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 |
Intended 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 PCP in human oral fluid collected via the Quantisal II Oral Fluid Collection Device. For prescription use in clinical laboratory settings to provide preliminary analytical results requiring confirmation by GC-MS or LC-MS/MS.
Predicate Devices
- RapidFRET Oral Fluid Assay for PCP, PCP Calibrator Set, PCP Control Set and RapidEase Oral Fluid Collector (K122703)
Related Devices
- K152176 — Immunalysis PCP Urine Enzyme Immunoassay, Immunalysis Multi-Drug Calibrators · Immunalysis Corporation · Sep 4, 2015
- K122703 — RAPIDFRET ORAL FLUID ASSAY FOR PCP, PCP CALIBRATOR SET, PCP CONTROL SET AND RAPIDEASE ORAL FLUID COLLECTOR · Biophor Diagnostics, Inc. · Apr 25, 2013
- K203489 — SEFRIA PCP Oral Fluid Enzyme Immunoassay · Immunalysis Corporation · Apr 20, 2021
- K993983 — SYVA EMIT II PLUS PHENCYCLIDINE ASSAY, MODEL 9J029UL · Syva Co. · Jan 27, 2000
- K150925 — Immunalysis Benzoylecgonine Urine Enzyme Immunoassay, Immunalysis Benzoylecgonine Urine Calibrators, Immunalysis Benzoylecgonine Urine Control Set · Immunalysis Corporation · Jun 29, 2015
Submission Summary (Full Text)
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January 24, 2019
Immunalysis Corporation Michelle Bodien Associate Director, Regulatory Affairs 829 Towne Center Drive Pomona, CA 91767
Re: k181135
Trade/Device Name: Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay Regulatory Class: Unclassified, 510(k) required Product Code: LCM Dated: December 13, 2018 Received: December 14, 2018
Dear Michelle Bodien:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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 Part
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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn
(http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
# Kellie B. Kelm -S
for 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
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# Indications for Use
510(k) Number (if known) k181135
#### Device Name
Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay
#### Indications for Use (Describe)
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.
Type of Use (Select one or both, as applicable)
| <span></span> | <span></span> Prescription Use (Part 21 CFR 801 Subpart D) |
|---------------|------------------------------------------------------------|
| <span></span> | <span></span> Over-The-Counter Use (21 CFR 801 Subpart C) |
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#### 510(k) SUMMARY k181135
#### A. GENERAL INFORMATION
| Applicant Name: | Immunalysis Corporation<br>829 Towne Center Drive<br>Pomona, CA 91767<br>Establishment # 2020952 |
|------------------|-------------------------------------------------------------------------------------------------------------------|
| Company Contact: | Michelle Bodien<br>Assoc. Director, Regulatory Affairs<br>Phone: (210)4058453<br>Email: michelle.bodien@alere.com |
| Date Prepared: | January 22, 2019 |
#### B. DEVICE IDENTIFICATION
| Trade or Proprietary Names: | Immunalysis SEFRIA™ PCP Oral Fluid Enzyme Immunoassay |
|-----------------------------|-------------------------------------------------------|
|-----------------------------|-------------------------------------------------------|
# C. REGULATORY INFORMATION
| Device Classification Name: | Enzyme Immunoassay, Phencyclidine |
|-----------------------------|----------------------------------------------------------------------------------------------------------------------|
| Product Codes: | LCM |
| Regulatory Class: | Class II |
| Classification Regulation: | Unclassified |
| Panel: | Toxicology (91) |
| Predicate Device: | RapidFRET Oral Fluid Assay for PCP, PCP Calibrator Set, PCP Control Set and RapidEase Oral Fluid Collector [K122703] |
#### D. DEVICE DESCRIPTION
The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay is a sensitive in vitro diagnostic test to detect the presence of PCP in human oral fluid samples collected with the Quantisal II Oral Fluid Collection Device.
Quantisal II Oral Fluid Collection Device is a collection system comprised of a dual pad collector and transport vials. The dual pad collector is separated after collection of oral fluid from a subject's mouth enabling each specimen-saturated collection pad to be placed into its own transport vial. The split specimen (referred to as "A" and "B") allows for one sample to be tested in a screening assay and confirmed by a quantitative laboratory method (such as liquid chromatography tandem mass spectrometry [LC-MS/MS] and the second sample to be stored for secondary confirmation if needed.
