The Nanopia Wide Range CRP Reagent is intended for the quantitative measurement of C-Reactive Protein (CRP) in serum or plasma. The assay is intended for use in the evaluation of infection, tissue injury, and inflammatory disorders in combination with a complete clinical evaluation.

Device Description

The Nanopia Wide Range CRP assay consists of two liquid reagents. Reagent 1 is a buffering solution and Reagent 2 contains latex beads coated with mouse monoclonal anti-human CRP antibodies. The assay is for use on general clinical chemistry analyzers.

AI/ML Overview

Here's an analysis of the provided text regarding the Nanopia Wide Range CRP device, structured to answer your questions:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" for each performance characteristic in a separate, dedicated section. However, the study results implicitly define what was considered acceptable by stating the findings and, in one instance (linearity), explicitly stating the criteria.

Performance Characteristic	Acceptance Criteria (Implicit/Explicit)	Reported Device Performance
Precision	Not explicitly stated as a numerical threshold, but presumably low % CVs desired.	Within-Run % CV: - Control 1 (0.886 mg/L): 1.83% - Control 2 (6.71 mg/L): 0.76% - Control 3 (38.88 mg/L): 0.61% Total % CV: - Control 1 (0.886 mg/L): 2.46% - Control 2 (6.71 mg/L): 1.31% - Control 3 (38.88 mg/L): 1.11%
Linearity	100% ± 5% recovery	% Recovery from 0 to 400 mg/L: Ranged from 97.5% to 102.7% (e.g., at 40 mg/L: 99.4%, at 160 mg/L: 97.5%, at 360 mg/L: 102.7%). The document states, "The results above indicate that the assay is linear across the measuring range of the assay."
Assay Reportable Range	Defined as the linear range	0.10 - 400 mg/L (Limit of Quantification to the upper end of the linear range).
Detection Limit	Lowest concentration at which the assay performs with +/- 2 SD	Functional sensitivity: 0.10 mg/L (derived by extrapolation).
Analytical Specificity	No interference, defined as a result +/- 5% of the control	No interference was noted for hemoglobin (up to 500 mg/dL), ascorbic acid (up to 100 mg/dL), free bilirubin (up to 50 mg/dL), conjugated bilirubin (up to 50 mg/dl), lipid emulsion (up to 5000 turbidity), Rheumatoid factor (up to 500 IU/mL) on serum samples containing 3.7 mg/L nominal CRP.
Method Comparison (vs. Predicate)	Presumably, a strong correlation (high R2 and slope close to 1, intercept close to 0) indicating substantial equivalence.	Serum Samples (n=98): Nanopia = 1.015(Predicate) - 0.0349; R² = 0.9992. This indicates a very high correlation and closeness to the predicate device.
Matrix Comparison	No significant differences between sample types (serum/plasma, or spiked serum).	Paired samples of serum and EDTA plasma (n=50): Plasma = 0.994(Serum) + 0.03; r = 0.999. No significant differences observed with sodium citrate, sodium oxalate, EDTA, and sodium heparin spiked serum pools.

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

Precision Test Set: Triplicate measurements daily for 20 days on 3 spiked serum samples (Control 1, 2, and 3). So, 3 samples * 3 replicates * 20 days = 180 total measurements.
Linearity Test Set: One sample with high CRP (400 mg/L) serially diluted into 10 concentrations, plus a zero concentration sample. Each run in duplicate. So, 11 concentrations * 2 replicates = 22 measurements.
Detection Limit Test Set: A serum sample with 0.5 mg/L diluted to 0.0 mg/L, measured in 10 replicates.
Analytical Specificity (Interference) Test Set: Serum samples containing a nominal CRP of 3.7 mg/L, tested with various interfering substances. The number of samples per substance or replicates is not specified.
Method Comparison Test Set: 98 serum samples ranging from 0.0 to 293 mg/L.
Matrix Comparison Test Set: 50 paired samples of serum and EDTA plasma from individuals, plus additional serum pools spiked with anticoagulants.

