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.

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:

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.

AI/ML Overview

The provided document describes the Lumipulse G B.R.A.H.M.S PCT Immunoreaction Cartridges and its associated calibrator set. This is an in-vitro diagnostic device, not an AI/ML medical device. Therefore, the questions related to AI/ML device acceptance criteria, performance studies (sample sizes, expert usage, adjudication, MRMC studies, standalone performance), and ground truth establishment are not applicable.

However, based on the provided text, the device's analytical performance and comparison studies can be summarized as follows:

1. A table of acceptance criteria and the reported device performance (for Analytical Performance):

The document refers to CLSI protocols for acceptance criteria, specifically for precision, linearity, and analytical specificity. The acceptance criteria themselves are generally implied by meeting the guidelines or by specific thresholds mentioned in conjunction with the results.

Performance Characteristic	Acceptance Criteria (Implied/Stated)	Reported Device Performance
Precision (20-day)	CV ≤ 10%	Controls: Total precision ranged from 3.3% to 4.7% CV. Panels: Total precision ranged from 1.8% to 3.1% CV. Overall: All results met the acceptance criteria of CV ≤ 10%.
Precision (Lot-to-Lot Reproducibility)	CV ≤ 10%	Controls: Total precision ≤ 5.3% CV. Panels: Total precision ≤ 3.0% CV. Overall: Total precision ranged from 1.8% to 5.3%. Between-lot precision ≤ 6.5%. All results met the targeted acceptance criteria of CV ≤ 10%.
Precision (Site-to-Site Reproducibility)	CV ≤ 10%	Controls: Total precision ≤ 4.9% CV. Panels: Total precision ≤ 4.8% CV. Overall: Total precision ranged from 2.9% to 4.9%. Between-site precision ≤ 4.7%. All results met the targeted acceptance criteria of CV ≤ 10%.
Linearity/Reportable Range	Consistent with CLSI EP6-A guidelines, demonstrating correlation with expected concentrations.	Linear in the range of 0.010 ng/mL to 104.260 ng/mL. 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.
Detection Limit (LoD/LoQ)	Consistent with CLSI EP17-A2 guidelines.	LoB = 0.0095 ng/mL. LoD = 0.0114 ng/mL. LoQ = 0.0114 ng/mL. Modeling analysis: 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 (Interference)	Average interference ≤ 10% for each compound.	Tested endogenous and therapeutic compounds showed average interference ≤ 10%.
Analytical Specificity (Cross-Reactivity)	Consistent with CLSI EP7-A2 guidelines.	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 (vs. predicate)	High correlation and acceptable agreement with the predicate device.	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: 0.185 ng/mL. Conclusion: 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.
Matrix Comparison	Slope for each tube type (vs. control) with 95% CI within 0.9-1.1 and correlation coefficients ≥ 0.9.	Slopes for each tube type (SST, K2EDTA, Lithium Heparin, Sodium Heparin, and Sodium Citrate) when compared to the control (Red top serum) had 95% confidence intervals entirely within 0.9 to 1.1, and correlation coefficients were ≥ 0.9.

2. Sample sizes used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective):

Precision (20-day): n=80 for each sample (Control Levels 1-3, Panels 1-8). Data generated at Fujirebio Diagnostics, Inc. (FDI).
Precision (Lot-to-Lot Reproducibility): n=120 for each sample (Control Levels 1-3, Panels 1-6).
Precision (Site-to-Site Reproducibility): n=120 for each panel (Control Levels 1-3, Panels 1-6). Performed at "several sites" (implied, typical for site-to-site reproducibility; specific sites or countries not mentioned).
Linearity/Reportable Range: High and low sample pools created using patient serum samples. Number of samples not specified, but the study was "consistent with the guidelines in the CLSI Protocol EP6-A."
Detection Limit (LoB/LoD/LoQ): Seven low-level specimens were tested over 3 days using two LUMIPULSE G1200 Systems and two Lumipulse G PCT lots, giving 120 determinations per panel for LoD. Number of unique samples for LoQ not specified, but involved "modeling analysis."
Analytical Specificity (Interference): Human serum specimen pools (approximately 0.25 and 2.0 ng/mL PCT) supplemented with potentially interfering compounds. Number of individual samples not specified.
Analytical Specificity (Cross-Reactivity): Human serum specimens (approximately 0.1, 0.25, 0.5, 2.0 and 80 ng/mL PCT) supplemented with potentially cross-reacting compounds. Number of individual samples not specified.
Method Comparison: n=207 lithium heparin specimens.
Expected Values/Reference Range: Population of 213 self-reported healthy individuals.

