(267 days)
The Pointe Scientific Cocaine Metabolite Enzyme Immunoassay is intended for the qualitative determination of benzoylecgonine (a cocaine metabolite) in human urine at a cutoff value of 150 ng/mL. Rx only.
This assay provides only a preliminary analytical test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas or Liquid Chromatograph/Mass Spectrometry (GC/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
The Cocaine Metabolite Enzyme Immunoassay consists of ready-to-use liquid reagents:
- . Reagent 1 contains a mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers and sodium azide (0.09%) as a preservative.
- Reagent 2 contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with . benzoylecgonine in buffer with sodium azide (0.09%) as a preservative.
The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, benzoylecgonine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when drug is present in the sample, antibody binds to the free drug; the unbound benzovlecgonine-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at a 340 nm primary wavelength.
The assay has a cutoff of 150 ng/mL benzoylecqonine.
Here's an analysis of the provided text to extract the acceptance criteria and study information, formatted as requested:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a numerical or categorical format for overall device performance (e.g., "sensitivity must be >X%"). Instead, it presents performance data for several metrics that implicitly represent the device's ability to perform as intended and demonstrate substantial equivalence to the predicate device.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (Mindray BS-480) | Reported Device Performance (Mindray BA-800M) |
|---|---|---|---|
| Method Comparison (Qualitative Agreement with LC/MS) | Device results should show good agreement with the LC/MS reference method. Exact thresholds not specified, but high percentages are expected for substantial equivalence. | ||
| % Agreement among positives | (Implicit: High agreement for positives) | 88.9% (40/45) | 93.3% (42/45) |
| % Agreement among negatives | (Implicit: High agreement for negatives) | 98.6% (68/69) | 98.6% (68/69) |
| Precision (Qualitative Results at Cutoff) | Low variability in qualitative results near the cutoff for both within-run and between-run testing, indicating consistent performance. | ||
| Within Run (150 ng/mL cutoff) | (Implicit: Consistent positive/negative results) | 19 Neg / 1 Pos | 7 Neg / 13 Pos |
| Between Run (150 ng/mL cutoff) | (Implicit: Consistent positive/negative results) | 68 Neg / 12 Pos | 41 Neg / 39 Pos |
| Interference (Endogenous Substances & pH/Specific Gravity) | No positive or negative interference at specified concentrations of endogenous substances, pH range, and specific gravity range. | Qualitative results identical for both analyzers (no interference observed). | Qualitative results identical for both analyzers (no interference observed). |
| Cross-Reactivity (Structurally Related Compounds) | Low percent cross-reactivity with non-benzoylecgonine cocaine-related compounds. | Cocaine: 1.52% (BA-800M), 1.62% (BS-480) | Cocaine: 1.50% (referenced) |
| Cross-Reactivity (Structurally Unrelated Pharmacological Compounds) | Negligible cross-reactivity with common pharmacological compounds. | Meperidine: 0.00% | Meperidine: 0.00% (referenced), and many others at 0.00% |
| Reference LC/MS Precision (for method comparison) | (Implicit: Good precision for the reference method to ensure reliability of comparison.) | Level 1: 5.3% CV, Level 2: 6.5% CV, Level 3: 5.3% CV | N/A |
| Reference LC/MS Accuracy (for method comparison) | (Implicit: Good accuracy for the reference method.) | % Recovery ranging from 93.2% to 109.7% for various levels | N/A |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size for Method Comparison: 114 unaltered clinical urine remnant samples.
- Data Provenance: The samples were obtained from a "third-party biorepository." The country of origin is not specified but is implied to be within the scope of the FDA's jurisdiction (likely the US). The data is retrospective as it uses remnant samples.
- Sample Size for Precision Studies: Drug-free urine was spiked at various concentrations (zero, -75%, -50%, -25% of cutoff, at cutoff, +25%, +50%, +75%, +100% of cutoff). For within-run studies, 20 observations were made for each concentration. For between-run studies, 80 observations were made for each concentration.
