(11 days)
The Pan Probe Biotech (PPB), Inc LiveSure™ Methadone Screen Test Card & Test Strip devices are rapid in vitro diagnostic (IVD) qualitative lateral flow competitive immuno-chromatographic urinary screening devices intended for detection of Methadone, its analogs and metabolites (collectively termed: screening at the NIDA (National Institute on Drug Abuse) and SAMHSA (Substance Abuse and Health Services Administration) cut-off level of 300 ng MED/ml of human urine. These PPB Mcharl Featur bervices Hand & Test Strip IVD immunoassay devices are designed for visual, qualitative screening, for professional use only, and are not intended for quantitative results, nor for quanuative berealling) for presentativeSure™ Methadone Test Card & Test Strip devices provide only ovel ate commal (or o) creening data for use to aid in the diagnosis of drug abuse or over use. A premium y quantitative alternative method must be used in order to obtain a confirmed analytical result. NIDA and SAMHSA have established gas chromatographic/mass spectrometry (GC/MS) as the result. NDTT and of micel considerations and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are indicated.
The Pan Probe Biotech LiveSure™ Methadone Screen Test Card and Test Strip (i.e., LiveSure™ Methadone) which are rapid qualitative chromatographic IVD immunoassays, in which chemically labeled drug conjugate competes with any Methadone (MED) drugs, analogs or metabolites that may be in the conjugure comples for limited specific antibody binding sites. LiveSure™ Methadone devices prescient in test annual bas been pre-coated both with a Methadone (MED-)drug conjugate at the test band, and is followed by a built-in reference band with a second antibody as a system control band. A test colored anti-MED monoclonal antibody-colloidal gold conjugate pad is placed to the right of a test strip. In the absence of MED drugs, analogs or metabolites in urine, pink colored antibody-colloidal gold conjugates move chromatographically along with the urinary samples on the membrane by capillary ection. Antibody-colloidal gold conjugate binds to MED-drug conjugate, forming an antibody-antigen complex. This antibody-MED-drug conjugate appears as second visible pink colored band and captured reagent at the test region. Any MED present in a sample urine act as antigens, competing with MED-drug reagon at the test band region for limited MED-antibody binding sites on antibody-colloidal gold conjugate. When a sufficient concentration of urinary MED drugs, analogs or metabolites are present, these analytes block the limited antibody binding sites. This blockage-binding process prevents attachment of anial colored antibody-colloidal gold conjugate at the MED-drug conjugate zone located at the test band region. To serve as a procedural control, a pink colored band in a control region will always appear, regardless of the presence of MED in urine samples. Thus, negative urine samples produce two pink colored bands, while positive urine samples produce only one pink colored band.
Here's an analysis of the provided text regarding the Pan Probe Biotech LiveSure™ Methadone Screen Test Card & Test Strip, structured according to your request:
Acceptance Criteria and Device Performance Study
The information provided describes the performance of the Pan Probe Biotech LiveSure™ Methadone Screen Test Card & Test Strip against a predicate device (EMIT® II) and a gold standard (GC/MS).
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to the predicate device and the GC/MS gold standard. The document doesn't explicitly state quantitative acceptance criteria in a formal "pass/fail" sense prior to presenting results, but rather demonstrates "substantial equivalence." However, we can infer the desired equivalency based on the reported performance.
| Performance Metric | Acceptance Criteria (Implied) | LiveSure™ Methadone Screen Test Card & Test Strip Performance (vs. GC/MS) | LiveSure™ Methadone Screen Test Card & Test Strip Performance (vs. EMIT® II) | EMIT® II Performance (vs. GC/MS) |
|---|---|---|---|---|
| Agreement for Positive Results (Sensitivity) | High agreement with GC/MS positive results | 100% | 98.4% (for both Card and Strip) | N/A (not directly stated as a separate metric) |
| Agreement for Negative Results (Specificity) | High agreement with GC/MS negative results | 99.0% | 99.4% (for both Card and Strip) | N/A (not directly stated as a separate metric) |
| False Positives (FP) | Minimize FPs, especially for samples below cut-off | 0 | N/A | 1 (for samples with GC/MS < 225 ng/ml) |
| False Negatives (FN) | Minimize FNs | 0 | N/A | 1 |
| Overall Accuracy | High overall accuracy against GC/MS | 299/301 (99.3%) | N/A | 296/301 (98.3%) |
| Equivalency to Predicate Device | Essental equivalency to EMIT® II Assay | Supported by agreement percentages | Directly compared | N/A |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 301 urine samples.
- Data Provenance: Independent clinical testing at an external reference laboratory. The country of origin is not explicitly stated, but the overall context of an FDA 510(k) submission for a US market suggests it was likely US-based or conducted under US regulatory standards. The study was prospective in the sense that the samples were tested against the new device (LiveSure™ Methadone), the predicate device (EMIT® II), and the confirmatory method (GC/MS) in the context of this evaluation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The ground truth was established by Gas Chromatography/Mass Spectrometry (GC/MS). Therefore, the "experts" in this context are the trained laboratory personnel who perform and interpret GC/MS results. The number of such personnel is not specified, nor are their individual qualifications beyond the implication that they operate an "external reference laboratory" providing professional GC/MS quantitative results. GC/MS is considered the definitive method for drug confirmation.
