(60 days)
The Atellica® CH Amylase_2 (AMY_2) assay is for in vitro diagnostic use in the quantitative determination of amylase activity in human serum, plasma (lithium heparin), and urine using the Atellica® CH Analyzer. Such measurements are used primarily in the diagnosis and monitoring of acute pancreatitis (inflammation of the pancreas).
The Atellica® CH Amylase_2 (AMY_2) assay is based on the procedure of Jensen and Wydeveld. The Atellica CH AMY 2 assay uses ethylidene blocked p-nitrophenylmaltoheptaoside as substrate. The indicator enzyme a-glucosidase, used to release pnitrophenol (PNP), is also employed in the assay. The terminal glucose of the substrate is chemically blocked, preventing cleavage by the indicator enzymes. The released pnitrophenol is measured at 410/694 nm.
The Siemens Healthcare Diagnostics Inc. Atellica® CH Amylase_2 (AMY_2) assay is an in vitro diagnostic device for the quantitative determination of amylase activity in human serum, plasma (lithium heparin), and urine. These measurements are used primarily in the diagnosis and monitoring of acute pancreatitis.
Here's an analysis of its acceptance criteria and the supporting study data:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" with pass/fail thresholds for each performance characteristic. Instead, it presents performance results which are implicitly considered acceptable for substantial equivalence to the predicate device. Based on the provided data, the table below summarizes the reported device performance for key analytical characteristics.
| Performance Characteristic | Acceptance Criteria (Implicit from Predicate & CLSI Guidelines) | Reported Device Performance (Atellica® CH Amylase_2) |
|---|---|---|
| Detection Limit (LoB) | Not explicitly stated; generally as low as feasible and clinically relevant. | 1 U/L (Serum/Plasma/Urine) |
| Detection Limit (LoD) | Not explicitly stated; generally as low as feasible and clinically relevant. | 7 U/L (Serum/Plasma), 9 U/L (Urine) |
| Quantitation Limit (LoQ) | Clinically relevant low end of the measuring interval with Total Error ≤ 30%. | 18 U/L (Serum/Plasma) with TE ≤ 30%; 19 U/L (Urine) with TE ≤ 30% |
| Linearity (Measuring Interval) | Linear across the claimed measuring interval; p-values of non-linear terms > 0.05, OR allowable bias ≤ 10% or ≤ 10 U/L. | Demonstrated linear from 20 to 1500 U/L (Serum, Plasma, Urine). |
| Precision (Repeatability CV) | Not explicitly stated; typically low CV% for analytical methods. | 0.2% - 1.7% (Depends on sample & concentration) |
| Precision (Within-Lab CV) | Not explicitly stated; typically low CV% for analytical methods. | 0.4% - 2.2% (Depends on sample & concentration) |
| Interferences (Bias) | Bias exceeding 10% is considered interference. | No significant interference for Hemoglobin (500 mg/dL), Bilirubin (conjugated 30 mg/dL, unconjugated 30 mg/dL), Lipemia (Intralipid® 650 mg/dL), Acetaminophen (30 mg/dL), Ascorbic Acid (20 mg/dL), Acetylsalicylic Acid (200 mg/dL). |
| Method Comparison (Correlation) | Not explicitly stated; typically good correlation (high 'r' value) and a regression equation close to y=x for substantial equivalence. | Serum: r=0.996, y = 1.09x + 0 U/L (vs. Roche Cobas) Urine: r=0.998, y = 1.11x - 1 U/L (vs. Roche Cobas) |
| Matrix Equivalency (Correlation) | Not explicitly stated; typically good correlation and a regression equation close to y=x. | Plasma (Lithium heparin) vs Serum: r=1.000, y = 1.00x + 0 U/L |
2. Sample sizes used for the test set and the data provenance
Detection Limit (LoB/LoD):
- Sample Size: LoB: 4 samples with no analyte tested (N=20 repetitions) for 3 days, using 3 reagent lots. LoD: 4 low analyte samples tested (N=20 repetitions) for 3 days, using 3 reagent lots. This totals to 240 replicates for LoB and 240 replicates for LoD.
- Data Provenance: Not explicitly stated, but implies laboratory-prepared control samples or de-identified human samples with near-zero or low analyte levels. Likely internal data from Siemens Healthcare Diagnostics Inc. R&D organization.
