(149 days)
The ONLINE TDM N-acetylprocainamide assay is for the quantitative determination of Nacetylprocainamide in human serum or plasma on Roche automated clinical chemistry analyzers. Measurements obtained from this device are used in the diagnosis and treatement of Nacetylprocainamide overdose and in monitoring the levels of N-acetylprocainamide to help ensure appropriate therapy.
The ONLINE TDM N-acetylprocainamide assay is for the quantitative determination of N-acetylprocainamide in human serum or plasma on Roche automated clinical chemistry analyzers. The proposed labeling indicates the Roche Hitachi 911, 912, 917 and Modular P analyzers can be used with the Roche ONLINE TDM N-acetylprocainamide reagent kits. The assay is based on a homogeneous enzyme immunoassay technique used for the quantitative analysis of N-acetylprocainamide in human serum or plasma. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the sample can be measured in terms of enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that is measured spectrophotometrically. Endogenous serum G6PDH does not interfere because the coenzyme functions only with the bacterial (Leuconostoc mesenteroids) enzyme employed in the assay.
Here's a breakdown of the acceptance criteria and study information for the ONLINE TDM N-acetylprocainamide device based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance:
The provided document doesn't explicitly state numerical "acceptance criteria" in the typical sense (e.g., "sensitivity must be >90%"). Instead, the acceptance is based on demonstrating "substantial equivalence" to a predicate device, meaning its performance characteristics (precision, method comparison, etc.) are "acceptable" and comparable to the predicate. Therefore, the "reported device performance" is the direct evidence of meeting this established equivalence.
| Performance Characteristic | Acceptance Criteria (Implied by Predicate Equivalence) | Reported Device Performance (ONLINE TDM N-acetylprocainamide) | Predicate Device Performance (COBAS FP N-acetylprocainamide or COBAS FARA II for method comparison) |
|---|---|---|---|
| NCCLS Precision, Within Run | |||
| Control 1 (Mean µg/ml) | Acceptable precision as demonstrated by the predicate device. | 1.7 | 5.4 |
| Control 1 (SD µg/ml) | ≤ 0.09 (based on predicate) | 0.07 | 0.09 |
| Control 1 (CV%) | ≤ 1.6% (based on predicate) | 3.9% | 1.6% |
| Control 2 (Mean µg/ml) | Acceptable precision as demonstrated by the predicate device. | 4.0 | 11.5 |
| Control 2 (SD µg/ml) | ≤ 0.18 (based on predicate) | 0.08 | 0.18 |
| Control 2 (CV%) | ≤ 1.6% (based on predicate) | 2.0% | 1.6% |
| Control 3 (Mean µg/ml) | Acceptable precision as demonstrated by the predicate device. | 8.2 | 20.9 |
| Control 3 (SD µg/ml) | ≤ 0.60 (based on predicate) | 0.17 | 0.60 |
| Control 3 (CV%) | ≤ 2.9% (based on predicate) | 2.1% | 2.9% |
| NCCLS Precision, Total | |||
| Control 1 (Mean µg/ml) | Acceptable precision as demonstrated by the predicate device. | 1.7 | 5.4 |
| Control 1 (SD µg/ml) | ≤ 0.15 (based on predicate) | 0.08 | 0.15 |
| Control 1 (CV%) | ≤ 2.8% (based on predicate) | 5.0% | 2.8% |
| Control 2 (Mean µg/ml) | Acceptable precision as demonstrated by the predicate device. | 4.0 | 11.5 |
| Control 2 (SD µg/ml) | ≤ 0.27 (based on predicate) | 0.16 | 0.27 |
| Control 2 (CV%) | ≤ 2.3% (based on predicate) | 4.0% | 2.3% |
| Control 3 (Mean µg/ml) | Acceptable precision as demonstrated by the predicate device. | 8.2 | 20.9 |
| Control 3 (SD µg/ml) | ≤ 0.68 (based on predicate) | 0.26 | 0.68 |
| Control 3 (CV%) | ≤ 3.2% (based on predicate) | 3.2% | 3.2% |
| Method Comparison (Linear Regression) | |||
| N (samples) | A sufficient number of samples to establish statistical correlation. | 54 | 153 |
| Range (µg/ml) | Comparable to the therapeutic range of the drug. | 0.5 - 16.3 | 0.5 - 29 |
| Slope (y = mx + b) | Close to 1.0 (indicating good agreement). | 1.03 | 0.978 (for predicate vs. COBAS FARA II) |
| Y-intercept (y = mx + b) | Close to 0.0 (indicating minimal systematic bias). | 0.09 | 0.059 (for predicate vs. COBAS FARA II) |
