(74 days)
The Methadone or Propoxyphene Urine Drugs of Abuse Calibrators are intended for in vitro diagnostic use for the calibration of their respective enzyme immunoassays to detect methadone or propoxyphene in human urine.
The Methadone or Propoxyphene Urine Drugs of Abuse Controls are intended for in vitro diagnostic use for the validation of their respective enzyme immunoassays to detect methadone or propoxyphene in human urine.
All of the Single Analyte Urine DAU Calibrators and Controls are human urine-based liquid, and ready to use. These Calibrators and Controls do not have any especially unique technical characteristics. Each contains a known concentration of a specific drug analyte.
The Negative DAU calibrator is a processed, drug-free human urine matrix. The Low, Cutoff, Intermediate, and High Calibrators, as well as the 2 levels of Controls are prepared by spiking known concentrations of drug analyte into the Negative DAU Calibrator matrix.
The provided document describes the acceptance criteria and study for Lin-Zhi International, Inc.'s Single Analyte (Methadone or Propoxyphene) Urine Drugs of Abuse Calibrators and Controls. These are not AI/ML devices, but rather laboratory calibrators and controls used for drug testing. Therefore, many of the typical AI/ML study components (like human reader studies, ground truth establishment by experts, training set details, etc.) are not applicable here.
Nevertheless, I can extract the relevant information regarding their performance characteristics and the supporting studies.
Here's a breakdown of the requested information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" for precision or accuracy in a numerical format that would typically be found in an AI/ML context (e.g., minimum sensitivity, specificity). Instead, it presents the results of performance studies (reproducibility and accuracy) and implicitly suggests that these results demonstrate acceptable performance for the intended use and for substantial equivalence to a predicate device.
The "reported device performance" are the results from the reproducibility and accuracy studies.
Reproducibility (Precision) - Based on %Coefficient of Variation (%CV)
| Calibrator/Control | Expected Concentrate (ng/mL) | Methadone EIA Reported %CV | Propoxyphene EIA Reported %CV |
|---|---|---|---|
| Neg. Cal | 0 | 0.4 | 0.6 |
| Low Cal | 150 | 0.8 | 0.8 |
| Cutoff Cal | 300 | 1.0 | 0.9 |
| Intermediate Cal | 600 | 0.8 | 0.6 |
| High Cal | 1000 | 0.4 | 0.7 |
| Control Level 1 | 225 | 3.4 | 1.3 |
| Control Level 2 | 375 | 3.5 | 2.0 |
Accuracy - Comparison of Expected vs. GC/MS Measured Concentrations (ng/mL)
| Calibrator/Control | Methadone Expected (ng/mL) | Methadone GC/MS (ng/mL) | Propoxyphene Expected (ng/mL) | Propoxyphene GC/MS (ng/mL) |
|---|---|---|---|---|
| Low Cal. | 150 | 157 | 150 | 158 |
| Cutoff Cal. | 300 | 288 | 300 | 307 |
| Intermediate Cal. | 600 | 584 | 600 | 593 |
| High Cal. | 1000 | 963 | 1000 | 973 |
| Level 1 Control | 225 | 214 | 225 | 222 |
| Level 2 Control | 375 | 374 | 375 | 387 |
Stability: The study indicated no significant difference between Calibrators and Controls stored at room temperature for 6 months compared to those stored at 2°C to 8°C. Real-time stability studies were ongoing with an anticipated shelf life of at least 12 months at 2°C to 8°C. Previous evaluations of artificial matrix controls showed >24 months real-time stability.
2. Sample size used for the test set and the data provenance
- Reproducibility Test Set: 12 vials each of Calibrators and Controls for both Methadone and Propoxyphene.
- Accuracy Test Set: The number of samples for GC/MS confirmation is not explicitly stated as a separate "test set" size. The table lists one GC/MS value per calibrator/control level.
- Data Provenance: Not specified, but implied to be from internal lab studies conducted by Lin-Zhi International, Inc. The products contain "human urine-based" matrix, but no geographic origin for the human urine is provided. The study is retrospective in the sense that the data presented is the result of completed tests.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. This device is a chemical calibrator/control, not an imaging or diagnostic AI/ML device that requires human expert interpretation for ground truth. The "ground truth" for calibrator concentrations is established by analytical methods (GC/MS).