- Sample Size for Interference Studies: Specific numbers are not given for each interfering substance, but the study involved "various concentrations" for endogenous compounds, and urine samples at 9 different pH levels and 12 different specific gravity levels.
- Sample Size for Cross-Reactivity Studies: "Various concentrations" of structurally related and unrelated compounds were spiked into drug-free urine. Specific numbers of replicates are not provided, except for the referenced study which likely involved a larger set.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- The ground truth for the method comparison study was established by Agilent 6460 LC/MS. This is an analytical instrument, not human experts.
- For the precision, interference, and cross-reactivity studies, the ground truth was established by spiking known concentrations of benzoylecgonine or interfering substances into drug-free urine or using urine samples with known characteristics (e.g., pH, specific gravity). This is also an analytical assessment.
- Therefore, no human experts were used to establish the ground truth in the traditional sense of consensus or adjudication. The "ground truth" was determined by the highly precise and accurate analytical methods of LC/MS and controlled spiking.
4. Adjudication Method for the Test Set:
- None. The primary analytical reference method (LC/MS) is considered the gold standard for quantitative determination of benzoylecgonine in this context. The comparison is directly between the candidate device and this analytical gold standard. Discrepancies are reported as "discordant results" without further human adjudication in the provided summary.
5. 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:
- No. This device is an in vitro diagnostic (IVD) assay designed for qualitative determination of a cocaine metabolite in urine. It does not involve human "readers" in the context of image interpretation or subjective diagnostic assessment. Therefore, an MRMC study or AI assistance is not applicable to this type of device.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is essentially a standalone algorithm/device performance study. The Pointe Scientific Cocaine Metabolite Enzyme Immunoassay operates as an automated assay on clinical chemistry analyzers (Mindray BS-480 and BA-800M). Its performance is evaluated intrinsically against an analytical gold standard (LC/MS) and under controlled laboratory conditions (precision, interference, cross-reactivity). It does not involve a human in the loop for interpreting its primary result, which is a qualitative "positive" or "negative" determination based on a defined cutoff.
7. The Type of Ground Truth Used:
- Analytical Gold Standard / Spiked Samples:
- For the method comparison, the ground truth was established by a fully validated and qualified Agilent 6460 LC/MS (Liquid Chromatograph/Mass Spectrometry), which is considered a highly accurate and precise reference method for quantitative drug analysis.
- For precision, interference, and cross-reactivity studies, the ground truth was established by spiking known, confirmed concentrations of benzoylecgonine or other substances into drug-free urine, or by using urine samples with precisely measured characteristics (pH, specific gravity).
8. The Sample Size for the Training Set:
- The document describes a 510(k) submission for a diagnostic assay, not a machine learning or AI algorithm. Therefore, the concept of a "training set" for an algorithm to learn from does not apply in this context. The assay's performance is based on its chemical and enzymatic reactions, which are designed and validated, not "trained" on data.
9. How the Ground Truth for the Training Set was Established:
- As explained above, there is no "training set" in the context of this chemical immunoassay. The device's operational characteristics are fixed by its chemical and biological components.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
March 12, 2020
MedTest Dx William Cripps Director, R&D, OA/RA 5449 Research Drive Canton, MI 48188
Re: K191638
Trade/Device Name: Pointe Scientific Cocaine Metabolite Enzyme Immunoassay Regulation Number: 21 CFR 862.3250 Regulation Name: Cocaine And Cocaine Metabolite Test System Regulatory Class: Class II Product Code: DIO Dated: January 27, 2020 Received: January 28, 2020
Dear William Cripps:
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.
Please note that if you modify your IVD in the future to exceed any of the limitations to the exemption found in 21 CFR 862.9(c), your device will require a new 510(k) prior to marketing this device in the United States and will not be exempt from the premarket notification requirements so long as it exceeds the limitations to the exemption found in 21 CFR 862.9.
