The PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit is intended for use with the Paragon CZE 2000 Capillary Electrophoresis System for the electrophoretic separation of proteins in human urine.

The PARAGON CZE® 2000 Urine Immunofixation by Subtraction (U-IFE/s) Electrophoresis Kit is intended for use with the Paragon CZE 2000 Capillary Electrophoresis System for the immunologic identification of monoclonal components in human urine.

Device Description

The PARAGON CZE® 2000 UPE and U-IFE/s kits are designed for optimal performance on the PARAGON CZE® 2000. The UPE kits contain one Segment package containing 20 Segments, five Desalting Column packages with 4 columns per package, and four 500 mL Desalting Reagent bottles. The U-IFE/s kits contain two Segment packages containing 10 Segments, one Desalting Column package with 4 columns per package, and one 500 mL Desalting Reagent bottle.

AI/ML Overview

This document describes the acceptance criteria and supporting studies for the Beckman Coulter PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit and Urine Immunofixation By Subtraction (U-IFE/s) Kit.

Acceptance Criteria and Device Performance

The provided document focuses on demonstrating substantial equivalence to predicate devices rather than establishing specific acceptance criteria for a novel device. The performance data presented in Section 8.0 serves to show that the new devices perform comparably to their gel electrophoresis predicate counterparts.

Here's a table summarizing the performance data, which implicitly acts as evidence for meeting "acceptance criteria" of comparable performance to the predicate:

Test	Acceptance Criteria (Implied by Comparison)	Reported Device Performance (PARAGON CZE 2000)
UPE Kit Method Comparison	High agreement with the PARAGON Gel Electrophoresis – SPE Kit	95% Agreement, 4% Partial Agreement, 1% Disagreement (n=100)
U-IFE/s Kit Method Comparison	High agreement with the PARAGON Gel Electrophoresis – IFE Kit	92.7% Full Agreement, 7.3% Disagreement (n=82)
UPE Imprecision (Albumin)	Low Coefficient of Variation (C.V.) for various imprecision types	Within-Run (System): 2.5% C.V.
		Within-Run (Desalting): 3.0% C.V.
		Total (Level 1): 2.5% C.V.
		Total (Level 2): 2.2% C.V.
		Total (Level 3): 9.2% C.V.
UPE Imprecision (BJP)	Low Coefficient of Variation (C.V.) for various imprecision types	Within-Run (System): 7.1% C.V.
		Within-Run (Desalting): 5.3% C.V.
		Total (Level 1): 5.9% C.V.
		Total (Level 2): 12.7% C.V.
		Total (Level 3): 2.0% C.V.
U-IFE/s Reproducibility	Visual agreement of electropherograms, no observable differences in morphology or subtraction, and Bence-Jones protein subtraction as expected, meeting an 80% specification for visual agreement.	Reproducibility meets the 80% specification for visual agreement for the replicate segments. No observable difference in morphology or subtraction was seen. BJP subtraction with kappa and lambda was as expected.

Study Information

The document describes studies conducted to demonstrate substantial equivalence of the new PARAGON CZE® 2000 UPE and U-IFE/s Kits to their respective predicate gel electrophoresis kits.

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

UPE Kit Method Comparison:
- Test Set Sample Size: 100 samples (indicated by 'n=100').
- Data Provenance: Not explicitly stated, but clinical laboratory samples are generally assumed to be retrospective or a mix of prospective/retrospective from a specific clinical setting. Given the year 2005, it's highly likely to be retrospective samples from a clinical lab. No country of origin is specified.
U-IFE/s Kit Method Comparison:
- Test Set Sample Size: 82 samples (indicated by 'n=82').
- Data Provenance: Not explicitly stated, but similar to the UPE kit, likely retrospective clinical samples. No country of origin is specified.
UPE Imprecision Studies:
- System Reproducibility: 21 runs for each urine pool (Albumin and BJP).
- Desalting Reproducibility: 21 runs for each urine pool (Albumin and BJP).
- Total Imprecision (EP 10-A): 15 runs for each of the three urine levels (Albumin and BJP).
- Data Provenance: These are laboratory studies, likely conducted internally by the manufacturer. No country of origin is specified.
U-IFE/s Reproducibility Studies:
- Test Set Sample Size: Not explicitly stated as a number, but the description mentions "the replicate segments tested."
- Data Provenance: These are laboratory studies, likely conducted internally by the manufacturer. No country of origin is specified.

3. Number of Experts and Qualifications for Establishing Ground Truth for the Test Set

The studies outlined (method comparison and imprecision) do not involve human expert consensus for "ground truth" in the way an imaging AI study would. Instead, the "ground truth" for the method comparison studies is established by the results from the predicate devices: the PARAGON Gel Electrophoresis – SPE Kit (for UPE) and the PARAGON Gel Electrophoresis – IFE Kit (for U-IFE/s).

