Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard immunoassay system for measuring procalcitonin levels and does not mention any AI or ML components in its operation or data analysis.

Therapeutic

No.
This device is an in vitro diagnostic (IVD) immunoassay system intended for quantitative determination of PCT (procalcitonin) to aid in risk assessment and decision making regarding antibiotic therapy. It does not provide any therapy or treatment.

Diagnostic

Yes

This device is a Chemiluminescent Enzyme Immunoassay (CLEIA) intended for the quantitative determination of PCT to aid in risk assessment for sepsis, assessing mortality risk, and decision-making for antibiotic therapy. These uses directly contribute to diagnosing and managing patient conditions.

SaMD (Software as a Medical Device)

No

The device description clearly states it is an "assay system, including a set of immunoassay reagents" and describes physical components like "Immunoreaction Cartridges" and "Calibrators set," which are hardware and chemical components, not software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use/Indications for Use: The document explicitly states "Lumipulse G B.R.A.H.M.S PCT Calibrators set is for in vitro diagnostic use in the calibration of Lumipulse G B.R.A.H.M.S.PCT on the LUMIPULSE G System." The primary assay is also described as a "Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative determination of PCT (procalcitonin) in human serum and plasma...". These are all hallmarks of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or screening.
Device Description: The description details the components of the assay system, including reagents and calibrators, which are used to perform tests on biological samples outside of the body.
Intended User / Care Setting: The intended users are "Clinical and Hospital laboratories," which are settings where in vitro diagnostic testing is performed.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Lumipulse G B.R.A.H.M.S PCT Immunoreaction Cartridges:

The Lumipulse G B•R•A•H•M•S PCT is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative determination of PCT (procalcitonin) in human serum and plasma (sodium heparin, sodium citrate or dipotassium EDTA) on the LUMIPULSE G System.

Used in conjunction with other laboratory findings and clinical assessments, Lumipulse G B.R.A.H.M.S PCT is intended for use 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.

· Aid in 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 a change in PCT level over time.

· Aid in 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.

· Aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.

Lumipulse G B.R.A.H.M.S PCT Calibrators set

Lumipulse G B R A H M S PCT Calibrators set is for in vitro diagnostic use in the calibration of Lumipulse G B.R.A.H.M.S.PCT on the LUMIPULSE G System.

Product codes

PRI, NTM, PMT

Device Description

Lumipulse G B+R•A•H•M•S PCT is an assay system, including a set of immunoassay reagents, for the quantitative measurement of PCT in specimens based on CLEIA technology by a two-step sandwich immunoassay method on the LUMIPULSE G1200 System.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Clinical and Hospital laboratories

