(315 days)
No
The device description and performance studies focus on a standard enzymatic, spectrophotometric assay for measuring acetaminophen concentration. There is no mention of AI, ML, or related concepts in the document.
No
The device is an in vitro diagnostic (IVD) device used to quantitatively measure acetaminophen levels, which aids in diagnosing and managing acetaminophen overdose toxicity. It does not directly provide therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that "Measurement of acetaminophen is used in the diagnosis and treatment of acetaminophen overdose toxicity." This indicates the device provides information for diagnostic purposes.
No
The device is an in vitro diagnostic (IVD) assay consisting of chemical reagents and is intended to be used on a clinical chemistry analyzer (hardware). It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states "Intended for the in vitro quantitative measurement of acetaminophen in serum, lithium heparin plasma." The term "in vitro" is a key indicator of an IVD.
- Device Description: The description details an "enzymatic, spectrophotometric assay" that measures a substance (acetaminophen) in biological samples (serum, plasma). This is characteristic of an IVD.
- Measurement of Analytes: The device measures the concentration of acetaminophen, which is an analyte in a biological sample.
- Clinical Purpose: The measurement is used "in the diagnosis and treatment of acetaminophen overdose toxicity," indicating a clinical purpose for the test results.
- Performance Studies: The performance studies described (Precision, Analytical Sensitivity, Linearity, Analytical Specificity, Method Comparison, Matrix Comparison) are typical studies performed to validate the analytical performance of an IVD.
- Predicate Device: The mention of a "Predicate Device" with a K number (K081938) further confirms that this device is being compared to a previously cleared IVD.
All of these factors strongly indicate that the SEKURE Acetaminophen L3K assay is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
Intended for the in vitro quantitative measurement of acetaminophen in serum, lithium heparin plasma. Measurement of acetaminophen is used in the diagnosis and treatment of acetaminophen overdose toxicity.
Product codes (comma separated list FDA assigned to the subject device)
LDP
Device Description
The SEKURE Acetaminophen L3K assay is an enzymatic, spectrophotometric assay for the measurement of acetaminophen concentration in serum, lithium heparin plasma and sodium heparin plasma. The assay consists two working reagents, an enzyme reagent and a color reagent. The enzyme reagent contains acyl amidohydrolase, which cleaves the amide bond of the acetaminophen, forming p-aminophenol which then reacts with the 2,5- dimethylphenol (contained the color reagent) in the presence of manganese. The product of that reaction causes increased absorbance at 605 nm which is directly proportional to the acetaminophen concentration in the sample. Testing is performed on open system clinical chemistry analyzers, such as the Hitachi 717 (K872494) in conjunction with a calibrator (510(k) exempt) which is included and controls which are provided separately.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
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Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
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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
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision: Testing was conducted according to CLSI EP05-A3. Two unaltered patient serum samples, two spiked patient serum samples and three levels of controls were assayed in duplicate twice a day for 20 days on the Hitachi 717 with daily calibration. Each sample was evaluated using three lots of Acetaminophen L3K Assay. The mean, standard deviation and coefficient of variation (%CV) were calculated using EP Evaluator. All precision studies passed the acceptance criteria of ≤ 4% CV for control 1.
Analytical Sensitivity:
- Limit of Blank (LoB) and Limit of Detection (LoD): Testing was based on CLSI EP17-A2. Testing was conducted using three lots of SEKURE Acetaminophen L3K reagent and two lots of calibrator on the Hitachi 717 analyzer. Testing involved analyzing five blank samples and five low concentration samples in quadruplicate over three operating days, producing a total of 60 measurements on each lot of reagent. The maximal LoB across the three lots was 1.0 µmol/L and maximal LoD was 2.4 µmol/L.
- Limit of Quantitation (LoQ): Testing was based on CLSI EP17-A2. Testing was conducted using three lots of SEKURE Acetaminophen L3K reagent and two lots of calibrator on the Hitachi 717 analyzer. Five low concentration samples were tested in forty replicates over five runs across three operating days on each reagent lot. The claimed LoQ for the assay is 8 µmol/L.
