The BioPlex™ 2200 Anti-CCP Kit is a multiplex flow immunoassay intended for the semi-quantitative detection of IgG antibodies to Cyclic Citrullinated Peptide (CCP) in human serum and EDTA or heparinized plasma. Detection of CCP antibodies may be used as an aid in the diagnosis of rheumatoid arthritis and should be used in conjunction with other clinical information.

The BioPlex 2200 Anti-CCP kit is intended for use with the Bio-Rad BioPlex 2200 system.

The BioPlex™ 2200 Anti-CCP Calibrator Set is intended for the calibration of the BioPlex 2200 Anti-CCP Reagent Pack.

The BioPlex™ 2200 Anti-CCP Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 instrument and BioPlex 2200 Anti-CCP Reagent Pack in the clinical laboratory. The performance of the BioPlex 2200 Anti-CCP Control Set has not been established with any other Anti-CCP assay.

Device Description

The BioPlex™ 2200 Anti-CCP IgG kit uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. "CCP IgG" is an acronym for the detection of IgG antibodies to Cyclic Citrullinated Peptide.

One (1) population of fluorescent beads is coated with antigens associated with cyclic citrullinated peptide (CCP). Three populations of fluorescent beads function as assay controls (see below). The BioPlex™ 2200 System combines an aliquot of patient sample, sample diluent, and bead reagent into a reaction vessel and incubates the mixture at 37°C. After a wash cycle to remove unbound antibody, anti-human IgG conjugated to phycoerythrin is added and the mixture is incubated at 37°C. Excess conjugate is removed in another wash cycle and the washed beads are re-suspended in wash buffer. The bead mixture then passes through the detector. The identity of the assay and control beads is determined by the fluorescence embedded in the surface of the bead and the amount of immobilized antibody is determined by the fluorescence of the anti-IgG reporter conjugate. Raw data are calculated in relative fluorescence intensity (RFI).

Three additional dyed beads, Internal Standard Bead (ISB), Serum Verification Bead (SVB) and Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum or plasma to the reaction and the absence of significant non-specific binding. Refer to the BioPlex™ 2200 System Operation Manual for more information.

The instrument is calibrated using a set of six distinct calibrator vials, supplied separately by Bio-Rad Laboratories. The six vials representing six different analyte concentrations are used for calibration. The cut-off value and assignment of the calibrators are determined by performing concordance and Receiver Operator Characteristic (ROC) analysis using Axis-Shield DIAStat Anti-CCP predicate results as the reference. The result for anti-CCP is expressed as arbitrary units (U/mL). Results of <3 U/mL are negative and results of > 3 U/mL as positive.

The BioPlex 2200 Anti-CCP Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 Instrument and BioPlex 2200 Anti-CCP Reagent Pack in the clinical laboratory. The Control Set includes a negative and a positive control. The BioPlex Anti-CCP Positive Control is manufactured to give positive results, with values above the cut-off for the analyte. The BioPlex Anti-CCP Negative Control is manufactured to give negative results, with values below the cut-off for the analyte. The recommended frequency for performing quality control is once every 24-hour testing period. Performing quality control is also necessary after each new assay calibration and certain service procedures.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the BioPlex™ 2200 Anti-CCP Kit, based on the provided 510(k) summary report:

Acceptance Criteria and Device Performance

Acceptance Criteria Category	Acceptance Criteria (Specifics from text)	Reported Device Performance
Precision/Reproducibility	Based on CLSI EP5-A2 and EP15-A2 guidelines.	CLSI EP5-A2 Reproducibility Study: Total precision (%CV) for serum samples ranged from 6.5% to 8.2%. For EDTA plasma samples, it ranged from 3.8% to 9.2%. For Heparin plasma samples, it ranged from 3.7% to 8.2%. CLSI EP15-A2 Reproducibility Study: Within-run precision (%CV) for positive samples near the cut-off (3 U/mL) in all sample matrices ranged from 3.5% to 5.3%. Total precision (%CV) for positive samples near the cut-off (3 U/mL) ranged from 4.0% to 5.3%. Specific %CV values for various samples and matrices are provided in the tables above, all falling within acceptable ranges.
Linearity/Reportable Range	Linear regression analysis of anti-CCP IgG recovery U/mL vs. sample dilution to determine if dilution curves exhibit statistically significant non-linear regression based on CLSI guideline EP06-A. For onboard dilution features, recovery must be within ±20% of manual dilution, and precision (U/mL CV) must be ≤ 10%.	The assay demonstrated linearity from 0 to 300 U/mL, with R-squared values for samples A, B, and C near 1.0 (0.9985, 0.9990, 0.9978 respectively). For onboard dilutions (1:4, 1:10, 1:100), recovery ranged from 87% to 104%, and onboard CVs ranged from 2.8% to 4.7%, meeting the specified criteria.
Limit of Detection (LoD)	Determined according to CLSI EP17-A.	The calculated LoD for the anti-CCP IgG assay is 0.2 U/mL.
Interfering Substances	No interference observed with specified endogenous and exogenous substances at maximum tested levels (based on CLSI EP7-A2).	No interference was observed with any of the substances tested (Hemoglobin, Bilirubin, Cholesterol, Red Blood Cells, Gamma Globulin, Triglycerides, Protein, Rheumatoid Factor, Ascorbic Acid, Lithium Heparin, Sodium Heparin, EDTA) at their maximum tested concentrations.
Cross-Reactivity	Evaluation with samples from various disease states and other potentially interfering factors.	Possible cross-reactivity observed with ANA samples (11%, including Centromere B at 23% and SS-A at 12%) and Myeloma IgG samples (30%). TPO IgG, VCA IgG, CMV IgG, and Lyme IgG showed 0% cross-reactivity. T. gondii IgG showed 10% cross-reactivity.
Assay Cut-off	Based on concordance and ROC analysis using predicate results as the standard, aiming for specified positive and negative agreement.	A cutoff of 3.0 U/mL was obtained, achieving a positive agreement of 92.9% and a negative agreement of 98.2% with the predicate Axis-Shield DIASTAT anti-CCP assay among 1394 patient samples.
Method Comparison	Performance evaluated against predicate device, Axis-Shield DIASTAT Anti-CCP immunoassay.	Positive Agreement: 97.5% (95% CI: 95.4 - 98.7%) (358/367). Negative Agreement: 91.4% (95% CI: 88.5 - 93.7%) (416/455).
Matrix Comparison	Plasma U/mL values compared to matched serum U/mL values (CLSI EP9-A2). The scatter plots and regression analysis (slope, intercept, correlation coefficient) should demonstrate strong correlation between matrices.	EDTA vs. Serum: Slope = 0.9636 (95% CI: 0.8753, 1.0519), Intercept = 2.5368 (95% CI: -2.5799, 7.6536), Correlation (r) = 0.9824 (95% CI: 0.9670, 0.9906). Heparin vs. Serum: Slope = 0.9642 (95% CI: 0.8995, 1.0289), Intercept = 2.5264 (95% CI: -1.4891, 6.5419), Correlation (r) = 0.9852 (95% CI: 0.9723, 0.9921). These results indicate a strong correlation, demonstrating acceptable matrix equivalency.
Clinical Sensitivity and Specificity	Evaluate on a cohort of healthy blood donors, diagnosed RA patients, and other rheumatic disease patients.	Clinical Sensitivity (for diagnosed RA): 83.1% (412/496) (95% CI: 79.5 – 86.1%). Clinical Specificity (for healthy blood donors and other rheumatic diseases): 97.8% (490/501) (95% CI: 96.1 – 98.8%).

