FastPack® High Sensitivity C-Reactive Protein Immunoassay is to be used for evaluation of conditions thought to be associated with inflammation, in otherwise healthy individuals. The FastPack® High Sensitivity C-Reactive Protein Immunoassay is intended for use with the FastPack® Analyzer. Not intended for Point-of-Care use.

FastPack® High Sensitivity C-Reactive Protein Calibrators are used for calibrating the quantitative FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.

FastPack® High Sensitivity C-Reactive Protein Controls are used for quality control of the FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.

FastPack® High Sensitivity C-Reactive Protein Verifiers are used in the quantitative verification of calibration and assay range of the quantitative FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.

Device Description

The FastPack® High Sensitivity C-Reactive Protein Immunoassay employs a Sandwich immunoassay principle. Endogenous CRP in a patient sample, calibrator, control, or verifier is dispensed into a FastPack® reagent pack. In the reagent pack, the sample binds with a monoclonal anti-CRP antibody covalently linked to alkaline phosphatase (ALP) and a different monoclonal anti-CRP antibody linked to biotin. After incubation, immunoreacted complex (Monoclonal anti-CRP antibody-ALP conjugate and anti-CRP antibody linked to biotin reacted with CRP in the sample) is mixed with streptavidin coated paramagnetic particles. After washing steps (using a Tris buffer containing detergents) to separate bound from unbound anti-CRP monoclonal antibody-ALP, a chemiluminogenic substrate mixture is added to the system. This mixture contains indoxyl-3-phosphate, a substrate for ALP, and lucigenin (N,N'-dimethyl-9,9'-biacridinium dinitrate). ALP dephosphorylates indoxyl-3-phosphate to indol-3-ol, which subsequently undergoes oxidation. As a result, lucigenin is reduced to form a dioxetane structure that is cleaved to yield Nmethylacridone. This compound produces a sustained luminescent glow following excitation. The raw relative luminescence units (RLUs) generated are measured by a photomultiplier tube in the FastPack® Analyzer and are directly proportional to the concentration of CRP in the sample. The entire reaction sequence takes place at 37 ± 0.5 ℃ and is protected from external light.

AI/ML Overview

The provided document describes the FastPack® High Sensitivity C-Reactive Protein Immunoassay (device) and its performance to demonstrate substantial equivalence to a predicate device.

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly list "acceptance criteria" as a separate section with pass/fail values. Instead, it presents performance characteristics and compares them to the predicate device or established guidelines (e.g., CLSI). Based on the provided sections, a table can be constructed as follows:

Acceptance Criteria (Implied)	FastPack® High Sensitivity C-Reactive Protein Immunoassay Performance	Predicate Device Performance (Olympus CRP Latex reagent K051564)
Precision
Within-run %CV	≤ 1.0% (across various CRP levels)	≤ 3.2%
Between-run %CV	≤ 5.2% (across various CRP levels)	N/A (Total: ≤ 3.8%)
Total %CV	≤ 9.0% (across various CRP levels)	≤ 3.8%
Limits (LOB, LOD, LOQ)
LOB	0.005 mg/L	Not explicitly stated, implied to be comparable as predicates are established assays.
LOD	0.032 mg/L
LOQ	0.063 mg/L
Linearity Range	0.063 mg/L to 15.0 mg/L	0.2 - 160 mg/L (High Sensitivity Application: 0.2 - 15.0 mg/L is comparable to FastPack's application range)
Interferences	No interference from specified endogenous and exogenous substances at noted concentrations.	No interference from high levels of bilirubin, hemoglobin, and triglycerides.
Cross-reactivity	No cross-reactivity from Rheumatoid factor (up to 1000 U/mL), human anti-mouse IgG (up to 4 ug/mL), and heterophile samples (up to 3641 ng/mL).	Not explicitly detailed for all substances, but implied to have established specificity.
Serum and Plasma Equivalence (vs. Serum)		N/A (Device-specific validation)
EDTA Plasma Slope	0.94
EDTA Plasma R	0.984
Lithium-Heparin Plasma Slope	1.00
Lithium-Heparin Plasma R	0.993
Method Comparison (vs. Predicate)
Correlation Coefficient (R)	0.99	0.999 (AU400 vs. AU640, a different comparison for predicate)
Slope	0.98 (95% CI: 0.95-1.02)	1.025 (Predicate's own method comparison)
y-intercept	-0.12 (95% CI: -0.23 to 0.00)	-0.022 (Predicate's own method comparison)

