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.

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. The 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 a result; it is not used in calibration. Levels 1 thru 5 are used for calibration of the CSAE method. Refer to the method insert sheet for instructions on calibration and making appropriate manual dilutions.

AI/ML Overview

The provided document describes the acceptance criteria and a study to prove the Dimension® Extended Range Cyclosporine Calibrator meets these criteria.

Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Allowable drift is less than or equal to the total precision % CV at the test concentration for stability testing.	Not explicitly stated with a specific value, but the document implies the device met this criterion as it was approved. They tested product stored at -20°C at various time points (0, 7, 14, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 390 days), and control material stored at -70°C at the same frequency.

Study Details

Due to the nature of the device (a calibrator material) and the provided 510(k) summary, the study described is not a typical clinical performance study involving human readers or patient outcomes, but rather a stability and value assignment study to ensure the calibrator's accuracy and reliability.

Sample size used for the test set and the data provenance:
- Sample Size: The document mentions that the product (calibrator) was tested at various time points (0, 7, 14, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 390 days) during its testing cycle. The control material was tested at the same frequency. These time points represent the "samples" for the stability study. The calibrator itself consists of 5 levels (plus a diluent level 0), meaning each "sample" involves testing these 5 levels at each time point.
- Data Provenance: Not explicitly stated but implied to be generated in-house through laboratory testing by Dade Behring Inc. The study is prospective in nature, as it involves real-time monitoring of the product's stability over an extended period.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This question is less applicable to a calibrator device. The "ground truth" for calibrators is primarily established through analytical and metrological traceability, not expert consensus on diagnostic interpretation.
- Traceability: The document states that Novartis Pharmaceutical Grade CSA powder was used to formulate a reference stock solution, and its concentration was assigned by HPLC. A reference lot was then formulated and assigned by LC/MS/MS. This establishes the highly accurate "ground truth" values for the cyclosporine concentrations.
- Qualifications: While not explicitly mentioned for the individual performing the HPLC or LC/MS/MS, these are standard analytical chemistry techniques that would be performed by qualified laboratory scientists with expertise in these methods.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. Adjudication methods like 2+1 or 3+1 are used in studies involving human interpretation (e.g., radiology reads) where there might be disagreement among experts. For an analytical calibrator, the ground truth is established chemically and instrumentally, not through subjective human interpretation requiring adjudication.
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:
- Not applicable. This device is a calibrator for a clinical chemistry system, not an AI-assisted diagnostic tool that would involve human readers interpreting cases.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, in a sense. The "standalone performance" of the calibrator is its ability to maintain its assigned values over time (stability) and for its assigned values to be accurate (traceability and value assignment). The performance characteristics section (L) directly addresses this for the calibrator itself, independent of operator interaction after its initial formulation and validation.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for the calibrator's concentrations is established through analytical and metrological techniques, specifically:
  - HPLC (High Performance Liquid Chromatography) for the initial stock solution concentration.
  - LC/MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry) for assigning the reference lot values.
  - Gravimetric procedures for preparing the cyclosporine stock solution.
The sample size for the training set:
- Not applicable in the conventional sense of an AI/machine learning model's training set. For a calibrator, the "training" analogous process is its initial development, formulation, and rigorous characterization to ensure its stability and accurate value assignment. The document describes the process of preparing stock solutions and calibrator levels using controlled methods, which is a form of "training" or establishment of the product.
How the ground truth for the training set was established:
- As mentioned above, the "ground truth" (i.e., the target concentrations of cyclosporine for each calibrator level) was established through:
  - Preparation of a cyclosporine stock solution using standard gravimetric procedures.
  - Confirmation of the stock solution concentration using HPLC.
  - Aliquots of this stock solution were then added to measured amounts of calibrator matrix (preserved whole blood hemolysate) to achieve the desired concentrations for each calibrator level.
  - The recovery of these levels was verified against a control calibrator lot and a frozen reference lot, with the reference lot assigned by LC/MS/MS.

