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 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.

AI/ML Overview

The Abbott Phenobarbital Assay demonstrated substantial equivalence to the predicate device (Abbott Aerosett Phenobarbital Assay (K993031)) through a series of performance studies. The studies assessed various analytical characteristics of the device to ensure it meets its intended use for the quantitative measurement of phenobarbital in human serum or plasma.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria	Reported Device Performance
Limit of Quantitation (LOQ)	Inter-assay precision ≤ 7% CV or 0.7 µg/mL SD; Bias ≤ 10% or 1.0 µg/mL	LOQ is 2.0 µg/mL, meeting design acceptance criteria.
Precision	Total run %CV ≤ 6.7%	Total run %CV was less than or equal to 6.7%, meeting design acceptance criteria.
Spike Recovery	Recover within ±10% or ±1.0 µg/mL error of HPLC results	All samples recovered within ±10% or ±1.0 µg/mL error of the HPLC results.
Method Comparison (vs. HPLC)	Correlate well with HPLC (specific metrics implied but not explicitly stated as acceptance criteria, but shown to be strong)	y = 0.933x + 0.68, R = 0.9887, n=108. (Strong correlation observed)
Specificity (Cross-Reactivity)	Minimal to no cross-reactivity to other medications; Minimal to no interference from endogenous substances	Showed minimal to no cross-reactivity to other potentially administered medications. Showed minimal to no interference to endogenous substances up to the concentrations tested.
Linearity	Linear performance throughout the assay range (2.0 to 80 µg/mL)	Demonstrated linear performance from 2.0 to 80 µg/mL.
Onboard Stability	Stable for a specified period	Reagents stable onboard for up to 45 days.
Standard Curve Calibration Stability	Stable for a specified period	Standard curve calibration stable for up to 14 days.
Reagent Shelf Life Stability	Stable for a specified period	Reagents will be stable at 2-8°C for 24 months.

2. Sample Size Used for the Test Set and Data Provenance

Limit of Quantitation (LOQ): The text indicates the LOQ was measured "over an extended period" but does not specify the exact number of samples or runs.
Precision: Not explicitly stated, but the study followed a CLSI protocol, which typically involves multiple samples tested over several runs and days.
Spike Recovery: "Negative serum samples were spiked with phenobarbital at concentrations across the assay range." The exact number of samples is not stated.
Method Comparison: 108 samples (n=108) were tested.
Matrix Comparison: The following matrices were tested: 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. The number of samples for each matrix is not specified.
Specificity (Cross-Reactivity/Interference): Not explicitly stated, but implies multiple substances were tested across various concentrations.
Linearity: "Samples were tested to demonstrate linearity throughout the assay range." The exact number of samples is not specified.
Onboard Stability, Standard Curve Calibration Stability, Reagent Shelf Life Stability: These studies involve testing over time with an unspecified number of samples or replicates.

Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of in vitro diagnostic device testing for regulatory submission, it is typically prospective, controlled laboratory studies using prepared samples (spiked, diluted, or well-characterized patient samples).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of submission for an in vitro diagnostic assay does not typically involve expert clinical readers or radiologists. The "ground truth" for the test set is established by:

Reference Methods: For method comparison, High-Performance Liquid Chromatography (HPLC) results are used as the reference method ("gold standard") for phenobarbital concentration. This approach does not involve human expert interpretation in the same way imaging studies might.
Known Concentrations: For studies like linearity, spike recovery, LOQ, and precision, samples are prepared with known, precisely measured concentrations of phenobarbital.
CLSI Protocols: The reference to CLSI protocols indicates established laboratory standards are followed for experimental design and data analysis, ensuring the rigor of the "ground truth" establishment through standardized procedures.

Therefore, there are no "experts" in the clinical interpretation sense involved in establishing the ground truth; rather, the ground truth is analytically derived.

4. Adjudication Method for the Test Set

Not applicable. As described above, the ground truth is established through analytical reference methods or known sample compositions, not through human adjudication of clinical findings.

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

Not applicable. This device is an in vitro diagnostic assay for quantitative measurement, not an AI-assisted diagnostic imaging or clinical decision support tool that involves human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

The entire performance evaluation is inherently a "standalone" or "algorithm-only" assessment in the context of an automated IVD assay. The Abbott Phenobarbital Assay, once calibrated, quantifies phenobarbital concentration based on its reaction kinetics. The performance studies detailed are evaluating this standalone analytical performance.

