals (e.g., PCT ≤ 0.1 ng/mL for healthy individuals).	95th percentile of 0.065 ng/mL with a 95% Confidence Interval (CI) of 0.054 - 0.085 ng/mL.
Matrix Comparison	Slopes and confidence intervals within acceptable ranges for comparison between serum (gel), serum (no gel), lithium heparin plasma, and EDTA plasma.	Serum (gel) vs. serum (no gel): Slope = 0.99 (95% CI: 0.98 to 1.00). Lithium heparin plasma vs. serum (no gel): Slope = 0.96 (95% CI: 0.95 to 0.97). EDTA plasma vs. serum (no gel): Slope = 1.03 (95% CI: 1.01 to 1.04). Lithium heparin plasma vs. serum gel: Slope = 0.97 (95% CI: 0.96 to 0.99). EDTA plasma vs. serum gel: Slope = 1.04 (95% CI: 1.03 to 1.05). EDTA plasma vs. lithium heparin plasma: Slope = 1.06 (95% CI: 1.05 to 1.08).
Carryover Study	Shift of ≤ 10% for assay carryover.	Individual estimates of carryover ranged from -6% to +8%, indicating no clear trend of positive or negative shifts, thus meeting criteria.

2. Sample Size Used for the Test Set and Data Provenance

Method Comparison: Approximately 207 serum samples. The provenance of these samples (country of origin, retrospective/prospective) is not explicitly stated in the provided text.
Expected Reference Intervals: 202 apparently healthy individuals. These samples were "prospectively procured." The country of origin is not explicitly stated.
Matrix Comparison: Forty-three (43) matched sets of serum gel, serum no gel, plasma lithium heparin, and plasma EDTA samples. The provenance of these samples is not explicitly stated.
Analytical Specificity and Interfering Substances: Serum patient samples. The number of samples is not explicitly stated, nor is their provenance.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This device is an in vitro diagnostic (IVD) assay for measuring a biomarker (procalcitonin). The "ground truth" for such assays is typically established by reference methods or validated comparative assays, not by expert human graders. The studies compare the device's performance against either a legally marketed predicate device (VIDAS® B·R·A·H·M·S PCT®) or accepted analytical standards (e.g., CLSI guidelines). Therefore, no human experts were used to establish ground truth in the traditional sense of image or clinical interpretation.

4. Adjudication Method for the Test Set
Not applicable. As an IVD assay, the performance is assessed by comparing quantitative measurements against a predicate device or pre-defined analytical acceptance criteria, not through an adjudication process involving human experts.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This is an IVD assay, not an AI-assisted diagnostic tool that relies on human readers or interpretation of complex medical images/cases.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are all standalone performance assessments of the Access PCT assay. The device quantitatively determines PCT levels, and its performance characteristics (accuracy, precision, limits, specificity, interference) are evaluated intrinsically or by comparison to another diagnostic test, without a human-in-the-loop component for result generation.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The "ground truth" in these studies is based on:

Reference Method/Comparative Device: For method comparison, the predicate device (VIDAS® B·R·A·H·M·S PCT®) serves as the comparator.
Analytical Standards: For characteristics like linearity, imprecision, LoB, LoD, LoQ, analytical specificity, and interference, the "ground truth" is established by predefined analytical criteria, often guided by CLSI guidelines (e.g., EP17-A2 for LoQ, EP07 for interference).
Clinically Relevant Concentrations: For some studies (e.g., analytical specificity, interference), specific PCT concentrations (e.g., 0.25 ng/mL, 0.5 ng/mL, 2.0 ng/mL) are used as reference points for evaluation.

8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI. This device is an immunoassay, not an AI algorithm that requires training data. The studies presented are primarily analytical performance verification and validation studies.

9. How the Ground Truth for the Training Set was Established
Not applicable, as this is an immunoassay and does not involve an AI training set in the conventional sense.

Summary

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November 26, 2019

Beckman Coulter, Inc. Jennifer Bennett Staff Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318-1084

Re: K192271

Trade/Device Name: Access PCT, Access PCT Calibrators 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: PTF Dated: August 21, 2019 Received: August 22, 2019

Dear Jennifer Bennett:

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.

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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 mediation-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.

