(270 days)
The ATAC Direct Bilirubin Reagent Kit, which contains both reagent and calibrator, is intended for use with the ATAC 8000 Random Access Chemistry System as a system for the quantitative determination of conjugated bilirubin in serum and plasma. Conjugated bilirubin results are used for the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.
This reagent is intended to be used by trained personnel in a professional setting and is not intended for home use.
The ATAC Direct Bilirubin Reagent Kit, which contains both reagent and calibrator, is substantially equivalent to the Trace Direct Bilirubin Reagent, product UG38 (Trace Scientific, Ltd. of Melbourne, Australia) calibrated with the Sigma Bilirubin Calibrator, Total and Direct, product no. B8652 (Sigma Diagnostics, Inc. St. Louis, MO). The effectiveness of ATAC Direct Bilirubin Reagent Kit on the ATAC 8000 Random Access Chemistry System is shown in the following studies.
The ATAC Direct Bilirubin Reagent determines conjugated bilirubin through its reaction with diazotized sulfanilic acid to form a red-purple complex. The resulting increase in absorbance at 546 nm is proportional to the direct bilirubin concentration in the sample.
This document describes the acceptance criteria and performance of the ATAC Direct Bilirubin Reagent Kit, a device intended for the quantitative determination of conjugated bilirubin in serum and plasma.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct pass/fail thresholds in the provided text. However, the reported device performance demonstrates the device's characteristics, which would implicitly meet internal acceptance based on established analytical standards for diagnostic reagents. We can infer the "acceptance" by the fact that these results are presented as evidence of the device's effectiveness and substantial equivalence.
| Acceptance Criteria (Inferred from reported performance) | Reported Device Performance (ATAC Direct Bilirubin Reagent Kit) |
|---|---|
| Linearity Range | Linear from 0.1 to 20 mg/dL |
| Linearity Regression (Correlation Coefficient) | r = 0.999 |
| Linearity Regression (Sy.x) | 0.29 mg/dL |
| Within Run Precision (Serum 1, 0.9 mg/dL) | 0.10 1SD, 10.3% CV |
| Within Run Precision (Serum 2, 3.8 mg/dL) | 0.11 1SD, 3.0% CV |
| Within Run Precision (Serum 3, 6.7 mg/dL) | 0.12 1SD, 1.9% CV |
| Total Precision (Serum 1, 0.9 mg/dL) | 0.09 1SD, 9.2% CV |
| Total Precision (Serum 2, 3.8 mg/dL) | 0.13 1SD, 3.4% CV |
| Total Precision (Serum 3, 6.7 mg/dL) | 0.18 1SD, 2.7% CV |
| Method Comparison (Deming Regression Slope) | 1.143 |
| Method Comparison (Deming Regression Intercept) | -0.10 mg/dL |
| Method Comparison (Sy.x) | 0.32 mg/dL |
| Detection Limit | 0.1 mg/dL |
| Onboard Reagent/Calibration Stability (Imprecision) | Less than 0.15 mg/dL or 3% over 5 days |
| Reconstituted Stability (Shift) | Less than 0.1 mg/dL or 6% over 14 days |
2. Sample Size for the Test Set and Data Provenance
- Sample Size for Linearity: n = 18 (for standard factor recoveries).
- Sample Size for Precision: n = 60 for each of the three control serum levels (total 180 assays)
- Sample Size for Method Comparison: n = 96 (after exclusions).
- Sample Size for Detection Limit: 125 results over 25 runs.
- Data Provenance: The document states that mixed serum and plasma specimens were collected from adult patients. The country of origin is not explicitly stated, but the predicate device is from Trace Scientific, Ltd. of Melbourne, Australia, and Sigma Diagnostics, Inc. St. Louis, MO, for the calibrator, suggesting a US/Australian context. The study appears to be prospective in nature, as indicated by the collection of patient specimens for the method comparison and repeated assays for precision and detection limit.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of those Experts
This device is an in vitro diagnostic reagent kit for quantitative determination of a biomarker (conjugated bilirubin). The "ground truth" for such devices is typically established through reference methods or highly accurate analytical techniques, not through expert human interpretation of images or clinical cases. Therefore:
- Number of Experts: Not applicable in the context of this type of diagnostic device.