4. Adjudication method for the test set
Not applicable. Not an AI/ML device requiring human adjudication.
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
Not applicable. Not an AI/ML device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Not applicable. This is not an algorithm. The device itself is the calibrator/control material. The performance characteristics described are how well the calibrators/controls perform in their intended use setting (i.e., in enzyme immunoassays).
7. The type of ground truth used
The "ground truth" for the concentration of the analytes (methadone and propoxyphene) in the calibrators and controls was established using Gas Chromatography/Mass Spectroscopy (GC/MS) technique. This is a highly accurate and widely accepted analytical method for confirming drug concentrations. The reference materials used for spiking were traceable to NIST standards (Methadone) or USP reference standards (Propoxyphene).
8. The sample size for the training set
Not applicable. This is not an AI/ML device that uses training sets. The calibrators and controls are manufactured to specific concentrations.
9. How the ground truth for the training set was established
Not applicable. As above, no training set is used. The ground truth for the product's declared concentrations is established through manufacturing processes and confirmed using GC/MS (as described in section 7). The calibrators are prepared by spiking known concentrations of drug analyte into a processed, drug-free human urine matrix.
{0}------------------------------------------------
DEC 1 6 2002
IC023316
510(k) Summary of Safety and Effectiveness
This summary of 510(k) safety and effectiveness information is heing submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
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.
Submitter name, Address, and Contact
Lin-Zhi International, Inc. 2391 Zanker Road, Suite 340 San Jose, CA 95131 Phone: (408) 944-0360 (408) 944-0359 Fax:
Contact: Chiu Chin Chang, Ph.D. VP, R&D
Device Name and Classification
| (a) Classification Name: | Calibrators, Drug Specific;Class II, DLJ (91 Toxicology), 21 CFR 862.3200 |
|---|---|
| Common/Usual Name: | Methadone Calibrators |
| Propoxyphene Calibrators | |
| Proprietary Name: | None |
| (b) Classification Name: | Drug Specific Control Materials; |
| Class I, LAS (91 Toxicology), 21 CFR 862.3280 | |
| Common/Usual Name: | Methadone Controls |
| Propoxyphene Controls | |
| Proprietary Name: | None |
Legally Marketed Predicate Device(s)
Lin-Zhi International, Inc.'s Single Analyte (Methadone or Propoxyphene) Urine Drugs of Abuse Calibrators and Controls are substantially equivalent to the Drugs of Abuse Urine Calibrators A and Controls A (Diagnostic Reagents, Inc., now Microgenics Corporation), cleared under premarket notifications (K983159) for Drugs of Abuse Urine Calibrators and Controls.
{1}------------------------------------------------
Device Description
All of the Single Analyte Urine DAU Calibrators and Controls are human urine-based liquid, and ready to use. These Calibrators and Controls do not have any especially unique technical characteristics. Each contains a known concentration of a specific drug analyte.
The Negative DAU calibrator is a processed, drug-free human urine matrix. The Low, Cutoff, Intermediate, and High Calibrators, as well as the 2 levels of Controls are prepared by spiking known concentrations of drug analyte into the Negative DAU Calibrator matrix. The various concentrations of each drug analyte in their corresponding calibrators and controls are summarized as follows:
| PropoxypheneEIA | MethadoneEIA | |
|---|---|---|
| Reference Material | Propoxyphene | Methadone |
| Low Calibrator | 150 ng/mL | 150 ng/mL |
| Cutoff Calibrator | 300 ng/mL | 300 ng/mL |
| Intermediate Calibrator | 600 ng/mL | 600 ng/mL |
| High Calibrator | 1000 ng/mL | 1000 ng/mL |
| Control Level 1 | 225 ng/mL | 225 ng/mL |
| Control Level 2 | 375 ng/mL | 375 ng/mL |
Intended Use
The Methadone or Propoxyphene Urine DAU Calibrators are intended for in vitro diagnostic use for the calibration of their respective enzyme immunoassays to detect methadone or propoxyphene in human urine.
The Methadone or Propoxyphene Urine DAU Controls are intended for in vitro diagnostic use for the validation of their respective enzyme immunoassays to detect methadone or propoxyphene in human urine.