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PCP was first synthesized in 1926 and later tested after World War II as a surgical anesthetic. Because of its adverse side effects, such as hallucinations, mania, delirium, and disorientation, it was shelved until the 1950s. The drug is easily synthesized by anyone with a basic knowledge of chemistry and has become one of the drugs most frequently used by drug abusers. It has a variety of street names, including "angel dust," "animal tranquilizer," "PCP," "peace pill," "crystal joints," and "peace weed," with the name often reflecting the form in which it is taken. It can be smoked, "snorted" through the nose, ingested, or taken intravenously. Phencyclidine has also been shown to cause schizophrenia-like changes in Nacetylaspartate and Nacetylaspartylglutamate in the rat brain, which are detectable both in living rats and upon necropsy examination of brain tissue. It also induces symptoms in humans that mimic schizophrenia. Behavioral effects can vary by dosage. Low doses produce numbness in the extremities and intoxication, characterized by staggering, unsteady gait, slurred speech, bloodshot eyes, and loss of balance. Moderate doses (5-10 mg intranasal, or 0.01-0.02 mg/kg intramuscular or intravenous) will produce analgesia and anesthesia. High doses may lead to convulsions. Users frequently do not know how much of the drug they are taking due to the tendency of the drug to be made illegally in uncontrolled conditions.
# E. INTENDED USE
# Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay
The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay is a homogenous 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.
| Attribute | Predicate Device<br>RapidFRET Oral Fluid Assay<br>for PCP [k122703] | Candidate Device<br>Immunalysis SEFRIA PCP<br>Oral Fluid Enzyme<br>Immunoassay |
|----------------|---------------------------------------------------------------------|--------------------------------------------------------------------------------|
| Similarities | | |
| Test Principle | Homogeneous enzyme<br>immunoassay | Same |
| Antibody | Antibodies to PCP | Same |
# F. COMPARISON WITH PREDICATE
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| Attribute | Predicate Device<br>RapidFRET Oral Fluid Assay<br>for PCP [k122703] | Candidate Device<br>Immunalysis SEFRIA PCP<br>Oral Fluid Enzyme<br>Immunoassay |
|--------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Materials | PCP specific antibody reagent,<br>PCP drug conjugate reagent | Same |
| Cutoff Level | 10 ng/mL | Same |
| User Environment | For use in laboratories | Same |
| Sample Matrix | Human oral fluid | Same |
| Reagent Storage | 2-8°C until expiration date | Same |
| | Differences | |
| Intended Use | Qualitative determination of<br>phencyclidine in human oral<br>fluid | Qualitative and semi-<br>quantitative determination of<br>phencyclidine in human oral<br>fluid. |
| Sample Collection Device | Neat oral fluid is collected with<br>the RapidEASE Oral Fluid<br>Collector via direct<br>expectoration. No diluent is used<br>and sample is stored in a glass<br>sample tube with inert screw<br>cap. | Oral fluid is collected with the<br>Quantisal II Oral Fluid<br>Collection Device. Sample is<br>stored in a plastic tube<br>containing preservative buffer<br>with snap cap. |
# G. PERFORMANCE CHARACTERISTICS
The following laboratory performance studies were performed to determine substantial equivalence of the Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay and Quantisal II Oral Fluid Collection Devices to the predicate device. Assay performance was established using the Beckman Coulter AU480 chemistry analyzer.
# 1. Precision/ Cutoff Characterization
Precision/ Cutoff Characterization study was performed over 15 days, two collection device runs per day with two collections per run (N=60) on three lots of Quantisal II oral fluid collection devices. Drug free negative urine was spiked to concentrations of assay cutoff and ±25%, ±50%, ±75%, ±100% of the cutoff and transferred to the collection devices. The spiked concentrations were confirmed by mass spectrometry (LC-MS/MS). The study established the repeatability of the testing system, including assay and oral fluid collection device. Test results in qualitative and semi-quantitative modes for a representative lot are presented in Tables 1 to 6.