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

Precision Study: 6 serum patient samples were used, each with 320 replicate determinations.
Limits of blank, detection, and quantitation: Information not provided about the specific "samples" used for these determinations.
Linearity Study: A high patient sample was intermixed with a low sample to generate 8 concentration levels, each tested in triplicate.
Interferences: Specific concentrations of various substances were tested. The number of samples/replicates isn't explicitly stated, but implies a controlled study.
Cross-reactivity: Specific concentrations of substances like Rheumatoid factor, human anti-mouse IgG, and heterophile samples were tested.
Serum and Plasma Equivalence: Blood collections from 41 volunteers.
Expected Values/Reference Intervals: Serum samples from 211 subjects.
Method Comparison: 131 samples.

Data Provenance:
The document states that the reference interval study employed serum samples from "211 subjects representing 4 different geographic regions of the United States." This indicates a prospective or retrospective collection of patient samples within the US for this specific study. For other studies (precision, linearity, interferences, serum/plasma equivalence, method comparison), specific provenance details like country of origin or retrospective/prospective nature are not explicitly stated, but are generally assumed to be carried out under controlled laboratory conditions often using commercially available or anonymized clinical samples.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts:

This information is not applicable to this type of device (in-vitro diagnostic immunoassay). The "ground truth" for a C-reactive protein immunoassay is typically the actual concentration of CRP in the sample, which is determined by established reference methods or by the device's own calibrated measurement. There are no human "experts" establishing ground truth in the sense of image interpretation or clinical diagnosis for this kind of analytical device. The "ground truth" for method comparison is the result obtained from the predicate device or a reference method.

4. Adjudication Method for the Test Set:

This information is not applicable for this type of device. Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies where multiple human readers interpret data (e.g., medical images) and their interpretations need to be resolved for ground truth. For an immunoassay, the results are quantitative measurements, not subjective interpretations requiring adjudication.

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:

This information is not applicable to this device. An MRMC study is relevant for AI-assisted diagnostic tools where human readers are part of the diagnostic workflow. The FastPack® Immunoassay is an automated analytical device that directly measures CRP concentration, not an AI system assisting human interpretation.

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

The device described, the FastPack® High Sensitivity C-Reactive Protein Immunoassay, is an automated immunoassay system. Its performance is inherently "standalone" in the sense that the analyzer performs the measurement without human intervention influencing the quantitative result. The performance data presented (precision, linearity, limits, interference, method comparison) is the standalone performance of the algorithm/system. There is no "human-in-the-loop" component in terms of result generation for this type of device.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):

The "ground truth" for the performance studies of this immunoassay primarily relies on:

Reference Methods/Predicate Device Results: For method comparison, the results obtained from a legally marketed predicate device (Olympus AU2700 for the method comparison) served as the reference for comparison.
Known Concentrations: For studies like linearity, limits of detection/quantitation, and precision, samples with known, spiked, or characterized CRP concentrations are used.
Clinical Samples: For serum and plasma equivalence and reference interval studies, collected human serum and plasma samples are used. The CRP concentrations in these samples, as measured by the device itself or a reference method, serve as the "true" or observed values for evaluating performance parameters.

8. The Sample Size for the Training Set:

This information is not applicable in the context of this document. This device is an immunoassay, not an AI/machine learning system that requires a "training set" in the computational sense. The device's operational parameters, calibration curves, and analytical procedures are established through manufacturing and analytical validation processes, not through machine learning training on a dataset.

9. How the Ground Truth for the Training Set was Established:

This information is not applicable as there is no "training set" for this type of immunoassay device in the context of an AI/machine learning system. The "ground truth" for calibrating immunoassays is established using reference materials with assigned values traceable to international standards (e.g., ERM-DA474/IFCC for CRP, as mentioned in the device's traceability). These reference materials are meticulously characterized using highly accurate and precise analytical methods.