4. Adjudication Method for the Test Set
There was no explicit "adjudication method" in the typical sense (e.g., 2+1 expert review). The GC/MS results served as the definitive quantitative ground truth against which all other results (LiveSure™ Methadone and EMIT® II) were compared. Any discrepancies between the rapid tests and GC/MS would be resolved by the GC/MS result being the accepted truth.
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. The LiveSure™ Methadone device is a "rapid qualitative chromatographic IVD immunoassay" designed for visual interpretation. While technicians would read the results, the study focuses on the device's accuracy against a gold standard, not on the variability or improvement in human reader performance with or without AI assistance. The device itself is not described as having an AI component to assist human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the study primarily presents standalone performance of the device. The LiveSure™ Methadone device itself (the test card/strip) is tested as an algorithm for detecting methadone. Its "algorithm" is the biochemical reaction and visual readout. There is no complex digital algorithm or "human-in-the-loop" described beyond a technician visually interpreting the bands. The performance metrics (sensitivity, specificity, accuracy) are for the device's inherent ability to produce a correct result.
7. The Type of Ground Truth Used
The primary and definitive ground truth used was GC/MS (Gas Chromatography/Mass Spectrometry) quantitative results. This is considered the "gold standard" for drug testing, providing objective, confirmatory, and quantitative data.
8. The Sample Size for the Training Set
The document does not explicitly state a training set sample size. The text describes "In-house testing" preceding the independent clinical testing, but it doesn't quantify this in-house testing as a separate "training set" in the machine learning sense. The device is a chemical immunoassay, not a machine learning algorithm that typically requires a large, separate training dataset. The development and internal validation of such a device involve optimization and testing, but these are generally considered part of the design process rather than a discrete "training set" for statistical model fitting.
9. How the Ground Truth for the Training Set Was Established
Since a distinct "training set" is not detailed or quantified in the provided text as it would be for AI/ML, the method for establishing its ground truth is also not explicitly stated. However, given the nature of the device and the later clinical study, it's highly probable that "in-house testing" and development would have also relied on GC/MS or similar confirmatory methods to validate prototype performance and optimize the assay parameters (e.g., antibody concentrations, cutoff levels) against known positive and negative samples. The document states "under Good Laboratory Practices guidelines," implying rigorous internal validation processes.
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Pan Probe Biotech LiveSure™ Methadone Screen Test Card & Test Strip
Pan Probe Biotech, Inc.
NOV 2 6 2001
( 0 13796 Revision B, October 22, 2001
SUMMARY STATEMENT OF SAFETY AND EFFECTIVENESS
The sponsor, Probe Biotech, Inc., has developed, manufactured, and tested under Good Laboratory Practices guidelines, in vitro diagnostic (IVD) devices for qualitative testing of urine samples for the presence of guidemics) in "The Canglessia (State (States) in an IVD screening format. The trade name of the devices are the Pan Methadone, 16 thatogo, and news on and Test Strip, having TDA assigned name: Methadone I love Diotech Livesure - Mediatone of Select I device per 21 CFR 862.3260, with product code: DJR. These IVD I est youth a casomethon as a caso eening of urines for Methadone, its analogs, and metabolites.
The Pan Probe Biotech LiveSure™ Methadone Screen Test Card and Test Strip (i.e., LiveSure™ Methadone) I which are rapid qualitative chromatographic IVD immunoassays, in which chemically labeled drug conjugate competes with any Methadone (MED) drugs, analogs or metabolites that may be in the conjugure comples for limited specific antibody binding sites. LiveSure™ Methadone devices prescient in test annual bas been pre-coated both with a Methadone (MED-)drug conjugate at the test band, and is followed by a built-in reference band with a second antibody as a system control band. A test colored anti-MED monoclonal antibody-colloidal gold conjugate pad is placed to the right of a test strip. In the absence of MED drugs, analogs or metabolites in urine, pink colored antibody-colloidal gold conjugates move chromatographically along with the urinary samples on the membrane by capillary ection. Antibody-colloidal gold conjugate binds to MED-drug conjugate, forming an antibody-antigen complex. This antibody-MED-drug conjugate appears as second visible pink colored band and captured reagent at the test region. Any MED present in a sample urine act as antigens, competing with MED-drug reagon at the test band region for limited MED-antibody binding sites on antibody-colloidal gold conjugate. When a sufficient concentration of urinary MED drugs, analogs or metabolites are present, these analytes block the limited antibody binding sites. This blockage-binding process prevents attachment of anial colored antibody-colloidal gold conjugate at the MED-drug conjugate zone located at the test band region. To serve as a procedural control, a pink colored band in a control region will always appear, regardless of the presence of MED in urine samples. Thus, negative urine samples produce two pink colored bands, while positive urine samples produce only one pink colored band.
