A11.__Attachment_1_-_2017_SYCAN_PWS.pdf

SYNTHETIC CANNABINOIDS SCREENING REAGENT STATEMENT OF WORK

1. GENERAL REQUIREMENTS FOR AN IMMUNOASSAY TEST REAGENT FOR THE DETECTION OF

SYNTHETIC CANNABINOIDS AND CROSS-REACTIVE SYNTHETIC CANNABINOID METABOLITES IN

URINE

1.1. Overview. The materials shall be provided as a homogenous immunoassay reagent for use in the initial screening test for the detection of synthetic cannabinoid (SYCAN) metabolites excreted in the urine from a broad spectrum of (SYCAN) compounds found in the drug culture. The reagent shall be compatible with the Beckman Coulter AU5800 series clinical chemistry analyzer systems in use at the Department of Defense (DoD) Forensic Toxicology Drug Testing Laboratories (FTDTLs), and shall be compatible without modification of the instruments. The reagent shall be compatible with the optimal throughput of the analyzer systems and shall not interfere with the optimum performance of the other immunoassay procedures conducted on these instruments. The reagent shall not impose additional maintenance or servicing requirements for the optimum performance of the contractor’s reagent on the analyzer. When using the offeror’s recommended calibrator, the reagent must be capable for the Government’s use of a offeror’s calibrator at a cutoff concentration of 10 ng/mL. The reagent should demonstrate calibration stability, as evaluated by a low frequency of control failures, and should require approximately one initial calibration during an 8 hour period. The reagent shall maintain reproducibility in quality control (QC) and quality assurance (QA) measurements within batch and between batch assays (200 specimens and controls per batch) over the course of an 8 hour period.

1.2. Sensitivity and Specificity. The reagent shall be used for the detection of various SYCAN metabolites excreted in urine resulting from a broad spectrum of SYCAN compounds found in the drug culture.

The reagent must be a single homogeneous immunoassay reagent system that will be evaluated on the capable of detecting the urine metabolites of JWH-018, JWH-073, UR-144, MAM-2201, 5F-PB-22, AB-CHMINACA, AB- PINACA, and AB-FUBINACA.

Using the offeror’s recommended calibrator at the DoD cutoff concentration of 10 ng/mL, if the various cross reactive urine metabolites associated with individual SYCAN compounds in Section 1.1.1. exceed a cumulative concentration equal to or greater than 10ng/mL, a positive response should be anticipated.

The reagent shall have minimum cross-reactivity with drugs or drug metabolites currently on the DoD Drug Test Panel cited below. The following initial immunoassay screen cutoffs concentrations (ng/mL) are used for other compounds on the DoD drug test panel.

o 11-nor-delta-9-THC-carboxylic acid (THC) 50 ng/mL;

o Benzoylecgonine (BZE) 150 ng/mL;

o morphine (MOR) 300 ng/mL;

o codeine (COD) 300 ng/mL;

o 6-acetylmorphine (6AM) 10 ng/mL;

o hydrocodone (HYDC) 300 ng/mL;

o hydromorphone (HYDM) 300 ng/mL;

o oxycodone (OXYC) 100 ng/mL;

o oxymorphone (OXYM) 100 ng/mL;

o d-amphetamine (AMP) 500 ng/mL;

o d-methamphetamine (MET) 500 ng/mL;

o methylenedioxymethamphetamine (MDMA) 500 ng/mL;

o methylenedioxyamphetamine (MDA) 500 ng/mL;

o benzodiazepines (BZD) nordiazepam (NORD) 200 ng/mL;

oxazepam (OXAZ) 200 ng/mL;

alpha hydroxy-alprazolam (AHAL) 200 ng/mL;;

lorazepam (LORA) 200 ng/mL;;

temazepam (TEMA) 200 ng/mL;

1.2.1. Specificity. The testing reagent shall be evaluated for its ability to detect specimens contain SYCAN metabolites of whose parent SYCAN compound is of interest to the DoD Drug Demand Reduction Program (DDRP) of drug deterrence and detection. The SYCAN compounds whose metabolites are of greatest interest in the DDRP are grouped as Tier One or Tier Two SYCANs. The Tier One SYCANs contains SYCAN compounds whose urine metabolites are most frequently encountered in the drug testing program. The Tier Two SYCANs contains SYCAN compounds for which DoD has developed confirmatory liquid chromatography tandem mass spectrometry (LC/MS/MS) procedures to quantify a specific urine metabolite of the SYCAN compound.

