(227 days)
No
The description details a homogeneous enzyme immunoassay and its associated reagents and calibrators/controls. There is no mention of AI or ML in the intended use, device description, or performance studies. The analysis is based on standard chemical reactions and measurements.
No.
Explanation: This device is an in-vitro diagnostic assay used for qualitative analysis of buprenorphine in human urine. It is explicitly stated that this assay "provides only a preliminary analytical test result" and that "a more specific alternative chemical method(s) must be used to obtain a confirmed analytical result." It is intended for use in laboratories to detect the presence of a drug, not to treat a condition or provide therapy.
Yes
Explanation: The device is an immunoassay intended for the qualitative analysis of buprenorphine in human urine, which falls under the definition of a diagnostic test to identify the presence or absence of a substance indicative of a medical condition or drug use.
No
The device is an in-vitro diagnostic assay kit consisting of chemical reagents (Reagent 1 and Reagent 2) and calibrators/controls, which are physical components. While it is designed for use with chemistry analyzers (which involve software), the core device itself is a collection of chemical substances, not software.
Based on the provided text, here's an analysis to determine if the device is an IVD:
Evidence supporting it is an IVD:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states the assay is "intended for use in laboratories for the qualitative analyses of buprenorphine in human urine." This indicates it's used to test human specimens.
- Device Description: The "Device Description" section describes the assay as a "homogeneous enzyme immunoassay" and details its components (reagents, calibrators, controls). These are typical components of in vitro diagnostic tests.
- Calibrators and Controls: The description of the "Emit® II Plus Specialty Drug Calibrators / Controls" and "Emit® II Plus Specialty Drug Control Negative and Emit® II Plus Specialty Drug Control Positive" explicitly states they are "in-vitro diagnostic products."
- Testing of Human Specimens: The assay is designed to test "human urine."
- Laboratory Use: The intended user is "laboratories."
- Performance Studies: The document includes details about performance studies (Precision, Specificity, Interference, Recovery/Linearity, Method Comparison) conducted using human urine samples. This is standard for IVD submissions.
- Predicate Devices: The mention of "Predicate Device(s)" with K numbers (K040316) and names of other assays and calibrators/controls strongly suggests this device is being compared to previously cleared IVDs.
Evidence not supporting or neutral:
- The text doesn't explicitly state "This device is an In Vitro Diagnostic." However, the cumulative evidence points strongly in that direction.
Conclusion:
Yes, based on the provided information, this device is an IVD (In Vitro Diagnostic). The intended use, device description, explicit labeling of calibrators and controls as IVD products, testing of human specimens in a laboratory setting, and the inclusion of performance studies and predicate devices all align with the characteristics of an IVD.
N/A
Intended Use / Indications for Use
Emit® II Plus Buprenorphine Assay
Emit® II Plus Buprenorphine Assay is a homogeneous enzyme immunoassay with a 5 ng/mL cutoff. The assay is intended for use in laboratories for the qualitative analyses of buprenorphine in human urine. Emit® II Plus assays are designed for use with a number of 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 LC/MS or Permitting laboratories to establish quality control procedures.
The Emit® II Plus Buprenorphine Assay provides only a preliminary analytical test result. A more specific alternative chemical method(s) must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/ MS) or LC/MS are the preferred confirmatory methods. 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.
Emit® II Plus Specialty Drug Calibrator/Control Level 1, Emit® II Plus Specialty Drug Calibrator/Control Level 2, Emit® II Plus Specialty Drug Calibrator/Control Level 3, Emit® II Plus Specialty Drug Calibrator/Control Level 4
The Emit® II Plus Specialty Drug Calibrators/Controls are used in the calibration of the Emit® II Plus Buprenorphine Assay. These products may also be used as quality control materials based on the Buprenorphine Assay cutoff.
Emit® II Plus Specialty Drug Control Negative and Emit® II Plus Specialty Drug Control Positive
The Emit® II Plus Specialty Drug Control Negative and Control Positive are for use with the Emit® II Plus Buprenorphine Assay.
