(141 days)
The Atellica™ CH Phencyclidine (Pcp) assay is for in vitro diagnostic use in the qualitative or semiquantitative analyses of phencyclidine in human urine using the Atellica CH Analyzer, using a cutoff of 25 ng/mL. The Pcp assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (OC/MS) is the preferred confirmatory method. 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 Spectrometty (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
The Atellica CH Pcp assay is a homogenous enzyme immunoassay based on competition between drug in the specimen and drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. G6PDH activity decreases upon binding to the antibody, so the drug concentration in the specimen can be measured in terms of enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD+) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically at 340/410 nm.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance |
|---|---|---|
| Precision/Cutoff Characterization (Qualitative) | - At -100%, -75%, -50%, -25% of cutoff (0, 6.25, 12.5, 18.75 ng/mL): 100% Negative results (80/80 replicates).- At +25%, +50%, +75%, +100% of cutoff (31.25, 37.5, 43.75, 50 ng/mL): 100% Positive results (80/80 replicates).- At Cutoff (25 ng/mL): Expected to show a mix of positive and negative results, demonstrating it acts as a boundary. | Qualitative Analysis (25 ng/mL cutoff):- 0 ng/mL: 80 Negative- 6.25 ng/mL: 80 Negative- 12.5 ng/mL: 80 Negative- 18.75 ng/mL: 80 Negative- 25 ng/mL (Cutoff): 60 Positive / 20 Negative- 31.25 ng/mL: 80 Positive- 37.5 ng/mL: 80 Positive- 43.75 ng/mL: 80 Positive- 50 ng/mL: 80 Positive Interpretation: The device meets the criteria by exhibiting clear negative results below the cutoff, clear positive results above the cutoff, and a mixed result at the cutoff, confirming its function as a boundary. |
| Precision/Cutoff Characterization (Semi-Quantitative) | - Demonstrates consistent mean values and acceptable repeatability (SD, CV%) across concentrations.- Accurately distinguishes negative and positive samples around the cutoff. | Semi-quantitative Analysis (25 ng/mL cutoff):- 0 ng/mL: Mean 0 ng/mL, 80 Negative- 6.25 ng/mL: Mean 7 ng/mL, CV 3.8% (Repeatability), CV 7.7% (Within-Lab), 80 Negative- 12.5 ng/mL: Mean 12 ng/mL, CV 2.2% (Repeatability), CV 4.0% (Within-Lab), 80 Negative- 18.75 ng/mL: Mean 18 ng/mL, CV 1.8% (Repeatability), CV 3.3% (Within-Lab), 80 Negative- 25 ng/mL (Cutoff): Mean 25 ng/mL, CV 1.6% (Repeatability), CV 3.4% (Within-Lab), 60 Positive / 20 Negative- 31.25 ng/mL: Mean 30 ng/mL, CV 2.2% (Repeatability), CV 2.7% (Within-Lab), 80 Positive- 37.5 ng/mL: Mean 37 ng/mL, CV 1.4% (Repeatability), CV 3.3% (Within-Lab), 80 Positive- 43.75 ng/mL: Mean 43 ng/mL, CV 1.5% (Repeatability), CV 4.6% (Within-Lab), 80 Positive- 50 ng/mL: Mean 51 ng/mL, CV 1.3% (Repeatability), CV 4.5% (Within-Lab), 80 Positive Interpretation: The device shows good semi-quantitative precision with low CVs and correct qualitative interpretation based on its quantitative output. |
| Recovery Study | - Expected % Recovery close to 100% for various spiked Pcp concentrations. | Recovery Study:- Samples spiked from 4.0 to 80.0 ng/mL. % Recovery ranged from 98.5% to 112.0%. Interpretation: The device demonstrates good analytical recovery of Pcp across a range of concentrations. |
| Method Comparison (Qualitative) | - High agreement (sensitivity and specificity) when compared to the reference method (GC/MS). | Summary of Qualitative Results (compared to GC/MS):- Atellica Positive / GC/MS Positive: 53- Atellica Negative / GC/MS Positive: 3 (False Negatives)- Atellica Positive / GC/MS Negative: 1 (False Positive)- Atellica Negative / GC/MS Negative: 55Qualitative Assay Performance for 25 ng/mL cutoff (compared to GC/MS):- Atellica Pos: 98% Agreement (for samples <13 ng/mL, 13-24 ng/mL, 25-38 ng/mL, >38 ng/mL)- Atellica Neg: 95% Agreement (for samples <13 ng/mL, 13-24 ng/mL, 25-38 ng/mL, >38 ng/mL) Interpretation: The device shows high agreement with the GC/MS reference method, indicating good performance in distinguishing positive and negative samples. |
