The Enzyme 5 Calibrator (ENZ 5 CAL) is an in vitro diagnostic product for the calibration of the lactate dehydrogenase (LDI) method on the Dimension Vista® System.

Device Description

ENZ 5 CAL is a liquid, bovine serum albumin based product containing lactate dehydrogenase (chicken heart). The calibrator, one level (Calibrator A), comes packaged with three vials at 1.5 mL per vial. System water, the zero level calibrator does not come packaged with the calibrator.

AI/ML Overview

The provided 510(k) summary for the Dimension Vista® System Enzyme 5 Calibrator (KC350) primarily focuses on establishing substantial equivalence to a predicate device, rather than defining specific acceptance criteria for performance metrics like sensitivity, specificity, or accuracy that would be typical for a diagnostic test.

Instead, the "acceptance criteria" here are related to the stability and traceability of the calibrator, which ensure its fitness for purpose as a calibration tool. The study presented is a series of laboratory experiments designed to demonstrate these characteristics.

Here’s a breakdown of the information based on your request, with an emphasis on how the provided document addresses "acceptance criteria" in this context:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria/Tests	Reported Device Performance/Findings
Stability (Shelf-life)	Target shelf life: 12 months at 2-8°C	Real-time data on file at Siemens Healthcare Diagnostics Inc. supported the assignment of a 12-month shelf life. (Specific recovery percentages or acceptable deviation ranges are not provided in this summary, but the conclusion implies they met internal targets).
Stability (Open Vial)	Stable for 30 days when stored at 2-8°C after opening.	Opened vials (re-capped, stored at 2-8°C, not on instrument) tested on days 0, 15, and 32, with fresh vials tested on days 15 and 32, demonstrated stability for 30 days. (Specific performance metrics like % change are not detailed in this summary).
Stability (Punctured Vial)	Stable for 7 days when stored on board the instrument after puncture.	Vials punctured by the instrument and stored on board were tested on days 0, 3, 8, and 15 (with fresh vials at each point). The results supported a 7-day stability for punctured vials stored on board. (Specific performance metrics like % change are not detailed in this summary).
Traceability	Assigned values traceable to IFCC Reference Measurement Procedure.	Assigned values for ENZ 5 CAL Master pools are traceable to the IFCC Reference Measurement Procedure, performed by a JCTLM-approved Reference Laboratory. Commercial calibrators are assigned values against these Masterpools.
Value Assignment	Consistent and accurate value assignment process.	Anchor Pools assigned by JCTLM-approved lab using IFCC LD RMP. Masterpools assigned from Anchor Pool curves (3 instruments, 3 reagent lots, 9 curves, 45 replicates per level). Commercial calibrators assigned against Masterpools (3 instruments, 3 reagent lots, 9 curves, 45 replicates).

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

Shelf-life Stability: The sample size is not explicitly stated in terms of number of vials or lots. It mentions comparing results of "the product" stored at 2-8°C with "control" stored at -20°C and -70°C. The study is prospective in nature, involving real-time storage and testing. The data provenance is internal to Siemens Healthcare Diagnostics Inc.
Open Vial Stability: "Vials are opened on day zero." The number of vials tested is not specified but the testing schedule (days 0, 15, 32 with fresh vials at 15 and 32) indicates a controlled prospective study. Data provenance: Siemens Healthcare Diagnostics Inc.
Punctured Vial Stability: "Four recapped vials are tested on day zero. Two recapped vials and eight punctured vials are tested on approximately days 3, 8 and 15. Two freshly opened vials are tested at each test point." This indicates a sample size of at least 14 vials for the punctured vial study (4 initial, 2+8 at day 3, 2+8 at day 8, 2+8 at day 15 – though some might be carried over). Data provenance: Siemens Healthcare Diagnostics Inc.
Traceability/Value Assignment:
- Anchor Pools: "Two levels of LD Anchor pools... using pooled human serum samples." The number of individual human serum samples contributing to the pools or the exact volume of the pools is not specified. Value assignment done by a "Reference Laboratory approved by the Joint Committee for Traceability in Laboratory Medicine (JCTLM)." This implies external, expert-validated data.
- Masterpools: "Two levels of LD Masterpools... using an aqueous Bovine Serum Albumin matrix." "Three instruments and three lactate dehydrogenase (LDI) reagent lots... 9 curves... five replicates each of Level 2 and Level 3... resulting in 45 replicates each." This indicates a robust internal study process. Data provenance: Siemens Healthcare Diagnostics Inc.
- Commercial Calibrator: "Three instruments and three LDI reagent lots... 9 standard curves. Five replicates of the commercial lot Calibrator A... yielding 45 replicates." Data provenance: Siemens Healthcare Diagnostics Inc.
- All these studies are prospective relating to the development and validation of the calibrator.