Product codes (comma separated list FDA assigned to the subject device)
DJG, DLJ, LAS
Device Description
Assav
The Emit® II Plus Buprenorphine assay is a homogeneous enzyme immunoassay with a 5 ng/mL cutoff. The assay, used for the detection of Buprenorphine in human urine, utilizes a two-reagent system. The Antibody/Substrate Reagent 1 is a liquid ready-to-use product comprised of mouse monoclonal antibodies to buprenorphine, glucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in a diluent containing bovine serum albumin (BSA), preservatives and stabilizers. The Enzyme Reagent 2 is a liguid. ready-to-use product containing norbuprenorphine labeled bacterial recombinant glucose-6 phosphate dehydrogenase (rG6PDH) in a diluent containing bovine serum albumin (BSA), Hepes buffer, preservatives and stabilizers.
The assay kit consists of Reagent 1 and Reagent 2 in plastic containers and is available in three sizes: large kit (1L), small kit (115 mL), and 28 mL Emit® II Plus assays are designed for use with a number of chemistry analyzers.
The Emit® II Plus Buprenorphine assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result.
Calibrators / Controls
Emit® II Plus Specialty Drug Calibrators / Controls are in-vitro diagnostic products used in the calibration of the Emit® II Plus Buprenorphine assay. These products may also be used as quality control materials based on the Buprenorphine Assay cutoff. The matrix is pooled, drug-free, human urine based product containing buprenorphine, preservatives and surfactants. Each level of calibrator is packaged and sold separately, 1 plastic bottle per box, 10 mL in a 15 mL bottle. Values are nominal and are verified with urine based buprenorphine anchor pool and adjusted if needed. The anchor pool levels are verified by LC/MS/MS and are within 10% of nominal drug concentration for levels 2.5 and 5.0 ng/mL and within 5 % of nominal concentrations for levels 15 and 25 ng/mL.
Emit® II Plus Specialty Drug Calibrator/Control levels are as follows:
| Specialty Drug Calibrator/Control | Targeted Buprenorphine Concentration
(ng/mL |
|-------------------|------------------------------------------------|
| Level 1 | 2.5 |
| Level 2 | 5 |
| Level 3 | 15 |
| Level 4 | 25 |
The Emit® Calibrator/Control Level 0, which contains no drug and was cleared under K993755 is used with the Emit® II Plus Buprenorphine Assay. There are no changes to the Calibrator Level 0 product. Controls
Emit® II Plus Specialty Drug Control Negative and Emit® II Plus Specialty Drug Control Positive are in-vitro diagnostic products are for use with the Emit® II Plus Buprenorphine assay. The matrix is pooled, drug-free, human urine based product containing buprenorphine, preservatives and surfactants. The Control Negative and Control Positive are packaged separately in 15 mL plastic vials with a 10 mL fill per vial. Values are nominal and are verified with urine based buprenorphine anchor pool and adjusted if needed. Anchor pool levels are verified by LC/MS/MS.
Emit® II Plus Specialty Drug Control Negative and Control Positive levels are as follows:
| Specialty Drug Control | Targeted Buprenorphine Concentration
(ng/mL) |
|------------------------|-------------------------------------------------|
| Negative | 3 |
| Positive | 7 |
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
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)
Performance of the Emit® II Plus Buprenorphine Assay was evaluated at Siemens Healthcare Diagnostics Inc. on a Viva-E® Analyzer.
A. Precision / Cutoff Characterization
Studies were conducted using urine pools prepared by spiking Buprenorphine into drug-free human urine at 8 concentrations (levels). The concentrations tested represent the following levels relative to the 5 ng/mL cutoff: 100, -50%, -40%, and -25% below the cutoff, at the cutoff, and +25%, +40%, +50%, and +100% of the cutoff. The drug-free human urine pool was also tested as the 0 ng/mL buprenorphine level. The studies were performed on Viva-E® analyzer. For each level, samples were analyzed in duplicate twice a day, for 20 days (N=80).
Precision: Qualitative Analysis and Semiqualitative Analysis:
- 0 ng/mL (-100% Cutoff): 80 Negative for both Repeatability and Within-Laboratory Results
- 2.5 ng/mL (-50% Cutoff): 80 Negative for both Repeatability and Within-Laboratory Results
- 3 ng/mL (-40% Cutoff): 80 Negative for both Repeatability and Within-Laboratory Results
- 3.75 ng/mL (-25% Cutoff): 80 Negative for both Repeatability and Within-Laboratory Results
- 5 ng/mL (Cutoff): 25 Negative / 55 Positive for both Repeatability and Within-Laboratory Results
- 6.25 ng/mL (+25% Cutoff): 80 Positive for both Repeatability and Within-Laboratory Results
- 7 ng/mL (+40% Cutoff): 80 Positive for both Repeatability and Within-Laboratory Results
- 7.5 ng/mL (+50% Cutoff): 80 Positive for both Repeatability and Within-Laboratory Results
- 10 ng/mL (+100% Cutoff): 80 Positive for both Repeatability and Within-Laboratory Results
An additional precision study was performed using urine pools prepared by spiking Buprenorphine into drug-free human urine at one concentration level relative to the 5 ng/mL cutoff: -75% below the cutoff and +75% above the cutoff. The studies were performed on Viva-E® analyzer. The samples were analyzed in duplicate, 40 times for a total of 80 replicates over one day.