Limit of Quantitation (LoQ):
- Sample Size: 4 low samples processed for 3 reagent lots for 3 days, on one instrument. This totals 120 measurements per lot.
- Data Provenance: Not explicitly stated, but likely internal data from Siemens Healthcare Diagnostics Inc. R&D organization, using prepared low-concentration samples.
Linearity:
- Sample Size: 9 samples spanning the assay measuring interval for serum specimens and 9 samples for urine specimens. Each sample was measured in 5 replicates.
- Data Provenance: Samples were prepared by mixing high and low concentration samples, and by spiking native serum or urine pools with amylase. Low pools were created by diluting with CH diluent. Origin of native serum/urine pools not specified, but likely internal or commercially sourced.
Precision:
- Sample Size: n=2 replicates, two times per day for at least 20 days, for a total of 80 replicates per sample. This was done for controls, serum, plasma, and urine pools.
- Data Provenance: Laboratory controls, serum, plasma, and urine pools were used. Likely internal data from Siemens Healthcare Diagnostics Inc. R&D organization.
Interferences:
- Sample Size: Not explicitly given for the number of distinct samples, but tests were conducted using "fresh sample pools" (low and high measurand levels in serum and urine) spiked with interferents.
- Data Provenance: Fresh sample pools implies human serum and urine, likely obtained or prepared internally.
Method Comparison:
- Sample Size: Serum: N=118 samples. Urine: N=114 samples.
- Data Provenance: Remnant de-identified samples were tested. The study included native and spiked samples. The studies were conducted internally by Siemens Healthcare Diagnostics Inc. R&D personnel and externally by a contracted laboratory. The country of origin for these remnant samples is not specified, but typically would be from US clinical labs if the filing is for the US market.
Matrix Equivalency:
- Sample Size: N=66 matched serum and lithium heparin plasma sets.
- Data Provenance: Matched serum and lithium heparin plasma sets. Some samples were spiked with amylase. Likely internal data, origin of native samples unspecified.
Expected Values (Reference Intervals):
- Sample Size: Not explicitly stated for the verification study, but reference intervals were "verified". CLSI EP28-A3 suggests a minimum of 20 samples for verification.
- Data Provenance: Verified on the Atellica® CH Analyzer. Reference "Data on file at Siemens Healthcare Diagnostics".
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This device is an in vitro diagnostic assay that measures amylase activity, not an imaging or a subjective diagnostic device requiring expert interpretation of results for ground truth. Therefore, no external experts were used to establish a "ground truth" for the test set in the way one might for diagnostic imaging or pathology. The ground truth (or 'true value') for quantitative assays is established through meticulous analytical methods, calibration using traceable reference materials (IRMM/IFCC-456 for this device), and comparison to a legally marketed predicate device.
The personnel conducting the method comparison study were "laboratory technicians with training similar to personnel who would conduct the tests in a hospital laboratory setting."
4. Adjudication method for the test set
Not applicable. As a quantitative assay, the results are numerical and objectively measured, not subject to individual interpretation and thus do not require an adjudication method among experts.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This is an in vitro diagnostic assay performed by an automated analyzer, not an AI-assisted diagnostic device that would involve human readers (e.g., radiologists, pathologists) interpreting images or clinical data.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the performance data presented (Detection Limit, LoQ, Linearity, Precision, Interferences, Method Comparison, Matrix Equivalency) are all standalone performance data of the Atellica® CH Amylase_2 analyzer and its reagents, without human-in-the-loop performance influencing the assay results directly. The device automatically performs the quantitative determination of amylase activity.
7. The type of ground truth used
The "ground truth" for this quantitative assay is established via:
- Calibration Traceability: Traceable to IRMM/IFCC-456 Pancreatic Alpha-Amylase Reference Material and commutable to the IFCC Alpha-Amylase Primary Reference Procedure.
- Comparison to Predicate: Performance is demonstrated as substantially equivalent to a legally marketed predicate device (Roche Cobas Amylase Reagent), implying that the predicate's established accuracy serves as a benchmark.
- Analytical Standards and Controls: Use of internal and external quality control materials with known target values.
- Spiked Samples: For linearity, method comparison, and matrix equivalency, samples were spiked with known concentrations of amylase to cover the measuring range.