Linearity/Assay Reportable Range: A linearity study was performed based on guidance from CLSI EP06-A. Linearity testing was conducted using three lots of SEKURE Acetaminophen L3K reagent and two lots of calibrator. Internally prepared linearity assessment material comprised nine samples from 100 to 2700 umol/L acetaminophen. Each sample was assayed in quadruplicate on each reagent lot. The linearity data met acceptance criteria (±10% deviation) and support an assay measuring range up to 2500 µmol/L.
Stability: Shelf-life claims based on testing performed according to CLSI EP25-A. Stability testing supports a shelf life of 12 months.
Analytical Specificity (Endogenous and Exogenous Interference):
- Endogenous Interference: An interference study was performed based on CLSI EP07-A2. All potential interferents were tested at acetaminophen concentrations of 33, 100, 199 and 900 µmol/L in replicates of five. Significant interference was identified as a percent difference greater than ±10% or 8 µmol/L from control. Various levels of Hemoglobin, Conjugated Bilirubin, Unconjugated Bilirubin, Ascorbic Acid, N-Acetylcysteine, and Intralipid were tested, and results presented concentrations with no significant interference at specific acetaminophen levels.
- Exogenous Drug Interference: Potential drug interference testing was performed based on CLSI EP07-A2. All potential drug interferents were tested at acetaminophen concentrations of approximately 33, 100, 199 and 900 µmol/L in replicates of five. Significant interference was identified as a percent difference greater than ±10% or 8 µmol/L from control. Various drugs like Theophylline, Phenylbutazone, Ibuprofen, Imipramine, Acetylsalicylic Acid, Levodopa, Ampicillin, Doxycycline, Amitriptyline, Metronidazole, Cefoxitin, Cyclosporin, Methyldopa, Rifampicin, and Salicylate were tested, and their concentrations with no significant interference were reported.
Method Comparison with Predicate Device: Method comparison testing was conducted based on CLSI EP09-A3 on the Roche Hitachi 717 analyzer using the modified SEKURE Acetaminophen L3K reagent as compared to the predicate Acetaminophen L3K reagent. Testing was completed on 105 patient specimens in duplicate over seven operating days. The samples were distributed evenly throughout the assay range (115 µmol/L - 2500 µmol/L, 17.4 µg/mL -377.5 µg/mL). Each sample was tested using three lots of the modified reagent and one lot of the predicate reagent. The SEKURE Acetaminophen L3K assay is designed to have a slope of 1.0 ± 0.1 and a correlation coefficient (r) of ≥ 0.975 when compared to the predicate method with Deming regression. All three lots (A, B, C) passed the acceptance criteria for slope, %Bias, and Correlation Coefficient.
Matrix Comparison: A matrix comparison study was performed to qualify plasma as a specimen for analysis with the SEKURE Acetaminophen L3K Assay. The study was performed using one lot of reagent and one lot of calibrator on one Hitachi 717 instrument. The acetaminophen concentrations spanned the assay range. A set of forty matched sets were collected and tested. The following tube types were compared to serum tubes (without gel in plastic) and recovered within the stated acceptance criteria and are therefore suitable specimens for analysis: Serum with gel in plastic (SST), Lithium heparin with gel in plastic (PST), Lithium heparin without gel in plastic, Lithium heparin Barricor tube, Sodium heparin without gel in plastic. All matrix comparison studies passed the acceptance criteria for slope, %Bias, and Correlation Coefficient.
Clinical studies: Not Applicable.
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.
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.
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
§ 862.3030 Acetaminophen test system.
(a)
Identification. An acetaminophen test system is a device intended to measure acetaminophen, an analgestic and fever reducing drug, in serum. Measurements obtained by this device are used in the diagnosis and treatment of acetaminophen overdose.(b)
Classification. Class II.