Data Provenance: The document does not explicitly state the country of origin for all patient samples or whether studies were retrospective or prospective, beyond "human serum," "patient serum samples," or "self-reported healthy individuals." The precision studies were conducted at "FDI" (Fujirebio Diagnostics, Inc. in Malvern, PA, USA) and "across several sites."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):

Not applicable. This is an immunoassay device for quantitative determination of Procalcitonin (PCT), where the "ground truth" is measured analytically by the device itself or compared to a predicate device. It does not involve human interpretation of images or other subjective data that would require expert consensus for ground truth.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Not applicable. As described above, this device is a quantitative immunoassay and does not involve human adjudication methods for its analytical performance or comparison studies.

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 in-vitro diagnostic device, not an AI/ML device, and does not involve human readers interpreting cases.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

Not applicable. This is an in-vitro diagnostic device, not an AI/ML device. The performance data presented are for the analytical device itself.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

For the analytical performance studies (precision, linearity, detection limits, specificity), the "ground truth" is typically defined by reference materials, spiked samples with known concentrations, or established analytical methods. For method comparison, the predicate device (B.R.A.H.M.S PCT sensitive KRYPTOR®) serves as the comparator. For establishing expected values, the measured PCT levels in a population of "self-reported healthy individuals" are used.

8. The sample size for the training set:

Not applicable in the context of AI/ML. For analytical performance, the samples used in the various studies (e.g., 20-day precision, lot-to-lot, site-to-site, linearity, detection limits, interference, cross-reactivity) are referred to as test samples or panels to evaluate the device's accuracy and reliability. There is no concept of a "training set" in the AI/ML sense for this type of IVD device.

9. How the ground truth for the training set was established:

Not applicable, as there is no "training set" in the AI/ML sense. The analytical performance is established through rigorous testing against reference materials and predicate devices following CLSI guidelines.

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

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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

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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:

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.

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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Image /page/3/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic on the left, consisting of blue and white shapes, possibly representing a water droplet or a stylized letter. To the right of the graphic is the company name, "FUJIREBIO" in large, bold, blue letters, with "Diagnostics, Inc." in a smaller font size underneath.

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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Image /page/4/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo consists of a stylized blue and teal graphic on the left, followed by the company name in blue text. The word "FUJIREBIO" is in a larger, bolder font than "Diagnostics, Inc.", which is positioned below it. The logo is clean and professional, suggesting a company in the medical or diagnostic field.

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 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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Image /page/5/Picture/1 description: The image shows the logo for FUJIREBIO Diagnostics, Inc. The logo consists of a blue abstract symbol on the left, followed by the company name in blue text. The word "FUJIREBIO" is in a larger, bolder font, and "Diagnostics, Inc." is in a smaller font below it. The logo is clean and professional, with a focus on the company name.