| Correlation Coefficient (r) | Close to 1.0 (indicating strong linear relationship). Typically > 0.95 for method comparison. | 0.995 | 0.997 (for predicate vs. COBAS FARA II) |
| SD (md 95) | Acceptable statistical agreement between methods. (Interpretation of this specific metric requires more context on "md 95" from the NCCLS guidelines, but generally indicates the agreement limit between methods). | 0.389 | Not directly provided for the predicate vs. ONLINE TDM, but the predicate itself had a method comparison with a different device, COBAS FARA II, suggesting its own agreement levels with an established method. |
Study Conclusion: The document states, "All of the performance characteristics including precision, lower detection limit, specificity, and interfering substances, method comparisons, and linearity provided acceptable results compared to the predicate device. These experiments provide evidence that the Roche ONLINE TDM N-acetylprocainamide assay is substantially equivalent to the currently marketed Roche COBAS INTEGRA N-acetylprocainamide assay."
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Sizes:
- Precision (NCCLS): The sample size for controls for the precision study is not explicitly stated as a number of individual samples, but NCCLS guidelines for precision studies typically involve multiple replicates (e.g., 20 or more) tested over several days. The results are reported as Means, Standard Deviations (SD), and Coefficient of Variation (CV%) for three different control levels.
- Method Comparison: N = 54 patient samples were used for the comparison between the ONLINE TDM N-acetylprocainamide and the COBAS FP N-acetylprocainamide (predicate).
- Data Provenance: The document does not specify the country of origin for the data or whether the data was retrospective or prospective. Typically, for a 510(k) submission of this type, the data would be generated from internal laboratory studies (prospective) using a mix of patient samples and spiked controls.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts:
This information is not applicable to this type of device (an in vitro diagnostic assay for drug level measurement). For these devices, "ground truth" for method comparison is established by comparing the candidate device's results against a previously cleared, established, and accepted method (the predicate device) or a reference method. It does not involve human expert consensus in the way a diagnostic imaging or pathology device might.
4. Adjudication Method for the Test Set:
This is not applicable as there is no human interpretation or subjective assessment involved that would require an adjudication process. The comparison is objective (numerical results from an automated analyzer).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of Human Readers Improve with AI vs. Without AI Assistance:
This is not applicable. This is an in vitro diagnostic assay, not an AI-powered image analysis or diagnostic support tool for human readers. Therefore, no MRMC study was performed, and there is no "human-in-the-loop" component in the interpretation of the results from this device.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done:
The performance shown (precision, method comparison, etc.) is the standalone performance of the assay on the automated clinical chemistry analyzers. As an in vitro diagnostic test, the device provides a quantitative numerical result; its "performance" is inherently "algorithm only" in the sense that it automates the measurement process. There is no human interpretation of the assay's direct output (e.g., reading a strip or visually interpreting a color change that would require a human-in-the-loop consideration).
7. The Type of Ground Truth Used:
The "ground truth" for the method comparison study was the results obtained from the predicate device, the COBAS INTEGRA N-acetylprocainamide (K951595). For precision studies, the "ground truth" is the inherent precision observed when repeatedly testing known control materials.