0
Image /page/0/Picture/0 description: The image contains two logos. The logo on the left is the Department of Health & Human Services - USA logo. The logo on the right is the FDA U.S. Food & Drug Administration logo. The FDA logo is in blue.
February 8, 2019
Sekisui Diagnostics PEI Inc. Pennv White Regulatory Affairs Manager 70 Watts Avenue Charlottetown, PE Canada, C1E 2B9
Re: K180835
Trade/Device Name: SEKURE Acetaminophen L3K Assay Regulation Number: 21 CFR 862.3030 Regulation Name: Acetaminophen test system Regulatory Class: Class II Product Code: LDP Dated: December 21, 2018 Received: December 26, 2018
Dear Penny White:
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.
1
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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/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 -S
for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K180835
Device Name SEKURE Acetaminophen L3K Assay
Indications for Use (Describe)
Intended for the in vitro quantitative measurement of acetaminophen in serum, lithium heparin plasma. Measurement of acetaminophen is used in the diagnosis and treatment of acetaminophen overdose toxicity.
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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3
510(k) Summary
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR §807.92. This is a Traditional 510(k).
| The assigned 510(k) number: | K180835 |
|---|---|
| Applicant Information and Date [807.92(a)(1)] | |
| Applicant Name and Address: | SEKISUI DIAGNOSTICS P.E.I. INC. |
| 70 Watts Avenue, Charlottetown, PE | |
| Canada, C1E 2B9 | |
| Establishment Registration Number: 8020316 | |
| Application correspondent: | Penny White |
| Regulatory Affairs Manager | |
| 902-628-0934 | |
| Penny.white@sekisuidiagnostics.com |
Date Summary prepared:
February 8, 2019
Device Name and Classification [807.92(a)(2)]
| Trade Name | Common Name | Classification Name | Classification | Product
Code |
|--------------------------------------|---------------|------------------------------|-----------------------------|-----------------|
| SEKURE
Acetaminophen
L3K Assay | Acetaminophen | Acetaminophen Test
System | Class II
21 CFR 862.3030 | LDP |
Identification of Legally Marketed Predicate Devices [807.92(a)(3)]
| Predicate Device | Predicate 510(k) Number |
|---|---|
| SEKURE Acetaminophen L3K Assay | K081938 |
4
Device Description [807.92(a)(4)]
| Trade Name | Device Description |
|---|---|
| SEKURE | |
| Acetaminophen | |
| L3K Assay | The SEKURE Acetaminophen L3K assay is an enzymatic, spectrophotometric assay for the measurement of acetaminophen concentration in serum, lithium heparin plasma and sodium heparin plasma. The assay consists two working reagents, an enzyme reagent and a color reagent. The enzyme reagent contains acyl amidohydrolase, which cleaves the amide bond of the acetaminophen, forming p-aminophenol which then reacts with the 2,5- dimethylphenol (contained the color reagent) in the presence of manganese. The product of that reaction causes increased absorbance at 605 nm which is directly proportional to the acetaminophen concentration in the sample. Testing is performed on open system clinical chemistry analyzers, such as the Hitachi 717 (K872494) in conjunction with a calibrator (510(k) exempt) which is included and controls which are provided separately. |
Intended Use [807.92(a)(5)]
For the in vitro quantitative measurement of acetaminophen in serum, lithium heparin plasma and sodium heparin plasma. Measurement of acetaminophen is used in the diagnosis and treatment of acetaminophen overdose toxicity.