8. The sample size for the training set
Not applicable. This is a traditional in vitro diagnostic assay based on enzymatic colorimetric reactions, not an AI/ML-based algorithm that would require a "training set" in the context of machine learning. The "training" for such a device involves chemical formulation, instrument design, and analytical validation.
9. How the ground truth for the training set was established
Not applicable, as there is no "training set" in the context of AI/ML for this device.
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July 30, 2019
Siemens Healthcare Diagnostics Inc. Catherine Daigle Regulatory Technical Specialist 500 GBC Drive P.O. Box 6101, M/S 514 Newark, DE 19714
Re: K191454
Trade/Device Name: Atellica® CH Amylase 2 (AMY 2) Regulation Number: 21 CFR 862.1070 Regulation Name: Amylase Test System Regulatory Class: Class II Product Code: JFJ Dated: May 30, 2019 Received: May 31, 2019
Dear Catherine Daigle:
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.
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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 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 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,
Kellie B. Kelm, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health 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) K191454
Device Name Atellica® CH Amylase_2 (AMY_2)
Indications for Use (Describe)
The Atellica® CH Amylase_2 (AMY_2) assay is for in vitro diagnostic use in the quantitative determination of amylase activity in human serum, plasma (lithium heparin), and urine using the Atellica® CH Analyzer. Such measurements are used primarily in the diagnosis and monitoring of acute pancreatitis (inflammation of the pancreas).
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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Image /page/3/Picture/0 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is written in teal, and the word "Healthineers" is written in orange below it. To the right of the words is a graphic of orange dots in a circular pattern.
Siemens Healthcare Diagnostics Inc. 500 GBC Drive, Mailstop 514 P.O. Box 6101 Newark, DE 19714-6101
510(k) Summary for Atellica® CH Amylase_2 (AMY_2)
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.
ASSIGNED 510(K) NUMBER
The assigned 510(k) number is: K191454
APPLICANT AND DATE
Catherine I. Daigle, MS Siemens Healthcare Diagnostics Inc. 500 GBC Drive, M/S 514 Newark, DE 19714-6101 Email: catherine.i.daigle@siemens-healthineers.com Phone: 302-631-7310 Fax: 302-631-6299
May 30, 2019
MANUFACTURER
Siemens Healthcare Diagnostics Inc. 511 Benedict Ave Tarrytown, NY 10591 Registration Number: 2432235
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REGULATORY INFORMATION
| Common Name: | Photometric Method, Amylase |
|---|---|
| Proprietary Name: | Atellica CH Amylase_2 (AMY_2) |
| Classification Name: | Amylase Test System |
| Regulation Number: | 21CFR862.1070 |
| Classification: | Class II |
| Product Code: | JFJ |
| Panel: | Clinical Chemistry |
| Predicate Device: | Roche Cobas Amylase Reagent(K903309) |
Requlatory Submission for the Atellica® CH Amvlase 2 (AMY 2)
DEVICE DESCRIPTION
ATELLICA CH AMYLASE 2 (AMY-2)
The Atellica® CH Amylase_2 (AMY_2) assay is based on the procedure of Jensen and Wydeveld. The Atellica CH AMY 2 assay uses ethylidene blocked p-nitrophenylmaltoheptaoside as substrate. The indicator enzyme a-glucosidase, used to release pnitrophenol (PNP), is also employed in the assay. The terminal glucose of the substrate is chemically blocked, preventing cleavage by the indicator enzymes. The released pnitrophenol is measured at 410/694 nm.
Reaction Equation
Image /page/4/Figure/7 description: This image shows two chemical reactions. In the first reaction, Ed-G7PNP is converted to Ed-Gn + Gn-PNP by alpha-amylase. In the second reaction, Gn-PNP is converted to PNP + Glucose by alpha-Glucosidase.
Serum, lithium heparin plasma and urine specimens may be used. The reagent is stored unopened at 2 - 8 °C and is stable for use on system for 31 days. Calibration is performed every 62 days for a reagent lot or every 31 days for an individual pack well.
-
- Jenson AP, Wydeveld A. α-(p-nitrophenyl) maltohexaside as a substrate for the assay of amylase. Nature. 1958; 182:525-526.
