Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay
Device Facts
| Record ID | K181135 |
|---|---|
| Device Name | Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay |
| Applicant | Immunalysis Corporation |
| Product Code | LCM · TX |
| Decision Date | Jan 24, 2019 |
| Decision | SESE |
| Submission Type | Traditional |
| Device Class | Class U |
Indications for Use
The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 10 ng/mL in neat oral fluid collected with the Quantisal II Oral Fluid Collection Device. The assay is intended for the qualitative and semi-quantitative analysis of PCP in human oral fluid with clinical analyzers. This assay is calibrated against PCP. This in vitro diagnostic device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/Mass Spectrometry (GC-MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical must be used in order 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 consideration and professional judgment should be applied to any test result, particularly when preliminary positive results are used.
Device Story
Device is an in vitro diagnostic homogeneous enzyme immunoassay for PCP detection in human oral fluid. Input: oral fluid collected using Quantisal II dual-pad system; sample split into two vials for screening and confirmation. Operation: assay performed on clinical chemistry analyzers (e.g., Beckman Coulter AU480); utilizes PCP-specific antibodies to detect drug presence via competitive binding. Output: qualitative (positive/negative) or semi-quantitative (concentration estimate) results. Used in clinical laboratories by technicians/scientists. Output informs clinical decision-making by identifying potential PCP presence, necessitating confirmatory testing via GC-MS or LC-MS/MS. Benefits: enables rapid screening of oral fluid samples for drug abuse monitoring.
Clinical Evidence
Bench testing only. Precision study (N=60 per concentration) over 15 days confirmed repeatability at cutoff ±25-100%. Method comparison study (N=80 clinical samples) against LC-MS/MS showed 100% agreement in both qualitative and semi-quantitative modes. Interference studies confirmed no impact from endogenous compounds, exogenous substances, or pH (3.0-11.0). Stability studies confirmed sample integrity in Quantisal II devices for 10 days at 30°C and 2 months at 2-8°C.
Technological Characteristics
Homogeneous enzyme immunoassay; utilizes PCP-specific antibodies and drug conjugate reagents. Form factor: liquid reagents for use on automated clinical chemistry analyzers. Sample collection: Quantisal II dual-pad collector with preservative buffer. Calibration: 14-day stability. Connectivity: compatible with standard clinical laboratory analyzers (e.g., Beckman Coulter AU480).
Indications for Use
Indicated for the qualitative and semi-quantitative detection of Phencyclidine (PCP) in human oral fluid collected via the Quantisal II Oral Fluid Collection Device. For prescription use only in clinical laboratory settings.
Predicate Devices
- RapidFRET Oral Fluid Assay for PCP, PCP Calibrator Set, PCP Control Set and RapidEase Oral Fluid Collector (K122703)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k181135
B. Purpose for Submission:
New device
C. Measurand:
Phencyclidine (PCP)
D. Type of Test:
Qualitative, lateral flow immunochromatographic
E. Applicant:
Immunalysis Corporation
F. Proprietary and Established Names:
Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay
G. Regulatory Information:
| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| LCM, Enzyme immunoassay, Phencyclidine | Class II | Unclassified | Toxicology (91) |
H. Intended Use:
1. Intended use(s):
Refer to Indications for Use.
2. Indication(s) for use:
The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of $10\mathrm{ng/mL}$ in neat oral fluid collected with the
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Quantisal II Oral Fluid Collection Device. The assay is intended for the qualitative and semi-quantitative analysis of PCP in human oral fluid with clinical analyzers. This assay is calibrated against PCP. This in vitro diagnostic device is for prescription use only.
The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/Mass Spectrometry (GC-MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.
The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order 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 consideration and professional judgment should be applied to any test result, particularly when preliminary positive results are used.
3. Special conditions for use statement(s):
For prescription use only.
For use with the Quantisal II Oral Fluid Collection Device only.