Summary

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized graphic of three human profiles facing to the right, stacked on top of each other.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

QUALIGEN, INC. MICHAEL POIRIER SENIOR VICE PRESIDENT, CSO/CTO 2042 CORTE DEL NOGAL CARLSBAD CA 92011

January 7, 2015

Re: K141689

Trade/Device Name: Fastpack High Sensitivity C-reactive Protein Immunoassay Fastpack High Sensitivity C-reactive Protein Calibrator Kit Fastpack High Sensitivity C-reactive Protein Controls, Fastpack High Sensitivity C-reactive Protein Method Verification Kit Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: II Product Code: DCK, JIT, JJX Dated: December 15, 2014 Received: December 18, 2014

Dear Mr. Poirier:

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 Parts 801 and 809); medical device reporting (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

{1}------------------------------------------------

electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Katherine Serrano -S

For : Courtney H. Lias, Ph.D.

Director Division of Chemistry and Toxicology 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) K141689

Device Name

FastPack® High Sensitivity C-Reactive Protein Immunoassay, FastPack® High Sensitivity C-Reactive Protein Calibrator Kit, FastPack® High Sensitivity C-Reactive Protein Controls . High Sensitivity C-Reactive Protein Method Verification Kit

Indications for Use (Describe)

FastPack® High Sensitivity C-Reactive Protein Calibrators are used for calibrating the quantitative FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.

FastPack® High Sensitivity C-Reactive Protein Control of the FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.

FastPack® High Sensitivity C-Reactive Protein Verifiers are used in the quantitative verification and assay range of the quantitative FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.

Type of Use (Select one or both, as applicable)

[X] Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

{3}------------------------------------------------

510(k) SUMMARY

{4}------------------------------------------------

REVISED 510(k) SUMMARY

This 510(k) Summary information is submitted in accordance with the requirements of 21 CFR § 807.92.

510(k) Number: K141689

Submitter:

Qualigen, Inc. 2042 Corte Del Nogal, Suite B Carlsbad, CA 92009

Telephone:	(760) 918-9165
Facsimile:	(760) 918-9127

Contact Person:

Mr. Michael Poirier Senior Vice President, Chief Scientific & Technical Officer Telephone: (760) 918-9165 x227 Facsimile: (760) 918-9127 Email: mpoirier@qualigeninc.com

Device Identification

Trade Names:	FastPack® High Sensitivity C-Reactive Protein Immunoassay
	FastPack® High Sensitivity C-Reactive Protein Calibrator Kit
	FastPack® High Sensitivity C-Reactive Protein Controls
	FastPack® High Sensitivity C-Reactive Protein Method
	Verification Kit

Common Names: C-reactive protein Assay C-reactive protein Calibrator C-reactive protein Controls C-reactive protein Verifiers

Classification names: Immunological Test Systems Calibrator Quality control material (assayed and unassayed)
Classifications: Class II (assay)

{5}------------------------------------------------

	Class II (calibrators)
	Class I, reserved (controls)
	Class I, reserved (verifiers)
Panel:	Chemistry (75)
Product Codes:	DCK - C-Reactive Protein, Antigen, Antiserum
	JIT - Calibrator, Secondary
	JJX - Quality control material (Assayed and Unassayed)
	Regulation Numbers: 21 CFR § 866.5270 - C-reactive protein immunological test system
	21 CFR § 862.1150 - Calibrator
	21 CFR § 862.1660 - Quality control material (Assayed and
	Unassayed)

Devices to Which Substantial Equivalence is Claimed

Olympus CRP Latex reagent Olympus America, Inc. 3500 Corporate Parkway PO Box 610 Center Valley, PA K051564

Liquichek™ Cardiac Markers Plus Control Bio-Rad Laboratories 4000 Alfred Nobel Drive Hercules, CA 94547 K050537

VITROS Chemistry Products hsCRP Performance Verifier I, II, and III Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, NY 14626-5101 K041799