| Method Comparison (Semi-Quantitative) | - High agreement (sensitivity and specificity) when compared to the reference method (GC/MS). | Summary of Semi-Quantitative Results (compared to GC/MS):- Atellica Positive / GC/MS Positive: 53- Atellica Negative / GC/MS Positive: 3 (False Negatives)- Atellica Positive / GC/MS Negative: 1 (False Positive)- Atellica Negative / GC/MS Negative: 55Semi-Quantitative Assay Performance for 25 ng/mL cutoff (compared to GC/MS):- Atellica Pos: 98% Agreement- Atellica Neg: 95% Agreement Interpretation: Similar high agreement as the qualitative assessment for the semi-quantitative mode. |
| Interference (pH, Specific Gravity, Endogenous Compounds, Unrelated Compounds) | - No false positive or false negative results within specified ranges/concentrations for various interfering substances. | Effect of pH: No interference observed across pH 3.1-11.0 for samples at -25% and +25% of cutoff.Effect of Specific Gravity: No interference observed across SG 1.000-1.030 for samples at -25% and +25% of cutoff.Effect of Endogenous Compounds: No false response for compounds like Acetone, Ascorbic Acid, Bilirubin, Creatinine, Ethanol, etc., at stated concentrations for samples at -25% and +25% of cutoff.Effect of Structurally Unrelated Compounds: No false response for numerous drugs (e.g., Acetaminophen, Amitriptyline, Caffeine, Ibuprofen, etc.) at high concentrations for samples at -25% and +25% of cutoff.Boric Acid: Noted as causing a "false negative result," with the package insert notifying users of this limitation. Interpretation: The device generally demonstrates good resistance to common interferences, except for Boric Acid, which is acknowledged as a limitation. |
| Cross-Reactivity (Structurally Similar Compounds) | - Quantified cross-reactivity for structurally similar compounds. The specific acceptance criteria for these percentages are not explicitly stated as pass/fail, but rather as performance characteristics to be reported. | Summary of Cross-reactivity: Various compounds showed cross-reactivity ranging from 0.01% (e.g., Diphenhydramine, Doxepin) to 74.38% (trans-4-phenyl-4-Piperidinocyclohexanol), with 4-Methoxyphencyclidine at 8.43%, 1-(1-Phenylcyclohexyl)pyrrolidine (PCPy) at 38.33% and 1-[1-(2-Thienyl)-cyclohexyl]piperidine (TCP) at 58.11%. Interpretation: The device shows varying degrees of cross-reactivity with structurally similar compounds, which is expected for immunoassay methods. The specific values are provided for user information. |
Study Details:
-
Sample size used for the test set and the data provenance:
- Precision/Cutoff Characterization: 80 replicates were used for each of the 9 concentration levels tested (a total of 720 measurements). The provenance is not explicitly stated but is implied to be laboratory-prepared urine pools.
- Recovery Study: 10 samples with varying spiked Pcp concentrations were tested. Provenance is laboratory-prepared drug-free urine spiked with Pcp.
- Method Comparison: Clinical urine samples were used. The document mentions "Anonymous, discarded clinical urine samples" and refers to "native urine samples." The exact number of clinical samples is not specified numerically, but the contingency tables show totals of 112 for both qualitative and semi-quantitative analysis against GC/MS (53+1+3+55).
- Interference Studies:
- pH, Specific Gravity, Endogenous, Unrelated Compounds: Samples spiked at -25% and +25% of the cutoff were used. The number of samples for each interferent is not specified, but typically this involves replicates. The provenance is laboratory-prepared drug-free urine containing target analytes and spiked interferents.
- Cross-reactivity: Structurally similar compounds were spiked into drug-free urine at indicated levels. The number of samples is not specified. Provenance is laboratory-prepared urine.