4. Special instrument requirements:
Beckman Coulter AU480 Clinical Chemistry Analyzer
I. Device Description:
The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay consists of the following:
- The Enzyme Acceptor/Antibody Reagent (EA) is provided as a liquid, ready to use, and contains EA protein and recombinant antibodies to PCP, in PIPES buffer with Sodium Azide as a preservative.
- The Enzyme Donor/Substrate Reagent (ED) is provided as a liquid, ready to use, and contains ED peptide labeled with PCP and CPRG substrate in malic acid buffer with Sodium Azide as a preservative.
- The Quantisal II Oral Fluid Collection Device consists of two cellulose pads affixed to a polypropylene stem (for collecting saliva samples), and two transport tubes with snap caps, each containing three mL of preservative buffer.
J. Substantial Equivalence Information:
1. Predicate device name(s):
Biophor Diagnostics, Inc., RapidFRET Oral Fluid Assay for PCP
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2. Predicate 510(k) number(s):
k122703
3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device | Predicate (k122703) |
| Intended Use | Same | Detection of PCP in oral fluid |
| Cutoff concentration | Same | 10 ng/mL |
| Intended user | Same | Prescription use only |
| Matrix | Same | Human oral fluid |
| Reagent composition | Same | PCP specific antibody reagent, PCP drug conjugate reagent |
| Reagent storage | Same | 2 – 8° C until expiration date |
| Differences | | |
| --- | --- | --- |
| Item | Candidate Device | Predicate (k122703) |
| Collection device | Oral fluid is collected with the Quantisal II Oral Fluid Collection Device. Sample is stored in a plastic tube containing preservative buffer with snap cap. One mL of oral fluid is diluted with three mL of preservative resulting in a x4 dilution. | Neat oral fluid is collected with the RapidEASE Oral Fluid Collector via direct expectoration. No diluent is used and sample is stored in a glass sample tube with inert screw cap. |
K. Standard/Guidance Document Referenced (if applicable):
- CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition
- ISO 14971:2007 Medical Devices – Application of Risk Management to Medical Devices
- EN ISO 14971:2012 Medical Devices – Application of Risk Management to Medical Devices
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L. Test Principle:
The SEFRIA technology is based on artificial fragments of the E. coli enzyme β galactosidase: Enzyme Acceptor (EA), created by deletion of a short sequence in the amino-terminal region of the enzyme, and Enzyme Donor (ED), containing a fragment of the carboxy-terminal sequence of the enzyme. EA and ED are inactive, but when combined form active β-galactosidase. For the Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay, ED peptides are modified by attachment of a derivative of PCP, which does not interfere with the formation of active β-galactosidase. However antibodies to PCP bind to the ED-PCP conjugate, and block complementation. The assay is based on the competition of free PCP in an oral fluid sample with the ED-PCP conjugate for the fixed amount of antibody binding sites. In the absence of the free drug in the sample, the antibody binds the ED-PCP conjugate, resulting in inhibition of enzyme formation. As the PCP concentration in the sample increases, ED-PCP becomes available for complementation, creating an inverse relationship between PCP concentration in the oral fluid and enzyme formation. The β-galactosidase activity is determined spectrophotometrically at 570 nm by the conversion of CPRG (orange) to chlorophenol red (red) and galactose.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
A study was performed using three lots of the Quantisal II collection device, over 15 days, with two runs per day with two collection devices per run (N=60 per collection device lot) to evaluate precision of the Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay. Oral fluid was collected using Quantisal II (including pad/tube “A” and pad/tube “B”) by dipping each collection pad into the spiked PCP pooled neat human oral fluid near the cutoff concentration, until the volume adequacy indicator activated and turned blue. The pads were then placed into the corresponding transport tubes containing three mL of preservative buffer, incubated overnight at room temperature to simulate the transportation time via common carrier to the laboratory and tested. Results from one representative lot in qualitative and semi-quantitative mode are summarized below.
