The Dimension® CSAE Cyclosporine Extended Range Calibrator is an in vitro diagnostic product intended to be used to calibrate the CSAE Cyclosporine Extended range method for the Dimension® clinical chemistry system and the Syva® Emit® 2000 Cyclosporine assay.

Device Description

The Dimension® CSAE Cyclosporine Extended Range Calibrator contains cyclosporine in a preserved whole blood hemolysate. The kit consists of 2 sets of the following: one vial of sample diluent (0.0 ng/ml of cyclosporine ) and one vial of levels 1 through 5. Target concentrations for the five calibrator levels are approximately 200, 400, 800, 1400 and 2000 ng/ml of cyclosporine.

Level 0 is included for dilution of over-range samples (>2000 ng/mL) in order to obtain results within the assay range; it is not used in calibration. Levels 1 thru 5 are used for calibration of the CSAE method.

AI/ML Overview

The provided text describes the Dimension® CSAE Cyclosporine Extended Range Calibrator (DC108A), a calibrator material used for the Syva® Emit® 2000 Cyclosporine assay and the Dimension® clinical chemistry system. The submission (K061503) concludes that the new device is substantially equivalent to a predicate device based on performance testing.

Here's an analysis of the acceptance criteria and study information provided, structured according to your request:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state numerical "acceptance criteria" for performance metrics like accuracy, precision, or detection limits typically associated with diagnostic devices. Instead, the performance characteristic described is stability, which is crucial for a calibrator material. The acceptance hinges on demonstrating that the new calibrator is "substantially equivalent" to its predicate device. This implies that the stability of the new device must be comparable to or meet the requirements that the predicate device satisfied for its clearance.

Performance Characteristic	Acceptance Criteria (Implied)	Reported Device Performance
Stability (Shelf Life)	Product stored at -15 to -25°C (recommended storage temperature) must not show significant analytical drift compared to product stored at -70°C (reference storage temperature) over the target shelf life of 12 months. This demonstrates dissociation of analytical system drift from calibrator drift.	The "Performance Characteristics" section implicitly states that studies will demonstrate that the calibrator meets its target shelf life of 12 months. The conclusion (`M. Comments on Substantial Equivalence/Conclusion`) states that "The performance testing according to the verification and validation test protocols demonstrate that the Dimension® CSAE Calibrator (DC108A) is substantially equivalent to the designated predicate device."
Traceability	Cyclosporine values in the calibrator should be traceable to a recognized standard (Novartis Pharmaceutical USP Grade CSA powder in this case) and verified by a definitive method.	Reference lot formulated using Novartis Pharmaceutical USP Grade CSA powder, diluted into whole blood hemolysate, and assigned by LC/MS/MS (a high-accuracy mass spectrometry method).
Value Assignment	New calibrator lots should be consistently assigned values that recover against a control calibrator lot and a frozen reference lot within acceptable limits. This ensures consistency between different production lots.	Cyclosporine stock solution prepared gravimetrically. Aliquots added to matrix to yield desired concentrations. Recovery of six levels verified against a control calibrator lot and a frozen reference lot.
Substantial Equivalence	The new device must demonstrate that it is as safe and effective as the predicate device and does not raise new questions of safety or effectiveness. This is the overarching "acceptance criterion" for 510(k) clearance.	Performance testing, including stability, traceability, and value assignment, demonstrated substantial equivalence to the predicate device (DC108).

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

Sample Size for Test Set: For stability studies, three (3) lots of product were used. Each lot was tested at 14 different time points over 13 months. This is a prospective study design for real-time stability.
Data Provenance: Not explicitly stated, but given that Dade Behring Inc. is located in Newark, DE (USA), and the calibrator is manufactured in Glasgow, Delaware, it is highly likely that the data was generated in the USA and retrospectively analyzed for the submission, though the studies themselves were prospectively conducted over time (real-time stability).

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

This information is not applicable and not provided for this device submission. This device is a calibrator material, which means its "ground truth" (i.e., the true concentration of cyclosporine) is established through analytical chemistry methods, not expert human interpretation of medical images or clinical outcomes. The ground truth for calibrators is typically formed by:

Primary Reference Materials: Using highly pure, certified reference materials (e.g., Novartis Pharmaceutical USP Grade CSA powder).
Reference Methods: Using highly accurate and precise analytical methods (e.g., LC/MS/MS).

