Predicate Devices

Alkaline Phosphatase (K023807)

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on standard clinical chemistry assay principles and validation methods, with no mention of AI or ML algorithms for data analysis or interpretation.

Therapeutic

No

Explanation: This device is for in vitro diagnostic use, quantitating alkaline phosphatase levels to aid in diagnosis and treatment monitoring, but it does not directly treat a disease or condition.

Diagnostic

Yes

The intended use explicitly states that measurements of alkaline phosphatase or its isoenzymes are to be used "as an aid in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases."

SaMD (Software as a Medical Device)

No

The device is described as an automated clinical chemistry assay for use on the ARCHITECT c System, which is a hardware platform. The description details the chemical reaction and measurement of absorbance, indicating a physical process involving reagents and instrumentation, not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states that the assay is used for the "quantitation of alkaline phosphatase in human serum or plasma." This indicates that the device is designed to analyze biological samples from the human body.
Indications for Use: The indications for use state that the measurements are to be used "as an aid in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases." This clearly indicates a medical purpose related to diagnosis and treatment, which is a core function of IVDs.
Device Description: The description details how the assay works by measuring the enzymatic activity of alkaline phosphatase in a sample. This process involves analyzing a biological sample (serum or plasma) to obtain a result that provides information about a patient's health status.
Performance Studies: The document includes a summary of performance studies, which are standard for IVD devices to demonstrate their analytical performance (accuracy, precision, linearity, etc.).
Predicate Device: The mention of a predicate device (K023807; Alkaline Phosphatase) further confirms that this device is being compared to a previously cleared IVD.

Based on these points, the Alkaline Phosphatase2 assay fits the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Alkaline Phosphatase2 assay is used for the quantitation of alkaline phosphatase in human serum or plasma on the ARCHITECT c System.

Measurements of alkaline phosphatase or its isoenzymes are to be used as an aid in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Product codes

CJE

Device Description

The Alkaline Phosphatase2 assay uses the principle of alkaline phosphatase in a sample catalyzing the hydrolysis of colorless para-nitrophenyl phosphate (p-NPP) to give para-nitrophenol (yellow phenoxide form at alkaline pH) and inorganic phosphate. The rate of absorbance increase at 404 nm is directly proportional to the alkaline phosphatase activity in the sample. Optimized concentrations of zinc and magnesium ions are present to activate the alkaline phosphatase in the sample. The device is an automated clinical chemistry assay for the quantitation of alkaline phosphatase in human serum or plasma on the ARCHITECT c System.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Reportable Interval:

Analytical Measuring Interval (AMI): 4-4522 U/L
Reportable Interval: 3-4522 U/L
(Based on CLSI EP34, 1st ed)

Within-Laboratory Precision:

Study type: Performed based on guidance from CLSI EP05-A3.
Sample size: 80 samples for each level (Control Level 1, Control Level 2, Panel A, Panel B, Panel C, Panel D) for both calibration and calibration factor methods.
Key results:
- Calibration method: Within-laboratory %CV ranged from 2.3-2.6% for controls and 2.3-11.8% for panels.
- Calibration Factor method: Within-laboratory %CV ranged from 2.3-2.6% for controls and 2.1-11.5% for panels.

System Reproducibility:

Study type: Performed based on guidance from CLSI EP05-A3.
Sample size: 90 samples for each control level.
Key results:
- Calibration method: Reproducibility %CV ranged from 1.4-2.5%.
- Calibration Factor method: Reproducibility %CV ranged from 1.8-3.0%.

Accuracy:

Study type: Estimation of bias relative to materials standardized to the IFCC reference method.
Key results:
- Calibration method: Bias was within ± 3.7%.
- Calibration Factor method: Bias was within ± 3.2%.

Lower Limits of Measurement:

Study type: Performed based on guidance from CLSI EP17-A2.
Key results:
- Calibration method: LoB = 1 U/L, LoD = 3 U/L, LoQ = 4 U/L.
- Calibration Factor method: LoB = 1 U/L, LoD = 3 U/L, LoQ = 4 U/L.

Linearity:

Study type: Performed based on guidance from CLSI EP06, 2nd ed.
Key results: Linear across the analytical measuring interval of 4 to 4522 U/L for both calibration and calibration factor methods.