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.
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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 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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Marianela Perez-Torres, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K191638
Device Name
Pointe Scientific Cocaine Metabolite Enzyme Immunoassay
Indications for Use (Describe)
Indications For Use: The Pointe Scientific Cocaine Metabolite Enzyme Immunoassay is intended for the qualitative determination of benzoylecgonine (a cocaine metabolite) in human urine at a cutoff value of 150 ng/mL. Rx only.
This assay provides only a preliminary analytical test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas or Liquid Chromatograph/Mass Spectrometry (GC/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) SUMMARY
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of Safe Medical Device Act of 1990 and 21 CFR 807.92.
a. Device Information
| Category | Comments |
|---|---|
| Sponsor | MedTest Dx5449 Research DriveCanton, MI 48188Phone: 734-487-8300Fax: 734-483-1592 |
| Correspondent ContactInformation | William CrippsDirector, R&D/RA/QAEmail: wcripps@medtestdx.comPhone: 734-487-8300 ext. 120Fax: 734-483-1592 |
| Device 510(k) Number | K191638 |
| Device Common Name | Cocaine Metabolite Enzyme Immunoassay |
| Trade or ProprietaryName | Pointe Scientific Cocaine Metabolite EnzymeImmunoassay |
| Candidate DeviceProduct Code,Classification,Classification Name &Panel | DIO, Class II, 21 CFR 862. 3250 – Cocaine MetaboliteTest System, 91 – Toxicology |
Predicate Device Information
| Predicate Device | Cocaine Metabolite Enzyme Immunoassay |
|---|---|
| Predicate DeviceManufacturer | Lin-Zhi International, Inc. |
| Predicate DevicePremarketNotification #: | K113139 |
b. Date Summary Prepared
June 17, 2019 Updated January 27, 2020 Updated February 3, 2020 Updated February 26, 2020
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c. Description of Device
The Cocaine Metabolite Enzyme Immunoassay consists of ready-to-use liquid reagents:
- . Reagent 1 contains a mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers and sodium azide (0.09%) as a preservative.
- Reagent 2 contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with . benzoylecgonine in buffer with sodium azide (0.09%) as a preservative.
The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, benzoylecgonine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when drug is present in the sample, antibody binds to the free drug; the unbound benzovlecgonine-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at a 340 nm primary wavelength.
The assay has a cutoff of 150 ng/mL benzoylecqonine.
d. Intended Use
The Pointe Scientific Cocaine Metabolite Enzyme Immunoassay is intended for the qualitative determination of benzoylecgonine (a cocaine metabolite) in human urine at a cutoff value of 150 ng/mL. Rx only.
This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or Liquid Chromatograph/Mass Spectrometry (GC/MS or LC/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
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e. Comparison to Predicate Device
The chart below illustrates the similarities between the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay and the predicate, Lin-Zhi International (LZI) Cocaine Metabolite Enzyme Immunoassay.
