(266 days)
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 Phosphatase2 assay is an automated clinical chemistry assay for the quantitation of alkaline phosphatase in human serum or plasma on the ARCHITECT c System. 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.
The provided document is a 510(k) Premarket Notification for a clinical chemistry assay (Alkaline Phosphatase2) and does not describe an AI medical device. Therefore, the questions related to AI-specific acceptance criteria, ground truth establishment by experts, adjudication methods, multi-reader multi-case studies, and human-in-the-loop performance are not applicable.
The document focuses on the analytical performance of the Alkaline Phosphatase2 assay, demonstrating its substantial equivalence to a legally marketed predicate device. The information details various non-clinical performance studies to establish the device's reliability and accuracy for quantitating alkaline phosphatase in human serum or plasma.
Here's a breakdown of the relevant information from the document, tailored to the context of a diagnostic assay's performance evaluation, substituting the AI-specific questions with applicable details:
Acceptance Criteria and Device Performance for Alkaline Phosphatase2 Assay
This submission (K223317) is for a clinical chemistry assay, not an AI medical device. The acceptance criteria and performance studies are focused on the analytical performance of the assay to demonstrate its intended use for quantitative measurement of alkaline phosphatase.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present a "table of acceptance criteria" for regulatory review, but it details various performance studies with implicit acceptance ranges. The reported device performance metrics are presented instead.
Performance Metrics of Alkaline Phosphatase2 Assay (Representative Values)
| Performance Metric | Acceptance Criteria (Implied by Study Design & Clinical Standards) | Reported Device Performance (Example Values) |
|---|---|---|
| Analytical Measuring Interval (AMI) | Defined range for acceptable linearity, imprecision, and bias. | 4-4522 U/L |
| Reportable Interval | Extends from LoD to upper limit of AMI. | 3-4522 U/L |
| Precision (Within-Laboratory - %CV) | (Example target from CLSI EP05-A3 guidelines) | Range from 0.3% to 11.5% |
| * Low-End Control (~115 U/L)* | (e.g., <5-10%) | 2.6% |
| * High-End Control (~430 U/L)* | (e.g., <5-10%) | 1.8% |
| * Low-End Panel (~9 U/L)* | (e.g., <15-20% for low concentrations) | 6.7% - 11.8% |
| * High-End Panel (~4300 U/L)* | (e.g., <5%) | 1.8% - 2.2% |
| Reproducibility (%CV) | (Example target from CLSI EP05-A3 guidelines) | Range from 1.4% to 2.5% |
| * Control Level 1 (~110 U/L)* | (e.g., <5%) | 2.3% - 2.5% |
| * Control Level 2 (~450 U/L)* | (e.g., <5%) | 1.4% - 1.8% |
| Accuracy (Bias) | Within a specified percentage relative to reference method. | Within ± 3.7% (Calibration method) |
| Within ± 3.2% (Calibration Factor method) | ||
| Lower Limits of Measurement | ||
| * Limit of Blank (LoB)* | Statistically determined 95th percentile. | 1 U/L |
| * Limit of Detection (LoD)* | Lowest concentration detectable with 95% probability. | 3 U/L |
| * Limit of Quantitation (LoQ)* | Lowest concentration meeting 20% CV precision. | 4 U/L |
| Linearity | Assay response directly proportional to analyte concentration. | Linear across 4 to 4522 U/L |
| Interference | No significant interference (within ± 10%) by common substances. | Mostly no significant interference observed, with noted exceptions for high concentrations of bilirubin and hemoglobin. |
| Method Comparison (Correlation Coefficient) | High correlation with predicate device. | 1.00 |
2. Sample Sizes Used for the Test Set and Data Provenance
The "test set" in this context refers to the samples used in the analytical performance studies.
- Precision Studies: 2 controls and 4 human serum panels were tested. Each sample type had n=80 replicates in the within-laboratory precision study. For system reproducibility, 5 levels of controls were tested with n=90 replicates.