Qualitative mode using Quantisal II A collector
| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| --- | --- | --- | --- |
| 0 | -100% | 60 | 60 Negative |
| 2.5 | -75% | 60 | 60 Negative |
| 5 | -50% | 60 | 60 Negative |
| 7.5 | -25% | 60 | 60 Negative |
| 10 | Cutoff | 60 | 29 Neg / 31 Pos |
| 12.5 | 25% | 60 | 60 Positive |
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| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| --- | --- | --- | --- |
| 15 | 50% | 60 | 60 Positive |
| 17.5 | 75% | 60 | 60 Positive |
| 20 | 100% | 60 | 60 Positive |
Semiquantitative mode using Quantisal II A collector
| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| --- | --- | --- | --- |
| 0 | -100% | 60 | 60 Negative |
| 2.5 | -75% | 60 | 60 Negative |
| 5 | -50% | 60 | 60 Negative |
| 7.5 | -25% | 60 | 60 Negative |
| 10 | Cutoff | 60 | 28 Neg / 32 Pos |
| 12.5 | 25% | 60 | 60 Positive |
| 15 | 50% | 60 | 60 Positive |
| 17.5 | 75% | 60 | 60 Positive |
| 20 | 100% | 60 | 60 Positive |
Qualitative mode using Quantisal II B collector
| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| --- | --- | --- | --- |
| 0 | -100% | 60 | 60 Negative |
| 2.5 | -75% | 60 | 60 Negative |
| 5 | -50% | 60 | 60 Negative |
| 7.5 | -25% | 60 | 60 Negative |
| 10 | Cutoff | 60 | 32 Neg / 28 Pos |
| 12.5 | 25% | 60 | 60 Positive |
| 15 | 50% | 60 | 60 Positive |
| 17.5 | 75% | 60 | 60 Positive |
| 20 | 100% | 60 | 60 Positive |
Semiquantitative mode using Quantisal II B collector
| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| --- | --- | --- | --- |
| 0 | -100% | 60 | 60 Negative |
| 2.5 | -75% | 60 | 60 Negative |
| 5 | -50% | 60 | 60 Negative |
| 7.5 | -25% | 60 | 60 Negative |
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| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| --- | --- | --- | --- |
| 10 | Cutoff | 60 | 29 Neg / 31 Pos |
| 12.5 | 25% | 60 | 60 Positive |
| 15 | 50% | 60 | 60 Positive |
| 17.5 | 75% | 60 | 60 Positive |
| 20 | 100% | 60 | 60 Positive |
A second precision study was performed over 20 days and produced similar results.
## Sample Volume:
The sponsor performed a study to validate the sample volume, and reproducibility of sample volume, collected using the Quantisal II Oral Fluid Collection Device. Oral fluid samples were collected using the Quantisal II Oral Fluid Collection Device from 125 individuals (50 non-drug abusers and 75 drug abusers). Prior to collection, each collector pad (A and B) was independently weighed. After the volume adequacy indicator turned blue on both A and B collector stems, each collector was weighed again. The difference in weight was noted, and the corresponding volume was calculated. The volumes collected from collector A ranged from 0.86 – 1.10 mL, and the volumes collected from collector B ranged from 0.90 – 1.09 mL.
## Collection Time:
The sponsor performed a study designed to validate the sample collection time for the Quantisal II Oral Fluid Collection Device. 125 oral fluid samples were collected using Quantisal II Oral Fluid Collection Device (from 50 non-drug abusers and 75 known drug abusers). For each collection, a timer was started at the time the collector was placed into subject's mouth, and was stopped when the volume adequacy indicator turned blue on both A and B collector stems and the collector was taken out of the mouth. The sponsor reported that 124/125 subjects were able to provide sufficient sample (i.e. the collection device's volume adequacy indicator showed adequate collection) within the recommended collection timeframe of ten minutes. The mean time required for collection was three minutes and 42 seconds. The maximum time required for collection was reported as 11 minutes and 0 seconds.