{2}------------------------------------------------
Comparison to Predicate Device
LZI's Single Analyte (Methadone or Propoxyphene) Urine DAU Calibrators and Controls are similar in intended use, matrix, and performance to the DRI's Drugs of Abuse Urine Calibrators A and Controls A.
Similarities:
- . Both are for the calibration and validation of DAU enzyme immunoassay to detect drug of abuse in human urine.
- The cutoff concentration for either methadone or propoxyphene is the same, at 300 . ng/mL.
- A total of 5 levels of calibrators including the negative calibrator for each analyte. ●
- The nominal concentrations of the analyte in the calibrators and controls are determined and confirmed by GC/MS.
- Both are urine-based liquids. ●
- Storage condition is the same, at 2℃ to 8℃. ●
- Performance characteristics on precision, accuracy and stability are similar. ●
Differences:
| Characteristics | DRI's Drugs of Abuse UrineCalibrators A and Controls A | LZI's Single Analyte UrineDAU Calibrators and Controls |
|---|---|---|
| No. of Analytes in EachCalibrator or Control | Multiple drugs in eachCalibrator and Control | Single drug only in eachCalibrator or Control. |
| No. of Calibrators | 3 levels* including theNegative Calibrator | 5 levels including the NegativeCalibrator |
| Nomenclature/Labelingof Calibrators | Negative, Low (= Cutoff),and High | Negative, Low, Cutoff,Intermediate and HighCalibrators |
| Concentration ofAnalyte | Methadone Controls: 200 and375 ng/mL | Methadone Controls: 225 and375 ng/mL |
| Propoxyphene Controls: 200and 375 ng/mL | Propoxyphene Controls: 225and 375 ng/mL |
- Additional calibrators are now available. Currently 5 levels of calibrators (Cal 0, 1, 2, 3, and 4) are available from DRI/Microgenics Corp. under the product name "Multi-drug Urine Calibrators and Controls".
Conclusion
The information provided in the premarket notification demonstrates that the LZI's Methadone or Propoxyphene Urine Drugs of Abuse Calibrators and Controls are substantially equivalent to previously approved predicate devices, notably the DRI's Drugs of Abuse Urine Calibrators A and Controls A, and safe and effective for its intended use.
{3}------------------------------------------------
Performance Characteristics
Reproducibility (Precision)
Multiple vials each of the Calibrators and Controls were used during the evaluation of performance of the LZI's Methadone Enzyme Immunoassay and Propoxyphene Enzyme Immunoassay. The reproducibility, description of the assay principle, and assay procedure can be found on the package insert of each immunoassay.
The following tables illustrate the precision of each set of Single analyte Urine DAU Calibrators and Controls in their corresponding enzyme Immunoassays. Twelve vials each of Calibrators and Controls were used in immunoassay. The enzyme rates of the calibrators from each run and the concentrations of the controls determined from the calibration curves from the same run were summarized. Data on Methadone EIA were collected on the Synchron CX4CE Analyzer and data on Propoxyphene EIA were collected on the Hitachi 717 Analyzer.
