Who is the manufacturer of Pointe Scientific Cocaine Metabolite Enzyme Immunoassay?

Medtest DX filed the 510(k) submission for Pointe Scientific Cocaine Metabolite Enzyme Immunoassay (K191638).

What is the FDA product code for Pointe Scientific Cocaine Metabolite Enzyme Immunoassay?

DIO. It is classified under 21 CFR 862.3250 as a Class 2 device in the Clinical Toxicology panel.

What is the regulatory pathway for Pointe Scientific Cocaine Metabolite Enzyme Immunoassay?

510(k) clearance (submission type: Traditional).

What are the predicate devices for Pointe Scientific Cocaine Metabolite Enzyme Immunoassay?

Cocaine Metabolite Enzyme Immunoassay (K113139).

Who can help prepare an FDA 510(k) submission like Pointe Scientific Cocaine Metabolite Enzyme Immunoassay?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

Pointe Scientific Cocaine Metabolite Enzyme Immunoassay

K191638 · Medtest DX · DIO · Mar 12, 2020 · Clinical Toxicology

Device Facts

Record ID	K191638
Device Name	Pointe Scientific Cocaine Metabolite Enzyme Immunoassay
Applicant	Medtest DX
Product Code	DIO · Clinical Toxicology
Decision Date	Mar 12, 2020
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.3250
Device Class	Class 2

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.

Device Story

In vitro diagnostic enzyme immunoassay for qualitative detection of benzoylecgonine in human urine; utilizes competitive binding between sample drug and enzyme-labeled drug (G6PDH) for monoclonal antibody sites; enzyme activity inversely proportional to drug concentration; active enzyme converts NAD to NADH, measured spectrophotometrically at 340 nm; intended for use on clinical chemistry analyzers (e.g., Mindray BS-480, BA-800M) in clinical laboratory settings; operated by laboratory technicians; provides preliminary screening results; positive results require confirmation by GC/MS or LC/MS; assists clinicians in identifying potential cocaine use; supports clinical decision-making regarding substance abuse management.

Clinical Evidence

Bench testing only. Method comparison studies performed on Mindray BS-480 and BA-800M analyzers using 114 clinical urine samples compared to LC/MS reference method. BS-480: 88.9% positive agreement, 98.6% negative agreement. BA-800M: 93.3% positive agreement, 98.6% negative agreement. Precision evaluated per CLSI EP05-A3 over 20 days. Interference studies (endogenous substances, pH, specific gravity) showed no significant interference. Cross-reactivity tested against structurally related and unrelated compounds.

Technological Characteristics

Competitive enzyme immunoassay; Reagent 1: mouse monoclonal anti-benzoylecgonine antibody, G6P, NAD, stabilizers, 0.09% sodium azide; Reagent 2: G6PDH-labeled benzoylecgonine, buffer, 0.09% sodium azide; Detection: spectrophotometric (340 nm); Storage: 2-8°C; Analyzers: Mindray BS-480, BA-800M; Traceability: NIST-traceable Cerilliant standards.

Indications for Use

Indicated for qualitative detection of benzoylecgonine in human urine at 150 ng/mL cutoff. For prescription use only. Requires confirmatory testing via GC/MS or LC/MS.

Regulatory Classification

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.

Special Controls

*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).

Predicate Devices

Cocaine Metabolite Enzyme Immunoassay (K113139)

Related Devices

K013004 — COCAINE · Abbott Laboratories · Mar 13, 2002
K020763 — COCAINE METABOLITE ENZYME IMMUNOASSAY MODELS #0030 (500 TESTS KIT), #0031 (5000 TESTS KIT) · Lin-Zhi International, Inc. · May 10, 2002
K113139 — LZI COCAINE METABOLITE HOMOGENEOUS ENZYME IMMUNOASSAY,CALIBRATORS,CONTROLS · Lin-Zhi International, Inc. · Nov 22, 2011
K062929 — QUEST DIAGNOSTICS URINE COCAINE METABOLITE EIA · Quest Diagnostics, Inc. · Dec 18, 2006
K211973 — DRI Cocaine Metabolite Assay · Microgenics Corporation · Sep 24, 2021

Submission Summary (Full Text)