Precision: Qualitative Analysis and Semiqualitative Analysis:
- 1.25 ng/mL (-75% Cutoff): 80 Negative for both Repeatability and Within-Laboratory Results
- 8.75 ng/mL (+75% Cutoff): 80 Positive for both Repeatability and Within-Laboratory Results
B. Specificity and Cross-reactivity
Buprenorphine Metabolite Recovery:
- Buprenorphine (5 ng/mL tested): 5.2 ng/mL Recovery, 103.2% Cross-reactivity
- Norbuprenorphine (5 ng/mL tested): 4.6 ng/mL Recovery, 92.6% Cross-reactivity
- Buprenorphine Glucuronide (1000 ng/mL tested): 0.9 ng/mL Recovery, 0.1% Cross-reactivity
- Norbuprenorphine Glucuronide (1000 ng/mL tested): 1.2 ng/mL Recovery, 0.1% Cross-reactivity
Cross-reactivity with the Structurally Related Compound: Samples were prepared by spiking drug-free human urine with individual cross-reactants. For all tested compounds (e.g., 6-acetylcodeine, 6-acetylmorphine, Codeine, Dextromethorphan, Dihydrocodeine, Heroin, Hydrocodone, Morphine, etc.) at 100000 ng/mL, both Qualitative and Semiqualitative Results were Negative, with %Cross-reactivity 7.5 ng/mL): 0 Emit® Negative, 49 Emit® Positive. % Agreement: 90%
- Combined Comparison Table (Emit® II Plus Buprenorphine vs. LC/MS/MS):
- Emit® Positive: 65 (LC/MS/MS +), 7 (LC/MS/MS -)
- Emit® Negative: 1 (LC/MS/MS +), 54 (LC/MS/MS -)
Discordant Result Summary:
- Sample ID 190: Emit® II Plus (5.6 ng/mL), LC/MS/MS (Bup 0, NorBup 3.92, Total 3.92), Emit® +, LC/MS/MS -
- Sample ID 193: Emit® II Plus (6.1 ng/mL), LC/MS/MS (Bup 0, NorBup 4.97, Total 4.97), Emit® +, LC/MS/MS -
- Sample ID 195: Emit® II Plus (5.4 ng/mL), LC/MS/MS (Bup 0, NorBup 4.06, Total 4.06), Emit® +, LC/MS/MS -
- Sample ID 226: Emit® II Plus (5.8 ng/mL), LC/MS/MS (Bup 0, NorBup 4.21, Total 4.21), Emit® +, LC/MS/MS -
- Sample ID 250: Emit® II Plus (5.1 ng/mL), LC/MS/MS (Bup 0, NorBup 4.13, Total 4.13), Emit® +, LC/MS/MS -
- Sample ID 77: Emit® II Plus (5.5 ng/mL), LC/MS/MS (Bup 0, NorBup 4.60, Total 4.60), Emit® +, LC/MS/MS -
- Sample ID 316: Emit® II Plus (5.7 ng/mL), LC/MS/MS (Bup 0, NorBup 3.86, Total 3.86), Emit® +, LC/MS/MS -
- Sample ID 338: Emit® II Plus (4.3 ng/mL), LC/MS/MS (Bup 5.12, NorBup 0, Total 5.12), Emit® -, LC/MS/MS +
F. Calibrator/Control and Cutoff Control Traceability
The Emit® II Plus Specialty Drug Calibrator/Control and Emit® II Plus Specialty Drug Control Neqative and Control Positive are traceable to Cerilliant Buprenorphine Cat. No. B-902. When stored refrigerated at 2-8°C the calibrators/controls are stable opened or unopened until the expiration date printed on the vial label.
