(167 days)
IMMULITE® Methamphetamine is a solid-phase, chemiluminescent enzyme immunoassay for use with the IMMULITE Automated Analyzer and designed for the qualitative measurement of methamphetamine in urine. It is intended strictly for in vitro diagnostic use in clinical laboratories, in the context of a program involving an established confirmatory test for methamphetamine. A cutoff of 500 ng/mL is used by the IMMULITE Methamphetamine assay to identify positive and negative results.
IMMULITE® Methamphetamine is a solid-phase, chemiluminescent enzyme immunoassay for use with the IMMULITE® Automated Analyzer.
Here's an analysis of the provided text regarding the IMMULITE® Methamphetamine device's acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for the IMMULITE® Methamphetamine assay. Instead, it presents the results of two comparison studies, implicitly suggesting that these results were deemed acceptable for substantial equivalence. The predicate device's performance (DPC's Coat-A-Count Methamphetamine, K885071) would likely serve as the benchmark for implicit acceptance.
However, based on the provided data, we can infer the reported performance:
| Performance Metric | Against Predicate Device (Coat-A-Count) | Against Gold Standard (GC/MS) |
|---|---|---|
| Relative Sensitivity | 92% | 88% |
| Relative Specificity | 100% | 86% |
| Agreement | 97% | 87% |
2. Sample Sizes Used for the Test Set and Data Provenance
-
Against Predicate Device (Coat-A-Count):
- Sample Size: 214 urine samples.
- Data Provenance: Samples were from "volunteer donors, presumed not to be drug abusers, and a reference lab." This suggests a mix of potentially healthy individuals and samples from a laboratory setting. The country of origin is not specified, but the manufacturer is based in Los Angeles, CA, USA, making it highly probable the data is from the USA.
- Retrospective/Prospective: Not explicitly stated, but the description "urine samples from volunteer donors... and a reference lab" sounds like it could be a collection of existing samples (retrospective) or newly collected for the study (prospective). Without further detail, it's difficult to definitively classify.
-
Against Gold Standard (GC/MS):
- Sample Size: 37 urine samples.
- Data Provenance: Samples were "obtained similarly as above," implying the same mix of volunteer donors and reference lab samples, likely from the USA.
- Retrospective/Prospective: Similar to the above, not explicitly stated.
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 to establish ground truth for either comparison study.
- For the comparison with the predicate device, the "ground truth" was established by the predicate device itself (Coat-A-Count Methamphetamine).
- For the comparison with GC/MS, the "ground truth" was established by GC/MS (Gas Chromatography/Mass Spectrometry), which is a highly accurate analytical method for drug detection. This method itself acts as the expert/definitive truth in this context, not human experts interpreting data.
4. Adjudication Method for the Test Set
Not applicable. There was no mention of human expert review or adjudication in either study for establishing ground truth. The comparisons were made directly to the results obtained from the predicate device or the GC/MS analysis.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) assay designed to provide a quantitative measurement (which is then interpreted qualitatively based on a cutoff), not an imaging or diagnostic AI requiring human interpretation. Therefore, a study comparing human readers with and without AI assistance is not relevant to this type of device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies reported are essentially standalone performance studies for the IMMULITE® Methamphetamine assay. The device itself generates a result (counts per second, which is then compared to a 500 ng/mL cutoff) without human intervention in the result generation process. The comparisons are between the device's output and the output of a predicate device or a gold standard method.
7. The Type of Ground Truth Used
- Against Predicate Device: The ground truth was the predicate device's measurement (Coat-A-Count Methamphetamine).
- Against GC/MS: The ground truth was the GC/MS result, which is considered an objective and highly accurate analytical method, often serving as a gold standard in toxicology.
8. The Sample Size for the Training Set
The document does not report any sample sizes for a training set. This is generally expected for IVD assays like this, where the "training" involves developing the assay's chemical reagents and protocols to achieve desired performance characteristics. There isn't an explicit "algorithm" that is trained on a dataset in the same way as an AI/ML model for image analysis, for example. The performance characteristics are intrinsic to the assay chemistry and mechanics.
9. How the Ground Truth for the Training Set Was Established
Since no training set is described or implied for a machine learning algorithm, this question is not applicable in the context of this traditional IVD device. The "ground truth" in the development of such assays typically refers to the known concentrations of analytes in calibrators and controls used during the assay's design and optimization phase, and ultimately validated against reference methods like GC/MS.