Tier One SYCANs o JWH-018 o JWH-073

Tier Two SYCANs o XLR-11 o UR-144 o MAM-2201 o 5F-PB22 o AB-CHMINACA o AB-PINACA o AB-FUBINACA

1.2.1.1 Immunoassay Specificity and LC/MS/MS Confirmatory Analysis. A specimen deemed positive above the immunoassay screen 10 ng/mL cutoff concentration will be evaluated by LC/MS/MS quantitative analysis for the following specific SYCAN urinary metabolite. Specimens that confirm for the presence of the following specific metabolite(s) at or above a 1.0 ng/mL LC/MS/MS cutoff concentration will be considered positive for the presence of the SYCAN compound(s) by immunoassay and LC/MS/MS testing methodologies

Tier One SYCAN Metabolites:

o JWH-018-N-5-pentanoic acid metabolite o JWH-073-N-4-butanoic acid metabolite

Tier Two SYCAN Metabolites:

o UR-144-N-5-pentanoic acid metabolite o AB-CHIMINACA (metabolite 4) [1-(cyclohexylmethyl)-1H-indazole-3-carboxylic acid] o 5-fluoro-PB22-3-carboxyindole metabolite o MAM-2201 N-pentanoic acid metabolite o AB-PINACA-pentanoic acid [5-(3-((1-amino-3-methyl-a-oxobutan-2-yl)carbamoyl0-1H-indazol-1-yl)-pentanoic acid] o AB-FUBINACA (metabolite 2) [4-amino-3-(1-(4-fluorobenzyl0-1H-indazole-3-coboxamido)-2-methyl-4-oxobutanoic acid]

1.3. Compliance with Good Manufacturing Practices. In general, immunoassay kits are usually considered medical devices. As such, the manufacturer shall adhere to good manufacturing processes (GMP) in the manufacture of the immunoassay kits and its components, independent of Food and Drug Administration (FDA) market clearance status. Any health related issue, product performance, safety problem, or any other mandatory recall action related to the immunoassay kits provided under the resulting contract shall require notification to the Contracting Officer within two working days of awareness or notification of the event.

1.4. Packaging. The materials provided shall be packaged in volumes convenient for refrigerated storage and applicable to the sample throughput at the military laboratories, and shall not result in the loss or unnecessary disposal of more than 3% of the working volume of reagent. Any individual bottle of reagent which would be prepared for use at one time shall not include materials for more than 5,000 tests. The contractor will not be required to provide calibrators and control materials for the drug reagent. (The military laboratories will separately obtain or provide calibrators and control materials to be used with the reagent.) The materials shall be provided with an instruction sheet that includes all requirements for instrument operation parameters, reagent preparation and storage, and shall include data demonstrating specific reagent performance characteristics, such as accuracy, precision, sensitivity, specificity, cross-reactivity with various SYCAN metabolites, and applicable safety precautions.

1.5. Shelf Life. Minimum shelf life of any unopened component of the assay shall be at least 180 days from date of delivery to the drug testing laboratory. Once kit container seals are broken and the components are opened, the shelf-life shall be at least 14 days. Once diluted, the material shall have a shelf life of at least 24 hours.

2.0. TESTING AND QUALITY CONTROL PROTOCOL

2.1. Instrument Calibration. The following testing and quality control protocol shall be used for testing. The reagents supplied shall be adaptable to the calibration requirements and characteristics of the Beckman Coulter AU5800 series clinical chemistry analyzer system. Using the offeror’s recommended calibrator at the DoD 10 ng/mL cutoff concentration, verification of calibration shall be evaluated using: a drug free control, and the offerors recommended cutoff calibrator at target concentrations of 50%, 150%, and 200% of the 10 ng/mL DoD calibrator cutoff concentration. Open and blind quality control urine specimens shall be randomly distributed throughout a test batch of approximately 200 specimens.