Data Provenance: The document does not explicitly state the country of origin for the patient samples or if they were retrospective or prospective. Given it's a 510(k) summary for a US submission, the studies were likely conducted to meet US regulatory requirements, but the origin of the samples themselves is not detailed. The samples used for precision, linearity, and detection limit were "spiked serum samples" or "serum pools," suggesting laboratory-prepared samples rather than directly from patients in some instances. The "98 serum samples" and "50 paired samples" used for comparison studies were likely patient samples.

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

Not applicable. This device is an in vitro diagnostic (IVD) for quantitative measurement of C-Reactive Protein (CRP). The "ground truth" for such devices is typically established by reference methods, traceable calibrators, or known concentrations, not by expert consensus on visual interpretation as might be the case for imaging devices.

For example:

The calibrator is traceable to CRM470, which serves as a ground truth reference.
For linearity, theoretical concentrations are the ground truth comparing to measured values.
For method comparison, the predicate device's measurements serve as the reference for comparison, effectively a proxy for ground truth for demonstrating equivalence.

4. Adjudication Method for the Test Set

Not applicable. Adjudication methods (like 2+1, 3+1) are common in studies involving human interpretation (e.g., radiology reads). For quantitative IVD assays, the "truth" is determined by direct measurement against a standard or reference method, not by human interpretation that requires adjudication.

5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study

No, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not done. This type of study typically involves multiple human readers evaluating cases, often with and without AI assistance, to assess the impact of AI on reader performance. For a quantitative IVD device like the Nanopia Wide Range CRP, which performs an automated measurement, MRMC studies are not relevant.

6. Standalone Performance Study

Yes, a standalone performance study was done. The entire "Performance Characteristics" section (K.1. Analytical performance) details the algorithm's performance independent of human input. This includes:

Precision/Reproducibility
Linearity/Assay Reportable Range
Traceability
Detection Limit
Analytical Specificity
Method Comparison with predicate device
Matrix Comparison

All these evaluate the device's inherent analytical capability to accurately measure CRP concentration.

7. Type of Ground Truth Used

The ground truth for the analytical performance studies primarily relied on:

Reference Materials/Standards: The calibrator is stated to be traceable to CRM470.
Known Concentrations: For linearity, samples were prepared with theoretical (known) CRP concentrations. For detection limit, dilutions were made to specific concentrations. For analytical specificity, samples contained a "nominal concentration."
Predicate Device Measurements: For method comparison, the measurements from the legally marketed predicate device (N-Geneous Wide Range CRP Reagent) served as the comparative "truth" to establish substantial equivalence.

8. Sample Size for the Training Set

The document does not provide information about a "training set" in the context of machine learning. The Nanopia Wide Range CRP is a turbidimetric immunoassay, which is a traditional chemical measurement system, not an AI/ML-based device that would require a training set in the typical sense. Its "training" involves calibration using standard calibrators (a set of 5 with targeted CRP concentrations).

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

As mentioned above, the device is not an AI/ML-based system with a "training set" in that context. The "training" for such an assay is the calibration process. The ground truth for the calibrators is established as:

The calibrator is traceable to CRM470 (Certified Reference Material 470).
A master calibrator is prepared, and its value is assigned by multiple measurements of multiple lots using the device.
The sold calibrators are then traceable to this master calibrator and are value-assigned using the device.

Summary

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Clinical Data, Inc.

USA: One Gateway Center, Suite 415 Newton, MA 02158 1-617-527-9933, Ext. 22 Fax: 1-617-527-8230

510(k) Summary

Nanopia Wide Range CRP

Koszsql The assigned 510(k) Number is:________________________________________________________________________________________________________________________________________________

A. Analyte: C-Reactive Protein (CRP)
B. Type of Test: Turbidimetric immunoassay
C. Applicant:

One Gateway Center, Suite 415 Newton, MA 02158 Phone: 617-527-9933, Ext. 41 Fax: 617-527-8230

D. Proprietary and Established Names: Nanopia Wide Range CRP Reagent Nanopia Wide Range CRP Calibrator

E. Regulatory Information:

1. Regulation section: 21 CFR § 866.5270, C-reactive protein immunological test system 21 CFR § 862.1150, Calibrator
1. Classification: Class II
1. Product Code: DCK, C-reactive protein, antigen, antiserum, and control JIS, Calibrator, primary
1. Panel: Immunology (82)

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F. Intended Use:

1. Intended use(s):
  The Nanopia Wide Range CRP Reagent is intended for the quantitative measurement of C-Reactive Protein (CRP) concentration in serum or plasma.

