The Alinity o Benzodiazepines Reagent Kit is a homogeneous enzyme immunoassay intended for the qualitative and/or semiquantitative determination of the presence of benzodiazepines and their metabolites in human urine at a cutoff concentration of 200 ng/mL (0.700 umol/L) on the Alinity c analyzer.

The semiquantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/Tandem Mass Spectrometry (LC- MS/MS) or permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method.

Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.

Device Description

The Alinity c Benzodiazepines Reagent Kit is a homogeneous enzyme immunoassay with liquid ready to-use reagents. The assay uses a specific antibody that can detect most benzodiazepines and their metabolites in urine. The assay is based on competition between a drug labeled with glucose-6- phosphate dehydrogenase (G6PDH), and free sample, for a fixed amount of specific antibody binding sites. In the absence of free drug from the sample, the specific antibody binds the druq labeled with G6PDH and causes a decrease in enzyme activity. In the presence of free drug occupies the antibody binding sites, allowing the drug bound G6PDH to interact with the substrate, resulting in enzyme activity. This phenomenon creates a direct relationship between the drug concentration in urine and enzyme activity is determined spectrophotometrically at 340 nm by measuring the conversion of nicotinamide adenine dinucleotide (NAD) to NADH.

Benzodiazepines are sedative-hypnotic drugs, which are subject to abuse. Benzodiazepines are include a wide variety of drugs such as alprazolam, diazepam, lorazepam, oxazepam, and triazolam. They are absorbed and metabolized at different rates, resulting in various psychoactive effects. Baselt describes the metabolism and toxicology of numerous benzodiazepines, including alprazeoam, chlordiazepoxide, clobazam, clorazepate, diazepan, estazolam, flunitrazepam, halazepam, medazepam, midazolam, nitrazepam, oxazepam, prazepam, quazepam, temazepam, and triazolam.

The Alinity c Benzodiazepines Reagent Kit is a first-line device, which may be used by medical personnel, along with clinical observations, as an aid for indicating Benzodiazeoine abuse through detection of benzodiazepines or their metabolites in urine

AI/ML Overview

The document provided is a 510(k) Premarket Notification for an in vitro diagnostic device, the Alinity c Benzodiazepines Reagent Kit. It focuses on demonstrating substantial equivalence to a predicate device, rather than proving the device meets a specific set of acceptance criteria for an AI model.

Therefore, many of the requested details regarding AI model acceptance criteria, ground truth establishment, expert adjudication, MRMC studies, and training/test set sample sizes for an AI study are not present in this document. This document describes the performance characteristics of a laboratory immunoassay, which is a chemical assay, not an AI or software algorithm that interprets images or complex data.

However, based on the provided text, I can extract the following information relevant to the device's analytical performance and its comparison to a predicate, which serves as a form of "acceptance criteria" for a diagnostic kit:

1. A table of acceptance criteria and the reported device performance:

The document doesn't explicitly state "acceptance criteria" in a typical table format for an AI model's performance metrics (e.g., sensitivity, specificity, AUC with predefined thresholds). Instead, it describes the performance observed and compares it to a predicate device, often noting if they are "identical" or "substantially equivalent." The performance data presented are for specific analytical studies of the reagent kit.

Here's an attempt to structure the performance characteristics as reported, which act as the evidence for "acceptance" (i.e., substantial equivalence):

