K Number
K130141
Date Cleared
2013-03-22

(59 days)

Product Code
Regulation Number
862.1050
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The S TEST Reagent Cartridge Alkaline Phosphatase (ALP) is intended for the quantitative measurement of alkaline phosphatase activity in serum, lithium heparinized plasma, or sodium citrate plasma using the HITACHI Clinical Analyzer. The S TEST Reagent Cartridge Alkaline Phosphatase (ALP) is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Device Description

The Hitachi Clinical Analyzer is an automatic, bench-top, wet chemistry system intended for use in clinical laboratories or physician office laboratories. The instrument consists of a desktop analyzer unit, an operations screen that prompts the user for operation input and displays data, a printer, and a unit cover. The analyzer unit includes a single probe, an incubation rotor, carousels for sample cups and reagent cartridges, and a multi-wavelength photometer. The single-use reagent cartridges may be placed in any configuration on the carousel, allowing the user to develop any test panel where the reagent cartridges are available.

The S TEST reagent cartridges are made of plastic and include two small reservoirs capable of holding two separate reagents (R1 and R2), separated by a reaction cell/photometric cuvette. The cartridges also include a dot code label that contains all chemistry parameters, calibration factors, and other production-related information, e.g., expiration dating. The dimensions of the reagent cartridges are: 13.5 mm (W) × 28 mm (D) × 20.2 mm (H).

System operation: After the sample cup is placed into the carousel, the analyzer pipettes the sample, pipettes the reagent, and mixes (stirs) the sample and reagent together. After the sample and reagent react in the incubator bath, the analyzer measures the absorbance of the sample, and based on the absorbance of the reactions, it calculates the concentration of analyte in the sample. The test system can measure analytes in serum or plasma and results are available in approximately 15 minutes per test. This submission is for Reagent Cartridge ALP.

Chemistry reactions: Alkaline phosphatase (ALP) in the sample reacts with its substrate, pnitrophenyl phosphate (p-NPP), in ethylaminoethanol (EAE) buffer, to release p-nitrophenol (yellow). The ALP activity is determined by measuring the rate of p-nitrophenol production.

AI/ML Overview

The provided text describes the performance characteristics and acceptance criteria for the Hitachi S TEST Reagent Cartridge Alkaline Phosphatase (ALP).

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" as a separate column for all metrics. However, the performance data provided implies that the reported results met the internal development criteria for each study. Where a specific acceptance range or threshold is mentioned (e.g., for interference testing), it is included.

Performance CharacteristicAcceptance Criteria (Implied/Stated)Reported Device Performance
Analytical Sensitivity (Limit of Detection)Not explicitly stated, but lower is better.1.8 U/L
Linearity RangePerformance within the specified range (predicate: 5 to 1,200 U/L)5 U/L to 1,000 U/L
Detection LimitMatch predicate (5 U/L)5 U/L
Precision (%CVs)For in-house, %CVs range from 4.4% to 5.8% (predicate). For external, performance is reported.In-house: 3.1% to 5.3% (Low), 3.8% to 5.8% (Middle), 2.5% to 4.4% (High). External site precision ranged from 3.0% to 9.2%.
Interference Testing (Recovery)Recoveries between 90% and 110% of the neat value.Hemoglobin: no interference up to 500 mg/dL. Unconjugated bilirubin: no interference up to 50 mg/dL. Lipemia: no interference up to 2,000 mg/dL. Ascorbic acid: no interference up to 50 mg/dL.
Method Comparison (Correlation coefficient 'r')High correlation, likely >0.90 for good agreement.In-house: 0.996. External sites: 0.99 for all three sites.
Method Comparison (Slope, in-house)Close to 1.0; 95% CI covering 1.0 or very close.0.926 (95% CI: 0.909 to 0.943)
Method Comparison (y-intercept, in-house)Close to 0; 95% CI covering 0 or very close.4.8 (95% CI: -0.2 to 9.8)
Matrices Comparison (Correlation coefficient 'r')High correlation, likely >0.90 for good agreement.Sodium Citrate Plasma: 0.999. Heparinized Plasma: 0.999.
Matrices Comparison (Slope, plasma types)Close to 1.0; 95% CI covering 1.0 or very close.Sodium Citrate Plasma: 1.03 (1.01 to 1.05). Heparinized Plasma: 1.01 (1.00 to 1.02).
Matrices Comparison (y-intercept, plasma types)Close to 0; 95% CI covering 0 or very close.Sodium Citrate Plasma: -11.2 (-15.5 to -7.0). Heparinized Plasma: -5.4 (-8.3 to -2.6).