- Accuracy: 2 materials standardized to the IFCC reference method were used across 3 reagent lots and 2 instruments. The specific number of replicates per material is not explicitly stated but implied by the bias calculation.
- Lower Limits of Measurement (LoB, LoD, LoQ): n ≥ 60 replicates of zero-analyte or low-analyte level samples were used.
- Linearity: The study used a dilution series across the analytical measuring interval. The exact number of points or samples is not specified but is typical for CLSI EP06.
- Interference: Each interfering substance was tested at 2 analyte levels. The number of replicates per level is not specified.
- Method Comparison: n=145 (Calibration method) and n=143 (Calibration Factor method) serum samples were used to compare with the predicate device.
- Tube Type: Samples were collected from a minimum of 40 donors.
Data Provenance: Not explicitly stated as "country of origin," but the studies were conducted by Abbott Ireland Diagnostics Division. The studies are non-clinical laboratory studies (analytical performance), using human serum/plasma samples. The studies are inherently prospective in their execution, as they involve performing tests on collected samples according to pre-defined protocols (e.g., CLSI guidelines) to establish performance characteristics.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
For an in vitro diagnostic (IVD) assay like this, "ground truth" is established by reference methods, certified reference materials, and established analytical principles, rather than expert human interpretation of images or clinical cases.
- Ground Truth Establishment: Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., EP05-A3, EP09-A3, EP17-A2, EP06, EP07, EP34) were meticulously followed for study design and data analysis.
- Expert Oversight: While not explicitly stated how many individual experts (e.g., clinical chemists) were involved in establishing the "ground truth" per se for the test samples, the studies adhere to recognized international standards and practices in clinical chemistry. The assumption is that qualified laboratory scientists and statisticians designed and executed these studies, and the reference methods themselves (like the IFCC reference method for Alkaline Phosphatase) are the "ground truth" standard.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are typically used for subjective assessments, such as image interpretation. For a quantitative diagnostic assay, the "adjudication" is achieved through:
- Statistical Analysis: Rigorous statistical methods (e.g., Passing-Bablok regression for method comparison, precision calculations) are employed to analyze the quantitative results.
- Reference Methods and Materials: The "truth" is determined by comparing the device's measurements to established reference methods (e.g., IFCC reference method) or certified reference materials, which are inherently objective.
- CLSI Guidelines: Adherence to CLSI guidelines ensures standardized and robust experimental design and data interpretation, minimizing subjective bias.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is an analytical performance study for an in vitro diagnostic assay, not an AI-assisted diagnostic tool involving human readers interpreting cases. Therefore, there is no MRMC study, and no effect size for human reader improvement with AI assistance.
6. Standalone Performance (Algorithm Only without Human-in-the-Loop)
This concept is less directly applicable but can be interpreted as the direct analytical performance of the instrument/reagent system. The presented non-clinical studies demonstrate the standalone performance of the Alkaline Phosphatase2 assay, meaning its performance characteristics (precision, accuracy, linearity, etc.) are evaluated intrinsically without direct human interpretation influencing the measurement itself. The human input is in setting up the test and interpreting the final quantitative result.
7. Type of Ground Truth Used
The ground truth for this diagnostic assay's performance evaluation largely relies on:
- Reference Methods: Specifically, the IFCC reference method for Alkaline Phosphatase is cited for accuracy studies.
- Certified Reference Materials: Standardized materials are used for calibration and accuracy verification.
- Statistical Definitions: For LoB, LoD, LoQ, and precision, the "ground truth" is established through statistical definitions based on replicate measurements of samples with known (or zero) analyte concentrations.
- Predicate Device Comparison: The predicate device's performance also serves as a comparative "ground truth" to demonstrate substantial equivalence, although the goal is to align with the IFCC standard.
8. Sample Size for the Training Set
Not applicable. This is a traditional IVD assay, not an AI model requiring a "training set" in the machine learning sense. The assay works based on established chemical principles, not on learned patterns from a large dataset. The reagent formulation and instrument algorithms are developed using R&D processes, not machine learning training.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of an AI/ML model for this diagnostic device. The "truth" for developing such an assay would be based on fundamental chemical and biological understanding, robust experimental data from R&D, and adherence to analytical standards.