Conclusion: The device is substantially equivalent to legally marketed predicate devices.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Qualitative Agreement with LC/MS/MS:
- Emit® Positive: 65 true positives, 7 false positives
- Emit® Negative: 1 false negative, 54 true negatives
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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 is a seal for the Department of Health & Human Services - USA. The seal is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. In the center of the seal is a stylized image of three human profiles facing to the right. The profiles are stacked on top of each other, creating a sense of depth and unity.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
October 23, 2015
SIEMENS HEALTHCARE DIAGNOSTICS, INC. FRANCES DILLON SR. MANAGER, REGULATORY AFFAIRS P.O. BOX 6101, M/S 514 NEWARK DE 19714-6101
Re: K150606
Trade/Device Name: Emit II Plus Buprenorphine Assay,
Emit II Plus Specialty Drug Calibrator/Control Level 1, Emit II Plus Specialty Drug Calibrator/Control Level 2, Emit II Plus Specialty Drug Calibrator/Control Level 3, Emit II Plus Specialty Drug Calibrator/Control Level 4. Emit II Plus Specialty Drug Control Negative, Emit II Plus Specialty Drug Control Positive
Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: II Product Code: DJG, DLJ, LAS Dated: September 4, 2015 Received: September 8, 2015
Dear Ms. Dillon:
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
1
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 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
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known) K150606
Device Name
Emit® II Plus Buprenorphine Assay, Emit® II Plus Specialty Drug Calibrator/Control Level 1, Emit® II Plus Specialty Drug Calibrator/Control Level 2, Emit® II Plus Specialty Drug Calibrator/Control Level 3, Emit® II Plus Specialty Drug Calibrator/Control Level 4, Emit® II Plus Specialty Drug Control Negative, Emit® II Plus Specialty Drug Control Positive,
Indications for Use (Describe) Emit® II Plus Buprenorphine Assay
Emit® II Plus Buprenorphine Assay is a homogeneous enzyme immunoassay with a 5 ng/mL cutoff. The assay is intended for use in laboratories for the qualitative analyses of buprenorphine in human urine. Emit® II Plus assays are designed for use with a number of 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 LC/MS or Permitting laboratories to establish quality control procedures.
The Emit® II Plus Buprenorphine Assay provides only a preliminary analytical test result. A more specific alternative chemical method(s) must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/ MS) or LC/MS are the preferred confirmatory methods. 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.
Emit® II Plus Specialty Drug Calibrator/Control Level 1, Emit® II Plus Specialty Drug Calibrator/Control Level 2, Emit® II Plus Specialty Drug Calibrator/Control Level 3, Emit® II Plus Specialty Drug Calibrator/Control Level 4
The Emit® II Plus Specialty Drug Calibrators/Controls are used in the calibration of the Emit® II Plus Buprenorphine Assay. These products may also be used as quality control materials based on the Buprenorphine Assay cutoff.
Emit® II Plus Specialty Drug Control Negative and Emit® II Plus Specialty Drug Control Positive
The Emit® II Plus Specialty Drug Control Negative and Control Positive are for use with the Emit® II Plus Buprenorphine Assay.
