Clinical Chemistry – The Sentinel Clin Chem Cal is a device intended for medical purposes for use in pancreatic amylase and cholinesterase assays to establish points of reference that are used in the determination of values in the measurement of pancreatic amylase and cholinesterase in human serum and plasma.

Device Description

The Sentinel Clin Chem Cal is a device intended for medical purposes for use in pancreatic amylase and cholinesterase assays to establish points of reference that are used in the determination of values in the measurement of pancreatic amylase and cholinesterase in human serum and plasma. Sentinel Clin Chem Cal contains the analytes in human serum matrix. The analytes consist of pancreatic amylase and cholinesterase.

AI/ML Overview

The provided text describes the acceptance criteria and the study that proves the device (Sentinel Clin Chem Cal) meets the acceptance criteria for Calibrator Shelf-life Stability and Calibrator After Reconstitution Stability.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and the Reported Device Performance

Parameter	Acceptance Criteria	Reported Device Performance
Calibrator Shelf-life Stability	95% to 105% recovery compared to Time zero	Calibrators showed stability for up to 33 months (See Table 1). For Pancreatic Amylase, % Recovery ranged from 97.2% to 103.6%. For Cholinesterase, % Recovery ranged from 97.9% to 101.8%. The claimed shelf-life is 24 months from the date of manufacture.
Calibrator After Reconstitution Stability (2-8°C)	100% ± 7% recovery (i.e., 93-107%) between days	Pancreatic Amylase (Table 2): After 2 days at 2-8°C, %R (2d vs To) for the three lots tested were 103%, 102%, and 101%, respectively. All within the 93-107% range. Cholinesterase (Table 3): After 2 days at 2-8°C, %R (2d vs To) for the three lots tested were 100%, 100%, and 100%, respectively. All within the 93-107% range.
Calibrator After Reconstitution Stability (-20°C)	100% ± 7% recovery (i.e., 93-107%) between days	Pancreatic Amylase (Table 2): After 14 days at -20°C, %R (30d vs To) for the three lots tested were 104%, 103%, and 102%, respectively. All within the 93-107% range. Cholinesterase (Table 3): After 14 days at -20°C, %R (30d vs To) for the three lots tested were 100%, 100%, and 100%, respectively. All within the 93-107% range.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Calibrator Shelf-life Stability: One lot of Sentinel Clin Chem Cal was used for the test. The stability was monitored prospectively by testing at multiple time points through a minimum of 30 months (and reported up to 33 months). The origin of the data is not explicitly stated but is implicitly from the manufacturer, Sentinel CH. Srl in Milan, Italy.
Calibrator After Reconstitution Stability: Three lots of calibrator were used for the test (one expired from 13 months, one expired from 8 months, and one still in validity). The study was prospective in nature, assessing stability at specific time points after reconstitution. The origin of the data is implicitly from the manufacturer, Sentinel CH. Srl in Milan, Italy.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This device is a calibrator for in-vitro diagnostic assays, not an AI or imaging device requiring expert ground truth for interpretation. The ground truth for this device's performance is based on analytical measurements against defined reference standards and the inherent property of a calibrator to maintain its assigned value over time and under specified conditions.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. This is not an imaging or diagnostic device requiring adjudication of human-interpreted results.

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

Not applicable. This is not an AI-assisted diagnostic device.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

Not applicable. This is an IVD calibrator, not an algorithm. The "standalone" performance is equivalent to the reported analytical performance of the calibrator itself.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The "ground truth" for the calibrator's assigned values and stability assessments is based on:

Traceability to Reference Standards: The Pancreatic Amylase is traceable to IFCC EPS / 37 °C using $\varepsilon$ p-Nitrophenol. Cholinesterase is traceable to DGKC Butyrylthiocholine 37 °C using $\varepsilon$ Hexacyano-ferrate (III).
Methodology of Value Assignment: Assigned values are determined by taking the mean of measurements from multiple replicates across different instruments (Hitachi 717 and Abbott ARCHITECT® c8000), calibrated against a previous calibrator lot. This establishes the initial "true" or assigned value.
Recovery Method: For stability studies, the performance is measured as a percentage recovery compared to the "time zero" measurement, which serves as the reference or ground truth for that specific lot.

8. The sample size for the training set

Not applicable. This is not a machine learning or AI device that typically requires a 'training set'.

9. How the ground truth for the training set was established

Not applicable. There is no training set for this type of device.