| Characteristics | Cocaine Metabolite Enzyme | Lin-Zhi International (LZI) |
|---|---|---|
| Immunoassay (Proposed Device) | K113139 (Predicate Device) | |
| Intended Use | The Pointe Scientific Cocaine MetaboliteEnzyme Immunoassay is intended for thequalitative determination ofbenzoylecgonine (a cocaine metabolite) inhuman urine at a cutoff value of 150 ng/mL.Rx only. | To be used for the qualitative andsemi-quantitative determination ofbenzoylecgonine in human urine, at acutoff value of 150 ng/mL. This assayis designed for prescription use with anumber of clinical chemistry analyzers. |
| This assay provides only a preliminaryanalytical test result. A more specificalternative chemical method must be usedin order to obtain a confirmed analyticalresult. Gas or Liquid Chromatograph/MassSpectrometry (GC/MS or LC/MS) are thepreferred confirmatory methods. Clinicalconsideration and professional judgmentshould be exercised with any drug of abusetest result, particularly when the preliminaryresult is positive. | The semi-quantitative mode is forpurposes of (1) enabling laboratoriesto determine an appropriate dilution ofthe specimen for confirmation by aconfirmatory method such as GCMS or(2) permitting laboratories to establishquality control procedures.This assay provides only a preliminaryanalytical test result. A more specificalternative chemical method must beused in order to obtain a confirmedanalytical result. Gas or LiquidChromatograph/Mass Spectrometry(GC/MS or LC/MS) is the preferredconfirmatory method. Clinicalconsideration and professionaljudgment should be exercised with anydrug of abuse test result, particularlywhen the preliminary result is positive. | |
| Contents | The assay consists of ready-to-use liquidreagents. Reagent 1 contains a mousemonoclonal anti-benzoylecgonine antibody,glucose-6-phosphate (G6P) nicotinamideadenine dinucleotide (NAD), stabilizers andsodium azide (0.09%) as a preservative.Reagent 2 contains glucose-6-phosphatedehydrogenase (G6PDH) labeled withbenzoylecgonine in buffer with sodium azide(0.09%) as a preservative | Same |
| Analyte | Benzoylecgonine | Same |
| Cutoff | 150 ng/mL | Same |
| Matrix | Urine | Same |
| Calibrators | 2 Levels (0 ng/mL, 150 ng/mL) | 5 Levels (0, 75, 150, 300, 1000 ng/mL) |
| Controls | 2 levels (112.5 ng/mL, 187.5 ng/mL) | Same |
| Storage | 2-8°C until expiration date | Same |
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f. Performance Data
Performance was evaluated at the MedTest Dx site on both the Mindray BS-480 and the Mindray BA-800M clinical chemistry analyzers.
Method Comparison Studies
Method comparison studies were performed following CLSI EP-12A2, using remnant urine samples obtained from a third-party biorepository. Results obtained through the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay were compared aqainst results obtained from a fully validated and qualified Agilent 6460 LC/MS. Included below is the precision and accuracy data for the analytical reference method on the Agilent 6460 LC/MS.
When analyzing Benzoylecqonine reference materials from Cerilliant with the reference LC/MS method, the following results were obtained.
| Benzoylecgonine Std | Mean (ng/mL) | %CV |
|---|---|---|
| Level 1 | 19.13 | 5.3 |
| Level 2 | 25.81 | 6.5 |
| Level 3 | 136.13 | 5.3 |
Precision
Accuracy
| Reference Level | Assigned Value | Recovered Value | % Recovery |
|---|---|---|---|
| Level 1 | 10 ng/mL | 10.70 ng/mL | 107.0 |
| Level 2 | 18.75 ng/mL | 20.11 ng/mL | 107.2 |
| Level 3 | 25 ng/mL | 25.80 ng/mL | 103.2 |
| Level 4 | 75 ng/mL | 69.89 ng/mL | 93.2 |
| Level 5 | 150 ng/mL | 149.89 ng/mL | 99.9 |
| Level 6 | 250 ng/mL | 274.49 ng/mL | 109.7 |
Traceability
All standards used in the LC/MS methods are certified reference materials obtained from Cerilliant.
BS-480:
114 unaltered clinical urine remnant samples were evaluated on 3 nonconsecutive days by the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay and compared to LC/MS. Results from the qualitative study are presented below.
