(150 days)
Not Found
No
The summary describes a standard enzyme immunoassay for drug detection and does not mention any AI or ML components in the device description or performance studies.
No
This device is an in-vitro diagnostic assay used for screening the presence of buprenorphine and its metabolites in human urine. It is not designed for therapeutic purposes, but rather for analytical testing and screening.
Yes
The "Intended Use / Indications for Use" section explicitly states "For In Vitro Diagnostic Use Only," indicating its purpose is to provide analytical results for diagnostic purposes.
No
The device description explicitly states that the assay consists of buffers and lyophilized reagents, which are physical components, not software. The device is an in vitro diagnostic assay that is used with clinical chemistry analyzers, which are hardware.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states: "For In Vitro Diagnostic Use Only." This is a clear declaration of its intended purpose.
- Nature of the Test: The assay is designed to detect the presence of buprenorphine and its metabolites in human urine. This involves testing a biological sample in vitro (outside the body) to provide diagnostic information (screening for the presence of a substance).
- Components: The device description lists reagents and calibrators used for performing the test on a biological sample.
- Performance Studies: The document details performance studies conducted to validate the assay's accuracy and reliability for its intended use in a laboratory setting.
- Care Setting: The assay is intended to be used in "laboratories," which is a typical setting for IVD testing.
All these factors align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
CEDIA Buprenorphine II Assay:
The CEDIA Buprenorphine II Assay is a homogeneous enzyme immunoassay for the qualitative and/or semiquantitative determination for the presence of buprenorphine and its metabolites in human urine at a cut-off concentration of 10 ng/ mL. The assay is intended to be used in laboratories and provides a simple and rapid analytical screening procedure to detect buprenorphine and its metabolites in human urine. The assay is designed for use with a number of clinical chemistry analyzers.
The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid chromatography/tandem mass spectrometry (LC-MS/ MS) or permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical test result. A more specific alternative chemical must be used to obtain a confirmed analytical result. Gas chromatography/ mass spectrometry (GC/MS) or Liquid chromatography/tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method.
Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.
CEDIA Buprenorphine II Calibrators:
The CEDIA Buprenorphine II calibrators and CEDIA Negative Calibrator II are intended for the calibration of the CEDIA Buprenorphine II Assay in human urine. For In Vitro Diagnostic Use Only.
CEDIA Buprenorphine II Control Set:
The CEDIA Buprenorphine II controls are used to validate the CEDIA Buprenorphine II Assay calibration in human urine. For In Vitro Diagnostic Use Only.
Product codes (comma separated list FDA assigned to the subject device)
DJG, DLJ, LAS
Device Description
The assay consists of buffers (1 and 2) and lyophilized reagents (1a and 2a). The components include mouse monoclonal anti-buprenorphine antibody, recombinant microbial "enzyme donor'' - buprenorphine conjugate, "enzyme acceptor", chlorophenol red ß-Dgalactopyranoside, stabilizers and preservatives. Calibrators and controls are sold separately.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Human urine
Indicated Patient Age Range
Not Found
Intended User / Care Setting
laboratories (for the assay)
Prescription users only (Intended Users from Comparison to Predicate Device)
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
- Analytical Performance: Performance evaluated at manufacturer's site on Beckman Coulter AU 680 Analyzer.
- Precision Study: 80 total samples (2 runs/day, twice a day, for 20 days).
- Samples spiked at cutoff, 25%, 50%, 75%, 100% above and below cutoff.
- Tested in qualitative and semi-quantitative modes.
- Results presented in tables for Qualitative and Semi-Quantitative.
- Spike Recovery: 20 replicates of 7.5 ng/mL (Negative) and 12.5 ng/mL (Positive) samples compared to 10 ng/mL spiked sample.
- Semi-quantitative mode: spiked samples recovered within 80-120% of nominal values.
- Analytical Recovery and Dilution Linearity: Drug-free urine spiked to 100 ng/mL Buprenorphine and diluted to 10 intermediate levels.
