THERMO SCIENTIFIC CEDIA PHENCYCLIDINE (PCP) OFT ASSAY
Device Facts
| Record ID | K101746 |
|---|---|
| Device Name | THERMO SCIENTIFIC CEDIA PHENCYCLIDINE (PCP) OFT ASSAY |
| Applicant | Microgenics Corp. |
| Product Code | LCM · CH |
| Decision Date | Apr 8, 2011 |
| Decision | SESE |
| Submission Type | Traditional |
| Device Class | Class U |
Indications for Use
The CEDIA® Phencyclidine (PCP) OFT Assay is intended for use in the qualitative determination of phencyclidine in human oral fluid at a cutoff concentration of 3.0 ng/mL in neat oral fluid. The specimen must be collected exclusively with the Oral-Eze™ Saliva Collection System. The assay is calibrated against PCP and performed on the MGC240. This in vitro diagnostic device is intended for clinical laboratory use only. The CEDIA® PCP OFT Assay provides only a preliminary analytical test result. A more specific alternative method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS-MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result particularly when preliminary positive results are used.
Device Story
Assay detects phencyclidine (PCP) in human oral fluid; requires Oral-Eze Saliva Collection System for specimen collection. Operates on MGC240 analyzer. Homogenous enzyme immunoassay (CEDIA) uses recombinant DNA-derived beta-galactosidase fragments; analyte in sample competes with PCP-conjugated enzyme donor for antibody binding sites. Active enzyme formation produces color change proportional to analyte concentration. Used in clinical laboratories; results are preliminary and require confirmation by GC/MS or LC-MS-MS. Assists clinicians in identifying potential drug use; professional judgment required for interpretation.
Clinical Evidence
Bench testing only. Precision studies (n=50 per concentration) evaluated performance across range of -75% to +200% of cutoff. Method comparison studies (n=40 and n=81) against LC-MS/MS showed 100% agreement for both positive and negative results. Analytical specificity evaluated against structurally related compounds and common medications; no significant interference observed.
Technological Characteristics
Homogenous enzyme immunoassay (CEDIA). Reagents: lyophilized mouse monoclonal anti-PCP antibody, enzyme acceptor, enzyme donor conjugated to PCP derivative, chlorophenol red-beta-D-galactopyranoside. Instrument: MGC240 analyzer. Matrix: Oral fluid collected via Oral-Eze system (includes preservative buffer, ~1/3 dilution). Stability: 24 months at 2-8°C; 60 days on-board. Qualitative detection.
Indications for Use
Indicated for qualitative determination of phencyclidine in human oral fluid at 3.0 ng/mL cutoff. For use in clinical laboratories by professional staff. Not for point-of-care settings. Requires confirmatory testing via GC/MS or LC-MS-MS.
Predicate Devices
- STC PCP Intercept Micro-plate EIA, OTI, Orasure Technologies Inc (k000399)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k101746
B. Purpose for Submission:
New device
C. Measurand:
Phencyclidine (PCP) in oral fluid
D. Type of Test:
Qualitative enzyme immunoassay
E. Applicant:
Microgenics Corporation, Thermo Fisher Scientific Clinical Diagnostic Division
F. Proprietary and Established Names:
Thermo Scientific CEDIA® Phencyclidine (PCP) OFT Assay
G. Regulatory Information:
| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| LCM, Enzyme immunoassay Phencyclidine | II | Unclassified | 91-Toxicology |
H. Intended Use:
1. Intended use(s):
See indication for use below
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2. Indication(s) for use:
The CEDIA® Phencyclidine (PCP) OFT Assay is intended for use in the qualitative determination of phencyclidine in human oral fluid at a cutoff concentration of 3.0 ng/mL in neat oral fluid. The specimen must be collected exclusively with the Oral-Eze™ Saliva Collection System. The assay is calibrated against PCP and performed on the MGC240. This in vitro diagnostic device is intended for clinical laboratory use only.
The CEDIA® PCP OFT Assay provides only a preliminary analytical test result. A more specific alternative method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS-MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result particularly when preliminary positive results are used.
3. Special conditions for use statement(s):
This is an in vitro diagnostic device.