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies

Precision/Reproducibility:
- 20 Day Precision: The total precision for the Lumipulse G B•R•A•H•M•S PCT assay was ≤ 4.7%. For the eight panels, it ranged from 1.8% to 3.1%. For the three controls, it ranged from 3.3% to 4.7%. All controls and panels met the acceptance criteria of a CV ≤ 10%. (n=80 for each sample)
- Lot-To-Lot Reproducibility: The total precision for Lumipulse G PCT was ≤ 5.3%. For the six panels, it was ≤ 3.0%. For the three controls, it was ≤ 5.3%. The total precision ranged from 1.8% to 5.3%. The between-lot precision was ≤ 6.5%. All controls and panels met the acceptance criteria of a CV ≤ 10%. (n=120 for each sample)
- Site to Site Reproducibility: The total precision for Lumipulse G B+R•A•H•M•S PCT was ≤ 4.9%. For the six panels, it was ≤ 4.8%. For the three controls, it was ≤ 4.9%. The total precision ranged from 2.9% to 4.9%. The between-site precision was ≤ 4.7%. All controls and panels met the acceptance criteria of a CV ≤ 10%. (n=120 for each panel)
Linearity/Assay Reportable Range:
- Study consistent with CLSI Protocol EP6-A.
- Linearity found in the range of 0.010 ng/mL to 104.260 ng/mL.
- Linear regression formula: y= 0.008734 + 0.856577; R-squared: 0.9979.
- No high dose effect observed for samples containing approximately 12,000 ng/mL of PCT.
Traceability, Stability, Expected values:
- Calibration traceable to in-house reference calibrators, correlated to Thermo Fisher Scientific Inc.'s B-R-A-H-M-S PCT sensitive Kryptor.
- Shelf life: 6 months at 2-10°C for Immunoreaction Cartridges and Calibrators.
- On-board stability (LUMIPULSE G1200): 30 days for Immunoreaction Cartridges; 30 days for calibrator curve storage.
Detection Limit:
- Limit of Blank (LoB): 0.0095 ng/mL.
- Limit of Detection (LoD): 0.0114 ng/mL (consistent with CLSI Protocol EP17-A2, tested with seven low-level specimens over 3 days using two systems and two lots, 120 determinations per panel).
- Limit of Quantitation (LoQ): 0.0114 ng/mL (consistent with CLSI Protocol EP17-A2).
- Modeling analysis for LoQ and lower cut-offs:
  - TE ≤ 11.4% at 0.25 ng/mL (% bias ≤ -5.7%, precision CV ≤ 2.8%)
  - TE ≤ 14.1% at 0.10 ng/mL (% bias ≤ -9.2%, precision CV ≤ 2.5%)
Analytical Specificity:
- 平均干扰≤10% for endogenous and therapeutic drug interferences (consistent with CLSI Protocol EP7-A2).
- Tested endogenous interferences: Free Bilirubin, Conjugated Bilirubin, Hemoglobin, Total Protein, Triglycerides, Immunoglobulin G, Biotin, Human Anti-Mouse Antibodies (HAMA), Rheumatoid Factor (RF).
- Tested therapeutic drug interferences (examples: Acetaminophen, Acetylsalicylic Acid, Ethanol, Azithromycin, Ibuprofen, Heparin, Vancomycin).
- Cross-reactivity evaluation (consistent with CLSI Protocol EP7-A2):
  - Human Calcitonin: -0.346%
  - Human Katacalcin: 0.076%
  - α-CGRP: 0.002%
  - β-CGRP: 0.001%
  - Salmon Calcitonin: -0.001%
  - Eel Calcitonin: -0.001%
Method Comparison:
- Study consistent with CLSI Protocol EP09-A3.
- Comparison: Lumipulse G B•R•A•H•M•S PCT vs. B•R•A•H•M•S PCT sensitive KRYPTOR.
- Weighted Deming regression used.
- Sample range: 0.054-58.156 ng/mL.
- n=207.
- Correlation Coefficient (r): 0.9535.
- Intercept (95% CI): -0.0044 (-0.0223 to 0.0135).
- Slope (95% CI): 1.0199 (0.9633 to 1.0765).
- Mean Difference (ng/mL): 0.185.
Matrix Comparison:
- Evaluated across tube types (SST, K2EDTA, Lithium Heparin, Sodium Heparin, and Sodium Citrate) vs. control samples (Red top serum).
- Consistent with CLSI guideline EP9-A3.
- Slope for each tube type when compared to control had 95% confidence intervals within 0.9 to 1.1.
- Correlation coefficients were ≥ 0.9.
Expected values/Reference range:
- 95th percentile upper reference range limit: 0.045 ng/mL (from a population of 213 self-reported healthy individuals).

Key Metrics

Precision (Total CV): ≤ 4.7% (20-day); ≤ 5.3% (Lot-to-Lot); ≤ 4.9% (Site-to-Site)
Linearity (R-squared): 0.9979
Detection Limits: LoB = 0.0095 ng/mL, LoD = 0.0114 ng/mL, LoQ = 0.0114 ng/mL
Analytical Specificity (Interference): Average interference ≤ 10%
Method Comparison (r): 0.9535

Predicate Device(s)

K171338

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

December 10, 2017

Fujirebio Diagnostics, Inc. Stacey Dolan Manager, Regulatory Affairs 201 Great Valley Parkway Malvern, Pennsylvania 19355

Re: K172713

Trade/Device Name: Lumipulse G B.R.A.H.M.S.PCT Immunoreaction Cartridges, Lumipulse G B•R•A•H•M•S PCT Calibrators set 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, NTM Dated: September 7, 2017 Received: September 8, 2017

Dear Stacey Dolan:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. 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.

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

1

801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/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 M. Roth - S
For:

Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

2

Indications for Use

510(k) Number (if known) K172713

Device Name

Lumipulse G B.R.A.H.M.S PCT Immunoreaction Cartridges Lumipulse G B•R•A•H•M•S PCT Calibrators set

Indications for Use (Describe) Lumipulse G B.R.A.H.M.S PCT Immunoreaction Cartridges:

The Lumipulse G B•R•A•H•M•S PCT is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative determination of PCT (procalcitonin) in human serum and plasma (sodium heparin, sodium citrate or dipotassium EDTA) on the LUMIPULSE G System.

Used in conjunction with other laboratory findings and clinical assessments, Lumipulse G B.R.A.H.M.S PCT is intended for use 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.

· Aid in 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 a change in PCT level over time.

· Aid in 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.

· Aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.

Lumipulse G B.R.A.H.M.S PCT Calibrators set

Lumipulse G B R A H M S PCT Calibrators set is for in vitro diagnostic use in the calibration of Lumipulse G B.R.A.H.M.S.PCT on the LUMIPULSE G System.

