(449 days)
The Amylase2 assay is used for the quantitation of amylase in human serum, plasma, or urine on the ARCHITECT c System. The Amylase2 assay is to be used primarily as an aid in the diagnosis and treatment of pancreation of the pancreas).
The Amylase2 assay is an automated clinical chemistry assay. The Amylase2 assay is a two-part reaction. Ethylidene-4-NP-G7 (EPS) is hydrolyzed by a-amylase to form 4,6ethylidene-α-(1,4)-D-glucopyranosyl-Gx and 4-nitrophenyl-α-(1,4)-glucopyranosyl-G(7-x). The 4-nitrophenyl-a-(1,4)-glucopyranosyl-G(7-x) is then hydrolyzed into glucose monomers and the assay chromophore (4-nitrophenol) by a-glucosidase. The resulting change in absorbance at 404 nm is proportional to the a-amylase concentration in the sample. Methodology: Enzymatic/Colorimetric. The device is a reagent kit.
Here's a breakdown of the acceptance criteria and the study details for the Amylase2 device, based on the provided FDA 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The FDA 510(k) summary does not explicitly list "acceptance criteria" in a singular table, but rather presents the results of various performance studies. I've extracted the performance metrics and their corresponding observed results to form this table, interpreting the reported successful values as meeting implicit acceptance criteria for substantial equivalence.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance (Amylase2) |
|---|---|---|
| Analytical Measuring Interval (AMI) | Defined range of accurate operation | Serum/Plasma: 3-3010 U/L Urine: 3-3010 U/L |
| Extended Measuring Interval (EMI) | Defined range with dilution/spiking | Serum/Plasma: 3010-5959 U/L Urine: 3010-8600 U/L |
| Reportable Interval | Overall range of reliable results | Serum/Plasma: 2-5959 U/L Urine: 1-8600 U/L |
| Within-Run Precision (Serum/Plasma) | %CV and SD within acceptable limits | %CV ≤ 7.4% (Panel A), SD ≤ 14.8 U/L (Panel C) |
| Within-Laboratory Precision (Serum/Plasma) | %CV and SD within acceptable limits | %CV ≤ 11.0% (Panel A), SD ≤ 51.6 U/L (Panel C) |
| Within-Run Precision (Urine) | %CV and SD within acceptable limits | %CV ≤ 5.4% (Panel A), SD ≤ 12.2 U/L (Panel E) |
| Within-Laboratory Precision (Urine) | %CV and SD within acceptable limits | %CV ≤ 7.9% (Panel A), SD ≤ 20.4 U/L (Panel D) |
| System Reproducibility (Serum/Plasma) | %CV and SD within acceptable limits | %CV ≤ 1.6% (Control Level A), SD ≤ 3.1 U/L (Control Level 2) |
| System Reproducibility (Urine) | %CV and SD within acceptable limits | %CV ≤ 1.3% (Control Level A), SD ≤ 2.4 U/L (Control Level B) |
| Accuracy (Calibration method) | Bias within acceptable range | Bias within ± 2.4% |
| Accuracy (Calibration Factor method) | Bias within acceptable range | Bias within ± 3.1% |
| Limit of Blank (LoB) | Very low or 0 U/L | Serum/Plasma: 0 U/L Urine: 0 U/L |
| Limit of Detection (LoD) | Low detection capability | Serum/Plasma: 2 U/L Urine: 1 U/L |
| Limit of Quantitation (LoQ) | Low quantification capability (%CV ≤ 20%) | Serum/Plasma: 2 U/L Urine: 3 U/L |
| Linearity | Linear response across AMI | Demonstrated across 3 to 3010 U/L for serum and urine |
| Endogenous Interference (Serum/Plasma) | Interference within ± 10% | No significant interference observed for listed substances |
| Exogenous Interference (Serum/Plasma) | Interference within ± 10% | No significant interference observed for listed substances |
| Endogenous Interference (Urine) | Interference within ± 10% | No significant interference for most; Ascorbate showed -18% to -21% interference at high levels. |
| Exogenous Interference (Urine) | Interference within ± 10% | No significant interference observed for listed substances |
| Method Comparison (Correlation Coefficient) | High correlation (e.g., close to 1.00) | Serum: 1.00, Urine: 1.00 |
| Method Comparison (Slope) | Close to 1 (e.g., 0.98-1.02) | Serum: 0.98, Urine: 0.93 |
| Method Comparison (Intercept) | Close to 0 | Serum: -1, Urine: -1 |
| Suitable Tube Types | Acceptable for use | Serum tubes, SST, Lithium heparin tubes, LHT, Sodium heparin tubes |
| Dilution Verification (Automated vs. Manual) | Acceptable difference | Serum/Plasma: -0.1% to 0.2% difference Urine: -3.0% to -1.9% difference |
2. Sample Sizes Used for the Test Set and Data Provenance
The document provides details on various studies, each with its own sample size and design:
- Precision (Serum/Plasma & Urine - Within-Laboratory):
- Sample Size: For each of the controls (2 levels) and panels (3 for serum/plasma, 5 for urine), N=80 data points were collected. This involved testing samples in duplicate, twice per day for 20 days.