- Each sample run in replicates of five in semi-quantitative mode.
- Average used to determine percent recovery compared to expected target value.
- Results presented in table.
- Method Comparison and Accuracy: 153 urine patient samples analyzed by CEDIA Buprenorphine II Assay (qualitative and semi-quantitative modes) and compared to LC-MS/MS.
- Tables show Candidate Device Results (Positive/Negative) against LC-MS/MS concentration ranges.
- Discordant samples summarized in a dedicated table showing EIA results (Qual and SQ ng/mL) against LC-MS/MS concentrations for Buprenorphine (Bup), Norbuprenorphine (NorBup), Buprenorphine-ß-D-glucuronide (Bup-Glu), and Norbuprenorphine-ß-D-glucuronide (NorBup-Glu), and Total by LC-MS/MS.
- Specificity (Cross-reactivity): Evaluated by adding known amounts of Buprenorphine and its metabolites to drug-free negative urine.
- Buprenorphine, Norbuprenorphine, and Norbuprenorphine-ß-D-glucuronide showed ≥ 100% cross-reactivity.
- Buprenorphine-ß-D-glucuronide showed 76.9% cross-reactivity.
- Table lists other Structurally Related Compounds and Other Opiates with tested concentrations, positive/negative results, and cross-reactivity (all
- Precision Study: 80 total samples (2 runs/day, twice a day, for 20 days).
§ 862.3650 Opiate test system.
(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate 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).
0
Image /page/0/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 an abstract symbol resembling an eagle or a stylized human profile, composed of three overlapping faces.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 April 6. 2017
MICROGENICS CORPORATION MINOTI PATEL SR. REGULATORY AFFAIRS SPECIALIST 46500 KATO ROAD FREMONT CA 94538
Re: K163101 Trade/Device Name: CEDIA Buprenorphine II Assay CEDIA Buprenorphine II Calibrators and CEDIA Negative Calibrator II CEDIA Buprenorphine II Control Set Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: II Product Code: DJG, DLJ, LAS Dated: March 17, 2017 Received: March 20, 2017
Dear Minoti Patel:
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
1
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Courtney H. Lias -S
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K163101
Device Name CEDIA Buprenorphine II Assay CEDIA Buprenorphine II Calibrators and CEDIA Negative Calibrator II CEDIA Buprenorphine II Control Set
Indications for Use (Describe)
CEDIA Buprenorphine II Assay:
The CEDIA Buprenorphine II Assay is a homogeneous enzyme immunoassay for the qualitative and/or semiquantitative determination for the presence of buprenorphine and its metabolites in human urine at a cut-off concentration of 10 ng/ mL. The assay is intended to be used in laboratories and provides a simple and rapid analytical screening procedure to detect buprenorphine and its metabolites in human urine. The assay is designed for use with a number of clinical chemistry analyzers.
The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid chromatography/tandem mass spectrometry (LC-MS/ MS) or permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical test result. A more specific alternative chemical must be used to obtain a confirmed analytical result. Gas chromatography/ mass spectrometry (GC/MS) or Liquid chromatography/tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method.
Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.
CEDIA Buprenorphine II Calibrators:
The CEDIA Buprenorphine II calibrators and CEDIA Negative Calibrator II are intended for the calibration of the CEDIA Buprenorphine II Assay in human urine. For In Vitro Diagnostic Use Only.