Study Details

Sample Sizes and Data Provenance (Test Set):
- Precision/Reproducibility:
  - CLSI EP5-A2: 3 panels (serum, EDTA plasma, heparinized plasma), each with 10 samples plus 2 controls. Each panel member was assayed 80 times (2 times in 2 separate daily runs over 20 days).
  - CLSI EP15-A2: 3 panels (serum, EDTA plasma, heparinized plasma), each with 10 samples plus 2 controls. Each panel member was tested in quadruplicate over 5 days (20 replicates).
- Linearity: 3 high anti-CCP IgG positive patient samples (ranging 241-270 U/mL) and their dilutions, assayed in replicates of four. For onboard dilution, 3 high positive samples for each dilution (1:4, 1:10, 1:100), assayed in replicates of ten.
- Limit of Detection: Low positive, high negative, and blank samples in replicates of fifty (50).
- Interfering Substances: Specific substances at various concentrations (e.g., Hemoglobin ≤ 500 mg/dL). Number of samples not explicitly stated for this specific test, but design follows CLSI EP7-A2.
- Cross-Reactivity: 163 ANA samples and 72 other samples containing potential cross-reactants.
- Assay Cut-off Determination: 1394 patient samples (177 normal, 504 RF-tested/positive, 82 older, 287 RA, 344 non-RA).
- Method Comparison: 997 specimens (300 healthy blood donors, 496 diagnosed RA patients, 201 other rheumatic disease patients). 822 samples within the detection range were evaluated.
- Matrix Comparison: 41 matched sets of serum and plasma (EDTA and heparin) from the same donor, spiked with high positive anti-CCP IgG serum, evaluated in replicates of two.
- Clinical Sensitivity and Specificity: Same 997 specimens as Method Comparison.
- Expected Values/Reference Range: 300 apparently healthy donors.
- Prevalence: 300 apparently healthy blood donors and 300 clinical samples submitted for RF/anti-CCP testing.
Data Provenance:
- The 997 specimens for Method Comparison and Clinical Sensitivity/Specificity were purchased from commercial suppliers and were frozen serum.
- Adjudication for RA diagnosis in these patients was by physician's diagnosis or ICD-9 code 714.0.
- The CLSI EP15-A2 Reproducibility Study was performed at "one clinical trial site."
- The report does not specify the country of origin for the data; it implies a single clinical site for some studies. The phrase "purchased from commercial suppliers" for patient specimens suggests retrospective data.
Number of Experts and Qualifications (Ground Truth for Test Set):
- The report does not explicitly state the number of experts or their specific qualifications for establishing the ground truth beyond:
  - For RA patients: "Patients previously diagnosed with RA were selected by either physicians' diagnosis or an ICD-9 code 714.0." This implies a physician's diagnosis as the primary ground truth for RA status.
  - For the assay cut-off, the BioPlex 2200 results were compared against the Axis-Shield DIASTAT anti-CCP predicate assay as the reference for confirming positive or negative status.
- This is not a traditional "expert consensus" in the sense of multiple radiologists reviewing images, but rather relies on a predicate device and existing clinical diagnoses.
Adjudication Method (Test Set):
- For RA diagnosis (ground truth): "Physicians' diagnosis or an ICD-9 code 714.0" serves as the primary adjudication for RA status for the clinical samples.
- For assay cut-off determination: "All samples were confirmed positive or negative by the Axis-Shield DIASTAT anti-CCP predicate assay." This indicates the predicate device acted as the gold standard for concordance.
- No "2+1" or "3+1" expert adjudication method is mentioned.
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described. This report focuses on the standalone performance of the in vitro diagnostic device (IVD) compared to a predicate IVD, rather than comparing human readers with and without AI assistance. The device is an automated assay, not an AI-based image analysis tool for human readers.
Standalone Performance:
- Yes, the entire study focuses on the standalone performance of the BioPlex™ 2200 Anti-CCP Kit relative to its intended use and a predicate device. The performance characteristics (precision, linearity, LoD, specificity, method comparison, clinical sensitivity/specificity) are all measures of the algorithm/device itself, without human interpretation as part of the primary diagnostic step.
Type of Ground Truth Used:
- Predicate Device Results: For assay cut-off determination and method comparison, the Axis-Shield DIASTAT Anti-CCP predicate immunoassay was used as the reference/ground truth.
- Clinical Diagnosis: For clinical sensitivity and specificity, the ground truth for "diagnosed RA patients" relied on physicians' diagnosis or ICD-9 code 714.0.
- Apparent Health Status: For healthy donor groups, "apparently healthy blood donors" formed the negative ground truth.
Sample Size for Training Set:
- The report does not explicitly mention a "training set" in the context of machine learning. This is a traditional IVD device, not an AI/ML-based diagnostic.
- The calibrators are fundamental to the assay's function and can be considered analogous to a training component. The BioPlex 2200 Anti-CCP Calibrator Set consists of six distinct calibrator vials. The cut-off value and assignment of the calibrators are determined by performing concordance and Receiver Operator Characteristic (ROC) analysis using Axis-Shield DIAStat Anti-CCP predicate results as the reference (as stated in section 2).
How Ground Truth for Training Set Was Established:
- As this is not an AI/ML device with a distinct "training set" in that sense, the concept of ground truth for a training set does not directly apply.
- For the calibrators, which define the assay's measurement scale and interpretation: "The BioPlex 2200 Anti-CCP Calibrators are assigned relative units from predicate Axis-Shield DIASTAT Anti-CCP Calibrators." BioPlex 2200 Anti-CCP Calibrators are prepared by blending defibrinated and delipidated human plasma units with known anti-CCP IgG activity in a processed human serum matrix. This means the ground truth for calibrator assignment is derived from measurements established by the predicate device and characterized human disease state plasma.