Kristian Roth, Ph.D. Branch Chief Bacterial Multiplex and Medical Counter Measures Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Ouality Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known) K192271

Device Name Access PCT, Access PCT calibrators

Indications for Use (Describe)

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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Access PCT 510(K) Summary

Immunodiagnostic Development Center

1000 Lake Hazeltine Drive Chaska, Minnesota 55318-1084

510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92(a)(1).

The assigned 510(k) number is

Submitted By:

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: (952) 368-1142 Fax: (952) 368-7610

Contact Person:

Jennifer Bennett 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: (952) 368-2040 Fax: (952) 368-7704

Alternate Contact: Kerrie Oetter

(952) 368-7858 (952) 368-7704 (fax)

Date Prepared:

August 22, 2019 November 18, 2019 (Updated)

Device Name:

Proprietary / Trade Name: Access PCT Reagent Common Name: Procalcitonin Immunoassay Classification Name: Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis Classification Regulation: 21 CFR 866.3215 Classification Product Code: PTF

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Predicate Device:

The Access PCT Reagent claims substantial equivalence to the VIDAS® B-R-A-H-M-S PCT®† assay kit by Biomerieux, FDA 510(k) Number K162827, cleared May 31, 2017.

Device Description:

A description of the reagent pack is provided below.

R1a: Dynabeads* paramagnetic particles coated with mouse anti-human ● Procalcitonin monoclonal antibody in a TRIS buffer with surfactant, protein (bovine), ≤ 0.1% sodium azide, and 0.1% ProClin**300
R1b: 0.10 N Sodium Hvdroxide ●
R1c: MOPS Buffer with surfactant and protein (bovine, murine). ≤ 0.1% . sodium azide, and 0.1% ProClin 300
R1d: Rat anti-Procalcitonin recombinant alkaline phosphatase conjugate in a ● MOPS buffer with surfactant and protein (bovine, murine, recombinant), ≤ 0.1% sodium azide, and 0.1% ProClin 300 *Dynabead® is a registered trademark of Dynal A.S., Oslo, Norway **ProClin™ is a trademark of The Dow Chemical Company ("Dow") or an affiliate company of Dow.

Intended Use:

Comparison to the Predicates:

The Access PCT Assay and the predicate device, VIDAS® B·R·A·H·M·S PCT®T assay (K162827), were compared. The information for the predicate device was derived from the predicate device 510(k) Summary and product labeling.

† VIDAS® is a registered trademark of bioMérieux SA. B·R·H·M·S PCT® is a registered trademark of B·R·A·H·M·S GmbH.

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	Predicate DeviceVIDAS® B·R·A·H·M·S PCT®†K162827	Proposed DeviceAccess PCT Assay on Access2 Immunoassay System
Intended Use/Indications forUse	VIDAS® B·R·A·H·M·S PCT®† (PCT) is an automated test for use on theinstruments of the VIDAS family for the determination of humanprocalcitonin in human serum or plasma (lithium heparinate) usingthe ELFA (Enzyme-LinkedFluorescent Assay) technique.Used in conjunction with other laboratory findings and clinicalassessments, VIDAS® B•R•A•H•M•S PCT®† is intended for use asfollows: · to aid in the riskassessment of critically ill patients on their first day of ICU admission forprogression to severe sepsis and septic shock, · to aid in assessingthe cumulative 28-day risk of all- cause mortality for patientsdiagnosed with severe sepsis or septic shock in the ICU or whenobtained in the emergency department or other medical wardsprior to ICU admission, using achange in PCT level over time, · to aid in decision making on antibiotictherapy for patients with suspected or confirmed lower respiratory tractinfections (LRTI) defined as community-acquired pneumonia(CAP), acute bronchitis, and acute exacerbation of chronic obstructivepulmonary disease (AECOPD) – in an inpatient setting or an emergencydepartment, · to aid in decision making on antibiotic discontinuationfor patients withsuspected or confirmed sepsis.	The Access PCT assay is a paramagnetic, chemiluminescentimmunoassay for in vitroquantitative determination of procalcitonin (PCT) levels inhuman serum and plasma(lithium heparin and EDTA)using the Access ImmunoassaySystems. Measurement of PCTin conjunction with other laboratory findings and clinicalassessments aids in the risk assessment of critically illpatients on their first day of ICUadmission for progression to severe sepsis and septic shock.
Characteristic	Predicate DeviceVIDAS® B-R-A-H-M-S PCT®†K162827	Proposed DeviceAccess PCT Assay on Access2 Immunoassay System
AnalyteMeasured	Procalcitonin (PCT)	Same
Sample Type	Human serum or plasma (lithiumheparinate)	Human Serum or Plasma (LiHepand EDTA)
Method	Automated Assay	Same
Format	ELFA (Enzyme-LinkedFluorescent Assay) technique	Chemiluminescent
Technology	Immunoassay based on sandwichprinciple	Same
PrimaryReagentMaterials	Solid Phase: Mouse monoclonalanti-procalcitoninimmunoglobinscoated on interior of the SPRConjugate: Alkaline phosphatase-labeled mouse monoclonal anti-human procalcitonin immunoglobins	Dynabeads* paramagneticparticles coated with mouseanti-human procalcitoninmonoclonal antibody
AssayDuration	Approximately 20 minutes	Same
SampleVolume	200 µL	35 µL
MeasuringRange	0.05 ng/mL to 100 ng/mL	0.05 ng/mL to 100 ng/mL
LoB	0.01 ng/mL	0.005 ng/mL
LoD	0.03 ng/mL	0.01 ng/mL
LoQ	0.05 ng/mL	0.02 ng/mL
Hook	No hook effect up to procalcitoninconcentrations of 2,600 ng/mL	No hook effect up to procalcitoninconcentrations of 5,000 ng/mL
ExpectedResults (UpperReferenceLimit)	99th percentile 0.09 ng/ml 95thpercentile < 0.05 ng/mL	95th percentile of 0.065 ng/mLwith a 95% Confidence Interval(CI) of 0.054 - 0.085 ng/mL

