Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on standard enzymatic/colorimetric assay methodology and analytical performance metrics, with no mention of AI or ML.

Therapeutic

No
The device is an in vitro diagnostic assay used for the diagnosis of a condition (pancreatitis) but does not provide direct treatment. Its use in "treatment of pancreatitis" refers to aiding clinical management, not providing therapy itself.

Diagnostic

Yes

The intended use explicitly states that the Amylase2 assay is to be used "primarily as an aid in the diagnosis and treatment of pancreatitis."

SaMD (Software as a Medical Device)

No

The device is described as a "reagent kit" and an "automated clinical chemistry assay," which are physical components used in laboratory testing, not software.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use: The description explicitly states the assay is used for the "quantitation of amylase in human serum, plasma, or urine" and is intended "as an aid in the diagnosis and treatment of pancreation of the pancreas)". This clearly indicates the device is used to examine specimens derived from the human body to provide information for diagnostic purposes.
Device Description: It is described as an "automated clinical chemistry assay" and a "reagent kit," which are typical components of IVD devices used in clinical laboratories.
Methodology: The methodology (Enzymatic/Colorimetric) is a common technique used in IVD assays.
Performance Studies: The document details various performance studies (Precision, Accuracy, Linearity, Method Comparison, etc.) which are standard evaluations for IVD devices to demonstrate their analytical performance.
Predicate Device: The mention of a predicate device with a K number (K981653) further confirms its classification as a medical device, specifically an IVD, as K numbers are associated with FDA clearances for medical devices.

All these characteristics align with the definition and typical features of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

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).

Product codes (comma separated list FDA assigned to the subject device)

JFJ

Device Description

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 4,6 ethylidene-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

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Pancreas

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Prescription Use (Part 21 CFR 801 Subpart D)

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:

Serum/Plasma: Analytical Measuring Interval (AMI) 3-3010 U/L, Extended Measuring Interval (EMI) 3010-5959 U/L, Reportable Interval 2-5959 U/L.
Urine: Analytical Measuring Interval (AMI) 3-3010 U/L, Extended Measuring Interval (EMI) 3010-8600 U/L, Reportable Interval 1-8600 U/L.

Within-Laboratory Precision - Serum/Plasma:

Study based on CLSI EP05-A3.
Testing with 3 lots of Amylase2 reagent, 3 lots of Consolidated Chemistry Calibrator, 1 lot of commercial controls, and 3 instruments.
Two controls and 3 serum panels tested in duplicate, twice per day for 20 days.
Results for Control Level 1 (Mean 77 U/L): SD 0.5 (Within-Run), %CV 0.6 (Within-Run), SD 1.5 (Within-Laboratory), %CV 2.0 (Within-Laboratory).
Results for Control Level 2 (Mean 413 U/L): SD 3.3 (Within-Run), %CV 0.8 (Within-Run), SD 6.7 (Within-Laboratory), %CV 1.6 (Within-Laboratory).
Results for Panel A (Mean 4 U/L): SD 0.3 (Within-Run), %CV 7.4 (Within-Run), SD 0.5 (Within-Laboratory), %CV 11.0 (Within-Laboratory).
Results for Panel B (Mean 162 U/L): SD 0.8 (Within-Run), %CV 0.5 (Within-Run), SD 3.3 (Within-Laboratory), %CV 2.1 (Within-Laboratory).
Results for Panel C (Mean 2629 U/L): SD 14.8 (Within-Run), %CV 0.6 (Within-Run), SD 51.6 (Within-Laboratory), %CV 2.0 (Within-Laboratory).

Within-Laboratory Precision - Urine:

Study based on CLSI EP05-A3.
Testing with 3 lots of Amylase2 reagent, 3 lots of Consolidated Chemistry Calibrator, 1 lot of commercial controls, and 3 instruments.
Two controls and 5 human urine panels tested in duplicate, twice per day for 20 days.
Results for Control Level 1 (Mean 55 U/L): SD 0.4 (Within-Run), %CV 0.8 (Within-Run), SD 0.5 (Within-Laboratory), %CV 1.0 (Within-Laboratory).
Results for Control Level 2 (Mean 180 U/L): SD 0.8 (Within-Run), %CV 0.4 (Within-Run), SD 1.3 (Within-Laboratory), %CV 0.7 (Within-Laboratory).
Results for Panel A (Mean 6 U/L): SD 0.3 (Within-Run), %CV 5.4 (Within-Run), SD 0.5 (Within-Laboratory), %CV 7.9 (Within-Laboratory).
Results for Panel B (Mean 18 U/L): SD 0.4 (Within-Run), %CV 2.1 (Within-Run), SD 0.4 (Within-Laboratory), %CV 2.4 (Within-Laboratory).
Results for Panel C (Mean 538 U/L): SD 2.7 (Within-Run), %CV 0.5 (Within-Run), SD 5.3 (Within-Laboratory), %CV 1.0 (Within-Laboratory).
Results for Panel D (Mean 1891 U/L): SD 10.2 (Within-Run), %CV 0.5 (Within-Run), SD 20.4 (Within-Laboratory), %CV 1.1 (Within-Laboratory).
Results for Panel E (Mean 2625 U/L): SD 12.2 (Within-Run), %CV 0.5 (Within-Run), SD 20.3 (Within-Laboratory), %CV 0.8 (Within-Laboratory).