Summary

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001 25 2005

510(k) Summary

Submitter's Name/Address Sentinel CH. Srl Via Principe Eugenio 5 20155 Milan - ITALY

Contact Person

Mr. Davide Spada Application Specialist Telephone: +39 02 345514.1 Facsimile: +39 02 345514.64 E-Mail: spada@sentinel.it

Date of Preparation of this Summary:	May, 28 2005
Device Trade or Proprietary Name:	Sentinel Clin Chem Cal
Device Common/Usual Name or Classification Name:	Calibrator
Classification Number/Class:	JIX/Class II

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: _KOS 1452

Test Description:

The Sentinel Sentinel Clin Chem Cal is a device intended for medical purposes for use in pancreatic amylase and cholinesterase assays to establish points of reference that are used in the determination of values in the measurement of pancreatic amylase and cholinesterase in human serum and plasma.

Intended Use:

Sentinel Clin Chem Cal must be used only for the calibration of clinical chemistry tests.

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Description of the Calibrator Material:

Sentinel Clin Chem Cal contains the analytes in human serum matrix. The analytes consist of pancreatic amylase and cholinesterase.

Assigned Values and Value Assignment Process:

Four vials of calibrator are reconstituted by weight (acceptability 2.970-3.030 g) following the Instruction for Use.

To evaluate vial variability, Pancreatic Amylase is assayed in three replicates on each vial and %CV is calculated for each vial. If %CV is equal to or greater than 4.5%, the vial is discarded from the analysis. At least 2 vials of calibrator can be used. If more than 3 vials are discarded, another set of four calibrator must be used.

The pool of all accepted vials is aliquoted in small volumes and stored at -20 ℃.

The Pancreatic Amylase and Cholinesterase assay are calibrated against the previous calibrator lot, stored at 2-8 ℃ and freshly reconstituted. During each testing run, two levels (normal and abnormal) of control materials are assayed to ensure the effectiveness of the measurements.

For three consecutive days (three runs), three replicates of Pancreatic Amylase and Cholinesterase are assayed on Hitachi 717. The average of all replicates is calculated (X1).

Pancreatic Amylase and Cholinesterase are also assayed on Abbott ARCHITECT® c8000 . Five vials of freshly reconstituted by weight vials are assayed in five replicates on c8000. The average of all replicates is calculated (X2).

The assigned value (Xm) is the mean of the two average: Xm=(X1+X2)/2

Directions for Use:

Refer to Draft Calibrator Labeling on page 17

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Performance Characteristics:

1. Precision/Reproducibility
  N/A

2. Linearity/assay reportable range

N/A

3. Traceability (controls, calibrators, or method)

The Sentinel Clin Chem Cal is traceable to the following referenced standards:

	Analyte	Method	Standardization
AmyP	PancreaticAmylase	IFCC EPS / 37 °C	$\varepsilon$ p-Nitrophenol
ChE	Cholinesterase	DGKC Butyrylthiocholine37 °C	$\varepsilon$ Hexacyano-ferrate (III)

4. Detection limit (functional sensitivity)

N/A

5. Analytical specificity

N/A

6. Assay cut-off

N/A

7. Calibrator Shelf-life Stability

The calibrator shelf-life stability was determined by the recovery method on one lots of Sentinel Clin Chem Cal. One lot of test calibrator were stored at 4℃. At the time of analysis was reconstituted with distilled water. Percent recovery was calculated for each calibrator level by dividing the result of the test calibrator at

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time zero by the result of control calibrators at every testing point. At each testing point, fresh reagent, control calibrators, and test calibrators were analyzed. Calibrators were tested at multiple test points through a minimum of 30 months. Target recovery was 95% to 105% for the test calibrators as compared to the Time zero. Results are found in Table 1.

The results show the calibrators are stable for up to 33 months. The resulting claim is 24 months from date of manufacture.

Since the calibrator is purchased from Roche which is the Predicate Device for ビ the Sentinel Clin Chem Cal, Shelf life of the calibrator is the same as the Predicate Device.

8. Calibrator After Reconstitution Stability

After Reconstitution stability was assessed on three lots of calibrator: one expired from 13 months (expiry date + 13 months), one expired from 8 months (expiry date + 8 months) and one still in validity.

The calibrator after reconstitution stability was determined by the recovery method. Percent recovery was calculated for each calibrator analyte by dividing the results of the reconstituted vial stored at 2 -- 8 ℃ after 2 days, and at -20 ℃ after 14 days by the results of a freshly reconstituted vial of the same lot. At each test point fresh reagents were used.