8. The Sample Size for the Training Set:
This information is not provided and is generally not applicable in the context of traditional in vitro diagnostic assays like this one. These assays are based on established biochemical reactions (homogeneous enzyme immunoassay) and spectrophotometric measurement, not on machine learning models that require "training sets." The development and optimization of such assays involve rigorous chemical and laboratory testing to define reagent formulations, reaction conditions, and calibration curves, but this isn't referred to as a "training set" in the machine learning sense.
9. How the Ground Truth for the Training Set Was Established:
As discussed above, the concept of a "training set" and "ground truth" for it, in the AI/machine learning sense, does not apply to this type of traditional IVD device. The assay's performance and accuracy are established through analytical validation studies (like precision, linearity, method comparison) against known standards and predicate methods.
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AUG 16 2006
| 510(k) Summary | |
|---|---|
| Introduction | According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence. |
| 1) Submittername, address,contact | Roche Diagnostics Corporation9115 Hague Rd.Indianapolis, IN 46250(317) 521-7688Contact Person: Dimitris Demirtzoglou |
| 2) Device name | Proprietary name: ONLINE TDM N-acetylprocainamideCommon name: Enzyme Immunoassay, N-acetylprocainamideClassification name: Enzyme Immunoassay, N-acetylprocainamide |
| 3) Predicatedevice | We claim substantial equivalence to the currently marketed COBASINTEGRA N-acetylprocainamide (K951595).Continued on next page |
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510(k) Summary, Continued
The ONLINE TDM N-acetylprocainamide assay is for the quantitative 4) Device determination of N-acetylprocainamide in human serum or plasma on Description Roche automated clinical chemistry analyzers. The proposed labeling indicates the Roche Hitachi 911, 912, 917 and Modular P analyzers can be used with the Roche ONLINE TDM N-acetylprocainamide reagent kits. The assay is based on a homogeneous enzyme immunoassay technique used for the quantitative analysis of N-acetylprocainamide in human serum or plasma.6,7 The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the sample can be measured in terms of enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that is measured spectrophotometrically. Endogenous serum G6PDH does not interfere because the coenzyme functions only with the bacterial (Leuconostoc mesenteroids) enzyme employed in the assay. The ONLINE TDM N-acetylprocainamide assay is for the quantitative 5.) Intended determination of N-acetylprocainamide in human serum or plasma on Use Roche automated clinical chemistry analyzers. N-acetylprocainamide measurements are used in monitoring levels of N-acetylprocainamide to ensure procainamide therapy. Continued on next page
R
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510(k) Summary, Continued
The Roche ONLINE TDM N-acetylprocainamide assay is substantially 6.) Comparison equivalent to other products in commercial distribution intended for similar to the Predicate equivalent to other products is substantially equivalent to the currently marketed Device Roche COBAS INTEGRA N-acetylprocainamide (K951595).
The Roche ONLINE TDM N-acetylprocainamide assay was evaluated for The Roone Order Order istics including precision, lower detection limit, several performance onarecificity, and interfering substances. All of the mentod comparisons, and acceptable results compared to the predicate device. These experiments provide evidence that the Roche ONLINE TDM N-These "experiments" provise "ubstantially equivalent to the currently marketed Roche COBAS INTEGRA N-acetylprocainamide assay. The following table summarizes the precision and method comparison results.