Potentially Interfering Endogenous and Exogenous Substances:

Study type: Performed based on guidance from CLSI EP07, 3rd ed.
Key results:
- No significant interference (within ± 10%) from Conjugated Bilirubin (15 mg/dL), Unconjugated Bilirubin (20 mg/dL), Hemoglobin (250 mg/dL), Total protein (15 g/dL), Triglycerides (1500 mg/dL).
- Interference beyond ± 10% was observed for Conjugated Bilirubin (40 mg/dL), Unconjugated Bilirubin (40 mg/dL and 60 mg/dL), and Hemoglobin (1000 mg/dL).
- No significant interference (within ± 10%) from various exogenous substances (Acetaminophen, Acetylcysteine, Acetylsalicylic acid, etc.) at specified concentrations.

Method Comparison:

Study type: Performed based on guidance from CLSI EP09-A3 using the Passing-Bablok regression method.
Sample size: Serum: 145 (Calibration method), 143 (Calibration Factor method).
Key results:
- Calibration method: Correlation Coefficient = 1.00, Intercept = -1 U/L, Slope = 1.07. Concentration Range = 8 - 4534 U/L.
- Calibration Factor method: Correlation Coefficient = 1.00, Intercept = -2 U/L, Slope = 1.08. Concentration Range = 8 - 4042 U/L.

Tube Type:

Study type: Evaluated suitability of specific blood collection tube types.
Sample size: Minimum of 40 donors.
Key results: Acceptable tube types: Serum tubes, Serum separator tubes, Lithium heparin tubes, Lithium heparin separator tubes, Sodium heparin tubes.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

Alkaline Phosphatase (K023807)

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

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.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo in blue, with the words "U.S. FOOD & DRUG" on top and "ADMINISTRATION" on the bottom.

July 21, 2023

Abbott Ireland Diagnostics Division Cherie Lipowsky Regulatory Affairs Project Manager Lisnarnuck, Longford Co. Longford. Ireland

Re: K223317

Trade/Device Name: Alkaline Phosphatase2 Regulation Number: 21 CFR 862.1050 Regulation Name: Alkaline Phosphatase Or Isoenzymes Test System Regulatory Class: Class II Product Code: CJE Dated: June 15, 2023 Received: June 16, 2023

Dear Cherie Lipowsky:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmp/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see

1

https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Paula V. Caposino -S

Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K223317

Device Name Alkaline Phosphatase2

Indications for Use (Describe)

The Alkaline Phosphatase2 assay is used for the quantitation of alkaline phosphatase in human serum or plasma on the ARCHITECT c System.

Measurements of alkaline phosphatase or its isoenzymes are to be used as an aid in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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Section 5: 510(k) Summary (Summary of Safety and Effectiveness)

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

I. 510(k) Number

K223317

II. Applicant Name

Abbott Ireland Diagnostics Division Lisnamuck, Longford Co. Longford, Ireland

Primary contact person for all communications:

Cherie Lipowsky, Project Manager, Regulatory Affairs Abbott Laboratories, Diagnostics Division Phone (224) 668-1435 Fax (224) 667-4836

Secondary contact person for all communications:

Julian Braz, Director, Regulatory Affairs Abbott Laboratories, Diagnostics Division Phone (224) 330-9230 Fax (224) 667-4836

Date Summary Prepared: July 20, 2023

III. Device Name

Trade Name: Alkaline Phosphatase2

Device Classification: Class II Classification Name: Alkaline phosphatase or isoenzymes test system Governing Regulation Number: 21 CFR §862.1050 Product Code: CJE

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IV. Predicate Device

Alkaline Phosphatase (K023807)

V. Description of Device

A. Principles of the Procedure

Alkaline Phosphatase in a sample catalyzes the hydrolysis of colorless para-nitrophenyl phosphate (p-NPP) to give para-nitrophenol (yellow phenoxide form at alkaline pH) and inorganic phosphate. The rate of absorbance increase at 404 nm is directly proportional to the alkaline phosphatase activity in the sample. Optimized concentrations of zinc and magnesium ions are present to activate the alkaline phosphatase in the sample.

Methodology: Para-nitrophenyl phosphate (p-NPP)

B. Reagents

The configurations of the Alkaline Phosphatase2 reagent kits are described below.

	List Number
	04S8720	04S8730
Tests per cartridge set	200	600
Number of cartridge sets per kit	8	8
Tests per kit	1600	4800
Reagent 1 (R1)	53.9 mL	53.9 mL
Reagent 2 (R2)	12.9 mL	33.6 mL

R1: Active ingredient: 2-amino-2-methylpropanol (AMP) (179.550 g/L). Preservative: sodium azide.

R2: Active ingredient: 4-nitrophenyl phosphate (30.430 g/L). Preservative: sodium azide.