4. Adjudication Method for the Test Set

This information is not applicable and not provided. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies where subjective human interpretation needs to be reconciled (e.g., radiologists interpreting images). For a chemical calibrator, the "ground truth" (target concentration) is determined analytically, not through human consensus.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This information is not applicable and not provided. This is a submission for a chemical calibrator, not a diagnostic imaging or AI-enabled device that would involve human readers or AI assistance.

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

This information is not applicable and not provided. This device is a chemical calibrator, and there is no algorithm or AI component involved. Its performance is evaluated through analytical testing.

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

The ground truth for the cyclosporine concentrations within the calibrator is established by:

Primary Reference Material: Novartis Pharmaceutical USP Grade CSA powder.
Definitive Analytical Method: LC/MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry). This is considered a highly accurate and precise method for quantifying drug concentrations, serving as the "gold standard" or definitive truth for chemical assays.
Gravimetric Procedures: For preparing stock solutions.

8. The Sample Size for the Training Set

This information is not applicable and not provided. Calibrators are not "trained" in the way an algorithm or AI model would be. Their formulation and value assignment are based on established chemical and analytical principles.

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

This information is not applicable and not provided for the reasons stated in point 8.

Summary

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JUN 222 2006

510(k) Summary for the Dimension® Extended Range Cyclosporine Calibrator Catalog # DC108A

A. 510(k) Number: K061503

B. Analyte: Cyclosporine Calibrator

C. Type of Test: Calibrator Material

D. Applicant:

Manufacturer: Dade Behring Inc., P.O. Box 6101, Newark, DE 19714-6101

Contact: Andrea M. Tasker, Regulatory Affairs and Compliance Manager (302) 631-9454

Date of Preparation: May 31, 2006

E. Proprietary and Established Names:

Dimension® Extended Range Cyclosporine Calibrator (DC108A)

F. Regulatory Information:

1. Regulation section: 862.3200 CLINICAL TOXICOLOGY CALIBRATOR
1. Classification: Class II
1. Product Code: DLJ CALIBRATORS, DRUG SPECIFIC
1. Panel: CLINICAL TOXICOLOGY

G. Intended Use:

1. Intended use(s):
  The Dimension® CSAE Cyclosporine Extended Range Calibrator is an in vitro diagnostic product intended to be used to calibrate the CSAE Cyclosporine Extended range method for the Dimension® clinical chemistry system and the Syva® Emit® 2000 Cyclosporine assay.

Indication(s) for use:

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

H. Device Description:

I. Substantial Equivalence Information:

Predicate device name(s): Dimension® CSAE Cyclosporine Extended Range Calibrator (DC108)
Predicate K number(s): K052015, Dimension® Cyclosporine Extended Range Calibrator (CSAE CAL - DC108) cleared on September 12, 2005 for the Dimension® system intended use

K053108, Dimension® Cyclosporine Extended Range Calibrator (CSAE CAL - DC108) cleared on January 12, 2006 for new Syva® Emit® 2000 intended use

Item	New Device	Predicate
	Dimension® CSAECyclosporine CalibratorDC108A	Dimension® CSAECyclosporine CalibratorDC108
Intended Use	The Dimension® CSAECyclosporine Extended RangeCalibrator is an in vitrodiagnostic product intended tobe used to calibrate the CSAECyclosporine Extended rangemethod for the Dimension®clinical chemistry system and	The Dimension® CSAECyclosporine Extended RangeCalibrator is an in vitrodiagnostic product intended tobe used to calibrate the CSAECyclosporine Extended rangemethod for the Dimension®clinical chemistry system and

