ATAC CALCIUM REAGENT AND ATAC CALIBRATOR by ELAN DIAGNOSTICS

The ATAC Calcium Reagent Kit, the ATAC Calibrator and the ATAC 8000 Random Access Chemistry System are intended for use as a system for the quantitation of calcium in serum and plasma. Calcium results are for the diagnosis and treatment of parathyroid disease, a variety of bone disease and tetany (intermittent muscular contractions or spasms).

Device Description

The ATAC Calcium Reagent Kit is intended for the quantitative determination of calcium in serum and plasma. Calcium results are for the diagnosis and treathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms). The ATAC Calcium Reagent determines calcium through binding by o-cresolphthalein complexone at alkaline pH. The resulting increase in absorbance at 578 nm is proportion al to the calcium concentration of the sample.

AI/ML Overview

The provided text describes the ATAC Calcium Reagent Kit and studies demonstrating its performance. However, it does not explicitly define "acceptance criteria" as a set of specific thresholds for the reported performance metrics. Instead, it presents the results of various validation studies and implicitly suggests that these results are deemed acceptable for the device's intended use and demonstrate substantial equivalence to a predicate device.

Here's an analysis of the provided information, framed to address your request for acceptance criteria and the supporting study, even if the "acceptance criteria" are implied rather than explicitly stated.

Interpretation of Acceptance Criteria:

Given that this is a 510(k) submission, the "acceptance criteria" are implicitly tied to demonstrating substantial equivalence to a predicate device (HiChem™ Calcium Reagent Kit) and proving that the device performs safely and effectively for its intended use. While explicit numerical cut-offs aren't listed as "acceptance criteria," the reported performance metrics in the studies are implicitly deemed acceptable by the manufacturer for this purpose.

1. Table of Acceptance Criteria and Reported Device Performance

Note: As explicit "acceptance criteria" are not provided, the table below lists the performance parameters evaluated and their reported results. The implied acceptance is that these results are clinically acceptable and demonstrate substantial equivalence to the predicate device.

Performance Parameter	Implied Acceptance Criteria (based on common IVD standards and predicate equivalence)	Reported Device Performance (ATAC Calcium Reagent Kit)
Linearity/Recovery	Demonstrated linearity across the usable range; high correlation (r > 0.99)	Linear from 0.2 to 15 mg/dL; r = 0.9984; (ATAC Recoveries) = 1.069 x (Standard Value); sy.x = 0.32 mg/dL; n = 21 (for regression)
Precision (Within Run)	Low %CV for different serum levels (e.g., < 2-3%)	Serum 1 (7.4 mg/dL): 1SD = 0.11 mg/dL, %CV = 1.4% Serum 2 (10.4 mg/dL): 1SD = 0.20 mg/dL, %CV = 1.9% Serum 3 (13.2 mg/dL): 1SD = 0.17 mg/dL, %CV = 1.3%
Precision (Total)	Low %CV for different serum levels (e.g., < 2-3%)	Serum 1 (7.4 mg/dL): 1SD = 0.14 mg/dL, %CV = 1.9% Serum 2 (10.4 mg/dL): 1SD = 0.21 mg/dL, %CV = 2.0% Serum 3 (13.2 mg/dL): 1SD = 0.23 mg/dL, %CV = 1.8%
Method Comparison (Correlation with Competitive Reagent)	Strong correlation (r > 0.95) and good agreement with a predicate or established method	ATAC 8000 = 0.7 mg/dL + 0.944 x Competitive Reagent; r = 0.942; n = 120; range = 6.4 - 11.5 mg/dL
Detection Limit	Ability to detect low clinically relevant concentrations	0.2 mg/dL (documented by repetitive assay of a diluted serum pool; SD of 30 replicates was 0.05 mg/dL)
Reagent Stability (On-board)	Demonstrated stability for claimed period; imprecision within acceptable limits	14-day stability documented; total imprecision of calcium recoveries over test period was < 0.2 mg/dL or 2%
Calibration Stability	Demonstrated stability for claimed period; imprecision within acceptable limits	4-hour stability documented; total imprecision of calcium recoveries over test period was < 0.2 mg/dL or 2%

Details of the Study Proving Device Meets Acceptance Criteria:

The provided document describes a series of studies performed to demonstrate the safety and effectiveness, and specifically the substantial equivalence, of the ATAC Calcium Reagent Kit to a legally marketed predicate device (HiChem™ Calcium Reagent Kit).

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

Linearity Study:
- Sample Size: n = 21 (number of regression points/standards).
- Data Provenance: Not explicitly stated, but likely laboratory-prepared linearity standards.
Precision Study:
- Sample Size: n = 60 for each of the three serum control levels (total 180 individual measurements for precision). These 60 measurements were likely split across two instruments as mentioned ("on two separate instruments").
- Data Provenance: Commercially available control serum.
Method Comparison Study:
- Sample Size: n = 120 patient specimens.
- Data Provenance: Mixed serum and plasma specimens collected from adult patients. The country of origin is not specified but is presumably the US, given the FDA submission. This is a prospective or retrospective collection of patient samples, but the method comparison itself is a prospective analysis.
Detection Limit Study:
- Sample Size: 30 replicates for a within-run precision study.
- Data Provenance: A diluted serum pool.

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

This information is not provided in the document. For in vitro diagnostic devices like reagent kits, "ground truth" is typically established by:

Using reference materials (e.g., for linearity).
Using validated control materials with known target values (e.g., for precision).
Comparing against a predicate device or a well-established, clinically accepted method (e.g., for method comparison).
Pathology or outcome data are not directly applicable here as it's a quantitative measurement of a biomarker.