Summary

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510(k) Summary Report BioPlex™ 2200 Anti-CCP Bio-Rad Laboratories, Inc.

K093954/

AUG 2 4 2010

Bio-Rad Laboratories, Inc. BioPlex Division 5500 East Second Street Benicia, CA 94510 Contact Person: Telephone: Date Prepared:

Applicant/Sponsor

Juang Wang 510-741-4609 August 19, 2010

Device Name 2.
Proprietary Name: BioPlex™ 2200 Anti-CCP Kit BioPlex™ 2200 Anti-CCP Calibrator Set BioPlex™ 2200 Anti-CCP Control Set

Multi-Analyte Detection System: Anti-CCP IgG Common/Usual Name:

Classification Name:	Antibodies, Anti-Cyclic Citrullinated Peptide (CCP)
	Calibrator, multi-analyte mixture
	Single-analyte controls, all kinds (assayed and unassayed)

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3. Regulatory Information

Product Code	Classification	Regulation Section	Panel
Antibodies, Anti-CyclicCitrullinated Peptide(CCP)(NHX)	Class II	21 CFR § 866.5775,Rheumatoid factorimmunological test system	Immunology
Calibrator, multi-analytemixture (JIX)	Class II	21 CFR § 862.1150 -Calibrator	Clinical Chemistry
single (specified)analyte controls(assayed andunassayed) (JJX)	Class I	21 CFR § 862.1660 –Quality control Material(Assayed and Unassayed)	Clinical Chemistry

Predicate Devices 4.

DIASTAT™ Anti-CCP K023285

Device Description ട.

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary August 19, 2010 Page 2 of 22

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BioPlex™ 2200 Anti-CCP Kit Components 6.

Vial	Description
Bead Set	One (1) 10 mL vial, containing dyed beads coated withCyclic Citrullinated Peptide, plus Internal Standard beads(ISB), Serum Verification beads (SVB), and ReagentBlank beads (RBB) in buffer with glycerol and proteinstabilizers (bovine). ProClin 300 (0.3%), sodium benzoate(0.1%) and sodium azide (<0.1%) as preservatives.
Conjugate	One (1) 5 mL vial, containing phycoerythrin conjugatedmurine monoclonal anti-human IgG antibody andphycoerythrin conjugated murine monoclonal anti-humanFXIII antibody, in buffer with protein stabilizers (bovine).ProClin 300 (0.3%), sodium benzoate (0.1%) and sodiumazide (< 0.1%) as preservatives
Sample Diluent	One (1) 10 mL vial, containing buffer with proteinstabilizers (bovine and murine). ProClin 300 (0.3%),sodium benzoate (0.1%) and sodium azide (< 0.1%) aspreservatives.

The BioPlex 2200 Anti-CCP kit (665-3250) contains supplies sufficient for 100 tests.

Additional Required Items, Available from Bio-Rad:

Catalog #	Description
663-3200	BioPlex 2200 Anti-CCP Calibrator Set: Six 0.5 mL vials,each containing human antibodies to Cyclic CitrullinatedPeptide, in a human serum matrix made from defibrinatedplasma, with protein stabilizers (bovine). All antibodies arederived from human disease state plasma. All calibratorscontain ProClin 300 (≤ 0.3%), sodium benzoate (0.1%)and sodium azide (< 0.1%) as preservatives

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary August 19, 2010 Page 3 of 22

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Catalog #	Description
663-3230	BioPlex 2200 Anti-CCP Control Set: Two 1.5 mL PositiveControl serum vials containing human antibodiesto Cyclic Citrullinated Peptide, in a human serum matrixmade from defibrinated plasma. Two 1.5 mL NegativeControl serum vials, in a human serum matrix made fromdefibrinated plasma. All antibodies are derived fromhuman disease state plasma. All controls contain ProClin300 (≤ 0.3%), sodium benzoate (0.1%) and sodium azide(< 0.1%) as preservatives.
660-0817	BioPlex 2200 Sheath Fluid: Two 4 L bottles containingPhosphate Buffered Saline (PBS). ProClin® 300 (0.03%)and sodium azide (<0.1%) as preservatives.
660-0818	BioPlex 2200 Wash Solution: One 10 L bottle containingPhosphate Buffered Saline (PBS) and Tween 20.ProClin® 300 (0.03%) and sodium azide (<0.1%) aspreservatives.
660-0000	BioPlex 2200 Instrument and Software System.

7 Intended Use

BioPlex™ 2200 Anti-CCP Kit

1. The BioPlex™ 2200 Anti-CCP kit is a multiplex flow immunoassay intended for the semi-quantitative detection of IgG antibodies to Cyclic Citrullinated Peptide (CCP) in human serum or plasma (EDTA or sodium heparin). Detection of CCP antibodies is used as an aid in the diagnosis of rheumatoid arthritis and should be used in conjunction with other clinical findings and laboratory results.
  The BioPlex 2200 Anti-CCP kit is intended for use with the Bio-Rad BioPlex 2200 System.

BioPlex™ 2200 Anti-CCP Calibrator Set

The BioPlex 2200 Anti-CCP Calibrator Set is intended for calibration of the BioPlex 2200 Anti-CCP Reagent Pack.

BioPlex™ 2200 Anti-CCP Control Set

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The BioPlex 2200 Anti-CCP Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 Instrument and BioPlex Anti-CCP Reagent Pack in the clinical laboratory. The performance of the BioPlex 2200 Anti-CCP Control Set has not been established with any other immunoassays.

Technological Characteristics and Substantial Equivalence 8.

The following tables summarize the similarities and differences between the BioPlex 2200 Anti-CCP kit and the predicate devices used in comparative studies with the BioPlex 2200 Anti-CCP kit.