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® GB•R•A•H•M•S PCT (ProposedDevice)	B•R•A•H•M•S PCT sensitiveKRYPTOR®(Predicate Device)K171338
Device Type	In vitro diagnostic	Same
Classification	Class II	Same
Similarities and Differences
	Lumipulse® GB·R·A·H·M·S PCT (ProposedDevice)	B·R·A·H·M·S PCT sensitiveKRYPTOR®(Predicate Device)K171338
Analyte	Procalcitonin	Same
Regulation Number	21CFR § 866.3215; Device todetect and measure non-microbial analyte(s) in humanclinical specimens to aid inassessment of patients withsuspected sepsis	Same
Product Usage	Clinical and Hospital laboratories	Same
Principle of Operation	Automated QuantitativeChemiluminscent EnzymeImmunoassay (CLEIA)	Time-Resolved AmplifiedCryptate Emission (TRACE)
Specimen CollectionMethod	Routine Phlebotomy Techniques	Same
Intended Use	The Lumipulse G B•R•A•H•M•SPCT is a ChemiluminescentEnzyme Immunoassay (CLEIA)for the quantitative determinationof PCT (procalcitonin) in humanserum and plasma (sodiumheparin, lithium heparin, sodiumcitrate or dipotassium EDTA) onthe LUMIPULSE G System.Used in conjunction with otherlaboratory findings and clinicalassessments, Lumipulse GB•R•A•H•M•S PCT is intended foruse as an:• Aid in the risk assessmentof critically ill patients ontheir first day of intensivecare unit (ICU) admissionfor progression to severesepsis and septic shock.• Aid in assessing thecumulative 28-day risk ofall-cause mortality forpatients diagnosed withsevere sepsis or septicshock in the ICU or when	The B-R·A·H·M·SPCT sensitiveKRYPTOR® is animmunofluorescentassay using Time-Resolved AmplifiedCryptate Emission(TRACE) technologyto determine theconcentration of PCT(procalcitonin) inhuman serum andEDTA or heparinplasma.The B-R·A·H·M·SPCT sensitiveKRYPTOR® isintended to beperformed on theB-R·A·H·M·SKRYPTOR® analyzerfamily.Used in conjunctionwith other laboratoryfindings and clinicalassessments,B·R·A·H·M·S PCTsensitive KRYPTOR®
Similarities and Differences
	Lumipulse® GB·R·A·H·M·S PCT (ProposedDevice)	B·R·A·H·M·S PCT sensitiveKRYPTOR®(Predicate Device)K171338
	department or othermedical wards prior to ICUadmission, using a changein PCT level over time.• Aid in decision making onantibiotic therapy forpatients with suspected orconfirmed lowerrespiratory tract infections(LRTI) – defined ascommunity acquiredpneumonia (CAP), acutebronchitis, and acuteexacerbation of chronicobstructive pulmonarydisease (AECOPD) – in aninpatient setting or anemergency department.• Aid in decision making onantibiotic discontinuationfor patients with suspectedor confirmed sepsis.	is intended for use asfollows:• to aid in the riskassessment ofcritically ill patientson their first day ofICU admission forprogression to severesepsis and septicshock,• to determine thechange in PCT levelover time as an aid inassessing the cumulative28-dayrisk of all-causemortality for patientsdiagnosed withsevere sepsis orseptic shock in theICU or whenobtained in theemergencydepartment or othermedical wards priorto ICU admission,• to aid in decisionmaking on antibiotictherapy, forinpatients or patientsin the emergencydepartment withsuspected orconfirmed lowerrespiratory tractinfections (LRTI) –defined ascommunity-acquiredpneumonia (CAP),acute bronchitis, andacute exacerbationof chronic
Similarities and Differences
	Lumipulse® GB-R・A・H・M・S PCT (ProposedDevice)	B-R・A・H・M・S PCT sensitiveKRYPTOR®(Predicate Device)K171338
		obstructivepulmonary disease(AECOPD),
		• to aid in decisionmaking on antibioticdiscontinuation forpatients withsuspected orconfirmed sepsis.
Instrument System	LUMIPULSE G System	The BRAHMS KRYPTORanalyzer
Assay Type	Two-step sandwichimmunoassay based onchemiluminescenttechnology	Immunofluorescent assay
Type of Specimen	Human serum and plasma(sodium heparin, lithium heparin,sodium citrate or dipotassiumEDTA)	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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Image /page/6/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic to the left of the company name. The graphic is a blue and white design. The text "FUJIREBIO" is in a bold, blue sans-serif font, with the registered trademark symbol next to "BIO". Below that, "Diagnostics, Inc." is in a smaller, less bold font.