For prescription use
For use in the clinical laboratory
Not for use in the Point-of-Care settings
4. Special instrument requirements:
For use with the MGC240 analyzer
I. Device Description:
The assay consists of lyophilized reagent and liquid reconstitution Buffer. Reagent 1 (EA Reconstitution Buffer) contains buffer salts, mouse monoclonal anti-PCP antibody, stabilizer and preservative, Reagent 1(a) (EA Reagent) contains Ezyme Acceptor (microbial), buffer salts and preservative. Reagent 2 (ED Reconstitution Buffer) contains buffer salts, stabilizers and preservative, Reagent 2(a) (ED Reagent) contains Enzyme Donor (microbial) conjugated to PCP derivative, chlorophenol red-β-D-galactopyranoside, stabilizers, detergent and preservative.
The calibrators and controls are to be sold separately. Calibrators were cleared in k101752.
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The Oral-Eze Saliva Collection System consists of Oral-Eze saliva collector and collection tube with preservative buffer. Oral-Eze saliva collector consists of an absorbent pad attached to a plastic handle. The saliva collector is provided with a volume adequacy indicator. The plastic handle has a round window where blue color will appear when sufficient volume of oral fluid is collected. Samples are collected by placing the collector pad and plastic shield between lower cheek and gum with the plastic shield facing the cheek. Oral fluid collection is done when blue color appears in the window of the handle. The pad is ejected in to the collection tube by placing thumb on the ridges on the handle and pushing the thumb forward. The collection tube is capped and sent to the laboratory for processing and testing.
## J. Substantial Equivalence Information:
1. Predicate device name(s):
STC PCP Intercept Micro-plate EIA, OTI, Orasure Technologies Inc
2. Predicate 510(k) number(s):
k000399
3. Comparison with predicate:
| Similarities/Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | Qualitative detection of phencyclidine | Same |
| Assay Type | Enzyme immunoassay | Same |
| Matrix | Oral Fluid | Same |
| Cutoff | 3.0 ng/mL in Neat Oral Fluid | 1.0 ng/mL when oral fluid collected with the Oral Specimen Collection Device |
## K. Standard/Guidance Document Referenced (if applicable):
CLSI EP05-A2 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guidelines - 2nd edition
CLSI EP09-A2 Method Comparison and Bias Estimation Using Patient Samples; Approved Guidelines - 2nd edition
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L. Test Principle:
CEDIA PCP OFT Assay uses recombinant DNA technology to produce a unique homogenous enzyme immunoassay system. The assay is based on the bacterial enzyme β-galactosidase, which has been genetically engineered into two inactive fragments. Analyte in the sample competes with analyte conjugates to one inactive fragment (enzyme donor) of β-galactosidase for antibody binding site. The amount of active enzyme formed (color change) and resultant absorbance change are directly proportional to the amount of analyte present in the sample.
The Oral-Eze Saliva Collection System contains a preservative buffer that dilutes the neat oral fluid sample. The assay result is reported as a positive or negative result relative to the neat oral fluid cutoff of 3.0 ng/mL.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
All analytical performance data was collected on neat human oral fluid samples and processed through the Oral-Eze Saliva Collection System and analyzed on the MGC 240 instrument. The Oral-Eze collection device includes a diluent that results in a dilution of approximately 1/3. The assay cannot be used to measure undiluted (neat) samples. Analyte concentrations refer to the neat oral fluid concentration, unless otherwise noted.
a. Precision/Reproducibility:
Precision studies were performed by spiking a PCP solution into neat oral fluid pools at concentrations of 0, 0.8, 1.62, 1.85, 2.61, 3.2, 3.86, 4.53 and 6.29 ng/mL. Concentrations were confirmed by LC-MS/MS. Each sample was then processed through the Oral-Eze Saliva Collection System to obtain a final concentration at approximately negative, -75%, -50%, -25%, cutoff, +25% and 50%, 75% and 200% of the cutoff calibrator. Testing was performed in replicates of 5, twice a day over 5 non-consecutive days for all concentrations. Testing was performed on one lot using three instruments and three operators. The results are presented in the table below:
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| Analyte | Sample concentration | Number of Determinations | Results | |
| --- | --- | --- | --- | --- |
| | | | Neg | Pos |
| PCP | Negative | 50 | 50 | 0 |
| PCP | -75% | 50 | 50 | 0 |
| PCP | -50% | 50 | 50 | 0 |
| PCP | -25% | 50 | 50 | 0 |
| PCP | Cutoff | 50 | 2 | 48 |
| PCP | 25% | 50 | 0 | 50 |
| PCP | 50% | 50 | 0 | 50 |
| PCP | 75% | 50 | 0 | 50 |
| PCP | 200% | 50 | 0 | 50 |
b. Linearity/assay reportable range:
Not applicable, this is a qualitative assay
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Collection device:
Shipment Stability:
Conditions simulating ground shipping, air shipping and various climate conditions (desert, tropical) were tested. Oral fluid samples were spiked with PCP to concentrations of -50% of the cutoff and +50% of the cutoff. One set was stored at room temperature and used as the control, while the other set was used for testing. All samples at -50% of the cutoff recovered as negative and all samples at +50% of the cutoff recovered as positive. The shipping temperature should not exceed >40°C.