SimilaritiesbetweenComponents /Materials	BioPlex™ 2200Anti-CCP Kit	Axis-Shield DIASTAT™Anti-CCP (K023285)
Intended Use	The BioPlex™ 2200 Anti-CCP kit is a multiplex flowimmunoassay intended forthe semi-quantitativedetection of IgG antibodiesto Cyclic CitrullinatedPeptide (CCP) in humanserum and EDTA orheparinized plasma.Detection of CCPantibodies may be used asan aid in the diagnosis ofrheumatoid arthritis andshould be used inconjunction with otherclinical information.The BioPlex 2200 Anti-CCPkit is intended for use withthe Bio-Rad BioPlex 2200System.	The DIASTAT™ Anti-CCPtest is a semi-quantitative/qualitativeenzyme-linkedimmunosorbent assay(ELISA) for the detectionof the IgG class ofautoantibodies specific tocyclic citrullinated peptide(CCP) in human serum orplasma (EDTA, Lithiumheparin or sodium citrate).It is intended to aid in thediagnosis of RheumatoidArthritis (RA) and is notdefinitive in isolation.Autoantibody levelsrepresent one parameterin a multicriteriondiagnostic process,encompassing bothclinical and laboratory-based assessments.
Capture Antigen	Cyclic citrullinated peptide(CCP), second generation	Same
Assay Type	Semi-Quantitativedetection	Same

BioPlex™ 2200 Anti-CCP Kit vs. Predicate Devices - Similarities

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary

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SimilaritiesbetweenComponents /Materials	BioPlex™ 2200Anti-CCP Kit	Axis-Shield DIASTAT™Anti-CCP (K023285)
Analyte Detected	Human IgG antibodiesto Cyclic CitrullinatedPeptide	Same
Specimen Type	Serum and plasma	Same
Controls	Negative and PositiveControls	Same
Calibrator(s)	Multiple Calibrators	Same
Quantitation	Results are determinedfrom a standard calibrationcurve utilizing a four-parameter logistic (4-PL)curve fit algorithm.	Same

BioPlex 2200 Anti-CCP Kit vs. Predicate Device - Differences

DifferencesbetweenComponents /Materials	BioPlex™ 2200Anti-CCP Kit	Axis-Shield DIASTAT™Anti-CCP (K023285)
AssayTechnology	Automated Multiplexflow immunoassay	Manual, microtitre plateformat, Enzyme-linkedImmunosorbent assay(ELISA)
ConjugateAntibody	Phycoerythrinconjugated murinemonoclonal anti-human IgG	Alkaline phosphataselabeled murine monoclonalantibody to human IgG
Substrate	None	Mg+2, phenolphthaleinmonophosphate (PMP)
Specimen Type	Serum and plasma(EDTA and heparin)	Serum and plasma (EDTA,lithium heparin, and sodiumcitrate)
Signal Detection	Fluorescence	Color, read at 550nm

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DifferencesbetweenComponents /Materials	BioPlex™ 2200Anti-CCP Kit	Axis-Shield DIASTAT™Anti-CCP (K023285)
Solid Phase	Antigen-coatedparamagneticmicrobead reagent.Microbeads areinfused with red andinfrared fluorescentdyes for beadclassification. Greenfluorescence from theimmunoassay label isused for analytemeasurement.	Antigen-coated solid phasemicrotitre wells
Calibrator(s)	6 levels of Calibrator	5 levels of Calibrator
Calibrator Range	0 - 300 U/mL	0 - 100 U/mL
Assay Type	Semi-Quantitativeassay	Semi-quantitative/qualitativeassay
Calibrators andControls	Sold separately	Kit components

. ഗ Performance Characteristics

A series of studies was conducted to evaluate the performance of the BioPlex™ 2200 Anti-CCP kit. The studies included reproducibility, linearity, limits of detection, interfering substances, cross-reactivity, assay cut-off, expected values and method comparison. The results of all studies demonstrated that the BioPlex 2200 Anti-CCP kit performed according to its specifications.

A. Analytical Performance

Precision/Reproducibility i.

Separate CLSI EP5-A2 and EP15-A2 reproducibility studies were conducted to evaluate the reproducibility of the BioPlex 2200 Anti-CCP kit on the BioPlex 2200 instrument. Reproducibility studies were based on the principles described in Clinical and Laboratory Standards Institute (CLSI) EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods and EP15-A2, User Verification of Performance for Precision and Trueness.

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Anti-CCP Serum Panel		Within Run		Between Run		Between Day		Total
Sample	N	Mean(U/mL)	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Negative 1	80	2.1	0.16	7.4	0.00	0.0	0.07	3.6	0.17	8.2
Negative 2	80	2.0	0.15	7.5	0.00	0.0	0.04	1.9	0.16	7.8
Near Cut-Off 1	80	2.8	0.14	5.2	0.07	2.5	0.13	4.7	0.21	7.5
Near Cut-Off 2	80	2.8	0.18	6.4	0.00	0.0	0.09	3.3	0.20	7.2
Low Positive 1	80	3.0	0.22	7.2	0.00	0.0	0.09	3.1	0.23	7.8
Low Positive 2	80	3.3	0.17	5.2	0.11	3.2	0.10	3.1	0.23	6.9
Positive 1	80	26.1	1.41	5.4	0.00	0.0	1.17	4.5	1.83	7.0
Positive 2	80	21.0	1.03	4.9	0.86	4.1	0.75	3.6	1.54	7.3
High Positive 1	80	128.5	8.08	6.3	0.00	0.0	2.12	1.6	8.35	6.5
High Positive 2	80	140.7	8.44	6.0	4.45	3.2	0.00	0.0	9.54	6.8
Pos. Control	80	15.0	1.04	7.0	0.00	0.0	0.51	3.4	1.16	7.8
Neg. Control	80	0.1	0.00	0.0	0.00	0.0	0.00	0.0	0.00	0.0
Anti-CCP EDTA Panel		Within Run		Between Run		Between Day		Total
Sample	N	Mean(U/mL)	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Negative 1	80	2.1	0.14	6.9	0.07	3.4	0.11	5.1	0.19	9.2
Negative 2	80	2.2	0.16	7.3	0.06	2.8	0.00	0.0	0.17	7.8
Near Cut-Off 1	80	3.0	0.21	7.1	0.08	2.7	0.07	2.2	0.24	7.9
Near Cut-Off 2	80	2.7	0.15	5.4	0.08	3.1	0.10	3.8	0.20	7.3
Low Positive 1	80	3.1	0.20	6.3	0.00	0.0	0.11	3.6	0.22	7.2
Low Positive 2	80	3.0	0.20	6.5	0.09	3.1	0.03	1.0	0.22	7.3
Positive 1	80	22.1	1.02	4.6	0.60	2.7	0.30	1.4	1.22	5.5
Positive 2	80	32.0	1.56	4.9	0.96	3.0	0.41	1.3	1.87	5.9
High Positive 1	80	133.5	10.35	7.8	0.00	0.0	3.30	2.5	10.86	8.1
High Positive 2	80	147.6	7.75	5.2	2.89	2.0	5.00	3.4	9.67	6.5
Anti-CCP Heparin Panel		Within Run		Between Run		Between Day		Total
Sample	N	Mean(U/mL)	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Negative 1	80	2.2	0.14	6.5	0.06	2.6	0.07	3.3	0.17	7.7
Negative 2	80	2.3	0.15	6.6	0.07	3.0	0.04	1.5	0.17	7.4
Near Cut-Off 1	80	2.7	0.16	5.9	0.05	1.8	0.05	1.7	0.17	6.4
Near Cut-Off 2	80	2.9	0.19	6.7	0.10	3.4	0.10	3.4	0.24	8.2
Low Positive 1	80	3.5	0.21	6.0	0.04	1.0	0.12	3.3	0.24	6.9
Low Positive 2	80	3.7	0.24	6.5	0.08	2.1	0.00	0.0	0.25	6.8
Positive 1	80	21.0	1.18	5.6	0.37	1.8	0.38	1.8	1.29	6.2
Positive 2	80	23.7	1.55	6.5	0.41	1.7	0.37	1.6	1.65	6.9
High Positive 1	80	126.2	6.28	5.0	0.00	0.0	3.26	2.6	7.08	5.6
High Positive 2	80	132.5	6.57	5.0	4.27	3.2	0.00	0.0	7.84	5.9