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Image /page/7/Picture/1 description: The image contains the logo for FUJIREBIO Diagnostics, Inc. The logo features a stylized graphic on the left, consisting of blue and green shapes that resemble a water droplet. To the right of the graphic, the text "FUJIREBIO" is displayed in a bold, blue sans-serif font. Below "FUJIREBIO", the words "Diagnostics, Inc." are written in a smaller, lighter font.

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Image /page/8/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic on the left, consisting of blue and green shapes. To the right of the graphic is the company name, "FUJIREBIO," in a bold, blue sans-serif font, with the registered trademark symbol next to it. Below the company name is the text "Diagnostics, Inc." in a smaller, lighter blue font.

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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Image /page/9/Picture/1 description: The image shows the logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic on the left, consisting of blue and green shapes resembling water droplets and vertical lines. To the right of the graphic, the word "FUJIREBIO" is written in large, bold, blue letters, with "Diagnostics, Inc." written in smaller, black letters below it.

. 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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Image /page/10/Picture/1 description: The image is a logo for Fujirebio Diagnostics, Inc. The logo consists of a blue and white abstract shape on the left, followed by the company name in blue, and the word "Diagnostics, Inc." in a smaller, darker font below the company name. The abstract shape appears to be a stylized representation of a water droplet or a similar fluid, possibly alluding to the company's work in diagnostics.

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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Image /page/11/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic element on the left, consisting of blue and white shapes. To the right of the graphic is the company name, "FUJIREBIO" in large, blue, sans-serif font, with the registered trademark symbol. Below the company name is the text "Diagnostics, Inc." in a smaller, sans-serif font, also in blue.

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

		BetweenLots		BetweenDay		BetweenRun		Within Runs(Repeatability)		Within-Laboratory(Total)
Sample	Mean(ng/L)	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Control Level1	0.634	0.030	4.7%	0.013	2.0%	0.030	4.7%	0.009	1.4%	0.033	5.3%
Control Level2	3.816	0.137	3.6%	0.016	0.4%	0.127	3.3%	0.055	1.4%	0.139	3.7%
Control Level3	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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Image /page/12/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized blue and white graphic on the left, resembling a water droplet or a stylized flower. To the right of the graphic, the text "FUJIREBIO" is displayed in a bold, blue sans-serif font, with the registered trademark symbol next to it. Below "FUJIREBIO", the text "Diagnostics, Inc." is written in a smaller, lighter blue font.

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

		BetweenSites		BetweenDays		BetweenRuns		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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Image /page/13/Picture/1 description: The image contains the logo for "FUJIREBIO Diagnostics, Inc." The logo consists of a stylized graphic on the left, featuring blue and white shapes, followed by the company name in blue text. The word "FUJIREBIO" is in a larger, bolder font, while "Diagnostics, Inc." is in a smaller font below it.

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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Image /page/14/Picture/1 description: The image contains the logo for FUJIREBIO Diagnostics, Inc. The logo features a stylized graphic element on the left, consisting of blue and white shapes. To the right of the graphic is the company name, "FUJIREBIO" in a bold, blue sans-serif font, with the word "Diagnostics, Inc." appearing in a smaller, black font below it.

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 DrugInterferences	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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Image /page/15/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic on the left, consisting of blue and white shapes, possibly representing water droplets or abstract forms. To the right of the graphic, the text "FUJIREBIO" is displayed in a bold, blue sans-serif font, with the words "Diagnostics, Inc." appearing in a smaller font size below it.

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 PCTsensitive KRYPTOR
n	CorrelationCoefficient(r)	Intercept(95% CI)	Slope(95% CI)	MeanDifference(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.

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.