| CandidateDeviceResults | Negative | < 75 ng/mLby LC/MS | 75-150ng/mL byLC/MS | 150-225ng/mL byLC/MS | >225 ng/mLby LC/MS |
|---|---|---|---|---|---|
| Positive | 0 | 0 | 1 | 4 | 36 |
| Negative | 56 | 8 | 4 | 5 | 0 |
% Agreement among positives is 88.9% (40/45)
% Agreement among negatives is 98.6% (68/69)
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Discordant Results
| Cutoff Value | Pointe Scientific Cocaine MetaboliteEnzyme Immunoassay Result | Drug Metabolite LC/MSValue Result |
|---|---|---|
| 150 ng/mL | Positive | Negative (102 ng/mL) |
| 150 ng/mL | Negative | Positive (222 ng/mL) |
| 150 ng/mL | Negative | Positive (214 ng/mL) |
| 150 ng/mL | Negative | Positive (156 ng/mL) |
| 150 ng/mL | Negative | Positive (165 ng/mL) |
| 150 ng/mL | Negative | Positive (164 ng/mL) |
BA-800M
114 unaltered clinical urine remnant samples were evaluated on 3 nonconsecutive days by the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay and compared to LC/MS. Results from the qualitative study are presented below.
| CandidateDeviceResults | Negative | < 75 ng/mLby LC/MS | 75-150ng/mL byLC/MS | 150-225ng/mL byLC/MS | >225 ng/mLby LC/MS |
|---|---|---|---|---|---|
| Positive | 0 | 0 | 1 | 6 | 36 |
| Negative | 56 | 8 | 4 | 3 | 0 |
% Agreement among positives is 93.3% (42/45)
% Agreement among negatives is 98.6% (68/69)
Discordant Results
| Cutoff Value | Pointe Scientific Cocaine MetaboliteEnzyme Immunoassay Result | Drug Metabolite LC/MSValue Result |
|---|---|---|
| 150 ng/mL | Positive | Negative (102 ng/mL) |
| 150 ng/mL | Negative | Positive (214 ng/mL) |
| 150 ng/mL | Negative | Positive (156 ng/mL) |
| 150 ng/mL | Negative | Positive (164 ng/mL) |
Precision Studies
Precision studies were conducted in accordance with CLSI EP05-A3. Precision was determined by spiking benzoylecgonine into drug free urine at various concentrations (zero, -75%, -50%, -25%, at the cutoff, 125%, 150%, 175% and 200% of the cutoff). Concentrations were confirmed by LC/MS. Testing for both the with-in run and betweenrun studies were performed by testing each sample in replicate, with two runs per day, for 20 days. The qualitative results are presented below as Positive/Negative.
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| Within Run | Between Run | |||
|---|---|---|---|---|
| Sampleconcentration(ng/mL) | No.Observations | # Neg/#Pos | No.Observations | # Neg/#Pos |
| 0 (negative) | 20 | 20/0 | 80 | 80/0 |
| 37.5 (-75% c/o) | 20 | 20/0 | 80 | 80/0 |
| 75 (-50% c/o) | 20 | 20/0 | 80 | 80/0 |
| 112.5 (-25% c/o) | 20 | 20/0 | 80 | 80/0 |
| 150 (cutoff) | 20 | 19/1 | 80 | 68/12 |
| 187.5 (+25% c/o) | 20 | 0/20 | 80 | 0/80 |
| 225 (+50% c/o) | 20 | 0/20 | 80 | 0/80 |
| 262.5 (+75% c/o) | 20 | 0/20 | 80 | 0/80 |
| 300 (+100% c/o) | 20 | 0/20 | 80 | 0/80 |
BS-480 Qualitative Results (Pos/Neg):
These results indicate that the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay has acceptable precision on the BS-480.
| Within Run | Between Run | |||
|---|---|---|---|---|
| Sampleconcentration(ng/mL) | No.Observations | # Neg/#Pos | No.Observations | # Neg/#Pos |
| 0 (negative) | 20 | 20/0 | 80 | 80/0 |
| 37.5 (-75% c/o) | 20 | 20/0 | 80 | 80/0 |
| 75 (-50% c/o) | 20 | 20/0 | 80 | 80/0 |
| 112.5 (-25% c/o) | 20 | 20/0 | 80 | 80/0 |
| 150 (cutoff) | 20 | 7/13 | 80 | 41/39 |
| 187.5 (+25% c/o) | 20 | 0/20 | 80 | 0/80 |
| 225 (+50% c/o) | 20 | 0/20 | 80 | 0/80 |
| 262.5 (+75% c/o) | 20 | 0/20 | 80 | 0/80 |
| 300 (+100% c/o) | 20 | 0/20 | 80 | 0/80 |
These results indicate that the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay has acceptable precision on the BA-800M.
