For in vitro diagnostic use in the quantitative determination of alkaline phosphatase (orthophosphoric - monoester phospho-hydrolase, alkaline optimum, EC 3.1.3.1) activity in human serum or plasma on T60 instruments according to the IFCC method.

The Alkaline Phosphatase test system is intended for quantitative in-vitro diagnostic determination of the activity of the enzyme Alkaline Phosphatase in serum and plasma on T60 instrument according to the IFCC method. Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver and bone diseases.

For in vitro diagnostic use on T60 instrument. eCal is used as a calibrator for enzyme tests using methods defined by Thermo Fisher Scientific Oy.

For in vitro diagnostic use for quantitative testing on T60 instrument. Nortrol is a control serum to monitor trueness and precision of the analytes listed in the separate Nortrol value sheet. The given values are valid for T60 Clinical Chemistry Instruments using methods defined by Thermo Fisher Scientific Oy.

For in vitro diagnostic use for quantitative testing on T60 instrument. Abtrol is a control serum to monitor trueness and precision of the analytes listed in the separate Abtrol value sheet. The given values are valid for T60 Clinical Chemistry Instruments using methods defined by Thermo Fisher Scientific Oy.

Device Description

Alkaline Phosphatase (IFCC) plus, codes 981832 and 981833. Common name: Alkaline Phosphatase (IFCC). Classification: Clinical Chemistry, Class II, Product Code: CJE.
eCal, code 981830. Common Name: Calibrator, Multi-Analyte Mixture. Classification: Clinical Chemistry, Class II, Product Code: JIX.
Nortrol, code 981043. Common Name: Multi-analyte Controls (Assayed and unassayed). Classification: Clinical Chemistry, Class I, Product Code: JJY.
Abtrol, code 981044. Common Name: Multi-analyte Controls (Assayed and unassayed). Classification: Clinical Chemistry, Class I, Product Code: JJY.

AI/ML Overview

The acceptance criteria and device performance for the Alkaline Phosphatase (IFCC) Plus test system are detailed below based on the provided 510(k) summary.

1. Table of Acceptance Criteria and Reported Device Performance

Attribute	Acceptance Criteria (Predicate Device Performance)	Reported Device Performance (New Device #1)
Measuring Range	0-1100 U/L	20 - 1000 U/L
Precision (Within run)
Level 68 U/l	SD= 0.9, CV(%)= 1.3	Level 91 U/l: SD= 0.7, CV(%)= 0.7
		Level 127 U/l: SD=0.9, CV(%)=0.7
		Level 374 U/l: SD= 2.0, CV(%)=0.5
		Level 41 U/l: SD= 0.5, CV(%)= 1.1
		Level 810 U/l: SD= 6.6, CV(%)=0.8
Precision (Within run)
Level 148 U/l	SD=2.1, CV(%)= 1.4	Level 91 U/l: SD= 0.8, CV(%)=0.9
		Level 127 U/l: SD= 1.1, CV(%)=0.9
		Level 374 U/l: SD= 2.0, CV(%)=0.5
		Level 41 U/l: SD= 1.4, CV(%)= 3.5
		Level 810 U/l: SD= 2.5, CV(%)=0.3
Precision (Total)
Level 68 U/l	SD= 2.2, CV(%)= 3.2	Level 91 U/l: SD= 2.9, CV(%)= 3.2
		Level 127 U/l: SD= 2.6, CV(%)= 2.0
		Level 374 U/l: SD= 8.4, CV(%)=2.3
		Level 41 U/l: SD= 1.5, CV(%)= 3.7
		Level 810 U/l: SD= 18.5, CV(%)= 2.3
Precision (Total)
Level 148 U/l	SD= 3.8, CV(%)= 2.6	(Not directly comparable levels)
Method Comparison	y = 1.00x + 1.1, r = 0.998, n = 402 (with Advia 1650)	y = 1.023x - 1.61, R = 0.998, N = 154
	y = 1.04x - 14.6, r = 0.998, n = 96 (with reference method)	(Comparison with predicate device)
Limitations (Lipemia)	No significant interference found up to 500 mg/dl	No interference found up to 1000 mg/dL
Limitations (Hemolysate)	No significant interference found up to 500 mg/dl	No interference found up to 300 mg/dl
Limitations (Bilirubin)	No significant interference found up to 25 mg/dl (unspecified type)	Conjugated: No interference up to 58 mg/dL; Unconjugated: No interference up to 21 mg/dL

Note: The table above primarily compares the new device's performance against the predicate device's stated performance, which is implicitly treated as the acceptance criteria for determining substantial equivalence.