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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Section 5 510(k) SUMMARY

Lumipulse® G PCT

Date: December 6, 2017

A. 510(k) Number: K172713

B. Purpose of Submission: New device

C. Measurand:

Procalcitonin

D. Type of Test:

Quantitative assay, automated chemiluminescent enzyme immunoassay (CLEIA)

E. Applicant:

Submitter: Fujirebio Diagnostics, Inc. 201 Great Valley Parkway Malvern, PA 19355
Contact Person: Stacey Dolan Manager, Regulatory Affairs Phone: (610) 240-3843 Fax: (610) 240-3803 Email: dolans@fdi.com

F. Proprietary and Established Names:

Lumipulse® G B•R•A•H•M•S PCT

G. Regulatory Information:

Regulation section: 1. 21 CFR § 866.3215
1. Classification: Class II
1. Product codes: PRI, NTM, PMT
1. Panel: 83, Microbiology

H. Intended Use:

1. Intended Use:

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Lumipulse G B .R .A .H .M .S PCT Immunoreaction Cartridges

The Lumipulse G B+R+A+H+M+S PCT is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative determination of PCT (procalcitonin) in human serum and plasma (sodium heparin, lithium heparin, sodium citrate or dipotassium EDTA) on the LUMIPULSE G System.

Used in conjunction with other laboratory findings and clinical assessments, Lumipulse G B•R•A•H•M•S PCT is intended for use 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.
. Aid in 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 a change in PCT level over time.
. Aid in 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.
Aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.

Lumipulse G B•R•A•H•M•S PCT Calibrators Set

Lumipulse G B+R+A•H•M•S PCT Calibrators set are for in vitro diagnostic use in the calibration of LUMIPULSE G B+R•A•H•M•S PCT on the LUMIPULSE G System.

1. Indications for use: Same as Intended Use.
1. Special conditions for use statement(s): Prescription use only.
1. Special instrument requirements: LUMIPULSE G1200 System

-Device Description:

Lumipulse G B+R•A•H•M•S PCT is an assay system, including a set of immunoassay reagents, for the quantitative measurement of PCT in specimens based on CLEIA technology by a two-step sandwich immunoassay method on the LUMIPULSE G1200 System.

Lumipulse G B.R.A.H.M.S PCT Immunoreaction Cartridges: | IRC 235058. The Lumipulse G B•R•A•H•M•S PCT Immunoreaction Cartridges consists of 3 x 14 tests. Each kit contains the following:

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1.) Antibody-Coated Particle Solution

(Liquid when used, 250 µL/Immunoreaction Cartridge) Contains 150 µg/mL anti-PCT monoclonal antibody (mouse) and anti-calcitonin monoclonal antibody (mouse) coated particles, protein stabilizers (bovine and mouse) and chemical stabilizers in 0.15 M sodium chloride/Tris buffer. This solution contains gelatin and turns into gel at 15°C or lower. Preservative: sodium azide.

2.) Enzyme-Labeled Antibody Solution

(Liquid, 350 µL/Immunoreaction Cartridge)

Contains 0.25 µg/mL alkaline phosphatase (ALP: calf)-labeled anti-katacalcin monoclonal antibody (mouse), protein stabilizers (bovine, calf and mouse) and chemical stabilizers in 0.1 M sodium chloride/MES buffer. Preservative: sodium azide.

Lumipulse G B+R+A+H+M+S PCT Calibrators set |CAL SET 234150, Lyophilized, 2 x 2 Concentrations

Each calibrator kit contains one bottle each of Calibrators 1 - 2, and Reconstituting Solution. The calibrator kit is packaged separately.

CAL 1

0 ng/mL PCT calibrator (2 x 0.5 mL/vial)

CAL 2 100 ng/mL PCT calibrator (2 x 0.5 mL/vial)

Contains procalcitonin in 0.15 M sodium chloride in Tris buffer with protein stabilizer (bovine). Preservative: ProClin 300.

RS Reconstituting Solution: Liquid, 1 x 10 mL Preservative: sodium azide.

These calibrators are lyophilized and have to be prepared by adding exactly 0.5 mL of Reconstituting Solution to each Iyophilized calibrator.

J. Substantial Equivalence:

1. Predicate device name(s): B•R•A•H•M•S PCT sensitive KRYPTOR®
1. Predicate 510(k) number(s): K171338
Comparison with predicate: 3.