| (N = 12) | Neg. Cal | Low Cal | Cutoff Cal | Intermediate Cal | High Cal |
|---|---|---|---|---|---|
| 0 ng/mL | 150 ng/mL | 300 ng/mL | 600 ng/mL | 1000 ng/mL | |
| Ave. Rate | 208.8 | 248.1 | 294.0 | 331.6 | 345.6 |
| Stdev | 0.9 | 2.1 | 3.0 | 2.6 | 1.3 |
| %CV | 0.4 | 0.8 | 1.0 | 0.8 | 0.4 |
Methadone EIA:
| (N=12) | Contl L1 | Contl L2 |
|---|---|---|
| 225 ng/mL | 375 ng/mL | |
| Ave. Conc. | 228.0 | 379.6 |
| Stdev | 7.8 | 13.2 |
| % CV | 3.4 | 3.5 |
Propoxyphene EIA:
| (N = 12) | Neg. Cal | Low Cal | Cutoff Cal | Intermediate Cal | High Cal |
|---|---|---|---|---|---|
| 0 ng/mL | 150 ng/mL | 300 ng/mL | 600 ng/mL | 1000 ng/mL | |
| Ave. Rate | 117.0 | 170.8 | 255.8 | 326.8 | 348.8 |
| Stdev | 0.8 | 1.4 | 2.3 | 1.9 | 2.5 |
| %CV | 0.6 | 0.8 | 0.9 | 0.6 | 0.7 |
| (N=12) | Contl L1 | Contl L2 |
|---|---|---|
| 225 ng/mL | 375 ng/mL | |
| Ave. Conc. | 232.6 | 378.0 |
| Stdev | 3.0 | 7.4 |
| % CV | 1.3 | 2.0 |
{4}------------------------------------------------
Accuracy
The concentrations of the LZI's Single Analyte (Methadone or Propoxyphene) Urine DAU Calibrators and Controls were determined and confirmed with gas chromatography/mass spectroscopy (GC/MS) technique. The observed concentration of the analyte in each calibrator or control, and its expected value are as follows:
| Methadone | Propoxyphene | |||
|---|---|---|---|---|
| Expected | GC/MS | Expected | GC/MS | |
| Low Cal. | 150 | 157 | 150 | 158 |
| Cutoff Cal. | 300 | 288 | 300 | 307 |
| Intermediate Cal. | 600 | 584 | 600 | 593 |
| High Cal. | 1000 | 963 | 1000 | 973 |
| Level 1 Control | 225 | 214 | 225 | 222 |
| Level 2 Control | 375 | 374 | 375 | 387 |
Methadone was purchased from Sigma and Aldrich, St. Louis, MO 63178 (Traceable to NIST standard.), and propoxyphene was purchased from Alltech Applied Science Lab., State College, PA 16801 (Traceable to USP reference standard.)
{5}------------------------------------------------
Stability
The LZI Methadone or Propoxyphene Urine DAU Calibrators and Controls were prepared according to established procedures. These Calibrators and Controls were stored at 2℃ to 8°C (Refrigerated) at all times until use.
To assess long-term stability an accelerated temperature stability study was carried out at room temperature (RT) for 6 months. Calibrators and Controls stored at RT were then evaluated and compared to those counter parts stored at 2°C to 8°C (Refrigerated). The results indicated there is no significant difference between the two.
Real time stability at refrigerated temperature is being continued. The product shelf life is anticipated to be at least 12 months at 2°C to 8°C storage conditions. Calibrators and Controls prepared in artificial matrix without the urine component have been evaluated earlier, and showed more than 24 months real time stability.
{6}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/6/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 three human profiles incorporated into its body. The eagle and profiles are black, and they are surrounded by a circular border containing the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in black lettering.
Food and Drug Administration 2098 Gaither Road ockville MD 20850
Chiu Chin Chang, Ph.D. VP. R&D Lin-Zhi International, Inc. 687 North Pastoria Avenue Sunnyvale, CA 94085
. Re: K023316
Trade/Device Name: Single Analyte (Methadone or Propoxyphene) Urine Drugs of Abuse Calibrators and Controls
Regulation Number: 21 CFR 862.3200 Regulation Name: Clinical Toxicology Calibrator Regulatory Class: Class II Product Code: DLJ, LAS Dated: September 30, 2002 Received: October 3, 2002
Dear Dr. Chang:
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).
{7}------------------------------------------------
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). Other general information on your responsibilities under the Act may be obtained 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 Putman
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
{8}------------------------------------------------
Premarket Notification
Indications for Use Statement
KO23316 510(k) Number (if known):
Device Name: Single Analyte (Methadone or Propoxyphene) Urine Drugs of Abuse Calibrators and Controls
Indications for Use:
The Methadone or Propoxyphene Urine Drugs of Abuse Calibrators are intended for in vitro diagnostic use for the calibration of their respective enzyme immunoassays to detect methadone or propoxyphene in human urine.
The Methadone or Propoxyphene Urine Drugs of Abuse Controls are intended for in vitro diagnostic use for the validation of their respective enzyme immunoassays to detect methadone or propoxyphene in human urine.
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)
Dean Cooper
(Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number --
§ 862.3200 Clinical toxicology calibrator.
(a)
Identification. A clinical toxicology calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. A clinical toxicology calibrator can be a mixture of drugs or a specific material for a particular drug (e.g., ethanol, lidocaine, etc.). (See also § 862.2 in this part.)(b)
Classification. Class II (special 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.