(146 days)
The ONLINE TDM Valproic Acid assay is for the quantitative determination of valproic acid in human serum or plasma on Roche automated clinical chemistry analyzers. Measurements muman serain of paintine were used in the diagnosis and treatement of valproic acid overdose and in monitoring the levels of valproic acid to help ensure appropriate therapy.
The ONLINE TDM Valproic Acid assay is for the quantitative determination of valproic acid 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 Valproic Acid reagent kits. The assay is based on a homogeneous enzyme immunoassay technique used for the quantitative analysis of valproic acid (free and protein-bound) 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.
This submission describes the Roche ONLINE TDM Valproic Acid assay, an in-vitro diagnostic device. As such, the concept of "acceptance criteria" and "study" in the context of imaging devices or algorithms with human interpretation is not directly applicable in the same way.
Instead, for this device, the "acceptance criteria" are based on demonstrating substantial equivalence to a predicate device (Roche COBAS INTEGRA Valproic Acid, K951595) through performance characteristics typically evaluated for quantitative assays.
Here's an analysis based on the provided text, reinterpreting the questions for this type of device:
1. Table of Acceptance Criteria and Reported Device Performance
For this in-vitro diagnostic, "acceptance criteria" are implied by acceptable ranges for analytical performance characteristics that demonstrate substantial equivalence to the predicate. The study aimed to show that the new device's performance aligns with or is comparable to the predicate.
| Acceptance Criteria (Implied for Substantial Equivalence to Predicate) | Reported Device Performance (Roche ONLINE TDM Valproic Acid) |
|---|---|
| Precision (Within-run CV%) | |
| Comparable to predicate control 1 (1.7%) | Control 1: 2.1% |
| Comparable to predicate control 2 (1.7%) | Control 2: 1.9% |
| Comparable to predicate control 3 (2.4%) | Control 3: 2.0% |
| Precision (Total CV%) | |
| Comparable to predicate control 1 (2.3%) | Control 1: 6.2% |
| Comparable to predicate control 2 (2.1%) | Control 2: 5.0% |
| Comparable to predicate control 3 (2.4%) | Control 3: 4.7% |
| Method Comparison (Linear Regression Slope) | |
| Close to 1.0 when compared to predicate | 1.017 (vs. COBAS FP Valproic acid) |
| Method Comparison (Linear Regression Intercept) | |
| Close to 0.0 when compared to predicate | -0.053 (vs. COBAS FP Valproic acid) |
| Method Comparison (Correlation Coefficient, r) | |
| High correlation (e.g., >0.95) | 0.995 (vs. COBAS FP Valproic acid) |
| Method Comparison (Standard Deviation of Mean Difference, SD (md 95)) | |
| Acceptably low | 4.801 (vs. COBAS FP Valproic acid) |
Note: The document doesn't explicitly state numerical acceptance criteria, but rather implies that the results should be "acceptable" and comparable to the predicate device to establish substantial equivalence. For precision, the values are compared directly. For method comparison, linearity, high correlation, and a near-zero intercept with a slope near one are generally expected.
2. Sample Size Used for the Test Set and the Data Provenance
- Precision Studies:
- The sample size per control level for precision studies is not explicitly stated in the summary table. It only shows "Mean", "SD", and "CV%", which are derived from multiple measurements.
- Data provenance is not specified (e.g., country of origin, retrospective/prospective).
- Method Comparison Study:
- N=54 samples were used for the comparison between ONLINE TDM Valproic Acid and COBAS FP Valproic acid.
- N=207 samples were used for the predicate comparison against COBAS FARA II (this is the predicate device's historical comparison, not the new device's).
- Data provenance is not specified (e.g., country of origin, retrospective/prospective). The samples are human serum or plasma.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This type of information is not applicable for this device. For an in-vitro diagnostic assay that measures a chemical concentration, the "ground truth" is typically established by reference methods or highly accurate analytical techniques, not by expert consensus or interpretation of images. The comparison is made against the predicate device, which itself has an established accuracy.
4. Adjudication Method for the Test Set
This is not applicable for this type of in-vitro diagnostic device. Adjudication typically refers to resolving discrepancies between multiple human readers or between human readers and an AI, which is not relevant here.
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
This is not applicable for this device. This assay is a standalone chemical measurement device, not an imaging device or an AI designed to assist human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented are effectively standalone performance studies of the device (the "algorithm" being the assay's chemical reaction and detection system). The reported precision and method comparison data reflect the performance of the device itself, without human interpretation as part of the measurement outcome.
7. The Type of Ground Truth Used
The "ground truth" in this context is the measurement obtained from the predicate device (COBAS FP Valproic acid) or, indirectly, from a well-established reference method or a previously validated assay against which the predicate itself was compared (e.g., COBAS FARA II in the predicate's comparison). The goal is to show agreement with an already accepted method for quantifying valproic acid.
8. The Sample Size for the Training Set
This is not applicable as this is not a machine learning or AI-based device that requires a training set in the conventional sense. The "training" of the assay involves optimizing its chemical reagents and reaction conditions, which is part of the assay development process, not a data-driven training set for an algorithm.
9. How the Ground Truth for the Training Set Was Established
This is not applicable as there is no "training set" for an algorithm in this context.