Comparison of Technological Characteristics to the Predicate (Assay)

† VIDAS® is a registered trademark of bioMérieux SA. B·R·A·H·M·S PCT is a registered trademark of B·R·A·H·M·S GmbH.

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*Dynabead® is a registered trademark of Dynal A.S., Oslo, Norway

† VIDAS® is a registered trademark of bioMérieux SA. B·R·A·H·M·S PCT® is a registered trademark of B·R·A·H·M·S GmbH.

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Summary of Studies

Method Comparison: A comparison of approximately 207 serum samples with PCT concentrations ranging from approximately 0.05 ng/mL to 100 ng/mL were run on both the Access PCT assay and the predicate VIDAS® B-R-A-H-M-S PCT®+ assay. The results were compared using Passing-Bablok regression and Pearson correlation with the predicate on the x-axis. The observed linear fit had a slope = 0.96 with 95% confidence interval of 0.94 to 0.99, an intercept =

0.02 nq/mL and a correlation coefficient (r) = 0.99. The slope specification is set at 0.90 ± 0.10 with correlation coefficient (r) ≥ 0.95.

Imprecision: The Access PCT assay exhibits total imprecision of ≤ 8.0% CV at concentrations ≥ 0.150 ng/mL, and standard deviation (SD) ≤ 0.012 ng/mL at concentrations < 0.150 ng/mL.

The Access PCT assay exhibits within run imprecision of ≤ 6.0% CV at concentrations ≥ 0.150 ng/mL, and a standard deviation (SD) ≤ 0.009 ng/mL at concentrations < 0.150 ng/mL.

High-dose Hook Effect: The Access PCT assay demonstrated no high-dose hook effect at concentrations up to at least 5,000 nq/mL.

The Access PCT assay has demonstrated to be linear across the range of Linearity: the assay (0.05 ng/mL to approximately 100 ng/mL).

Dilution Recovery: The Access PCT assay has been demonstrated to dilute recover across the range of the assay (0.05 ng/mL to approximately 100 ng/mL) in serum, lithium heparin plasma, and EDTA plasma samples. Samples containing procalcitonin concentrations up to 1,000 ng/mL can be diluted 10-fold with an overall average recovery of 100 ± 10% and an individual sample dose recovery within ± 15%.

† VIDAS® is a registered trademark of bioMérieux SA. B·R·H·M·S PCT® is a registered trademark of B·R·A·H·M·S GmbH.

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Limit of Blank (LoB):

The highest measurement result observed with no analyte present in a serum sample is ≤ 0.005 ng/mL.