Summary

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SEP 1 2 2005

K052.015

510(k) Summary for the

Dimension® Extended Range Cyclosporine Calibrator Catalog # DC108

A. 510(k) Number:

B. Analyte: Cyclosporine Calibrator

C. Type of Test: Calibrator Material

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

E. Proprietary and Established Names:

Dimension® Extended Range Cyclosporine Calibrator (DC108)

F. Regulatory Information:

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

G. Intended Use:

l. Intended use(s):

2. Indication(s) for use:

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

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H. Device Description:

The 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 ni a of sample diluent (0.0 ng/ml of cyclosporine ) and one vial of levels 1 through 5. vial of sample antacht (or the five calibrator levels are approximately 200, 400, 800, 1400 and 2000 ng/ml of cyclosporine.

and 2000 ng/m or of eyeresponsive
Level 0 is included for dilution of over-range samples (>2000 ng/mL) in order to obtain Ecvel o is metaded for unance it is not used in calibration. Levels 1 thru 5 are used for calibration of the CSAE method. Refer to the method insert sheet for instructions on calibration and making appropriate manual dilutions.

I. Substantial Equivalence Information:

1. Substantian Dquivated Information Cyclosporine Calibrator Catalog # DC89
  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2. Predicate K number(s): K011112

3. Comparison with predicate:

Item	DeviceDimension® CSAECyclosporine Calibrator	PredicateDimension® CSACyclosporine Calibrator
Intended Use	To calibrate the CSAECyclosporine Extendedrange method for theDimension® clinicalchemistry system.	To calibrate the CSACyclosporine method for theDimension® clinicalchemistry system.
Matrix	Preserved whole bloodhemolysate	Preserved whole bloodhemolysate
Number of levels	5	5
TargetConcentrations	200, 400, 800, 1400 and2000 ng/ml of cyclosporinea	0, 80, 180, 300 and 500 ng/mlof cyclosporine

a. This calibrator material is similar to the predicate in terms of intended use, matrix, and number of levels. Cyclosporine calibrator levels are different compared to the predicate in order to accommodate a higher assay range.

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J. Standard/Guidance Document Referenced:

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

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.

L. Performance Characteristics:

1. Stability

Product is stored at -20℃ and throughout testing cycle and tested at days 0, 7, 14, 30, 1 roduct is stored at - 2 - 40, 270, 300, 330, 390. The control material is stored at -70 °C and tested at the same frequency.

Acceptance Criteria: Allowable drift is less than or equal to the total precision % CV at the test concentration.

2. Traceability:

Novartis Pharmaceutical Grade CSA powder used to formulate a reference stock solution. The concentration of the stock solution is assigned by HPLC. A reference lot is formulated by diluting the stock into whole blood hemolysate with preservatives at six different levels and stored -20° C. The reference lot is assigned by LC/MS/MS.

3. Value Assignment

A cyclosporine stock solution is prepared using standard gravimetric procedure and the concentration of the stock solution is established with high performance liquid chromatography (HPLC). Aliquots of the stock solution are added to measured amounts of calibrator matrix to yield 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 a frozen reference lot.

Final: September 2, 2005

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. 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 symbol resembling an eagle or bird in flight, composed of three curved lines.

SEP 1 2 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Andrea M. Tasker Regulatory Affairs and Compliance Manager Dade Behring, Inc. P.O. Box 6101 Glasgow Bldg. 500 Newark, DE 19714

Re: K052015

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: August 30, 2005 Received: September 1, 2005

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 5 [0(k) This letter whi anow you to oegin mancetting your and equivalence of your device to a legally premarket notification: "The PDT Internation 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 (c.vice, If you desire specific information acourtising of your device, please contact the Office of In
or questions on the promotion and advertising of your and advertising office of of questions on the promotion and Safety at (240) 276-0484. Also, please note the VITO Diagnostic Device Developments and reacle to premarket notification" (21CFR Part 807.97). Tegulation childed, "Misording of Priser on your responsibilities under the Act from the I bu may obtain only general mornational 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,

Carol C. Benson

Carol C. Benson, M.A. Acting 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):

Device Name:

Dimension® CSAE Cyclosporine Extended Range Calibrator

Indications for Use:

The CSAE Calibrator is an in vitro diagnostic product intended to be used to calibrate the Cyclosporine Extended Range (CSAE) method for the Dimension® clinical chemistry system.

Jan M. Tauer

Andrea M. Tasker Regulatory Affairs and Compliance Manager June 27, 2005

P 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)

AFC

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K052015

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.