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AUG – 8 2006
510(k) Summary
Introduction According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
| 1) Submitter name, address, contact | Roche Diagnostics Corporation9115 Hague Rd.Indianapolis, IN 46250(317) 521-7688Contact Person: Dimitris DemirtzoglouDate Prepared: March 10, 2006 |
|---|---|
| 2) Device name | Proprietary name: ONLINE TDM Valproic AcidCommon name: Enzyme Immunoassay, Valproic acidClassification name: Enzyme Immunoassay, Valproic acid |
| 3) Predicate device | We claim substantial equivalence to the currently marketed COBAS INTEGRA Valproic Acid (K951595). |
Continued on next page
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510(k) Summary, Continued
| 4) Device Description | The ONLINE TDM Valproic Acid assay is for the quantitative determination of valproic acid 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 Valproic Acid reagent kits. The assay is based on a homogeneous enzyme immunoassay technique used for the quantitative analysis of valproic acid (free and protein-bound) 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. |
|---|---|
| 5.) Intended Use | The ONLINE TDM Valproic Acid assay is for the quantitative determination of valproic acid in human serum or plasma on Roche automated clinical chemistry analyzers. |
Continued on next page
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510(k) Summary, Continued
The Roche ONLINE TDM Valproic Acid assay is substantially equivalent to 6.) Comparison other products in commercial distribution intended for similar use. Most to the Predicate notably, it is substantially equivalent to the currently marketed Roche Device COBAS INTEGRA Valproic Acid (K951595).
The Roche ONLINE TDM Valproic Acid assay was evaluated for several performance characteristics including precision, lower detection limit, method comparison, specificity, and interfering substances. All of the evaluation studies gave acceptable results compared to the predicate device. These experiments provide evidence that the Roche ONLINE TDM Valproic Acid assay is substantially equivalent to the currently marketed Roche COBAS INTEGRA Valproic Acid assay. The following table summarizes the precision and method comparison results.
| Roche ONLINE TDM Valproic Acid | Roche COBAS FP Valproic Acid(Predicate) | |||||
|---|---|---|---|---|---|---|
| NCCLS Precision,Within run | Control 1 | Control 2 | Control 3 | Control 1 | Control 2 | Control 3 |
| Mean (µg/ml) | 33.3 | 74.9 | 107.8 | 26.2 | 60.1 | 102.0 |
| SD (µg/ml) | 0.69 | 1.42 | 2.11 | 0.46 | 1.05 | 2.46 |
| CV% | 2.1 | 1.9 | 2.0 | 1.7 | 1.7 | 2.4 |
| NCCLS Precision,Total | Control 1 | Control 2 | Control 3 | Control 1 | Control 2 | Control 3 |
| Mean (µg/ml) | 33.3 | 74.9 | 107.8 | 26.2 | 60.1 | 102.0 |
| SD (µg/ml) | 2.07 | 3.75 | 5.02 | 0.61 | 1.26 | 2.46 |
| CV% | 6.2 | 5.0 | 4.7 | 2.3 | 2.1 | 2.4 |
| MethodComparison | Linear Regression: ONLINE TDMValproic acid Vs. COBAS FP Valproic acid | Linear Regression: COBAS FP Valproicacid Vs. COBAS FARA II | ||||
| N=54, Range = 15.0 -132.1 µg/mly = 1.017 x - 0.053r = 0.995SD (md 95) = 4.801 | N=207, Range = 3.2 - =150 µg/mly=1.041x - 1.365r=0.998 |
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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 stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The eagle is black, and the text is also black.
Re:
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Dimitris Demirtzoglou Regulatory Affairs Consultant Roche Diagnostics, Inc. 9115 Hague Road Indianapolis, IN 46250-0457
AUG - 8 2006
K060690 Trade/Device Name: ONLINE TDM Valproic Acid Regulation Number: 21 CFR§ 862.3645 Regulation Name: Neuroleptic drugs radioreceptor assay test system Regulatory Class: Class II Product Code: LEG Dated: July 19, 2006 Received: July 20, 2006
Dear Mr. Demirtzoglou:
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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Page 2 –
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 (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 G
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
KOGGG 510(k) Number (if known):
Device Name: ONLINE TDM Valproic Acid
Indications For Use:
The ONLINE TDM Valproic Acid assay is for the quantitative determination of valproic acid in human serum or plasma on Roche automated clinical chemistry analyzers. Measurements muman serain of paintine were used in the diagnosis and treatement of valproic acid overdose and in monitoring the levels of valproic acid 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)
AC
Jivision Sign-Oil
Office of the Vitro Diagnostic Device Evaluation and Safety
060690
Page 1 of
§ 862.3645 Neuroleptic drugs radioreceptor assay test system.
(a)
Identification. A neuroleptic drugs radioceptor assay test system is a device intended to measure in serum or plasma the dopamine receptor blocking activity of neuroleptic drugs and their active metabolites. A neuroleptic drug has anti-psychotic action affecting principally psychomotor activity, is generally without hypnotic effects, and is a tranquilizer. Measurements obtained by this device are used to aid in determining whether a patient is taking the prescribed dosage level of such drugs.(b)
Classification. Class II.