- Qualifications of Experts: Not applicable.
4. Adjudication Method for the Test Set
Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies involving subjective interpretations (e.g., imaging studies where multiple readers interpret results and discrepancies need to be resolved). For a quantitative chemical assay, the "adjudication" is inherent in the analytical methodology itself, such as repeat measurements, statistical analysis, and comparison to a predicate device or reference method.
- Adjudication Method: Not applicable in the traditional sense. The method comparison study involved comparing the ATAC 8000 results with those from another commercially available method, and statistical analysis (Deming regression) was used to assess agreement. Outliers were excluded based on statistical criteria (poor reproducibility and residuals exceeding 6 standard errors).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Was an MRMC study done? No. This type of study is relevant for devices involving human interpretation of results, such as imaging diagnostics. This is a quantitative chemical assay that provides a numerical output.
- Effect size of human readers improve with AI vs without AI assistance: Not applicable.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- Was a standalone study done? Yes, the entire evaluation presented (linearity, precision, method comparison, detection limit, stability) represents the standalone performance of the ATAC Direct Bilirubin Reagent Kit on the ATAC 8000 Random Access Chemistry System. This is an automated system; once the sample is loaded, the measurement is performed by the instrument and reagents without real-time human intervention in the result generation process.
7. The Type of Ground Truth Used
- Ground Truth Type:
- Reference Standards: For linearity, the ground truth was established by "standard values" which are specific concentrations of conjugated bilirubin used for calibration curves.
- Commercially Available Control Serum: For precision, the ground truth was the expected range of values for these control sera.
- Comparison to a Predicate Device/Method: For method comparison, the ground truth was established by "another commercially available method" (the "Competitive Reagent"). This approach demonstrates substantial equivalence, where the predicate serves as the de facto "ground truth" for comparative performance.
- Diluted Serum Pool: For the detection limit, the ground truth involved a diluted serum pool to assess the lowest measurable concentration.
8. The Sample Size for the Training Set
This document describes the validation of a chemical reagent kit, not a machine learning or AI-based algorithm that typically uses "training sets." The linearity standards, control sera, and patient samples used in the performance studies are for validation/testing, not for "training" the reagent itself.
- Sample Size for the Training Set: Not applicable.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the context of this device, this question is not applicable. The device's operational parameters (e.g., absorbance at 546 nm proportional to concentration) are based on established chemical principles, not on a trained algorithm.
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SEP 2 9 2003
Brea, CA 92821 T (714) 672-3553 F (714) 672-3554
SUMMARY OF 510(K) SAFETY AND EFFECTIVENESS INFORMATION
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The ATAC Direct Bilirubin Reagent Kit is intended for the quantitative determination of conjugated billrubin in serum and plasma. Conjugated bilirubin results are used for the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block. The ATAC Direct Bilirubin Reagent determines conjugated bilirubin through its reaction with diazotized sulfanilic acid to form a red-purple complex. The resulting increase in absorbance at 546 nm is proportional to the direct bilirubin concentration in the sample.
The ATAC Direct Bilirubin Reagent Kit, which contains both reagent and calibrator, is substantially equivalent to the Trace Direct Bilirubin Reagent, product UG38 (Trace Scientific, Ltd. of Melbourne, Australia) calibrated with the Sigma Bilirubin Calibrator, Total and Direct, product no. B8652 (Sigma Diagnostics, Inc. St. Louis, MO). The effectiveness of ATAC Direct Bilirubin Reagent Kit on the ATAC 8000 Random Access Chemistry System is shown in the following studies.