- Data Provenance: The device performance studies appear to be laboratory-based ("clinical urine samples," "drug-free urine pool," "spiked... stock"). There is no mention of country of origin, but given the FDA submission, it's likely US-based or following international standards accepted by the FDA. The nature of the samples ("discarded clinical urine samples," "spiked") indicates a retrospective approach to sample collection for the method comparison, while the other studies are prospective in design (laboratory testing).
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- For the Method Comparison study, the ground truth was established by Gas Chromatography/Mass Spectrometry (GC/MS), which is stated as the "preferred confirmatory method." GC/MS is an objective analytical method; therefore, human experts are not directly involved in establishing the truth for individual samples in the same way they would for image interpretation. The expertise lies in operating and interpreting GC/MS data, but the "ground truth" itself is the chemical analysis result.
- For other studies (Precision, Recovery, Interference), the ground truth is based on the known concentrations of Pcp in the spiked or prepared samples.
-
Adjudication method for the test set:
- No adjudication method (e.g., 2+1, 3+1) is mentioned as the ground truth for the method comparison was established by GC/MS, a definitive chemical analysis.
-
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- This is an in vitro diagnostic (IVD) device for chemical analysis (enzyme immunoassay for Phencyclidine in urine). Therefore, no MRMC comparative effectiveness study was done as it's not applicable for this type of device. There are no human "readers" or "AI assistance" in the context of interpreting results. The device performs the test and provides a result.
-
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is effectively a standalone device performance study. The Atellica CH Phencyclidine (Pcp) assay operates as an automated system (Atellica CH Analyzer) without human intervention in the analytical process itself. The performance data presented (precision, recovery, method comparison, interference, cross-reactivity) are all based on the algorithm/instrument's output alone. While human technicians operate the analyzer, the decision-making for a result (positive/negative) is driven by the instrument's measurement against the defined cutoff of 25 ng/mL.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The primary ground truth for the Method Comparison study was Gas Chromatography/Mass Spectrometry (GC/MS) results, which is a definitive analytical method for phencyclidine.
- For Precision, Recovery, Interference, and Cross-reactivity studies, the ground truth was based on known, prepared concentrations of phencyclidine or interfering substances in urine samples.
-
The sample size for the training set:
- The document describes performance testing data for the Atellica CH Phencyclidine (Pcp) assay. It does not mention a "training set" in the context of an AI/machine learning model. This is an immunoassay, which is a chemical reaction-based test, not a software algorithm that undergoes training. Therefore, N/A for a training set in the AI sense.
-
How the ground truth for the training set was established:
- As this is not an AI/machine learning device, the concept of a "training set" and its associated ground truth establishment is not applicable. The device's performance is based on its fixed chemical assay design.
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Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter of the circle. In the center of the circle are three stylized human profiles facing to the right, stacked on top of each other.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
April 6, 2017
SIEMENS HEALTHCARE DIAGNOSTICS, INC. LAURA J. DUGGAN, Ph.D., RAC REGULATORY TECHNICAL SPECIALIST 500 GBC DRIVE, PO BOX 6101 MS 514 NEWARK DE 19711
Re: K163220
Trade/Device Name: Atellica CH Phencvclidine (Pcp) Regulation Number: Unclassified Regulation Name: Enzyme Immunoassay. Phencyclidine Regulatory Class: Unclassified, 510(k) required Product Code: LCM Dated: February 14, 2017 Received: February 15, 2017
Dear Dr. Laura Duggan:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Courtney H. Lias -S
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known)
Device Name Atellica CH Phencyclidine (Pcp)
Indications for Use (Describe)
The Atellica™ CH Phencyclidine (Pcp) assay is for in vitro diagnostic use in the qualitative or semiquantitative analyses of phencyclidine in human urine using the Atellica CH Analyzer, using a cutoff of 25 ng/mL. The Pcp assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (OC/MS) is the preferred confirmatory method. 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 Spectrometty (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ------------------------------------------------- | -- |
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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10. 510(K) SUMMARY
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.
ASSIGNED 510(K) NUMBER
The assigned 510(k) number is K163220.