5
| Characteristic | Predicate Device | Modified Device |
|---|---|---|
| SEKURE Acetaminophen L3K Assay | SEKURE Acetaminophen L3K Assay | |
| Intended Use | For the in vitro quantitative measurement | |
| of acetaminophen in serum and plasma. | ||
| Measurement of acetaminophen is used | ||
| in the diagnosis and treatment of | ||
| acetaminophen overdose toxicity. | Similar | |
| For the in vitro quantitative measurement | ||
| of acetaminophen in serum, lithium | ||
| heparin plasma and sodium heparin | ||
| plasma. Measurement of acetaminophen | ||
| is used in the diagnosis and treatment of | ||
| acetaminophen overdose toxicity. | ||
| Platform | Hitachi 717 (K872494) | SAME |
| Methodology | Enzymatic (Acyl amidohydrolase) and | |
| Spectrophotometric (2,5-dimethylphenol | ||
| chromophore) | SAME | |
| Specimen type | Serum and lithium heparin plasma | Similar |
| Serum, lithium heparin plasma | ||
| and | ||
| sodium heparin plasma | ||
| Measuring | ||
| interval | 0.6 to 377.5 µg/mL (4 to 2500 µmol/L) | Similar |
| 17.4 to 377.5 µg/mL (115 to 2500 | ||
| µmol/L) |
Technological Similarities and Differences to the Predicate [807.92(a)(6)]
6
Summary of Non-Clinical Performance Data [807.92 (b)(1), 807.92 (b)(3)|
Precision
Testing was conducted according to CLSI EP05-A3. Two unaltered patient serum samples, two spiked patient serum samples and three levels of controls were assayed in duplicate twice a day for 20 days on the Hitachi 717 with daily calibration. Each sample was evaluated using three lots of Acetaminophen L3K Assay. The mean, standard deviation and coefficient of variation (%CV) were calculated using EP Evaluator. The acetaminophen data in umol/L are summarized in the following table.
| Lot | Sample | N | Mean Acetaminophen (µmol/L) | Repeatability | Within Laboratory | Acceptance Criteria | Pass/Fail | ||
|---|---|---|---|---|---|---|---|---|---|
| 1 | Control 1 | 80 | 68 | 1.8 | 2.7 | 2.5 | 3.8 | ≤ 4% CV | Pass |
| 1 | Control 2 | 80 | 238 | 4.4 | 1.9 | 6.1 | Pass | ||
| 1 | Control 3 | 80 | 764 | 13.4 | 1.8 | 14.3 | 1.9 | Pass | |
| 4 | Unaltered P1 | 80 | 170.3 | 2.1 | 1.2 | 2.4 | 1.4 | Pass | |
| 4 | Unaltered P2 | 80 | 195.5 | 2.4 | 1.2 | 2.6 | 1.4 | Pass | |
| 4 | Spiked 1 | 80 | 1295.9 | 11.5 | 0.9 | 19.7 | 1.5 | Pass | |
| 4 | Spiked 2 | 80 | 2278.6 | 17.3 | 0.8 | 51.0 | 2.2 | Pass | |
| 2 | Control 1 | 80 | 68 | 1.1 | 1.7 | 2.4 | 3.5 | Pass | |
| 2 | Control 2 | 80 | 238 | 3.9 | 1.7 | 5.8 | 2.4 | Pass | |
| 2 | Control 3 | 80 | 764 | 14.2 | 1.9 | 14.2 | 1.9 | Pass | |
| 5 | Unaltered P1 | 80 | 169.5 | 1.5 | 0.9 | 2.1 | 1.2 | Pass | |
| 5 | Unaltered P2 | 80 | 195.4 | 2.6 | 1.3 | 2.6 | 1.3 | Pass | |
| 5 | Spiked 1 | 80 | 1294.3 | 12.8 | 1.0 | 21.4 | 1.7 | Pass | |
| 5 | Spiked 2 | 80 | 2281.5 | 15.9 | 0.7 | 52.3 | 2.3 | Pass | |
| 3 | Control 1 | 80 | 68 | 1.4 | 2.0 | 2.4 | 3.5 | Pass | |