Sample Storage and Stability:
The stability of oral fluid samples in the preservative buffer was evaluated in real time. The stability protocol was reviewed and found acceptable. Oral fluid samples can be stored at 2-8°C or at room temperature (21-25°C) for 21 days.
Reagent Stability:
Real time stability testing was conducted. The stability protocol was reviewed and found acceptable. The testing supports the stability at 2-8°C for 24 months. The on board stability of reconstituted reagents is 60 days (2-8°C).
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d. Detection limit:
Analytical performance of the device around the cutoff is described in the precision section 1.a above.
e. Analytical specificity:
Cross-reactivity was evaluated by spiking various concentrations (which could be found in a neat oral fluid sample) of structurally related compounds into drug-free neat oral fluid pool, than added to the oral fluid collection device. The various concentrations were evaluated against the cutoff calibrator. The table below lists the concentration of each compound that gave a response approximately equal to the cutoff.
| Compound | Tested Concentration (ng/mL) | Response equivalent to cutoff |
| --- | --- | --- |
| N.N-Diethyl-1-phenyl-cyclohexylamine (N,N-Diethyl PCA) | 195 | Positive |
| N-Ethyl-1-phenylcyclohexylamine (PCE) | 120 | Positive |
| 1-(1-Phencyclohexyl)-morpholine (PCM) | 300 | Positive |
| 4-Phenyl-4-piperidinocyclohexanol (4-OH-PCP) | 840 | Positive |
| 1-1-Phenylcyclohexyl pyrrolidine (PHP) | 6 | Positive |
| 1-1-(2-Thienyl)-cyclohexyl piperidine (TCP) | 2.1 | Positive |
Potential interference from structurally unrelated compounds and various common over-the-counter medications were tested by spiking the potentially interfering compound into neat oral fluid, and then processed through the oral fluid collection device.
| Compound | Tested Concentration in neat Oral Fluid (ng/mL) | Response Equivalent to the cutoff |
| --- | --- | --- |
| Acetaminophen | 1,800,000 | Negative |
| Acetylsalicylic acid | 1,800,000 | Negative |
| Alprazolam | 30,000 | Negative |
| Amobarbital | 30,000 | Negative |
| Amoxicillin | 240,000 | Negative |
| Amphetamine | 240,000 | Negative |
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| Compound | Tested Concentration in neat Oral Fluid (ng/mL) | Response Equivalent to the cutoff |
| --- | --- | --- |
| Ampicillin | 30,000 | Negative |
| Atropine | 30,000 | Negative |
| Benzoylecgonine | 30,000 | Negative |
| Δ-Phenethylamine | 30,000 | Negative |
| Butabarbital | 30,000 | Negative |
| Butalbital | 30,000 | Negative |
| Caffeine | 60,000 | Negative |
| Captopril | 1,800,000 | Negative |
| Chlordiazepoxide | 240,000 | Negative |
| Chlorpromazine | 30,000 | Negative |
| Cimetidine | 600,000 | Negative |
| Clonazepam | 30,000 | Negative |
| Clorazepate | 30,000 | Negative |
| Cocaethylene | 30,000 | Negative |
| Cocaine | 30,000 | Negative |
| Codeine | 12,000 | Negative |
| Cotinine | 30,000 | Negative |
| Cyclizine | 30,000 | Negative |
| Dextromethorphan | 120,000 | Negative |
| Diacetylmorphine | 30,000 | Negative |
| Diazepam | 60,000 | Negative |
| Digoxin | 120,000 | Negative |
| Diphenhydramine | 120,000 | Negative |
| Enalapril | 600,000 | Negative |
| Fluoxetine | 600,000 | Negative |
| Gentisic acid | 30,000 | Negative |
| Hydrocodone | 30,000 | Negative |
| Hydromorphone | 30,000 | Negative |
| Ibuprofen | 600,000 | Negative |
| Imipramine | 30,000 | Negative |
| l-Ephedrine | 30,000 | Negative |
| Levothyroxine | 600,000 | Negative |
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| Compound | Tested Concentration in neat Oral Fluid (ng/mL) | Response Equivalent to the cutoff |
| --- | --- | --- |
| Lidocaine | 30,000 | Negative |
| Loperamide | 30,000 | Negative |
| Medazepam | 30,000 | Negative |
| Meperidine | 30,000 | Negative |
| Methadone | 120,000 | Negative |
| Methamphetamine | 240,000 | Negative |
| Metoprolol | 30,000 | Negative |