3. PERFORMANCE TESTING FACTORS.

3.1. Sensitivity to Specific SYCAN Metabolites. Relative to the offeror’s calibrator at a 10 ng/mL concentration, the percent cross-reactivity of the individual SYCAN metabolite cited in section 1.2.1.1 will be evaluated at various concentrations. Higher cross-reactivity to the individual metabolites in section 1.2.1.1 at or above 100% is favored as well as the number of individual metabolites in section 1.2.1.1. with a cross-reactivity above 50% and 25% will be evaluated.

3.2. SYCAN Positive Specimens. When using the offeror’s recommended calibrator, the reagent will be evaluated for the ability to identify the presence of various metabolites of individual SYCAN compounds cited in section 1.1.1. when the cumulative concentration of a individual SYCAN compound is equal to or greater than the DoD 10 ng/mL cutoff concentration. Performance of the offeror’s reagent will be determined in analysis of archived specimens reported positive for the presence of SYCAN metabolites identified in Section 1.2.1.1 Differences between offerors’ screening performance will be evaluated by LC/MS/MS for the presence of SYCAN specific metabolites cited in section 1.2.1.1. at or above the LC/MS/MS cutoff concentration of 1.0 ng/mL.

3.3. SYCAN Negative Specimens. When using the offeror’s recommended calibrator, the reagent must be capable of identifying specimens as negative for the presence of various SYCAN metabolite(s) in physiological urine when present in human urine at concentration below the DoD 10 ng/mL cutoff concentration. Performance of the offeror’s reagent will be determined in a side by side comparison of the offeror’s reagent to the current immunoassay utilized in the military laboratories. Differences in performance will be evaluated by LC/MS/MS for the absence of SYCAN specific metabolites cited in section 1.2.1.1. below the LC/MS/MS cutoff concentration of 1.0 ng/mL.

3.4. False Positive Screen. When using the offeror’s calibrator, the reagent must minimize the number of "false positive" specimens that screen positive at or above the DoD 10 ng/mL cutoff concentration; but, fail to confirm by LC/MS/MS at or above the DoD 1.0 ng/mL cutoff concentration for any of the specific SYCAN metabolites cited in section 1.2.1.1.. The percent “false positive” is [1 – (the number of specimens confirmed positive for the presence of a section 1.2.1.1. metabolite divided by the number of specimens sent for confirmation analysis)] times 100.

3.4.1. False Negative Screen. When using the offeror’s calibrator, the reagent must minimize the number of "false negative" specimens that screen negative below the DoD 10 ng/mL cutoff concentration; but, upon LC/MS/MS analysis, any of the specific SYCAN metabolites cited in section 1.2.1.1. if detected at or above the DoD 1.0 ng/mL cutoff concentration. The percent “false negative” is [1- (number of specimens confirmed positive for the presence of a section 1.2.1.1 metabolite divided by the actual number of specimens positive for the presence of a section 1.2.1.1. metabolite)] times 100.

3.5. Confirmation Rates of Screen Positive Specimens. When using the offeror’s calibrator, the offeror’s reagent shall be evaluated in terms of confirmation rate relative to screen positive rate (the number of specimens confirmed positive for a specific SYCAN metabolite cited in section 1.2.1.1 by LC/MS/MS at 1.0 ng/mL divided by the number of specimens screened positive at 10 ng/mL x 100). A higher percent confirmation rate will be considered a better value than a lower percent confirmation rate.

3.6. Solicitation Minimum Requirements. The reagent must be capable of meeting the Minimum Requirements established in Evaluation Factor C: Performance Test – Minimum Requirements. Data obtained during the Performance Test will be analyzed to determine the reagent’s ability to meet the solicitation Minimum Requirements.

