The VALIDATE Chem 4 Calibration Verification Test Set is used by trained laboratory professionals for quantitatively verifying calibration, validating reportable ranges, and determining linearity of automated, semi-automated and manual chemistry systems for the following analytes: alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase, creatine kinase, gamma-glutamyl transferase, lactate dehydrogenase, lipase, total bilirubin and direct bilirubin.

Device Description

VALIDATE Chem 4 Calibration Verification Test Set contains purified enzymes in a solution of bovine albumin stabilized with ethylene glycol. Multiple levels are provided to establish the relationship between theoretical operation and actual performance of each of the included analytes. Each set contains six (6) levels, including zero. Each bottle contains 5 milliliters.

AI/ML Overview

This document describes the premarket notification (510(k)) for the VALIDATE Chem 4 Calibration Verification Test Set. The primary goal of the study was to demonstrate substantial equivalence to predicate devices, not to establish specific acceptance criteria for standalone performance and then prove the device meets them. Instead, the "acceptance criteria" are implied by the demonstration of strong correlation and similar regression characteristics compared to already-marketed equivalent devices.

Here's an analysis based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly state quantitative acceptance criteria in the typical sense (e.g., "sensitivity must be >X%"). Instead, the performance is demonstrated through comparison with predicate devices, using linear regression analysis and correlation coefficients. The implied "acceptance criteria" for substantial equivalence are high correlation coefficients (close to 1) and regression equations that indicate a similar relationship between the test set and the predicate.

Implied Acceptance Criteria for Substantial Equivalence and Reported Device Performance:

Analyte	Implied Acceptance Criterion (Correlation Coefficient `r` near 1)	VALIDATE Chem 4 vs Predicate 1 (DOCUMENT Enzyme Linearity Test Set)	VALIDATE Chem 4 vs Predicate 2 (DOCUMENT Total/Direct Bilirubin Test Set)	VALIDATE Chem 4 vs Predicate 3 (Sigma Diagnostics Lipase LIN-TROL)
ALT	Ideally `r` > 0.99 (high correlation)	`r` = 0.999945	N/A	N/A
AST	Ideally `r` > 0.99 (high correlation)	`r` = 0.99964	N/A	N/A
GGT	Ideally `r` > 0.99 (high correlation)	`r` = 0.99995	N/A	N/A
CK	Ideally `r` > 0.99 (high correlation)	`r` = 0.99113	N/A	N/A
LD	Ideally `r` > 0.99 (high correlation)	`r` = 0.99971	N/A	N/A
ALP	Ideally `r` > 0.99 (high correlation)	`r` = 0.99999	N/A	N/A
AMY	Ideally `r` > 0.99 (high correlation)	`r` = 0.99998	N/A	N/A
LIP	Ideally `r` > 0.99 (high correlation)	N/A (compared to specific Lipase predicate)	N/A	`r` = 0.99879
Total Bilirubin	Ideally `r` > 0.99 (high correlation)	N/A (compared to specific Bilirubin predicate)	`r` = 0.99956	N/A
Direct Bilirubin	Ideally `r` > 0.99 (high correlation)	N/A (compared to specific Bilirubin predicate)	`r` = 0.99627	N/A

Note: The regression equations (Y = intercept + slope(X)) are also part of the comparison, aiming for slopes close to 1 and intercepts close to 0, which further indicates equivalence. The table shows these for each comparison, and they generally align with this goal.

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

Sample Size: The document does not explicitly state the numerical sample size (number of test instances, runs, or measurements) for the test set. It mentions "pre-production lots of VALIDATE Chem 4 Calibration Verification Test Set" were used. For calibration verification devices, the "sample size" typically refers to the number of levels tested (which is 6, including zero, for the VALIDATE Chem 4 Test Set and its predicates) and the number of replicates performed at each level, but this detail is not provided.
Data Provenance: The data comes from internal testing by Maine Standards Company, LLC, comparing their device against predicate devices on a "Roche Diagnostics Hitachi 911 instrument system." The country of origin of the data is implicitly the United States, given the submitter's address. The study is a prospective comparison of a new device against existing predicate devices.

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

This type of information (number of experts, their qualifications for establishing ground truth) is not applicable to this submission. This is a technical performance study for an in vitro diagnostic (IVD) calibration verification device, not a diagnostic imaging or clinical decision support device requiring human expert consensus for "ground truth." The "ground truth" for this device is the known concentrations or values of the analytes in the predicate devices, which are themselves established through standardized analytical methods.