Number of Experts: Not applicable in the context of this type of IVD device study. The predicate device's results are considered the reference.
Qualifications of Experts: Not applicable. The "ground truth" is derived from a previously cleared diagnostic method.

4. Adjudication Method for the Test Set

Method Comparison Studies (UPE and U-IFE/s): The comparison method involves results from the new device being assessed against the predicate device. The results are categorized as "Agreement," "Partial Agreement," or "Disagreement" for UPE, and "Full Agreement" or "Disagreement" for U-IFE/s. It is implied that laboratory personnel or study investigators evaluated these agreements based on established protocols for comparing quantitative or qualitative results from two different methods. The specific adjudication method (e.g., 2+1, 3+1) is not specified as it's not a common paradigm for these types of IVD performance studies where instrument results are directly compared.
Imprecision and Reproducibility Studies: These are quantitative measurements. Adjudication is statistical (e.g., calculation of Mean, SD, %C.V.). For U-IFE/s visual reproducibility, it states "electro-pherograms were visually inspected," but it doesn't specify if multiple readers were involved or an adjudication process for discrepancies.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study was not done. This type of study (comparing human readers with and without AI assistance) is typically performed for AI/CADe (Computer-Aided Detection/Diagnosis) devices, especially in medical imaging. The devices in this submission (UPE and U-IFE/s Kits) are in vitro diagnostic kits that automate protein analysis, not an AI/CADe system for human interpretation enhancement. The comparison is between a new automated method (capillary electrophoresis) and an older automated/semi-automated method (gel electrophoresis).

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

Yes, the studies presented are essentially standalone performance evaluations of the devices. The "device performance" refers to the automated analysis performed by the PARAGON CZE® 2000 system using these kits. While a human operator initiates the test and interprets the final electropherograms (especially for U-IFE/s with visual inspection), the studies quantify the device's ability to perform the separation and detection reliably and accurately relative to a predicate, independent of variable human interpretation during the core analytical process.

7. The Type of Ground Truth Used

For Method Comparison studies: The "ground truth" is implicitly the analytical result obtained from the predicate devices (PARAGON Gel Electrophoresis – SPE Kit for UPE, and PARAGON Gel Electrophoresis – IFE Kit for U-IFE/s).
For Imprecision and Reproducibility studies: The ground truth is the expected performance within laboratory quality control parameters, with various urine pools (with known or characterized levels of Albumin and BJP) serving as reference samples.

8. The Sample Size for the Training Set

The document is a 510(k) submission for in vitro diagnostic kits, not an AI/machine learning device. Therefore, the concept of a "training set" for an algorithm, as understood in AI development, does not apply here. The kits are reagents and consumables for an existing analytical instrument (PARAGON CZE® 2000). The development of the methodology and reagents would have involved internal validation and optimization, but there isn't a "training set" in the sense of data used to train a predictive model.

9. How the Ground Truth for the Training Set Was Established

As stated above, the concept of a "training set" for an algorithm is not applicable to the development and validation of these IVD kits. The "ground truth" in the development of such kits would involve:

Analytical Chemistry Principles: The fundamental principles of capillary electrophoresis and immunofixation.
Reference Materials: Using certified reference materials or well-characterized patient samples with known protein compositions/concentrations.
Comparison to Established Methods: Extensive internal testing and optimization against existing, validated methods (like the predicate gel electrophoresis systems) to fine-tune reaction conditions, reagent formulations, and instrument parameters to achieve desired performance characteristics.

This information is derived from the provided 510(k) summary document.

Summary

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Ko50119

MAY - 6 21:5

510(k) Summary Beckman Coulter PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit and Urine Immunofixation By Subtraction (U-IFE/s) Kit

Submitted By: 1.0

Kim Walker Requlatory Affairs Manager Beckman Coulter, Inc. 200 S. Kraemer Blvd., W-515 Brea, California 92822-8000 Telephone: (714) 961-4912 FAX: (714) 961-3969

2.0 Date Submitted:

January 14, 2005

3.0 Device Name(s):

Proprietary Names 3.1

PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit

PARAGON CZE® 2000 Urine Immunofixation by Subtraction (U-IFE/s) Electrophoresis Kit

3.2 Classification Name

UPE & U-IFE/s - Bence-Jones proteins immunological test (21 CFR $ 866.5150)

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Predicate Devices: 4.0

Candidate	Predicate	Manufacturer	DocketNumber
PARAGON CZE2000 UPE Kit	PARAGON SPE Kit	BeckmanCoulter, Inc.	K802592
PARAGON CZE2000 U-IFE/s Kit	PARAGON IFE Kit	BeckmanCoulter, Inc.	K823884

5.0 Description:

6.0 Intended Use:

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Comparison to Predicate(s): 7.0

The following tables show similarities and differences between the predicate identified in Section 4.0 of this summary.