3. Comparison with predicate:

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	the Syva® Emit® 2000Cyclosporine assay.	the Syva® Emit® 2000Cyclosporine assay.
Matrix	Preserved whole bloodhemolysate	Preserved whole bloodhemolysate
Number of levelsused for calibration	5 Levels	5 Levels
TargetConcentrations	200, 400, 800, 1400 and 2000ng/ml of cyclosporine	200, 400, 800, 1400 and 2000ng/ml of cyclosporine
Storage	This is a frozen product	This is a frozen product
Differences
Item	New Device	Predicate
	Dimension® CSAECyclosporine CalibratorDC108A	Dimension® CSAECyclosporine CalibratorDC108
Packaging	The kit consists of 6 glassVials (Level 0 - Level 5),2.0 mL each.	The kit consists of 6 plasticVials (Level 0 - Level 5),2.0 mL each.
StorageTemperature	Unopened vials should bestored between -15 and -25°C.	Unopened vials should bestored between -17 and -27°C.
Traceability(Reference lotFormulation)	Reference lot stock solutionformulatedFinal Reference lot sent toexternal reference lab forLC/MS/MS value assignment	Reference lot stock solutionformulated and tested byLC/MSFinal Reference lot sent toexternal reference lab forLC/MS/MS value assignment
ValueAssignment(New CalibratorLot)	Stock solution for newCalibrator Lot formulated	Stock solution for newCalibrator Lot formulated andtested by LC/MS
	New Calibrator Lot recoveryverses the Reference Lot andverses Control Calibrator lot(Control Calibrator Lot =Any Approved Calibrator Lot)	New Calibrator Lot recoveryverses the Reference Lot andverses Control Calibrator lot(Control Calibrator Lot =Any Approved Calibrator Lot)
ProductionSite	Calibrator manufactured byDade Behring Inc. in GlasgowDelaware	Calibrator prepared by anOEM Manufacturer for DadeBehring Inc.

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J. Standard/Guidance Document Referenced:

1. Guidance;

Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA, Document issued on: September 16, 2002.

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® CSAE Cyclosporine Extended Range Calibrator contains cyclosporine in a preserved whole blood hemolysate. It is intended to be used to calibrate the high range cyclosporine assay on the Dimension® clinical chemistry systems and the Syva® Emit® 2000 Cyclosporine assay.

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L. Performance Characteristics:

1. Stability

Target shelf life for the Dimension® CSAE Calibrator (DC108A) is 12 months. Studies require 13 months of real time testing on three lots of product. Calibrator shelf life is determined by comparing results of the product stored at -15 to -25℃ (recommended storage temperature) with product stored at -70°C (reference storage temperature) to ensure that analytical system drift is dissociated with calibrator drift. Product is tested at days 0, 7, 14, 30, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360, 390.

2. Traceability:

Novartis Pharmaceutical USP Grade CSA powder is used to formulate a reference stock solution. A reference lot is formulated by diluting the stock into whole blood hemolysate with preservatives at six different levels and stored -70°C. The reference lot is assigned by LC/MS/MS.

3. Value Assignment

A cyclosporine stock solution is prepared using standard gravimetric procedure. Aliquots of the stock solution are added to measured amounts of calibrator matrix to vield the desired concentration for each calibrator level. Cyclosporine calibrators are prepared in preserved whole blood hemolysate. The recovery of the six levels are verified verses a control calibrator lot (control calibrator = any approved calibrator lot) and verses the frozen reference lot.

M. Comments on Substantial Equivalence/Conclusion

The performance testing according to the verification and validation test protocols demonstrate that the Dimension® CSAE Calibrator (DC108A) is substantially equivalent to the designated predicate device.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The logo is black and white.

Public Health Service

JUN 222 2006

Food and Druq Administration 2098 Gaither Road Rockville MD 20850

Ms. Andrea M. Tasker Regulatory Affairs and Compliance Manager Dade Behring Inc. Glasgow Business Community PO Box 6101 MS 514 Newark, DE 19714-6101

Re: K061503

Trade/Device Name: Dimension® CSAE cyclosporine Extended Range Calibrator Regulation Number: 21 CFR§862.3200 Regulation Name: Clinical toxicology calibrator Regulatory Class: Class II Product Code: DLJ Dated: May 31, 2006 Received: June 1, 2006

Dear Ms. Tasker:

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 marketed predicate 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 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 vours.

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

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Indications For Use Statement

510(k) Number (if known):

06/503

Device Name:

Dimension® CSAE Cyclosporine Extended Range Calibrator

Indications for Use:

Prescription Use X (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)

GAC

Division Sign-Off

Office of the Vitro Diagnostic Device Evaluation and Safet

100k) K061503

Regulation Number and Section

§ 862.3200 Clinical toxicology calibrator.

(a)
Identification. A clinical toxicology 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. A clinical toxicology calibrator can be a mixture of drugs or a specific material for a particular drug (e.g., ethanol, lidocaine, etc.). (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.