B•R•A•H•M•S PCT sensitive KRYPTOR®
Similarities and Differences
	Lumipulse® G
B•R•A•H•M•S PCT (Proposed
Device)	B•R•A•H•M•S PCT sensitive
KRYPTOR®
(Predicate Device)
K171338
Device Type	In vitro diagnostic	Same
Classification	Class II	Same
Similarities and Differences
	Lumipulse® G
B·R·A·H·M·S PCT (Proposed
Device)	B·R·A·H·M·S PCT sensitive
KRYPTOR®
(Predicate Device)
K171338
Analyte	Procalcitonin	Same
Regulation Number	21CFR § 866.3215; Device to
detect and measure non-
microbial analyte(s) in human
clinical specimens to aid in
assessment of patients with
suspected sepsis	Same
Product Usage	Clinical and Hospital laboratories	Same
Principle of Operation	Automated Quantitative
Chemiluminscent Enzyme
Immunoassay (CLEIA)	Time-Resolved Amplified
Cryptate Emission (TRACE)
Specimen Collection
Method	Routine Phlebotomy Techniques	Same
Intended Use	The Lumipulse G B•R•A•H•M•S
PCT is a Chemiluminescent
Enzyme Immunoassay (CLEIA)
for the quantitative determination
of PCT (procalcitonin) in human
serum and plasma (sodium
heparin, lithium heparin, sodium
citrate or dipotassium EDTA) on
the LUMIPULSE G System.
Used in conjunction with other
laboratory findings and clinical
assessments, Lumipulse G
B•R•A•H•M•S PCT is intended for
use 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.
• Aid in assessing the
cumulative 28-day risk of
all-cause mortality for
patients diagnosed with
severe sepsis or septic
shock in the ICU or when	The B-R·A·H·M·S
PCT sensitive
KRYPTOR® is an
immunofluorescent
assay using Time-
Resolved Amplified
Cryptate Emission
(TRACE) technology
to determine the
concentration of PCT
(procalcitonin) in
human serum and
EDTA or heparin
plasma.
The B-R·A·H·M·S
PCT sensitive
KRYPTOR® is
intended to be
performed on the
B-R·A·H·M·S
KRYPTOR® analyzer
family.
Used in conjunction
with other laboratory
findings and clinical
assessments,
B·R·A·H·M·S PCT
sensitive KRYPTOR®
Similarities and Differences
	Lumipulse® G
B·R·A·H·M·S PCT (Proposed
Device)	B·R·A·H·M·S PCT sensitive
KRYPTOR®
(Predicate Device)
K171338
	department or other
medical wards prior to ICU
admission, using a change
in PCT level over time.

• Aid in 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.

• Aid in decision making on
antibiotic discontinuation
for patients with suspected
or confirmed sepsis. | is intended for use as
follows:

• 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,

• to determine the
change in PCT level
over time as an aid in
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,

• to aid in decision
making on antibiotic
therapy, for
inpatients or patients
in the emergency
department with
suspected or
confirmed lower
respiratory tract
infections (LRTI) –
defined as
community-acquired
pneumonia (CAP),
acute bronchitis, and
acute exacerbation
of chronic |
| Similarities and Differences | | |
| | Lumipulse® G
B-R・A・H・M・S PCT (Proposed
Device) | B-R・A・H・M・S PCT sensitive
KRYPTOR®
(Predicate Device)
K171338 |
| | | obstructive
pulmonary disease
(AECOPD), |
| | | • to aid in decision
making on antibiotic
discontinuation for
patients with
suspected or
confirmed sepsis. |
| Instrument System | LUMIPULSE G System | The BRAHMS KRYPTOR
analyzer |
| Assay Type | Two-step sandwich
immunoassay based on
chemiluminescent
technology | Immunofluorescent assay |
| Type of Specimen | Human serum and plasma
(sodium heparin, lithium heparin,
sodium citrate or dipotassium
EDTA) | Human serum and plasma
(EDTA, heparin) |
| Assay Range | 0.020 - 100 ng/mL | 0.02-5000ng/mL |
| Sample Volume | 60 μl | 50μl |

Comparison between the Lumipulse® G B-R-A-H-M-S PCT and

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K. Standard/Guidance Document Referenced (if applicable):

CLSI EP5-A3 - Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - Third Edition
CLSI EP7-A2 - Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition
CLSI EP28-A3c Defining, Establishing, and Verifying Reference Intervals in the Clinical . Laboratory; Approved Guideline-Third Edition
CLSI EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement . Procedures; Approved Guideline Second Edition
CLSI EP6-A - Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
. CLSI EP9-A3 – Measurement Procedure Comparison and Bias Estimation Using Patient Samples; approved Guideline - Third Edition
CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents: Approved Guideline ●
Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover ● Human Specimens that are Not Individually Identifiable - Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff
Test Principle: Guidance for Industry and Food and Drug Administration Staff - eCopy Program for Medical Device Submissions (December 31, 2012)

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. Guidance for Industry and Food and Drug Administration Staff - Refuse to Accept Policy for 510(k)s (August 4, 2015)

L. Test Principle:

Lumipulse G B.R.A.H.M.S PCT is an assay system, including a set of immunoassay reagents, for the quantitative measurement of PCT in specimens based on CLEIA technology by a twostep sandwich immunoassay method on the LUMIPULSE G1200 System.