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

For Stability Studies: The document doesn't explicitly mention "experts" for establishing ground truth for the stability test sets in the same way one would for clinical image analysis. The "ground truth" for stability is defined by the initial state of the calibrator and its performance over time relative to that initial state, and often compared against a highly stable reference (like the -70°C control in the shelf-life study). The internal Siemens R&D/Quality Control personnel performing these tests would be the qualified individuals, but their specific qualifications are not detailed.
For Traceability/Value Assignment: The "ground truth" for the LD values in the Anchor Pools is established by a JCTLM-approved Reference Laboratory using the IFCC LD Reference Measurement Procedure. This implies the highest level of expert qualification for method and procedure. The number of individual experts from that lab is not specified but the accreditation of the lab and the procedure itself serve as the expert validation.

4. Adjudication Method for the Test Set

Adjudication methods like "2+1" are typically used for qualitative or subjective assessments (e.g., image interpretation). This device is a quantitative calibrator. Therefore, traditional adjudication methods are not applicable.
For value assignment, the method involves:
- Reference Laboratory adherence to IFCC LD RMP.
- Multiple measurements (e.g., 45 replicates) on different instruments and reagent lots, with the assigned value being the mean of these replicates. This statistical approach across multiple test conditions serves as an objective method to establish the value, rather than subjective adjudication.

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

No, an MRMC study was not done. MRMC studies are relevant for diagnostic devices where human readers interpret results (e.g., radiology, pathology). This device is a chemical calibrator; its performance is assessed through analytical accuracy, precision, and stability, not human interpretation.

6. Standalone (Algorithm Only Without Human-in-the-loop Performance) Study

Yes, the studies described are standalone performance assessments of the calibrator itself. The calibrator's performance (stability, value assignment) is evaluated as a physical reagent product. While it's used with an instrument, the "human-in-the-loop" concept typically refers to human interpretation of diagnostic results, which is not applicable here. The instrument is a tool for measuring the calibrator's characteristics, not a diagnostic algorithm.

7. The Type of Ground Truth Used

The primary ground truth for the lactate dehydrogenase (LD) concentration values is the IFCC LD Reference Measurement Procedure as performed by a JCTLM-approved Reference Laboratory. This is a highly robust, internationally recognized reference method for establishing the true value of an analyte.
For stability studies, the "ground truth" for comparison is the initial, freshly-assigned value of the calibrator, often with highly stable reference materials (-70°C stored controls).

8. The Sample Size for the Training Set

This device is a calibrator, not an AI/ML algorithm that requires a "training set" in the conventional sense. The process of "value assignment" involves careful measurement, but it's not a training phase for a predictive model.
However, if we consider the "training" for the value assignment process, it involves:
- "pooled human serum samples" for Anchor Pools (number not specified).
- "appropriate volume of LD stock" for Masterpools.
- "a stock solution" of LD for commercial calibrators.
- The "training" of the instruments and reagent lots for these assignments involves 9 calibration curves (3 instruments x 3 reagent lots) for Masterpool assignment and another 9 standard curves for commercial calibrator assignment. This ensures robustness across manufacturing and operational variability.

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

As above, given this is not an AI/ML device, a traditional "training set" with ground truth in that context is not applicable.
For the value assignment process, which is analogous to establishing reference points:
- Anchor Pools: Ground truth values were established by a JCTLM-approved Reference Laboratory using the IFCC LD Reference Measurement Procedure. This is the highest level of ground truth for quantitative chemical measurements.
- Masterpools: Values were assigned based on calibration against the Anchor Pools, effectively transferring the ground truth established by the Reference Laboratory.
- Commercial Calibrators: Values are assigned based on calibration against the Masterpools, further disseminating the traceability from the IFCC RMP.