CLSI EP5-A2 Reproducibility Study

Three (3) panels made from serum and plasma (EDTA and heparinized). Each panel composed of 10 samples covering the measuring range of the device was assayed two times in two separate daily runs over 20 days (n=80) plus one negative and one positive control according to CLSI EP5-A2 guideline.

The data were analyzed for within-run, between-run, between-day, and total precision and the standard deviation (SD) and percent coefficient of variation (% CV) were calculated. Precision results from EP5-A2 reproducibility study are summarized below for all samples covering the measuring range.

August 19, 2010 Page 8 of 22

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CLSI EP15-A2 Reproducibility Study

The study was performed at one clinical trial site. One lot each of BioPlex 200 Anti-CCP reagent pack, Calibrator Set and Control Set was evaluated. Three panels were made from serum and plasma (EDTA and heparinized) plus two controls (one negative and one positive). Each panel of 10 samples covering the assay measuring range was tested in quadruplicate over five days (4 replicates x 1 run x 5 days x 1 testing site = 20 replicates per panel member) according to CLSI EP15-A2 guideline.

The data were analyzed for within-run, between-day, and total precision and the standard deviation (SD) and percent coefficient of variation (% CV) were calculated.

The within-run precision (%CV) for positive samples near the cut-off (3 U/mL) in all sample matrices ranged from 3.5% to 5.3%. The total precision (%CV) for positive samples near the cut-off (3 U/mL) ranged from 4.0% to 5.3%. Precision results from EP15-A2 Reproducibility study are listed below.

Anti-CCP Serum Panel			Within-Run		Between-Day		Total
		Mean
Sample	N	(U/mL)	SD	%CV	SD	%CV	SD	%CV
Negative 1	20	1.7	0.09	4.9	0.07	3.9	0.11	6.2
Negative 2	20	1.7	0.09	5.5	0.04	2.3	0.10	5.9
Near Cutoff 1	20	2.7	0.12	4.3	0.00	0.0	0.12	4.3
Near Cutoff 2	20	3.1	0.12	3.8	0.11	3.4	0.16	5.1
Low positive 1	20	23.2	1.16	5.0	1.22	5.3	1.68	7.2
Low positive 2	20	19.3	1.13	5.8	0.69	3.6	1.32	6.8
High Positive 1	20	113.4	6.85	6.0	0.45	0.4	6.87	6.1
High Positive 2	20	128.3	5.97	4.7	1.86	1.4	6.25	4.9
Very High Positive 1	20	251.0	9.55	3.8	8.19	3.3	12.58	5.0
Very High Positive 2	20	238.4	16.23	6.8	0.00	0.0	16.23	6.8
Control-1	20	0.02	0.04	244.2	0.00	0.0	0.04	244.2
Control -2	20	13.4	0.67	5.0	0.31	2.3	0.74	5.5
Anti-CCP EDTA Panel			Within-Run		Between-Day		Total
		Mean
Sample	N	(U/mL)	SD	%CV	SD	%CV	SD	%CV
Negative 1	20	2.1	0.13	6.1	0.06	2.6	0.14	6.6
Negative 2	20	1.8	0.08	4.6	0.08	4.5	0.12	6.4
Near Cutoff 1	20	3.0	0.14	4.6	0.06	2.1	0.15	5.1
Near Cutoff 2	20	3.1	0.13	4.2	0.00	0.0	0.13	4.2
Low positive 1	20	20.2	0.68	3.4	0.42	2.1	0.80	4.0
Low positive 2	20	29.3	1.05	3.6	0.86	2.9	1.36	4.6
High Positive 1	20	124.6	4.68	3.8	0.00	0.0	4.68	3.8
High Positive 2	20	136.3	6.46	4.7	0.00	0.0	6.46	4.7
Very High Positive 1	20	224.2	8.40	3.7	9.61	4.3	12.76	5.7
Very High Positive 2	20	236.6	17.25	7.3	0.00	0.0	17.25	7.3

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary August 19, 2010 Page 9 of 22

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Anti-CCP Heparin Panel			Within-Run		Between-Day		Total
		Mean
Sample	N	(U/mL)	SD	%CV	SD	%CV	SD	%CV
Negative 1	20	1.7	0.08	4.7	0.00	0.0	0.08	4.7
Negative 2	20	1.8	0.12	6.5	0.00	0.0	0.12	6.5
Near Cutoff 1	20	2.9	0.10	3.5	0.06	1.9	0.12	4.0
Near Cutoff 2	20	3.0	0.16	5.3	0.00	0.0	0.16	5.3
Low positive 1	20	18.7	0.64	3.4	0.36	1.9	0.73	3.9
Low positive 2	20	20.8	1.46	7.0	1.24	6.0	1.92	9.2
High Positive 1	20	113.3	4.45	3.9	3.69	3.3	5.78	5.1
High Positive 2	20	119.5	4.16	3.5	1.42	1.2	4.40	3.7
Very High Positive 1	20	223.3	13.12	5.9	3.39	1.5	13.55	6.1
Very High Positive 2	20	227.7	11.38	5.0	5.38	2.4	12.59	5.5

ii. Linearity/Assay Reportable Ranges

Three (3) high anti-CCP IgG positive patient samples ranging from 241 to 270 U/mL were tested to demonstrate linearity. These samples were diluted with immunodepleted serum according to CLSI EP06-A, Evaluation of the Linearity of Quantitative Measruement Procedures: A Statistical Approach.