| 3 | Control 2 | 80 | 238 | 4.0 | 1.6 | 5.8 | 2.4 | Pass | |
| 3 | Control 3 | 80 | 764 | 13.6 | 1.7 | 14.2 | 1.8 | Pass | |
| 6 | Unaltered P1 | 80 | 175.0 | 1.6 | 0.9 | 2.0 | 1.2 | Pass | |
| 6 | Unaltered P2 | 80 | 202.0 | 2.7 | 1.3 | 3.0 | 1.5 | Pass | |
| 6 | Spiked 1 | 80 | 1339.3 | 13.8 | 1.0 | 22.5 | 1.7 | Pass | |
| 6 | Spiked 2 | 80 | 2357.9 | 17.5 | 0.7 | 50.0 | 2.1 | Pass |
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Analytical Sensitivity
Limit of Blank (LoB) and Limit of Detection (LoD)
Limit of Blank and Limit of Detection testing was based on CLSI EP17-A2. Testing was conducted using three lots of SEKURE Acetaminophen L3K reagent and two lots of calibrator on the Hitachi 717 analyzer. Testing involved analyzing five blank samples and five low concentration samples in quadruplicate over three operating days, producing a total of 60 measurements on each lot of reagent. The LoB for each lot was determined using a non-parametric approach to determine the rank position value at the 95th percentile. The LoD for each lot was determined using a parametric approach using the pooled SDs across low level samples.
| Lot | Limit of Blank
(µmol/L) | Limit of Detection
(µmol/L) |
|-----|----------------------------|--------------------------------|
| 1 | 1.0 | 2.38 |
| 2 | 1.0 | 1.95 |
| 3 | 1.0 | 2.23 |
The stated LoB and LoD are the maximal values across the three lots. The LoB is 1.0 µmol/L and the LoD is 2.4 umol/L.
Limit of Quantitation (LoQ)
Limit of Quantitation testing was based on CLSI EP17-A2. Testing was conducted using three lots of SEKURE Acetaminophen L3K reagent and two lots of calibrator on the Hitachi 717 analyzer. Five low concentration samples were tested in forty replicates over five runs across three operating days on each reagent lot. The stated LoQ is the highest value across the three lots. The mean, standard deviation, bias and %TE (calculated using the Westgard model) were determined for each low level sample.
| Theoretical
Acetaminophen
(µmol/L) | N | Lot 1 | | Lot 2 | | Lot 3 | | Total Error
Limit |
|------------------------------------------|----|------------------|--------------------|------------------|--------------------|------------------|--------------------|----------------------|
| | | Mean
(µmol/L) | Total
Error (%) | Mean
(µmol/L) | Total
Error (%) | Mean
(µmol/L) | Total
Error (%) | |
| 12 | 40 | 12.48 | 15.89 | 11.93 | 16.36 | 12.45 | 15.04 | |
| 10 | 40 | 10.53 | 18.83 | 9.90 | 19.00 | 10.43 | 18.49 | |
| 8 | 40 | 8.28 | 20.41 | 7.70 | 23.52 | 7.90 | 22.28 | ≤25% |
| 6 | 40 | 6.05 | 22.12 | 5.53 | 34.05 | 5.90 | 21.35 | |
| 4 | 40 | 4.00 | 25.32 | 3.35 | 54.73 | 3.80 | 35.38 | |
The LoQ for each reagent lot was determined as the lowest acetaminophen concentration at which the %TE was ≤25%. The claimed LoQ for the assay is the maximal value obtained across the three lots. The LoQ claimed is 8 umol/L.