| Concentration<br>(ng/mL) | % of cutoff | # of<br>determinations | Result |
|--------------------------|-------------|------------------------|-------------|
| 0 | -100% | 60 | 60 Negative |
# Table 1. Precision - Quantisal II "A" - Qualitative
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| Concentration<br>(ng/mL) | % of cutoff | # of<br>determinations | Result |
|--------------------------|-------------|------------------------|----------------|
| 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 |
| 15 | 50% | 60 | 60 Positive |
| 17.5 | 75% | 60 | 60 Positive |
| 20 | 100% | 60 | 60 Positive |
# Table 2. Precision – Quantisal II "A" - Semi-Quantitative
| Concentration<br>(ng/mL) | % of cutoff | # of<br>determinations | Mean Conc.<br>(ng/mL) | Result |
|--------------------------|-------------|------------------------|-----------------------|-----------------|
| 0 | -100% | 60 | 0.5 | 60 Negative |
| 2.5 | -75% | 60 | 2.7 | 60 Negative |
| 5 | -50% | 60 | 5.5 | 60 Negative |
| 7.5 | -25% | 60 | 7.8 | 60 Negative |
| 10 | Cutoff | 60 | 10.1 | 28 Neg / 32 Pos |
| 12.5 | 25% | 60 | 12.5 | 60 Positive |
| 15 | 50% | 60 | 15.5 | 60 Positive |
| 17.5 | 75% | 60 | 17.4 | 60 Positive |
| 20 | 100% | 60 | 20.2 | 60 Positive |
# Table 3. Precision – Quantisal II "B" - Qualitative
| Concentration<br>(ng/mL) | % of cutoff | # of<br>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 |
# Table 4. Precision – Quantisal II "B" - Semi-Quantitative
| Concentration<br>(ng/mL) | % of cutoff | # of<br>determinations | Mean Conc.<br>(ng/mL) | Result |
|--------------------------|-------------|------------------------|-----------------------|-------------|
| 0 | -100% | 60 | 0.5 | 60 Negative |
| 2.5 | -75% | 60 | 2.7 | 60 Negative |
| 5 | -50% | 60 | 5.5 | 60 Negative |
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| Concentration<br>(ng/mL) | % of cutoff | # of<br>determinations | Mean Conc.<br>(ng/mL) | Result |
|--------------------------|-------------|------------------------|-----------------------|-----------------|
| 7.5 | -25% | 60 | 8.0 | 60 Negative |
| 10 | Cutoff | 60 | 10.1 | 29 Neg / 31 Pos |
| 12.5 | 25% | 60 | 12.7 | 60 Positive |
| 15 | 50% | 60 | 15.5 | 60 Positive |
| 17.5 | 75% | 60 | 17.5 | 60 Positive |
| 20 | 100% | 60 | 20.2 | 60 Positive |
# 2. Specificity and Cross-Reactivity
Structurally and functionally similar compounds were spiked into drug free oral fluid at levels that will yield a result that is equivalent to the cutoff. The study verified assay performance relative to the ability of the device to exclusively determine certain drugs, in both the qualitative and semi-quantitative modes. Cross-reactivity test results for qualitative and semi-quantitative modes are presented in Table 7.
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| Compound | Compound<br>Conc.<br>(ng/mL) | PCP<br>Equivalent<br>Conc.<br>(ng/mL) | Result | Cross-<br>Reactivity<br>(%) |
|----------------------------------|------------------------------|---------------------------------------|--------|-----------------------------|
| Amitriptyline | 22,000 | 10 | POS | 0.05 |
| Chlorpromazine | 5,200 | 10 | POS | 0.19 |
| Clomipramine | 22,000 | 10 | POS | 0.05 |
| Cyclobenzaprine | 1,900 | 10 | POS | 0.53 |
| Desipramine | 40,000 | <10 | NEG | <0.03 |
| Dextromethorphan | 40,000 | <10 | NEG | <0.03 |
| Diphenhydramine | 37,000 | 10 | POS | 0.03 |
| Doxepin | 5,600 | 10 | POS | 0.18 |
| Doxylamine | 40,000 | <10 | NEG | <0.03 |
| EDDP | 40,000 | <10 | NEG | <0.03 |
| 4-Hydroxyphencyclidine<br>(PCHP) | 85 | 10 | POS | 11.76 |
| Imipramine | 13,400 | 10 | POS | 0.07 |
| Methoxetamine | 34,000 | 10 | POS | 0.03 |
| Nortriptyline | 40,000 | <10 | NEG | <0.03 |
| Protriptyline | 40,000 | <10 | NEG | <0.03 |
| Thioridazine | 8,600 | 10 | POS | 0.12 |
| Trimipramine | 40,000 | <10 | NEG | <0.03 |
| Venlafaxine | 40,000 | <10 | NEG | <0.03 |
# Table 5. Cross-Reactivity - Qualitative
# 3. Interference – Structurally Unrelated Compounds
Structurally unrelated compounds were evaluated in qualitative and semi-quantitative modes by spiking the potential interferent into drug free oral fluid containing PCP at ±25% of the cutoff. All potential interferents analyzed verified that assay performance is unaffected by externally ingested compounds. The levels of structurally unrelated compounds that did not interfere in the assay are presented in Table 8.