4. Adjudication Method for the Test Set

Not applicable. As explained above, this is a technical performance study comparing analytical values, not a study requiring human adjudication for diagnostic discrepancies.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a MRMC comparative effectiveness study was not done. This type of study is typically performed for diagnostic devices where human readers interpret results (e.g., radiologists reading images) and the AI's impact on reader performance is being evaluated. This submission is for an in vitro diagnostic (IVD) calibration verification test set, which is an analytical tool, not a diagnostic interpretation tool requiring human reader involvement in the same way.

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

Yes, a standalone performance assessment was conducted. The entire study is essentially a standalone performance evaluation of the VALIDATE Chem 4 Calibration Verification Test Set. It evaluates the device's ability to correlate linearly with established predicate devices when run on a specific instrument system (Roche Diagnostics Hitachi 911), without human interpretation influencing the measurement outcomes. The "performance" here refers to its analytical characteristics (correlation, linearity) relative to the predicate devices.

7. The Type of Ground Truth Used

The "ground truth" for this study is not clinical outcomes or pathology. It is the known analytical values and linearity performance of the predicate devices. The predicate devices themselves are accepted standards for calibration verification and linearity assessment. Therefore, the "ground truth" is established by the analytical performance of the legally marketed predicate devices.

8. The Sample Size for the Training Set

Not applicable. This submission is for an IVD device that does not use machine learning or AI algorithms requiring a "training set." The device is a chemical reagent set, and its "performance" is determined by its inherent analytical properties when measured, not by being "trained" on data.

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

Not applicable. As stated in point 8, there is no training set for this device.

Summary

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MAINE STANDARDS COMPANY, LLC

AUG 2 0 2001

510(k) SUMMARY

"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 assigned 510(k) number is: Holalao .."

Submitter:	Maine Standards Company
Address:	765 Roosevelt TrailWindham, ME 04062
Telephone:	207-892-1300
Fax:	207-892-2266
Contact:	Christine Beach, Mgr. RA/QA

Summary prepared on: June 29, 2001

Proprietary Name:	VALIDATE Chem 4 Calibration Verification Test Set
Common Name:	Calibration Verification
Classification Name:	Calibrator, Multi-Analyte

Predicate Devices:

DOCUMENT Enzyme Linearity Test Set, K932458, manufactured by 1. CASCO NERL Diagnostics.
DOCUMENT Total/Direct Bilirubin Test Set, K924493, manufactured by 2. CASCO NERL Diagnostics.
Lipase LIN-TROL, K863751, manufactured by Sigma Diagnostics, Inc. ന്

Device description: VALIDATE Chem 4 Calibration Verification Test Set contains purified enzymes in a solution of bovine albumin stabilized with ethylene glycol. Multiple levels are provided to establish the relationship between theoretical operation and actual performance of each of the included analytes. Each set contains six (6) levels, including zero. Each bottle contains 5 milliliters.

Intended use: VALIDATE Chem 4 Calibration Verification Test Set is intended for in vitro diagnostic use in quantitatively verifying calibration, validating reportable ranges, and determining linearity in automated, semi-automated and manual chemistry systems for the following analytes: alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase, creatine kinase, gamma-glutamyl transferase, lactate dehydrogenase, lipase, total bilirubin, and direct bilirubin.

Office location . 765 Roosevelt Trail . Windham, Maine 04062 Mailing address · P.O. Box 8360 · Portland, ME 04104-8360 Tel. 207-892-1300 · Fax 207-892-2266 · Toll Free 800-377-9684

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Comparison to Predicate Devices:

	VALIDATE	DOCUMENT	DOCUMENT	Sigma
	CHEM 4	Enzyme	Total/Direct	Lipase Lin-Trol
	Calibration	Linearity Test	BilirubinTest Set
	Verification TestSet	Set

Catalog #	10004	E-100	M-107	L 1401
	For in vitro	For in vitro	For in vitro	For estimating the
		diagnostic use in	diagnostic use in	limits of linearity
		the quantitative	the quantitative	and/or calibration
		determination of	determination of	verification of
		linearity in	linearity in	reagent/
		manual,	manual,	instrument
		automated and	automated and	systems.
Intended Use		semi-automated	semi-automated
		ranges, and	chemistry	chemistry
		determining	systems.	systems.
		linearity in
		automated, semi-
		automated and
		manual chemistry
	systems.
	ALT, AST, CK,
	LD, ALP, AMY,	ALT, AST, CK,	Total Bilirubin	Lipase
Analytes	LIP, GGT, Total	LD, ALP, AMY,	Direct Bilirubin
	Bilirubin, and	GGT
	Direct Bilirubin
	Bovine Serum	Bovine Serum		Human Serum
Matrix	Albumin	Albumin	Human Serum	Base with PorcineLipase
	stabilized with	stabilized with	Albumin
	Ethylene Glycol	Ethylene Glycol

Number of				1 Preparation
Levels	6 including Zero	8 including Zero	5	with variousdilutions
Preparation	Liquid,	Liquid,	Liquid,
	ready to use	ready to use	ready to use	Lyophilized
				3 mL freeze dried
Packaging	5.0 mL each level	5.0 mL each level	4.0 mL each level	concentrate
Stability	Until Expiration	Until Expiration	Until Expiration	Until Expiration
Storage	-10 to -20° C.	-10 to -20° C.	-10 to -20° C.	2- 4° C.