CEDIA Buprenorphine II Control Set:
The CEDIA Buprenorphine II controls are used to validate the CEDIA Buprenorphine II Assay calibration in human urine. For In Vitro Diagnostic Use Only.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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3
510(k) Summary
| A. Device Information
| Category | Comments |
|---|---|
| Sponsor: | Microgenics Corporation |
| Thermo Fisher Scientific | |
| 46500 Kato Road | |
| Fremont, CA 94538 | |
| Phone: 510-979-5000 | |
| FAX: 510-979-5002 | |
| Correspondent Contact | |
| Information: | Minoti Patel, RAC |
| Sr. Regulatory Affairs Specialist | |
| Email: Minoti.patel@thermofisher.com | |
| Phone: 510-749-5000 | |
| FAX: 510-749-5002 | |
| Device Common Name: | Buprenorphine Immunoassay Test System |
| Trade or Proprietary Name | CEDIA® Buprenorphine II Assay |
| CEDIA® Buprenorphine II Calibrators | |
| CEDIA® Negative Calibrator II | |
| CEDIA® Buprenorphine II Control Set | |
| Predicate Device Product | |
| Code, Classification, | |
| Classification Name & Panel | DJG, Class II, 21 CFR 862.3650 – Opiate test system, |
| 91 - Toxicology | |
| DLJ, Class II, 21 CFR 862.3200 – Clinical toxicology | |
| control material, 91 – Toxicology | |
| LAS, Class I, reserved; 21 CFR 862.3280 – Clinical | |
| toxicology control material. 91 - Toxicology |
A. Device Information
Predicate Device Information:
| Predicate Device: | CEDIA® Buprenorphine Assay
CEDIA® Negative Calibrator II
CEDIA® Buprenorphine Calibrators
CEDIA® Buprenorphine Control Set |
|----------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Predicate Device
Manufacturer: | Microgenics Corporation |
| Predicate Device Common
Name: | Buprenorphine Immunoassay Test System |
| Predicate Device Premarket
Notification #: | K040316 |
| Predicate Device Product
Code, Classification,
Classification Name & Panel | DJG, Class II, 21 CFR 862.3650 – Opiate test system,
91 - Toxicology
DLJ, Class II, 21 CFR 862.3200 – Clinical toxicology
control material, 91 – Toxicology
LAS, Class I, reserved; 21 CFR 862.3280 – Clinical
toxicology control material. 91 - Toxicology |
4
B. Date Summary Revised
April 04, 2017
C. Description of Device
The assay consists of buffers (1 and 2) and lyophilized reagents (1a and 2a). The components include mouse monoclonal anti-buprenorphine antibody, recombinant microbial "enzyme donor'' - buprenorphine conjugate, "enzyme acceptor", chlorophenol red ß-Dgalactopyranoside, stabilizers and preservatives. Calibrators and controls are sold separately.
D. Intended Use
Intended Use:
CEDIA® Buprenorphine II Assay:
The CEDIA® Buprenorphine II Assay is a homogeneous enzyme immunoassay for the qualitative and/or semiquantitative determination for the presence of buprenorphine and its metabolites in human urine at a cut-off concentration of 10 ng/mL. The assay is intended to be used in laboratories and provides a simple and rapid analytical screening procedure to detect buprenorphine and its metabolites in human urine. The assay is designed for use with a number of clinical chemistry analyzers.
The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid chromatography/tandem mass spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.
The 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) or Liquid chromatography/tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method.
Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.
CEDIA® Buprenorphine II Calibrators:
The CEDIA® Buprenorphine II calibrators and CEDIA® Negative Calibrator II are intended for the calibration of the CEDIA® Buprenorphine II Assay in human urine. For In Vitro Diagnostic Use Only.
CEDIA® Buprenorphine II Control Set:
The CEDIA® Buprenorphine II controls are used to validate the CEDIA® Buprenorphine II Assay calibration in human urine. For In Vitro Diagnostic Use Only.