The recovery of conjugated bilirubin using the ATAC Direct Bilirubin Reagent is linear from 0.1 to 20 mg/dL, as shown by the recovery of linearity standards that span the usable range. Regression statistics compare standard recoveries to standard values. These statistics are shown below.
(ATAC Recoveries) = 0.11 mg/dL + 6.66 x (Standard Factor), r = 0.999, sy.x = 0.29 mg/dL, n = 18
Precision is demonstrated by the replicate assay of commercially available control serum. Precision statistics, calculated analogous to the method described in NCCLS Guideline EP3-T, are shown below.
| Sample | n | mean | Within Run | Total | ||
|---|---|---|---|---|---|---|
| 1SD | %CV | 1SD | %CV | |||
| Serum 1 | 60 | 0.9 | 0.10 | 10.3% | 0.09 | 9.2% |
| Serum 2 | 60 | 3.8 | 0.11 | 3.0% | 0.13 | 3.4% |
| Serum 3 | 60 | 6.7 | 0.12 | 1.9% | 0.18 | 2.7% |
Precision of Conjugated Bilirubin Recoveries in mg/dl
Mixed serum and plasma specimens, collected from adult patients, were assayed in duplicate for conjugated bilirubin using the ATAC 8000 Random Access Chemistry System and another commercially available method. Each pair of duplicate assays were examined and five specimens were excluded for poor reproducibility. The first assay values for the remaining duplicates were compared by Deming regression. Two additional results were excluded because their residuals exceeded 6 standard errors of regression statistics for the accepted results are shown below.
ATAC 8000 = - 0.10 mg/dL + 1.143 x Competitive Reagent Sy.x = 0.32 mg/dL n = 96 range = 0.0 - 17.5 mg/dL
The detection limit of 0.1 mg/dL is documented through the repetitive assay of a diluted serum pool. The observed total standard deviation of 125 results over 25 runs was 0.09 mg/dL. Consequently, the detection limit is reported as the round-off error of the assay.
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The 5 day onboard reagent stability and calibration stability claims are documented through the assay of serum controls over the claimed periods. In all cases, estimates of the total imprecision of conjugated bilirubin recoveries over the test periods are less than 0.15 mg/dL or 3%.
The 14 day reconstituted stability claim is documented through the assay of serum pools and linearity standards. Observed shifts in recoveries over the 14 day period are less than 0.1 mg/dL or 6%.
Wyman Stocker
Wynn Stocking Manager of Regulatory Affairs June 30, 2003
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Image /page/2/Picture/0 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo features a stylized caduceus, a symbol often associated with healthcare, with three lines forming the snake and a wavy line at the bottom. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" is arranged in a circular fashion around the caduceus.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
SEP 2 9 2003
Mr. Wynn Stocking Manager, Regulatory Affairs Elan Diagnostics 1075 W. Lambert Road - Suite D Brea, CA 92821
K030003 Re: Trade/Device Name: ATAC Direct Bilirubin Reagent and Calibrator Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: Class II Product Code: CIG; JIS Dated: June 30, 2003 Received: July 1, 2003
Dear Mr. Stocking:
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. 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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
Steven Butman
Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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510(k) Number (if known):
Device Name:
ATAC Direct Bilirubin Reagent and Calibrator
Indications for Use:
The ATAC Direct Bilirubin Reagent Kit, which contains both reagent and calibrator, is intended for use with the ATAC 8000 Random Access Chemistry System as a system for the quantitative determination of conjugated bilirubin in serum and plasma. Conjugated bilirubin results are used for the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.
This reagent is intended to be used by trained personnel in a professional setting and is not intended for home use.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Sean Cooper
(Division Sign-Off) Division of Clinical Laboratory Devices > 510(k) Number -
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________
(Optional Format 1-2-96)
§ 862.1110 Bilirubin (total or direct) test system.
(a)
Identification. A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.(b)
Classification. Class II.