Device Description

{6}------------------------------------------------

phosphatase (ALP) and a different monoclonal anti-CRP antibody linked to biotin. After incubation, immunoreacted complex (Monoclonal anti-CRP antibody-ALP conjugate and anti-CRP antibody linked to biotin reacted with CRP in the sample) is mixed with streptavidin coated paramagnetic particles. After washing steps (using a Tris buffer containing detergents) to separate bound from unbound anti-CRP monoclonal antibody-ALP, a chemiluminogenic substrate mixture is added to the system. This mixture contains indoxyl-3-phosphate, a substrate for ALP, and lucigenin (N,N'-dimethyl-9,9'-biacridinium dinitrate). ALP dephosphorylates indoxyl-3-phosphate to indol-3-ol, which subsequently undergoes oxidation. As a result, lucigenin is reduced to form a dioxetane structure that is cleaved to yield Nmethylacridone. This compound produces a sustained luminescent glow following excitation. The raw relative luminescence units (RLUs) generated are measured by a photomultiplier tube in the FastPack® Analyzer and are directly proportional to the concentration of CRP in the sample. The entire reaction sequence takes place at 37 ± 0.5 ℃ and is protected from external light.

Intended Use

FastPack® High Sensitivity C-Reactive Protein Immunoassay is to be used for evaluation of conditions thought to be associated with inflammation, in otherwise healthy The FastPack® High Sensitivity C-Reactive Protein Immunoassay is individuals. intended for use with the FastPack® Analyzer. Not intended for Point-of-Care use.

FastPack® High Sensitivity C-Reactive Protein Calibrators are used for calibrating the quantitative FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.

FastPack® High Sensitivity C-Reactive Protein Controls are used for quality control of the FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.

{7}------------------------------------------------

		Comparison of new nevice to preated devices
	CHARACTERISTIC	Qualigen FastPack® High	Olympus America, Inc. CRP
		Sensitivity C-Reactive Protein	Latex reagent
		Immunoassay	K051564
	Intended Use/	FastPack® High Sensitivity C-	Olympus System Reagent and
	Indications for Use	Reactive Protein Immunoassay is	calibrators for the quantitative
		to be used for evaluation of	determination of C-Reactive
		conditions thought to be associated	Protein on OLYMPUS
		with inflammation, in otherwise	Analyzers. Measurement of
		healthy individuals. The	CRP is useful for the detection
		FastPack® High Sensitivity C-	and evaluation of infection,
		Reactive Protein Immunoassay is	tissue injury, inflammatory
		intended for use with the	disorders, and associated
		FastPack® Analyzer. Not intendedfor Point-of-Care use.	diseases. Measurements mayalso be used as an aid in the
			identification of individuals at
			risk of future cardiovascular
			disease. High sensitivity CRP
			(hsCRP) measurements, when
			used in conjunction with
			traditional clinical laboratory
			evaluation of acute coronary
			syndromes, may be useful as an
			independent marker of prognosis
			for recurrent events, in patients
			with stable coronary disease or
			acute coronary syndromes.
	Sample Type	Serum or plasma(EDTAor	Same
lithium heparin)
	Sample Preparation	Standard processing for serum or	Same
		plasma
	Interpretation of	Standard Curve	Same
	Results
	Reagent Storage	2-8 °C	Same
	Temperature
	Testing Environment	Professional use	Same
	Precision (% CV)	Within-run: ≤ 1.0%	Within-run: ≤ 3.2%
		Between-run: ≤ 5.2%	Total: ≤ 3.8%
		Total: ≤ 9.0%
	Linearity	Assay linear from 0.2 to 15.0 mg/L	Assay linear from 0.2 - 160 mg/L
		in High Sensitivity Application
	Interfering	No interference from high levels of	No interference from high levels
	Substances/Specificity	conjugated bilirubin, unconjugated	of bilirubin, hemoglobin, and
		hemoglobin,bilirubin,	triglycerides
		triglycerides.humanserum
		L-ascorbicalbumin,acid.
		oxaloaceticacid,glutathione,
		L-DOPA; noisoniazid,and -fromrheumatoidinterference