Interference (Endogenous Substances) Study
Interference studies were conducted following a modification to CLSI EP07.
The following endogenous compounds were added into drug-free urine, urine sample spiked to 75% of benzoylecgonine and urine spiked to 125% of benzoylecgonine at various concentrations. The substances listed in the table below were determined not to interfere at the concentration shown.
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To test for possible positive and/or negative interference from pH, urine samples having pH from 3, 4, 5, 6, 7, 8, 9, 10 and 11 were used. Each of these samples were divided into two aliquots for each drug and spiked to 75% of the cutoff and 125% of the cutoff. No positive or negative interference due to pH was observed.
Qualitative results were identical for the BS-480 and BA-800M analyzers.
| Qualitative Result | ||||
|---|---|---|---|---|
| InterferingSubstances | Spiked[](mg/dL) | 0 ng/mL(Pos/Neg) | 112.5 ng/mLControl(Pos/Neg) | 187.5 ng/mLControl(Pos/Neg) |
| Acetaminophen | 10 | Neg | Neg | Pos |
| Acetone | 1000 | Neg | Neg | Pos |
| Ascorbic Acid | 400 | Neg | Neg | Pos |
| Aspirin | 10 | Neg | Neg | Pos |
| Caffeine | 10 | Neg | Neg | Pos |
| Creatinine | 500 | Neg | Neg | Pos |
| Ethanol | 1000 | Neg | Neg | Pos |
| Galactose | 10 | Neg | Neg | Pos |
| r-Globulin | 500 | Neg | Neg | Pos |
| Glucose | 1500 | Neg | Neg | Pos |
| Hemoglobin | 300 | Neg | Neg | Pos |
| Human SerumAlbumin | 500 | Neg | Neg | Pos |
| Ibuprofen | 10 | Neg | Neg | Pos |
| Oxalic Acid | 100 | Neg | Neg | Pos |
| Riboflavin | 7.5 | Neg | Neg | Pos |
| Sodium Chloride | 3000 | Neg | Neg | Pos |
| Urea | 2000 | Neg | Neg | Pos |
BS-480 and BA-800M Interference
To test for possible positive and/or negative interference from pH, urine samples having pH from 3, 4, 5, 6, 7, 8, 9, 10 and 11 were used. Each of these samples were divided into two aliquots for each drug and spiked to 75% of the cutoff and 125% of the cutoff. No positive or negative interference due to pH was observed.
| Interfering pH | Spiked[](mg/dL) | Qualitative Result | ||
|---|---|---|---|---|
| 0 ng/mL(Pos/Neg) | 112.5 ng/mLControl(Pos/Neg) | 187.5 ng/mLControl(Pos/Neg) | ||
| pH 3 | --- | Neg | Neg | Pos |
| pH 4 | --- | Neg | Neg | Pos |
| pH 5 | --- | Neg | Neg | Pos |
| pH 6 | --- | Neg | Neg | Pos |
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| Interfering pH | Spiked[](mg/dL) | Qualitative Result | ||
|---|---|---|---|---|
| 0 ng/mL(Pos/Neg) | 112.5 ng/mLControl(Pos/Neg) | 187.5 ng/mLControl(Pos/Neg) | ||
| pH 7 | --- | Neg | Neg | Pos |
| pH 8 | --- | Neg | Neg | Pos |
| pH 9 | --- | Neg | Neg | Pos |
| pH 10 | --- | Neg | Neg | Pos |
| pH 11 | --- | Neg | Neg | Pos |
To test for possible positive and/or negative interference from specific gravity, urine samples having specific gravity ranging from 1.000 g/mL to 1.031 g/mL were used. Each of these samples were divided into three aliquots and two were spiked to 75% of the cutoff and 125% of the cutoff, the third was not spiked. No positive or negative interference due to specific gravity was observed.