Acceptance criteria is 100 ± 7%.

Results are found in Table 2 and Table 3.

Stability of reconstituted material: 2 days at 2 to 8 °C or 14 days at -20 °C if aliquoted in small volumes.

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Table 1 Sentinel Sentinel Clin Chem Cal Real Time Stability - Pancreatic Amylase and Cholinesterase

Time	Cholinesterase(U/L)	P - Amylase(U/L)
0 Monhts	4581	148.8
1 Mo	4618	150.6
% Rec	100.8	101.2
4 Mo	4627	151.3
% Rec	101.0	101.7
8 Mo	4590	152.4
% Rec	100.2	102.4
11 Mo	4636	150.6
% Rec	101.2	101.2
14 Mo	4503	144.6
% Rec	98.3	97.2
17 Mo	4595	151.0
% Rec	100.3	101.5
20 Mo	4485	151.5
% Rec	97.9	101.8
23 Mo	4508	147.2
% Rec	98.4	98.9
26 Mo	4576	150.0
% Rec	99.9	100.8
29 Mo	4663	154.2
% Rec	101.8	103.6
33 Mo	4636	148.7
% Rec	101.2	99.9

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Table 2

Sentinel Sentinel Clin Chem Cal After Reconstitution Stability - Pancreatic Amylase

product:	Clin chem Cal	ref 16550	at 2-8°C and - 20°C					SENTINEL
Used Material
Instrument.	HITACHI 717				17631	lot	31147	exp : mar/2005
reagent lot	Pancreatic amylase						exp : jun/2006
	Clin Chem Cal				REF 16550	lot	P0690
	Clin Chem Cal			REF 16550			lot	3 differents lots
Calibration/Check system:				Acceptability criteria1) The D% (factor and controls) between days must be less 5%2) all replicates of controls must be in the target range
Stability after recostitution Calibrator:							1) The % Recovery (%R) between days must range 93-107%
				Calibration /Check system (reagents+ instruments)			time 0	2 days(2-8°C)	14 days(-20°C)
sample	supplier	lot	Expired date	time ofvalutation	expectedvalue	replicates	value	value	%R(2d vs To)	value	D%(30d vs To)
blank						Dabs	0.0005	0.0002		0.0000
						Dabs	0.0473	0.0449		0.0455
calibrator	Sentinel	P0690	jun / 2006	2 months aftermanufacturing	151	factor	3226	3378	4.7%	3319	2.9%
Precinom U	Roche	apr/2004	still valid	12 monthsaftermanufacturing	39 ±7	1	42	40		43
						2	39	39		37
						3	37	41		38
Precipath U	roche	feb/2004	still valid	14 monthsaftermanufacturing	102 ± 18	1	108	103		107
						2	106	107		102
						3	105	105		109
mean		control		Precinom UPrecipath U		Rocheroche	apr/2004feb/2004		39.3	40.0	1.7%	39.3	0.0%
								106.3	105.0	-1.3%	106.0	-0.3%
The factor and controls meet the criteria of acceptability					P YES	* NO
			3 lots calibrator stability after recostitution					time 0	2 days(2-8°C)		14 days(-20°C)
sample	supplier	lot	Expired date	time ofvalutation	expectedvalue	replicates	value	value	%R(2d vs To)	value	%R(30d vs To)
		M0750	sep/2002	13 monthsexpired	183target NA	1	191	197		204
						2	184	201		198
						3	199	194		194
Clin Chem Cal	Sentinel	M0796	jan/2003	8 monthsexpired	172target NA	1	180	185		183
						2	173	187		188
						3	186	178		185
		P0690	jun/2006	still valid	151target NA	1	153	155		154
						2	150	155		157
						3	153	150		153
Mean		calibrator	Clin Chem Cal	Sentinel	M0750M0796P0690		191.3	197.3	103%	198.7	104%
							179.7	183.3	102%	185.3	103%
							152.0	153.3	101%	154.7	102%
Conclusion			The calibrator meet the acceptability criteria and the stability after recostitution is :2 days at 2-8°C or 14 days at -20°C
QC (date Signature)		02/10/2003
									Ezio MarelliTechnical ManagerSENTINEL CH.
		SENTINEL		SENTINEL For - Via Pens no Cugemo 6				20135 Milan - 400V
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Sentinel Clin Chem Cal 510(k)
May 28, 2005