	factor, human anti-mouse IgG, and
Comparative Testing vsEstablished Methods	transferrinFastPack® vs. Olympus AU2700N = 131Range of observations:0.21 to 15.0 mg/LDeming regression:Slope (95% CI): 0.98 (0.95-1.02)y (95% CI): -0.12 (-0.23 to 0.00)R (95% CI) = 0.99 (0.99-0.99)Sy\x = 0.629	AU400 vs. AU640N = 109Range of observations:0.28-147.2 mg/LDeming regression:Slope = 1.025y = -0.022R = 0.999
ExpectedValues/ReferenceIntervals	0.2 - 11.4 mg/L	Cardiac risk assessmentcategories:Low < 1 mg/LAverage 1.0 to 3.0 mg/LHigh > 3.0 mg/L

Comparison of new device to predicate devices

{8}------------------------------------------------

Differences between FastPack® and Olympus High-Sensitivity C-Reactive Protein

Assays
CHARACTERISTIC	Qualigen FastPack®High-Sensitivity C-ReactiveProtein Immunoassay	Olympus America, Inc. CRPLatex reagentK051564
Methodology	The FastPack® High Sensitivity C-Reactive Protein Immunoassay is a paramagnetic particle, chemiluminescent immunoassay employing specific monoclonal antibodies.	The Olympus CRP Latex reagent is a turbidimetric assay employing rabbit antibodies coated on latex particles.
Assay principle	Chemiluminescence	Turbidimetry
Assay procedure	Automated	Automated
Approximate assay time	8 minutes	3.5 minutes
Assay range	0.2 - 15.0 mg/L in High Sensitivity Application	0.2 - 160 mg/L (provides measurements both for “Normal Application” and “Highly Sensitive Application”)
Traceability	Traceable to the ERM-DA474/IFCC reference which serves as the Primary Reference Material	“…traceable to an external standard.” (K051564 510(k) Decision Summary)

{9}------------------------------------------------

CHARACTERISTIC	Qualigen FastPack®High-Sensitivity C-Reactive ProteinImmunoassay	Olympus America, Inc. CRPLatex reagentK051564
Intended Use/Indication for Use	For in-vitro diagnosticuse in calibratingFastPack® High-Sensitivity C-ReactiveProtein Immunoassay	Olympus System Reagent andcalibrators for the quantitativedetermination of C-ReactiveProtein on Olympus Analyzers.
Antigen used in calibrators	Human CRP	Same
Matrix	Liquid human serummatrix containing apredetermined level ofhuman CRP	Liquid human serum matrixcontaining predetermined levels ofhuman CRP
Storage temperature	2-8 °C	Same

Similarities between FastPack® and Olympus CRP Calibrators

Differences between FastPack® and Olympus CRP Calibrators

CHARACTERISTIC	Qualigen FastPack®High-Sensitivity C-Reactive ProteinImmunoassay	Olympus America, Inc. CRPLatex reagentK051564
Number of calibrators	1	5 (additional calibrators providedat higher concentrations to enableCRP measurements in the “NormalApplication”)

{10}------------------------------------------------

CHARACTERISTIC	Qualigen FastPack®High-Sensitivity C-ReactiveProtein Immunoassay	Bio-Rad LaboratoriesLiquichek™ CardiacMarkers Plus ControlK050537
Intended Use/Indication for Use	For in-vitro diagnostic use tomonitor the precision andaccuracy of the FastPack®High-Sensitivity C-ReactiveProtein Immunoassay on theFastPack® Analyzer.	Liquichek™ CardiacMarkers Plus Control areintended for use as qualitycontrol serum to monitorthe precision of laboratorytesting procedures listing inthe package insert.
Antigen used in controls	Human CRP	B-type Natriuretic Peptide,Creatine Kinase (Total), C-Reactive Protein,Homocysteine, Digitoxin,N-terminal pro-B-typeNatriuretic Peptide, CK-MB, Myoglobin, TroponinI, Troponin T
Matrix	Liquid human serum matrixcontaining a predeterminedlevel of human CRP	Prepared from humanserum with addedconstituents of human andanimal origin,preservatives, andstabilizers. The controls arein liquid form.
Storage temperature	2-8 °C	2-8 °C (Opened), or -20 to -70 °C (Unopened)