Each sample and dilution was evaluated in replicates of four using one anti-CCP IgG lot on one instrument. Linear and polynomial regression analysis of anti-CCP IqG recovery U/mL vs. sample dilution was performed to determine if the dilution curves exhibit statistically significant non-linear regression based on the CLSI guideline EP06-A. The regression parameters (slope, intercept and r') of the observed values vs. predicted values are show below. The dilution linearity graphs are also presented below. The BioPlex 2200 Anti-CCP IgG assay demonstrated linearity from 0 to 300 U/mL.

Sample (U/mL)	Slope	Intercept	r2
Sample A (270.2)	1.0000	-0.0011	0.9985
Sample B (263.1)	0.9999	0.0106	0.9990
Sample C (240.9)	1.0002	-0.0166	0.9978

Image /page/9/Figure/5 description: The image shows a scatter plot titled "Dilution Linearity: Positive Anti-CCP Patient Sample A". The x-axis is labeled "Predicted Result, U/mL", and the y-axis is labeled "Observed Result, U/mL". A linear regression line is plotted on the scatter plot, and the equation of the line is y = 1.0000x - 0.0011, with an R-squared value of 0.9985.

Bio-Rad Laboratories, ----BioPlex™ 2200 Anti-CCP 510(k) Summary August 19, 2010 Page 10 of 22

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Image /page/10/Figure/0 description: The image shows two scatter plots, each displaying dilution linearity for a positive Anti-CCP patient sample. The top plot, labeled "Patient Sample B," shows a linear relationship with the equation y = 0.9999x + 0.0106 and an R-squared value of 0.9990. The bottom plot, labeled "Patient Sample C," also shows a linear relationship, but with the equation y = 1.0002x - 0.0166 and an R-squared value of 0.9978.

The BioPlex 2200 system also offers an on-board dilution features for testing over-range samples. The dilution prior to analysis was evaluated for 1:4, 1:10 and 1:100. Three different high positive anti-CCP samples for each dilution feature were also diluted manually to compare to onboard dilution by the

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary August 19, 2010 · Page 11 of 22

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BioPlex 2200. All samples were assayed in replicates of ten. Results for samples diluted onboard the BioPlex 2200 were displayed as the sample result multiplied by the dilution factor. Recovery of samples diluted onboard must be within ±20% of that of the same sample diluted manually and precision (U/mL CV) must be ≤ 10%.

The results below indicated that the onboard sample dilution feature of the BioPlex 2200 system can be used to dilute over-range samples 1:4, 1:10 or 1:100 for the anti-CCP assay. Onboard values shown are the reported values divided by the dilution factor. The percent recovery is the percent ratio of the adjusted onboard dilution U/mL value to the manual dilution U/mL value.

Dilution	Sample	Manual U/mL	Onboard U/mL	Recovery	Manual CV	Onboard CV
1:100	1	16	17	104%	3.7%	4.3%
	2	15	15	103%	2.9%	3.6%
	3	11	11	100%	3.4%	3.7%
1:10	4	32	28	88%	4.0%	3.7%
	5	27	24	90%	2.5%	2.9%
	6	24	22	91%	1.6%	3.1%
1:4	7	98	92	93%	3.8%	4.7%
	8	84	73	87%	2.7%	3.2%
	9	73	69	94%	7.6%	2.8%

iii. Traceability of Calibrators/Controls

No international or certified reference material for anti-CCP IgG is available.

The BioPlex 2200 Anti-CCP Calibrators are assigned relative units from predicate Axis-Shield DIASTAT Anti-CCP Calibrators. BioPlex 2200 Anti-CCP Calibrators are prepared by blending defibrinated and delipidated human plasma units with known anti-CCP IgG activity in a processed human serum matrix made from immunodepleted, defibrinated plasma. These calibrators are used to assay characterized patient samples with the BioPlex 2200 Anti-CCP IgG assay.

Both Negative and Positive Controls were made in a human serum matrix from defibrinated plasma. All antibodies are derived from human disease state plasma.

iv. Limit of Detection

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary

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The Limit of Detection (LoD) of BioPlex 2200 Anti-CCP was determined by assaying low positive, high negative and blank samples in replicates of fifty (50). The LoD was calculated according to CLSI EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantitation. The calculated LoD for the anti-CCP IgG assay is 0.2 U/mL.

v. Analytical Specificity

Interfering Substances

An interfering substances study was conducted to evaluate the potential interference of specific endogenous and exogenous substances with the BioPlex 2200 Anti-CCP assay. The study was conducted based on the principles described in Clinical and Laboratory Standards Institute (CLSI) EP7-A2, Interference Testing in Clinical Chemistry. No interference was observed with any of the substances tested. The substances and the maximum levels tested are shown in the table below.

Substance	Concentration
Hemoglobin	≤ 500 mg/dL
Bilirubin, Unconjugated	≤ 20 mg/dL
Bilirubin, Conjugated	≤ 30 mg/dL
Cholesterol	≤ 500 mg/dL -
Red Blood Cells	≤ 0.4% (v/v)
Gamma Globulin	≤ 6 g/dL
Triglycerides	≤ 3300 mg/dL
Protein (total)	≤ 12 g/dL
Rheumatoid Factor	≤ 200 IU/mL
Ascorbic Acid	≤ 3 mg/dL
Lithium Heparin	≤ 8000 units/dL
Sodium Heparin	≤ 8000 units/dL
EDTA	≤ 800 mg/dL

Interfering Substances

Cross-Reactivity

A cross-reactivity study was performed to determine if samples from various disease states and other potentially interfering factors interfere with test results from the BioPlex 2200 Anti-CCP kit. Samples known to be positive for one of the potential cross reactants listed in the table below were evaluated with the BioPlex 2200 Anti-CCP assay.