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INTENDED USE / INDICATIONS FOR USE
ATELLICA CH AMYLASE_2 (AMY-2)
The Atellica® CH Amylase_2 (AMY_2) assay is for in vitro diagnostic use in the quantitative determination of amylase activity in human serum, plasma (lithium heparin), and urine using the Atellica® CH Analyzer. Such measurements are used primarily in the diagnosis and monitoring of acute pancreatitis (inflammation of the pancreas).
COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
Below is a features comparison for the Atellica® CH Amylase_2 (AMY_2) assay and the predicate device:
| Feature | Predicate Device:Roche Cobas Amylase Reagent(K903309) | New Device:Atellica® CH Amylase_2 (AMY_2) |
|---|---|---|
| Intended Use : | In vitro test for the quantitativedetermination of α-amylase inhuman serum, plasma and urineon Roche/Hitachi cobas csystems. | The Atellica® CH Amylase_2(AMY_2) assay is for in vitrodiagnostic use in the quantitativedetermination of amylase activityin human serum, plasma (lithiumheparin), and urine using theAtellica® CH Analyzer. Suchmeasurements are used primarilyin the diagnosis and monitoring ofacute pancreatitis (inflammation ofthe pancreas). |
| DeviceTechnology: | Enzymatic colorimetric assay | Same |
| Sample Type: | Serum, Li-Heparin Plasma andUrine | Same |
| Expected Values: | Serum/Li-Heparin Plasma:Men/Women: 28-100 U/LSpontaneously Voided Urine:Men: 16-491 U/LWomen: 21-447 U/L | Serum/Li-Heparin Plasma: 30-118 U/LUrine: ≤ 650 U/L |
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| Feature | Predicate Device:Roche Cobas Amylase Reagent(K903309) | New Device:Atellica® CH Amylase_2 (AMY_2) |
|---|---|---|
| Standardization: | This method has beenstandardized against Rochesystem reagent using calibratedpipettes together with a manualphotometer providing absolutevalues and substrate-specificabsorptivity, ε. | Traceable to IRMM/IFCC-456Pancreatic Alpha-AmylaseReference Material andcommutable to the IFCC Alpha-Amylase Primary ReferenceProcedure as established bypatient sample correlation. |
| CalibrationFrequency: | After reagent lot change As required following quality control procedures | 62 days for a reagent lot; 31 daysfor an individual pack well |
| AnalyticalMeasuringInterval: | Serum/Plasma/Urine:3-1500 U/L | Serum/Plasma/Urine:20-1500 U/L |
| Interferences: | No significant interference for:Bilirubin (Conjugated) at aconcentration of: 60 mg/dLBilirubin (Unconjugated) at aconcentration of: 60 mg/dLLipemia (Intralipid®) at aconcentration of: 1500 mg/dLHemoglobin at a concentration of:500 mg/dL | No significant interference for:Bilirubin (Conjugated) at aconcentration of: 30 mg/dLBilirubin (Unconjugated) at aconcentration of: 30 mg/dLLipemia (Intralipid®) at aconcentration of: 650 mg/dLHemoglobin at a concentration of:500 mg/dL |
SUMMARY OF PERFORMANCE TESTING
Assay performance comparison results for the Atellica® CH Amylase_2 (AMY_2) were obtained by processing the appropriate body fluids. Summary statistics for each are provided. These data demonstrate substantial equivalency of the Atellica® CH Amylase_2 (AMY_2) compared to the predicate device. The following data represent typical assay performance.
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DETECTION LIMIT
The Limit of Blank (LoB) and Limit of Detection (LoD) were evaluated in accordance with CLSI EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures.
Assessment of LoB was the 95th percentile of all values (sorted from lowest to highest), using non-parametric approach.
| Atellica ® CH Amylase_2 (AMY_2) – Detection Capability | ||
|---|---|---|
| Limit | Protocol | Result |
| LoB | 4 samples with no analytewere tested (N=20) for 3days, one run per day, 3reagent lots | 1 U/L Serum/Plasma/Urine |
| LoD | 4 low analyte samples weretested (N=20) for 3 days, onerun per day, 3 reagent lots | 7 U/L Serum/Plasma |
| 9 U/L Urine |
LoB Rank Position = 0.5 +0.95*B, where B=total reps=240; Rank = 228.5
LoQ
The Limit of Quantitation (LoQ) for serum/plasma and urine was determined as described in CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures. Total Error is calculated using: TE = |bias| + 2 * SD.