Similarities between FastPack® and Predicate Controls

Differences between FastPack® and Predicate Controls

CHARACTERISTIC	Qualigen FastPack®High-Sensitivity C-ReactiveProtein Immunoassay	Bio-Rad LaboratoriesLiquichek™ CardiacMarkers Plus ControlK050537
Number of levels	2	3

{11}------------------------------------------------

CHARACTERISTIC	Qualigen FastPack®High-Sensitivity C-ReactiveProtein Immunoassay	Ortho-ClinicalDiagnostics, Inc. VITROChemistry ProductshsCRP PerformanceVerifier, I, II, and IIIK041799
Intended Use/Indication for Use	For use in the quantitativeverification of calibration andassay range of the quantitativeFastPack® High-Sensitivity C-Reactive Protein Immunoassayon the FastPack® Analyzer.	VITROS hsCRPPerformance Verifiers areassayed controls to monitorperformance of hsCRPReagent on VITROS 5,1 FSChemistry Systems
Antigen used	Human CRP	Same
Storage temperature	2-8 °C	Same
Matrix	Low Verifier: HEPES bufferwith Bovine Serum Albumin(BSA) and Detergent(Cremophor A25)Mid and High Verifiers: Liquidhuman serum matrix containinga predetermined level of humanCRP	A base matrix of humanplasma proteins to whichstabilizers and preservativehave been added.
Number of levels	3	Same

Similarities between FastPack® CRP Verifiers and Predicate Verifiers

Performance Summary

Precision

Precision was evaluated following the CLSI EP5-A2 guidance. Six serum patient samples with concentrations of ~0.5, 1.0, 2.0, 5.0, 7.5, and 12.5 mg/L CRP were tested in duplicate determinations in each of two runs per day on each of two FastPack® reagent lots, two FastPack® Analyzers per reagent lot, over a period of 20 days to yield 320 replicate determinations of each sample. A single FastPack® calibrator lot was utilized for all runs. Within-run, between-run, between-day, and residual components of variation were calculated as well as total imprecision using a general linear model. The table below presents the results:

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

		Within-Run		Between-Run		Between-Day		Residual		Total
Sample	Overall Mean	SD	% CV	SD	% CV	SD	% CV	SD	% CV	SD	% CV
Serum Sample 1	0.38	0.002	0.53	0.014	3.68	0.005	1.32	0.029	7.74	0.033	8.68
Serum Sample 2	1.00	0.004	0.43	0.038	3.80	0.013	1.30	0.077	7.71	0.087	8.70
Serum Sample 3	2.06	0.008	0.39	0.071	3.45	0.030	1.46	0.162	7.89	0.180	8.74
Serum Sample 4	5.01	0.023	0.46	0.206	4.11	0.073	1.46	0.288	5.74	0.362	7.23
Serum Sample 5	7.67	0.035	0.46	0.314	4.09	0.111	1.45	0.596	7.78	0.684	8.92
Serum Sample 6	12.54	0.073	0.58	0.649	5.18	0.230	1.83	0.843	6.72	1.091	8.70

Limits of blank, detection, and quantitation

The Limit of Blank (LOB), the Limit of Detection (LOD), and the Limit of Quantitation (LOQ) of the FastPack® C-Reactive Protein Immunoassay were determined according to CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation. The following are the limits determined:

LOB = 0.005 mg/L LOD = 0.032 mg/L LOQ=0.063 mg/L

Linearity

Linearity was determined following CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: a Statistical Approach: Approved Guideline. A high patient sample was intermixed with a low sample to generate 8 concentration levels each tested in triplicate determinations. Linear results were compared to 2nd and 3th order polynomial fits against a pre-specified allowable error. The linearity range was found to extend from the LOQ (0.063 mg/L) to 15.0 mg/L. Samples recovering above the range may be diluted using Sample Diluent A.