VI. Intended Use of the Device

The Alkaline Phosphatase2 assay is used for the quantitation of alkaline phosphatase in human serum or plasma on the ARCHITECT c System.

Measurements of alkaline phosphatase or its isoenzymes are to be used as an aid in the

diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

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VII. Comparison of Technological Characteristics

The Alkaline Phosphatase2 assay (subject device) is an automated clinical chemistry assay for the quantitation of alkaline phosphatase in human serum or plasma on the ARCHITECT c System.

The similarities and differences between the subject device and the predicate device are presented in the following table.

Similarities and Differences Between
Device & Predicate Device
	Device:
Alkaline Phosphatase2	Predicate Device:
Alkaline Phosphatase (LN 7D55)
(K023807)
General Device Similarities
Platform	ARCHITECT c System	Same
Intended Use and
Indications for Use	The Alkaline Phosphatase2 assay is
used for the quantitation of alkaline
phosphatase in human serum or
plasma on the ARCHITECT c System.
Measurements of alkaline phosphatase
or its isoenzymes are to be used as an
aid in the diagnosis and treatment of
liver, bone, parathyroid, and intestinal
diseases.	The Alkaline Phosphatase assay is
intended to measure alkaline
phosphatase in serum or plasma.
Measurement of alkaline phosphatase
is used in the diagnosis and treatment
of liver, bone, parathyroid, and
intestinal diseases.
Methodology	Para-nitrophenyl phosphate ( p -NPP)	Same
Specimen Type	Human serum or plasma	Same
Similarities and Differences Between
Device & Predicate Device	Device:
Alkaline Phosphatase2	Predicate Device:
Alkaline Phosphatase (LN 7D55)
(K023807)
Assay Principle /
Principle of
Procedure	Alkaline Phosphatase in a sample
catalyzes the hydrolysis of colorless
para-nitrophenyl phosphate (p-NPP) to
give para-nitrophenol (yellow
phenoxide form at alkaline pH) and
inorganic phosphate. The rate of
absorbance increase at 404 nm is
directly proportional to the alkaline
phosphatase activity in the sample.
Optimized concentrations of zinc and
magnesium ions are present to activate
the alkaline phosphatase in the sample.	Alkaline phosphatase in the sample
catalyzes the hydrolysis of colorless
p-nitrophenyl phosphate (p-NPP) to
give p-nitrophenol and inorganic
phosphate. At the pH of the assay
(alkaline), the p-nitrophenol is in the
yellow phenoxide form.
The rate of absorbance increase at
404 nm is directly proportional to the
alkaline phosphatase activity in the
sample. Optimized concentrations of
zinc and magnesium ions are present
to activate the alkaline phosphatase in
the sample.
Use of Controls	Yes	Same
Tube Types	Serum:

Serum tubes
Serum separator tubes

Plasma:

Lithium heparin tubes
Lithium heparin separator tubes
Sodium heparin tubes | Serum:
Glass or plastic tubes with or without
gel barrier

Plasma:

Glass or plastic tubes
Lithium heparin (with or without gel
barrier)
Sodium heparin |
| | General Device Differences | |
| Standardization | IFCC* traceable material | Molar extinction of p-nitrophenol
(non-IFCC method) |
| Calibration
method | Calibration and Calibration Factor
method | Factor method |
| Assay Range | Analytical Measuring Interval:
4-4522 U/L
Reportable Interval: 3-4522 U/L | Analytical Measuring Interval:
5—4555 U/L |
| Similarities and Differences Between | | |
| Device & Predicate Device | | |
| | Device:
Alkaline Phosphatase2 | Predicate Device:
Alkaline Phosphatase (LN 7D55)
(K023807) |
| Lower Limits of
Measurement | Limit of Blank: 1 U/L
Limit of Detection: 3 U/L
Limit of Quantitation: 4 U/L | Limit of Detection: 5.0 U/L
Limit of Quantitation: 5.0 U/L |

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IFCC = International Federation of Clinical Chemistry and Laboratory Medicine

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VIII. Summary of Nonclinical Performance

A. Reportable Interval

Based on the limit of detection (LoD), limit of quantitation (LoQ), precision, and linearity, the ranges over which results can be reported are provided below according to the definitions from CLSI EP34, 1st ed. *

	U/L
Analytical Measuring Interval (AMI)a	4-4522
Reportable Intervalb	3-4522

ª AMI: The AMI is determined by the range of values in U/L that demonstrated acceptable performance for linearity, imprecision, and bias.

b The reportable interval extends from the LoD to the upper limit of the AMI.