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JAN 2 0 2000
510 (k) Summary Safety and Effectiveness
This summary of safety and effectiveness information has been prepared in accordance This sammary of SMDA 1990 and 21 CFR Part 807.92.
| Name: | Diagnostic Products Corporation |
|---|---|
| Address: | 5700 West 96th StreetLos Angeles, CA 90045 |
| Telephone Number: | (310) 645-8200 |
| Facsimile Number: | (310) 645-9999 |
| Contact Person: | Edward M. Levine, Ph.D.Director of Clinical Affairs |
| Date of Preparation: | November 29, 1999 |
| Device Name: | |
| Trade: | IMMULITE® Methamphetamine |
| Catalog Number: | LKMA1 (100 tests), LKMA5 (500 tests) |
| CFR: | An amphetamine test system is a device intended tomeasure amphetamine, a central nervous systemstimulating drug, in plasma and urine. Measurementsobtained by this device are used in the diagnosis andtreatment of amphetamine use or overdose and inmonitoring levels of amphetamine to ensure appropriatetherapy. |
| Common: | Reagent system for the determination of methamphetaminein urine. |
| Classification: | Class II device, 91-DKZ (21 CFR 862.3100) |
| Panel: | Toxicology |
| CLIA Complexity Category: | We believe the category to be moderate, based on previousclassification of analogous tests. |
| Manufacturer: | Diagnostic Products Corporation (DPC)5700 West 96th StreetLos Angeles, CA 90045-5597 |
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Establishment Registration #:
DPC's establishment Registration No. is 2017183
| Substantially EquivalentPredicate Device: | DPC's Coat-A-Count Methamphetamine (K885071) |
|---|---|
| Description of Device: | IMMULITE® Methamphetamine is a solid-phase,chemiluminescent enzyme immunoassay for use with theIMMULITE® Automated Analyzer. |
| Intended Use of theDevice: | IMMULITE® Methamphetamine is a solid-phase,chemiluminescent enzyme immunoassay for use with theIMMULITE Automated Analyzer and designed for thequalitative measurement of methamphetamine in urine. Itis intended strictly for in vitro diagnostic use in clinicallaboratories, in the context of a program involving anestablished confirmatory test for methamphetamine. Acutoff of 500 ng/mL is used by the IMMULITEMethamphetamine assay to identify positive and negativeresults. |
Summary and Explanation of the test:
Methamphetamine is a potent sympathomimetic amine capable of stimulating the central nervous system with less peripheral actions than amphetamine. It is structurally similar to amphetamine and methylphenidate and, like them, acts through increasing the release of norepinephrine as well as through direct stimulation of postsynaptic norepinephrine receptors. There are two stereoisomers: d-methamphetamine is 10 times more potent as a CNS stimulant than I-methamphetamine, while I-methamphetamine (I-desoxyephedrine) is used in nasal inhalers for peripheral vasoconstriction Amphetamines induce euphoria, irritability and anxiety. Tolerance and dependence have been observed.
Methamphetamine is metabolized to the active metabolite, amphetamine, hydroxylated metabolites and deaminated to hippuric and benzoic acid. It is a metabolite of benzphetamine and selegiline. About 70% of a dose is excreted in the urine in 24 hours. Methamphetamine is excreted primarily unchanged (44% to 76%) with a small fraction as 4-hydroxymethamphetamine (15%) or amphetamine (6%). The half-life of methamphetamine varies from 12 to 34 hours and is a function of urinary pH. The excretion of unchanged methamphetamine is increased in acidic urine, while in alkaline urine it is reduced to less than 5% of the dose. After a single 10 mg dose, urine concentrations ranged from 0.5 to 4.0 µg/mL in the first 24 hours. After chronic administration, methamphetamine concentrations of 25 to 300 µg/mL and amphetamine concentrations of 1 to 90 ug/mL are found in urine. However, the length of time
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following drug use for which a positive result may occur is dependent upon several factors including the frequency and amount of drug, metabolic rate, excretion rate, drug half-life, and the drug user's age, weight, activity, and diet.
Technological Comparison to Predicate:
Methamphetamine is a solid-phase, chemiluminescent enzyme IMMULITE immunoassay. The solid-phase, a polystyrene bead enclosed within an IMMULITE Test Unit, is coated with a monoclonal antibody specific for methamphetamine.