The device labeling states that if the indicator has not turned blue within 15 minutes, the pad should be removed from the mouth and discarded, and that another collection should be attempted with a new collector.
## b. Linearity/assay reportable range:
The sponsor performed a study to evaluate the recovery of PCP, using the semi-quantitative mode of the Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay, across the claimed concentration range. Pooled drug-free oral fluid
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was spiked with a high concentration of the drug analyte PCP (at 10% above the highest calibrator level) and was used as the high value specimen (44 ng/mL). Additional pools were made by serially diluting the high value specimen in human drug-free oral fluid in increments of approximately 10%. The 0 ng/mL sample was drug free oral fluid. Quantisal II oral fluid collection devices were dipped into aliquots from each pool until the adequacy indicator turned blue and were then placed into the associated transport tubes containing the preservative buffer per the package insert instructions. Each tube was analyzed in triplicate for drug recovery in semi-quantitative mode. The recovery at the claimed cutoff concentration of 10 ng/mL was 102.3% and the range of recoveries at concentrations from four to 44 ng/mL was 97.5 – 111.4 %.
## Sample Recovery
The sponsor also performed a study to evaluate the recovery of PCP from the Quantisal II Oral Fluid Collection Device independent of the Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay. Neat drug-free oral fluid was spiked with PCP at target concentrations of ±25% and +50% of the cutoff (7.5 ng/mL, 12.5 ng/mL and 15 ng/mL), and concentrations were verified by LC-MS/MS. Three Quantisal II collectors were introduced sequentially into each aliquot and removed after the volume adequacy indicator turned blue. The collectors were then placed into the transport tubes, sealed with snap caps and stored overnight at room temperature. The next day the liquids in the tubes were analyzed by LC-MS/MS in replicates of three for a total of nine replicates per concentration. Recoveries of PCP ranged from 86.2% – 105.7%.
### c. Traceability, Stability, Expected values (controls, calibrators, or methods):
#### Sample Storage Stability:
The sponsor performed a study to evaluate the stability of PCP in oral fluid samples at the recommended storage temperatures of 2 – 8°C and at room temperature (30°C was used). Drug-free oral fluid was spiked with PCP to a concentration approximately 50% above the cutoff. An aliquot was tested for its initial concentration by LC-MS/MS and another aliquot was processed through three independent Quantisal II Oral Fluid Collection Devices and stored at the above storage temperatures. Samples were analyzed for PCP at day five and day ten (for the 30°C storage condition), and at one, two, three and six months (for the 2 – 8°C storage condition). Recoveries at all test conditions and time points ranged from 91.0 – 105.7%.
The results of the study support the sponsor's stability claims in labeling that PCP in oral fluid is stable for up to 10 days when stored in Quantisal II at ambient temperature up to 30°C and for up to two months when stored in Quantisal II at 2°C – 8°C.
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Sample Transportation Stability
The sponsor performed a study to evaluate the stability of PCP in oral fluid samples after being transported under shipping conditions anticipated in the United States.
Drug free oral fluid was spiked with the drug analyte PCP at concentrations approximately ±50% of the cutoff (five ng/mL and 15 ng/mL). Three Quantisal II Oral Fluid Collection Devices were introduced sequentially into each aliquot and removed after the volume adequacy indicator turned blue. The collector was then placed into the transport tube, sealed with a snap cap and packed in standard boxes used by common freight carriers. During the simulated transportation study, the samples were stored in an oven and a freezer and cycled between temperatures ranging from -20°C to 40°C. Samples were also agitated during the shipping transportation study to simulate conditions of actual shipping. These temperatures were selected to include the extremes of temperature likely to occur during shipment of products. All conditions were evaluated for a minimum of 24 hours and a maximum of 63 hours. After the simulated shipping, LC-MS/MS testing was performed in replicates of two for each sample and compared to the reference sample. All samples at all shipping conditions recovered within ±10% from the reference sample.