| Roche ONLINE TDM N-acetylprocainamide | Roche COBAS FP N-acetylprocainamide (Predicate) | |||||
|---|---|---|---|---|---|---|
| NCCLS Precision,Within run | Control 1 | Control 2 | Control 3 | Control 1 | Control 2 | Control 3 |
| Mean (µg/ml) | 1.7 | 4.0 | 8.2 | 5.4 | 11.5 | 20.9 |
| SD (µg/ml) | 0.07 | 0.08 | 0.17 | 0.09 | 0.18 | 0.60 |
| CV% | 3.9 | 2.0 | 2.1 | 1.6 | 1.6 | 2.9 |
| NCCLS Precision,Total | Control 1 | Control 2 | Control 3 | Control 1 | Control 2 | Control 3 |
| Mean (µg/ml) | 1.7 | 4.0 | 8.2 | 5.4 | 11.5 | 20.9 |
| SD (µg/ml) | 0.08 | 0.16 | 0.26 | 0.15 | 0.27 | 0.68 |
| CV% | 5.0 | 4.0 | 3.2 | 2.8 | 2.3 | 3.2 |
| MethodComparison | Linear Regression: ONLINE TDM N-acetylprocainamide Vs. COBAS FP N-acetylprocainamide | Linear Regression: COBAS FP N-acetylprocainamide Vs. COBAS FARA II | ||||
| N=54, Range = 0.5 -16.3 µg/mly = $1.03 x + 0.09$r = 0.995SD (md 95) = 0.389 | N=153, Range = 0.5 - 29 µg/mly= $0.978x +0.059$r=0.997 |
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
AUG 1 6 2006
Mr. Dimitris Demirtzoglou Regulatory Affairs Consultant Roche Diagnostics Operations, Inc. 9115 Hague Road Indianapolis, IN 46250
K060738 Re:
K000738
Trade/Device Name: ONLINE TDM N-acetylprocainamide Regulation Number: 21 CFR 862.3320 Regulation Name: Digoxin test system Regulatory Class: Class II Product Code: LAN Dated: July 20, 2006 Received: July 24, 2006
Dear: Mr. Demirtzoglou
We have reviewed your Section 510(k) premarket not intent to market the device We have reviewed your Section 510(x) promution is substantially equivalent (for the indications
referenced above and have determined the devices marketed in interstate referenced above and nave determined the devices marketed in interstate for use stated in the enclosure) to tegally manced te of the Medical Device Amendments, or to
commerce prior to May 28, 1976, the enactment of the Regisions of the Federal Fo commerce prior to May 20, 1970, the chance with the provisions of the Federal Food, Drug, devices that have been reclassified in accordance with as proval application (PMA).
and Cosmetic Act (Act) that do not require approval of a provisions of the Act. The and Cosmetic Act (Act) that do not require approval controls provisions of the Act. The
You may, therefore, market the device, subject to the generation, lighten of You may, therefore, market the ucvice, subject to the gents for annual registration, listing of
general controls provisions of the Act include requires withings apping misbra general controls provisions of the Act mende requirements of the security misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), ( If your device is classified (see adove) into enter regulations affecting your device
it may be subject to such additional controls. it may be subject to such additional comions. Existing mayor regals 800 to 895. In addition, FDA
can be found in Title 21, Code of Federal Regulations (CFR), Farse Register can be found in Title 21, Couc of I ederal regarations (1 - 177)
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 Please be advised that FDA s issualited of a substition with other requirements of the Act
that FDA has made a determination that your device address . You must that FDA has made a delemination that your derres sompler Federal agencies. You must or any Federal statures and regulations administers of existiration and listing (21
comply with all the Act's requirements, including, but not most consection comply with an the Act s requirements, moraaling, or and good manufacturing practice
CFR Part 807); labeling (21 CFR Parts 801 and 800 CFR Part 807), labeling (21 CFR Parts 60 Parts (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, nr questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. 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/industry/support/index.html.
Sincerely yours,
Alberto Gutz
Alberto Guticarez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known):
Device Name: ONLINE TDM N-acetylprocainamide
Indications For Use:
The ONLINE TDM N-acetylprocainamide assay is for the quantitative determination of Nacetylprocainamide in human serum or plasma on Roche automated clinical chemistry I nalyzers. Measurements obtained from this device are used in the diagnosis and treatement of Nacetylprocainamide overdose and in monitoring the levels of N-acetylprocainamide to help ensure appropriate therapy.
Prescription Use (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Jivision Sign-Off
Office of In Vita Diagnostic Device Evaluation and Safety
Page 1 of
§ 862.3320 Digoxin test system.
(a)
Identification. A digoxin test system is a device intended to measure digoxin, a cardiovascular drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure appropriate therapy.(b)
Classification. Class II.