August 19, 2010 Page 13 of 22 న్న

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A total of 163 ANA samples and 72 other samples containing potential cross reactants were evaluated by the BioPlex Anti-CCP. The following table summarizes the potential percent cross reactivity rate of the BioPlex 2200 Anti-CCP kit. Of the 163 ANA samples, some samples contained more than one analyte such as dsDNA, Chromatin, Scl-70, Sm, Centromere B, SmRNP, RiboP, SS-B, SS-A, RNP, and Jo-1.

Possible cross reactivity at 11% was observed with ANA samples, inclusive of all analytes. More specifically, Centromere B (23%) and SS-A (12%) appear to have the highest potential cross reactivity rates. Samples containing Myeloma IgG may also cross react with the BioPlex 2200 Anti-CCP kit (30%).

ﺐ

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Potential Cross Reactant	N	% Cross Reactivity
ANA	163	18/163 (11%)
dsDNA		2/27 (7%)
Chromatin		5/45 (11%)
Scl-70		2/24 (8%)
Sm		2/19 (11%)
Centromere B*		7/23 (23%)
SmRNP		4/37 (11%)
Ribo P		0/9 (0%)
SS-B		0/18 (0%)
SS-A*		8/66 (12%)
RNP		3/34 (9%)
Jo-1		0/8 (0%)
TPO IgG	13	0/13 (0%)
VCA IgG	17	0/17 (0%)
T. gondii IgG	10	1/10 (10%)
CMV IgG	12	0/12 (0%)
Myeloma IgG	10	3/10 (30%)
Lyme IgG	10	0/10 (0%)

Cross-Reactivity

Anti-CCP antibodies have been documented in patients with primary Sjögren's Syndrome (See references below).

Reference:

1. Atzeni. F., et al., Anti-cyclic citrullinated peptide antibodies in primary Sjögren's Syndrome may be associated with nonerosive synovitis. Arthritis Research & Therapy 2008. 10(3):R51
1. Zendman, A.J.W., et al., Use and significance of anti-CCP autoantibodies in rheumatoid arthritis. Rheumatology 2006. 45:20-25. (review article)
1. Nakamura H., et al., Anti-centromere antibody-seropositive Sjögren's Syndrome differs from conventional subgroup in clinical and pathological study. BMC Musculoskeletal Disorders, 2010. 11:140.

vi. Assay Cut-off

The cutoff value and assignment of the calibrators are determined by performing concordance testing and Receiver Operator Characteristic (ROC) analysis, using predicate results as the standard.

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary August 19, 2010 Page 15 of 22

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A total of 1394 patient samples including 177 normal patients, 504 patients with either Rheumatoid Factor (RF) tested or positive, 82 older patients (age >70), 287 Rheumatoid Arthritis (RA) diagnosed patients and 344 non-RA patients were evaluated to determine the anti-CCP IgG assay cutoff. All samples were confirmed positive or negative by the Axis-Shield DIASTAT anti-CCP predicate assay. A cutoff of 3.0 U/mL was obtained to achieve the percent positive and negative agreement at 92.9% and 98.2%, respectively.

B. Comparative Performance

i. Comparative Testing

Method Comparison

Performance of the BioPlex 2200 Anti-CCP kit was evaluated against predicate device, Axis-Shield DIASTAT Anti-CCP immunoassay.

The performance of the BioPlex 2200 Anti-CCP was evaluated using a total of 997 specimens: 300 apparently healthy blood donors, 496 patients previously diagnosed with Rheumatoid Arthritis (RA), and 201 patients with other rheumatic diseases were tested at one clinical site. Patient specimens were purchased from commercial suppliers and were frozen serum. Each sample was unique and was unlinked to patient identity and not individual identifiable. Eight hundred twenty-two (822) samples within the detection range were evaluated.

Patients previously diagnosed with RA were selected by either physicians' diagnosis or an ICD-9 code 714.0.

Patients diagnosed with other rheumatic or inflammatory diseases include 3 Atherosclerotic disease, 2 CREST Syndrome, 18 Crohn's disease, 15 Fibromyalgia, 19 Gout, 16 Inflammatory Arthritis, 8 Osteoarthritis, 18 Scleroderma, 21 Sjögren's Syndrome, 31 Systemic Lupus Erythematosus, 17 Ulcerative Colitis and 2 Wegener's Granulomatosis.

BioPlex 2200 Anti-CCP

The results are presented in the table below.

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary

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		Positive	Negative	Total	% PositiveAgreement(95% CI)	% NegativeAgreement(95% CI)
PredicateImmunoassay	Positive	358	9	367	97.5% (358/367)	91.4% (416/455)
	Negative	39	416	455	95% CI95.4 - 98.7%	95% CI88.5 - 93.7%
	Total	397	425	822

Positive Agreement (95% CI) = 97.5% (358/367) (95.4 - 98.7%)

Negative Agreement (95% Cl) = 91.4% (416/455) (88.5 - 93.7%)

Matrix Comparison

Testing for matrix effects was conducted in accordance with CLSI EP9-A2 (Vol. 22, No. 19). Forty-one matched sets of serum and plasma (EDTA and heparin) samples drawn from the same donor were acquired from commercial sources. The matched sets were spiked with high positive anti-CCP IgG serum in order to cover the measuring range of the assay from 0.5 to 300 U/mL. All samples were evaluated in replicates of two. Plasma U/mL values were compared to matched serum U/mL values. Scatter plots using the first replicate results to compare the performance of EDTA and heparin plasma samples against serum samples along with the corresponding slopes of regression and correlation coefficient (r) are shown below.

Matrix Comparison	N	Slope(95% CI)	Intercept(95% CI)	Correlation ( r )(95% CI)
EDTA vs. Serum	41	0.9636(0.8753, 1.0519)	2.5368(-2.5799, 7.6536)	0.9824(0.9670, 0.9906)
Heparin vs. Serum	41	0.9642(0.8995, 1.0289)	2.5264(-1.4891, 6.5419)	0.9852(0.9723, 0.9921)

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Image /page/17/Figure/0 description: The image contains two scatter plots comparing plasma and serum measurements. The left plot compares Heparin Plasma (U/mL) to Serum (U/mL), with a regression equation of y = 0.9642x + 2.5264 and a correlation coefficient of r = 0.9852. The right plot compares EDTA Plasma (U/mL) to Serum (U/mL), with a regression equation of y = 0.9636x + 2.5368 and a correlation coefficient of r = 0.9824. Both plots show a strong positive correlation between plasma and serum measurements, with data points clustered closely around the regression line.