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

  • Analytical Sensitivity (Limits of Detection): Not specified, but likely involved multiple replicates for statistical analysis as per CLSI EP17-A.
  • Linearity: Not specified, but involved samples spanning 5 U/L to 1,000 U/L as per CLSI EP-6A.
  • 20-day In-house Precision: Three levels of samples, each tested in two runs, twice a day, for 20 days. This means 80 data points per level (2 runs/day * 2 times/run * 20 days). Total around 240 data points across 3 levels.
  • Interference Testing: Two serum pools tested.
  • Method Comparison (in-house): 97 clinical specimens. Data provenance: Not explicitly stated, but implied to be in-house or from a domestic source. Retrospective.
  • Matrices Comparisons: 38 matched serum/plasma samples. Data provenance: Not explicitly stated, but implied to be in-house or from a domestic source. Retrospective.
  • External Site Precision: Each site tested three blinded serum samples, six times per day for five days. This means 30 replicates per sample per site. With 3 sites and 3 samples, approximately 270 data points (30 * 3 * 3).
  • External Site Method Comparison: Approximately 70 serum specimens per site, for a total of around 210 specimens (3 sites * ~70 samples/site). Data provenance: Not explicitly stated, but typically from within the country where the study is conducted (likely USA, given the FDA submission). Retrospective.

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

This information is not applicable as the device is a quantitative chemical analyzer. The "ground truth" for the test sets (samples used in the studies) is established by the reference methods or known concentrations, not by expert interpretation.

4. Adjudication Method for the Test Set:

This information is not applicable as the device is a quantitative chemical analyzer. Ground truth is determined objectively through reference methods or known concentrations, not through expert adjudication.

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. The device is a diagnostic instrument (chemistry analyzer) and not an AI-based imaging or diagnostic aid that involves human readers.

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

The studies described (precision, linearity, method comparison, interference, matrices comparison) represent the standalone performance of the Hitachi Clinical Analyzer with the S TEST Reagent Cartridge ALP. This is the direct measurement by the instrument, without a human interpretation step.

7. The Type of Ground Truth Used:

The ground truth for the performance studies was established using:

  • Reference Methods: For method comparison studies, the Hitachi system was compared against a "standard laboratory system" (predicate device or another established method).
  • Known Concentrations/Values: For linearity, precision, and interference studies, samples with known or carefully characterized concentrations of ALP and potential interferents were used.
  • CLSI Guidelines: Studies followed established Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., EP17-A for detection limit, EP-6A for linearity, EP5-A2 for precision, EP7-A2 for interference).

8. The Sample Size for the Training Set:

This information is not applicable. This device is a traditional chemical analyzer, not an AI/machine learning system that requires a "training set" in the computational sense. The device's parameters are set during its manufacturing and calibration process, not through a data-driven training phase.

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

This information is not applicable for the reason stated in point 8.

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HITACHI
Inspire the Next

MAR 2 2 2013

SECTION 8 510(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 K130141.