Clinical and Laboratory Standards Institute (CLSI). Establishing and Verifying an Extended Measuring Interval Through Specimen Dilution and Spiking. Ist ed. CLSI Document EP34. Wayne, PA: CLSI; 2018.

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B. Within-Laboratory Precision

Within-Laboratory Precision

A study was performed based on guidance from CLSI EP05-A3. Testing was conducted using 3 lots of the Alkaline Phosphatase2 reagents, 3 lots of the Consolidated Chemistry Calibrator, 1 lot of commercially available controls, and 3 instruments. Two controls and 4 human serum panels were tested in a minimum of 2 replicates, twice per day on 20 days on 3 reagent lot/calibrator lot/instrument combinations, where a unique reagent lot and a unique calibrator lot are paired with 1 instrument. The performance from a representative combination is shown in the following table.

| | | | Within-Run
(Repeatability) | | Within-Laboratorya | |
|-----------------|----|---------------|-------------------------------|---------------------|---------------------|-------------------|
| Sample | n | Mean
(U/L) | SD
(Rangeb) | %CV
(Rangeb) | SD
(Rangeb) | %CV
(Rangeb) |
| Control Level 1 | 80 | 116 | 0.8
(0.8 - 1.0) | 0.7
(0.7 - 0.8) | 3.0
(2.7-3.0) | 2.6
(2.3-2.6) |
| Control Level 2 | 80 | 428 | 1.4
(1.2 - 1.7) | 0.3
(0.3 - 0.4) | 7.8
(7.5-8.4) | 1.8
(1.7-2.0) |
| Panel A | 80 | 9 | 0.6
(0.6 - 1.1) | 6.3
(6.3 - 11.7) | 0.6
(0.6-1.1) | 6.7
(6.7-11.8) |
| Panel B | 80 | 42 | 0.7
(0.7 - 0.9) | 1.6
(1.6-2.3) | 1.0
(1.0-1.2) | 2.3
(2.3-2.9) |
| Panel C | 80 | 2045 | 6.8
(6.3 - 13.3) | 0.3
(0.3 - 0.6) | 43.6
(40.5-43.6) | 2.1
(1.9-2.1) |
| Panel D | 80 | 4306 | 14.6
(14.6-28.0) | 0.3
(0.3 - 0.6) | 77.7
(77.7-98.7) | 1.8
(1.8-2.2) |

Calibration method

ª Includes within-run, between-run, and between-day variability.

b Minimum and maximum SD or %CV across the 3 reagent lot/calibrator lot/instrument combinations.

Clinical and Laboratory Standards Institute (CLSI). Evaluation of Quantitative Measurement Procedures; Approved Guideline—Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.

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Calibration Factor method

| Sample | n | Mean
(U/L) | Within-Run
(Repeatability) | | Within-Laboratorya | |
|-----------------|----|---------------|-------------------------------|------------------------|---------------------|-------------------|
| | | | SD
(Rangeb) | %CV
(Rangeb) | SD
(Rangeb) | %CV
(Rangeb) |
| Control Level 1 | 80 | 114 | 0.9
(0.8 – 0.9) | 0.8
(0.7 – 0.8) | 3.0
(2.7–3.1) | 2.6
(2.3–2.6) |
| Control Level 2 | 80 | 423 | 1.3
(1.2 – 1.7) | 0.3
(0.3 – 0.4) | 7.9
(7.5–8.3) | 1.9
(1.7–1.9) |
| Panel A | 80 | 9 | 0.7
(0.7 – 1.0) | 7.2
(7.2 –
11.3) | 0.7
(0.7–1.1) | 7.2
(7.2–11.5) |
| Panel B | 80 | 41 | 0.7
(0.7 – 0.9) | 1.7
(1.6–2.2) | 0.9
(0.9–1.2) | 2.1
(2.1–2.9) |
| Panel C | 80 | 2017 | 6.7
(6.4 – 13.4) | 0.3
(0.3 – 0.6) | 44.9
(39.5–44.9) | 2.2
(1.8–2.2) |
| Panel D | 80 | 4248 | 14.4
(14.4 – 28.5) | 0.3
(0.3 – 0.6) | 81.0
(81.0–94.5) | 1.9
(1.9–2.1) |

ª Includes within-run, between-run, and between-day variability.

b Minimum and maximum SD or %CV across the 3 reagent lot/calibrator lot/instrument combinations.