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary August 19, 2010 Page 18 of 22

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ii. Clinical Sensitivity and Specificity

The clinical studies involved testing 997 specimens including 300 apparently healthy blood donors, 496 diagnosed RA patients, and 201 other rheumatic disease patients. The BioPlex 2200 Anti-CCP Sensitivity and Specificity are shown below.

Anti-CCP ClinicalSensitivity andSpecificity	Positive	Negative	Total	BioPlex 2200 Anti-CCP% Sensitivity(95% CI)	% Specificity(95% CI)
PreviouslyDiagnosedRheumatoidArthritis	412	84	496	83.1%(412/496)	97.8% (490/501)
Healthy BloodDonors andPatients with OtherRheumatic Diseases	11	490	501	95% CI79.5 – 86.1%	95% CI96.1 – 98.8%
Total	423	574	997

iii. Expected Values

Expected Values/Reference Range:

300 samples from apparently healthy donors including 114 males ranging in age from 4 to 84 and 186 females ranging in age from 4 to 88 were tested with BioPlex 2200 Anti-CCP assay. The Anti-CCP results range from <0.5 to 1.5 U/mL as shown below. Results of <3.0 U/mL are reported as negative and results > 3.0 U/mL are reported as positive.

BioPlex 2200Anti-CCP(U/mL)	Gender	Minimum	Maximum	N
Apparentlyhealthy donors	Male	<0.5	1.5	114
Apparentlyhealthy donors	Female	<0.5	1.2	186

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary August 19, 2010 Page 19 of 22

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Note: Each laboratory should establish its own reference range pertinent to their specific patient populations.

Prevalence:

The observed prevalence for the Anti-CCP assay was determined using samples collected from apparently healthy blood donors (N=300) including 114 males ranging in age from 4 to 84 and 186 females ranging in age from 4 to 88 as well as in clinical samples submitted for RF and/or anti-CCP testing (N=300) from 156 males ranging in age from 12 to 92 and 144 females ranging in age from 27 to 93. The results are presented in the tables below.

Note: Each laboratory should establish frequency distributions for their specific patient populations.

Prevalence in Samples from Apparently Healthy Blood Donors BioPlex2200 Anti-CCP Positive Results by Age and Gender

Age	Gender	BioPlex 2200Anti-CCP
		Pos/Total	% Prevalence
0-10	F	0/6	0%
0-10	M	0/3	0%
11-20	F	0/34	0%
11-20	M	0/19	0%
21-30	F	0/26	0%
21-30	M	0/15	0%
31-40	F	0/34	0%
31-40	M	0/10	0%
41-50	F	0/51	0%
41-50	M	0/12	0%
51-60	F	0/24	0%
51-60	M	0/32	0%
61-70	F	0/6	0%

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary August 19, 2010 Page 20 of 22

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Age	Gender	BioPlex 2200Anti-CCP
		Pos/Total	% Prevalence
71-80	M	0/16	0%
	F	0/4	0%
81+	M	0/5	0%
	F	0/1	0%
	M	0/2	0%
Total		0/300	0%

Prevalence in Samples sent to the lab with RF or CCP Test Ordered BioPlex2200 Anti-CCP Results by Age and Gender

Age	Gender	BioPlex 2200Anti-CCP
		Pos/Total	% Prevalence
11-20	F	0/0	0%
11-20	M	0/1	0%
21-30	F	0/3	0%
21-30	M	0/1	0%
31-40	F	1/4	25%
31-40	M	0/3	0%
41-50	F	0/17	0%
41-50	M	0/6	0%
51-60	F	0/37	0%
51-60	M	0/27	0%
61-70	F	1/37	2.7%
61-70	M	0/44	0%

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary August 19, 2010 Page 21 of 22

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		BioPlex 2200Anti-CCP
Age	Gender	Pos/Total	%Prevalence
71-80	F	0/30	0%
	M	0/52	0%
81-90	F	0/13	0%
	M	2/20	10%
91+	F	0/3	0%
	M	0/2	0%
Total		4/300	1.3%

Bio-Rad Laboratories, Inc. BioPlex™ 2200 Anti-CCP 510(k) Summary

. . . . . . . .

August 19, 2010 Page 22 of 22

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Image /page/22/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle-like symbol with three curved lines representing the body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the symbol.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

Bio-Rad Laboratories, Inc. c/o Mr. Juang Wang Regulatory Affairs Representative BioPlex Division 5500 East Second Street Benicia, CA 94510

AUG 2 4 2010

Re: K093954

Trade/Device Name: BioPlex™ 2200 Anti-CCP Kit BioPlex™ 2200 Anti-CCP Calibrator Set

Image /page/22/Picture/8 description: The image shows a black and white drawing of a plant. The plant has a stem and several leaves. The leaves are thin and pointed. The plant is drawn in a simple style. The drawing is not very detailed.

BioPlex™ 2200 Anti-CCP Control Set Regulation Number: 21 CFR 866.5575 Regulation Name: Rheumatoid factor immunological test system Regulatory Class: Class II Product Code: NHX, JIX, JJY Dated: August 20, 2010 Received: August 23, 2010

Dear Mr. Wang:

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. Ilsting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into class II (Special Controls), 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

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Page 2 - Mr. Juang Wang

CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); 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.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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/ReportalProblem/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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Mana mchan

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indication(s) for use

510(k) Number (if known): Unknown. Ko 9394 4

Device Name: BioPlex 2200 Anti-CCP Kit

AUG 2 4 2010

Indications for Use: ·

The BioPlex 2200 Anti-CCP kit is intended for use with the Bio-Rad BioPlex 2200 system.

The BioPlex™ 2200 Anti-CCP Calibrator Set is intended for the calibration of the BioPlex 2200 Anti-CCP Reagent Pack.

Prescription Use _____________________________________________________________________________________________________________________________________________________________ Over-the-Counter Use AND/OR (21 CFR 801 Subpart C) (Part 21 CFR 801 Subpart D)

(Please do not write below this line-Continue on another page of needed)

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

iai mchan

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K093954

Page 1 of 1

Regulation Number and Section

§ 866.5775 Rheumatoid factor immunological test system.

(a)
Identification. A rheumatoid factor immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.(b)
Classification. Class II (performance standards).