ABBOTT PHENOBARBITAL ASSAY

K123271 · Microgenics Corp. · DLZ · Apr 26, 2013 · Clinical Toxicology

Device Facts

• Record ID: K123271
• Device Name: ABBOTT PHENOBARBITAL ASSAY
• Applicant: Microgenics Corp.
• Product Code: DLZ · Clinical Toxicology
• Decision Date: Apr 26, 2013
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3660
• Device Class: Class 2

Intended Use

The Abbott Phenobarbital assay is for in vitro diagnostic use for the quantitative measurement of phenobarbital in human serum or plasma on the ARCHITECT cSystems. The measurements obtained are used in the diagnosis and treatment of phenobarbital overdose and in monitoring levels of phenobarbital to help ensure appropriate therapy.

Device Story

The Abbott Phenobarbital Assay is a quantitative, in vitro diagnostic immunoassay for use on the ARCHITECT c8000 clinical chemistry analyzer. It utilizes a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) principle. The assay involves competition between phenobarbital in the patient sample and phenobarbital coated onto microparticles for binding sites on a mouse anti-phenobarbital antibody reagent. In the absence of the drug, the microparticles agglutinate; the presence of phenobarbital in the sample inhibits this agglutination. The analyzer measures the rate of absorbance change photometrically, which is inversely proportional to the phenobarbital concentration. The device is intended for use in clinical laboratory settings by trained personnel. Results are provided to clinicians to assess therapeutic levels or identify overdose, aiding in clinical decision-making regarding patient medication management.

Clinical Evidence

Bench testing only. Precision studies (inter-assay) performed on the ARCHITECT c8000 analyzer using serum-based controls and spiked patient samples showed total CVs ranging from 1.2% to 6.7%. Linearity was confirmed across the 2.0–80.0 μg/mL range (R²=0.998). Method comparison against the predicate (N=118) yielded a slope of 1.003 and R=0.9949. Analytical specificity and interference studies confirmed no significant cross-reactivity or interference from common compounds or endogenous substances.

Technological Characteristics

PETINIA (particle-enhanced turbidimetric inhibition immunoassay). Reagents: liquid, ready-to-use antibody reagent and phenobarbital-coated microparticle reagent. Analyzed on ARCHITECT c8000 clinical chemistry analyzer. Standards: CLSI EP5-A2 (precision), CLSI EP17-A2 (LoD/LoQ). Storage: 2-8°C. Quantitative measurement via photometric rate of absorbance change.

Indications for Use

Indicated for the quantitative measurement of phenobarbital in human serum or plasma to assist in the diagnosis and treatment of phenobarbital overdose and therapeutic drug monitoring.

Regulatory Classification

Identification

A phenobarbitol test system is a device intended to measure phenobarbital, an antiepileptic and sedative-hypnotic drug, in human specimens. Measurements obtained by this device are used in the diagnosis and treatment of phenobarbital use or overdose and in monitoring levels of phenobarbital to ensure appropriate therapy.

Predicate Devices

• Abbott Aeroset® Phenobarbital Assay (k993031)

Submission Summary (Full Text)

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# 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: k123271

#### Company / Contact Person

Karen Lee Regulatory Affairs Specialist . Thermo Fisher Scientific, Clinical Diagnostics Division 46360 Fremont Blvd. Fremont, CA 94538 Phone: [phone] x31814 [phone] Fax: E-mail: [e-mail]

#### Date Prepared

October 17, 2012

#### Regulatory Declarations

| Common / Usual Name | Phenobarbital Assay |
|---------------------------|----------------------------|
| Trade / Proprietary Name | Abbott Phenobarbital Assay |
| Classification Regulation | 21 CFR 862.3660 |
| Device Class | Class II |
| Device Regulation Panel | Toxicology |
| Product Code | DLZ |

#### Intended Use

#### Phenobarbital Assay

The Abbott Phenobarbital assay is for in vitro diagnostic use for the quantitative measurement of phenobarbital in human serum or plasma on the ARCHITECT cSystems. The measurements obtained are used in the diagnosis and treatment of phenobarbital overdose and in monitoring levels of phenobarbital to help ensure appropriate therapy.

