(69 days)
The Emit® II Plus Propoxyphene Assay is a homogeneous drugs-of-abuse enzyme immunoassay with a 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of propoxyphene in human urine. Emit® II Plus assays are designed for use with a number of chemistry analyzers.
The Emit® II Plus Propoxyphene Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
The Syva Emit® II Plus Propoxyphene Assay is a homogenous enzyme assay intended for use in qualitative and semiquantitative analysis of propoxyphene in urine.
The provided text describes the Syva Emit® II Plus Propoxyphene Assay, a homogeneous enzyme immunoassay for the qualitative and semiquantitative analysis of propoxyphene in human urine. The submission is a 510(k) for substantial equivalence to a predicate device.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Comparative Analysis | Equivalent to the predicate device (Syva Emit® II Propoxyphene Assay) with regard to intended use, assay sample, and overall performance characteristics. High agreement in finding samples negative and positive compared to the predicate method. | "The Syva Emit® II Plus Propoxyphene Assay showed excellent correlation to the predicate method. The comparative analysis to the predicate method resulted in 98% agreement in finding samples negative and positive." |
| Spiked Sample Recovery (Qualitative) | Consistently distinguish negative and positive samples around the 300 ng/mL cutoff: - Spiked at ≤ -25% of cutoff (0 to 225 ng/mL) should be consistently negative. - Spiked at ≥ +25% of cutoff (375 to 1500 ng/mL) should be consistently positive. | "In qualitative spike analysis, the Emit® II Plus Propoxyphene Assay using a 300 ng/mL cutoff correctly identified the spiked specimens as being negative and positive. Known levels of propoxyphene, spiked at levels less than or equal to minus 25% of the cutoff (0 to 225 ng/mL) were consistently distinguished as negative and those spiked at levels greater than or equal to plus 25% of the cutoff (375 to 1500 ng/mL) were consistently distinguished as positive." |
| Spiked Sample Recovery (Semiquantitative Accuracy) | For known concentrations within the semiquantitative range (75 to 450 ng/mL), drug recovery should be accurate, with a specified margin of error. | "Within this range [75 to 450 ng/mL], recovery ranged up to ± 13% of nominal concentrations of spiked analyte." |
| Precision (Qualitative) | Acceptable within-run and total precision statistics, demonstrated by Coefficients of Variation (CV) for rates of controls and cutoff calibrator. | "Qualitative results, determined from rates for controls and cutoff calibrator, demonstrated within-run precision with coefficients of variation (CV) of 0.4% and total precision with CV ranging from 0.7 - 0.8%." |
| Precision (Semiquantitative) | Acceptable within-run and total precision statistics, demonstrated by Coefficients of Variation (CV) for concentrations of controls and cutoff calibrator. | "Semiquantitative results, determined from concentrations for controls and cutoff calibrator, demonstrated within-run precision with CV ranging from 1.6 - 2.2% and total precision with CV ranging from 3.0 - 3.8%." |
| Sensitivity | The lowest concentration of propoxyphene that can be distinguished from 0 ng/mL with a 95% confidence level should be below a certain threshold. | "The sensitivity level of the Emit® II Plus Propoxyphene Assay is less than 60 ng/mL. This level represents the lowest concentration of propoxyphene that can be distinguished from 0 ng/mL with a confidence level of 95%." |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample sizes for the test sets used in each performance study (comparative analysis, spiked sample recovery, precision, sensitivity). It describes the methodology (e.g., "known levels of propoxyphene, spiked at levels," "Negative human urine specimens were spiked").
The data provenance is not explicitly stated regarding country of origin. The studies appear to be retrospective in nature, as they involve testing urine samples (both clinical and spiked) in a laboratory setting to evaluate the assay's performance. There is no indication of a prospective study where the assay is used on real-time patient samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not mention the use of experts or their qualifications for establishing ground truth within the studies described. For an in vitro diagnostic (IVD) device like this, ground truth is typically established by:
- Predicate device results: For the comparative analysis, the predicate device itself serves as a "ground truth" reference.
- Known spike concentrations: For spiked sample recovery, the known concentrations of propoxyphene added to the samples serve as the ground truth.
- Analytical methods: For sensitivity and precision, the ground truth is derived from the inherent analytical properties of the assay and statistical calculations.
4. Adjudication Method for the Test Set
No adjudication method (e.g., 2+1, 3+1, none) is mentioned. This is typical for IVD device performance studies where ground truth is established analytically (known concentrations, predicate device results) rather than by human interpretation requiring consensus.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic assay, not an imaging device or a system requiring human interpretation comparison, so MRMC studies are not applicable in this context.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described are standalone performance studies of the assay itself. The results reported are direct measurements of the assay's ability to detect and quantify propoxyphene in urine, without human intervention in the analytical process or interpretation of raw signals for diagnosis. The assay yields a result (qualitative positive/negative, or a semiquantitative concentration), which then might be reviewed by a human, but the performance metrics here are about the assay's analytical capabilities.
7. The Type of Ground Truth Used
The types of ground truth used are:
- Predicate device results: For the comparative analysis.
- Known concentrations (spiking): For spiked sample recovery studies.
- Analytical definitions: For precision and sensitivity, the ground truth is based on the inherent analytical properties of the assay and statistical calculations to determine limits and variations.
8. The Sample Size for the Training Set
The document does not mention a "training set" in the context of an algorithm or machine learning model. This is an immunoassay, not an AI/ML-based device. Therefore, the concept of a training set as a distinct dataset used to train an algorithm is not applicable here. The development and optimization of the assay would involve various experimental stages, but these are not referred to as "training sets."