3.7. Enhancing Factors. If the reagent meets all Minimum Requirements in Evaluation Factor C, data obtained during the Performance Test will be analyzed to determine the reagent’s increased or decreased value based on its ability to meet the Evaluation Factors D: Performance Test – Enhancing Factors.

4. OFFEROR’S QUALITY ASSURANCE PROGRAM – OFFEROR’S SHALL POSSESS CURRENT ISO-9000

SERIES CERTIFICATION OR INCLUDE DOCUMENTATION OF THE FOLLOWING ELEMENTS:

4.1. Chemicals and Reagents

4.1.1. Quality and Authenticity. All materials used in the preparation of reagents shall be verified as to authenticity and purity. Methods may include, but are not limited to, the determination of melting points, LC/MS/MS, Nuclear Magnetic Resonance (NMR), and spectrophotometric measurements.

4.1.2. Stability. The kit and each kit component shall be shown to be stable and at the correct concentration over the period of use of the kit. Components that are homogeneous solutions shall not deteriorate throughout the period of use of the kit (from date of preparation to date of expiration).

4.2. Manufacturer’s Equipment.

4.2.1. Preventive Maintenance. Routine preventive maintenance procedures, periodic calibration, and any unscheduled maintenance shall be fully documented and in accordance with recommendations of the manufacturer of the equipment.

4.2.2. Calibration and Operational Checks. All instruments that are used to check a physical parameter of a solution or material shall be calibrated and have documentation available to demonstrate that all required operational checks have been completed. This includes pH meters, spectrometers, micropipettes, etc.

4.2.3. Temperature Checks. Water baths, refrigerators, freezers, and other equipment that is intended to maintain a given temperature shall be periodically validated for accuracy and routinely verified for correct settings.

4.2.4. Glassware and Other Reusable Laboratory Supplies. Appropriate procedures for cleaning and inspecting glassware and other reusable materials shall be established and compliance documented.

4.3. Antibody Drug Molecule(s).

4.3.1. Authenticity. The prepared antibody drug molecule(s) shall be verified to be authentic and its purity established.

4.3.2. Stability. The antibody drug shall be documented to be stable to the expiration date and the immunoassay shall meet all contract specifications to the end of expiration date (which is 180 days minimum).

4.4. Antibody Specificity. Antibody specificity shall be verified for each lot and the specificity re-evaluated at routine intervals to ensure uniformity and quality of preparations. The offeror shall provide performance characteristics in terms of sensitivity and specificity for detection of various SYCAN metabolites as may be applicable to the SYCANs listed is section

4.5. Immunoassays.

4.5.1. Technical Performance. Performance of each lot of kits shall be verified. The verification shall establish, as a minimum, the appropriate response to the target molecule and that all other parameters as specified in the contract are met.

4.5.2. Stability. The performance parameters involved in the testing procedures shall be verified and documented to be consistent throughout the shelf life of the kit.

4.5.3. Manufacturer's Production Manual. Procedures and criteria required to validate all components (and materials) employed during the manufacture of the reagents in the test kits and the operation of the completed kit over the entire period of shelf-life of the kit shall be described in detail. All steps of each quality control procedure shall be described thoroughly.

4.5.4. Records. The production and quality assurance records generated by each procedure performed above shall be maintained in a systematic fashion to permit the verification of completion of all production parameters and shall be available for inspection during the term of the contract.

4.5.5. Corrective Action(s). When a specified quality control parameter is found to be out of limits, the action(s) taken to ensure correction for existing kits (i.e., notification) shall be documented and action taken to ensure that the deficiency does not reoccur and all records shall be retained. The Contracting Officer shall be notified within 2 working days of any deficiencies in existing kits and of all corrective actions for consideration, i.e., delivery of replacement kits at no cost to the Government. As may be required, the FDA shall be notified according to its regulations.

4.5.6. Lot Numbers. Lot numbers shall be used to identify reagent and other preparations to allow tracking of all immunoassay components. The procedures used to assign unique lot numbers for each solution or reagent shall be described.

A single lot number for a kit shall suffice if all materials used in that lot number can be tracked to identify the materials and procedures used in the preparation of that kit.

(End of provision)