- Provenance: Human serum/plasma and human urine panels were used. No specific country of origin is mentioned, but the context implies an in-vitro diagnostic study conducted under CLSI guidelines, likely in a controlled laboratory setting. It is a prospective study as samples were tested according to a pre-defined protocol.
- System Reproducibility (Serum/Plasma & Urine):
- Sample Size: For each of the controls (5 for serum/plasma, 4 for urine), N=90 data points were collected. This involved testing samples in a minimum of 3 replicates at 2 separate times per day on 5 different days across 3 instruments and 3 technicians.
- Provenance: The study used controls, implying commercially prepared materials or pooled biological samples. It is a prospective study.
- Accuracy:
- Sample Size: Not explicitly stated but implies a set of calibrator materials and potentially patient samples based on "material standardized to the Certified Reference Material IRMM/IFCC-456."
- Provenance: Relies on certified reference materials and likely patient samples.
- Lower Limits of Measurement (LoB, LoD, LoQ):
- Sample Size: n ≥ 60 replicates of zero-analyte and low-analyte level samples for each determination (LoB, LoD, LoQ).
- Provenance: Control materials or spiked biological samples designed to have specific low analyte levels. Prospective.
- Linearity:
- Sample Size: Not explicitly stated, but typically involves a series of diluted/spiked samples to cover the analytical range.
- Provenance: Spiked or diluted biological samples. Prospective.
- Potentially Interfering Substances (Serum/Plasma & Urine):
- Sample Size: Not explicitly stated, but each substance was tested at 2 levels of the analyte (approximately 50 U/L and 200 U/L for serum/plasma; 450 U/L and 1400 U/L for urine). This implies numerous replicates for each interferent and analyte level.
- Provenance: Biological samples (serum/plasma/urine) spiked with various endogenous and exogenous substances. Prospective.
- Method Comparison:
- Sample Size: 124 serum samples and 103 urine samples.
- Provenance: Human serum and urine samples. The description doesn't explicitly state if prospective or retrospective, but typically such studies involve prospectively collected samples from a diverse patient population. No country of origin specified.
- Tube Type:
- Sample Size: Samples collected from a minimum of 40 donors.
- Provenance: Human blood samples collected into different tube types. Prospective.
- Dilution Verification:
- Sample Size: 5 human serum samples and 5 urine samples, each tested in replicates of 5 after automated and manual dilution.
- Provenance: Human serum and urine samples spiked with α-amylase from porcine pancreas. Prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the document. For an in-vitro diagnostic device, "ground truth" often refers to the true concentration of the analyte, which is usually established by highly precise reference methods, certified reference materials, or by comparison with a well-established predicate device, rather than expert consensus on images or clinical diagnoses. The document indicates standardization against IRMM/IFCC-456, which is a reference material for amylase, and comparison to a predicate device (AMY, K981653). These serve as the "ground truth" or reference for the device's performance.