{0}------------------------------------------------ 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. {1}------------------------------------------------ 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 {2}------------------------------------------------ # 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) | | |------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------| | <div style="display:flex; align-items:center;">☑ Prescription Use (Part 21 CFR 801 Subpart D)</div> | <div style="display:flex; align-items:center;">☐ Over-The-Counter Use (21 CFR 801 Subpart C)</div> | #### CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {3}------------------------------------------------ # 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 Dx 5449 Research Drive Canton, MI 48188 Phone: 734-487-8300 Fax: 734-483-1592 | | Correspondent Contact Information | William Cripps Director, R&D/RA/QA Email: wcripps@medtestdx.com Phone: 734-487-8300 ext. 120 Fax: 734-483-1592 | | Device 510(k) Number | K191638 | | Device Common Name | Cocaine Metabolite Enzyme Immunoassay | | Trade or Proprietary Name | Pointe Scientific Cocaine Metabolite Enzyme Immunoassay | | Candidate Device Product Code, Classification, Classification Name & Panel | DIO, Class II, 21 CFR 862. 3250 – Cocaine Metabolite Test System, 91 – Toxicology | ## Predicate Device Information | Predicate Device | Cocaine Metabolite Enzyme Immunoassay | |--------------------------------------------------|---------------------------------------| | Predicate Device Manufacturer | Lin-Zhi International, Inc. | | Predicate Device Premarket Notification #: | K113139 | # b. Date Summary Prepared June 17, 2019 Updated January 27, 2020 Updated February 3, 2020 Updated February 26, 2020 {4}------------------------------------------------ # 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. {5}------------------------------------------------ # 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 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. | To be used for the qualitative and semi-quantitative determination of benzoylecgonine in human urine, at a cutoff value of 150 ng/mL. This assay is designed for prescription use with a number of clinical chemistry analyzers. | | | 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. | The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GCMS or (2) permitting laboratories to establish quality control procedures. 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) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. | | Contents | The assay 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 | 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 | {6}------------------------------------------------ ## 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. | Candidate Device Results | Negative | < 75 ng/mL by LC/MS | 75-150 ng/mL by LC/MS | 150-225 ng/mL by LC/MS | >225 ng/mL by 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) {7}------------------------------------------------ Discordant Results | Cutoff Value | Pointe Scientific Cocaine Metabolite Enzyme Immunoassay Result | Drug Metabolite LC/MS Value 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. | Candidate Device Results | Negative | < 75 ng/mL by LC/MS | 75-150 ng/mL by LC/MS | 150-225 ng/mL by LC/MS | >225 ng/mL by 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 Metabolite Enzyme Immunoassay Result | Drug Metabolite LC/MS Value 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. {8}------------------------------------------------ | | Within Run | | Between Run | | |------------------------------------|---------------------|------------|---------------------|------------| | Sample concentration (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 | | |------------------------------------|---------------------|------------|---------------------|------------| | Sample concentration (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. {9}------------------------------------------------ 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 | | |---------------------------|-------------------------|----------------------|-------------------------------------|-------------------------------------| | Interfering Substances | Spiked [] (mg/dL) | 0 ng/mL (Pos/Neg) | 112.5 ng/mL Control (Pos/Neg) | 187.5 ng/mL Control (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 Serum Albumin | 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/mL Control (Pos/Neg) | 187.5 ng/mL Control (Pos/Neg) | | pH 3 | --- | Neg | Neg | Pos | | pH 4 | --- | Neg | Neg | Pos | | pH 5 | --- | Neg | Neg | Pos | | pH 6 | --- | Neg | Neg | Pos | {10}------------------------------------------------ | Interfering pH | Spiked [] (mg/dL) | Qualitative Result | | | |----------------|-------------------------|----------------------|-------------------------------------|-------------------------------------| | | | 0 ng/mL (Pos/Neg) | 112.5 ng/mL Control (Pos/Neg) | 187.5 ng/mL Control (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 of Specimen (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 of Specimen | Qualitative Result 0 ng/mL (Pos/Neg) | Qualitative Result 112.5 ng/mL Control (Pos/Neg) | Qualitative Result 187.5 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 | Target Concentration (ng/mL) | %Cross Reactivity Calculated based on Analyzer Recovered Concentration | %Cross Reactivity Calculated based on Cutoff Concentration | |-----------------|------------------------------------|------------------------------------------------------------------------------------|------------------------------------------------------------------------| | 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 | Target Concentration (ng/mL) | %Cross Reactivity | | |-----------------|------------------------------------|---------------------------------------------------------------|------------------------------------------------| | | | Calculated based on Analyzer Recovered Concentration | Calculated based on Cutoff Concentration | | 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.