| Morphine | 120,000 | Negative |
| Naproxen | 30,000 | Negative |
| Niacinamide | 30,000 | Negative |
| Nicotine | 30,000 | Negative |
| Nifedipine | 3,000,000 | Negative |
| Norchlordiazepoxide | 30,000 | Negative |
| Nordiazepam | 30,000 | Negative |
| Penicillin | 30,000 | Negative |
| Pentobarbital | 30,000 | Negative |
| Phenobarbital | 120,000 | Negative |
| Phenylephrine | 30,000 | Negative |
| Phenylpropanolamine | 30,000 | Negative |
| Procainamide | 30,000 | Negative |
| Procaine | 30,000 | Negative |
| Propoxyphene | 120,000 | Negative |
| Pseudoephedrine | 30,000 | Negative |
| Quinidine | 30,000 | Negative |
| Ranitidine | 600,000 | Negative |
| Salbutamol | 30,000 | Negative |
| Salicyluric Acid | 300,000 | Negative |
| Secobarbital | 240,000 | Negative |
| Temazepam | 30,000 | Negative |
| Δ⁹-THC | 30,000 | Negative |
| 11-nor-Δ⁹-THC-COOH | 15,000 | Negative |
| Theophylline | 30,000 | Negative |
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| Compound | Tested Concentration in neat Oral Fluid (ng/mL) | Response Equivalent to the cutoff |
| --- | --- | --- |
| Tolmetin | 30,000 | Negative |
| Verapamil | 600,000 | Negative |
| Zomepirac | 30,000 | Negative |
Potential interference from endogenous and exogenous substances and pH were spiked into neat oral fluid containing PCP at $+/- 50\%$ of the cutoff, and then processed through the oral fluid collection device. No interference was observed with the interfering substances and pH 5-9. The results are presented in the table below:
| Compounds | Tested Conc. in Neat Oral Fluid (ng/mL) | PCP OFT Assay | |
| --- | --- | --- | --- |
| | | -50% PCP | +50% PCP |
| Cotinine | 0.03 | Negative | Positive |
| Nicotine | 0.03 | Negative | Positive |
| Hemoglobin | 0.6 | Negative | Positive |
| Human serum albumin | 24 | Negative | Positive |
| Sodium Chloride | 18 | Negative | Positive |
| Cholesterol | 45 | Negative | Positive |
| Acetaminophen | 0.3 | Negative | Positive |
| Acetylsalicylic Acid | 0.3 | Negative | Positive |
| Caffeine | 0.3 | Negative | Positive |
| Ibuprofen | 0.3 | Negative | Positive |
| Coffee | 6% v/v | Negative | Positive |
| Milk | 6% v/v | Negative | Positive |
| Orange Juice | 6% v/v | Negative | Positive |
| Cranberry Juice | 6% v/v | Negative | Positive |
| Soft drink (Coke) | 6% v/v | Negative | Positive |
| Toothpaste | 6% v/v | Negative | Positive |
| Mouthwash | 6% v/v | Negative | Positive |
| Tea | 6% v/v | Negative | Positive |
| | | -50% PCP | +50% PCP |
| Denture Adhesive | 6% v/v | Negative | Positive |
| Alcohol | 6% v/v | Negative | Positive |
| Baking Soda | 6% v/v | Negative | Positive |
| Cough Syrup | 6% v/v | Negative | Positive |
| Whole Blood | 6% v/v | Negative | Positive |
| Hydrogen Peroxide | 6% v/v | Negative | Positive |
| pH | 5-9 | Negative | Positive |
| Sodium Chloride | 18 | Negative | Positive |
| Cholesterol | 45 | Negative | Positive |
| Acetaminophen | 0.3 | Negative | Positive |
| Acetylsalicylic Acid | 0.3 | Negative | Positive |
| Caffeine | 0.3 | Negative | Positive |
| Ibuprofen | 0.3 | Negative | Positive |
| Coffee | 6% v/v | Negative | Positive |
| Milk | 6% v/v | Negative | Positive |
| Orange Juice | 6% v/v | Negative | Positive |
| Cranberry Juice | 6% v/v | Negative | Positive |
| Soft drink (Coke) | 6% v/v | Negative | Positive |
| Toothpaste | 6% v/v | Negative | Positive |
| Mouthwash | 6% v/v | Negative | Positive |
| Tea | 6% v/v | Negative | Positive |
| | | -50% PCP | +50% PCP |
| Denture Adhesive | 6% v/v | Negative | Positive |
| Alcohol | 6% v/v | Negative | Positive |
| Baking Soda | 6% v/v | Negative | Positive |
| Cough Syrup | 6% v/v | Negative | Positive |
| Whole Blood | 6% v/v | Negative | Positive |
| Hydrogen Peroxide | 6% v/v | Negative | Positive |
| pH | 5-9 | Negative | Positive |
| Sodium Chloride | 18 | Negative | Positive |
| Cholesterol | 45 | Negative | Positive |
| Acetaminophen | 0.3 | Negative | Positive |
| Acetylsalicylic Acid | 0.3 | Negative | Positive |