4. Adjudication Method for the Test Set
This section is not applicable as this is an in-vitro diagnostic (IVD) device for quantitative measurement of amylase. Adjudication methods like "2+1" or "3+1" are typically used in clinical studies involving interpretation of medical images or subjective evaluations, where multiple experts independently assess data and discrepancies are resolved. For an IVD, the "ground truth" is measured quantitatively against a reference standard or predicate.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
This information is not provided and is not applicable to this device. An Amylase2 assay is an automated clinical chemistry assay, not an AI-powered diagnostic imaging device that requires human "readers" or involves AI assistance in interpretation. Therefore, an MRMC study comparing human readers with and without AI assistance is not relevant to this product.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The Amylase2 assay is an automated clinical chemistry assay, meaning its performance is inherently "standalone" in the sense that it provides a quantitative result without direct human intervention in the measurement process itself, beyond sample loading and general instrument operation. The studies described (precision, accuracy, linearity, interference, method comparison) are all evaluating the algorithm/reagent system's performance independently.
7. The Type of Ground Truth Used
The ground truth for the Amylase2 device's performance studies relies on:
- Reference Materials: For accuracy, the device was compared against "material standardized to the Certified Reference Material IRMM/IFCC-456."
- Predicate Device: For method comparison, the Amylase2 assay was compared to the predicate device, Amylase assay (List Number 7D58), which serves as the established reference standard in this context.
- Spiked Samples: For linearity, lower limits of measurement, interference, and dilution verification, samples were often "spiked" with known concentrations of α-amylase or interfering substances to create samples with a known "true" value.
- Commercial Controls: For precision and reproducibility studies, commercially available controls with known target ranges were used.
8. The Sample Size for the Training Set
The document describes studies for validation and verification purposes (test sets). For an IVD like Amylase2, the "training set" would refer to the data used by the manufacturer during the assay development phase to optimize reagents, calibrate the instrument response, and refine the measurement algorithms. This specific information about the development/training data size is not provided in the 510(k) summary, as the summary focuses on the performance of the final device.
9. How the Ground Truth for the Training Set Was Established
Similar to point 8, the specific details on how ground truth was established for any internal "training set" used during development are not provided. Typically, for such IVDs, this would involve a rigorous process of using purified analytes, gravimetric/volumetric standards, certified reference materials, and comparison to established reference methods to assign "true" values to a large panel of samples during the assay's development and optimization.
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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, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
May 26, 2022
Magdalena Suszko Manager, Regulatory Affairs Lisnarnuck Longford, Ireland
Re: K210633
Trade/Device Name: Amylase2 Regulation Number: 21 CFR 862.1070 Regulation Name: Amylase Test System Regulatory Class: Class II Product Code: JFJ Dated: March 29, 2022 Received: March 29, 2022
Dear Magdalena Suszko:
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/cfpmn/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
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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 https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) 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 mediation-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,
Marianela Perez-Torres, Ph.D. Deputy Director Division of Chemistry and 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) K210633
Device Name Amylase2
Indications for Use (Describe)
The Amylase2 assay is used for the quantitation of amylase in human serum, plasma, or urine on the ARCHITECT c System. The Amylase2 assay is to be used primarily as an aid in the diagnosis and treatment of pancreation of the pancreas).
| 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 SMDA 1990 and 21 CFR 807.92.
I. 510(k) Number
II. Applicant Name
Abbott Ireland Diagnostics Division Lisnamuck, Longford Longford, IE
Primary contact person for all communications:
Magdalena Suszko, Manager, Regulatory Affairs Abbott Diagnostics Division Phone (224) 667-9025 Fax (224) 667-4836
Secondary contact person for all communications:
Elizabeth Molina Campos, Regulatory Affairs Project Manager Abbott Diagnostics Division Phone (224) 667-0037 Fax (224) 667-4836
Date Summary Prepared: March 28, 2022
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III. Device Name
Amylase2
Reagents
Trade Name: Amylase2 Device Classification: Class II Classification Name: Amylase test system Governing Regulation Number: 21 CFR 862.1070 Product Code: JFJ
IV. Predicate Device
AMY (K981653)
V. Description of Device
A. Principles of the Procedure
The Amylase2 assay is an automated clinical chemistry assay. The Amylase2 assay is a two-part reaction. Ethylidene-4-NP-G7 (EPS) is hydrolyzed by a-amylase to form 4,6ethylidene-α-(1,4)-D-glucopyranosyl-Gx and 4-nitrophenyl-α-(1,4)-glucopyranosyl-G(7-x). The 4-nitrophenyl-a-(1,4)-glucopyranosyl-G(7-x) is then hydrolyzed into glucose monomers and the assay chromophore (4-nitrophenol) by a-glucosidase. The resulting change in absorbance at 404 nm is proportional to the a-amylase concentration in the sample.