E. Comparison to Predicate Device
Both devices use similar reagent and instrument systems. Both devices detect buprenorphine. The predicate device's specific antibody detects buprenorphine and buprenorphine glucuronide at cutoff concentration of 5 ng/mL. The CEDIA device's specific antibody detects buprenorphine, buprenorphine glucuronide, norbuprenorphine and norbuprenorphine
5
glucuronide at a buprenorphine cutoff concentration of 10 ng/ml. Other differences and similarities are presented below.
| Similarities - Assay | ||
|---|---|---|
| Item | Device | K040316 - Microgenics |
| CEDIA Buprenorphine | ||
| Assay | ||
| Intended Use | Same | Detection of |
| buprenorphine in human | ||
| urine | ||
| Methodology | Same | CEDIA (Cloned Enzyme |
| Donor Immunoassay) | ||
| Intended Users | Same | Prescription users only |
| Reagents Form | Same | Lyophilized (requiring |
| reconstitution) and liquid | ||
| ready to use | ||
| Antibody | Same | Mouse monoclonal |
| Storage | Same | 2 – 8° C until expiration |
| date | ||
| Target Analyte | Same | Buprenorphine |
| Differences - Assay | ||
|---|---|---|
| Item | Device | Predicate |
| Cutoff | 10 ng/mL | 5 ng/mL |
| Similarities – Calibrators | ||
|---|---|---|
| Item | Device | Predicate |
| Form | Same | Liquid – ready to use |
| Storage | Same | 2–8° C until expiration date |
| Differences - Calibrators | ||
|---|---|---|
| Item | Device | Predicate |
| Calibrator Name | CEDIA® | |
| Buprenorphine II calibrators and controls | CEDIA® | |
| Buprenorphine calibrators and controls | ||
| Calibrator Levels | 0, 10, 20, 50, 100 ng/mL | 0, 5, 20, 50, 75 ng/mL |
6
| Similarities – Controls | ||
|---|---|---|
| Item | Device | Predicate |
| Form | Same | Liquid – ready to use |
| Storage | Same | 2 – 8° C until expiration |
| date |
| Item | Device | Predicate |
|---|---|---|
| Control Names | CEDIA® | |
| Buprenorphine II controls | CEDIA® | |
| Buprenorphine controls | ||
| Control Levels | 7.5 and 12.5 ng/mL | 3 and 7 ng/mL |
| Form | Same | Liquid - ready to use |
| Storage | Same | 2 – 8° C until |
| expiration date |
F. Test Principle
The assay is based on bacterial enzyme ß-galactosidase genetically engineered to two inactive fragments, one of which is conjugated to buprenorphine. Buprenorphine in the sample competes with the enzyme fragment-conjugated buprenorphine for binding to antibuprenorphine antibody. In the absence of buprenorphine in the sample, the fragment binds antibody and does not re-associate to form active enzyme. If buprenorphine is present in the sample it binds to the antibody, allowing the enzyme fragments to re-associate. The reassociated enzyme cleaves the substrate, generating a color change that can be measured spectrophotometrically (570/660 nm). The amount of active enzyme is proportional to the analyte present.
G. Summary of Supporting Data
1. Analytical Performance:
Performance is evaluated at the manufacturer's site on Beckman Coulter AU 680 Analyzer.
- a) Precision Study is performed for two runs per day, twice a day, for 20 days (total n=80). Samples are prepared by spiking Buprenorphine into drug free urine at the cutoff, 25%, 50%, 75% & 100% above and below the cutoff and tested in both qualitative and semi-quantitative modes. Representative data is presented below.
| % of
Cutoff | Spiked Conc.
(ng/mL) | LC-MS/MS
(ng/mL) | Within Run (n=80) | |
|----------------|-------------------------|---------------------|---------------------------|------------------------|
| | | | Number of
determinants | Immunoassay
Results |
| -100% | 0 | 0 | 80 | 80 Neg |
| -75% | 2.5 | 2.99 | 80 | 80 Neg |
| -50% | 5 | 5.31 | 80 | 80 Neg |
| -25% | 7.5 | 7.63 | 80 | 80 Neg |
| 100% | 10 | 10.99 | 80 | 27 Neg/53 Pos |
| +25% | 12.5 | 12.97 | 80 | 80 Pos |
Oualitative Results:
7
| % of
Cutoff | Spiked Conc.