Summary

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K083462

FEB. 2 7 2009

510 (k) Summary for the Dimension Vista® System Enzyme 5 Calibrator (KC350)

510 (k) Number: Lactate dehydrogenase Analyte: Calibrator Material Type of Test: Applicant: Siemens Healthcare Diagnostics Inc P.O. Box 6101 Newark, DE 19714-6101 Helen M. Lee Regulatory Affairs and Compliance Manager Office Phone: 302.631.8706 Fax: 302.631.6299 Proprietary and Established Name: Dimension Vista® System Enzyme 5 Calibrator Requlatory Information: Requlation Section: 21 CFR § 862.1150 - Calibrator Classification: Class II Product Code: JIT - Calibrator, Secondary

Panel: Clinical Chemistry

Intended Use:

The Enzyme 5 Calibrator (ENZ 5 CAL) is an in vitro diagnostic product for the calibration of the lactate dehydrogenase (LDI) method on the Dimension Vista® System.

Device Description:

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Substantial Equivalence Information:

Comparison of the Dimension Vista® System Enzyme 5 Compansen of the Bithoice) to the predicate Dimension® clinical chemistry system Enzyme I Calibrator.

Item	New Device	Predicate Device
Analyte	Lactate dehydrogenase.	Lactate dehydrogenase.
Intended Use	For the calibration of the lactatedehydrogenase (LDI) method on theDimension Vista® System.For in vitro diagnostic use.	For the calibration of the lactatedehydrogenase (LDI) method on theDimension® clinical chemistry system.For in vitro diagnostic use.
Matrix	Liquid bovine serum albumin basewith lactate dehydrogenase ofchicken liver origin.	Liquid bovine serum albumin base withlactate dehydrogenase of chicken liverorigin.
Form	Liquid	Liquid
Traceability	IFCC LD at 37° C primary referencemethod.	IFCC LD at 37° C primary referencemethod

Similarities

Differences

Item	New Device	Predicate Device
CalibratorPackaging	One Level – Calibrator A	Two Levels – Level 2 and Level 3
CalibrationLevels	Two Levels:· System water is Level 1· Calibrator A is Level 2	Three Levels:· Purified Water Diluent or reagentgrade water is Level 1· Level 2 Calibrator· Level 3 Calibrator

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Standard/Guidance Documents Referenced:

1. Guidance: Guidance for Industry Abbreviated 510 (k) Submissions for In Vitro Diagnostic Calibrators; February 22, 1999
1. Standards: CEN 13640 Stability testing of In-Vitro Diagnostic Devices ISO 14971:2000 Medical devices - Application of risk management to medical devices

Performance Characteristics:

1. Stability:
- Shelf-life

Target shelf life for the Dimension Vista® ENZ 5 CAL is 12 months. Calibrator shelf life is determined by comparing results of the product stored at 2-8℃ with control stored at -20°C and -70°C. The method is calibrated each month with the -70°C control material. The 2-8°C and -20°C materials are recovered versus the calibration. Recovery versus time is monitored and percent change over time is determined. Shelf life stability (expiration) dating assignment at commercialization reflects the real-time data on file at Siemens Healthcare Diagnostics Inc.

Open Vial

Vials are opened on day zero. A quantity sufficient for multiple calibrations is removed; the vials are recapped and stored at 2-8°C. Opened vials are tested on days 0, 15 and 32; freshly opened vials are also tested on days 15 and 32. An open vial, not on board the instrument, but recapped and stored at 2-8°C is stable for 30 days.

Punctured Vial

Vials are punctured on day zero with the appropriate quantity removed, leaving sufficient volume for one calibration and dead volume. Punctured vials are recapped and stored at 2-8°. Four recapped vials are tested on day zero. Two recapped vials and eight punctured vials are tested on approximately days 3, 8 and 15. Two freshly opened vials are tested at each test point.

A vial punctured by the instrument and stored on board is stable for seven days.

Traceability: The assigned values for the Dimension Vista® ENZ 5 CAL are assigned from Master pools that are traceable to the IFCC Reference Measurement Procedure.

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Value Assignment:

Anchor Pool

Two levels of LD Anchor pools (Levels 2 and 3) are prepared using pooled human serum samples with normal and elevated LD values; the final target concentrations of Level 2=625 U/L and Level 3=1250 U/L. Values are assigned to the Anchor Pools by the IFCC LD Reference Measurement Procedure by a Reference Laboratory approved by the Joint Committee for Traceability in Laboratory Medicine (JCTLM). Level 1(system water) is assigned a value of zero U/L.