Methodology: Enzymatic/Colorimetric
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B. Reagents
The configuration of the Amylase2 reagent kit is described below.
| List Number | |
|---|---|
| 04S8920 | |
| Tests per cartridge set | 160 |
| Number of cartridge sets per kit | 4 |
| Tests per kit | 640 |
| Reagent 1 (R1) | 14.5 mL |
| Reagent 1 (R2) | 13.4 mL |
Active ingredient: α-glucosidase 16.000 KU/L. Preservative: sodium azide. Reagent 1
Active ingredient: Ethylidene-4-NP-G7 (EPS) 6.501 g/L. Preservative: Reagent 2 sodium azide.
VI. Intended Use of the Device
The Amylase2 assay is used for the quantitation of amylase in human serum, plasma, or urine on the ARCHITECT c System.
The Amylase2 assay is to be used primarily as an aid in the diagnosis and treatment of pancreatitis (inflammation of the pancreas).
VII. Comparison of Technological Characteristics
The Amylase2 assay (subject device) is an automated clinical chemistry assay for the quantitation of amylase in human serum, plasma, or urine on the ARCHITECT c System.
The similarities and differences between the subject device and the predicate device are presented in the following table.
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| Comparison of Subject Device (Amylase2) to Predicate Device (AMY) | ||
|---|---|---|
| Characteristics | Subject DeviceAmylase2 (List No. 04S89) | Predicate DeviceAMY (K981653; List No. 7D58) |
| Platform | ARCHITECT c System | Same* |
| Intended Use andIndications forUse | The Amylase2 assay is used for thequantitation of amylase in human serum,plasma, or urine on the ARCHITECT cSystem.The Amylase2 assay is to be usedprimarily as an aid in the diagnosis andtreatment of pancreatitis (inflammationof the pancreas). | The Amylase assay is used for thequantitation of amylase in humanserum, plasma, or urine. |
| Methodology | Enzymatic/Colorimetric | Same(2-chloro-4-nitrophenyl-α-D-maltotrioside [CNPG3] Substrate) |
| Specimen Type | Human serum, plasma, urine | Same |
| Assay Principle /Principle ofProcedure | The Amylase2 assay is a two-partreaction. Ethylidene-4-NP-G7 (EPS) ishydrolyzed by α-amylase to form 4,6-ethylidene-α-(1,4)-D-glucopyranosyl-Gx and 4-nitrophenyl-α-(1,4)-glucopyranosyl-G(7-x). The 4-nitrophenyl-α-(1,4)-glucopyranosyl-G(7-x) is then hydrolyzed into glucosemonomers and the assay chromophore(4-nitrophenol) by α-glucosidase. Theresulting change in absorbance at 404nm is proportional to the α-amylaseconcentration in the sample. | α-Amylase hydrolyzes the 2-chloro-4-nitrophenyl-α-D-maltotrioside(CNPG3) to release 2-chloro-4-nitrophenol (CPNP) and form2-chloro-4-nitrophenyl-α-D-maltoside(CNPG2), maltotriose, and glucose.The rate of formation of the 2-chloro-4-nitrophenol can be detectedspectrophotometrically at 404 nm togive a direct measurement of α-amylaseactivity in the sample. |
| Standardization | IRMM/IFCC†-456 | Molar extinction coefficient of CNP(non-IFCC method)IFCC† reference method 2006‡ |
| Use ofCalibrators | Yes | No |
| CalibrationMethod | Calibration and Calibration Factormethod | Factor method |
| Use of Controls | Yes | Same |
| Comparison of Subject Device (Amylase2) to Predicate Device (AMY) (Continued) | ||
| Characteristics | Subject DeviceAmylase2 (List No. 04S89) | Predicate DeviceAMY (K981653; List No. 7D58) |