4. Adjudication Method for the Test Set:

This information is not applicable and therefore not provided. Adjudication methods (like 2+1, 3+1) are typically used in imaging studies where subjective interpretation by multiple readers is involved to establish a consensus ground truth. For a quantitative chemistry assay, the "ground truth" for validation is based on the inherent properties of the reference materials/controls or the results from a comparison method.

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 therefore not provided. MRMC studies are specific to imaging and AI-assisted interpretation, where human readers interact with AI. The ATAC Calcium Reagent Kit is a standalone chemical assay, not an imaging device or an AI-powered diagnostic tool requiring human interpretation.

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

Yes, the studies described are solely for the standalone performance of the ATAC Calcium Reagent Kit on the ATAC 8000 Random Access Chemistry System. There is no human-in-the-loop component in the "performance" described; it's the analytical performance of the reagent and instrument system.

7. The Type of Ground Truth Used:

For Linearity: The ground truth was established by standard values of linearity standards.
For Precision: The ground truth was established by the labeled target values of commercially available control serum.
For Method Comparison: The ground truth was effectively established by the results from a "competitive reagent" (another commercially available method), which serves as the reference method in this comparison to demonstrate substantial equivalence.
For Detection Limit: The ground truth was established by the known dilution of a serum pool and the statistical variation measured at that low concentration.

8. The Sample Size for the Training Set:

This information is not applicable and therefore not provided. This device is a chemical reagent, not a machine learning or AI model that requires a "training set" in the computational sense. The "development" or "optimization" of such a reagent kit might involve many experiments, but these are not referred to as a "training set" in this context.

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

This information is not applicable as there is no "training set" in the context of this device.

Summary

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

K023/05

MAR 1 3 2003

Image /page/0/Picture/2 description: The image shows the word "élan" in a stylized font. The "é" has a unique design, with the top half of the letter being a solid black circle and the bottom half being a white circle. Above the "é" is a black parallelogram with a textured pattern. The rest of the word "lan" is written in a cursive font.

1075 W. Lambert Road Building D Brea, California 92821 T (714) 672 3553 F (714) 672 3554

SUMMARY OF 510(K) SAFETY AND EFFECTIVENESS INFORMATION

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The ATAC Calcium Reagent Kit is substantially equivalent to the HiChem" Calcium Reagent Kit, product no. 88815, which is marketed by Elan Inc. of Brea California. The effectiveness of ATAC Calcium Reagent Kit on the ATAC 8000 Random Access Chemistry System is shown by the following studies.

The recovery of calcium using the ATAC Calcium Reagent is linear from 0.2 to 15 mg/dL, as shown by the recovery of linearity standards that span the usable range. Regression statistics, which are forced through the origin, compare standard recoveries to standard values. These statistics are shown below.

r = 0.9984, (ATAC Recoveries) = 1.069 x (Standard Value), sy.x = 0.32 mg/dL, n = 21

Precision is demonstrated by the replicate assay of commercially available control serum on two separate instruments, Precision statistics, calculated analogous to the method described in NCCLS Guideline EP3-T, are shown below.

Sample	n	mean	Within Run		Total
			1SD	%CV	1SD	%CV
Serum 1	60	7.4	0.11	1.4%	0.14	1.9%
Serum 2	60	10.4	0.20	1.9%	0.21	2.0%
Serum 3	60	13.2	0.17	1.3%	0.23	1.8%

Mixed serum and plasma specimens, collected from adult patients, were assayed for calcium using the ATAC 8000 Random Access Chemistry System and another commercially available method. Results were compared by least squares linear regression and the following statistics were obtained.

ATAC 8000 = 0.7 mg/dL + 0.944 x Competitive Reagent r = 0.942 n = 120 range = 6.4 - 11.5 mg/dL

The detection limit of 0.2 mg/dL is documented through the repetitive assay of a diluted serum pool. The observed standard deviation of a 30 replicate within run precision study was 0.05 mg/dL. Consequently, the detection limit is reported as twice the round-off error of the assay.

The 14 day on board reagent stability and 4 hour calibration stability claims are documented through the assay of serum controls over the claimed periods. In all cases, the total imprecision of calcium recoveries over the test than 0.2 mg/dL or 2%.

Wynn Staley

Wynn Stocking Manager of Regulatory Affairs Elan

510(k) Notification, ATAC Calcium Reagent Kit, 17 September, 2002, p 49

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

Image /page/1/Picture/1 description: The image shows a logo for the Department of Health & Human Services - Visa. The logo features a stylized image of an eagle with three lines representing its wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - VISA" is arranged in a circular pattern around the eagle image.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Wynn Stocking Regulatory Affairs Manager Elan Diagnostics 1075 W. Lambert Road Building D Brea, CA 92821

MAR 1 3 2003

Re: K023105

Trade/Device Name: ATAC Calcium Reagent Regulation Number: 21 CFR 862.1145 Regulation Name: Calcium test system Regulatory Class: Class II Product Code: CIC Dated: January 21, 2003 Received: January 22, 2003

Dear Mr. Stocking:

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).

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

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,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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

510(k) Number (if known):

K023105

Device Name:

ATAC Calcium Reagent

Indications for Use:

This reagent is intended to be used by trained personnel in a professional setting and is not intended for home use.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Jean Cooper

(Division Sign-Off) Division of Clinical Laboratory De 510(k) Number .

Prescription Use L (Per 21 CFR 801.109)

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.1145 Calcium test system.

(a)
Identification. A calcium test system is a device intended to measure the total calcium level in serum. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).(b)
Classification. Class II.