| Compound | Conc. Tested (ng/mL) |
|-----------------------------------------|----------------------|
| 4-Bromo-<br>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 |
| Table 6. Non-Interfering Structurally Unrelated Compounds- Qualitative and Semi-quantitative | | | |
|----------------------------------------------------------------------------------------------|--|--|--|
| | | | |
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| Compound | Conc. Tested (ng/mL) |
|----------------------------------|----------------------|
| 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 |
| 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 |
| Compound | Conc. Tested (ng/mL) |
| 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 |
| N-desmethyltapentadol | 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 |
| Compound | Conc. Tested (ng/mL) |
| 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 |
| 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 |
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# 4. Interference - Endogenous Compounds and Exogenous Compounds
Endogenous compounds and exogenous compounds were evaluated in qualitative and semiquantitative modes by spiking the potential interferent into drug free oral fluid containing PCP at ±25% of the cutoff. Additional orally used products were tested by collecting oral fluid using
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Quantisal II Oral Fluid Collection Devices from volunteers after use of the substances. Assay performance is unaffected by all of the substances tested. Endogenous compounds and exogenous compounds tested are presented in Tables 9 and 10. Orally used compounds tested are presented in Table 11.
| Compound | Concentration Tested |
|---------------------|----------------------|
| Ascorbic Acid | 3 mg/mL |
| Bilirubin | 0.15 mg/mL |
| Cholesterol | 0.45 mg/mL |
| γ-Globulin | 0.8 mg/mL |
| Hemoglobin | 3 mg/mL |
| Human Serum Albumin | 15 mg/mL |
| IgA | 1 mg/mL |
| IgG | 1 mg/mL |
| IgM | 0.5 mg/mL |
| Salivary-α-amylase | 1000 U/mL |
Table 7. Non-interfering Endogenous Compounds
#### Table 8. Non-interfering Exogenous Compounds
| Compound | Concentration Tested |
|----------------------------|----------------------|
| Acetaminophen | 0.1 mg/mL |
| Acetylsalicylic Acid | 0.1 mg/mL |
| Baking Soda | 0.6% v/v |
| Cotinine | 0.03 mg/mL |
| Denture Adhesive | 0.6% w/v |
| Ibuprofen | 0.1 mg/mL |
| Alcohol (Ethanol) | 6% v/v |
| Caffeine | 0.1 mg/mL |
| Coffee | 6% v/v |
| Cranberry Juice | 6% v/v |
| Hydrogen Peroxide (3% OTC) | 0.5% v/v |
| Milk | 1% v/v |
| Mouthwash | 6% v/v |
| Naproxen | 0.1 mg/mL |
| Orange Juice | 6% v/v |
| Soft Drink (Pepsi) | 6% v/v |
| Sodium Chloride | 18 mg/mL |
| Sugar | 20 mg/mL |
| Tea | 6% v/v |
| Toothpaste | 6% v/v |
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| Compound | Concentration Tested |
|----------------------------|--------------------------|
| Teeth Whitener | 2 strips |
| Hydrogen Peroxide (3% OTC) | Neat (2 min mouth rinse) |
| Cigarette | 1 cigarette |
| Hard Candy | 1 piece |
| Chewing Gum | 1 piece |
| Cough Syrup | 2 Teaspoons |
Table 9. Non-interfering Orally Used Exogenous Products
# 5. Interference - pH
To evaluate potential interference from the effect of oral fluid pH, device performance in the qualitative and semi-quantitative modes was tested using a range of oral fluid pH values (3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0 and 11.0). All test samples were prepared in drug free oral fluid containing PCP at ±25% of the cutoff. No positive or negative interference was observed at oral fluid pH values ranging from 3.0 to 11.0 for each test mode.