| Assay Range | Serum/Plasma:Analytical Measuring Interval:3-3010 U/LExtended Measuring Interval:3010-5959 U/LReportable Interval:2-5959 U/LUrine:Analytical Measuring Interval:3-3010 U/LExtended Measuring Interval:3010-8600 U/LReportable Interval:1-8600 U/L | Serum/Plasma/Urine:Analytical Measuring Interval:3-3010 U/LFlex Rate Linearity: 6554 U/L |
| Precision | Serum/Plasma:Samples with amylase concentrationsbetween 4 and 2629 U/L wereevaluated. The samples demonstrated% coefficients of variation (%CV)≤ 2.2% and standard deviations (SD)≤ 0.5 U/L.Urine:Samples with amylase concentrationsbetween 6 and 2625 U/L wereevaluated. The samples demonstrated%CV ≤ 2.9% and SD ≤ 0.5 U/L. | Serum/Plasma:Samples with amylase concentrationsbetween 46.9 and 476.4 U/Ldemonstrated %CV values rangingfrom 2.1% to 3.7%.Urine:Samples with amylase concentrationsbetween 40.9 and 179.0 U/Ldemonstrated %CV values rangingfrom 1.3% to 2.0%. |
| Lower Limits ofMeasurement | Serum/Plasma:Limit of Blank: 0 U/LLimit of Detection: 2 U/LLimit of Quantitation: 2 U/LUrine:Limit of Blank: 0 U/LLimit of Detection: 1 U/LLimit of Quantitation: 3 U/L | Serum/Plasma/Urine:Limit of Detection: 2.0 U/LLimit of Quantitation: 2.4 U/L |
| Comparison of Subject Device (Amylase2) to Predicate Device (AMY) (Continued) | ||
| Characteristics | Subject DeviceAmylase2 (List No. 04S89) | Predicate DeviceAMY (K981653; List No. 7D58) |
| 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 lithium heparin tubeswith or without gel barrier- Glass or plastic sodium heparin tubes |
* In accordance with FDA Guidance Document "Data for Commercialization of Original Equipment Manufacturer, Secondary and Generic Reagent for Automated Analyzers", issued June 10, 1996, the assay equivalency study on ARCHITECT c System vs. the original platform, AEROSET, was performed and submitted under K980367/A005 in May 2002.
* IFC = International Federation of Clinical Chemistry Medicine; IRMM = Institute for Reference Materials and Measurent
‡ The assay was re-standardized against IFCC reference method 2006 in 2015.
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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. *
Serum/Plasma
| U/L | |
|---|---|
| Analytical Measuring Interval (AMI)a | 3-3010 |
| Extended Measuring Interval (EMI)b | 3010-5959 |
| Reportable Intervalc | 2-5959 |
a AMI: The AMI is determined by the range of values in U/L that demonstrated acceptable performance for linearity, imprecision, and bias.
b EMI: The EMI extends from the ULoQ to the ULoQ × dilution factor.
6 The reportable interval extends from the LoD to the upper limit of the EMI.
Urine
| U/L | |
|---|---|
| Analytical Measuring Interval (AMI)a | 3-3010 |
| Extended Measuring Interval (EMI)b | 3010-8600 |
| Reportable Intervalc | 1-8600 |
a AMI: The is determined by the range of values in U/L that demonstrated acceptable performance for linearity, imprecision, and bias.
b EMI: The EMI extends from the ULoQ to the ULoQ × dilution factor.
& The reportable interval extends from the LoD to the upper limit of the EMI.
Clinical and Laboratory Standards Institute (CLS). Establishing and Verifying an Extended Measuring Interval Through Specinen Dilution and Spiking. 1st ed. CLSI Document EP34. Wayne, PA: CLSI; 2018.