The performance of VALIDATE Chem 4 Calibration Verification Test Set solutions on the Roche Diagnostics Hitachi 911 instrument system as compared to DOCUMENT Enzyme Linearity Test Set, DOCUMENT Total/Direct Bilirubin Test Set, and Sigma Diagnostics Lipase LIN-TROL has been shown to be substantially equivalent using pre-production lots of VALIDATE Chem 4 Calibration Verification Test Set. The results of correlation comparisons between the VALIDATE Chem 4 Calibration Verification Test Set and the predicate devices are presented in Table 2.

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K012120

Table 2.	Linear Regression Statistical Comparison between VALIDATE Chem 4Calibration Verification Test Set and the predicate devices.
----------	----------------------------------------------------------------------------------------------------------------------------------

	VALIDATE Chem 4CalibrationVerification Test Set		DOCUMENTEnzyme LinearityTest Set		DOCUMENTTotal/Direct BilirubinTest Set		Sigma DiagnosticsLipase LIN-TROL
Analyte	CorrelationCoefficient(r)	RegressionEquationY=intercept+ slope(X)	CorrelationCoefficient(r)	RegressionEquationY=intercept+ slope(X)	CorrelationCoefficient(r)	RegressionEquationY=intercept+ slope(X)	CorrelationCoefficient(r)	RegressionEquationY=intercept+ slope(X)
ALT	0.999945	6.121 +.928	1.00000	-.141 +.996	N/A	N/A	N/A	N/A
AST	0.99964	4.351 +.949	0.99992	-4.055 +1.022	N/A	N/A	N/A	N/A
GGT	0.99995	-.026 +.989	0.99997	-2.83 +1.006	N/A	N/A	N/A	N/A
CK	0.99113	-8.94 +.937	0.99992	10.354 +.951	N/A	N/A	N/A	N/A
LD	0.99971	8.228 +.953	0.99988	3.402 +.954	N/A	N/A	N/A	N/A
ALP	0.99999	-1.285 +1.001	0.99999	-.59 +1.001	N/A	N/A	N/A	N/A
AMY	0.99998	-3.311 +1.003	0.99979	27.07 +.945	N/A	N/A	N/A	N/A
LIP	0.99879	-1.399 +.965	N/A	N/A	N/A	N/A	0.99935	6.885 +1.001
T. BILI	0.99956	.236 +.952	N/A	N/A	1.00000	.02 +.99X	N/A	N/A
D.BILI	0.99627	.477 +.86	N/A	N/A	0.99999	.027 +1.018	N/A	N/A

Summary:

Linear regression analysis was carried out on recovered values for each analyte and the VALIDATE Chem 4 Calibration Verification Test Set has been shown to be functionally equivalent for calibration verification and linearity assessment to DOCUMENT Enzyme Linearity Test Set, DOCUMENT Total/Direct Billrubin Test Set, and Sigma Diagnostics Lipase LIN-TROL.

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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 circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird in flight, composed of three curved lines.

AUG 2 0 2001

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Christine V. Beach Manager, RA/QA Maine Standards Company, LLC 765 Roosevelt Trail Windham, ME 04062

510(k) Number: K012120 Re: Trade/Device Name: VALIDATE Chem 4 Calibration Verification Test Set Regulation Number: 862.1660 Regulatory Class: Class I, Reserved Product Code: JJY Dated: July 3, 2001 Received: July 6, 2001

Dear Ms. Beach:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent to 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/cdrb/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE STATEMENT

510(k) Number: Kolalao

Device Name: VALIDATE Chem 4 Calibration Verification Test Set

Indications for Use:

Concurrence of CDRH, Office of Device Evaluation (ODE)

× Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use

Kesia Alexander Inchan Cooper
(Division Sign-Off)

Division of Clinical Laboratory Devices
510(k) Number K012120

2-1

Regulation Number and Section

§ 862.1660 Quality control material (assayed and unassayed).

(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.