# 6. Linearity/Recovery
A linearity study in the semi-quantitative mode was conducted by spiking a drug free oral fluid pool with a high concentration of PCP above the highest calibrator. Additional pools were made by serially diluting the high concentration specimen with drug free oral fluid to achieve concentrations ranging from 4 ng/mL to 44 ng/mL specimen was made from drug free oral fluid. Each pool was collected using Quantisal II oral fluid collection devices and tested in triplicate to calculate the mean concentration values that were used to calculate drug recovery. Linearity test results in semi-quantitative mode are presented in Tables 12 to 14.
| Expected Concentration<br>(ng/mL) | Mean Concentration<br>(ng/mL) | Recovery (%) |
|-----------------------------------|-------------------------------|--------------|
| 0 | 1.5 | N/A |
| 4 | 4.2 | 105.0 |
| 8 | 8.5 | 105.8 |
| 10 | 10.0 | 100.0 |
| 12 | 11.7 | 97.2 |
| 16 | 15.8 | 98.5 |
| 20 | 21.2 | 105.8 |
| 24 | 24.6 | 102.4 |
| 28 | 28.5 | 101.9 |
| 32 | 31.5 | 98.3 |
| 36 | 35.5 | 98.6 |
| 40 | 42.1 | 105.3 |
| 44 | 46.0 | 104.5 |
Table 10. Linearity/Recovery - Quantisal II "A"
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| Expected Concentration<br>(ng/mL) | Mean Concentration<br>(ng/mL) | Recovery (%) |
|-----------------------------------|-------------------------------|--------------|
| 0 | 1.3 | N/A |
| 4 | 3.7 | 92.5 |
| 8 | 8.2 | 102.1 |
| 10 | 10.3 | 102.7 |
| 12 | 12.3 | 102.5 |
| 16 | 16.0 | 99.8 |
| 20 | 19.0 | 94.8 |
| 24 | 24.1 | 100.6 |
| 28 | 27.7 | 98.9 |
| 32 | 33.9 | 105.8 |
| 36 | 36.6 | 101.8 |
| 40 | 42.0 | 105.1 |
| 44 | 46.4 | 105.5 |
# Table 11. Linearity/Recovery - Quantisal II "B"
# 7. Calibration Duration
Drug free negative oral fluid spiked with PCP at ±25% of the cutoff were tested in qualitative mode at time points up to 14 days. At the initial time point calibration curve was established. This calibration was used through the duration of this study. The test results met acceptance criteria at each time point. The recommended frequency of calibration is 14 days.
# 8. PCP Stability in Oral Fluid
Drug free negative oral fluid spiked with PCP at +50% of the cutoff were collected and stored in Quantisal II Oral Fluid Collection Device and tested by LC-MS/MS at each time point at 30°C and at 2℃ - 8℃. Test results indicated that oral fluid samples containing PCP are stable for up to 10 days stored in Quantisal II transport tubes at ambient temperature up to 30°C and up to 2 months stored in Quantisal II transport tubes at 2℃ - 8℃.
#### 9. Sample Transportation Stability
Drug free negative oral fluid spiked with PCP at ±50% of the cutoff were collected and stored in Quantisal II Oral Fluid Collection Device and packed in standard boxes used by common carrier (FedEx). During the 4-day (96 hours) simulated transportation study, the samples were stored in oven/freezer at temperatures ranged from -20°C to 40°C to encompass the temperatures likely to occur during shipment of products. The device used as the reference (unstressed) condition was stored continuously at the recommended storage condition at 2℃ - 8℃. LC-MS/MS testing was performed in replicates of two and compared to the reference sample. The studies demonstrated the PCP concentration of the sample collected by Quantisal II Oral Fluid Collection Device is within 20% of initial value during transportation.
#### 10. Sample Recovery
Drug free negative oral fluid spiked with PCP at ±25%, +50% of the cutoff were collected and stored in Quantisal II Oral Fluid Collection Devices overnight at room temperature. LC-MS/MS testing was performed the next day to determine percentage recovery. The studies demonstrated
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that the Quantisal II Collection Device recovers PCP at greater than 80% of the original concentration.