For both serum/plasma and urine fluids, 4 low samples were processed on three reagent lots for three days, on one instrument for a total of 120 measurements per lot. For serum/plasma, the measured LoQ was 18 U/L in support of the low end of the measuring interval of 20 U/L for serum and plasma samples. For urine, the measured LoQ was 19 U/L in support of the low end of the measuring interval of 20 U/L for urine samples. The LoQ claim of 20 U/L for serum/plasma and urine are each based on a total of 120 determinations with a total error goal of ≤ 30% for serum/plasma specimens and ≤ 30% for urine specimens.
LINEARITY
Linearity was evaluated with 9 samples which spanned the assay measuring interval for serum specimens and 9 samples which spanned the assay measuring interval for urine specimens. Each was prepared by mixing high and low concentration samples across the measurement interval as described in CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures. The high sample was prepared by spiking
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native serum or urine pools with amylase. Low pools were created by diluting serum and urine samples with CH diluent. Five replicates were measured for each sample. The mean of these replicates was used for the calculations.
The assay was considered linear across the measuring interval if the p-values of nonlinear terms in the quadratic and cubic fit equations are nonsignificant (p > 0.05). If any of the aforementioned p-values are ≤ 0.05, then linearity was determined via an allowable bias of ≤ 10% or ≤ 10 U/L, whichever is greater, for the observed values vs. the linear fit. Linearity of the Atellica CH Amylase 2 (AMY 2) was demonstrated with both serum and urine specimens to encompass the measuring interval of 20 to 1500 U/L for serum, plasma, and urine specimens.
PRECISION
Precision testing was performed in accordance with CLS/ EP05-A3, Evaluation of Precision Performance of Quantitative Measurement Methods. Precision was tested using n = 2 replicates, two times per day for at least 20 days for a total of 80 replicates per sample with controls, serum, plasma, and urine pools on one instrument. Analysis of variance (ANOVA) was used to evaluate the data consistent with the recommendations of EP05-A3. The data are summarized in the following table.
| Repeatability | Within-Lab Precision | |||||
|---|---|---|---|---|---|---|
| Sample Type | n | MeanU/L | SDaU/L | CVb(%) | SDaU/L | CVb(%) |
| Sample 1 | 80 | 52 | 0.6 | 1.1 | 0.7 | 1.4 |
| Serum QC | 80 | 187 | 0.8 | 0.4 | 1.1 | 0.6 |
| Sample 2 | 80 | 1128 | 2.2 | 0.2 | 4.3 | 0.4 |
| Urine QC | 80 | 58 | 1.0 | 1.7 | 1.3 | 2.2 |
| Urine 1 | 80 | 183 | 0.8 | 0.4 | 2.3 | 1.3 |
| Urine 2 | 80 | 1260 | 9.3 | 0.7 | 21.5 | 1.7 |
ª SD = standard deviation
b CV = coefficient of variation
INTERFERENCES
CLSI EP07-A2, Interference Testing in Clinical Chemistry, was followed for the interference testing. The interference study was conducted using a "paired difference worst case scenario" approach where these compounds were spiked into fresh sample pools containing either low or high levels of measurand in serum and urine pools.
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Bias is the difference in the results between the control sample (without the interferent) and the test sample (contains the interferent) expressed in percent. Bias exceeding 10% is considered interference. Dilution studies were conducted to determine the level at which the spiked substance no longer displayed significant interference. Dilution studies were conducted at two analyte concentrations, if both sample pools show significant interference. This study was conducted as needed for both serum pools.
| Approximate Concentration (within 15%) of Analytes in Test Pools | |||
|---|---|---|---|
| Analyte | Matrix | Low | High |
| Amylase | Serum | 100 U/L | 400 U/L |
| Amylase | Urine | 100 U/L | 400 U/L |
No interference was detected a the following analyte concentrations.
| Substance | Substance Test ConcentrationCommon Unit |
|---|---|
| Hemoglobin | 500 mg/dL |
| Bilirubin, conjugated | 30 mg/dL |
| Bilirubin, unconjugated | 30 mg/dL |
| Lipemia (Intralipid®) | 650 mg/dL |
| Acetaminophen | 30 mg/dL |
| Ascorbic Acid | 20 mg/dL |
| Acetylsalicylic Acid | 200 mg/dL |
Interference Testing for Serum and Urine
METHOD COMPARISON
The predicate device selected for the method comparison study was the Roche Cobas Amylase (AMYL2) Reagent. Remnant de-identified samples were tested. No patient history information was obtained on these samples. Inclusion/exclusion data criteria are not applicable. The study included native and spiked samples to properly span the assay measuring interval.