Interferences

The following substances normally present in blood were tested and found not to interfere in the FastPack® High Sensitivity C-Reactive Protein Immunoassay at the noted concentrations:

Bilirubin (conjugated)	Tested to 40 mg/dL
Bilirubin (unconjugated)	Tested to 40 mg/dL
Hemoglobin	Tested to 750 mg/dL
Lipids	Tested to 1000 mg/dL

{13}------------------------------------------------

Human serum albumin Transferrin Human IgG

Tested to 7.7 g/dL Tested to 567 mg/dL Tested to 2961 ug/mL

The following exogenous substances potentially present in blood were tested and found not to interfere in the FastPack® High Sensitivity C-Reactive Protein Immunoassay at the noted concentrations:

L-ascorbic acid	Tested to 200 mg/dL
Oxaloacetic acid	Tested to 300 μΜ
Glutathione	Tested to 300 μΜ
Isoniazid	Tested to 300 μΜ
L-DOPA	Tested to 300 μΜ

Cross-reactivity

Rheumatoid factor at up to 1000 U/mL and human anti-mouse IgG at up to 4 ug/mL do not cross-react in the FastPack® High Sensitivity C-Reactive Protein Immunoassay. Additionally, heterophile samples with activity up to 3641 ng/mL do not interfere in the assay.

Serum and plasma equivalence

Blood collections were obtained from 41 volunteers and processed in parallel to serum, EDTA plasma, and lithium-heparin plasma. Measurements in FastPack® High Sensitivity C-Reactive Protein Immunoassay were compared via Deming regression and indicated equivalence between the three matrices.

Parameter	Result
N compared	41
Range of observations, mg/L	Serum: 0.33 – 14.72EDTA Plasma: 0.29 – 14.76
Absolute bias, mg/L	-0.225
% Bias	-6.1
Deming regression results
Slope	0.94
y-intercept	0.0
R	0.984
R2	0.967

Serum versus EDTA plasma

{14}------------------------------------------------

Parameter	Result
N compared	41
Range of observations, mg/L	Serum: 0.33 - 14.72Lithium-Heparin Plasma: 0.31 – 14.86
Absolute bias, mg/L	0.002
% Bias	0.5
Deming regression results
Slope	1.00
y-intercept	0.00
R	0.993
R2	0.986

Serum versus lithium-heparin plasma

Expected Values/Reference Intervals

A reference interval study employing serum samples from 211 subjects representing 4 different geographic regions of the United States yielded the results in the table below. The non-parametric 2.5th - 97.5th percentile of 0.2 - 11.4 mg/L provides the reference interval determined from this study.

Observed values
Mean (SD)	3.2 (3.1) mg/L
Median (Min - Max)	1.9 (0.2 - 13.1) mg/L
2.5th - 97.5th percentile	0.2 - 11.4 mg/L

Newborns with no evidence of infection have CRP concentrations of < 2 mg/L (Soldin OP, Bierbower LH, Choi JJ, et al. Serum iron, ferritin, transferrin, total iron binding capacity, hs-CRP, LDL cholesterol and magnesium in children; new reference intervals using the Dade Dimension Clinical Chemistry System; Clin Chim Acta 2004;342:211-7.).

Method Comparison

Human serum samples were tested with the FastPack® High Sensitivity C-Reactive Protein Immunoassay and the obtained results were compared to the predicate method. A total of 131 samples ranging from 0.21 to 15.0 mg/L were tested in both assays. The FastPack® High Sensitivity C-Reactive Protein Immunoassay correlated well with the predicate method with correlation coefficient (R) of 0.99, slope = 0.98, and y-intercept = -0.12 mg/L.

{15}------------------------------------------------

Parameter	Result
Slope (95% CI)	0.98 (0.95-1.02)
y-intercept (95% CI)	-0.12 (-0.23 to 0.00)
R (95% CI)	0.99 (0.99 - 0.99)

SUMMARY

The information provided in this pre-market notification indicates that the FastPack® High Sensitivity C-Reactive Protein Immunoassay is substantially equivalent to the stated predicate device. The information further indicates that the FastPack® High Sensitivity C-Reactive Protein Immunoassay is safe and effective for its stated intended use.

Regulation Number and Section

§ 866.5270 C-reactive protein immunological test system.

(a)
Identification. A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.(b)
Classification. Class II (performance standards).