System Reproducibility - Serum/Plasma:

Study based on CLSI EP05-A3.
Testing with 1 lot of Amylase2 reagent, 1 lot of Consolidated Chemistry Calibrator, 1 lot of commercial controls, and 3 instruments (each by a different technician).
Five controls tested in minimum of 3 replicates, twice per day for 5 days (n=90 for each).
Results for Control Level 1 (Mean 74 U/L): Repeatability SD 0.4, %CV 0.6; Within-Laboratory SD 0.6, %CV 0.8; Reproducibility SD 0.6, %CV 0.9.

System Reproducibility - Urine:

Study based on CLSI EP05-A3.
Testing with 1 lot of Amylase2 reagent, 1 lot of Consolidated Chemistry Calibrator, 1 lot of commercial controls, and 3 instruments (each by a different technician).
Four controls tested in minimum of 3 replicates, twice per day for 5 days (n=90 for each).
Results for Control Level 1 (Mean 54 U/L): Repeatability SD 0.5, %CV 1.0; Within-Laboratory SD 0.5, %CV 1.0; Reproducibility SD 0.6, %CV 1.1.

Accuracy:

Study to estimate bias relative to IRMM/IFCC-456.
Calibration method: Bias within +/- 2.4% with 3 lots of Amylase2 reagent, 2 lots of Consolidated Chemistry Calibrator, and 1 instrument.
Calibration Factor method: Bias within +/- 3.1% with 3 lots of Amylase2 reagent and 1 instrument.

Lower Limits of Measurement:

Study based on CLSI EP17-A2.
Testing with 3 lots of Amylase2 reagent kit on 2 instruments for minimum of 3 days.
Serum/Plasma: LoB 0 U/L, LoD 2 U/L, LoQ 2 U/L.
Urine: LoB 0 U/L, LoD 1 U/L, LoQ 3 U/L.

Linearity:

Study based on CLSI EP06-A.
Demonstrated linearity across 3 to 3010 U/L for both serum and urine.

Potentially Interfering Endogenous and Exogenous Substances - Serum/Plasma:

Study based on CLSI EP07, 3rd ed.
No significant interference (within +/- 10%) observed for Bilirubin (conjugated 60 mg/dL, unconjugated 60 mg/dL), Hemoglobin (1000 mg/dL), Total protein (15 g/dL), Triglycerides (1500 mg/dL).
No significant interference observed for various exogenous substances at specified levels (e.g., Acetaminophen 160 mg/L, Ibuprofen 220 mg/L).

Potentially Interfering Endogenous and Exogenous Substances - Urine:

Study based on CLSI EP07, 3rd ed.
No significant interference (within +/- 10%) observed for Ascorbate (150 mg/dL), Glucose (1000 mg/dL), Protein (50 mg/dL).
Interference beyond +/- 10% observed for Ascorbate at 200 mg/dL (-21% at 450 U/L analyte level, -18% at 1400 U/L analyte level).
No significant interference observed for various exogenous substances at specified levels (e.g., Acetaminophen 16 mg/dL, Ibuprofen 22 mg/dL).

Method Comparison:

Study based on CLSI EP09-A3 using Passing-Bablok regression.
Compared Amylase2 to Amylase assay (List Number 7D58) on ARCHITECT c System.
Serum (n=124): Correlation Coefficient 1.00, Intercept -1, Slope 0.98, Concentration Range 6–2788 U/L.
Urine (n=103): Correlation Coefficient 1.00, Intercept -1, Slope 0.93, Concentration Range 4–2916 U/L.

Tube Type:

Evaluated suitability of blood collection tube types for Amylase2 assay (minimum 40 donors).
Acceptable serum tube types: Serum tubes, Serum separator tubes.
Acceptable plasma tube types: Lithium heparin tubes, Lithium heparin separator tubes, Sodium heparin tubes.

Dilution Verification - Serum/Plasma:

Evaluated performance of automated dilution protocol (1:2) versus manual dilution.
Difference values of -0.1% to 0.2% demonstrated acceptable performance.

Dilution Verification - Urine:

Evaluated performance of automated dilution protocol (1:3) versus manual dilution.
Difference values of -3.0% to -1.9% demonstrated acceptable performance.

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.

K981653

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

§ 862.1070 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.

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, 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

1

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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3

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

K210633

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

5

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.