APPLICANT AND DATE
Laura J. Duggan, Ph. D., RAC Siemens Healthcare Diagnostics Inc. 500 GBC Drive, M/S 514 Newark, DE 19714-6101 Email: laura.j.duggan@siemens.com Phone: 302-631-7654 Fax: 302-631-6299
March 10, 2017
MANUFACTURER
Siemens Healthcare Diagnostics Inc. 511 Benedict Ave Tarrytown, NY 10591 Registration Number: 2432235
REGULATORY INFORMATION
Requlatory Submission for the Atellica™ CH Phencyclidine (Pcp)
| Common Name: | enzyme immunoassay,phencyclidine |
|---|---|
| Proprietary Name: | Atellica CH Phencyclidine (Pcp) |
| Classification Name: | Enzyme Immunoassay,Phencyclidine |
| Regulation Number: | Unclassified |
| Classification: | Unclassified, 510(k) required |
| Product Code: | LCM |
| Panel: | Toxicology |
| Predicate Device: | URINE PHENCYCLIDINE (PCP)SCREEN FLEX REAGENTCARTRIDGE (K000462) |
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ATELLICA CH PHENCYCLIDINE (PCP)
The Atellica CH Pcp assay is a homogenous enzyme immunoassay based on competition between drug in the specimen and drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. G6PDH activity decreases upon binding to the antibody, so the drug concentration in the specimen can be measured in terms of enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD+) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an
absorbance change that is measured spectrophotometrically at 340/410 nm.
Image /page/4/Figure/3 description: The image shows two reaction equations. The first equation shows Ab + PCP + PCP-G6PDH reacting to form Ab-PCP + Ab-PCP-G6PDH (inhibited) + PCP-G6PDH (active). The second equation shows Glucose-6-Phosphate + NAD+ reacting with PCP-G6PDH (active) to form 6-phosphogluconolactone + NADH + H+ (340/410 nm). The image also defines Ab as an antibody reactive to phencyclidine, PCP as phencyclidine, and PCP-G6PDH as phencyclidine conjugated to recombinant glucose-6-phosphate dehydrogenase.
Urine is the only specimen type. The reagent is stored unopened at 2 - 8 °C and is stable for use on system for 30 days. Calibration is performed every 60 days for a reagent lot or every 19 days for an individual pack.
INTENDED USE/INDICATIONS FOR USE
ATELLICA CH PHENCYCLIDINE (PCP)
The Atellica™ CH Phencyclidine (Pcp) assay is for in vitro diagnostic use in the qualitative or semiquantitative analyses of phencyclidine in human urine using the Atellica CH Analyzer, using a cutoff of 25 ng/mL. The Pcp assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. 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. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result. particularly when preliminary positive results are used.
COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
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Below is a features comparison for the Atellica CH Phencyclidine (Pcp) assay and the predicate device:
| Feature | Predicate Device:URINE PHENCYCLIDINE(PCP) SCREEN FLEXREAGENT CARTRIDGE(K000462) | New Device:Atellica CH Phencyclidine (Pcp) |
|---|---|---|
| Intended Use : | The Urine PhencyclidineScreen Flex® reagentcartridge used on theDimension®clinical chemistry systemprovides reagents for an invitro diagnostic test intendedfor the qualitative and semi-quantitative determination ofphencyclidine in humanurine. Measurementsobtained with the PCPmethod are used in thediagnosis and treatment ofphencyclidine use oroverdose. The PCP methodprovides only a preliminaryanalytical test result. A morespecific alternate chemicalmethod must be used inorder to obtain a confirmedanalytical result. Gaschromatography/massspectrometry (GC/MS) is thepreferred confirmatorymethod. Other chemicalconfirmation methods areavailable. Clinicalconsideration andprofessional judgmentshould be applied to anydrug of abuse test result,particularly when preliminarypositive results are used. | The Atellica™ CHPhencyclidine (Pcp) assay isfor in vitro diagnostic use inthe qualitative orsemiquantitative analyses ofphencyclidine in human urineusing the Atellica™ CHAnalyzer. The Pcp assayprovides only a preliminaryanalytical test result. A morespecific alternative chemicalmethod must be usedto obtain a confirmedanalytical result. The semi-quantitative mode is forpurposes of enablinglaboratories to determine anappropriate dilution of thespecimen for confirmation bya confirmatory method suchas Gas Chromatography/Mass Spectrometry (GC-MS)or Liquid Chromatography/Tandem Mass Spectrometry(LCMS/MS) or permittinglaboratories to establishquality control procedures.Clinical consideration andprofessional judgment shouldbe applied to any drug-of-abuse test result, particularlywhen preliminary positiveresults are used. |
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| Type of Product: | Analytical Reagents | Same |
|---|---|---|
| Measured Analyte: | PCP | Same |
| Test Matrix: | Urine | Same |
| Device Technology: | Enzyme Immunoassay | Same |
| Materials: | Matched lots of polyclonal antibody reactive to phencyclidine and phencyclidine labeled with glucose-6-phosphate dehydrogenase are used in this Syva® Emit® II Plus methodology. | Same |
| Cutoff Levels: | 25 ng/mL PCP | Same |
| Confirmatory Method: | Gas Chromatography/mass spectrometry | Same |
| Calibration Frequency: | 30 days | 60 days |
SUMMARY OF PERFORMANCE TESTING
Assay performance comparison results for the Atellica CH Phencyclidine (Pcp) were obtained by processing the appropriate body fluids. Summary statistics for each are provided. These data demonstrate substantial equivalency of the Atellica CH Phencyclidine (Pcp) compared to the predicate device. The following data represent typical assay performance.