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System Reproducibility

A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 1 lot of the Alkaline Phosphatase2 reagents, 1 lot of the Consolidated Chemistry Calibrator, 1 lot each of 2 commercially available control sets, and 3 instruments. Each instrument was operated by a different technician, and each technician prepared an individual sample set. Five levels of controls were tested in a minimum of 3 replicates at 2 separate times per day on 5 different days.

| Sample | n | Mean
(U/L) | Repeatability | | Within-Laboratorya | | Reproducibilityb | |
|--------------------|----|---------------|---------------|-----|--------------------|-----|------------------|-----|
| | | | SD | %CV | SD | %CV | SD | %CV |
| Control
Level 1 | 90 | 113 | 1.1 | 1.0 | 2.6 | 2.3 | 2.6 | 2.3 |
| Control
Level 2 | 90 | 460 | 2.6 | 0.6 | 5.6 | 1.2 | 6.6 | 1.4 |
| Control
Level A | 90 | 71 | 0.8 | 1.2 | 0.9 | 1.3 | 1.1 | 1.5 |
| Control
Level B | 90 | 177 | 1.7 | 0.9 | 4.4 | 2.5 | 4.4 | 2.5 |
| Control
Level C | 90 | 359 | 2.1 | 0.6 | 6.3 | 1.8 | 7.0 | 2.0 |

Calibration method

ª Includes within-run, between-run, and between-day variability.

b Includes within-run, between-run, between-day, and between-instrument variability.

Clinical and Laboratory Standards Institute (CLSI). Evaluation of Quantitative Measurement Procedures; Approved Guideline—Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.

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		Mean	Repeatability		Within-Laboratorya		Reproducibilityb
Sample	n	(U/L)	SD	%CV	SD	%CV	SD	%CV
Control
Level 1	90	108	1.0	0.9	2.4	2.3	2.7	2.5
Control
Level 2	90	443	2.6	0.6	5.4	1.2	8.0	1.8
Control
Level A	90	68	0.8	1.2	0.9	1.3	1.5	2.2
Control
Level B	90	171	1.6	0.9	4.4	2.6	5.2	3.0
Control
Level C	90	345	2.1	0.6	6.1	1.8	8.9	2.6

Calibration Factor method

ª Includes within-run, between-run, and between-day variability.

b Includes within-run, between-run, between-day, and between-instrument variability.

C. Accuracy

A study was performed to estimate the bias of the Alkaline Phosphatase2 assay relative to materials standardized to the IFCC reference method.

Calibration method

Testing was conducted with each of the 2 materials standardized to the IFCC reference method using 3 lots of the Alkaline Phosphatase2 reagents, 1 lot of the Consolidated Chemistry Calibrator, and 2 instruments. The bias was within ± 3.7%.

Calibration Factor method

Testing was conducted with each of the 2 materials standardized to the IFCC reference method using 3 lots of the Alkaline Phosphatase2 reagents and 2 instruments. The bias was within ± 3.2%.

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D. Lower Limits of Measurement

A study was performed based on guidance from CLSI EP17-A2. * Testing was conducted using 3 lots of the Alkaline Phosphatase2 reagents on each of 2 instruments over a minimum of 3 days. The limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) values are summarized below.

Calibration method

	U/L
LoBa	1
LoDb	3
LoQc	4

a The LoB represents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.

b The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.

6 The LoQ is defined as the lowest concentration at which a maximum allowable precision of 20 %CV was met and was determined from n ≥ 60 replicates of low-analyte level samples.

Calibration Factor method
---------------------------

	U/L
LoBa	1
LoDb	3
LoQc	4

a The LoB represents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.

b The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.

^ The LoQ is defined as the lowest concentration at which a maximum allowable precision of 20 %CV was met and was determined from n ≥ 60 replicates of low-analyte level samples.

Clinical and Laboratory Standards Institute (CLSI). Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition. CLSI Document EP17-A2. Wayne, PA: CLSI; 2012.

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E. Linearity

A study was performed based on guidance from CLSI EP06, 2nd ed. * This assay is linear across the analytical measuring interval of 4 to 4522 U/L for both the calibration and calibration factor methods.

F. Potentially Interfering Endogenous and Exogenous Substances

A study was performed based on guidance from CLSI EP07, 3rd ed. * Each substance was tested at 2 levels of the analyte (approximately 70 U/L and 200 U/L).

Potentially Interfering Endogenous Substances

No significant interference (interference within ± 10%) was observed at the following concentrations.