d. Detection limit:
Not applicable.
e. Analytical specificity:
Cross-reactivity:
A study was performed to evaluate the cross-reactivity of the Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay to compounds that are structurally similar to PCP. Structurally related compounds were spiked into drug-free oral fluid at high concentrations, and then if a given compound produced a positive result on the device, it was retested to identify the lowest concentration that yielded a result that is equivalent to the 10 ng/mL cutoff of PCP in neat oral fluid. Each compound sample was tested in replicates of five in qualitative and semi-quantitative modes; no differences in results were seen between the semi-quantitative and qualitative modes. Cross-reactivity was calculated as the cutoff divided by the lowest concentration of potential cross-reactant tested, and the results are summarized below.
| Compound | Concentration Equivalent to the cutoff (ng/mL) | Cross-Reactivity (%) |
| --- | --- | --- |
| Amitriptyline | 22,000 | 0.05 |
| Chlorpromazine | 5,200 | 0.19 |
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| Compound | Concentration Equivalent to the cutoff (ng/mL) | Cross-Reactivity (%) |
| --- | --- | --- |
| Clomipramine | 22,000 | 0.05 |
| Cyclobenzaprine | 1,900 | 0.53 |
| Desipramine | 40,000 | <0.03 |
| Dextromethorphan | 40,000 | <0.03 |
| Diphenhydramine | 37,000 | 0.03 |
| Doxepin | 5,600 | 0.18 |
| Doxylamine | 40,000 | <0.03 |
| EDDP | 40,000 | <0.03 |
| 4-Hydroxyphencyclidine (PCHP) | 85 | 11.76 |
| Imipramine | 13,400 | 0.07 |
| Methoxetamine | 34,000 | 0.03 |
| Nortriptyline | 40,000 | <0.03 |
| Protriptyline | 40,000 | <0.03 |
| Thioridazine | 8,600 | 0.12 |
| Trimipramine | 40,000 | <0.03 |
| Venlafaxine | 40,000 | <0.03 |
Interference from exogenous substances and pH:
Structurally unrelated compounds, endogenous compounds, exogenous compounds and effect of pH were evaluated for potential interference with the Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay.
Test solutions for each compound were prepared by spiking the potential interfering compound into drug-free negative oral fluid containing a PCP concentration of 7.5 ng/mL and 12.5 ng/mL (±25% of the 10 ng/mL cutoff) and were one to four diluted using Quantisal preservative buffer. Each compound was an independent spike and no drug mixes were used. Each compound sample was tested in replicates of five in qualitative and semi-quantitative modes. None of the structurally unrelated compounds listed below caused positive or negative interference with the assay at the concentrations listed, and no differences were seen between the semi-quantitative and qualitative modes, at the concentrations tested below.