PRECISION/CUTOFF CHARACTERIZATION
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Precision was determined according to the CLSI Document EP05-A3. The study was performed for 20 days, 2 runs per day with 2 replicates (N=80) on concentrations of ±25%, ±50%, ±75% and ±100% of the cutoff. The study verified that the cutoff serves as a boundary between a negative and positive interpretation of a qualitative result.
- a) The following is summary table of the Qualitative Analysis for the 25 ng/mL cutoff test data results.
| Qualitative Analysis (25 ng/mL cutoff) | |||||
|---|---|---|---|---|---|
| [Urine Pool] (ng/mL) | % of Cutoff | # of Results | Result | ||
| 0 | -100 | 80 Negative80 | |||
| 6.25 | -75 | 80 | 80 Negative | ||
| 12.5 | -50 | 80 | 80 Negative | ||
| 18.75 | -25 | 80 | 80 Negative | ||
| 25 | Cutoff | 80 | 60 Positive / 20 Negative | ||
| 31.25 | 25 | 80 | 80 Positive | ||
| 37.5 | 50 | 80 | 80 Positive | ||
| 43.75 | 75 | 80 | 80 Positive | ||
| 50 | 100 | 8080 Positive |
- b) The following is summary table of the semi-quantitative analysis for the 25 ng/mL cutoff test data results.
| Semi-quantitative Analysis (25 ng/mL cutoff) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Urine Pool (ng/mL) | % of Cutoff | # of Results | Mean (ng/mL) | Repeatability | Within-Lab | Repeatability Results | Within-Laboratory Results | ||
| SD (ng/mL) | CV (%) | SD (ng/mL) | CV (%) | ||||||
| 0 | -100 | 80 | 0 | 0 | N/A | 1 | N/A | 80 Negative | 80 Negative |
| 6.25 | -75 | 80 | 7 | 0 | 3.8 | 1 | 7.7 | 80 Negative | 80 Negative |
| 12.5 | -50 | 80 | 12 | 0 | 2.2 | 0 | 4.0 | 80 Negative | 80 Negative |
| 18.75 | -25 | 80 | 18 | 0 | 1.8 | 1 | 3.3 | 80 Negative | 80 Negative |
| 25 | Cutoff | 80 | 25 | 0 | 1.6 | 1 | 3.4 | 60 Positive / 20 Negative | 60 Positive / 20 Negative |
| 31.25 | 25 | 80 | 30 | 1 | 2.2 | 1 | 2.7 | 80 Positive | 80 Positive |
| 37.5 | 50 | 80 | 37 | 1 | 1.4 | 1 | 3.3 | 80 Positive | 80 Positive |
| 43.75 | 75 | 80 | 43 | 1 | 1.5 | 2 | 4.6 | 80 Positive | 80 Positive |
| 50 | 100 | 80 | 51 | 1 | 1.3 | 2 | 4.5 | 80 Positive | 80 Positive |
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RECOVERY STUDY
A drug free urine pool was spiked with high concentration PCP analyte stock to various target values.