The reference laboratory uses the IFCC LD Reference Measurement Procedure to assign values to the Anchor Pools against calibrators with Reference Measurement Procedure values. The calibrators are prepared by the Reference Laboratory using pooled human sera with Reference Measurement Procedure values for the catalytic concentration of the LD enzyme. They are used for calibration of the Reference Laboratory measurements. The performance and the long term stability of the calibrators have been confirmed by the Reference Laboratory.

The Control used during the assignment of Anchor Pools at the Reference Laboratory is also produced and certified by the Reference Laboratory and is used to ascertain the accuracy of the test runs performed to assign values to the Siemens Anchor Pools.

Masterpool

Two levels of LD Masterpools (Levels 2 and 3) are produced by adding the appropriate volume of LD stock with a known concentration into an aqueous Bovine Serum Albumin matrix. Level 1 of the LD Masterpool, system water, is assigned zero U/L. Levels 2 and 3 of the LD Masterpool are assigned from Anchor Pool calibration curves, using three instruments and three lactate dehydrogenase (LDI) reagent lots. Each instrument is calibrated three times with Anchor Pools for a total of 9 curves. Values for five replicates each of Level 2 and Level 3 of the Masterpool are determined from each Anchor Pool curve, resulting in 45 replicates each for LD Masterpool Level 3. A commercial quality control material, Bio-rad Multiqual QC, assayed for the IFCC LD method, is used as a control in the assignment of the Masterpools. The LD Anchorpools and Masterpools are stored at -70°C.

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3. Value Assignment (cont):

Commercial Calibrator

For commercial calibrators, a stock solution is made by adding LD powder gravimetrically to the stock solution at the target concentration. The commercial calibrator is made by adding calculated quantities of stock solution to the calibrator base at the appropriate concentration for Calibrator A. Before vial filling, the concentration of the calibrator is Masterpools. verified by measuring LD recovery on an instrument calibrated with LD

For value assignment of the commercial calibrators Siemens uses a three point LD Masterpool Linear curve. After filling, the final bottle values are assigned to Calibrator A, using LD Masterpools. The final bottle values of the commercial lots are assigned against the LD Masterpools using three instruments and three LDI reagent lots. Each instrument is calibrated three times with LD Masterpools for a total of 9 standard curves. Five replicates of the commercial lot Calibrator A are tested with each Masterpool curve yielding 45 replicates. The assigned Calibrator A value is the mean of the 45 replicates. A previously assigned commercial lot is used as the control for the assignment of new commercial lots.

Comments on Substantial Equivalence:

Both the proposed Dimension Vista® Enzyme 5 Calibrator and the predicate Dimension® Enzyme I Calibrator are traceable to IFCC reference method and are used to calibrate IFCC traceable lactate dehydrogenase methods.

Conclusion:

The Dimension Vista® Enzyme 5 Calibrator is substantially equivalent to Dimension® Enzyme I Calibrator based upon the information above.

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Image /page/5/Picture/0 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 a stylized image of an eagle with its wings spread.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Siemens Healthcare Diagnostics c/o Helen M. Lee Regulatory Affairs and Compliance Manager 500 GBC Drive M/S 514 Newark, DE 19714-6101

FEB 27 2005

Re: K083462

Trade/Device Name: Dimension Vista® System Enzyme 5 Calibrator (ENZ 5 CAL) Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIT Dated: November 21, 2008 Received: December 15, 2008

Dear Helen M. Lee:

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 iudications for use stated in the enclosure) to legally marketed predicate devices marketed in intelligence 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, Drig 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 registments of insting 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 devive can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In additions FDA may publish further announcements concerning your device in the Federal Parater.

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 COMP 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 220).

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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 (301) 594-3084. 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/dsma/dsmamain.html.

Sincerely yours,

Coty C. He

Courtney C. Harper, Ph.D. Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

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Indication for Use

: 510(k) Number (if known): K083462

Device Name: Dimension Vista® System Enzyme 5 Calibrator (ENZ 5 CAL)

Indication For Use: The ENZ 5 CAL is an in vitro diagnostic product for the calibration of the lactate dehydrogenase (LDI) method on the Dimension Vista® System.

Prescription Use _ ਮ (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Ruthecharlen

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

510(k) K083462

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.