8
Linearity/Assay Reportable Range
A linearity study was performed based on guidance from CLSI EP06-A. Linearity testing was conducted using three lots of SEKURE Acetaminophen L3K reagent and two lots of calibrator. Internally prepared linearity assessment material comprised nine samples from 100 to 2700 umol/L acetaminophen. Each sample was assayed in quadruplicate on each reagent lot. The mean and deviation of the measured mean from theoretical values were calculated using EP Evaluator.
| Theoretical
Acetaminophen
(µmol/L) | N | Lot 1 | | Lot 2 | | Lot 3 | | Acceptance
Criteria | Pass/Fail |
|------------------------------------------|---|----------------------|------------------|----------------------|------------------|----------------------|------------------|------------------------|-----------|
| | | Observed
(µmol/L) | Deviation
(%) | Observed
(µmol/L) | Deviation
(%) | Observed
(µmol/L) | Deviation
(%) | | |
| 100 | 4 | 98.8 | -1.2% | 99.3 | -0.7% | 101.3 | 1.3% | ±10% | Pass |
| 115 | 4 | 116.3 | 1.1% | 115.5 | 0.4% | 118.5 | 3.0% | | Pass |
| 125 | 4 | 125.3 | 0.2% | 124.5 | -0.4% | 128.8 | 3.0% | | Pass |
| 250 | 4 | 251.0 | 0.4% | 251.5 | 0.6% | 260.3 | 4.1% | | Pass |
| 500 | 4 | 489.5 | -2.1% | 493.0 | -1.4% | 509.8 | 2.0% | | Pass |
| 1000 | 4 | 1015.8 | 1.6% | 1022.8 | 2.3% | 1048.8 | 4.9% | | Pass |
| 2000 | 4 | 2018 | 0.9% | 2020.0 | 1.0% | 2079.5 | 4.0% | | Pass |
| 2500 | 4 | 2515 | 0.6% | 2501.3 | 0.0% | 2587.3 | 3.5% | | Pass |
| 2700 | 4 | 2690.3 | -0.4% | 2686.5 | -0.5% | 2784.5 | 3.1% | | Pass |
The linearity data met acceptance criteria and support an assay measuring range up to 2500 umol/L.
Traceability, Stability, Expected Values (controls calibrators or methods)
Value Assignment
The SEKURE Acetaminophen Calibrator is prepared gravimetrically from USP grade reference acetaminophen material to a concentration of 151 ug/mL (1000 umo/L). The calibrator preparation is verified against the master calibrator (an internal reference standard). Two lots of Acetaminophen Calibrator were verified and met acceptance criteria.
Stability
Shelf-life claims based on testing performed according to CLSI EP25-A. Stability testing supports a shelf life of 12 months.
9
Analytical Specificity (Endogenous and Exogenous Interference)
Endogenous Interference
An interference study was performed based on CLSI EP07-A2 to assess common or known substances that could interfere with the Acetaminophen L3K Assay. Interference testing was conducted using three lots of SEKURE Acetaminophen L3K reagent. All potential interferents were tested at acetaminophen concentrations of 33, 100, 199 and 900 umol/L in replicates of five. Significant interference was identified as a percent difference greater than ±10% or 8 µmol/L from control.