The patient sample and alkaline phosphatase-conjugated methamphetamine are simultaneously introduced into the Test Unit and incubated for approximately 30 minutes at 37 ℃ with intermittent agitation. During this time, methamphetamine in the sample competes with enzyme-labeled methamphetamine for a limited number of antibody binding sites on the bead. Unbound enzyme conjugate is then removed by a centrifugal wash, after which substrate is added and the Test Unit is incubated for a further 10 minutes.
The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to vield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex and thus also the photon output, as measured by the luminometer - is inversely proportional to the concentration of methamphetamine in the sample. A qualitative result is then obtained by comparing the counts per second (cps) of the patient sample to those of a sample - the Adjustor supplied with the kit - representing the assay's 500 ng/mL cutoff.
The Coat-A-Count Methamphetamine procedure is a solid-phase radioimmunoassay, wherein 1331-labeled methamphetamine competes for a fixed time with methamphetamine in the patient sample for methamphetamine-specific antibody sites. Because the antibody is immobilized to the wall of a polypropylene tube, simply decanting the supernatant suffices to terminate the competition and to isolate the antibody-bound fraction of the radiolabeled methamphetamine, which is then counted in a gamma counter. The Qualitative Procedure vields positive and negative results relative to a reference chosen as a cutoff.
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Performance Equivalence:
Diagnostic Products Corporation asserts that the IMMULITE® Methamphetamine substantially equivalent results to other commercially marketed produces methamphetamine assays, such as the Coat-A-Count Methamphetamine assay. Each product is designed for the qualitative measurement of methamphetamine in urine. Each product is intended strictly for in vitro diagnostic use in the context of a program involving an established confirmatory test for methamphetamine.
Method Comparison:
IMMULITE Methamphetamine was compared to DPC's Coat-A-Count (CAC) Methamphetamine on 214 urine samples from volunteer donors, presumed not to be drug abusers, and a reference lab. The samples ranged from undetectable to approximately 1500 ng/mL (3 times the cutoff value). A cutoff of 500 ng/mL was used for both procedures.
IMMULITE Methamphetamine
| CAC Methamphetamine | Positive | Negative | Relative sensitivity: | 92% |
|---|---|---|---|---|
| Positive | Relative Specificity: | 100% | ||
| Negative | ાર્ ર | Agreement: | 97% |
IMMULITE Methamphetamine was also compared to GC/MS on 37 urine samples obtained similarly as above. The samples ranged from 212 ng/mL to 972 ng/mL on GC/MS. A cutoff of 500 ng/mL was used for both procedures.
IMMULITE Methamphetamine
| GC/MS | Positive | Negative | Sensitivity: | 88% |
|---|---|---|---|---|
| Positive | 14 | 2 | Specificity: | 86% |
| Negative | 3 | 18 | Agreement: | 87% |
Conclusion:
The data presented in this summary of safety and effectiveness is the data that the Food and Drug Administration used in granting DPC substantial equivalence for IMMULITE® Methamphetamine.
Edward Levin
Edward M. Levine, Ph.D. Director of Clinical Affairs
1/29/99
Date
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Image /page/4/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" around the perimeter. Inside the circle is a stylized symbol featuring three abstract human profiles facing right, with flowing lines beneath them, possibly representing water or movement.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JAN 2 0 2000
Edward M. Levine, Ph.D. Director of Clinical Affairs Diagnostic Products Corporation 5700 West 96th Street Los Angeles, California 90045-5597
Re: K992634
Trade Name: IMMULITE® Methamphetamine Regulatory Class: II Product Code: LAF Dated: November 29, 1999 Received: November 30, 1999
Dear Dr. Levine:
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 (QS) 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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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.
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"(21 CFR 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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16992634 510(k) Number (if known): Device Name: IMMULITE® Methamphetamine
Indications For Use:
IMMULITE® Methamphetamine is a solid-phase, chemiluminescent enzyme immunoassay for use with the IMMULITE Automated Analyzer and designed for the qualitative measurement of methamphetamine in urine. It is intended strictly for in vitro diagnostic use in clinical laboratories, in the context of a program involving an established confirmatory test for methamphetamine. A cutoff of 500 ng/mL is used by the IMMULITE Methamphetamine assay to identify positive and negative results
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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)
§ 862.3610 Methamphetamine test system.
(a)
Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of methamphetamine use or overdose.(b)
Classification. Class II (special controls). A methamphetamine 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).