(83 days)
The DRI® Cotinine Enzyme Immunoassay is intended for the Qualitative and Semi-Quantitative determination of Cotinine in human urine at a cutoff level of 500 ng/mL. This assay is intended for in vitro diagnostic use only. The assay is intended as an aid in the detection of cotinine after use or exposure to tobacco products.
The DRI® Cotinine EIA Assay is a liquid ready-to-use homogeneous enzyme immunoassay. The assay uses specific antibodies, which can detect cotinine drugs in urine. The assay is based on competition between a drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) enzyme, and free drug from the urine sample for a fixed amount of specific antibody binding sites. In the absence of free drug from the sample. the specific antibody binds the drug labeled with G6PDH causing a decrease in enzyme activity. This phenomenon creates a direct relationship between drug concentration in urine and enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.
Here's an analysis of the provided K030649 document regarding the acceptance criteria and the study proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The document provides performance data, but it does not explicitly state pre-defined acceptance criteria for most metrics. The comparison is made against a predicate device and general good laboratory practice.
| Performance Metric | Acceptance Criteria (Implicit/Inferred) | Reported Device Performance (DRI® Cotinine EIA Assay) |
|---|---|---|
| Accuracy | Comparable to predicate device (93.6% sens, 74.0% spec) and high agreement with reference method | 98% Total Agreement (110 true positives, 80 true negatives) against GC/MS reference method. |
| Sensitivity (LOD) | Good sensitivity (not explicitly quantified as an acceptance criterion) | 34 ng/mL |
| Precision | Not explicitly quantified as an acceptance criterion, but good reproducibility is expected. | %CVs for total and within-run testing were ≤ 9.4% (at critical points of measurement range). |
| Specificity | Not affected by common interfering substances. | Not affected by common endogenous substances, variations in urinary pH levels, structurally unrelated pharmaceutical compounds, or potentially cross-reacting compounds. |
2. Sample Size Used for the Test Set and Data Provenance
The document states:
- Accuracy Study Test Set: The accuracy study reported "110 true positives, 80 true negatives", implying a total of 190 samples were used in this specific comparison.
- Precision Study Test Set: No specific sample size is given for the precision study, only that it was conducted at 3 analyte concentration levels (300 ng/mL, 500 ng/mL, and 700 ng/mL).
- Sensitivity (LOD) Study Test Set: Not specified.
- Specificity Study Test Set: Not specified.
Data Provenance: The document does not explicitly state the country of origin for the data or whether the studies were retrospective or prospective. Given the nature of a 510(k) submission for an IVD, these are typically laboratory-based validation studies.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- Accuracy Study Ground Truth: The ground truth for the accuracy study was established using a GC/MS (Gas Chromatography/Mass Spectrometry) reference method. This is a highly accurate and widely accepted analytical technique for confirming the presence and concentration of substances. Therefore, human experts were not directly establishing the ground truth for individual samples; rather, the GC/MS result served as the objective truth.
- Other Studies: Not applicable as these studies (precision, sensitivity, specificity) evaluate the device's technical performance characteristics rather than a diagnostic decision against a clinical truth.
4. Adjudication Method for the Test Set
Not applicable. As the ground truth for accuracy was established by a reference laboratory method (GC/MS) and not human reader consensus, there was no need for an adjudication method.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This device is an in vitro diagnostic (IVD) assay designed for quantitative and semi-quantitative determination of a biomarker in urine, not for human interpretation of images or other subjective data. Therefore, the concept of "human readers improving with AI vs. without AI assistance" is not relevant to this type of device.
6. Standalone (Algorithm Only Without Human-in-the Loop Performance) Study
Yes, the performance studies described (accuracy, precision, sensitivity, specificity) represent standalone performance of the assay. The device itself performs the measurement and provides a result; there is no human interpretation component in the direct operation of the assay. The "aid in the detection" statement in the intended use implies a clinician will interpret the result in the broader clinical context, but the assay's performance itself is standalone.
7. Type of Ground Truth Used
- Accuracy Study: Reference laboratory method (GC/MS).
- Other Studies: The ground truth for precision, sensitivity, and specificity studies would typically be established by preparing samples with known concentrations of cotinine or interfering substances, which are then run on the device.