807.92 (a)(1): Name:Hitachi Chemical Diagnostics
Address:630 Clyde CourtMountain View, CA 94043
Phone:(650) 961 5501
FAX:(650) 969 2745
Contact:Mr. Charles Tsou

807.92 (a)(2): Device name- trade name and common name, and classification

Trade name: S TEST Reagent Cartridge Alkaline Phosphatase (ALP)

Common Name: Routine chemistry analyzer for ALP

Classifications: 21 CFR § 862.1050 Alkaline Phosphatase (ALP)

807.92 (a)(3): Identification of the legally marketed predicate devices

Cobas c systems ALP2 (Roche Diagnostics, Inc., Indianapolis, IN)- K100853

807.92 (a)(4): Device Description

The Hitachi Clinical Analyzer is an automatic, bench-top, wet chemistry system intended for use in clinical laboratories or physician office laboratories. The instrument consists of a desktop analyzer unit, an operations screen that prompts the user for operation input and displays data, a printer, and a unit cover. The analyzer unit includes a single probe, an incubation rotor, carousels for sample cups and reagent cartridges, and a multi-wavelength photometer. The single-use reagent cartridges may be placed in any configuration on the carousel, allowing the user to develop any test panel where the reagent cartridges are available.

The S TEST reagent cartridges are made of plastic and include two small reservoirs capable of holding two separate reagents (R1 and R2), separated by a reaction cell/photometric cuvette. The cartridges also include a dot code label that contains all chemistry parameters, calibration factors, and other production-related information, e.g., expiration dating. The dimensions of the reagent cartridges are: 13.5 mm (W) × 28 mm (D) × 20.2 mm (H).

Page 1 of 6

Hitachi Chemical Diagnostics, Inc.
630 Clyde Court, Mountain View, CA 94043-2239 Tel: 800 233 6278 Fax: 650 969 2745
www.hcdiagnostics.com

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Image /page/1/Picture/0 description: The image shows the logo for Hitachi. The word "HITACHI" is in large, bold, black letters. Below the company name is the slogan "Inspire the Next" in a smaller font size. The logo is simple and modern.

System operation: After the sample cup is placed into the carousel, the analyzer pipettes the sample, pipettes the reagent, and mixes (stirs) the sample and reagent together. After the sample and reagent react in the incubator bath, the analyzer measures the absorbance of the sample, and based on the absorbance of the reactions, it calculates the concentration of analyte in the sample. The test system can measure analytes in serum or plasma and results are available in approximately 15 minutes per test. This submission is for Reagent Cartridge ALP.

Chemistry reactions: Alkaline phosphatase (ALP) in the sample reacts with its substrate, pnitrophenyl phosphate (p-NPP), in ethylaminoethanol (EAE) buffer, to release p-nitrophenol (yellow). The ALP activity is determined by measuring the rate of p-nitrophenol production.

807.92 (a)(5): Intended Use

The S TEST Reagent Cartridge Alkaline Phosphatase (ALP) is intended for the quantitative measurement of alkaline phosphatase activity in serum, lithium heparinized plasma, or sodium citrate plasma using the HITACHI Clinical Analyzer. The S TEST Reagent Cartridge Alkaline Phosphatase (ALP) is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only,

Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Page 2 of 6

Hitachi Chemical Diagnostics, Inc.

w.hcdjagnostics.com

530 Clyde Court, Mountain View, CA 94043-2239 Tel: 800 233 6278 Fax: 650 969 2745

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807.92 (a)(6): Technological Similarities and Differences to the Predicate

The following chart describes similarities and differences between the two test systems.

CharacteristicHitachi S TEST SystemsPREDICATE
Instrument PlatformHitachi Clinical Analyzer(originally cleared under K111753)Roche cobas c systems - K100853
Alkaline Phosphatase (ALP)K number- pendingRoche K number- K100853
Device Class, Regulation CodeClass II, 21 CFR 862.1050Same
Classification Product CodeCJECJE
Intended UseQuantitative determination of ALPSame
Testing EnvironmentPhysician office or clinical labClinical lab
Test PrincipleIn the presence of magnesium ions,ALP reacts with p-NPP to release p-nitrophenol.In the presence of magnesium andzinc ions, p-NPP is cleaved byphosphatases into phosphate and p-nitrophenol
Specimen TypeHuman serum or plasmaSame
Reportable Range10 to 1,000 U/L5 to 1,200 U/L
Detection Wavelength405/508 nm480/450 nm
Detection Limit5 U/LSame
Linearity5 to 1,000 U/L5 to 1,200 U/L
Precision%CVs range from 4.4% to 5.8%%CVs range from 0.6% to 2.4%