| Sample ID | Spiked Pcp (ng/mL) | Mean Pcp (ng/mL) | % Recovery |
|---|---|---|---|
| 1 | 4.0 | 4.3 | 107.5 |
| 2 | 5.0 | 5.6 | 112.0 |
| 3 | 10.0 | 10.1 | 101.0 |
| 4 | 15.0 | 15.0 | 100.0 |
| 5 | 20.0 | 19.7 | 98.5 |
| 6 | 25.0 | 25.1 | 100.4 |
| 7 | 30.0 | 30.0 | 100.0 |
| 8 | 40.0 | 41.0 | 102.5 |
| 9 | 60.0 | 60.9 | 101.5 |
| 10 | 80.0 | 83.7 | 104.6 |
METHOD COMPARISON
Anonymous, discarded clinical urine samples were analyzed with the test device. Method Comparison was tested by comparison to the reference method, which is GC/ MS. Six samples were prepared by pooling two native urine samples to span the assay measuring interval. All of the remaining samples were unaltered native samples.
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a) Summary of Qualitative Results
| GC/MS | |||
|---|---|---|---|
| (+) | (+) | (-) | |
| (+) | 53 | 1 | |
| Atellica | (-) | 3 | 55 |
b) Summary of the Qualitative Assay Performance for the 25 ng/mL cutoff
| GC/MS Results | |||||
|---|---|---|---|---|---|
| Atellica | Neg (< 13 ng/mL) | Neg Within 50% below the cutoff (13 - 24 ng/mL) | Pos Within 50% above the cutoff (25 - 38 ng/mL) | Pos (> 38 ng/mL) | % Agreement |
| Qualitative | |||||
| Atellica Pos | 0 | 1 | 17 | 36 | 98% |
| Atellica Neg | 48 | 7 | 3 | 0 | 95% |
c) Summary of Semi-Quantitative Results
| GC/MS | |||
|---|---|---|---|
| (+) | (-) | ||
| (+) | 53 | 1 | |
| Atellica | (-) | 3 | 55 |
d) Summary of the Semi-Quantitative Assay Performance for the 25 ng/mL cutoff
· . .
| GC/MS Results | |||||||
|---|---|---|---|---|---|---|---|
| Atellica | Neg (< 13 ng/mL) | Neg Within 50% below the cutoff (13 - 24 ng/mL) | Pos Within 50% above the cutoff (25 - 38 ng/mL) | Pos (> 38 ng/mL) | % Agreement | ||
| Semi-Quantitative | |||||||
| Atellica Pos | 0 | 1 | 17 | 36 | 98% | ||
| Atellica Neg | 48 | 7 | 3 | 0 | 95% |
- e) Summary of Discordant Results
| Sample ID | Atellica CH (ng/mL) | GC/MS (ng/mL) | Atellica CH vs. GC/MS (POS/NEG) |
|---|---|---|---|
| 53 | 25 | 23.7 | +/- |
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| 57 | 23 | 25.3 | -/+ |
|---|---|---|---|
| 59 | 23 | 28.2 | -/+ |
| 61 | 22 | 30.0 | -/+ |
| INTERFERENCES |
Interference was determined in accordance with CLSI Document EP07-A2. Structurally non-similar compounds, endogenous compounds, the effect of pH, the effect of specific gravity and boric acid were evaluated by spiking the potential interferent into drug free urine containing the target analyte at ±25% of the cutoff. All potential interferents analyzed verified that the assay performance is unaffected by externally ingested compounds or an internally existing physiological conditions. Any test compound that was shown to produce a false response at the test concentration optionally underwent does-response testing until a false response was not obtained.
| pH Value | -25% Cutoff (19 ng/mL) | +25% Cutoff (31 ng/mL) | ||
|---|---|---|---|---|
| Result | Intereference? | Result | Intereference? | |
| 3.1 | Negative | No | Positive | No |
| 4.0 | Negative | No | Positive | No |
| 5.0 | Negative | No | Positive | No |
| 6.0 | Negative | No | Positive | No |
| 7.0 | Negative | No | Positive | No |
| 8.0 | Negative | No | Positive | No |
| 9.0 | Negative | No | Positive | No |
| 10.1 | Negative | No | Positive | No |
| 11.0 | Negative | No | Positive | No |
a) Summary of the Effect of pH
{11}------------------------------------------------
- b) Summary of the Effect of Specific Gravity
| ടG | -25% CutoffPool Result(19 ng/mL) | Intereference? | +25% CutoffPool Result(31 ng/mL) | Intereference? |
|---|---|---|---|---|
| 1.000 | Negative | No | Positive | No |
| 1.002 | Negative | No | Positive | No |
| 1.005 | Negative | No | Positive | No |
| 1.010 | Negative | No | Positive | No |
| 1.015 | Negative | No | Positive | No |
| 1.020 | Negative | No | Positive | No |
| 1.025 | Negative | No | Positive | No |
| 1.030 | Negative | No | Positive | No |
- c) Summary of the Effect of Endogenous Compounds
At the stated concentration, the sample did not give a false response relative to the 25 ng/mL cutoff.