These studies were conducted internally by Siemens Healthcare Diagnostic Inc. R&D organization personnel, and externally by a contracted laboratory. The personnel conducting the study were laboratory technicians with training similar to personnel who would conduct the tests in a hospital laboratory setting. They were trained on the operation of both the device and the predicate device. A split sample method comparison, following CLSI EP09-A3, Measurement Procedure Comparision and Bias Estimation Using Patient Samples, demonstrated good agreement between the Atellica® CH Amylase_2 (AMY_2) and the predicate Roche Cobas Amylase (AMYL2) assay with patient samples.
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The results across the full assay intervals were analyzed using weighted Deming regression. For the serum method comparison, one replicate was processed on the Cobas while two replicates were processed on the Atellica. For the urine method comparison two replicates were processed for each sample on both systems. Only the first replicate results were used in statistical analysis. Indicated samples were spiked with pancreatic amylase to span the assay measuring interval.
| SpecimenType | ComparisonAssay (x) | N | r | RegressionEquation | Sample Range (on theRoche Cobas) |
|---|---|---|---|---|---|
| Serum | Roche CobasAMYL2 | 118 | 0.996 | y = 1.09x + 0 U/L | 28-1294 U/L |
| Urine | Roche CobasAMYL2 | 114 | 0.998 | y = 1.11x - 1 U/L | 20-1194 U/L |
MATRIX EQUIVALENCY
Matched serum and lithium heparin plasma sets were processed with N= 2 replicates using only the first replicate for analysis on the Atellica® CH Amylase 2 (AMY 2) assay. Some samples were spiked with amylase to obtain samples spanning the assay measuring interval. The table below summarizes the Deming linear regression statistics.
| Specimen Type | Comparison Assay (x) | N | r | Regression Equation | Sample Range |
|---|---|---|---|---|---|
| Plasma (Lithium heparin) | Atellica® CH AMY_2 serum | 66 | 1.000 | y = 1.00x + 0 U/L | 36 - 1419 U/L |
EXPECTED VALUES
Reference intervals for healthy adults were verified on the Atellica® CH Analyzer in accordance with CLSI EP28-A3, Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory. As with all in vitro diagnostic assays, each laboratory should determine its own reference interval for the diagnostic evaluation of patient results. Consider these values as guidance only.
| Group | Specimen type | Reference Intervalcommon unit (SI unit) |
|---|---|---|
| Adults | Serum/plasma1 | 30 to 118 U/L |
| Adults | Urine2 | ≤ 650 U/L |
- Data on file at Siemens Healthcare Diagnostics. (Evidence-based Medicine and Test Utilization Developing Reference Intervals for Clinical Chemistry Systems Using the CLSI C28-A2 Guideline)
-
- Wu AHB. Tietz Clinical Guide to Laboratory Tests. 4th ed. Philadelphia, PA: WB Saunders Co; 2006:104.
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EXTENDED MEASURING INTERVAL
The Atellica® CH Amylase_2 assay parameters support both serum/plasma and urine extended ranges 3x the upper measuring interval.
Using CH Diluent, 3-fold manual dilutions of 5 serum and 5 urine pools were made. Both the undiluted and diluted pools were processed with N=4 replicates; where the undiluted samples were auto-diluted on the Atellica CH system.
The serum/plasma and urine extended measuring interval is up to 4500 U/L.
STANDARDIZATION
The Atellica® CH AMY_2) assay is traceable to the IRMM/IFCC-456 reference material and commutable to the IFCC Alpha-Amylase Primary Reference Procedure as established by patient sample correlation.
Assigned values for calibrators are traceable to this standardization.
CONCLUSION
The Atellica® CH Amylase_2 (AMY_2) is substantially equivalent to the Roche Cobas Amylase Reagent in principle and performance based on the similarity of device designs and function demonstrated through method comparison and other performance attributes.
§ 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.