807.92 (b)(1): Brief Description of Nonclinical Data

A series of studies were performed that evaluated the following nonclinical performance characteristics for each analytical sensitivity (limits of detection), linearity, 20-day in-house precision, interference testing, in-house method comparisons, and matrices comparison between serum and heparin plasma.

Analytical Sensitivity (Limits of Detection)

www.hediaonostics.com

The study followed CLSI EP17-A, and the limit of detection was found to be 1.8 U/L

Linearity

The study followed CLSI EP-6A, and the range of linearity was 5 U/L to 1,000 U/L.

20-day In-house Precision

The studies followed CLSI EP5-A2, where three levels of samples were each tested in two runs, twice a day, for 20 days. The results were as follows:

Page 3 of 6

Hitachi Chemical Dlagnostics, Inc.

Court, Mountain View, CA 94043-2239 Tel: 800 233 6278 Fax: 650 989 2745

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Precision Summary:

ALP- Low, Level 1, Summary

ALPWithin-RunTotal
Mean (U/L)42.742.7
SD (U/L)1.302.25
%CV3.1%5.3%

ALP- Middle, Level 2, Summary

ALPWithin-RunTotal
Mean (U/L)80.580.5
SD (U/L)3.074.65
%CV3.8%5.8%

ALP- High, Level 3, Summary

ALPWithin-RunTotal
Mean (U/L)555.6555.6
SD (U/L)13.9924.69
%CV2.5%4.4%

Interference Testing (per CLSI EP7-A2)

The data demonstrated that the ALP test system was not affected by high levels of the following substances at the levels noted:

Hemoglobin: no interference up to 500 mg/dL Unconjugated bilirubin: no interference up to 50 mg/dL Lipemia: no interference up to 2,000 mg/dL Ascorbic acid: no interference up to 50 mg/dL

Lack of interference was defined as recoveries between 90% and 110% of the neat value, and assay performance claims were established on the HITACHI Clinical Analyzer by testing two serum pools containing approximately 12 mg/L and 80 U/L ALP.

Method Comparison

A total of 97 clinical specimens spanning the dynamic range (11 to 926 U/L), were assayed in singleton and in a blinded fashion by both the Hitachi system and a standard laboratory system. The comparative data were analyzed by linear regression and are shown below. (CI = confidence interval)

nrSlope(95% CI)y-intercept(95% CI)X meanY mean
970.9960.926(0.909 to 0.943)4.8(-0.2 to 9.8)203 U/L193 U/L

ALP Regression Statistics:

Page 4 of 6

Chemical Chemical Diagnost

630 Clyde Court, Mountain View, CA 94043-2239 Tel: 800 233 6278 Fax: 650 969 2745

www.hediagnostics.com

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Matrices Comparisons

A study was performed to validate the use of two plasma types as an alternative to serum for the Hitachi Clinical Analyzer with S TEST Reagent Cartridge Alkaline Phosphatase (ALP). The plasma types were sodium citrate and lithium heparin. Thirty-eight (38) matched serum/plasma samples that spanned the dynamic range (13 to 967) were assayed in singleton and the results were compared using linear regression (plasma = y-axis, each type). The performance characteristics were as follows.