| Substance Tested | Highest Tested Concentration with No
Significant Interference | Acetaminophen Concentration |
|---------------------------|------------------------------------------------------------------|-----------------------------|
| Hemoglobin | 200 mg/dL (31 µmol/L) | 4.5 µg/mL (30 µmol/L) |
| Hemoglobin | 200 mg/dL (31 µmol/L) | 14.0 µg/mL (93 µmol/L) |
| Hemoglobin | 400 mg/dL (62 µmol/L) | 28.4 µg/mL (188 µmol/L) |
| Hemoglobin | 1000 mg/dL (155 µmol/L) | 130 µg/mL (861 µmol/L) |
| Conjugated Bilirubin | 2 mg/dL (23.7 µmol/L) | 4.7 µg/mL (31 µmol/L) |
| Conjugated Bilirubin | 2 mg/dL (23.7 µmol/L) | 14.8 µg/mL (98 µmol/L) |
| Conjugated Bilirubin | 32 mg/dL (364 µmol/L) | 17.4 µg/mL (115 µmol/L) |
| Conjugated Bilirubin | 40 mg/dL (475 µmol/L) | 30.2 µg/mL (200 µmol/L) |
| Conjugated Bilirubin | 40 mg/dL (475 µmol/L) | 144 µg/mL (957 µmol/L) |
| Unconjugated
Bilirubin | 2 mg/dL (34.2 µmol/L) | 5.0 µg/mL (33 µmol/L) |
| Unconjugated
Bilirubin | 4 mg/dL (68 µmol/L) | 14.8 µg/mL (98 µmol/L) |
| Unconjugated
Bilirubin | 32 mg/dL (547 µmol/L) | 17.4 µg/mL (115 µmol/L) |
| Unconjugated
Bilirubin | 24 mg/dL (410 µmol/L) | 30.2 µg/mL (200 µmol/L) |
| Unconjugated
Bilirubin | 40 mg/dL (475 µmol/L) | 144 µg/mL (958 µmol/L) |
| Ascorbic Acid | 3000 µg/dL (170 µmol/L) | 4.5 µg/mL (30 µmol/L) |
| Ascorbic Acid | 3000 µg/dL (170 µmol/L) | 16.2 µg/mL (107 µmol/L) |
| Ascorbic Acid | 3000 µg/dL (170 µmol/L) | 32.5 µg/mL (215 µmol/L) |
| Ascorbic Acid | 3000 µg/dL (170 µmol/L) | 142.8 µg/mL (946 µmol/L) |
| N-Acetylcysteine | 1500 mg/L | 4.5 µg/mL (30 µmol/L) |
| N-Acetylcysteine | 1500 mg/L | 16.6 µg/mL (110 µmol/L) |
| N-Acetylcysteine | 1500 mg/L | 32.5 µg/mL (215 µmol/L) |
| N-Acetylcysteine | 1500 mg/L | 139.2 µg/mL (922 µmol/L) |
| Intralipid | 600 mg/dL [1800 mg/dL (20 mmol/L)
Simulated Triglycerides] | 4.8 µg/mL (32 µmol/L) |
| Intralipid | 1000 mg/dL [3000 mg/dL (34 mmol/L)
Simulated Triglycerides] | 15.1 µg/mL (100 µmol/L) |
| Intralipid | 1000 mg/dL [3000 mg/dL (34 mmol/L)
Simulated Triglycerides] | 30.7 µg/mL (203 µmol/L) |
| Intralipid | 1000 mg/dL [3000 mg/dL (34 mmol/L)
Simulated Triglycerides] | 135.6 µg/mL (898 µmol/L) |
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Exogenous Drug Interference
Potential drug interference testing was performed based on CLSI EP07-A2 to assess common or known drugs that could interfere with the Acetaminophen L3K Assay. All potential drug interferents were tested at acetaminophen concentrations of approximately 33, 100, 199 and 900 umol/L in replicates of five. Significant interference was identified as a percent difference greater than ±10% or 8 umol/L from control.
| Substance Tested | Concentration with No Significant Interference |
|---|---|
| Theophylline | 222 µmol/L |
| Phenylbutazone | 2.89 mmol/L |
| Ibuprofen | 2425 µmol/L |
| Imipramine | 2.5 µmol/L |
| Acetylsalicylic Acid | 6.51 mmol/L |
| Levodopa | 25.3 µmol/L |
| Ampicillin | 152 µmol/L |
| Doxycycline | 67.5 µmol/L |
| Amitriptyline | 3.61 µmol/L |
| Metronidazole | 701 µmol/L |
| Cefoxitin | 1546 µmol/L |
| Cyclosporin | 10.0 µmol/L |
| Methyldopa | 71 µmol/L |
| Rifampicin | 78.1 µmol/L |
| Salicylate | 4.34 mmol/L |
Summary of Method Comparison
Method Comparison with Predicate Device
Method comparison testing was conducted based on CLSI EP09-A3 on the Roche Hitachi 717 analyzer using the modified SEKURE Acetaminophen L3K reagent a as compared to the predicate Acetaminophen L3K reagent. Testing was completed on 105 patient specimens in duplicate over seven operating days. The samples were distributed evenly throughout the assay range (115 umol/L - 2500 umol/L, 17.4 ug/mL -377.5 ug/mL). Each sample was tested using three lots of the modified reagent and one lot of the predicate reagent.