(ng/mL) | LC-MS/MS
(ng/mL) | Within Run (n=80) | |
|----------------|-------------------------|---------------------|------------------------|---------------------|
| | | | Number of determinants | Immunoassay Results |
| +50% | 15 | 15.05 | 80 | 80 Pos |
| +75% | 17.5 | 18.92 | 80 | 80 Pos |
| +100% | 20 | 20.38 | 80 | 80 Pos |
Semi-Quantitative Results:
| % of
Cutoff | Spiked Conc.
(ng/mL) | LC-MS/MS
(ng/mL) | Within Run (n=80) | |
|----------------|-------------------------|---------------------|---------------------------|------------------------|
| | | | Number of
determinants | Immunoassay
Results |
| -100% | 0 | 0 | 80 | 80 Neg |
| -75% | 2.5 | 2.99 | 80 | 80 Neg |
| -50% | 5 | 5.31 | 80 | 80 Neg |
| -25% | 7.5 | 7.63 | 80 | 80 Neg |
| 100% | 10 | 10.99 | 80 | 35 Neg/45 Pos |
| +25% | 12.5 | 12.97 | 80 | 80 Pos |
| +50% | 15 | 15.05 | 80 | 80 Pos |
| +75% | 17.5 | 18.92 | 80 | 80 Pos |
| +100% | 20 | 20.38 | 80 | 80 Pos |
-
b) Spike Recovery All 20 replicates of spiked 7.5 ng/mL and 12.5 ng/mL sample detect as Negative and Positive, respectively, when compared to 10 ng/mL spiked sample.
In semi-quantitative mode, the spiked samples recover within 80-120% of the nominal values. -
c) Analytical Recovery and Dilution Linearity To demonstrate the dilution linearity for purpose of sample dilution and quality control of the entire assay range, drug free urine is spiked to the high calibrator level of Buprenorphine (100 ng/mL) and diluted with drug free urine to generate 10 intermediate levels.
Each sample is run in replicates of five in semi-quantitative mode and the average is used to determine percent recovery compared to the expected target value. Representative data is presented below.
| Level | Target
Concentration
(ng/mL) | Observed
Concentration
(ng/mL) | Recovery (%) |
|-------|------------------------------------|--------------------------------------|--------------|
| 1 | 0 | -0.09 | n/a |
| 2 | 5 | 5.99 | 119.8 |
| 3 | 10 | 10.97 | 109.7 |
| 4 | 20 | 19.66 | 98.3 |
| 5 | 30 | 33.03 | 110.1 |
| 6 | 40 | 43.83 | 109.6 |
8
| Level | Target
Concentration
(ng/mL) | Observed
Concentration
(ng/mL) | Recovery (%) |
|-------|------------------------------------|--------------------------------------|--------------|
| 7 | 50 | 52.98 | 106.0 |
| 8 | 60 | 67.28 | 112.1 |
| 9 | 70 | 77.54 | 110.8 |
| 10 | 80 | 85.14 | 106.4 |
| 11 | 90 | 95.38 | 106.0 |
| 12 | 100 | 104.70 | 104.7 |
- d) Method Comparison and Accuracy One hundred and fifty three urine patient samples are analyzed by the CEDIA® Buprenorphine II Assay in both qualitative and semiquantitative modes and the results are compared to LC-MS/MS.
Qualitative mode using stratified Buprenorphine values by LC-MS/MS
| Candidate
Device
Results | Negative | 15ng/mL) |
|--------------------------------|----------|--------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------|
| Positive | 31* | 11* | 4* | 5 | 45 |
| Negative | 49 | 2 | 6 | 0 | 0 |
- Discordant samples summarized in table 5 below.
Semi-Quantitative mode using stratified Buprenorphine values by LC-MS/MS
| Candidate
Device
Results | Negative | 15ng/mL) |
|--------------------------------|----------|--------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------|
| Positive | 32*‡ | 11* | 4* | 5 | 45 |
| Negative | 48 | 2 | 6 | 0 | 0 |
- Discordant samples summarized in table 5 below.