| Specific Gravity ofSpecimen(g/mL) | 0 ng/mL(Pos/Neg) | 112.5 ng/mL Control(Pos/Neg) | 187.5 ng/mL Control(Pos/Neg) |
|---|---|---|---|
| 1.000 | Neg | Neg | Pos |
| 1.000 | Neg | Neg | Pos |
| 1.004 | Neg | Neg | Pos |
| 1.010 | Neg | Neg | Pos |
| 1.013 | Neg | Neg | Pos |
| 1.017 | Neg | Neg | Pos |
| 1.018 | Neg | Neg | Pos |
| 1.020 | Neg | Neg | Pos |
| 1.021 | Neg | Neg | Pos |
| 1.021 | Neg | Neg | Pos |
| 1.025 | Neg | Neg | Pos |
| 1.031 | Neg | Neg | Pos |
BS-480 Specific Gravity Interference
BA-800M Specific Gravity Interference
| Specific Gravity ofSpecimen | Qualitative Result0 ng/mL(Pos/Neg) | Qualitative Result112.5 ng/mL Control(Pos/Neg) | Qualitative Result187.5 ng/mL Control(Pos/Neg) |
|---|---|---|---|
| 1.009 | Neg | Neg | Pos |
| 1.012 | Neg | Neg | Pos |
| 1.017 | Neg | Neg | Pos |
| 1.018 | Neg | Neg | Pos |
| 1.020 | Neg | Neg | Pos |
| 1.020 | Neg | Neg | Pos |
| 1.024 | Neg | Neg | Pos |
| 1.026 | Neg | Neg | Pos |
| 1.029 | Neg | Neg | Pos |
{11}------------------------------------------------
Cross Reactivity
Cross-reactivity was established by spiking various concentrations of structurally related and unrelated compounds into drug-free urine. Following a "least burdensome approach", manufacturer studies performed on another analyzer have been referenced after completing proof of principle testing on a subset of structurally and non-structurally related compounds. Right to Reference Letter is located in Appendix F.
Proof of Principle Testing performed on Mindray BA-800M and Mindray BS-480:
| Cross Reactant | TargetConcentration(ng/mL) | %Cross ReactivityCalculated basedon AnalyzerRecoveredConcentration | %CrossReactivityCalculated basedon CutoffConcentration |
|---|---|---|---|
| Benzoylecgonine | 150 | 113.43% | 100.00 % |
| Cocaine | 10,000 | 1.52% | 1.50 % |
BA-800M Structurally Related Compounds
BA-800M Structurally Unrelated Pharmacological Compounds:
| Cross-reactant | Target Concentration(ng/mL) | % Cross Reactivity |
|---|---|---|
| Meperidine | 500,000 | 0.00 % |
BS-480 Structurally Related Compounds
| Cross Reactant | TargetConcentration(ng/mL) | %Cross Reactivity | |
|---|---|---|---|
| Calculated basedon AnalyzerRecoveredConcentration | Calculated basedon CutoffConcentration | ||
| Benzoylecgonine | 150 | 105.37% | 100.00 % |
| Cocaine | 10,000 | 1.62% | 1.50 % |
BS-480 Structurally Unrelated Pharmacological Compounds:
| Cross-reactant | Target Concentration(ng/mL) | % Cross Reactivity |
|---|---|---|
| Meperidine | 500,000 | 0.00 % |
Referenced Cross Reactivity Testing on Hitachi 717:
The following tables summarizes the approximate quantity of each compound that is equivalent in assay reactivity to the 150 ng/mL benzoylecgonine cutoff. Results are expressed as a minimum concentration of metabolite or compound required to produce a response approximately equivalent to the cutoff concentration of the assay or the maximal concentration of the compound tested that gave a response with crossreactivity below the cutoff calibrator. The percent cross-reactivity of those compounds are presented below.