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B. Within-Laboratory Precision
Within-Laboratory Precision - Serum/Plasma
A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 3 lots of the Amylase2 reagent, 3 lots of the Consolidated Chemistry Calibrator, 1 lot of commercially available controls, and 3 instruments. Two controls and 3 serum panels were tested in duplicate, twice per day on 20 days on 3 reagent lot/calibrator lot/instrument combinations, where a unique reagent lot and a unique calibrator lot is paired with 1 instrument. The performance from a representative combination is shown in the following table.
| Sample | n | Mean(U/L) | Within-Run(Repeatability) | Within-Laboratorya | ||
|---|---|---|---|---|---|---|
| SD | %CV | SD(Rangeb) | %CV(Rangeb) | |||
| Control Level 1 | 80 | 77 | 0.5 | 0.6 | 1.5(1.3-1.5) | 2.0(1.7-2.0) |
| Control Level 2 | 80 | 413 | 3.3 | 0.8 | 6.7(6.5-6.7) | 1.6(1.6-1.6) |
| Panel A | 80 | 4 | 0.3 | 7.4 | 0.5(0.3-0.5) | 11.0(6.7-11.0) |
| Panel B | 80 | 162 | 0.8 | 0.5 | 3.3(3.2-3.5) | 2.1(2.0-2.2) |
| Panel C | 80 | 2629 | 14.8 | 0.6 | 51.6(51.6-54.5) | 2.0(2.0-2.1) |
a Includes within-run, between-run, and between-day variability.
b Minimum and maximum SD or %CV across all reagent lot and instrument combinations.
Clinical and Laboratory Standards Institute (CLS). Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
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Within-Laboratory Precision - Urine
A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 3 lots of the Amylase2 reagent, 3 lots of the Consolidated Chemistry Calibrator, 1 lot of commercially available controls, and 3 instruments. Two controls and 5 human urine panels were tested in duplicate, twice per day on 20 days on 3 reagent lot/calibrator lot/instrument combinations, where a unique reagent lot and a unique calibrator lot is 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 | %CV | SD(Rangeb) | %CV(Rangeb) |
| Control Level 1 | 80 | 55 | 0.4 | 0.8 | 0.5(0.5-0.6) | 1.0(1.0-1.1) |
| Control Level 2 | 80 | 180 | 0.8 | 0.4 | 1.3(1.3-1.9) | 0.7(0.7-1.1) |
| Panel A | 80 | 6 | 0.3 | 5.4 | 0.5(0.3-0.5) | 7.9(5.0-8.8) |
| Panel B | 80 | 18 | 0.4 | 2.1 | 0.4(0.3-0.5) | 2.4(1.4-2.9) |
| Panel C | 80 | 538 | 2.7 | 0.5 | 5.3(5.3-6.8) | 1.0(1.0-1.3) |
| Panel D | 80 | 1891 | 10.2 | 0.5 | 20.4(20.4-23.7) | 1.1(1.1-1.2) |
| Panel E | 80 | 2625 | 12.2 | 0.5 | 20.3(19.6-20.3) | 0.8(0.7-0.8) |
a Includes within-run, between-run, and between-day variability.
b Minimum and maximum SD or %CV across all reagent lot and instrument combinations.
Clinical and Laboratory Standards Institute (CLS). Evaluation of Quantitative Measurement Procedures; Approved Guideline Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
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System Reproducibility - Serum/Plasma
A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 1 lot of the Amylase2 reagent, 1 lot of the Consolidated Chemistry Calibrator, 1 lot of commercially available controls, and 3 instruments. Each instrument was operated by a different technician, and each technician prepared an individual sample set. Five 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 | 74 | 0.4 | 0.6 | 0.6 | 0.8 | 0.6 | 0.9 |
| ControlLevel 2 | 90 | 416 | 2.5 | 0.6 | 3.0 | 0.7 | 3.1 | 0.7 |
| ControlLevel A | 90 | 37 | 0.4 | 1.0 | 0.5 | 1.3 | 0.6 | 1.6 |
| ControlLevel B | 90 | 113 | 0.8 | 0.7 | 0.8 | 0.7 | 0.9 | 0.8 |
| ControlLevel C | 90 | 351 | 1.2 | 0.4 | 1.3 | 0.4 | 1.6 | 0.4 |
a Includes repeatability (within-run), between-run, and between-day variability.
b Includes repeatability (within-run), between-day, and between-instrument variability.