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| Compound | Concentration Tested (ng/mL) |
| --- | --- |
| 4-Bromo-2,5,Dimethoxyphenethylamine | 5,000 |
| 6-Acetylcodeine | 40,000 |
| 6-Acetylmorphine | 40,000 |
| Alprazolam | 40,000 |
| 7-Aminoclonazepam | 40,000 |
| 7-Aminoflunitrazepam | 40,000 |
| 7-Aminonitrazepam | 40,000 |
| S-(+)-Amphetamine | 40,000 |
| Benzylpiperazine | 40,000 |
| Bromazepam | 40,000 |
| Buprenorphine | 40,000 |
| Bupropion | 40,000 |
| Butabarbital | 40,000 |
| Butalbital | 40,000 |
| Caffeine | 40,000 |
| Cannabidiol | 40,000 |
| Cannabinol | 40,000 |
| Carbamazepine | 40,000 |
| Carisoprodol | 40,000 |
| Chlordiazepoxide | 40,000 |
| cis-Tramadol | 40,000 |
| Clobazam | 40,000 |
| Clonazepam | 40,000 |
| Clozapine | 40,000 |
| Cocaine | 40,000 |
| Codeine | 40,000 |
| Cotinine | 40,000 |
| Demoxepam | 40,000 |
| Desalkylflurazepam | 40,000 |
| Dihydrocodeine | 40,000 |
| Diazepam | 40,000 |
| Digoxin | 40,000 |
| Dehydronorketamine | 40,000 |
| Delta-9-THC | 40,000 |
| Ecgonine | 40,000 |
| Ecgonine Methyl Ester | 40,000 |
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| Compound | Concentration Tested (ng/mL) |
| --- | --- |
| EMDP | 40,000 |
| 1R,2S(-)-Ephedrine | 40,000 |
| 1S,2R(+)-Ephedrine | 40,000 |
| Ethyl-β-D-Glucuronide | 40,000 |
| Ethylmorphine | 40,000 |
| Fenfluramine | 40,000 |
| Fentanyl | 20,000 |
| Flunitrazepam | 40,000 |
| Fluoxetine | 40,000 |
| Flurazepam | 40,000 |
| Haloperidol | 40,000 |
| Heroin | 40,000 |
| Hexobarbital | 40,000 |
| Hydrocodone | 40,000 |
| Hydromorphone | 40,000 |
| 11-hydroxy-delta-9-THC | 40,000 |
| Ibuprofen | 40,000 |
| Ketamine | 40,000 |
| Lamotrigine | 40,000 |
| Levorphanol | 40,000 |
| Lidocaine | 40,000 |
| Lorazepam | 40,000 |
| Lorazepam Glucuronide | 40,000 |
| Lormetazepam | 40,000 |
| LSD | 40,000 |
| Maprotiline | 40,000 |
| MDA | 40,000 |
| MDEA | 40,000 |
| MDMA | 40,000 |
| Meperidine | 40,000 |
| Meprobamate | 40,000 |
| S(+)-Methamphetamine | 40,000 |
| Methadone | 40,000 |
| Methaqualone | 40,000 |
| Methylone | 40,000 |
| Methylphenidate | 40,000 |
| Midazolam | 40,000 |
| Morphine | 40,000 |
| Morphine-3-Glucuronide | 40,000 |
| Morphine-6-Glucuronide | 40,000 |
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| Compound | Concentration Tested (ng/mL) |
| --- | --- |
| N-desmethyltentadol | 40,000 |
| N-desmethyl tramadol | 40,000 |
| N-desmethyl venlafaxine | 40,000 |
| Nalorphine | 40,000 |
| Naloxone | 40,000 |
| Naltrexone | 40,000 |
| Naproxen | 40,000 |
| Nitrazepam | 40,000 |
| 11-nor-9 carboxy THC | 40,000 |
| Norbuprenorphine | 40,000 |
| Norcodeine | 40,000 |
| Nordiazepam | 40,000 |
| Norketamine | 40,000 |
| Normorphine | 40,000 |
| Noroxycodone | 40,000 |
| Noroxymorphone | 40,000 |
| Norpropoxyphene | 20,000 |
| Norpseudoephedrine | 2,000 |
| O-desmethyl tramadol | 40,000 |
| O-desmethyl venlafaxine | 40,000 |
| Oxycodone | 40,000 |
| Oxymorphone | 40,000 |
| Olanzapine | 40,000 |
| Oxazepam | 40,000 |
| Pentazocine | 40,000 |
| Pentobarbital | 40,000 |
| Phenobarbital | 40,000 |
| Phentermine | 40,000 |
| Phenylephrine | 40,000 |
| Phenytoin | 40,000 |
| Phenylpropanolamine | 40,000 |
| PMA | 40,000 |
| Prazepam | 40,000 |
| Propranolol | 40,000 |
| Propoxyphene | 40,000 |
| R,R(-)-Pseudoephedrine | 40,000 |