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the AI/ML sense, this question is not applicable. The assay's parameters would have been optimized during its development through a series of experiments and iterations, likely involving known concentrations of propoxyphene and comparisons to reference methods, but this is part of the assay development process, not the training of a discrete algorithm.
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FEB 1 2000
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510(k) SUMMARY OF SAFETY AND EFFECTIVENESS For Syva Emit® II Plus Propoxyphene Assay
1. Manufacturer and Contact Information:
| Manufacturer: | Syva Company – Dade Behring Inc.3403 Yerba Buena Rd.P.O. Box 49013San Jose, CA 95161-9013 |
|---|---|
| --------------- | ------------------------------------------------------------------------------------------------------- |
Contact Information: Paul Rogers Syva Company 3403 Yerba Buena Road San Jose, CA 95161-9013 Tel: 408-239-2000
2. Device Classification Name:
The Clinical Chemistry and Clinical Toxicology Devices Panel have classified "Propoxyphene Test System" as Class II.
3. Intended Use:
Syva Emit® II Plus Propoxyphene Assay is a homogeneous enzyme immunoassay. The assay is intended for use in the qualitative and semiquantitative analysis of propoxyphene in human urine.
4. Device Description and Characteristics:
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of SMDA 1990.
The Syva Emit® II Plus Propoxyphene Assay is a homogenous enzyme assay intended for use in qualitative and semiquantitative analysis of propoxyphene in urine.
The Syva Emit® II Plus Propoxyphene Assay has been found to be equivalent to the predicate device: Syva Emit® II Propoxyphene Assay with regard to intended use, assay sample, and overall performance characteristics.
Comparative Analysis: The Syva Emit® II Plus Propoxyphene Assay showed excellent correlation to the predicate method. The comparative analysis to the predicate method resulted in 98% agreement in finding samples negative and positive.
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510(k) SUMMARY OF SAFETY AND EFFECTIVENESS For Syva Emit Propoxyphene Assay (cont.)
Spiked Sample Recovery: In qualitative spike analysis, the Emit® II Plus Propoxyphene Assay using a 300 ng/mL cutoff correctly identified the spiked specimens as being negative and positive. Known levels of propoxyphene, spiked at levels less than or equal to minus 25% of the cutoff (0 to 225 ng/mL) were consistently distinguished as negative and those spiked at levels greater than or equal to plus 25% of the cutoff (375 to 1500 ng/mL) were consistently distinguished as positive.
The semiquantitative attribute was assessed by determining the accuracy of recovery for analyte-spiked samples by the Emit® II Plus Propoxyphene Assay. Negative human urine specimens were spiked with concentrations of propoxyphene at levels throughout the semiquantitative range of 75 to 450 ng/mL. For each known concentration, drug recovery was calculated using the average concentration obtained by the Emit® II Plus Propoxyphene Assay. Within this range, recovery ranged up to ± 13% of nominal concentrations of spiked analyte.
Precision: A precision study was performed using Syva Emit® II Plus Propoxyphene Assay in both the qualitative and semiqualitative modes. Acceptable within-run and total precision statistics for both the qualitative and semiquantitative assays were observed.
Qualitative results, determined from rates for controls and cutoff calibrator, demonstrated within-run precision with coefficients of variation (CV) of 0.4% and total precision with CV ranging from 0.7 - 0.8%.
Semiquantitative results, determined from concentrations for controls and cutoff calibrator, demonstrated within-run precision with CV ranging from 1.6 - 2.2% and total precision with CV ranging from 3.0 - 3.8%.
Sensitivity: The sensitivity level of the Emit® II Plus Propoxyphene Assay is less than 60 ng/mL. This level represents the lowest concentration of propoxyphene that can be distinguished from 0 ng/mL with a confidence level of 95%.
5. Substantial Equivalence:
In conclusion, Syva Company - Dade Behring Inc. considers the Syva Emit® II Plus Propoxyphene Assay to be substantially equivalent to the Emit® II Propoxyphene Assay with regard to intended use, assay sample, and overall performance characteristics.
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Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). 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 symbol resembling a caduceus or a representation of human figures.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
1 2000 FEB
Mr. Paul L. Rogers Jr. Senior Manager, Regulatory Affairs Syva Company - Dade Behring Inc. P.O. Box 49013 3403 Yerba Buena Road San Jose, California 95161-9013
Re: K993981
Trade Name: Syva Emit® II Plus Propoxyphene Assay Regulatory Class: II Product Code: JXN Dated: November 23, 1999 Received: November 24, 1999
Dear Mr. Rogers:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations. Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
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This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers 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 Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Device Name: Syva Emit® II Plus Propoxyphene Assay
Indications for Use:
The Emit® II Plus Propoxyphene Assay is a homogeneous drugs-of-abuse enzyme immunoassay with a 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of propoxyphene in human urine. Emit® II Plus assays are designed for use with a number of chemistry analyzers.
The Emit® II Plus Propoxyphene Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
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| Concurrence of CDRH, Office of Device Evaluation (ODE) | ||
|---|---|---|
| P. Beinhardt for Dig. Cooper(Division Sign-Off) | ||
| Division of Clinical Laboratory Services | ||
| 510(k) Number: K992981 | ||
| Prescription Use(Per 21 CFR 801.109) | OR | Over-The-Counter Use(Optional Format 1-2-96) |
§ 862.3700 Propoxyphene test system.
(a)
Identification. A propoxyphene test system is a device intended to measure propoxyphene, a pain-relieving drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of propoxyphene use or overdose or in monitoring levels of propoxyphene to ensure appropriate therapy.(b)
Classification. Class II (special controls). A propoxyphene test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. 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, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).