7. The Type of Ground Truth Used

The ground truth used in these studies is primarily:

Reference Method Assays: For method comparison, HPLC (High-Performance Liquid Chromatography) served as the reference method for confirming phenobarbital concentrations.
Known Concentrations: For precision, linearity, LOQ, and spike recovery, samples were prepared with known, established concentrations of phenobarbital.

8. The Sample Size for the Training Set

The document describes performance testing for a finished device. It does not provide information about a "training set" in the context of machine learning, as this is a chemical assay, not an AI/ML device. Therefore, the concept of a training set as understood in AI/ML is not applicable here. The assay is "trained" or optimized during its development phase through iterative experimentation, but the data for this is not detailed in a 510(k) summary (which focuses on verification and validation).

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no "training set" in the AI/ML sense. The "ground truth" for the development and optimization of the assay would have been established through precisely prepared samples with known phenobarbital concentrations and comparisons to established analytical methods during the research and development phases of the assay.

Summary

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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: (510) 979-5000 x31814 (510) 979-5422 Fax: E-mail: karen.lee@thermofisher.com

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

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

Component	Description	Configuration
R1 AntibodyReagent	<2.0% Anti-Phenobarbital monoclonal antibody (mouse)in Tris buffer and <0.09% sodium azide as preservative.	3 x 23 mL
R2 MicroparticleReagent	<1.0% Phenobarbital-coated microparticles containing<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
ProprietaryName	Abbott Phenobarbital Assay	Abbott Aeroset® Phenobarbital Assay(K993031)
Intended Use	The Phenobarbital assay is used for the invitro quantitative measurement ofphenobarbital in human serum or plasmaon the ARCHITECT cSystems.	The assay is intended for use in thequantitative analysis of Phenobarbital inhuman serum or plasma.
Test Principle	The Phenobarbital assay is ahomogeneous particle-enhancedturbidimetric inhibition immunoassay(PETINIA) used for the analysis ofphenobarbital in serum or plasma. Theassay is based on competition betweendrug in the sample and drug coated onto amicroparticle for antibody binding sites ofthe phenobarbital antibody reagent. Thephenobarbital-coated microparticle reagentis rapidly agglutinated in the presence ofthe anti-phenobarbital antibody reagent andin the absence of any competing drug inthe sample. The rate of absorbancechange is measured photometrically, and isdirectly proportional to the rate ofagglutination of the particles. When asample containing phenobarbital is added,the agglutination reaction is partiallyinhibited, slowing down the rate ofabsorbance change. A concentration-dependent classic agglutination inhibitioncurve can be obtained, with maximum rateof agglutination at the lowest phenobarbitalconcentration and the lowest agglutinationrate at the highest phenobarbitalconcentration.	The Phenobarbital assay is ahomogeneous enzyme immunoassaytechnique used for the analysis ofphenobarbital in biological fluids. Theassay is based on competition for antibodybinding sites between the analyte drug inthe specimen and exogenous drug labeledwith the enzyme glucose-6-phosphatedehydrogenase (G6PDH). Since G6PDHactivity decreases upon binding to theantibody, the concentration of drug in thespecimen can be measured in terms ofenzyme activity. Active G6PDH reducesnicotinamide adenine dinucleotide (NAD) toNADH, resulting in an absorbance changethat is measured spectrophotometrically.Endogenous serum G6PDH does notinterfere because the coenzyme NADfunctions only with the bacterial(Leuconostoc mesenteroides) enzymeemployed in the assay.
Sample Matrix	Human Serum or Human Plasma	Human Serum or Human Plasma
Reagent	Liquid Ready-to-Use (Antibody reagent,Phenobarbital-coated microparticlereagent)	Liquid Ready-to-Use (Antibody reagent,Phenobarbital-labeled enzyme reagent)
Storage	2-8°C	2-8°C
Calibrator	Liquid Ready-to-Use, six levels (0.0, 5.0,10.0, 20.0, 40.0, and 80.0 µg/mL)	Liquid Ready-to-Use, six levels (0.0, 5.0,10.0, 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

ristics

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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 (800) 638-2041 or (301) 796-7100 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:

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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Regulation Number and Section

§ 862.3660 Phenobarbital test system.

(a)
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.(b)
Classification. Class II.