| S,S(+)-Pseudoephedrine | 40,000 |
| Ritalinic Acid | 40,000 |
| Salicylic Acid | 40,000 |
| Secobarbital | 40,000 |
| Sertraline | 40,000 |
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| Compound | Concentration Tested (ng/mL) |
| --- | --- |
| Sufentanil | 40,000 |
| Tapentadol | 40,000 |
| Temazepam | 40,000 |
| Theophylline | 40,000 |
| Trazadone | 40,000 |
| Triazolam | 40,000 |
| Trifluoromethylphenyl-piperazine | 40,000 |
| Verapamil | 40,000 |
| Zolpidem Tartrate | 40,000 |
Food and dental products:
Additional potential exogenous interferents, including common food and dental products, were evaluated by collecting oral fluid in Quantisal II oral fluid collectors from volunteers after use of the substances. Oral fluid of one volunteer was collected for each compound tested, spiked with PCP at the concentrations noted below, and tested with the Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay. No negative or positive interference was observed in either the qualitative or semi-quantitative mode. Results are summarized as follows:
| Compound | Compound Conc. | -25% Cutoff (7.5 ng/mL) | | +25% Cutoff (12.5 ng/mL) | |
| --- | --- | --- | --- | --- | --- |
| | | Result | Interference (Yes/No)? | Result | Interference (Yes/No)? |
| Acetaminophen | 0.1 mg/mL | NEG | No | POS | No |
| Acetylsalicylic Acid | 0.1 mg/mL | NEG | No | POS | No |
| Baking Soda | 0.6% v/v | NEG | No | POS | No |
| Cotinine | 0.03 mg/mL | NEG | No | POS | No |
| Denture Adhesive | 0.6% w/v | NEG | No | POS | No |
| Ibuprofen | 0.1 mg/mL | NEG | No | POS | No |
| Alcohol (Ethanol) | 6% v/v | NEG | No | POS | No |
| Caffeine | 0.1 mg/mL | NEG | No | POS | No |
| Coffee | 6% v/v | NEG | No | POS | No |
| Cranberry Juice | 6% v/v | NEG | No | POS | No |
| Hydrogen Peroxide (3% OTC) | 0.5% v/v | NEG | No | POS | No |
| Milk | 1% v/v | NEG | No | POS | No |
| Mouthwash | 6% v/v | NEG | No | POS | No |
| Naproxen | 0.1 mg/mL | NEG | No | POS | No |
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| Compound | Compound Conc. | -25% Cutoff (7.5 ng/mL) | | +25% Cutoff (12.5 ng/mL) | |
| --- | --- | --- | --- | --- | --- |
| | | Result | Interference (Yes/No)? | Result | Interference (Yes/No)? |
| Orange Juice | 6% v/v | NEG | No | POS | No |
| Soft Drink (Pepsi) | 6% v/v | NEG | No | POS | No |
| Sodium Chloride | 18 mg/mL | NEG | No | POS | No |
| Sugar | 20 mg/mL | NEG | No | POS | No |
| Tea | 6% v/v | NEG | No | POS | No |
| Toothpaste | 6% v/v | NEG | No | POS | No |
| Teeth Whitener | 2 strips | NEG | No | POS | No |
| Hydrogen Peroxide (3% OTC) | Neat (2 min mouth rinse) | NEG | No | POS | No |
| Cigarette | 1 cigarette | NEG | No | POS | No |
| Hard Candy | 1 piece | NEG | No | POS | No |
| Chewing Gum | 1 piece | NEG | No | POS | No |
| Sugar | 2 Teaspoons | NEG | No | POS | No |
| Cough Syrup | 2 Teaspoons | NEG | No | POS | No |
Endogenous substances:
The sponsor evaluated common endogenous substances that could be present in oral fluid to determine if these compounds had any effect on Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay results. The potential interferents were spiked at the concentrations below into oral fluid containing PCP at $\pm 25\%$ of the cutoff. No negative or positive interference was observed in either the qualitative or semi-quantitative mode.