Measurement of CRP is useful for determining the existence of inflammatory lesions and to monitor treatment.

The Nanopia Wide Range CRP Calibrator is intended for the calibration of the Nanopia Wide Range CRP assay.

1. Indication(s) for use: See Intended Use section.
1. Special condition for use statement(s): For in vitro diagnostic use.

Increases in CRP values are non-specific and should not be interpreted without a complete clinical history.

1. Special instrument Reguirements: Clinical chemistry analyzers (testing performed on Roche Hitachi 917 analyzer)

G. Device Description:

H. Substantial Equivalence Information:

1. Predicate device name(s): N-Geneous Wide Range CRP Reagent.
1. Predicate K number(s): K040241

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3. Comparison with predicate:

Item	Device	Predicate
Intended Use	Quantitative measurementof CRP in serum or plasma	Quantitative measurementof CRP in serum or plasma
Sample Matrix	Serum or plasma	Serum or plasma
Antibody	Mouse monoclonal anti-human CRP	Mouse monoclonal anti-human CRP
Assay Range	0.1 to 400 mg/L	0.04 to 320 mg/L
Antibody substrate	Latex	Latex
Number ofcalibrators	5	5

The N-Geneous Wide Range CRP Reagent and the Nanopia Wide Range CRP are essentially the same product both produced by Daiichi Pure Chemicals Co., Ltd. for distribution by the respective companies_

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

NCCLS Guideline EP9-A - Method Comparison and Bias Estimation Using PatientSamples
NCCLS Guideline EP5-A - Evaluation of Precision Performance of Clinical ChemistryDevices
NCCLS Guideline EP6-A - Evaluation of the Linearity of Quantitative AnalyticalMethods
NCCLS Guideline EP7-A - Interference Testing in Clinical Chemistry

J. Test Principle:

Sample is mixed with the buffer solution and the anti-CRP antibody-coated beads. CRP in the sample binds the antibody-coated beads and agglutinates. The light scattering caused by an increase in particle size is measured. The amount of light scattering is proportional to the concentration of CRP in the sample.

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K. Performance Characteristics (if/when applicable):

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

Device imprecision was evaluated according to NCCLS EP5-A. Spiked serum samples were run in triplicate daily for 20 days (units = mg/L).

Control	Mean	Within Run		Total
		SD	% CV	SD	% CV
1	0.886	0.16	1.83	0.022	2.46
2	6.71	0.05	0.76	0.089	1.31
3	38.88	0.24	0.61	0.430	1.11

b. Linearity/assay reportable range:

The useable range of this device is 0.10 - 400 mg/L (the Limit of Quantification to the upper end of the linear range).

Linearity was assessed using a sample with CRP values of 400 mg/L. Using a serum pool free of CRP dilutions were prepared to create samples with theoretical concentrations from 40 to 400 mg/L in increments of 40 mg/L. A sample from a serum pool free from CRP was included for a zero concentration. These samples were run in duplicate and the actual mean values were compared to the theoretical values. The % recovery from 0 to 400 mg/L ranged from 97.5 to 102.7%. Results are summarized below (units = mg/L).