2. Sample Size and Data Provenance for the Test Set

Method Comparison (New device vs. Predicate device):
- Sample size (N): 154
- Data Provenance: Not explicitly stated, but given that the submitter is Thermo Fisher Scientific Oy (Finland), it is likely that parts of the study were conducted in Finland or other relevant locations. The data type is prospective, as it involves testing the device against clinical samples.
Limitations (Interference):
- The sample size for interference studies (Lipemia, Hemolysate, Bilirubin) is not specified.
- Data Provenance: Not explicitly stated, but assumed to be from internal studies conducted by Thermo Fisher Scientific Oy. This would be prospective data generated under controlled conditions.

3. Number of Experts and Qualifications for Ground Truth

This document describes an In Vitro Diagnostic (IVD) assay for measuring alkaline phosphatase activity. For such assays, "ground truth" is typically established by:

Reference Methods: The document states the new device is "traceable to the molar absorbance coefficient of p-nitrophenol" and the predicate device is "traceable to the IFCC reference method via patient sample correlation."
Consensus or Clinical Outcomes: For IVD tests, the "ground truth" for patient samples is usually the result obtained from a well-established, often older or gold-standard, clinical laboratory method or a reference laboratory test.
For this specific document: The "ground truth" for the method comparison study (N=154) was the measurements produced by the identified predicate device (Bayer ADVIA 2400 Chemistry System) or the reference method mentioned for the predicate. The document does not mention the involvement of "experts" in the sense of clinicians or radiologists establishing ground truth by medical review or interpretation. The ground truth here is the quantitative measurement provided by the comparative method.

4. Adjudication Method for the Test Set

Not applicable. This is a quantitative diagnostic assay, not an image-based diagnostic or clinical decision-support system requiring adjudication of interpretations by clinical experts. The comparison is based on numerical results.

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

Not applicable. This is an IVD device measuring an enzymatic activity directly, not an AI system assisting human readers in interpreting clinical cases. Therefore, there is no "human readers improve with AI vs without AI assistance" effect to measure.

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

Yes, this study is inherently a standalone performance study. The Alkaline Phosphatase (IFCC) Plus test system, as an IVD, operates autonomously to measure the analyte concentration. Its performance (precision, measuring range, method comparison, limitations) is evaluated based on its own output, independent of human interaction or interpretation beyond running the assay and interpreting the numerical result.

7. Type of Ground Truth Used

The ground truth used for the method comparison study was quantitative measurements obtained from the predicate device (Bayer ADVIA 2400 Chemistry System) or a referenced IFCC method. This is a form of comparative measurement data or reference method equivalency. The internal validation "ground truth" for linearity, precision, and interference would be based on known concentrations or controlled interference levels.

8. Sample Size for the Training Set

The document does not specify a separate "training set" or its sample size. For an IVD assay like this, method development and optimization (which could be analogous to "training") typically involve numerous experiments with various reagents, concentrations, and conditions. However, the document focuses on the validation or test set used for substantial equivalence demonstration.

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

As no specific "training set" is mentioned in the context of machine learning, this question is not directly applicable. For the development of the assay, the "ground truth" during optimization would be established through standard analytical chemistry techniques, using known concentrations of alkaline phosphatase, reference materials, and established biochemical principles (e.g., spectrophotometry for p-nitrophenol formation) to ensure the assay accurately measures the intended activity.

Summary

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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:

Introduction: A.

According to the requirements of 21 CFR 807.92 the following information provides sufficent detail to understand the basis for a determination of substantial equivalence.

B.	Submitter's information
	Name:	Thermo Fisher Scientific Oy
	Address:	Ratastie 2
		P.O. Box 100
		FIN-01621 Vantaa
		Finland
	Phone:	+358 (9) 329 100 tel
	Fax:	+358 (9) 3291 0500 fax
	Contact person:	Päivi Sormunen, Vice President of QRC
	Date of Preparation:	February 13th, 2008
C.	Device name
	Proprietary name:	Alkaline Phosphatase (IFCC) plus, codes 981832
		and 981833
	Common name:	Alkaline Phosphatase (IFCC)
	Classification:	Clinical Chemistry
	Class:	II
	Product Code:	CJE
	Proprietary name:	eCal, code 981830
	Common Name:	Calibrator, Multi-Analyte Mixture
	Classification:	Clinical Chemistry
	Class:	II
	Product Code:	JIX
	Proprietary name:	Nortrol, code 981043
	Common Name:	Multi-analyte Controls (Assayed and unassayed)
	Classification:	Clinical Chemistry
	Class:	I
	Product Code:	JJY
	Proprietary name:	Abtrol, code 981044
	Common Name:	Multi-analyte Controls (Assayed and unassayed)
	Classification:	Clinical Chemistry
	Class:	I
	Product Code:	JJY

Thermo Fisher Scientific Oy

Ratastic 2 P.O. Box 100 FIN-01621 Vantaa Finland

+358 (9) 329 100 tel +358 (9) 3291 0500 fax Y-tunnus 0921547-0 VAT No FI09215470 Domicile Helsinki

www.thermo.com

183 28

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D. Intended Use

Alkaline Phosphatase (IFCC)

eCal

For in vitro diagnostic use on T60 instrument. eCal is used as a calibrator for enzyme tests using methods defined by Thermo Fisher Scientific Oy.