Kit	Aspect/Characteristic	Comments
UPE Kit	Basic Technology (Electrophoretic Migration)	Same as BeckmanParagon SPE Kit
	Urine Sample Type
	Shelf Life Stability
	Specificity
	Qualitative Results
U-IFE/s Kit	Basic Technology (Electrophoretic Migrationwith Immunofixation)	Same as BeckmanParagon IFE Kit
	Urine Sample Type
	Qualitative Results
	Shelf Life Stability
	Antisera Storage
	Antisera Specificity

Similarities to the Predicate

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Differences From The Predicate

Kit	Aspect/Characteristic	Comments
UPE Kit	Intended Use	The Paragon CZE 2000 Urine Protein Electrophoresis(UPE) Kit is intended for use with the Paragon CZE2000 Capillary Electrophoresis System for theelectrophoretic separation of proteins in human urine.The Paragon Serum Protein Electrophoresis (SPE) Kitis intended for the electrophoretic separation ofproteins in human serum, cerebrospinal fluid, and urine.
	Sample Preparation	UPE - No concentration required for urine sampleswith a total protein of 20-4800 mg/dL. Must desaltbefore running sample on CZE. Any samples <20mg/dL must be concentrated and >4800 mg/dL mustbe diluted.SPE - Concentration required for all urine samples<700 mg/dL total protein.
	Interferences	UPE- Any materials that would absorb at 214 nm andnot removed by desalting. Hemoglobin co-migrateswith transferrin.SPE - Lipemic and hemolyzed samples.
	Lowest DetectibleLimit	UPE - 0.5-2.0 mg/dL of Kappa and Lambda BenceJones Proteins were visible when no other co-migrating proteins were present.SPE - No claims made.
	Methodology	UPE - Capillary ElectrophoresisSPE - Gel Electrophoresis
	Sample Size	UPE - 0.5 mL Desalted UrineSPE - 3-5 uL Concentrated or Neat Urine
	StorageTemperature	UPE-2-30°CSPE - 18 - 26°C
	Analytic Range	UPE - Single Protein Component 0.5 - 2.0 mg/dL to4600 mg/dL & Total Protein 0.02 - 4.80 g/dLSPE - Total Protein >700 mg/dL
Kit	Aspect/Characteristic	Comments
U-IFE/sKit	Intended Use	The Paragon CZE 2000 Urine Immunofixation bySubtraction (U-IFE/s) Electrophoresis Kit is intendedfor use with the Paragon CZE 2000 CapillaryElectrophoresis System for the immunologicidentification of monoclonal components in humanurine.The Paragon Immunofixation Electrophoresis (IFE) Kitis for the immunologic identification of proteins inhuman serum, cerebrospinal fluid, and urine.
	Sample Preparation	U-IFE/s - No concentration required for urine samplesw/ monoclonal components of 5 - 300 mg/dL. Mustdesalt before running sample on CZE. Any samples<5 mg/dL of monoclonal components or <2.5 - 10.0mg/dL of monoclonal components must beconcentrated & >300 mg/dL of monoclonalcomponents must be diluted.IFE - Concentration required for all urine samples<100 mg/dL total protein for the detection of Bence-Jones Proteins. Concentration up to 800 - 1000mg/dL should be conducted on all urine samples forthe detection of immunoglobulins.
	Interferences	U-IFE/s- Any materials that would absorb at 214 nmand not removed by desalting. Hemoglobin co-migrates w/ transferrin.IFE - Fibrinogen containing, IgM Immune complexcontaining & hemolyzed samples.
	Lowest DetectibleLimit	U-IFE/s – 2.5-5.0 mg/dL of Lambda & 5.0-10.0 mg/dLof Kappa Bence-Jones proteins were visible when noother co-migrating proteins were present.IFE - No claims made.
	Methodology	U-IFE/s - Capillary ElectrophoresisIFE - Gel Electrophoresis
	Sample Size	U-IFE/s – 300-700 μL Desalted Urine depending onthe dilution usedIFE - 3-5 uL Concentrated or Neat Urine
	StorageTemperature otherthan Antisera	U-IFE/s – 2 - 30°CIFE – 18 - 26°C
	Analytic Range	U-IFE/s – 2.5 - 5.0 mg/dL to 300 mg/dL Lambda & 5.0- 10.0 mg/dL to 300 mg/dL KappaIFE - Total Protein >100 mg/dL for detection of Bence-Jones Proteins. Total Protein >800-1000 mg/dL fordetection of immunoglobulins.