N = 38

Range (serum) = 13 to 967 U/L

Sodium Citrate PlasmaHeparinized Plasma
Slope (95% CIs)1.03 (1.01 to 1.05)1.01 (1.00 to 1.02)
y-intercept (95% CIs)-11.2 (-15.5 to -7.0)-5.4 (-8.3 to -2.6)
r0.9990.999

807.92 (b)(2): Brief Description of Clinical Data

Studies for precision and method comparison (accuracy) were performed at three external POL-type sites to evaluate the Hitachi Clinical Analyzer with S TEST Reagent Cartridges Alkaline Phosphatase (ALP) in one of its targeted intended use environments, the physician's office laboratory.

For the external site precision study, each site received three blinded serum samples (the Precision Panel, labeled A, B, and C) that were chosen to represent low, middle, and high concentrations of ALP. Each sample was assayed six times per day for five days, reporting 30 results per level. Precision estimates for total precision were as follows:

n = 30 replicates per sample per site
SiteSampleMeanTotal Precision
SD (U/L)%CV
Site 1Low13.20.967.3%
Site 2Low12.81.007.8%
Site 3Low13.41.239.2%
Site IMiddle76.22.263.0%
Site 2Middle68.85.247.6%
Site 3Middle70.06.289.0%
Site 1High408.626.016.4%
Site 2High390.123.216.0%
Site 3High402.912.333.1%

ALP (U/L)

Page 5 of 6

Hitachi Chemical Diagnostics, In

www.hcdiagnostics.com

630 Clyde Court, Mountain View, CA 94043-2239 Tel: 800 233 6278 Fax: 650 969 2745

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For the external site method comparison study, a series of approximately 70 serum specimens with ALP values ranging from 11 to 745 U/L were assayed on the Hitachi Clinical Analyzer at three sites using S TEST Reagent Cartridge Alkaline Phosphatase (ALP) (y) and a comparative method as the reference method (x). Linear regression analysis (least squares) yielded the following results:

Site #nHitachiRangeRegressionEquation"r"95% CISlope95% CIIntercept
17713 to 745y = 0.967x + 2.90.990.949 to 0.984-0.6 to 6.4
27211 to 688y = 0.942x - 0.70.990.925 to 0.960-4.4 to 2.9
37212 to 736y = 0.980x + 0.80.990.961 to 0.999-3.2 to 4.7

POL ACCURACY DATA SUMMARY- ALP (U/L)

807.92 (b)(3): Conclusions from Nonclinical and Clinical Testing

Nonclinical and clinical testing was performed for the Hitachi Clinical Analyzer with S TEST Reagent Cartridge Alkaline Phosphatase (ALP). The test system was shown to be safe and effective for its intended use.

Page 6 of 6

O Hitachi Chemical Diagnostics,

630 Clyde Court, Mountain View, CA 94043-2239 Tel: 800 233 6278 Fax: 650 969 2745

www.hcdiagnostics.com

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes representing the agency's mission to promote health, well-being, and human services. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

March 22, 2013

Hitachi Chemical Diagnostics, Inc. c/o Erika Ammirati 630 Clyde Court Mountain View, CA 94043

Re: K130141

Trade/Device Name: S TEST Reagent Cartridge Alkaline Phosphatase (ALP) Regulation Number: 21 CFR §862.1050 Regulation Name: Alkaline Phosphatase or isoenzymes test system Regulatory Class: Class II Product Code: CJE Dated: January 18, 2013 Received: January 22, 2013

Dear Ms. Ammirati:

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 additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office

of Surveillance and Biometrics/Division of Postmarket Surveillance.

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) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Carol C. Benson -S for

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K130141

Device Name:

S TEST Reagent Cartridge Alkaline Phosphatase (ALP)

Indications for Use:

The S TEST Reagent Cartridge Alkaline Phosphatase (ALP) is intended for the quantitative measurement of alkaline phosphatase activity in serum, lithium heparinized plasma, or sodium citrate plasma using the HITACHI Clinical Analyzer. The S TEST Reagent Cartridge Alkaline Phosphatase (ALP) is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

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 Diagnostics and Radiological Health (OIR)

Ruth A. Cheslêr -S

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health (OIR)

K130141 510(k)

§ 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.