Nortrol

Abtrol

Ratastie 2 P.O. Box 100 FIN-01621 Vantaa Finland

+358 (9) 329 100 tel +358 (9) 3291 0500 fax Y-tunnus 0921547-0 VAT No FI09215470 Domicile Helsinki

ww.thermo.com

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Indications for use E.

For eCal Calibrator, Nortrol and Abtrol see intended use.

Substantial Equivalence F.

Bayer Corporation, model Bayer ADVIA 2400 Chemistry System.

Bayer Corporation item: Bayer ADVIA Alkaline Phosphatase (ALPAMP) assay.

Substantial equivalence -similarities G.

Alkaline Phosphatase (IFCC) Plus is substantially equivalent to other devices legally marketed in United States. We claim equivalence to the Bayer ADVIA Alkaline Phosphatase (ALPAMP) assay (K991576).

Thermo Fisher Scientific Oy

Ratastie 2 P.O. Box 100 FIN-01621 Vantaa Finland

+358 (9) 329 100 tel +358 (9) 3291 0500 fax Y-tunnus 0921547-0 VAT No FI09215470 Domicile Helsinki

www.themo.com

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The following table compares the Alkaline Phosphatase with the predicate device.
Table 1

Attribute	New device #1	Predicate device #1
Intended Use	For in vitro diagnostic use in thequantitative determination ofalkaline phosphatase(orthophosphoric - monoesterphospho-hydrolase, alkalineoptimum, EC 3.1.3.1) activity inhuman serum or plasma on T60instruments according to the IFCCmethod (1).	For in vitro diagnostic use inthe quantitative determinationof alkaline phosphatase inhuman serum or plasma on theADVIA Chemistry systems.Such measurements are usedin the diagnosis and treatmentof hepatobiliary and bonedisease.
Indication for Use	The Alkaline Phosphatase testsystem is intended for quantitativein-vitro diagnostic determinationof the activity of the enzymeAlkaline Phosphatase in serumand plasma on T60 instrumentaccording to the IFCC method.Measurements of alkalinephosphatase are used in thediagnosis and treatment of liverand bone diseases.	See intended use.
Assay Protocol	ALP catalyzes the hydrolysis ofp-nitrophenylphosphate. Theformation of p-nitrophenol inalkaline solution is followed at405 nm.	Alkaline phosphatasehydrolyzes pNPP substrate toform p-nitrophenol. Thereaction isfollowed by the colorimetricmeasurement of the rate offormation of p-nitrophenol at410/478 nm, which isproportional to the alkalinephosphatase activity.
Traceability/Standardization	The Alkaline Phosphatase (IFCC)Plus method is traceable to themolar absorbance coefficient of p-nitrophenol.	The ADVIA AlkalinePhosphatase (ALPAMP)method standardization istraceable to the IFCCreference method via patientsample correlation.
Sample Type	Serum, plasma (Li-heparin)	Serum, plasma (Li-heparin)
Reagent Storage	Reagents in unopened vials arestable at 2...8 °C until theexpiration date printed on the	Unopened reagents are stableuntil the expiration dateprinted on the
Thermo Fisher Scientific Oy	Ratastie 2P.O. Box 100FIN-01621 VantaaFinland	+358 (9) 329 100 tel+358 (9) 3291 0500 fax
Attribute	New device #1	Predicate device #1
	label when protected from light.	product label when stored at2° - 8°C.
Expected Values	Male: 53 - 128 U/l (0.9 - 2.18µkat/l) at 37 °CFemale: 42 - 98 U/l (0.71 - 1.67µkat/l) at 37 °C	45-129 U/L
Instrument	T60 and DPC T60i, DPC T60iKusti	ADVIA® 2400 Chemistrysystem.
Measuring Range	20 - 1000 U/L	0-1100 U/L
Attribute	New device #1	Predicate device #1
Precision	Within run	Within run
	Level 91 U/lSD= 0.7CV(%)= 0.7	Level 68 U/lSD= 0.9CV(%)= 1.3
	Level 127 U/lSD=0.9CV(%)=0.7	Level 148 U/lSD=2.1CV(%)= 1.4
	Level 374 U/lSD= 2.0CV(%)=0.5	Total
	Level 41 U/lSD= 0.5CV(%)= 1.1	Level 68 U/lSD= 2.2CV(%)= 3.2
	Level 810 U/lSD= 6.6CV(%)=0.8	Level 148 U/lSD= 3.8CV(%)= 2.6
	Between run
	Level 91 U/lSD= 0.8CV(%)=0.9
	Level 127 U/lSD= 1.1CV(%)=0.9
	Level 374 U/lSD= 2.0CV(%)=0.5
	Level 41 U/lSD= 1.4CV(%)= 3.5
	Level 810 U/lSD= 2.5CV(%)=0.3
	Total
	Level 91 U/lSD= 2.9CV(%)= 3.2
	Level 127 U/lSD= 2.6CV(%)= 2.0
	Level 374 U/lSD= 8.4CV(%)=2.3
	Level 41 U/lSD= 1.5CV(%)= 3.7
	Level 810 U/lSD= 18.5CV(%)= 2.3
Thermo Fisher Scientific Oy	Ratastie 2P.O. Box 100	Y-tunnus 0921547-0VAT NO FI09215470www.thermo.com
	+358 (9) 329 100 tel+358 (9) 3291 0500 fax	Domicile Helsinki
Attribute	New device #1	Predicate device #1
Method Comparison	$y = 1.023x - 1.61$$R = 0.998$range from 14 to 1752 U/lN = 154	Comparison with Advia 1650(serum):$y = 1.00x + 1.1$$r = 0.998$$n = 402$range: 26 to 693 U/l
		Comparison with referencemethod (serum):$y = 1.04x - 14.6$$r = 0.998$$n = 96$range: 49 to 1050 U/l
Limitations	Lipemia:No interference found up to 1000mg/dL (10 g/l) of Intralipid.	Lipemia (from Intralipid):No significant interferencefound up to 500 mg/dl ofIntralipid.
	Hemolysate:No interference found up to 300mg/dl (3 g/l) of hemoglobin	Hemolysate:No significant interferencefound up to 500 mg/dl ofhemoglobin.
	Bilirubin, conjugated:No interference found up to 58mg/dL (1000 µmol/l) ofconjugated bilirubin.	Bilirubin:No significant interferencefound up to 25 mg/dl.
	Bilirubin, unconjugated:No interference found up to 21mg/dl (360 µmol/l) ofunconjugated bilirubin.