| Compound | Compound Conc. | -25% Cutoff (7.5 ng/mL) | | +25% Cutoff (12.5 ng/mL) | |
| --- | --- | --- | --- | --- | --- |
| | | Result | Interference (Yes/No)? | Result | Interference (Yes/No)? |
| Ascorbic Acid | 3 mg/mL | NEG | No | POS | No |
| Bilirubin | 0.15 mg/mL | NEG | No | POS | No |
| Cholesterol | 0.45 mg/mL | NEG | No | POS | No |
| γ-Globulin | 0.8 mg/mL | NEG | No | POS | No |
| Hemoglobin | 3 mg/mL | NEG | No | POS | No |
| Human Serum Albumin | 15 mg/mL | NEG | No | POS | No |
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| Compound | Compound Conc. | -25% Cutoff (7.5 ng/mL) | | +25% Cutoff (12.5 ng/mL) | |
| --- | --- | --- | --- | --- | --- |
| | | Result | Interference (Yes/No)? | Result | Interference (Yes/No)? |
| IgA | 1 mg/mL | NEG | No | POS | No |
| IgG | 1 mg/mL | NEG | No | POS | No |
| IgM | 0.5 mg/mL | NEG | No | POS | No |
| Salivary-α-amylase | 1000 U/mL | NEG | No | POS | No |
Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay performance was tested for potential interference of oral fluid pH at pH levels of 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0 and 11.0. All test samples used drug-free oral fluid spiked with PCP to concentrations of 7.5 ng/mL and 12.5 ng/mL (±25% of the 10 ng/mL cutoff). No positive or negative interference was seen in either the qualitative or semi-quantitative mode.
f. Assay cut-off:
See section M.1.a., above.
2. Comparison studies:
a. Method comparison with predicate device:
80 unaltered, oral fluid samples collected by expectoration were analyzed by LC-MS/MS. A separate aliquot was processed through the Quantisal II Oral Fluid Collection Device and analyzed using the Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay in qualitative and semi-quantitative modes, and collected specimens from each of the collection device’s two collection pads (A and B) were compared to the LC-MS/MS-determined concentration. Results are summarized below:
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| Quantisal II “A” collection pad | | | | | |
| --- | --- | --- | --- | --- | --- |
| Immunalysis SEFRIA PCP Oral Fluid EIA Result | LC-MS/MS PCP Neat Oral Fluid Concentration | | | | |
| | | < 5 ng/mL (less than -50% cutoff) | 5 – 9 ng/mL (between -50% cutoff and cutoff) | 10 – 15 ng/mL (between cutoff and +50% cutoff) | > 15 ng/mL (greater than +50% cutoff) |
| Qualitative | Positive | 0 | 0 | 5 | 35 |
| | Negative | 36 | 4 | 0 | 0 |
| Semiquantitative | Positive | 0 | 0 | 5 | 35 |
| | Negative | 36 | 4 | 0 | 0 |
| Quantisal II “B” collection pad | | | | | |
| --- | --- | --- | --- | --- | --- |
| Immunalysis SEFRIA PCP Oral Fluid EIA Result | LC-MS/MS PCP Neat Oral Fluid Concentration | | | | |
| | | < 5 ng/mL (less than -50% cutoff) | 5 – 9 ng/mL (between -50% cutoff and cutoff) | 10 – 15 ng/mL (between cutoff and +50% cutoff) | > 15 ng/mL (greater than +50% cutoff) |
| Qualitative | Positive | 0 | 0 | 5 | 35 |
| | Negative | 36 | 4 | 0 | 0 |
| Semiquantitative | Positive | 0 | 0 | 5 | 35 |
| | Negative | 36 | 4 | 0 | 0 |
b. Matrix comparison:
Not applicable.
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable.
b. Clinical specificity:
Not applicable.
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c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable.
4. Clinical cut-off:
Not applicable.
5. Expected values/Reference range:
Not applicable.
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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