In-house testing of LiveSure™ Methadone Screen Test Card and Test Strip devices against EMIT® II In house to as a predicate device provided data essentially showing equivalency between the Card and Strip devices, and to the predicate EMIT® II Assay. Additionally, independent clinical testing of 301 urine samples against LiveSure™ Methadone Screen Test Card and Test Strip devices, as well as EMIT® II Assay at an external reference laboratory resulted in a 100% percent agreement with all GC/MS quantitative positive results. Moreover, LiveSure™ Methadone Test Card or Strip gave both 99.0% agreement with GC/MS negative results. In comparing the Test Card and Test Strip positives with EMIT® II positives, both gave 98.4% respective agreement with EMIT® II positives. Specificity of Test Card and Test Strip negatives with EMIT® II negatives was shown to be 99.4% for both. In terms of overall accuracy of values at and below the ±25% range of the NIDA/SAMHSA cut-off of 300 ng Methadone/ml, however, the LiveSure™ Methadone Screen Test Card and Strip yielded no false positives (FP), whereas EMIT®II resulted in 1 FP value for urine samples with GC/MS results below 225 ng/ml. Also EMIT® II apparently had 1 false negative (1FN), while Test Card & Test Strip gave zero FN results vs. GC/MS. Finaly, the LiveSure™ Methadone Test Card and the Test Strip gave overall accuracy results of 299/301 (99.3%) for both versus GC/MS data, whereas 296/301 (98.3%) accuracy was obtained with EMTT®II immunoassay. Thus, the LiveSure™ Methadone Test Card and Test Strip devices were determined to be substantially equivalent in performance to the approved predicate EMTT® II Methadone immunoassay device, and the LiveSure™ Methadone Test Card and Test Strip devices were shown to be substantially equivalent to each other in performance, each versus the external GC/MS Methadone laboratory results.
Additional information on this submission may be obtained by contacting Alice Yu, Vice President, Pan Probe Biotech, Inc. at: 1- 858-689-9936 or by fax at 1-858-689-6896.
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Image /page/1/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized abstract design, resembling a bird or a flowing shape, with three curved lines. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the design.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV 2 6 2001
Pan Probe Biotech, Inc. c/o Raymond Wilson, Pharm. D. California Department of Health Services Food and Drug Branch 714/744 P Street P.O. Box 942732 (MS-357) Sacramento, CA 94234-7320
K013796 Re:
Trade/Device Name: PanProbe Biotech, Inc. LiveSure™ Methadone Screen Test Card & Test Strip
Regulation Number: 21 CFR 862.3620 Regulation Name: Methadone test system Regulatory Class: Class II Product Code: DJR Dated: November 2, 2001 Received: November 15, 2001
Dear Dr. Wilson:
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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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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 nredicate 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 1 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 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/cdrb/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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510k Submission for Pan Probe Biotech LiveSure™ Methadone Screen Test Card & Test Strip 19 Revision B, October 22, 2001 Proprietary Information Pan Probe Biotech, Inc.
510(k) Regulatory No. (if known): 21 CFR 862.3620; Product Code: DJR
DEVICE NAME: Pan Probe Biotech, Inc. LiveSure™ Methadone Screen Test Card & Test Strip
INDICATIONS FOR USE STATEMENT
The Pan Probe Biotech (PPB), Inc LiveSure™ Methadone Screen Test Card & Test Strip devices are rapid in vitro diagnostic (IVD) qualitative lateral flow competitive immuno-chromatographic urinary screening devices intended for detection of Methadone, its analogs and metabolites (collectively screening at the NIDA (National Institute on Drug Abuse) and SAMHSA (Substance Abuse and termed: Health Services Administration) cut-off level of 300 ng MED/ml of human urine. These PPB Mcharl Featur bervices Hand & Test Strip IVD immunoassay devices are designed for visual, qualitative screening, for professional use only, and are not intended for quantitative results, nor for quanuative berealling) for presentativeSure™ Methadone Test Card & Test Strip devices provide only ovel ate commal (or o) creening data for use to aid in the diagnosis of drug abuse or over use. A premium y quantitative alternative method must be used in order to obtain a confirmed analytical result. NIDA and SAMHSA have established gas chromatographic/mass spectrometry (GC/MS) as the result. NDTT and of micel considerations and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are indicated.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Thomas C. Durto
(Division Sign-Off) Division of Clinical Laboratory Devices Kor3196 510(k) Number
/ Prescription Use
Over the Counter Use
§ 862.3620 Methadone test system.
(a)
Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by this device are used in the diagnosis and treatment of methadone use or overdose and to determine compliance with regulations in methadone maintenance treatment.(b)
Classification. Class II (special controls). A methadone 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).