Limit of Detection (LoD):

The limit of detection (LoD) for the Access PCT assay is ≤ 0.01 ng/mL.

Limit of Quantitation (LoQ): The limit of quantitation (LoQ) based on 20% within-laboratory imprecision for the Access PCT assay is ≤ 0.02 ng/mL.

Total Error: The LoQ was established using a 20% CV acceptance goal as recommended in CLSI guideline EP17-A2 for cases where no generally accepted reference standard is available. To supplement the within-laboratory %CV LoQ analysis, a modeling analysis was performed to estimate the Total Error at each clinical cutoff (0.5 ng/mL and 2.0 ng/mL). The slope and intercept estimates that were derived from the method comparison study were used to obtain estimates of bias and %bias at each concentration listed above. A precision profile model was fit to the estimated within-laboratory %CV values from the imprecision study samples with concentration values covering approximately 0.1 ng/mL to 8 ng/mL. Because the range of samples included in both the method comparison and the imprecision study cover the concentrations 0.1 ng/mL to 2.0 ng/mL, the bias estimates and precision profile estimates can be combined to provide an estimate of total error (TE) and %TE at each medical decision point.

The estimated %TE at the medical decision points 0.5 ng/mL and 2.0 ng/mL is ≤ 9.4% based on estimates from Weighted Deming regression and ≤ 11.3% from Passing Bablok regression.

Concentration(ng/mL)	Bias (%)	CV (%)	Total Error (%)
0.5	0.6%	4.5%	9.4%
2	0.7%	4.2%	8.9%

Percent Total Error Estimates Based on Bias Estimates Using Weighted Deming

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Concentration(ng/mL)	Bias (%)	CV (%)	Total Error (%)
0.5	-0.6%	4.5%	9.4%
2	-3.1%	4.2%	11.3%

Percent Total Error Estimates Based on Bias Estimates Using Passing Bablok

Analytical Specificity: Potential cross-reactive substances were added to serum patient samples at three concentrations of procalcitonin (approximately

0.25 ng/mL, 0.5 ng/mL, and 2.0 ng/mL). Stock solutions of potential cross- reactants were prepared volumetrically using calibrated pipettes and the appropriate solvent. This stock solution was 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 crossreactant added. Control and test samples were tested on the Access 2 instrument within 24 hours of preparation, using three reagent lots. Testing of human calcitonin, human katacalcin, human alpha CGRP and human beta CGRP, with Access PCT found that there is no significant cross-reactivity, as defined by a change in concentration between the diluent control and the test samples within ± 10%. The acceptance criteria of ±10% was set to ensure that the potential for cross-reactivity is sufficiently mitigated while accommodating the expected imprecision of the assay when performing cross-reactivity testing.

Interfering Substances:

Known concentrations of potential interferents, as per CLSI EP07 (Interference Testing in Clinical Chemistry-Approved Guideline, Third Edition), were added to the patient samples. Results from these spiked test patient samples were evaluated against that of the unspiked control sample. In accordance with CLSI EP07, interference testing was completed on patient serum samples containing four levels of procalcitonin at three clinically relevant concentrations of 0.25 ng/mL, 0.5 ng/mL and 2.0 ng/mL and an additional procalcitonin concentration of approximately 80 ng/mL. See the interfering substance table below for the list of substances and interference concentrations tested.

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The study was run at an internal site on three Access 2 instruments, using three reagent pack lots and one calibrator lot. Five replicates were tested for each control sample and each spiked test sample preparation.

Of the substances tested, none were found to cause significant interference, as defined by a change in concentration between the diluent control and test sample within ± 10%. The acceptance criteria of ±10% was set to ensure that the potential for interference is sufficiently mitigated while accommodating the expected imprecision of the assay when performing interference testing.