PCT in specimens specifically binds to anti-PCT monoclonal antibody (mouse) and anti-calcitonin monoclonal antibody (mouse) on the particles, and antigen-antibody immunocomplexes are formed. The particles are washed and rinsed to remove unbound materials. Alkaline phosphatase (ALP: calf)-labeled anti-katacalcin monoclonal antibody (mouse) specifically binds to PCT of the immunocomplexes on the particles, and additional immunocomplexes are formed. The particles are washed and rinsed to remove unbound materials. Substrate Solution is added and mixed with the particles. AMPPD contained in the Substrate Solution is dephosphorylated by the catalysis of ALP indirectly conjugated to particles. Luminescence (at a maximum wavelength of 477 nm) is generated by the cleavage reaction of dephosphorylated AMPPD. The luminescent signal reflects the amount of PCT.

M. Performance Characteristics

Data were generated using the LUMIPULSE G1200 System.

1. Analytical performance:
- a. Precision/Reproducibility:

20 Day

The results of the 20-day precision calculations for Lumipulse G B.R.A.H.M.S PCT performed at FDI are shown below:

Lot A ICs/Lot A Calibrators for Control Levels 1-3 and Panels 1-6 .
. Lot D ICs/Lot D Calibrators for Panels 7 and 8

The analyses determined the total precision for the Lumipulse G B•R•A•H•M•S PCT assay to be ≤ 4.7%. The total precision of the Lumipulse G B•R•A•H•M•S PCT for the eight (8) panels ranged from 1.8% to 3.1%. The total precision of the Lumipulse G B+R+A+H+M+S PCT for the three (3) controls ranged from 3.3% to 4.7%. The precision of all controls and panels for the 20-day Precision Study met the acceptance criteria of a CV ≤ 10%.

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Summary for FDI 20-day Precision (n=80 for each sample) for Lot A (Controls and Panels 1-6) and Lot D (Panels 7 and 8)

Sample	Mean (ng/mL)	Within-Run (Repeatability)		Between Run				Within-Laboratory (Total)
		SD	%CV	Between-Day		SD	%CV	SD	%CV
Control Level 1	0.662	0.010	1.6%	0.026	3.9%	0.014	2.1%	0.031	4.7%
Control Level 2	3.911	0.045	1.2%	0.129	3.3%	0.026	0.7%	0.139	3.6%
Control Level 3	14.978	0.163	1.1%	0.393	2.6%	0.245	1.6%	0.490	3.3%
Panel 1	0.300	0.005	1.6%	0.004	1.5%	0.003	1.0%	0.007	2.4%
Panel 2	2.219	0.032	1.5%	0.016	0.7%	0.027	1.2%	0.045	2.0%
Panel 3	12.323	0.129	1.0%	0.144	1.2%	0.098	0.8%	0.217	1.8%
Panel 4	36.217	0.379	1.0%	0.308	0.8%	0.445	1.2%	0.661	1.8%
Panel 5	54.132	0.596	1.1%	0.529	1.0%	0.642	1.2%	1.024	1.9%
Panel 6	80.361	1.265	1.6%	0.879	1.1%	0.632	0.8%	1.666	2.1%
Panel 7	0.112	0.002	2.0%	0.002	2.2%	0.001	1.1%	0.004	3.1%
Panel 8	0.534	0.010	1.9%	0.008	1.5%	0.003	0.6%	0.013	2.5%

Lot-To-Lot Reproducibility for Combined Data

The precision analyses for the combined lot-to-lot analysis for Lots A, B and C determined the total precision for Lumipulse G PCT to be ≤ 5.3% in this study. The total precision for Lumipulse G B+R•A•H•M•S PCT to be ≤ 3.0% for the six (6) panels. The total precision for Lumipulse G PCT to be ≤ 5.3% for the three (3) controls. The total precision of Lumipulse G B+R+A+H+M+S PCT ranged from 1.8% to 5.3%. The between-lot precision for Lumipulse G B•R•A•H•M•S PCT was ≤ 6.5%.

The precision of controls and panels for the lot-to-lot reproducibility met the targeted acceptance criteria of a CV ≤ 10%.