6

	Comparison of Subject Device (Amylase2) to Predicate Device (AMY)
Characteristics	Subject Device
Amylase2 (List No. 04S89)	Predicate Device
AMY (K981653; List No. 7D58)
Platform	ARCHITECT c System	Same*
Intended Use and
Indications for
Use	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).	The Amylase assay is used for the
quantitation of amylase in human
serum, 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 of
Procedure	The Amylase2 assay is a two-part
reaction. Ethylidene-4-NP-G7 (EPS) is
hydrolyzed 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 glucose
monomers and the assay chromophore
(4-nitrophenol) by α-glucosidase. The
resulting change in absorbance at 404
nm is proportional to the α-amylase
concentration in the sample.	α-Amylase hydrolyzes the 2-chloro-4-
nitrophenyl-α-D-maltotrioside
(CNPG3) to release 2-chloro-4-
nitrophenol (CPNP) and form
2-chloro-4-nitrophenyl-α-D-maltoside
(CNPG2), maltotriose, and glucose.
The rate of formation of the 2-chloro-4-
nitrophenol can be detected
spectrophotometrically at 404 nm to
give a direct measurement of α-amylase
activity in the sample.
Standardization	IRMM/IFCC†-456	Molar extinction coefficient of CNP
(non-IFCC method)
IFCC† reference method 2006‡
Use of
Calibrators	Yes	No
Calibration
Method	Calibration and Calibration Factor
method	Factor method
Use of Controls	Yes	Same
	Comparison of Subject Device (Amylase2) to Predicate Device (AMY) (Continued)
Characteristics	Subject Device
Amylase2 (List No. 04S89)	Predicate Device
AMY (K981653; List No. 7D58)
Assay Range	Serum/Plasma:
Analytical Measuring Interval:
3-3010 U/L
Extended Measuring Interval:
3010-5959 U/L
Reportable Interval:
2-5959 U/L
Urine:
Analytical Measuring Interval:
3-3010 U/L
Extended Measuring Interval:
3010-8600 U/L
Reportable Interval:
1-8600 U/L	Serum/Plasma/Urine:
Analytical Measuring Interval:
3-3010 U/L
Flex Rate Linearity: 6554 U/L
Precision	Serum/Plasma:
Samples with amylase concentrations
between 4 and 2629 U/L were
evaluated. The samples demonstrated
% coefficients of variation (%CV)
≤ 2.2% and standard deviations (SD)
≤ 0.5 U/L.

Urine:
Samples with amylase concentrations
between 6 and 2625 U/L were
evaluated. The samples demonstrated
%CV ≤ 2.9% and SD ≤ 0.5 U/L. | Serum/Plasma:
Samples with amylase concentrations
between 46.9 and 476.4 U/L
demonstrated %CV values ranging
from 2.1% to 3.7%.

Urine:
Samples with amylase concentrations
between 40.9 and 179.0 U/L
demonstrated %CV values ranging
from 1.3% to 2.0%. |
| Lower Limits of
Measurement | Serum/Plasma:
Limit of Blank: 0 U/L
Limit of Detection: 2 U/L
Limit of Quantitation: 2 U/L

Urine:
Limit of Blank: 0 U/L
Limit of Detection: 1 U/L
Limit of Quantitation: 3 U/L | Serum/Plasma/Urine:
Limit of Detection: 2.0 U/L
Limit of Quantitation: 2.4 U/L |
| Comparison of Subject Device (Amylase2) to Predicate Device (AMY) (Continued) | | |
| Characteristics | Subject Device
Amylase2 (List No. 04S89) | Predicate Device
AMY (K981653; List No. 7D58) |
| 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 lithium heparin tubes
with 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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8

9

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.

10

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 |
| Control
Level 1 | 90 | 74 | 0.4 | 0.6 | 0.6 | 0.8 | 0.6 | 0.9 |
| Control
Level 2 | 90 | 416 | 2.5 | 0.6 | 3.0 | 0.7 | 3.1 | 0.7 |
| Control
Level A | 90 | 37 | 0.4 | 1.0 | 0.5 | 1.3 | 0.6 | 1.6 |
| Control
Level B | 90 | 113 | 0.8 | 0.7 | 0.8 | 0.7 | 0.9 | 0.8 |
| Control
Level 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 |
| Control
Level 1 | 90 | 54 | 0.5 | 1.0 | 0.5 | 1.0 | 0.6 | 1.1 |
| Control
Level 2 | 90 | 171 | 1.2 | 0.7 | 1.2 | 0.7 | 1.6 | 0.9 |
| Control
Level A | 90 | 66 | 0.4 | 0.7 | 0.5 | 0.8 | 0.9 | 1.3 |
| Control
Level 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 Interfering
Substance | Interferent
Level | Potentially Interfering
Substance | Interferent
Level |
|--------------------------------------|----------------------|--------------------------------------|----------------------|
| 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	Correlation
Coefficient	Intercept	Slope	Concentration
Range
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.