| Compound | ConcentrationTested | -25% ofCutoff(19 ng/mL) | +25% ofCutoff(31 ng/mL) |
|---|---|---|---|
| Acetone | 1.0 g/dL | Negative | Positive |
| Ascorbic Acid | 0.75 g/dL | Negative | Positive |
| Conjugatedbilirubin | 0.25 mg/dL | Negative | Positive |
| Creatinine | 0.5 g/dL | Negative | Positive |
| Ethanol | 1.0 g/dL | Negative | Positive |
| Gamma Globulin | 0.5 g/dL | Negative | Positive |
| Galactose | 0.01 g/dL | Negative | Positive |
| Glucose | 2.0 g/dL | Negative | Positive |
| Hemoglobin | 115 mg/dL | Negative | Positive |
| Human SerumAlbumin | 0.5 g/dL | Negative | Positive |
| Oxalic Acid | 0.1 g/dL | Negative | Positive |
| Riboflavin | 7.5 mg/dL | Negative | Positive |
| Sodium Azide | 1% (w/v) | Negative | Positive |
| Sodium Chloride | 1.5 g/dL | Negative | Positive |
| Sodium Fluoride | 1% (w/v) | Negative | Positive |
| Urea | 6.0 g/dL | Negative | Positive |
| Concentration Tested | -25% of Cutoff | +25% of Cutoff | |
| Compound | (ng/mL) | (19 ng/mL) | (31 ng/mL) |
| Acetaminophen | 500,000 | Negative | Positive |
| I-a-Acetylmethadol (LAAM) | 25,000 | Negative | Positive |
| N-Acetyl procainamide(NAPA) | 100,000 | Negative | Positive |
| Acetylsalicylic Acid | 500,000 | Negative | Positive |
| Amitriptyline | 8,750 | Negative | Positive |
| S-(+)-Amphetamine | 100,000 | Negative | Positive |
| Benzoylecgonine | 100,000 | Negative | Positive |
| Buprenorphine | 100,000 | Negative | Positive |
| Caffeine | 500,000 | Negative | Positive |
| Cannabinol | 100,000 | Negative | Positive |
| Carbamazepine | 100,000 | Negative | Positive |
| Chlordiazepoxide | 100,000 | Negative | Positive |
| Cimetidine | 100,000 | Negative | Positive |
| Clonidine | 100,000 | Negative | Positive |
| Codeine | 25,000 | Negative | Positive |
| Cotinine | 100,000 | Negative | Positive |
| Desipramine | 75,000 | Negative | Positive |
| Dextrorphan | 781 | Negative | Positive |
| Diazepam | 100,000 | Negative | Positive |
| Digoxin | 100,000 | Negative | Positive |
| 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine(EDDP) | 12,500 | Negative | Positive |
| EMDP | 100,000 | Negative | Positive |
| 1R,2S-Ephedrine | 100,000 | Negative | Positive |
| 1S,2R-Ephedrine | 100,000 | Negative | Positive |
| Fluoxetine | 75,000 | Negative | Positive |
| Flurazepam | 50,000 | Negative | Positive |
| Glutethimide | 100,000 | Negative | Positive |
| Haloperidol | 100,000 | Negative | Positive |
| Heroin | 25,000 | Negative | Positive |
| Hydrocodone | 25,000 | Negative | Positive |
| Ibuprofen | 500,000 | Negative | Positive |
| Ketamine | 75,000 | Negative | Positive |
| Ketorolac Tromethamine | 100,000 | Negative | Positive |
| Lidocaine | 100,000 | Negative | Positive |
| Lorazepam | 100,000 | Negative | Positive |
| Lormetazepam | 100,000 | Negative | Positive |
| LSD | 100,000 | Negative | Positive |
| MDMA | 100,000 | Negative | Positive |
| Meperidine | 1,563 | Negative | Positive |
| Methadone | 50,000 | Negative | Positive |
| Compound | Concentration Tested(ng/mL) | -25% of Cutoff(19 ng/mL) | +25% of Cutoff(31 ng/mL) |
| S(+) - Methamphetamine | 100,000 | Negative | Positive |
| Methaqualone | 100,000 | Negative | Positive |