Type of Use (Select one or both, as applicable)
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
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K150606
1. Submitter
Siemens Healthcare Diagnostics Inc. P.O. Box 6101 Newark, DE 19714
Tel: 302-631-6951 FAX: 3023-631-6299
Contact Person: Frances Dillon Date of Preparation: October 20, 2015
2. Device Information
| Trade Name: | Emit® II Plus Buprenorphine Assay |
|---|---|
| Common Name: | Buprenorphine Assay |
| Classification Name: | Opiates test system - 21CFR 862.3650 |
| Regulatory Class: | II |
| Product Code: | DJG - Enzyme Immunoassay, Opiates |
| Panel: | Clinical Toxicology (91) |
| Trade Name: | Emit® II Plus Specialty Drug Calibrator/Control Level 1 |
| Emit® II Plus Specialty Drug Calibrator/Control Level 2 | |
| Emit® II Plus Specialty Drug Calibrator/Control Level 3 | |
| Emit® II Plus Specialty Drug Calibrator/Control Level 4 | |
| Common Name: | Buprenorphine Calibrator/Control |
| Classification Name: | Clinical Toxicology Calibrator - 21CFR 862.3200 |
| Clinical Toxicology Control Material - 21CFR 862.3280 | |
| Regulatory Class: | II (Calibrator) |
| I (Control) | |
| Product Code: | DLJ - Calibrators, Drug Specific |
| LAS - Drug Specific Control Materials | |
| Panel: | Clinical Toxicology (91) |
| Trade Name: | Emit® II Plus Specialty Drug Control Negative |
| Emit® II Plus Specialty Drug Control Positive | |
| Common Name: | Buprenorphine Negative Control and Buprenorphine |
| Positive Control | |
| Classification Name: | Clinical Toxicology Control material - 21CFR 862.3280 |
| Regulatory Class: | I |
| Product Code: | LAS - Drug Specific Control Materials |
| Panel: | Clinical Toxicology (91) |
4
3. Predicate Device
| Assay: | Microgenics CEDIA® Buprenorphine Assay, K040316. |
|---|---|
| Calibrator: | Microgenics CEDIA® Buprenorphine Calibrators, K040316. |
| Control: | Microgenics CEDIA® Buprenorphine Controls, K040316. |
4. Device Description
Assav
The Emit® II Plus Buprenorphine assay is a homogeneous enzyme immunoassay with a 5 ng/mL cutoff. The assay, used for the detection of Buprenorphine in human urine, utilizes a two-reagent system. The Antibody/Substrate Reagent 1 is a liquid ready-to-use product comprised of mouse monoclonal antibodies to buprenorphine, glucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in a diluent containing bovine serum albumin (BSA), preservatives and stabilizers. The Enzyme Reagent 2 is a liguid. ready-to-use product containing norbuprenorphine labeled bacterial recombinant glucose-6 phosphate dehydrogenase (rG6PDH) in a diluent containing bovine serum albumin (BSA), Hepes buffer, preservatives and stabilizers.
The assay kit consists of Reagent 1 and Reagent 2 in plastic containers and is available in three sizes: large kit (1L), small kit (115 mL), and 28 mL Emit® II Plus assays are designed for use with a number of chemistry analyzers.
The Emit® II Plus Buprenorphine assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result.
Calibrators / Controls
Emit® II Plus Specialty Drug Calibrators / Controls are in-vitro diagnostic products used in the calibration of the Emit® II Plus Buprenorphine assay. These products may also be used as quality control materials based on the Buprenorphine Assay cutoff. The matrix is pooled, drug-free, human urine based product containing buprenorphine, preservatives and surfactants. Each level of calibrator is packaged and sold separately, 1 plastic bottle per box, 10 mL in a 15 mL bottle. Values are nominal and are verified with urine based buprenorphine anchor pool and adjusted if needed. The anchor pool levels are verified by LC/MS/MS and are within 10% of nominal drug concentration for levels 2.5 and 5.0 ng/mL and within 5 % of nominal concentrations for levels 15 and 25 ng/mL.
Emit® II Plus Specialty Drug Calibrator/Control levels are as follows:
| Specialty Drug Calibrator/Control | Targeted Buprenorphine Concentration
(ng/mL |
|-----------------------------------|------------------------------------------------|
| Level 1 | 2.5 |
| Level 2 | 5 |
| Level 3 | 15 |
| Level 4 | 25 |
5
The Emit® Calibrator/Control Level 0, which contains no drug and was cleared under K993755 is used with the Emit® II Plus Buprenorphine Assay. There are no changes to the Calibrator Level 0 product. Controls
Emit® II Plus Specialty Drug Control Negative and Emit® II Plus Specialty Drug Control Positive are in-vitro diagnostic products are for use with the Emit® II Plus Buprenorphine assay. The matrix is pooled, drug-free, human urine based product containing buprenorphine, preservatives and surfactants. The Control Negative and Control Positive are packaged separately in 15 mL plastic vials with a 10 mL fill per vial. Values are nominal and are verified with urine based buprenorphine anchor pool and adjusted if needed. Anchor pool levels are verified by LC/MS/MS.
Emit® II Plus Specialty Drug Control Negative and Control Positive levels are as follows:
| Specialty Drug Control | Targeted Buprenorphine Concentration
(ng/mL) |
|------------------------|-------------------------------------------------|
| Negative | 3 |
| Positive | 7 |
5. Indications for Use
Emit® II Plus Buprenorphine Assay
Emit® II Plus Buprenorphine Assay is a homogeneous enzyme immunoassay with a 5 nq/mL cutoff. The assay is intended for use in laboratories for the qualitative and/or semiquantitative analyses of buprenorphine in human urine. Emit® II Plus assays are designed for use with a number of 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 LC/MS or permitting laboratories to establish quality control procedures.
