The Dimension® CCRP Calibrator is an in vitro diagnostic product intended to be used to calibrate the Dimension® CardioPhase® high sensitivity C-reactive protein (Cat. No. RC434) method for the Dimension® clinical chemistry system with the heterogeneous immunoassay module. This product was designed to meet the needs of users to assure accurate results over the assay range of this method.

Device Description

The high sensitivity C-reactive protein Calibrator is a liquid bovine serum albumin-based product. Levels 2 -5 contain a human C-reactive protein.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Dimension® CardioPhase® high sensitivity CRP Calibrator (CCRP Calibrator - RC434), based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria	Reported Device Performance
Stability (Shelf Life)	"Linear regression across the shelf life interval for each test sample versus test day will have non-significant slopes (p> 0.05) or observed drift within +/-5% for non-zero samples and +/-0.05 mg/L at 0 mg/L CRP over a 12 month interval. The shelf life of the product will be 6 months after the successful completion of 7 months of real time stability on three lots of product."	The document states, "The shelf life of the product will be 6 months after the successful completion of 7 months of real time stability on three lots of product." This implies the acceptance criteria were met by passing this stability study, but the specific performance data (e.g., actual slopes, drift percentages) is not explicitly detailed in the provided summary. The approval of the 510(k) suggests compliance.
Traceability	Calibrator values are standardized to IFCC, BCR, and CAP reference preparations (specifically Lot No. 91/0619=CRM470=RPPHS 91/0619).	"The assigned values of the CCRP calibrator are standardized to the International Federation of Clinical Chemistry (IFCC) International Reference Preparation for Plasma Proteins, the Community Bureau of Reference (BCR) and the College of American Pathologists (CAP). The basis of this international standardization is the IFCC/BCR/CAP reference preparation for 14 human serum proteins (Lot No. 91/0619=CRM470=RPPHS 91/0619) (lot V)." (This indicates the criteria were met.)
Value Assignment	"The acceptable recovery of an approved CCRP Calibrator lot must be obtained."	"Three Dimension® clinical chemistry analyzers are calibrated with the approved CCRP Masterpool. The acceptable recovery of an approved CCRP Calibrator lot must be obtained. Test calibrator levels are then tested on three separate analyzers with different CCRP flex lots. The grand mean of all 5 replicate test means of all 9 curves is the value assignment for each Calibrator Level." (This describes the method for value assignment, which implies it's performed to ensure acceptable recovery, but doesn't provide specific numerical performance data.)

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

The provided document does not explicitly define a "test set" in the traditional sense for assessing diagnostic performance against an external reference. Instead, the studies described are related to the calibrator's internal performance (stability, traceability, and value assignment).

Stability Study:
- Sample Size: "three lots of product" were used for real-time stability testing.
- Data Provenance: The data is implicitly prospective, as it involves real-time monitoring of the product's stability. The country of origin of the data is not specified but is presumably where Dade Behring Inc. conducts its manufacturing and testing, which is in the USA (Newark, DE).
Value Assignment Study:
- Sample Size: "Three Dimension® clinical chemistry analyzers" and "different CCRP flex lots" (number of lots not specified beyond "different"), with "5 replicate test means of all 9 curves" implying a total of 45 measurements per calibrator level in this specific part of the assignment process.
- Data Provenance: Implicitly prospective and internal to the manufacturer. Country of origin not specified, but likely USA.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable. For a calibrator, the "ground truth" is established by its direct traceability to recognized international reference standards (IFCC/BCR/CAP CRM 470), not by expert consensus on clinical cases.

4. Adjudication Method for the Test Set
Not applicable, as there's no "test set" in the clinical diagnostic sense requiring expert adjudication.

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 is relevant for diagnostic devices that involve human interpretation of results (e.g., imaging devices, pathology slides). The device in question is a calibrator, which provides known concentrations for calibrating an automated assay.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was Done
Yes, the performance characteristics described are "standalone" in the sense that they evaluate the calibrator material itself and its interaction with the Dimension® clinical chemistry system, without direct human intervention in the result generation or interpretation after the initial setup. The calibrator's function is to provide known reference points for an automated assay.

7. The Type of Ground Truth Used

The ground truth for the calibrator's values is based on traceability to internationally recognized reference materials.

For the Calibrator values: IFCC/BCR/CAP reference preparation for 14 human serum proteins (Lot No. 91/0619=CRM470=RPPHS 91/0619). This is a highly standardized and globally accepted reference material.

8. The Sample Size for the Training Set
Not applicable. The concept of a "training set" is generally used for machine learning algorithms. This device is a calibrator for a traditional immunoassay system and does not involve an algorithm that requires a training set.

9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for this device.

Summary

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

K053104

DEC 2 3 2005

Page 1 of 4

510(k) Summary for the Dimension® CardioPhase® high sensitivity CRP Calibrator (CCRP Calibrator - RC434)

A. 510(k) Number:

B. Analyte: C-Reactive Protien Calibrator

C. Type of Test: Calibrator Material

D. Applicant:

Dade Behring Inc., P.O. Box 6101, Newark, DE 19714-6101 Contact: Andrea M. Tasker, Regulatory Affairs and Compliance Manager (302) 631-9454

E. Proprietary and Established Names: Dimension® CardioPhase® high sensitivity CRP Calibrator (CCRP Calibrator- RC434)

F. Regulatory Information:

1. Regulation section: 21 CFR § 862-1150 CALIBRATOR
1. Classification: Class II
1. Product Code: JIS CALIBRATORS, PRIMARY
1. Panel: CLINICAL CHEMISTRY

G. Intended Use:

Intended use(s):

2. Indication(s) for use:

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

1. Special condition for use statement(s): none
1. Special instrument Requirements: none

H. Device Description:

The high sensitivity C-reactive protein Calibrator is a liquid bovine serum albumin-based product. Levels 2 -5 contain a human C-reactive protein.