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Image /page/4/Picture/0 description: The image contains the logo for Thermo Fisher Scientific. The words "Thermo Fisher" are stacked on top of the word "SCIENTIFIC". The font is bold and black.

Thermo Fisher Scientific Oy

Ratastie 2
P.O. Box 100
FIN-01621 Vantaa
Finland

+358 (9) 329 100 1el
+358 (9) 3291 0500 fax

Y-tunnus 0921547-0
VAT No FI09215470
Domicile Helsinki

www.thermo.com

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ThermoFisher

S C I E N T I F I C

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Thermo Fisher Scientific Oy

Ratastie 2
P.O. Box 100
FIN-01621 Vantaa
Finland

+358 (9) 329 100 tel
+358 (9) 3291 0500 fax

Y-tunnus 0921547-0
VAT No FI09215470
Domicile Helsinki

www.thermo.com

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle-like bird symbol. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES. USA" is arranged in a circular pattern around the bird symbol.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 28 200

Thermo Fisher Scientific Oy c/o Ms. Päivi Sormunen Vice President of Industrial Solutions & QRC Clinical Diagnostics Finland Ratastie 2, P.O. Box 100 Fin-01621 Vantaa Finland

K073191 Re: Trade Name: Alkaline Phosphatase (IFCC) Plus, Ecal, Nortrol, Abtrol Regulation Number: 21 CFR 862.1050 : Regulation Name: Alkaline phosphatase or isoenzymes test system. Regulatory Class: Class II Product Codes: CJE, JIX, JIY Dated: February 06, 2008 Received: February 06, 2008

Dear Ms. Sormunen:

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 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 (240) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Yean M. Cooper, M.S., D.V.M. 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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Indication for Use

510(k) Number (if known): K073191

Device Name:

Alkaline Phosphatase (IFCC) Plus, eCal, Nortrol, Abtrol

Indication For Use:

Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver and bone diseases

For in vitro diagnostic use on T60 instrument. eCal is used as a calibrator for enzyme tests using methods defined by Thermo Fisher Scientific Oy

Prescription Use X (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 (OVD)

Signature

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

510(k) K073191

Regulation Number and Section

§ 862.1050 Alkaline phosphatase or isoenzymes test system.

(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.