The Emit® II Plus Buprenorphine Assay provides only a preliminary analytical test result. A more specific alternative chemical method(s) must be used to obtain a confirmed analytical result. GC/MS and LC/MS are the preferred confirmatory methods. 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.
Emit® II Plus Specialty Drug Calibrator / Control Level 1, Level 2, Level 3, and Level 4
The Emit® II Plus Specialty Drug Calibrators/Controls are used in the calibration of the Emit® II Plus Buprenorphine Assay. These products may also be used as quality control materials based on the Buprenorphine Assay cutoff.
Emit® II Plus Specialty Drug Control Negative and Emit® II Plus Specialty Drug Control Positive
6
The Emit® II Plus Specialty Drug Control Negative and Control Positive are for use with the Emit® Il Plus Buprenorphine Assay.
| Attributes | Predicate Device
CEDIA® Buprenorphine Assay
(K040316) | Proposed Device
Emit® II Plus
Buprenorphine Assay |
|--------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------|
| Similarities | | |
| Intended Use | A homogeneous enzyme
immunoassay for qualitative or
semi-quantitative determination of
the presence of buprenorphine in
human urine at a cutoff
concentration of 5 ng/mL.
Preliminary analytical test result. | Same |
| Analyte | Buprenorphine | Same |
| Antibody | Mouse monoclonal antibody to
buprenorphine | Same |
| Test System | Homogeneous enzyme
immunoassay | Same |
| Detection | Absorbance change measured
spectrophotometrically | Same |
| Sample type | Human urine | Same |
| Cutoff Level | 5 ng/mL | Same |
| Instrument | Automated clinical analyzers
capable of maintaining a constant
temperature, pipetting, mixing
reagents, measuring enzymatic
rates, and timing the reaction. | Same |
| Calibrator levels | 0 ng/mL + four (4) levels | Same |
| Control Levels | High Control 7 ng/mL
Low Control 3 ng/mL | Same |
| Differences | | |
| Assay
methodology | Uses CEDIA® technology | Uses EMIT® technology |
| Detection | Absorbance change measured
spectrophotometrically at 660 nm. | Absorbance change
measured
spectrophotometrically at
340 nm. |
| Reference
Methodology | GC/MS | LC/MS |
| Reagents Form | R1 and R2: Lyophilized
(Reconstitution Required) | R1: Liquid - Ready to use
R2: Liquid - Ready to use |
| Calibrator levels | 0, 5, 20, 50, and 75 ng/mL | 0, 2.5, 5, 15, and 25 ng/mL |
6. Comparison of Technological Characteristics with the Predicate Device
7
Comparison of Calibrator/Control Similarities and Differences
| Attributes | Predicate Device
CEDIA® Buprenorphine
Calibrator (K040316) | Proposed Device
Emit® II Plus Specialty
Drug Calibrator / Control |
|-----------------------------------------------|-----------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------|
| Similarities | | |
| Intended Use | The CEDIA® Buprenorphine
calibrators are used to
calibrate the CEDIA®
Buprenorphine Assay in
human urine. | Same |
| Matrix | Human urine | Same |
| Analyte | Buprenorphine | Same |
| Preparation | Liquid - Ready to use | Same |
| Storage | 2 – 8 °C | Same |
| Differences | | |
| Target
Concentrations for
Buprenorphine | 0, 5, 20, 50, and 75 ng/mL | 2.5, 5, 15, and 25 ng/mL
(0 ng/mL calibrator is Emit®
Calibrator/Control Level 0) |
Comparison of Control Similarities
| Attributes | Predicate Device
CEDIA® Buprenorphine
Negative Control and
Positive Control (K040316) | Proposed Device
Emit® II Plus Specialty
Drug Control Negative
and Control Positive |
|-----------------------------------------------|---------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------|
| Similarities | | |
| Intended Use | The CEDIA® Buprenorphine
controls are used to qualify
the CEDIA® Buprenorphine
Assay in human urine. | Same |
| Matrix | Human urine | Same |
| Analyte | Buprenorphine | Same |
| Target
Concentrations for
Buprenorphine | High Control 7 ng/mL
Low Control 3 ng/mL | Same |
| Preparation | Liquid, ready to use | Same |
| Storage | 2 – 8ºC | Same |
7. Performance Data
Performance of the Emit® II Plus Buprenorphine Assay was evaluated at Siemens Healthcare Diagnostics Inc. on a Viva-E® Analyzer.