No Significant Interference (Interference within ± 10%)
Potentially Interfering Substance	Interferent Level
Bilirubin - conjugated	15 mg/dL
Bilirubin - unconjugated	20 mg/dL
Hemoglobin	250 mg/dL
Total protein	15 g/dL
Triglycerides	1500 mg/dL

Clinical and Laboratory Standards Institute (CLSI). Evaluation of Quantitative Measurement Procedure. 2nd ed. CLSI Document EP06. Wayne, PA: CLSI; 2020.
Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.

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Interference beyond ± 10% (based on 95% Confidence Intervals [CI]) was observed at the concentration shown below for the following substance.

Interference beyond ± 10% (based on 95% CI)
Potentially Interfering
Substance	Interferent Level	Analyte Level	% Interference
(95% CI)
Bilirubin - conjugated	40 mg/dL	70 U/L	28%
(27%, 29%)
Bilirubin - conjugated	40 mg/dL	200 U/L	11%
(10%, 11%)
Bilirubin - unconjugated	40 mg/dL	70 U/L	21%
(20%, 22%)
Bilirubin - unconjugated	60 mg/dL	200 U/L	10%
(10%, 11%)
Hemoglobin	1000 mg/dL	70 U/L	-33%
(-34%, -31%)
Hemoglobin	1000 mg/dL	200 U/L	-13%
(-14%, -13%)

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Potentially Interfering Exogenous Substances

No significant interference (interference within ± 10%) was observed at the following concentrations.

No Significant Interference (Interference within ± 10%)
Potentially Interfering Substance	Interferent Level
Acetaminophen	160 mg/L
Acetylcysteine	150 mg/L
Acetylsalicylic acid	30 mg/L
Ampicillin-Na	80 mg/L
Ascorbic acid	60 mg/L
Biotin	4250 ng/mL
Ca-dobesilate	60 mg/L
Cefotaxime	60 mg/dL
Cefoxitin	6600 mg/L
Cyclosporine	2 mg/L
Desacetylcefotaxime	6 mg/dL
Doxycycline	20 mg/L
Ibuprofen	220 mg/L
Levodopa	8 mg/L
Magnesium sulfate	50 mg/dL
Methyldopa	25 mg/L
Metronidazole	130 mg/L
Phenylbutazone	330 mg/L
Rifampicin	50 mg/L
Sodium heparin	4 U/mL
Theophylline (1,3-dimethylxanthine)	60 mg/L

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G. Method Comparison

A study was performed based on guidance from CLSI EP09-A3 * using the Passing-Bablok regression method.

Calibration method

Alkaline Phosphatase2 vs Alkaline Phosphatase on the ARCHITECT c8000 System
	n	Units	Correlation
Coefficient	Intercept	Slope	Concentration
Rangea
Serum	145	U/L
(µkat/L)	1.00	-1
(-0.02)	1.07b	8 - 4534
(0.12-75.59)

ª Alkaline Phosphatase (7D55) comparator range.

b Slope relative to non-IFCC traceable Alkaline Phosphatase.

Calibration Factor method

Alkaline Phosphatase2 vs Alkaline Phosphatase on the ARCHITECT c8000 System
	n	Units	Correlation
Coefficient	Intercept	Slope	Concentration
Rangea
Serum	143	U/L	1.00	-2	1.08b	8 - 4042

ª Alkaline Phosphatase (7D55) comparator range.

b Slope relative to non-IFCC traceable Alkaline Phosphatase.

Clinical and Laboratory Standards Institute (CLSI). Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline—Third Edition. CLSI Document EP09-A3. Wayne, PA: CLSI; 2013.

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H. Tube Type

A study was performed to evaluate the suitability of specific blood collection tube types for use with the Alkaline Phosphatase2 assay. Samples were collected from a minimum of 40 donors and evaluated across tube types. The following blood collection tube types were determined to be acceptable for use with the Alkaline Phosphatase2 assay:

Serum

. Serum tubes
Serum separator tubes .

Plasma

Lithium heparin tubes •
. Lithium heparin separator tubes
Sodium heparin tubes

IX. Summary of Clinical Performance

This section does not apply.

X. Conclusion Drawn from Nonclinical Laboratory Studies

The similarities and differences between the subject device and predicate device are presented in Section 5-VII. The results presented in this 510(k) demonstrate that the subject device Alkaline Phosphatase2 is as safe and effective as the predicate. Any differences between the subject device and the predicate device shown in the tables do not raise different questions of safety and effectiveness.

There is no known potential adverse effect to the operator when using this in vitro device according to the Alkaline Phosphatase2 reagent package insert instructions.