The SEKURE Acetaminophen L3K assay is designed to have a slope of 1.0 ± 0.1 and a correlation coefficient (t) of ≥ 0.975 when compared to the predicate method with Deming regression.
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Method Comparison Summary
| Lot | Sample
Range | Slope | | | | % Bias | | | Correlation Coefficient | | | |
|-----|-----------------------------|---------|--------|-------------------|---------------|--------|--------|---------------|-------------------------|---------|---------------|--|
| | | Target | Deming | Passing
Bablok | Pass/
Fail | Target | Result | Pass/
Fail | Target | Result | Pass/
Fail | |
| ಗಿ | 115.5 -
2446.5
umol/L | 1.0±0.1 | 0.974 | 0.975 | Pass | ± 5.0% | -2.27% | Pass | > 0.975 | 0.99999 | Pass | |
| B | | | 0.984 | 0.988 | Pass | | -1.38% | Pass | | 0.99992 | Pass | |
| C | | | 1.009 | 1.009 | Pass | | 1.55% | Pass | | 0.9998 | Pass | |
Matrix Comparison
A matrix comparison study was performed to qualify plasma as a specimen for analysis with the SEKURE Acetaminophen L3K Assay. The study was performed using one lot of reagent and one lot of calibrator on one Hitachi 717 instrument. The acetaminophen concentrations spanned the assay range. A set of forty matched sets were collected and tested.
The following tube types were compared to serum tubes (without gel in plastic) and recovered within the stated acceptance criteria and are therefore suitable specimens for analysis:
- Serum with gel in plastic (SST)
- Lithium heparin with gel in plastic (PST)
- Lithium heparin without gel in plastic ●
- Lithium heparin Barricor tube ●
- Sodium heparin without gel in plastic
Matrix Comparison Summary
| Tube
Type | Sample
Range | Slope | | | | | % Bias | | | Correlation Coefficient | | |
|--------------------|-------------------|-----------|---------|--------|--------------------|---------------|--------|--------|---------------|-------------------------|--------|---------------|
| | | Target | Regular | Deming | Passing-
Bablok | Pass/
Fail | Target | Result | Pass/
Fail | Target | Result | Pass/
Fail |
| SST | 115 – 2322 µmol/L | 1.0 ± 0.1 | 1.012 | 1.012 | 1.007 | Pass | ± 5.0% | 1.1% | Pass | ≥ 0.975 | 1.000 | Pass |
| Lithium
Heparin | | | 1.015 | 1.015 | 1.012 | Pass | | 1.2% | Pass | | 1.000 | Pass |
| PST | | | 1.009 | 1.009 | 1.000 | Pass | | 0.8% | Pass | | 1.000 | Pass |
| Sodium
Heparin | | | 1.012 | 1.012 | 1.006 | Pass | | 1.1% | Pass | | 1.000 | Pass |
| Barricor | | | 1.004 | 1.005 | 1.000 | Pass | | 0.2% | Pass | | 1.000 | Pass |
Clinical studies
(clinical sensitivity, clinical specificity, other clinical supportive data)
Not Applicable
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Expected values/Reference Range
The package insert contains the following reference ranges cited from literature. (Tietz Textbook of Clinical Chemistry, Second Edition, pp 1168, 2212, W.B. Saunders Company, Philadelphia (1994))
Therapeutic concentration: 10-30 µg/mL (66-199 µmol/L) Toxic concentration: > 200 µg/mL (1324 µmol/L) These values are suggested guidelines. It is recommended that each laboratory establish its own expected range.
Proposed Labeling
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10
Conclusion
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.