a. Precision / Cutoff Characterization
Studies were conducted using urine pools prepared by spiking Buprenorphine into drug-free human urine at 8 concentrations (levels). The concentrations tested represent the following levels relative to the 5 ng/mL cutoff: 100, -50%,
8
-40%, and -25% below the cutoff, at the cutoff, and +25%, +40%, +50%, and +100% of the cutoff. The drug-free human urine pool was also tested as the 0 ng/mL buprenorphine level. The studies were performed on Viva-E® analyzer. For each level, samples were analyzed in duplicate twice a day, for 20 days (N=80).
| Urine Pool
(ng/mL) | % of
Cutoff | # of
Results | Repeatability
Results | Within-
Laboratory
Results |
|-----------------------|----------------|-----------------|-----------------------------|----------------------------------|
| O | -100% | 80 | 80 Negative | 80 Negative |
| 2.5 | -50% | 80 | 80 Negative | 80 Negative |
| 3 | -40% | 80 | 80 Negative | 80 Negative |
| 3.75 | -25% | 80 | 80 Negative | 80 Negative |
| 5 | cutoff | 80 | 25 Negative/
55 Positive | 25 Negative/
55 Positive |
| 6.25 | +25% | 80 | 80 Positive | 80 Positive |
| 7 | +40% | 80 | 80 Positive | 80 Positive |
| 7.5 | +50% | 80 | 80 Positive | 80 Positive |
| 10 | +100% | 80 | 80 Positive | 80 Positive |
Precision: Qualitative Analysis
Precision: Semi-quantitative Analysis
| Urine Pool
(ng/mL) | % of
Cutoff | # of
Results | Repeatabilitv
Results | Within-
Laboratory
Results |
|-----------------------|----------------|-----------------|-----------------------------|----------------------------------|
| 0 | -100% | 80 | 80 Negative | 80 Negative |
| 2.5 | -50% | 80 | 80 Negative | 80 Negative |
| 3 | -40% | 80 | 80 Negative | 80 Negative |
| 3.75 | -25% | 80 | 80 Negative | 80 Negative |
| 5 | cutoff | 80 | 25 Negative/
55 Positive | 25 Negative/
55 Positive |
| 6.25 | +25% | 80 | 80 Positive | 80 Positive |
| 7 | +40% | 80 | 80 Positive | 80 Positive |
| 7.5 | +50% | 80 | 80 Positive | 80 Positive |
| 10 | +100% | 80 | 80 Positive | 80 Positive |
An additional precision study was performed using urine pools prepared by spiking Buprenorphine into drug-free human urine at one concentration level
9
relative to the 5 ng/mL cutoff: -75% below the cutoff and +75% above the cutoff. The studies were performed on Viva-E® analyzer. The samples were analyzed in duplicate, 40 times for a total of 80 replicates over one day.
| Urine Pool
(ng/mL) | % of
Cutoff | # of
Results | Repeatability
Results | Within-
Laboratory
Results |
|-----------------------|----------------|-----------------|--------------------------|----------------------------------|
| 1.25 | -75% | 80 | 80 Negative | 80 Negative |
| 8.75 | +75% | 80 | 80 Positive | 80 Positive |
Precision: Qualitative Analysis
Precision: Semi-Quantitative Analysis
| Urine Pool
(ng/mL) | % of
Cutoff | # of
Results | Repeatability
Results | Within-
Laboratory
Results |
|-----------------------|----------------|-----------------|--------------------------|----------------------------------|
| 1.25 | -75% | 80 | 80 Negative | 80 Negative |
| 8.75 | +75% | 80 | 80 Positive | 80 Positive |
b. Specificity and Cross-reactivity
Buprenorphine Metabolite Recovery - Buprenorphine and the buprenorphine metabolites norbuprenorphine, buprenorphine glucuronide and norbuprenorphine glucuronide were spiked into aliquots of drug free urine at the levels shown and run at n=5 replicates. The samples were assayed and the mean recovery results were determined.