Substance	InterferentConcentration Tested	Substance	InterferentConcentration Tested
Acetaminophen	20 mg/dL	Hemoglobin	400 mg/dL
Acetylsalicylic Acid	100 mg/dL	Heparin	8000 IU/L
	1.20 mg/dL	Human SerumAlbumin	12 g/dL
Azithromycin		Ibuprofen	50 mg/dL
Bilirubin (Conjugated)	40 mg/dL		18 mg/dL
Bilirubin(Unconjugated)	40 mg/dL	Imipenem
Caffeine	6.0 mg/dL	Levoflaxacin	1.75 mg/dL
Cefotaxime/Cefotaxin	90 mg/dL	Loratadine	0.03 mg/dL
Celecoxib	24 mg/dL	Naproxen	50 mg/dL
Cetirizine HCL	0.36 mg/dL	Nicotine	0.1 mg/dL
Dextromethorphan	0.14 mg/dL	Noradrenaline	0.2 mg/dL
Dobutamine	1.12 mg/dL	Oxymetazoline HCL	0.009 mg/dL
Dopamine	13 mg/dL	Phenylephrine	0.018 mg/dL
Doxycycline	5.0 mg/dL	Prednisolone	0.3 mg/dL
Epinephrine(adrenaline)	0.18 mg/dL	Salmeterol	0.006 mg/dL
Ethanol	400 mg/dL	Theophylline	10 mg/dL
Fentanyl	1.0 mg/dL	Tiotropium	0.0022 mg/dL
	5.98 mg/dL	Triglycerides(Intralipids)	3000 mg/dL
Furosemide

Interfering Substances

Expected Reference Intervals: Samples were prospectively procured from two hundred and two (202), apparently healthy individuals ≥ 21 years of age, that were not experiencing an acute bacterial or viral illness. The established Reference Interval (RI) is consistent with commonly used reference intervals for apparently healthy individuals of PCT ≤ 0.1 ng/mL.

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PCT Sample Statistics
Number ofSubjects	Medianng/mL	95th PercentileUpper Reference Range	95% Nonparametric Clof 95th percentileReference Range
202	0.025	0.065 ng/mL	[0.054 - 0.085 ng/mL]

Matrix Comparison: A comparison of forty-three (43) matched sets of serum gel, serum no gel, plasma lithium heparin, and plasma EDTA samples with procalcitonin concentrations ranging from approximately 0.19 to 86 ng/mL were compared using Passing-Bablok linear regression analysis.

The observed linear fit for serum (gel) vs. serum (no gel) had an estimated slope = 0.99 with a 95% confidence interval (CI) of 0.98 to 1.00. The observed linear fit for lithium heparin plasma vs. serum (no gel) had an estimated slope = 0.96 with a 95% Cl of 0.95 to 0.97. The observed linear fit for EDTA plasma vs. serum (no gel) had an estimated slope of 1.03, with a 95% Cl of 1.01 to 1.04. The observed linear fit for lithium heparin plasma vs. serum gel had an estimated slope of 0.97 with a 95% Cl of 0.96 to 0.99. The observed linear fit of EDTA plasma vs. serum gel had an estimated slope = 1.04 with a 95% Cl of 1.03 to 1.05. The observed linear fit of EDTA plasma vs. lithium heparin plasma had an estimated slope

= 1.06 with a 95% CI of 1.05 to 1.08.

Carryover Study: The PCT assay utilizes a sodium hydroxide wash between tests to mitigate the potential occurrence of carryover. Based on the expectation that carryover is minimized by this design feature, the acceptance criteria of ±10% was set to ensure that the potential for carryover is sufficiently mitigated while accommodating the expected imprecision of the assay when performing carryover testing.

Verification studies were performed to determine potential assay carryover for the Access PCT assay on the Access 2 instrument. The test used samples at 0.25 ng/mL and the medical decision points of 0.5 ng/mL and 2.0 ng/mL. Testing alternated low samples with high samples for each level tested and used a serum sample spiked with antigen and the highest calibrator. Testing met result criteria as all results had a shift of ≤ 10% for assay carryover.

Individual estimates of carryover ranged from -6% to +8% and indicate no clear trend of positive or negative shifts. This observation provides additional evidence that the potential

{12}------------------------------------------------

for carryover is sufficiently mitigated. If carryover of a high sample into a lower sample were present, we would expect to observe a positive bias only.

Conclusion:

The Access PCT assay is substantially equivalent to the currently marketed VIDAS® B•R•A•H•M•S PCT®† assay (K162827). The verification and validation data provided in this submission demonstrates that the safety and efficacy of this device is substantially equivalent to the predicate device.

† VIDAS® is a registered trademark of bioMérieux SA. B·R·H·M·S PCT® is a registered trademark of B·R·A·H·M·S GmbH.

Regulation Number and Section

§ 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.