8. Sample Size for the Training Set
No training set information is provided. This device is a homogeneous enzyme immunoassay kit, not a machine learning or AI-based diagnostic that would typically involve a "training set" in the computational sense. Its performance is based on biochemical reactions.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no mention of a "training set" in the context of this traditional immunoassay.
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MAY 2 2 2003
510(K) Summary
This 510(k) summary is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(K) number is: Unknown
| Submitter Information (21 CFR 807.92(a)(1)) | |
|---|---|
| Submitter: | Microgenics Corporation |
| 46360 Fremont Boulevard | |
| Fremont, CA 94538 | |
| phone: (510) 979-5023 | |
| fax: (510) 979-5223 | |
| Contact: | Name: Lakshmi Anne |
| Title: Director of Product Development | |
| Summary date: | February 27, 2003 |
| Name of Device and Classification (21 CFR 807.92(a)(2)) | |
| Name (trade): | DRI® Cotinine EIA Assay |
| Name (usual): | Cotinine Assay |
| Classification: | Cotinine Enzyme Immunoassay has been placed in Class II (MKU) by theBureau of Medical Devices. |
Identification of Legally Marketed Predicate Device(s) (21 CFR 807.92 (a)(3)) DRI® Cotinine EIA Assay is substantially equivalent to OTI AUTO-LYTE® Cotinine EIA Assay (OraSure Technologies, Inc, Bethlehem, PA), cleared under premarket notification K072481.
DRI® Cotinine EIA Assay is identical or similar to its predicate in terms of intended use, method principle, risk to the patient, and clinical performance.
Description of Device (21 CFR 807.92 (a)(4))
The DRI® Cotinine EIA Assay is a liquid ready-to-use homogeneous enzyme immunoassay. The assay uses specific antibodies, which can detect cotinine drugs in urine. The assay is based on competition between a drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) enzyme, and free drug from the urine sample for a fixed amount of specific antibody binding sites. In the absence of free drug from the sample. the specific antibody binds the drug labeled with G6PDH causing a decrease in enzyme activity. This phenomenon creates a direct relationship between drug concentration in urine and enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.
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Intended Use (21 CFR 807.92 (a)(5))
«The DRI® Cotinine Enzyme Immunoassay is intended for the Qualitative and Semi-Quantitative determination of Cotinine in human urine at a cutoff level of 500 ng/mL. This assay is intended for in vitro diagnostic use only. The assay is intended as an aid in the detection of cotinine after use or exposure to tobacco products."
Similarities to the Predicate(s) (21 CFR 807.92 (a)(6))
A summary table of the similarities and differences between DRI® Cotinine EIA Assay and the predicate device follows.
| Device Name | AUTO-LYTE® Cotinine EIA | DRI® Cotinine EIA Assay |
|---|---|---|
| (K072481) | ||
| Indications forUse | "The OraSure Technologies, Inc. (OTI)AUTO-LYTE® Cotinine EIA is ahomogeneous immunoassay intended forthe Qualitative and Semi-Quantitativeanalysis of cotinine in human urine.Cotinine is a metabolite of nicotine, andthe OTI kit is used as an aid in thedetection of cotinine after use of tobaccoproducts or other products containingnicotine. FOR IN VITRO DIAGNOSTICUSE." | "The DRI® Cotinine EnzymeImmunoassay is intended for theQualitative and Semi-Quantitativedetermination of Cotinine in human urineat a cutoff level of 500 ng/mL. Thisassay is intended for in vitro diagnosticuse only. The assay is intended as an aid inthe detection of cotinine after use orexposure to tobacco products." |
| MethodPrinciple | The OTI AUTO-LYTE® Cotinine EIA is ahomogeneous enzyme immunoassayused for the analysis of cotinine in urine.The assay is based on competitionbetween drug in the sample and druglabeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) forantibody binding sites. Enzyme activitydecreases upon binding to the antibody;free drug in the sample is proportional toenzyme activity. Active enzyme convertsoxidized nicotinamide adeninedinucleotide (NAD) to NADH, resultingin an absorbance change that is measuredspectrophotometrically at 340 nm. | The DRI® Cotinine Assay is a liquid,ready-to-use homogeneous enzymeimmunoassay. The assay is based oncompetition between cotinine labeledwith glucose-6-phosphate dehydrogenase(G6PDH) enzyme and free cotinine fromin the sample for a fixed amount ofcotinine-specific antibody binding sites.The enzyme G6PDH activity isdetermined spectrophotometrically at 340nm by measuring its ability to convertnicotinamide adenine dinucleotide (NAD)to NADH. |