Buprenorphine and Buprenorphine Metabolite Recovery
| Compound | Concentration
Tested
(ng/mL) | Semi-quantitative
Results | |
|---------------------------------|------------------------------------|------------------------------|------------------------|
| | | Recovery
(ng/mL) | % Cross-
reactivity |
| Buprenorphine | 5 | 5.2 | 103.2 |
| Norbuprenorphine | 5 | 4.6 | 92.6 |
| Buprenorphine
Glucuronide | 1000 | 0.9 | 0.1 |
| Norbuprenorphine
Glucuronide | 1000 | 1.2 | 0.1 |
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Structurally Related Compounds - Samples were prepared by spiking drug-free human urine with individual cross-reactants to the targeted level. The samples were evaluated on the Viva-E® analyzer. All samples were tested in replicates of n=5.
For qualitative analysis, cross-reactivity is reported as the level of crossreactant that produces a rate response ≥ the cutoff. For semi-quantitative analysis the percent cross-reactivity was calculated.
| Qualitative Results | Semi-quantitative Results | |||
|---|---|---|---|---|
| Compound | Conc. Tested (ng/mL) | Qualitative Result | Semi-Quantitative Result | %Cross-reactivity |
| 6-acetylcodeine | 100000 | Negative | Negative | 7.5 ng/mL) |
| Qualitative | ||||
| Emit® Positive | 0 | 7 | 16 | 49 |
| Emit® Negative | 45 | 9 | 1 | 0 |
| Semi-quantitative | ||||
| Emit® Positive | 0 | 7 | 16 | 49 |
| Emit® Negative | 45 | 9 | 1 | 0 |
Emit® II Plus Buprenorphine Assay vs. LC/MS/MS
Comparison Table for Qualitative and Semi-quantitative Assay Performance
| LC/MS/MS | |||
|---|---|---|---|
| + | - | ||
| Emit® II Plus | |||
| Buprenorphine | + | 65 | 7 |
| - | 1 | 54 |
Discordant Result Summary
| Sample
ID | Emit® II Plus
Buprenorphine
(ng/mL) | LC/MS/MS | | | Emit
+/- | LC/MS/
MS
+/- |
|--------------|-------------------------------------------|----------------|-------------------|-----------------------|-------------|---------------------|
| | | Bup
(ng/mL) | NorBup
(ng/mL) | Bup+NorBup
(ng/mL) | | |
| 190 | 5.6 | 0 | 3.92 | 3.92 | + | - |
| 193 | 6.1 | 0 | 4.97 | 4.97 | + | - |
| 195 | 5.4 | 0 | 4.06 | 4.06 | + | - |
| 226 | 5.8 | 0 | 4.21 | 4.21 | + | - |
| 250 | 5.1 | 0 | 4.13 | 4.13 | + | - |
| 77 | 5.5 | 0 | 4.60 | 4.60 | + | - |
| 316 | 5.7 | 0 | 3.86 | 3.86 | + | - |
| 338 | 4.3 | 5.12 | 0 | 5.12 | - | + |
Bup = Buprenorphine; NorBup = Norbuprenorphine
16
Calibrator/Control and Cutoff Control Traceability f.
The Emit® II Plus Specialty Drug Calibrator/Control and Emit® II Plus Specialty Drug Control Neqative and Control Positive are traceable to Cerilliant Buprenorphine Cat. No. B-902. When stored refrigerated at 2-8°C the calibrators/controls are stable opened or unopened until the expiration date printed on the vial label.
8. Conclusion
The information provided in this premarket notification demonstrates the Emit® II Plus Buprenorphine Assay, Emit® II Plus Specialty Drug Calibrator / Control, Emit® II Plus Specialty Drug Control Negative and Control Positive are substantially equivalent to the legally marketed predicate devices for their general intended use. Substantial equivalence was demonstrated through comparison of intended use and technological features to the commercially available predicate devices and confirmed by liquid chromatography/ tandem mass spectrometry (LC/MS/MS), a reference analytical method. The information in this pre-market notification provides reasonable assurance that the Emit® II Plus Buprenorphine Assay. Emit® II Plus Specialty Drug Calibrator / Control, Emit® II Plus Specialty Drug Control Negative and Control Positive demonstrate safety and effectiveness similar to the predicate devices - Microgenics CEDIA® Buprenorphine Assay, CEDIA® Buprenorphine Calibrators, and CEDIA® Buprenorphine Controls (cleared under K040316).