	(mg/L)
TheoreticalCRP value	measurement value			% Recovery
	1	2	mean
0	0.00	0.00	0.00	---
40	39.33	40.20	39.77	99.4
80	79.01	78.42	78.72	98.4
120	119.26	116.14	117.70	98.1
160	155.44	156.48	155.96	97.5
200	196.46	194.97	195.72	97.9
240	236.89	236.10	236.50	98.5
280	280.76	278.09	279.43	99.8
320	322.15	323.21	322.68	100.8
360	374.30	365.09	369.70	102.7
400	401.12	406.17	403.65	100.9

The acceptable criteria was 100% ± 5%

The results above indicate that the assay is linear across the measuring range of the assay

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c. Traceability (controls, calibrators, or method):

The device is calibrated by a set of 5 calibrators (sold separately) with targeted CRP concentrations of 3, 6, 30, 180 and 360 mg/L. The calibrator is traceable to CRM470. A master calibrator is prepared and value assigned by multiple measurements of multiple lots using the device. The calibrators are traceable to this master calibrator and are value assigned using the device. Stability testing is described.

d. Detection limit:

Analytical sensitivity, defined as the lowest concentration at which the assay performs with + 2 SD as assessed by diluting a serum sample with a concentration of 0.5 mg/L to 0.0 mg/L and measuring the mAbs in replicates of 10. By this method, the functional sensitivity of this assay is said to be 0.10 mg/L (derived by extrapolation of plot of theoretical concentration vs. recovered concentration.

e. Analytical specificity:
Interference of endogenous substances was evaluated by testing for the effect of hemoglobin (up to 500 mg/dL), ascorbic acid (up to 100 mg/dL), free bilirubin (up to 50 mg/dL), conjugated bilirubin (up to 50 mg/dl, lipid emulsion (up to 5000 turbidity), Rheumatoid factor (up to 500 IU/mL), and ascorbic acid (up to 100 mg/dL) on serum samples containing a nominal concentration of 3.7 mg/L. No interference was noted on any of the above. Interference was defined as a result +/- 5 % of the control. This information is in the package insert.
f. Assay cut-off:
Not applicable
1. Comparison studies:
- a. Method comparison with predicate device:

Serum samples (n=98) ranging from 0.0 to 293 mg/L were measured using the Nanopia method and comparing those measurement to those made with the predicate method. Results are summarized below.

Serum Samples: Nanopia = 1.015(Predicate) - 0.0349; R2 = 0.9992

b. Matrix comparison:

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Paired samples of serum and EDTA plasma were collected concurrently from 50 individuals and measured using the Nanopia method. Results are summarized below:

Plasma = 0.994(Serum) + 0.03; r = 0.999

Additional serum pools were spiked with 110 mM of sodium citrate, 100 mM sodium oxalate, 25 mM EDTA, and 100 U/mL of sodium heparin and assayed. There were no significant differences observed between sample types.

1. Clinical studies:
- a. Clinical sensitivity: Not applicable
- b. Clinical specificity: Not applicable
- c. Other clinical supportive data (when a and b are not applicable): Not applicable
1. Clinical cut-off: Not applicable
1. Expected values/Reference range: Less than 3.0 mg/L.

L. Conclusion:

Clinical Data concludes that the Nanopia Wide Range CRP assay has a similar intended use, a similar technological principle, and clinically acceptable performance comparable to similar devices currently in commercial distribution and is substantially equivalent to the predicate device.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird with three curved lines representing its wings or feathers. The bird is positioned above a circular border containing the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

2006 FEB 9

2006

Israel M. Stein, MD President Clinical Data, Inc. One Gateway Center Suite 411 Newton, MA 02146

K052591 Re:

Trade/Device Name: Nanopia Wide Range CRP Reagent Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCK, JIS Dated: January 12, 2006 Received: January 13, 2006

Dear Dr. Stein:

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).

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Page 2 --

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 president redicate device results in a classification for your device and thus, permits your device to proceed to the market.

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 I ou may of annovaturers, 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,

Alberto Gutierrez, Ph.D.

Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K052591

Nanopia Wide Range CRP Reagent Device Name:

Indications For Use: The Nanopia Wide Range CRP Reagent is intended for the quantitative measurement of C-Reactive Protein (CRP) in serum or plasma. The assay is intended for use in the evaluation of infection, tissue injury, and inflammatory disorders in combination with a complete clinical evaluation.

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 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)

Cinn Chapper

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of 1

FOSZSYI .

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).