#### Legally Marketed Device to Which Equivalency is Claimed

The Phenobarbital Assay is substantially equivalent to the previously cleared Abbott Aerosett Phenobarbital Assay (k993031).

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## Device Description

The Phenobarbital Assay kit is supplied ready-to-use in liquid form, for storage at 2 to 8°C. Each Phenobarbital Assay kit is packaged in a rectangular cardboard box divided into three sections. One section will contain three bottles of Antibody Reagent (R1), one section will contain three bottles of Microparticle Reagent (R2), and the last section will contain the package insert. Each kit is sufficient for 300 tests. The configuration is as follows:

| Component | Description | Configuration |
|-----------------------------|-----------------------------------------------------------------------------------------------------------------|---------------|
| R1 Antibody<br>Reagent | <2.0% Anti-Phenobarbital monoclonal antibody (mouse)<br>in Tris buffer and <0.09% sodium azide as preservative. | 3 x 23 mL |
| R2 Microparticle<br>Reagent | <1.0% Phenobarbital-coated microparticles containing<br><0.09% sodium azide as preservative. | 3 x 9 mL |

Image /page/1/Figure/3 description: The image shows a kit box with a kit box insert and package inserts. There are labels indicating "R1 RGT (3 Bottles)" and "R2 RGT (3 Bottles)" on the left and right sides of the box, respectively. The package inserts are located in the middle of the box. The image provides a visual representation of the kit's components and their arrangement within the box.

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| Comparison | Proposed Device | Predicate |
|---------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Proprietary<br>Name | Abbott Phenobarbital Assay | Abbott Aeroset® Phenobarbital Assay<br>(k993031) |
| Intended Use | The Phenobarbital assay is used for the in<br>vitro quantitative measurement of<br>phenobarbital in human serum or plasma<br>on the ARCHITECT cSystems. | The assay is intended for use in the<br>quantitative analysis of Phenobarbital in<br>human serum or plasma. |
| Test Principle | The Phenobarbital assay is a<br>homogeneous particle-enhanced<br>turbidimetric inhibition immunoassay<br>(PETINIA) used for the analysis of<br>phenobarbital in serum or plasma. The<br>assay is based on competition between<br>drug in the sample and drug coated onto a<br>microparticle for antibody binding sites of<br>the phenobarbital antibody reagent. The<br>phenobarbital-coated microparticle reagent<br>is rapidly agglutinated in the presence of<br>the anti-phenobarbital antibody reagent and<br>in the absence of any competing drug in<br>the sample. The rate of absorbance<br>change is measured photometrically, and is<br>directly proportional to the rate of<br>agglutination of the particles. When a<br>sample containing phenobarbital is added,<br>the agglutination reaction is partially<br>inhibited, slowing down the rate of<br>absorbance change. A concentration-<br>dependent classic agglutination inhibition<br>curve can be obtained, with maximum rate<br>of agglutination at the lowest phenobarbital<br>concentration and the lowest agglutination<br>rate at the highest phenobarbital<br>concentration. | The Phenobarbital assay is a<br>homogeneous enzyme immunoassay<br>technique used for the analysis of<br>phenobarbital in biological fluids. The<br>assay is based on competition for antibody<br>binding sites between the analyte drug in<br>the specimen and exogenous drug labeled<br>with the enzyme glucose-6-phosphate<br>dehydrogenase (G6PDH). Since G6PDH<br>activity decreases upon binding to the<br>antibody, the concentration of drug in the<br>specimen can be measured in terms of<br>enzyme activity. Active G6PDH reduces<br>nicotinamide adenine dinucleotide (NAD) to<br>NADH, resulting in an absorbance change<br>that is measured spectrophotometrically.<br>Endogenous serum G6PDH does not<br>interfere because the coenzyme NAD<br>functions only with the bacterial<br>(Leuconostoc mesenteroides) enzyme<br>employed in the assay. |
| Sample Matrix | Human Serum or Human Plasma | Human Serum or Human Plasma |
| Reagent | Liquid Ready-to-Use (Antibody reagent,<br>Phenobarbital-coated microparticle<br>reagent) | Liquid Ready-to-Use (Antibody reagent,<br>Phenobarbital-labeled enzyme reagent) |
| Storage | 2-8°C | 2-8°C |
| Calibrator | Liquid Ready-to-Use, six levels (0.0, 5.0,<br>10.0, 20.0, 40.0, and 80.0 µg/mL) | Liquid Ready-to-Use, six levels (0.0, 5.0,<br>10.0, 20.0, 40.0, and 80.0 µg/mL) |
| Assay Range | 2.0 to 80.0 µg/mL | 0.5 to 80.0 µg/mL |