| Morphine | 75,000 | Negative | Positive |
| Naproxen | 100,000 | Negative | Positive |
| Nordiazepam | 100,000 | Negative | Positive |
| Nortriptyline | 75,000 | Negative | Positive |
| Oxazepam | 100,000 | Negative | Positive |
| Oxycodone | 100,000 | Negative | Positive |
| Phenobarbital | 100,000 | Negative | Positive |
| Phenylephrine | 100,000 | Negative | Positive |
| Phenytoin | 100,000 | Negative | Positive |
| Promethazine | 3,125 | Negative | Positive |
| Propoxyphene | 100,000 | Negative | Positive |
| Propranolol | 100,000 | Negative | Positive |
| Protriptyline | 75,000 | Negative | Positive |
| R,R - Pseudoephedrine | 100,000 | Negative | Positive |
| S,S - Pseudoephedrine | 100,000 | Negative | Positive |
| Ranitidine | 100,000 | Negative | Positive |
| Ritalinic Acid | 100,000 | Negative | Positive |
| Salicylic Acid | 100,000 | Negative | Positive |
| Scopolamine | 100,000 | Negative | Positive |
| Secobarbital | 100,000 | Negative | Positive |
| Tapentadol | 50,000 | Negative | Positive |
| 11-nor-A9-THC-9-COOH | 100,000 | Negative | Positive |
| Tramadol | 50,000 | Negative | Positive |
| Trazodone | 100,000 | Negative | Positive |
| Tyramine | 100,000 | Negative | Positive |
| Verapamil | 60,000 | Negative | Positive |
| Zidovudine (AZT) | 100,000 | Negative | Positive |
| Zolpidem | 100,000 | Negative | Positive |
{12}------------------------------------------------
- d) Summary of the Effect of Structurally Unrelated Compounds
At the stated concentration, the sample did not give a false response relative to the 25 ng/mL cutoff.
{13}------------------------------------------------
Boric acid results in a false negative result. The package insert notifies the user of this limitation.
______________________________________________________________________________________________________________________________________________________________________________
Specificity was determined in accordance with CLSI Document EP07-A2. Structurally similar compounds were spiked into drug free urine at the levels indicated. Crossreactivity was calculated.
Summary of Cross-reactivity:
{14}------------------------------------------------
| Test Compound | ConcentrationTested(ng/mL) | Cross-Reactivity(%) |
|---|---|---|
| Chloropromazine | 100000 | 0.02 |
| Clomipramine | 100000 | 0.02 |
| Cyclobenzaprine | 25000 | 0.03 |
| Dextromethorphan | 80000 | 0.02 |
| Diphenhydramine | 100000 | 0.01 |
| Doxepin | 90000 | 0.01 |
| Imipramine | 100000 | 0.01 |
| Methoxetamine | 36000 | 0.03 |
| 4-Methoxyphencyclidine | 700 | 8.43 |
| Thioridazine | 100000 | 0.04 |
| Venlafaxine | 100000 | 0.01 |
| 1-(4-Hydroxypiperidino)phenylcyclohexane | 419 | 5.97 |
| 1-(1-Phenylcyclohexyl)pyrrolidine(PCPy) | 54 | 38.33 |
| 1-[1-(2-Thienyl)-cyclohexyl]piperidine(TCP) | 37 | 58.11 |
| trans-4-phenyl-4-Piperidinocyclohexanol | 32 | 74.38 |
CONCLUSION
The Atellica CH Phencyclidine (Pcp) is substantially equivalent to the Urine Phencyclidine Screen Flex® reagent cartridge used on the Dimension clinical chemistry system in principle and performance based on the similarity of device designs and function demonstrated through method comparison and other performance attributes.
N/A