| Components | - Reagent A- Reagent B | - Antibody/Substrate Reagent- Enzyme Conjugate Reagent |
| Anti-CotinineAntibody | Sheep Polyclonal | Mouse Monoclonal |
| Risk to patient | Not included in package insert. | This assay provides only a preliminaryanalytical result. A more specificalternate chemical method must be usedin order to obtain a confirmed analytical |
Comparison Table:
AUTO-LYTE® Cotinine EIA (K072481) and DRI® Cotinine EIA Assay
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| Device Name | AUTO-LYTE® Cotinine EIA (K072481) | DRI® Cotinine EIA Assay |
|---|---|---|
| result. Gas chromatography/massspectrometry (GC/MS) is the preferredconfirmatory method. | ||
| ClinicalPerformance | Accuracy: Accuracy against a CarbonMonoxide Monitor reference methodindicated a relative sensitivity of 93.6%and a relative specificity of 74.0% | Accuracy: Accuracy against a GC/MSreference method was 98% (110 truepositives, —80 true negatives) |
| Total Imprecision: Percent rate CVsacross 4 levels of analyte concentration(300 ng/mL-5000 ng/mL) were ≤ 1.09%. | Total Imprecision: Percent rate CVsacross 3 levels of analyte concentration(300 ng/mL, 500 ng/mL, and 700 ng/mLwere ≤ 0.8%.) |
Brief Discussion of Nonclinical/Clinical Data (21 CFR 807.92(b)(1, 2))
The DRI® Cotinine EIA Assay was evaluated via a series of traditional laboratory studies. These studies included the performance characteristics of sensitivity, linearity, specificity, precision, and accuracy.
The assay showed good sensitivity with an LOD of 34 ng/mL.
Precision studies indicated good reproducibility of results at the critical points of the measurement range (distinguishing positive from negative interpretations), as dose %CVs for both total and within-run testing were ... 9.4%.
Accuracy studies showed good performance of the DRI® Cotinine EIA Assay as compared to the GC/MS reference method. The % Total Agreement is 98%.
Specificity testing demonstrated that the DRI® Cotinine EIA Assay is not affected by common endogenous substances, variations in urinary pH levels, structurally unrelated pharmaceutical compounds, or potentially cross-reacting compounds.
Performance Data - Conclusions (21 CFR 807.92 (b)(3))
The DRI® Cotinine EIA Assay has been shown to be substantially equivalent to the predicate device. and safe and effective for its intended use.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/3/Picture/1 description: The image is a logo for the Department of Health & Human Services. The logo features a stylized image of an eagle with three lines representing its body and wings. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle.
Public Health Service
Food and Drug Administratio 2098 Gaither Road Rockville MD 20850
Ms. Lakshmi Anne Director of Product Development Microgenics Corporation 46360 Fremont Boulevard Fremont, CA 94538
MAY 2 2 2003
Re: K030649 Trade/Device Name: DRI® Cotinine EIA Assay Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIT, MKU Dated: February 27, 2003 Received: February 28, 2003
Dear Ms. Anne:
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 (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 Sutman
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):
DRI® Cotinine Enzyme Immunoassay Device Name:
Indications For Use:
"The DRI® Cotinine Enzyme Immunoassay is intended for the Qualitative and Semi-Quantitative determination of Cotinine in human urine at a cutoff level of 500 ng/mL. This assay is intended for in vitro diagnostic use only. The assay is intended as an aid in the detection of cotinine after use or exposure to tobacco products."
Sean Cooper
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K030649
(PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use (Per 21 CFR 801.109)
OR
Over-The-Counter Use
(Optional Format 1-2-96)
§ 862.3220 Carbon monoxide test system.
(a)
Identification. A carbon monoxide test system is a device intended to measure carbon monoxide or carboxyhemoglobin (carbon monoxide bound to the hemoglobin in the blood) in blood. Measurements obtained by this device are used in the diagnosis and treatment of or confirmation of carbon monoxide poisoning.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.