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#### Summary of Performance Testing

#### Limit of Quantitation (LOQ)

The limit of quantitation determines the lowest concentration which results in inter-assay precision at 7% CV or 0.7 µg/mL SD and bias to be within 10% or 1.0 µg/mL that has been measured over an extended period. The results demonstrate that the LOQ is 2.0 µg/mL and meets design acceptance criteria.

#### Precision

Phenobarbital samples tested for precision following a CLSI protocol. In the study, the total run %CV was less than or equal to 6.7% and meets design acceptance criteria.

#### Spike Recovery

Negative serum samples were spiked with phenobarbital at concentrations across the assay range. All of the samples recover within ±10% or ±1.0 µg/mL error of the HPLC results.

#### Method Comparison

Samples were tested in the Phenobarbital Assay and compared to HPLC. The assay correlated well with HPLC as follows: y = 0.933x + 0.68, R = 0.9887, n=108.

#### Matrix Comparison

The following matrices were tested and may be suitable for use in the Phenobarbital Assay: serum in glass, serum in plastic, serum separator tube (SST) in plastic, plasma with sodium fluoride/potassium oxalate in plastic, plasma with sodium heparin in plastic and glass, plasma with lithium heparin in plastic with or without gel, plasma with K3 EDTA in glass and plastic, plasma with K2 EDTA in plastic, and sodium citrate in plastic and glass.

#### Specificity

The assay showed minimal to no cross reactivity to other medications potentially administered The assay also showed minimal to no interference to endogenous with phenobarbital. substances up to the concentrations tested.

#### Linearity

Samples were tested to demonstrate linearity throughout the assay range. Results demonstrate that the assay performs in a linear fashion from 2.0 to 80 µg/mL.

#### Onboard Stability

Using the Abbott Architect cSystem, the reagents were stable onboard for up to 45 days.

#### Standard Curve Calibration Stability

Using the Abbott Architect cSystem, the standard curve calibration was stable for up to 14 days.

#### Reagent Shelf Life Stability

Studies showed that the reagents will be stable at 2-8°C for 24 months.

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#### Conclusion

ﺎ

Substantial equivalence of the Phenobarbital Assay to the previously cleared Abbott Aeroset® Phenobarbital Assay (k993031) has been demonstrated through performance testing (Section 18) to verify that the device functions as intended and design specifications have been satisfied.

and the comments of the country

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### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird-like figure with three stylized lines forming the body and wings.

#### Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

April 26, 2013

Microgenics Corp. C/O Karen Lee. Regulatory Affairs Specialist Thermo Fisher Scientific, Clinical Diagnostics Division 46360 Fremont Blvd FREMONT CA 94538

. ← – – – – Re: K123271

> Trade/Device Name: Abbott Phenobarbital Assay Regulation Number: 21 CFR 862.3660 Regulation Name: Phenobarbital test system Regulatory Class: II Product Code: DLZ Dated: February 27, 2013 Received: March 18, 2013

Dear Ms. Lee:

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 Part 801); 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 regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

# Carol C. Benson -S for

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number: k123271

#### Device Name:

Abbott Phenobarbital Assay

#### Indications For Use:

The Abbott Phenobarbital assay is for in vitro diagnostic use for the quantitative measurement of phenobarbital in human serum or plasma on the ARCHITECT cSystems. The measurements obtained are used in the diagnosis and treatment of phenobarbital overdose and in monitoring levels of phenobarbital to help ensure appropriate therapy.

Prescription Use X AND/OR

(Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Yung WDC han-S

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

k123271 510(k)

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