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Table 3 Sentinel Sentinel Clin Chem Cal After Reconstitution Stability – Cholinesterase

			STABILITY AFTER RECOSTITUTION							SENTINEL
product:	Clin chem Calref 16550at 2-8°C and - 20°C
Instrument.	HITACHI 717
reagent lot		Cholinesterase liquid			REF 17019A	lot	30863			exp : Oct/2004
	Clin Chem Cal				REF 16550	lot	P0690exp : jul/2006
	Clin Chem Cal			REF 16550lot			3 differents lots
Calibration/Check system:				Acceptability criteria1) The D% (factor and controls) between days must be less 5%2) all replicates of controls must be in the target range
Stability after recostitution Calibrator:					1) The % Recovery (%R) between days must range 93-107%
			Calibration /Check system (reagents+ instruments)				time 0	2 days(2-8°C)		14 days(-20°C)
sample	supplier	lot	Expired date	time ofvalutation	expectedvalue	replicates	value	value	D%(2d vs To)	value	D%(30d vs To)
blank						Dabs	-0.0036	-0.0029		-0.0031
calibrator	Sentinel	P0690	jun / 2006	2 months aftermanufacturing	5920	Dabsfactor	0.0399-87774	-0.0396-86817	-1.1%	-0.0407-84724	-3.5%
Precinorm U	Roche	apr/2004	still valid	12 monthsaftermanufactoring	6700 ± 1100	123	672166416734	664167016851		663867036890
Precipath U	roche	feb/2004	still valid	14 monthsaftermanufacturing	6300 ± 1000	123	627862736185	628663406204		624562696265
mean	control		Precinorm U	Roche	apr/2004		6698.7	6731.0	0.5%	6743.7	0.7%
			Precipath U	roche	feb/2004		6245.3	6276.7	0.5%	6259.7	0.2%
The factor and controls meet the criteria of acceptability				P YES	* NO
			3 lots calibrator stability after recostitution				time 0	2 days(2-8°C)		14 days(-20°C)
sample	supplier	lot	Expired date	time ofvalutation	expectedvalue	replicate	value	value	D%(2d vs To)	value	D%(30d vs To)
		M0750	sep/2002	13 monthsexpired	4850target NA	123	467747854891	467747854891		486847544661
Clin Chem Cal	Sentinel	M0796	jan/2003	8 monthsexpired	5010target NA	123	500150145104	500150145104		510150074980
		P0690	jun/2006	still valid	5920target NA	123	582158115945	582158115945		590458015901
Mean	calibrator		Clin Chem Cal	Sentinel	M0750M0796P0690		4784.3	4784.3	100%	4761.0	100%
							5039.7	5039.7	100%	5029.3	100%
							5859.0	5859.0	100%	5868.7	100%
Conclusion			The calibrator meet the acceptability criteria and the stability after recostitution is :2 days at 2-8°C or 14 days at -20°C
QC (date Signature)		02/10/2003								Ezio MarelliTechnical ManagerSENTINEL CH.
		SENTINELDACNU	SENTINEL CHVia Principe Eugenio, 5 20155 Milano, ItalyPh. +39(02) 4655141 Fax +39(02) 46551454 www.sentinel.it sentinel@sentinel.it

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OCT 2 5 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Davide Spada Application Specialist Sentinel CH S.r.l. Via Principe Eugenio, 5 20155 Milan-Italy

Re: K051452

Trade/Device Name: Sentinel Clinical Chemistry Calibrator Regulation Number: 21 CFR 862.1150 Regulation Name: Multi-Analyte Calibrator Regulatory Class: Class II Product Codc: JIX Dated: August 5, 2005 Received: August 19, 2005

Dear Mr. Spada:

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 adultcration.

If your device is classified (sec 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 complics 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) I ins letter whilanon you to ough indias of substantial equivalence of your device to a legally premation notification: "The 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 guestions on the promotion and advertising of your device, please contact the Office of In of quostions on the promotion 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 I ou may oount other generers, 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.

Sincercly yours,

Alberto Gutierrez Ph.D.

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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510(k) Number (if known): ي 05 1452

Sentinel Clin Chem Cal Device Name:

Indications For Use:

Prescription Use
(Part 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)

Lucy Phillips
Division Sign-Off

Page 1 of 1

Office of In Vitre Diagnostic Device Evaluation and Sulety

051450

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.