# 11. Quantisal II Sample Volume
Fifty oral fluid samples were collected using Quantisal II collectors (collection pad with plastic stem) from fifty volunteers. Prior to collection, each collector (A and B) was 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. Specific gravity of saliva was rounded to 1.000 to compute the volume collection. The results confirmed consistency of sample volume of 1 mL collected by each of Quantisal II collectors in this population.
Additional seventy-five oral fluid samples from known drug users were collected using Quantisal II collector. After the volume adequacy indicator turned blue on both A and B collector stems, each collector was weighed and compared to the average weight of collector before collection. The difference in weight was noted. Specific gravity of saliva was rounded to 1.000 to compute the volume collection. The results confirmed consistency of sample volume of 1 mL collected by each of Quantisal II collectors in this population.
# 12. Quantisal II Sample Collection Time
Fifty oral fluid samples from volunteers and seventy-five oral fluid samples from known drug users were collected using Quantisal II collection pad with plastic stem). The collection time was documented. The results verified the sample collection time for Quantisal II Oral Fluid Collection Device is within the claimed time of 10 minutes in over 90% of subjects.
# 13. Method Comparison
Eighty deidentified, unaltered clinical oral fluid samples collected by Quantisal II Oral Fluid Collection Devices were obtained from drug treatment facilities, analyzed for PCP at assay cutoff with the Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay in both qualitative and semi-quantitative modes and compared to Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) results with neat oral fluid collected by expectoration (spitting). The instruments used were the Beckman Coulter AU480 chemistry analyzer and an Agilent 6430 Liquid Chromatography-Tandem Mass Spectrometry. Method comparison test results in qualitative and semi-quantitative modes are presented from Tables 15 to 17.
| Immunalysis SEFRIA<br>PCP Oral Fluid<br>Enzyme Immunoassay<br>Result | | LC-MS/MS PCP Neat Oral Fluid Concentration | | | | Agreement<br>(%) |
|----------------------------------------------------------------------|----------|-----------------------------------------------|--------------------------------------------------------|------------------------------------------------------------|------------------------------------------------|------------------|
| | | < 5<br>ng/mL<br>(less than<br>-50%<br>cutoff) | 5 - 9 ng/mL<br>(between -<br>50% cutoff<br>and cutoff) | 10 - 15<br>ng/mL<br>(between<br>cutoff and<br>+50% cutoff) | > 15 ng/mL<br>(greater<br>than +50%<br>cutoff) | |
| Qual. | Positive | 0 | 0 | 5 | 35 | 100% (40/40) |
| | Negative | 36 | 4 | 0 | 0 | 100% (40/40) |
| Semi-<br>Quant. | Positive | 0 | 0 | 5 | 35 | 100% (40/40) |
| | Negative | 36 | 4 | 0 | 0 | 100% (40/40) |
Table 12. Method Comparison - Quantisal II "A"
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| Immunalysis SEFRIA<br>PCP Oral Fluid<br>Enzyme Immunoassay<br>Result | | LC-MS/MS PCP Neat Oral Fluid Concentration | | | | |
|----------------------------------------------------------------------|----------|--------------------------------------------|--------------------------------------------------------|---------------------------------------------------------|------------------------------------------------|------------------|
| | | < 5 ng/mL<br>(less than<br>-50%<br>cutoff) | 5 – 9 ng/mL<br>(between -<br>50% cutoff<br>and cutoff) | 10 - 15 ng/mL<br>(between<br>cutoff and<br>+50% cutoff) | > 15 ng/mL<br>(greater<br>than +50%<br>cutoff) | Agreement<br>(%) |
| Qual. | Positive | 0 | 0 | 5 | 35 | 100% (40/40) |
| | Negative | 36 | 4 | 0 | 0 | 100% (40/40) |
| Semi-<br>Quant. | Positive | 0 | 0 | 5 | 35 | 100% (40/40) |
| | Negative | 36 | 4 | 0 | 0 | 100% (40/40) |
# H. CONCLUSION
The information provided in this pre-market notification demonstrates that the Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay and Immunalysis Quantisal II Oral Fluid Collection Device are substantially equivalent to the legally marketed predicate device for their intended uses.