Clinical and Laboratory Standards Institute (CLS). Evaluation of Quantitative Measurement Procedures; Approved Guideline Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
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System Reproducibility - Urine
A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 1 lot of the Amylase2 reagent, 1 lot of the Consolidated Chemistry Calibrator, 1 lot of commercially available controls, and 3 instruments. Each instrument was operated by a different technician, and each technician prepared an individual sample set. Four 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 | 54 | 0.5 | 1.0 | 0.5 | 1.0 | 0.6 | 1.1 |
| ControlLevel 2 | 90 | 171 | 1.2 | 0.7 | 1.2 | 0.7 | 1.6 | 0.9 |
| ControlLevel A | 90 | 66 | 0.4 | 0.7 | 0.5 | 0.8 | 0.9 | 1.3 |
| ControlLevel B | 90 | 232 | 1.6 | 0.7 | 2.2 | 1.0 | 2.4 | 1.0 |
ª Includes repeatability (within-run), between-run, and between-day variability.
b Includes repeatability (within-run), between-day, and between-instrument variability.
Clinical and Laboratory Standards Institute (CLS). Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
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C. Accuracy
A study was performed to estimate the bias of the Amylase2 assay relative to material standardized to the Certified Reference Material IRMM/IFCC-456.
Calibration method
Testing was conducted using 3 lots of the Amylase2 reagent, 2 lots of the Consolidated Chemistry Calibrator, and 1 instrument. The bias was within ± 2.4%.
Calibration Factor method
Testing was conducted using 3 lots of the Amylase2 reagent and 1 instrument. The bias was within ± 3.1%.
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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 Amylase2 reagent kit on each of 2 instruments over a minimum of 3 days. The maximum observed limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) values are summarized below.
| U/L | |
|---|---|
| LoBa | 0 |
| LoDb | 2 |
| LoQc | 2 |
| Urine | |
| U/L | |
| LoBa | 0 |
| LoDb | 1 |
| LoQc | 3 |
Serum/Plasma
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.
E. Linearity
A study was performed based on guidance from CLSI EP06-A. * This assay demonstrated linearity across the analytical measuring interval of 3 to 3010 U/L for both serum and urine applications.
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.
* Clinical and Laboratory Standards Institute (CLS). Evaluation of the Linearity of Quanitiative Measurement Procedures: A Statistical Approach; Approved Guideline. CLSI Document EP06-A. Wayne, PA: CLSI; 2003.
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F. Potentially Interfering Endogenous and Exogenous Substances
Serum/Plasma
A study was performed based on guidance from CLSI EP07, 3rd ed. * Each substance was tested at 2 levels of the analyte (approximately 50 U/L and 200 U/L).
No significant interference (interference within ± 10%) was observed at the following concentrations.
Potentially Interfering Endogenous Substances
| Potentially Interfering Substance | Interferent Level |
|---|---|
| Bilirubin - conjugated | 60 mg/dL |
| Bilirubin - unconjugated | 60 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Total protein | 15 g/dL |
| Triglycerides | 1500 mg/dL |
Potentially Interfering Exogenous Substances
| Potentially InterferingSubstance | InterferentLevel | Potentially InterferingSubstance | InterferentLevel |
|---|---|---|---|
| Acetaminophen | 160 mg/L | Ibuprofen | 220 mg/L |
| Acetylcysteine | 150 mg/L | Icodextrin | 3.6 mg/dL |
| Acetylsalicylic acid | 30 mg/L | Levodopa | 8 mg/L |
| Ampicillin-Na | 80 mg/L | Methyldopa | 25 mg/L |
| Ascorbic acid | 60 mg/L | Metronidazole | 130 mg/L |
| Biotin | 4250 ng/mL | Pancreozymin | 314 pg/mL |
| Ca-dobesilate | 60 mg/L | Phenylbutazone | 330 mg/L |
| Cefotaxime | 53 mg/dL | Rifampicin | 50 mg/L |
| Cefoxitin | 6600 mg/L | Sodium heparin | 4 U/mL |
| Cyclosporine | 2 mg/L | Theophylline | 60 mg/L |
| Doxycycline | 20 mg/L |
Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
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Urine
A study was performed based on guidance from CLSI EP07, 3rd ed. * Each substance was tested at 2 levels of the analyte (approximately 450 U/L and 1400 U/L).
No significant interference (interference within ± 10%) was observed at the following concentrations.