Additional discordant sample (ID #53) in Lot #3 Semi-quantitative mode shown in table 5 below.
9
*Table for Discordant Samples
| EIA | LC-MS/MS Concentration (ng/mL) | ||||||
|---|---|---|---|---|---|---|---|
| Sample | |||||||
| ID | Qual | ||||||
| mode | SQ | ||||||
| (ng/mL) | Bup*** | NorBup# | Bup-Glu | NorBup- | |||
| Glu† | Total by | ||||||
| LC-MS/MS | |||||||
| 51 | Pos | 10.08 | 100.01 | 100.01 | 100.01 | 100.01 | 100.01 |
| 84 | Pos | 63.54 | 0.86 | 7.41 | 29.46 | 31.38 | 69.11 |
| 85 | Pos | 20.48 | 0.90 | 5.42 | 11.54 | 100.01 | 0.91 |
| 87 | Pos | 46.32 | 2.00 | 12.03 | 13.58 | 16.24 | 43.85 |
| 88 | Pos | >100.01 | 2.00 | 6.83 | 193.42 | 131.65 | 333.90 |
| 89 | Pos | >100.01 | 2.02 | 75.75 | 174.74 | 442.98 | 695.49 |
| 90 | Pos | 66.32 | 2.48 | 6.53 | 57.67 | 1.52 | 68.20 |
| 91 | Pos | >100.01 | 3.63 | 80.26 | 733.7 | 624.02 | 1441.61 |
| 91 | Pos | >100.01 | 3.63 | 80.26 | 733.7 | 624.02 | 1441.61 |
| 92 | Pos | >100.01 | 4.38 | 69.28 | 146.16 | 349.33 | 569.15 |
| 93 | Pos | >100.01 | 4.45 | 59.03 | 55.01 | 17.31 | 135.80 |
| 100 | Pos | >100.01 | 8.64 | 36.91 | >ULOQ** | 224.42 | >1000 |
| 101 | Pos | >100.01 | 8.94 | 51.32 | 497.32 | 55.06 | 612.64 |
| 102 | Pos | >100.01 | 5.22 | 35.13 | 85.99 | 22.24 | 148.58 |
| 103 | Pos | 77.36 | 6.60 | 147.58 | 195.67 | 40.28 | 390.13 |
** ULOQ: Upper Limit of Quantitation (1000ng/mL);
*** Bup: Buprenorphine;
NorBup: Norbuprenorphine;
-
Bup-Glu: Buprenorphine-ß-D-glucuronide;
-
NorBup-Glu: Norbuprenorphine-ß-D-glucuronide;
Additional discordant sample for Lot #3 Semi-Quantitative mode
- e) Specificity The cross-reactivity of Buprenorphine and its metabolites is evaluated by adding known amounts of each analyte to drug-free negative urine. As indicated by the results in the table below, Buprenorphine, Norbuprenorphine and Norbuprenorphine-B-Dglucuronide exhibit ≥ 100% cross-reactivity. Buprenorphine-ß-D-glucuronide showed 76.9% cross-reactivity.
| Buprenorphine and its metabolites | Tested Concentration
(ng/mL) | Positive/
Negative | Cross-
reactivity
(%) |
|--------------------------------------------------------------|---------------------------------|-----------------------|-----------------------------|
| Buprenorphine | 10 | Positive | 100 |
| Norbuprenorphine | 8 | Positive | 125 |
| Buprenorphine-β-D-glucuronide | 13 | Positive | 76.9 |
| Norbuprenorphine-β-D-
glucuronide | 10 | Positive | 100 |
| Structurally Related Compounds and
Other Opiates | Tested Concentration
(ng/mL) | Positive/
Negative | Cross-
reactivity (%) |
| 6-Acetyl morphine | 100,000 | Negative |