| Caffeine | 0.3 | Negative | Positive |
| Ibuprofen | 0.3 | Negative | Positive |
| Coffee | 6% v/v | Negative | Positive |
| Milk | 6% v/v | Negative | Positive |
| Orange Juice | 6% v/v | Negative | Positive |
| Cranberry Juice | 6% v/v | Negative | Positive |
| Soft drink (Coke) | 6% v/v | Negative | Positive |
| Toothpaste | 6% v/v | Negative | Positive |
| Mouthwash | 6% v/v | Negative | Positive |
| Tea | 6% v/v | Negative | Positive |
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Potential interference from additional food and dental compounds was tested by collecting neat oral fluid from volunteers after use of the following substances: hard candy, chewing gum, chewing tobacco, cigarettes and tooth whitening strips.
| Compounds | Tested Concentration in Neat Oral Fluid | PCP OFT Assay Results | |
| --- | --- | --- | --- |
| | | -50% PCP | +50% PCP |
| Water | n/a | Negative | Positive |
| Chewing Tobacco | n/a | Negative | Positive |
| Cigarettes | n/a | Negative | Positive |
| Gum | n/a | Negative | Positive |
| Hard Candy | n/a | Negative | Positive |
| Tooth Whitening Strips | n/a | Negative | Positive |
f. Assay cut-off:
Characterization of how the device performs analytically around the claimed cutoff concentration appears in the precision above.
2. Comparison studies:
a. Method comparison with predicate device:
Two method comparison studies were performed.
Study 1:
40 unaltered neat oral fluid samples were collected from rehabilitation clinics. The neat oral fluid samples were processed using the Oral-Eze collection device. The diluted samples were tested in the CEDIA PCP OFT Assay and compared to the neat and diluted oral fluid samples tested by LC/MS/MS. The results reflect the performance of the entire system including the collection step.
| Candidate Device Results | Less than half the cutoff concentration by GC/MS | Near Cutoff Negative (Between 50% below the cutoff | Near Cutoff Positive (Between the cutoff and 50% | High Positive (greater than 50% above the cutoff |
| --- | --- | --- | --- | --- |
| | | between 50% and 50% | | |
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| | analysis | and the cutoff concentration) | above the cutoff concentration) | concentration) |
| --- | --- | --- | --- | --- |
| Positive | 0 | 0 | 2 | 18 |
| Negative | 18 | 2 | 0 | 0 |
% Agreement among positive and negative is 100%.
LC/MS/MS values used to categorize samples in this table are based on the concentration found in the neat oral fluid sample.
## Study 2:
A total of 81 samples (41 negative and 40 positive) were evaluated by the candidate device and GC/MS. This study was performed on samples already collected with the Oral-Eze Saliva collection device. When the GC/MS values of the diluted samples were compared to the candidate device, the following results were obtained. Therefore the results below do not reflect any inaccuracy inherent in the collection process itself.
Note: this study was performed on samples already collected with the Intercept collection device. When the LC/MS/MS values of the diluted samples were compared to the immunoassay values, the following results were obtained. Therefore the results below do not reflect any inaccuracy inherent in the collection process itself.
| Candidate Device Results | Negative | Less than half the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- | --- |
| Positive | 0 | 0 | 0 | 4 | 36 |
| Negative | 37 | 0 | 4 | 0 | 0 |
% Agreement among positives is 100% (41/41)
% Agreement among negatives is 100% (40/40)
## b. Matrix comparison:
Not applicable. The assay is intended for only one sample matrix.
## 3. Clinical studies:
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a. Clinical Sensitivity:
Not applicable
b. Clinical specificity:
Not applicable
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 Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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