Potentially Interfering Endogenous Substances
| Potentially Interfering Substance | Interferent Level |
|---|---|
| Ascorbate | 150 mg/dL |
| Glucose | 1000 mg/dL |
| Protein | 50 mg/dL |
Interference beyond ± 10% |based on 95% Confidence Interval (CI)] was observed at
the concentrations shown below for the following substances.
| Potentially Interfering Substance | Interferent Level | Analyte Level | % Interference(95% CI) |
|---|---|---|---|
| Ascorbate | 200 mg/dL | 450 U/L | -21% (-21%, -20%) |
| Ascorbate | 200 mg/dL | 1400 U/L | -18% (-19%, -17%) |
Potentially Interfering Exogenous Substances
| Potentially Interfering Substance | Interferent Level |
|---|---|
| Acetaminophen | 16 mg/dL |
| Acetylcysteine | 15 mg/dL |
| Biotin | 4250 ng/mL |
| Boric acid | 250 mg/dL |
| Ibuprofen | 22 mg/dL |
| Sodium carbonate | 1.25 g/dL |
| Sodium fluoride | 400 mg/dL |
| Sodium oxalate | 60 mg/dL |
Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
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G. Method Comparison
A study was performed based on guidance from CLSI EP09-A3* using the Passing-Bablok regression method. The study compared the Amylase2 assay to the Amylase assay (List Number 7D58).
| Amylase2 vs Amylase on the ARCHITECT c System | ||||||
|---|---|---|---|---|---|---|
| n | Units | CorrelationCoefficient | Intercept | Slope | ConcentrationRange | |
| Serum | 124 | U/L | 1.00 | -1 | 0.98 | 6–2788 |
| Urine | 103 | U/L | 1.00 | -1 | 0.93 | 4-2916 |
H. Tube Type
A study was performed to evaluate the suitability of specific blood collection tube types for use with the Amylase2 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 Amylase2 assay:
Serum
- Serum tubes •
- Serum separator tubes
Plasma
- Lithium heparin tubes .
- Lithium heparin separator tubes •
- Sodium heparin tubes
Clinical and Laboratory Standards Institute (CLS). 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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I. Dilution Verification
Serum/Plasma
A study was performed to evaluate the performance of the Amylase2 automated dilution protocol relative to the manual dilution procedure on the ARCHITECT c System. Five human serum samples were created by spiking a-amylase from porcine pancreas stock solution into a serum pool to target concentration values of 3800, 4500, 5200, 5900, and 6600 U/L. Each sample was divided into multiple aliquots. An aliquot of each sample was tested using the 1:2 automated dilution protocol on the ARCHITECT c System. The additional aliquots were divided such that 2 technicians prepared 3 manual dilutions (1:2 dilution with saline) of each sample. Each sample preparation from a given technician was tested in a separate run.
The samples were tested in replicates of 5 using 1 lot each of reagents, calibrators, and controls on the ARCHITECT c System. The difference values of -0.1% to 0.2% of the Amylase2 automated dilution protocol relative to the manual dilution procedure demonstrated acceptable performance.
Urine
A study was performed to evaluate the performance of the Amylase2 automated dilution protocol relative to the manual dilution procedure on the ARCHITECT c System. Five urine samples were created by spiking a-amylase from porcine pancreas stock solution into a urine pool to target concentration values of 3800, 4500, 5900, and 6600 U/L. Each sample was divided into multiple aliquots. An aliquot of each sample was tested using the 1:3 automated dilution protocol on the ARCHITECT c System. The additional aliquots were divided such that 2 technicians prepared 3 manual dilutions (1:3 dilution with saline) of each sample. Each sample preparation from a given technician was tested in a separate run.
The samples were tested in replicates of 5 using 1 lot each of reagents, calibrators, and controls on the ARCHITECT c System. The difference values of -3.0% to -1.9% of the Amylase2 automated dilution protocol relative to the manual dilution procedure demonstrated acceptable performance.
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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) provide reasonable assurance that the subject device Amylase2 is safe and effective for the stated intended use. 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 Amylase2 reagent package insert instructions.
§ 862.1070 Amylase test system.
(a)
Identification. An amylase test system is a device intended to measure the activity of the enzyme amylase in serum and urine. Amylase measurements are used primarily for the diagnosis and treatment of pancreatitis (inflammation of the pancreas).(b)
Classification. Class II.