I. Substantial Equivalence Information:

1. Predicate device name(s): N Rheumatology Standard SL on the BN Systems.
1. Predicate K number(s): K964527
1. Comparison with predicate:

Similarities
Item	DeviceDimension® CardioPhase®(CCRP) Calibrator	PredicateN Rheumatology StandardSL
Intended Use	The Dimension® CCRPCalibrator is an in vitrodiagnostic product intended tobe used to calibrate theDimension® CardioPhase®high sensitivity C-reactiveprotein method for theDimension® clinical chemistrysystem with the heterogeneousimmunoassay module.	Establishment of referencecurves for theimmunonephelometricdetermination of rheumatoidfactors (RF), anti-streptolysinO (ASL) and C-reactiveprotein (CRP) using the BNSystems.
Traceability	IFCC/BCR/CAPCRM 470	IFCC/BCR/CAPCRM 470

{2}------------------------------------------------

Differences
Item	Device	Predicate
	Dimension® CardioPhase®hsCRP (CCRP) Calibrator	N Rheumatology StandardSL
Matrix	liquid bovine serum albumin-based	human sera based
Number of levels	Multi-Point5 levels provided	Multi-Point1 level provided(instrument prepares6 standard dilutions)
Reference CurveFit Calculation	Logit	4 Parameter Logit Log

J. Standard/Guidance Document Referenced:

1. Guidance;

Review Criteria for Assessment of C-Reactive Protein (CRP), High Sensitivity C Reactive Protein (hsCRP) and Cardiac C-Reactive Protein (cCRP) Assays Document issued on: September 22, 2005

2. Standards;
GP22-A	Continuous Quality Improvement Essential Management Approaches
CEN 13640	Stability testing of In-Vitro Diagnostic Devices
ISO 14971:2000	Medical devices -Application of risk management to medicaldevices
ISO 15223	Medical devices - Symbols to be used with medical device labelingand information to be supplied

K. Test Principle:

The Dimension® CCRP Calibrator is an in vitro diagnostic product intended to be used to calibrate the Dimension® CardioPhase® high sensitivity C-reactive protein (Cat. No. RF434) method for the Dimension® clinical chemistry system with the heterogeneous immunoassay module. The hsCRP method is a one step enzyme immunoassay based on the "sandwich" principle.

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

L. Performance Characteristics:

1. Stability

Calibrator shelf life is determined by comparing results of the product stored at 4°C with product stored at -70°C to ensure that analytical system drift is dissociated with calibrator drift. Linear regression across the shelf life interval for each test sample versus test day will have non-significant slopes (p> 0.05) or observed drift within +/-5% for non-zero samples and +/-0.05 mg/L at 0 mg/L CRP over a 12 month interval The shelf life of the product will be 6 months after the successful completion of 7 months of real time stability on three lots of product.

2. Traceability:

The assigned values of the CCRP calibrator are standardized to the International Federation of Clinical Chemistry (IFCC) International Reference Preparation for Plasma Proteins, the Community Bureau of Reference (BCR) and the College of American Pathologists (CAP). The basis of this international standardization is the IFCC/BCR/CAP reference preparation for 14 human serum proteins (Lot No. 91/0619=CRM470=RPPHS 91/0619) (lot V).

3. Value Assignment

Three Dimension® clinical chemistry analyzers are calibrated with the approved CCRP Masterpool. The acceptable recovery of an approved CCRP Calibrator lot must be obtained. Test calibrator levels are then tested on three separate analyzers with different CCRP flex lots. The grand mean of all 5 replicate test means of all 9 curves is the value assignment for each Calibrator Level.

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

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/4/Picture/2 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract image of an eagle with three lines representing its wings and tail feathers.

DEC 2 3 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Andrea M. Tasker Regulatory Affairs and Compliance Dade Behring Inc. Glasgow Business Community PO Box 6101, Building 500 Newark, DE 19714-6101

Re: K053104

K033104
Trade/Device Name: Dimension® CardioPhase® high sensitivity C-reactive protein Calibrator (CCRP Calibrator -RC434) Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIS Dated: November 2, 2005 Received: November 4, 2005

Dear Ms. Tasker:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your becared on the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for assession 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 r ou may, thereforey isions 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).

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

Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) This letter will anow you to begin maxions of sybstantial equivalence of your device to a legally premation notification "Te 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 you desire specific mostion and advertising of your device, please contact the Office of In or quotions on the program and Safety at (240) 276-0484. Also, please note the v Itto Diagnoutied, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the r ou may other generational 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 G

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

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

Indications For Use Statement

510(k) Number (if known): K053104

Device Name:

Dimension® CardloPhase® high sensitivity C-reactive protein Calibrator (CCRP Calibrator - RC434)

Indications for Use:

The Dimension® CCRP Calibrator is an in vitro diagnostic product intended to be used to calibrate the Dimension® CardioPhase® high sensitivity C-reactive protein (Cat. No. RF434) method for the Dimension® clinical chemistry system with the heterogeneous immunoassay module. This product was designed to meet the needs of users to assure accurate results over the assay range of this method.

Ann Chappie
Division

Office of in Vier Tingnoma ರಿಕಾರಿ ಕಾರದಿಂದರೆಯ ಮನೆ ಕಿಡ್ಡೆತಿ /

510(k) K053104

× Prescription Use (Per 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)

Regulation Number and Section

§ 862.1150 Calibrator.

(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.