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Summary of the Lot-to-Lot Reproducibility for the Combined Data for Lots A, B and C (n=120 for each sample)

| | | Between
Lots | | Between
Day | | Between
Run | | Within Runs
(Repeatabilit
y) | | Within-
Laboratory
(Total) | |
|--------------------|----------------|-----------------|------|----------------|------|----------------|------|------------------------------------|------|----------------------------------|------|
| Sample | Mean
(ng/L) | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Control Level
1 | 0.634 | 0.030 | 4.7% | 0.013 | 2.0% | 0.030 | 4.7% | 0.009 | 1.4% | 0.033 | 5.3% |
| Control Level
2 | 3.816 | 0.137 | 3.6% | 0.016 | 0.4% | 0.127 | 3.3% | 0.055 | 1.4% | 0.139 | 3.7% |
| Control Level
3 | 14.875 | 0.313 | 2.1% | 0.141 | 0.9% | 0.434 | 2.9% | 0.164 | 1.1% | 0.487 | 3.3% |
| Panel 1 | 0.290 | 0.012 | 4.3% | 0.004 | 1.3% | 0.006 | 2.0% | 0.005 | 1.8% | 0.009 | 3.0% |
| Panel 2 | 2.163 | 0.075 | 3.4% | 0.021 | 1.0% | 0.038 | 1.8% | 0.026 | 1.2% | 0.048 | 2.2% |
| Panel 3 | 12.332 | 0.320 | 2.6% | 0.221 | 1.8% | 0.133 | 1.1% | 0.122 | 1.0% | 0.280 | 2.3% |
| Panel 4 | 38.147 | 2.280 | 6.0% | 0.363 | 1.0% | 0.467 | 1.2% | 0.367 | 1.0% | 0.701 | 1.8% |
| Panel 5 | 57.114 | 3.392 | 5.9% | 0.856 | 1.5% | 0.625 | 1.1% | 0.674 | 1.2% | 1.248 | 2.2% |
| Panel 6 | 86.233 | 5.585 | 6.5% | 1.018 | 1.2% | 1.138 | 1.3% | 1.489 | 1.7% | 2.141 | 2.5% |

Site to Site Reproducibility for Combined Data

The precision analyses for the combined site-to-site analysis for Lots A determined the total precision for Lumipulse G B+R•A•H•M•S PCT to be ≤ 4.9% in this study. The total precision for Lumipulse G B+R+A+H+M+S PCT to be ≤ 4.8% for the six (6) panels. The total precision for Lumipulse G PCT to be ≤ 4.9% for the three (3) controls. The total precision of Lumipulse G B+R•A•H•M•S PCT ranged from 2.9% to 4.9%. The betweensite precision for Lumipulse G B+R•A•H•M•S PCT was ≤ 4.7%.

The precision of the controls and panels for the site-to-site reproducibility met the targeted acceptance criteria of a CV ≤10%.

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Summary of the Site-to-Site Reproducibility for the Combined Data for Lot A (n=120 for each panel)

| | | Between
Sites | | Between
Days | | Between
Runs | | Within Runs
(Repeatability) | | Reproducibility
(Total) | |
|-----------------|-----------------|------------------|------|-----------------|------|-----------------|------|--------------------------------|------|----------------------------|------|
| Sample | Mean
(ng/mL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Control Level 1 | 0.647 | 0.019 | 2.9% | 0.023 | 3.5% | 0.020 | 3.0% | 0.012 | 1.8% | 0.032 | 4.9% |
| Control Level 2 | 3.872 | 0.077 | 2.0% | 0.109 | 2.8% | 0.096 | 2.5% | 0.054 | 1.4% | 0.149 | 3.8% |
| Control Level 3 | 15.062 | 0.085 | 0.6% | 0.337 | 2.2% | 0.312 | 2.1% | 0.166 | 1.1% | 0.481 | 3.2% |
| Panel 1 | 0.291 | 0.008 | 2.8% | 0.008 | 2.7% | 0.010 | 3.6% | 0.005 | 1.9% | 0.014 | 4.8% |
| Panel 2 | 2.170 | 0.033 | 1.5% | 0.049 | 2.3% | 0.061 | 2.8% | 0.032 | 1.5% | 0.075 | 3.5% |
| Panel 3 | 12.297 | 0.375 | 3.0% | 0.222 | 1.8% | 0.417 | 3.4% | 0.170 | 1.4% | 0.485 | 3.9% |
| Panel 4 | 37.074 | 1.303 | 3.5% | 0.586 | 1.6% | 1.182 | 3.2% | 0.361 | 1.0% | 1.354 | 3.6% |
| Panel 5 | 55.428 | 2.043 | 3.7% | 1.144 | 2.1% | 1.385 | 2.5% | 0.613 | 1.1% | 1.846 | 3.3% |
| Panel 6 | 82.850 | 3.868 | 4.7% | 1.006 | 1.2% | 1.719 | 2.1% | 1.285 | 1.6% | 2.365 | 2.9% |

b. Linearity/assay reportable range:

Lumipulse G B+R+A+H•M•S PCT on the LUMIPULSE G1200 System demonstrated linearity in a study consistent with the guidelines in the CLSI Protocol EP6-A.9) High and low sample pools were created using patient serum samples that contained naturally expressed PCT. The linearity was found in the range of 0.010 ng/mL to 104.260 ng/mL. Lumipulse G B+R+A+H•M•S PCT correlated with expected concentrations according to the linear regression formula:

o y= 0.008734 + 0.856577; R-squared: 0.9979

High dose effect is a phenomenon whereby very high level specimens may read within the dynamic range of the assay. For Lumipulse G B+R+A+H•M•S PCT on the LUMIPULSE G1200 System, no high dose effect was observed for samples containing approximately 12,000 ng/mL of PCT.

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Calibration of the Lumipulse G B·R·A·H·M·S PCT is traceable to in-house reference calibrators, whose values have been assigned to correlate to Thermo Fisher Scientific Inc.'s B-R-A-H-M-S PCT sensitive Kryptor.

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Cal Set Contains Cal 1 and Cal 2 (2 x 0.5 mL/vial) and Reconstituting Solution (1 x 10 mL). Preservative: ProClin 300. The calibrators are at the following concentrations:

Calibrator Level	PCT Concentration (ng/mL)
CAL 1	0
CAL 2	100

Master calibration data are recorded in a two-dimensional bar code on the Lumipulse G B+R+A+H+M+S PCT Immunoreaction Cartridge case. The calibration curve is created based on the recorded master calibration data and measured calibration data. The PCT concentration of a specimen is automatically calculated from the calibration curve. The result of the calculation is reported in ng/mL.

Shelf life

The shelf life for Lumipulse G B+R+A+H•M•S PCT Immunoreaction Cartridges and the Lumipulse G B.R.A.H.M.S PCT Calibrators is 6 months at 2-10°C.

On board the LUMIPULSE G1200

The Lumipulse G B•R•A•H•M•S PCT Immunoreaction Cartridges are sealed unit dose stored at 2-10°C. To reduce risk for any misuse, the package insert states The Lumipulse G B•R•A•H•M•S PCT Cartridges can be stored on-board the LUMIPULSE G System for a maximum of 30 days.

The package insert recommends calibrator curve storage on the LUMIPULSE G1200 for a maximum of 30 days.

Transport Conditions

Lumipulse G B R . A . H . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B•R•A•H•M•S PCT Calibrators are shipped at 2-10°C.

Materials will be shipped to the end user using an insulated container and a predetermined configuration of gel (cold and/or frozen) packs to maintain the product for up to 72 hours when stored at ambient temperature.

d. Detection limit:
The Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) of Lumipulse G B+R•A•H•M•S PCT on the LUMIPULSE G1200 System is ≤0.0114 ng/mL.

1)LoB and LoD

The LoB for Lumipulse G B+R+A+H+M+S PCT was 0.0095 ng/mL. The LoD for Lumipulse G PCT on the LUMIPULSE G1200 System was 0.0114 ng/mL, determined consistent with the guidelines in the CLSI Protocol EP17-A2, Seven low level specimens were tested over 3 days using two LUMIULSE G1200 Systems and two Lumipulse G PCT lots giving 120 determinations per panel.

2)LoQ

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The LoQ for Lumipulse G B.R.A.H+M+S PCT on the LUMIPULSE G1200 System was 0.0114 ng/mL, determined consistent with the guidelines in the CLSI Protocol EP17-A2.

A modeling analysis was conducted to evaluate the LOQ and for each lower cut-off (i.e., 0.10 ng/mL and 0.25 ng/mL). The Max % Total Error, % bias and %CV were calculated, see below.

TE ≤ 11.4% at 0.25 ng/mL (with a % bias ≤ -5.7% and a precision CV ≤ 2.8%)

TE ≤ 14.1% at 0.10 ng/mL (with a % bias ≤ -9.2% and a precision CV ≤ 2.5%)

e. Analytical specificity:

Lumipulse G B+R•A•H•M•S PCT on the LUMIPULSE G1200 System demonstrated an average interference of ≤10% (for each compound) in a study consistent with the guidelines in the CLSI Protocol EP7-A2 Human serum specimen pools with procalcitonin concentrations of approximately 0.25 and 2.0 ng/mL were supplemented with potentially interfering compounds. The following compounds were tested using Lumipulse G B•R•A•H•M•S PCT and found not to interfere with the assay.