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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
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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
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 andIndications for Use | The Alkaline Phosphatase2 assay isused for the quantitation of alkalinephosphatase in human serum orplasma on the ARCHITECT c System.Measurements of alkaline phosphataseor its isoenzymes are to be used as anaid in the diagnosis and treatment ofliver, bone, parathyroid, and intestinaldiseases. | The Alkaline Phosphatase assay isintended to measure alkalinephosphatase in serum or plasma.Measurement of alkaline phosphataseis used in the diagnosis and treatmentof liver, bone, parathyroid, andintestinal 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 ofProcedure | Alkaline Phosphatase in a samplecatalyzes the hydrolysis of colorlesspara-nitrophenyl phosphate (p-NPP) togive para-nitrophenol (yellowphenoxide form at alkaline pH) andinorganic phosphate. The rate ofabsorbance increase at 404 nm isdirectly proportional to the alkalinephosphatase activity in the sample.Optimized concentrations of zinc andmagnesium ions are present to activatethe alkaline phosphatase in the sample. | Alkaline phosphatase in the samplecatalyzes the hydrolysis of colorlessp-nitrophenyl phosphate (p-NPP) togive p-nitrophenol and inorganicphosphate. At the pH of the assay(alkaline), the p-nitrophenol is in theyellow phenoxide form.The rate of absorbance increase at404 nm is directly proportional to thealkaline phosphatase activity in thesample. Optimized concentrations ofzinc and magnesium ions are presentto activate the alkaline phosphatase inthe sample. |
| Use of Controls | Yes | Same |
| Tube Types | Serum:- Serum tubes- Serum separator tubesPlasma:- Lithium heparin tubes- Lithium heparin separator tubes- Sodium heparin tubes | Serum:- Glass or plastic tubes with or withoutgel barrierPlasma:- Glass or plastic tubes- Lithium heparin (with or without gelbarrier)- Sodium heparin |
| General Device Differences | ||
| Standardization | IFCC* traceable material | Molar extinction of p-nitrophenol(non-IFCC method) |
| Calibrationmethod | Calibration and Calibration Factormethod | Factor method |
| Assay Range | Analytical Measuring Interval:4-4522 U/LReportable 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 ofMeasurement | Limit of Blank: 1 U/LLimit of Detection: 3 U/LLimit of Quantitation: 4 U/L | Limit of Detection: 5.0 U/LLimit 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 | |||
| ControlLevel 1 | 90 | 113 | 1.1 | 1.0 | 2.6 | 2.3 | 2.6 | 2.3 |
| ControlLevel 2 | 90 | 460 | 2.6 | 0.6 | 5.6 | 1.2 | 6.6 | 1.4 |
| ControlLevel A | 90 | 71 | 0.8 | 1.2 | 0.9 | 1.3 | 1.1 | 1.5 |
| ControlLevel B | 90 | 177 | 1.7 | 0.9 | 4.4 | 2.5 | 4.4 | 2.5 |
| ControlLevel 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 |
| ControlLevel 1 | 90 | 108 | 1.0 | 0.9 | 2.4 | 2.3 | 2.7 | 2.5 |
| ControlLevel 2 | 90 | 443 | 2.6 | 0.6 | 5.4 | 1.2 | 8.0 | 1.8 |
| ControlLevel A | 90 | 68 | 0.8 | 1.2 | 0.9 | 1.3 | 1.5 | 2.2 |
| ControlLevel B | 90 | 171 | 1.6 | 0.9 | 4.4 | 2.6 | 5.2 | 3.0 |
| ControlLevel 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 InterferingSubstance | 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 | CorrelationCoefficient | Intercept | Slope | ConcentrationRangea | |
| 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 | CorrelationCoefficient | Intercept | Slope | ConcentrationRangea | |
| 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.
§ 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.