{12}------------------------------------------------
| Cross-reactant | Target Concentration(ng/mL) | % Cross Reactivity |
|---|---|---|
| Benzoylecgonine | 150 | 96.03 % |
| Benzoylecgonine | 300 | 102.10 % |
| Cocaethylene | 4,000 | 4.58 % |
| Cocaine | 25,000 | 0.62% |
| Ecgonine | 400,000 | 0.03 % |
| Ecgonine, Methyl Ester | 500,000 | 0.00 % |
| Norcocaine | 30,000 | 0.68 % |
| Atropine | 500,000 | 0.00 % |
Structurally Related Cocaine Compound (as found in Appendix F):
Structurally Unrelated Pharmacological Compounds (as found in Appendix F):
| Cross-reactant | Target Concentration(ng/mL) | % Cross Reactivity |
|---|---|---|
| Acetaminophen | 500,000 | 0.00 % |
| Acetylsalicylic Acid | 500,000 | 0.00 % |
| Amobarbital | 500,000 | 0.00 % |
| Amoxicillin | 500,000 | 0.00 % |
| Amphetamine | 500,000 | 0.00 % |
| Bupropion | 500,000 | 0.00 % |
| Captopril | 500,000 | 0.00 % |
| Caffeine | 500,000 | 0.00 % |
| Chlordiazepoxide | 500,000 | 0.00 % |
| Chlorpheniramine | 500,000 | 0.00 % |
| Chlorpomazine | 500,000 | 0.00 % |
| Codeine | 500,000 | 0.00 % |
| Dextromethorphan | 500,000 | 0.00 % |
| Diazepam | 500,000 | 0.00 % |
| Digoxin | 500,000 | 0.00 % |
| Enalapril | 500,000 | 0.00 % |
| Fluoxetine | 100,000 | 0.01 % |
| Glyburide | 500,000 | 0.00 % |
| Ibuprofen | 500,000 | 0.00 % |
| Lidocaine | 500,000 | 0.00 % |
| Meperidine | 500,000 | 0.00 % |
| Methadone | 100,000 | 0.01 % |
| Methamphetamine | 500,000 | 0.00 % |
| Methaqualone | 500,000 | 0.00 % |
| Morphine | 500,000 | 0.00 % |
| Nicodine | 500,000 | 0.00 % |
| Nifedipine | 100,000 | 0.00 % |
| Oxazepam | 100,000 | 0.00 % |
| Phencyclidine | 500,000 | 0.00 % |
| Phenobarbital | 500,000 | 0.00 % |
{13}------------------------------------------------
| Cross-reactant | Target Concentration(ng/mL) | % Cross Reactivity |
|---|---|---|
| Propoxyphene | 100,000 | 0.00 % |
| Ranitidine | 500,000 | 0.00 % |
| Salicyluric acid | 500,000 | 0.00 % |
| Secobarbital | 500,000 | 0.00 % |
| 11-nor- THC-COOH | 500,000 | 0.00 % |
| Valproic Acid | 500,000 | 0.00 % |
| Verapamil | 500,000 | 0.00 % |
Traceability
Two levels of calibrators (0 and 150 ng/mL) and two levels of control material (112.5 ng/mL, 187.5 ng/mL) are available for use with the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay. A commercially available benzoylecgonine standard solution from Cerilliant Analytical Reference Standards is used and traceable to NIST standard. This standard solution is made into a secondary (lower concentration) stock solution. The secondary stock solution is then spiked into the calibrators and controls to the desired concentration. The concentrations are confirmed by GC/MS.
Conclusion
We feel that the enclosed data supports a determination that the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay is substantially equivalent in terms of composition and performance to the product marketed by Lin-Zhi International.
§ 862.3250 Cocaine and cocaine metabolite test system.
(a)
Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.(b)
Classification. Class II (special controls). A cocaine and cocaine metabolite test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).