Endogenous Interferences	Test Concentration
Free Bilirubin (unconjugated)	50 mg/dL
Conjugated Bilirubin	50 mg/dL
Hemoglobin	400 mg/dL
Total Protein (Human Serum Albumin)	12 g/dL
Triglycerides (Intralipid 20% Emulsion)	2500 mg/dL
Immunoglobulin G (IgG)	5 g/dL
Biotin	19.7 mg/dL
Human Anti-Mouse Antibodies (HAMA)	1,000 ng/mL
Rheumatoid Factor (RF)	1,000 IU/mL

| Therapeutic Drug

Interferences	Test Concentration (mg/dL)
Acetaminophen	20.01
Acetylsalicylic Acid	65.22
1% Ethanol	789.00
Azithromycin	2.00
Caffeine	6.00
Celecoxib	24.00
Cetirizine HCI	0.55
Dextromethorphan	0.10
Dobutamine	1.13
Dopamine	13.00
Doxycycline	5.00
Epinephrine	0.18
Furosemide	2.00
Heparin	8000.00
Ibuprofen	50.03
Imipenem	118.00
Levofloxacin	2.93

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Loratadine	0.05
Nicotine	0.10
Noradrenaline (norepinephrine)	0.20
Oxymetazoline HCl	0.09
Phenylephrine	6.00
Prednisolone	0.30
Salmeterol	0.006
Tiotropium	0.0022
Vancomycin	300.00

Lumipulse G B+R+A+H+M+S PCT on the LUMIPULSE G1200 System was evaluated for crossreactivity of the assay with other substances that are similar in structure to PCT in a study consistent with the guidelines in the CLSI Protocol EP7-A2. Human serum specimens with PCT concentrations of approximately 0.1, 0.25, 0.5, 2.0 and 80 ng/mL were supplemented with potentially cross-reacting compounds. The compounds were tested at the concentrations listed below and found to have the following percent cross-reactivity:

Cross-reactant	Test Concentration	Mean % Cross Reactivity
Human Calcitonin	10 ng/mL	-0.346%
Human Katacalcin	10 ng/mL	0.076%
α-CGRP	10,000 ng/mL	0.002%
β-CGRP	10,000 ng/mL	0.001%
Salmon Calcitonin	13.2 µg/mL	-0.001%
Eel Calcitonin	7.5 µg/mL	-0.001%

f. Assay cut-off: See Clinical Cutoff in 4 below.
1. Comparison studies:
a. Method Comparison

The Lumipulse G B•R•A•H•M•S PCT method comparison was performed on the LUMIPULSE G1200 System in a study consistent with the quidelines in CLSI Protocol EP09-A3.

The weighted Deming regression method was used to compare Lumipulse G B+R+H+M+S PCT to B•R•A•H•M•S PCT sensitive KRYPTOR. The lithium heparin specimens tested ranged from 0.054-58.156 ng/mL for Lumipulse G B+R+A•H•M•S PCT. The data are summarized in the following table.

| Lumipulse G B•R•A•H•M•S PCT vs. B•R•A•H•M•S PCT

sensitive KRYPTOR
n	Correlation
Coefficient
(r)	Intercept
(95% CI)	Slope
(95% CI)	Mean
Difference
(ng/mL)
207	0.9535	-0.0044
(-0.0223 to	1.0199
(0.9633 to	0.185

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0.0135) 1.0765)

b. Matrix Comparison
The Lumipulse G B•R•A•H•M•S PCT matrix comparison study was performed to evaluate the difference across tube types (SST, K2EDTA, Lithium Heparin, Sodium Heparin, and Sodium Citrate) versus the means of the control samples (Red top serum) analyzed per CLSI quideline EP9-A3. The slope for each tube type when compared to the control had 95% confidence intervals that lay entirely within the range 0.9 to 1.1 and the correlation coefficients were ≥ 0.9.
1. Clinical studies:
- a. Clinical sensitivity:

Not applicable

b. Clinical specificity:
Not applicable
ﯼ ﻧ Other clinical supportive data (when a. and b. are not applicable):
Not applicable
1. Clinical cut-off:
  See Expected Values below.
1. Expected values/Reference range:
  In a population of 213 self-reported healthy individuals, the 95th percentile, upper reference range limit was calculated at 0.045 ng/mL.

It is recommended that each laboratory establish its own range, which may be unique to the population it serves depending upon geographical, patient, and environmental factors.

N. Proposed Labeling

The labeling satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion

The results of these analytical) and clinical studies demonstrate that the Lumipulse G B•R•A•H•M•S PCT assay is substantially equivalent to the performance of the B•R•A•H•M•S PCT sensitive KRYPTOR.