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Summary of Performance Data: 8.0

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to chemistry test systems already in commercial distribution. Equivalence is demonstrated through method comparison, stability, linearity/sensitivity, and precision/ reproducibility experiments.

Instrument	Agreement	PartialAgreement	Disagreement	n	ComparisonMethod
PARAGONCZE 2000– UPE Kit	95	4	1	100	PARAGON GelElectrophoresis –SPE Kit

Method Comparison Study Results

Instrument	Full Agreement	Disagreement	n	Comparison Method
PARAGONCZE 2000– U-IFE/sKit	76(92.7%)	6(7.3%)	82	PARAGON GelElectrophoresis – IFEKit

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Type ofImprecision	Sample	Fraction	Mean(Relative %)	S.D.(Relative %)	%C.V.	N
Within-Run Imprecision
SystemReproducibility	UrinePool	Albumin	55.1	1.38	2.5	21
		BJP	13.2	0.93	7.1	21
DesaltingReproducibility	UrinePool	Albumin	54.8	1.65	3.0	21
		BJP	13.5	0.71	5.3	21
Total Imprecision
Total(EP 10-A)	UrineLevel 1	Albumin	28.8	0.7	2.5	15
		BJP	13.4	0.8	5.9	15
	UrineLevel 2	Albumin	60.8	1.3	2.2	15
		BJP	6.5	0.8	12.7	15
	UrineLevel 3	Albumin	9.2	0.8	9.2	15
		BJP	72.1	1.5	2.0	15

UPE Imprecision Results

U-IFE/s Reproducibility Results

The electropherograms were visually inspected to ensure that at least 80% were within agreement. No observable difference in morphology or subtraction was seen between the segments for each of the samples BJP subtraction with kappa and lambda was as expected. tested. Reproducibility meets the 80% specification for visual agreement for the replicate segments.

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

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Image /page/7/Figure/0 description: The image is a flowchart outlining the process for determining substantial equivalence under Section 510(k) of the FDA regulations. The flowchart starts with the question of whether the new device is compared to a marketed device. The flowchart then proceeds through a series of questions about the device's indications, intended use, technological characteristics, and the availability of performance data. The flowchart ends with a determination of whether the device is substantially equivalent or not.

CZE_UPE & UIFES 510K_Section1, January 2005

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/8/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features a stylized eagle with three lines forming its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.

MAY - 6 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Kim Walker, RAC Regulatory Affairs Manager Beckman Coulter, Inc. 200 S. Kraemer Boulevard M/S W-515 Brea, California 92822-8000

Re: K050119

Trade/Device Name: PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit and Urine Immunofixation by Subtraction (U-IFE/s) Kit Regulation Number: 21 CFR § 866.5150 Regulation Name: Bence-Jones proteins immunological test Regulatory Class: II Product Code: JKM, CFF, DFH, DEH Dated: March 30, 2005 Received: March 31, 2005

Dear Ms Walker:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

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Page 2 –

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

Robert Beckerh

Robert L. Becker, Jr., MD, PK.D Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

Koro 119

510(k) Number (if known):

Device Name:

PARAGON CZE® 2000 Urine Protein Electrophoresis (UPE) Kit and Urine Immunofixation By Subtraction (U-IFE/s) Kit

Indications for Use:

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Sunshine Burutta

Division Sign

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K050119

Beckman Coulter, Inc., Section 510(k) Notification PARAGON CZE® 2000 UPE & U-IFE/s Kits CZE_UPE & UIFEs 510K_Section1 Final.doc, January 2005 Page 1 of ____________________________________________________________________________________________________________________________________________________________________

Regulation Number and Section

§ 866.5150 Bence-Jones proteins immunological test system.

(a)
Identification. A Bence-Jones proteins immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the Bence-Jones proteins in urine and plasma. Immunoglobulin molecules normally consist of pairs of polypeptide chains (subunits) of unequal size (light chains and heavy chains) bound together by several disulfide bridges. In some cancerous conditions, there is a proliferation of one plasma cell (antibody-producing cell) with excess production of light chains of one specific kind (monoclonal light chains). These free homogeneous light chains not associated with an immunoglobulin molecule can be found in urine and plasma, and have been called Bence-Jones proteins. Measurement of Bence-Jones proteins and determination that they are monoclonal aid in the diagnosis of multiple myeloma (malignant proliferation of plasma cells), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins by spleen and bone marrow cells), leukemia (cancer of the blood-forming organs), and lymphoma (cancer of the lymphoid tissue).(b)
Classification. Class II (performance standards).