Performance Characteristic	Predicate Device Performance (DRI Benzodiazepine Assay K173963)	Candidate Device Performance (Alinity c Benzodiazepines Reagent Kit)	Comparison / "Acceptance Criteria" Met
Indications for Use	The same	The same	Identical
Intended Use	The same, for detection of benzodiazepines and metabolites in human urine at 200 ng/mL cutoff. Calibrated against Oxazepam.	The same, for detection of benzodiazepines and metabolites in human urine at 200 ng/mL cutoff (0.700 µmol/L). Calibrated against oxazepam.	Identical (except for brand name and analyzer name, which don't impact intended use)
Specificity (cross-reactivity)	N/A (implied to be acceptable)	N/A (implied to be acceptable)	Identical, as study is not instrument dependent
Interference	N/A (implied to be acceptable)	N/A (implied to be acceptable)	Identical, as study is not instrument dependent
Specific Gravity	N/A (implied to be acceptable)	N/A (implied to be acceptable)	Identical, as study is not instrument dependent
Shelf-life Stability	N/A (implied to be acceptable)	N/A (implied to be acceptable)	Identical, as study is not instrument dependent
Traceability	N/A (implied to be acceptable)	N/A (implied to be acceptable)	Identical, as study is not instrument dependent
Accuracy and Method Comparison (Qualitative & Semiquantitative at 200 ng/mL cutoff)	≥90% negative, positive, and overall percent agreement with LC-MS/MS.	Positive Agreement: 100.00%Negative Agreement: 96.96%Overall Agreement: 98.41%	Substantially equivalent to predicate, both achieved ≥90% agreement with LC-MS/MS.
Accuracy by Recovery and Dilution Linearity (Semiquantitative mode)	%Recovery within ±20% of expected/target concentration for each sample.	%Recovery between 92.5% and 108.3%.	Substantially equivalent to predicate; %Recovery met acceptance criterion (±20% from expected).
On-Board Reagent Stability	N/A (predicate designed for multiple analyzers)	56 days for qualitative and semiquantitative modes.	Candidate device demonstrated 56 days on-board stability.
Precision (Within-Laboratory Precision)	≥95% of samples spiked at -25%, -50%, -75%, -100% below cutoff read as negative, and ≥95% of samples spiked at +25%, +50%, +75%, +100% above cutoff read as positive.	≥95% of samples spiked at -25%, -50%, -75%, -100% below cutoff read as negative, and ≥95% of samples spiked at +25%, +50%, +75%, +100% above cutoff read as positive.	Substantially equivalent; performance data comparable.
Precision (Reproducibility)	N/A (Data might be implied under "Precision")	100% of samples < 200 ng/mL read as negative; 100% of samples > 200 ng/mL read as positive.	Met acceptance criteria for reproducibility on multiple Alinity c analyzers.
Specimen Storage and Stability	Documented guidelines (e.g., 2-8°C for 2 months, -20°C for longer)	Room Temperature: 24 hours2 to 8°C: 30 daysBelow -20°C: Indefinite (avoid repeated freeze/thaw)	Modernized to reflect accurate present guidelines and clearer handling instructions.

2. Sample size used for the test set and the data provenance:

Test Set Sample Size:
- Accuracy and Method Comparison: The document states that the Alinity c Benzodiazepines Reagent Kit demonstrated "equivalent performance" when compared to LC-MS/MS, yielding "positive agreement was 100.00%, negative agreement was 96.96%, and overall agreement was 98.41%". While percentages are given, the absolute number of samples used for this accuracy study is not explicitly stated in the provided text.
- Accuracy by Recovery and Dilution Linearity: A "series of samples" were analyzed, but the specific number is not stated.
- Precision (Within-Laboratory and Reproducibility): The percentages of correctly read samples are given, but the underlying number of samples/tests performed is not explicitly stated.
- On-Board Reagent Stability: "one lot" was used, but the number of tests or samples is not explicitly stated.
Data Provenance (country of origin, retrospective/prospective): Not specified in the provided text.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This is not applicable as this is an in vitro diagnostic (IVD) chemical assay, not an AI product requiring expert review of medical images or data for ground truth. The ground truth for chemical assays is typically established by a reference method.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Not applicable, as this is an IVD chemical assay, not an AI product. Ground truth is established by a reference method.

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, as this is an IVD chemical assay, not an AI product involving human readers.

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

The device (Alinity c Benzodiazepines Reagent Kit) is a standalone diagnostic test (specifically, an enzyme immunoassay) that provides results without human interpretation of raw assay data. The results (qualitative or semiquantitative determination of benzodiazepine presence) are generated by the Alinity c analyzer using the reagent kit. This is inherently a "standalone" analytical performance.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

For the Accuracy and Method Comparison study, the reference method (ground truth) used was Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS). This is explicitly stated: "The Alinity c Benzodiazepines Reagent Kit demonstrated equivalent performance on the Alinity c analyzer when compared to the reference LC-MS/MS". The document also mentions GC/MS or LC-MS/MS as the "preferred confirmatory method" in the Indications for Use.

8. The sample size for the training set:

Not applicable. This is an IVD chemical assay; there is no "training set" in the context of machine learning model development. The assays are developed and validated using a different process than AI models.

9. How the ground truth for the training set was established:

Not applicable, as there is no training set for an AI model. For the chemical assay, "ground truth" for development and validation would involve well-characterized samples and reference methods like LC-MS/MS. The calibrators and controls for the assay are stated to contain Oxazepam and are traceable to a commercial source with 98% purity.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and 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. Underneath the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

December 11, 2024

Microgenics Corporation Nikhita Tandon Manager, Regulatory Affairs 46500 Kato Road Fremont, California 94538

Re: K243498

Trade/Device Name: Alinity c Benzodiazepines Reagent Kit Regulation Number: 21 CFR 862.3170 Regulation Name: Benzodiazepine Test System Regulatory Class: Class II Product Code: JXM Dated: November 11, 2024 Received: November 12, 2024

Dear Nikhita Tandon:

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 (the 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 available 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.

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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 mediation-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-regulatory

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assistance/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,

Image /page/2/Picture/3 description: The image shows the name "Joseph A. Kotarek -S" and a digital signature. The digital signature states that it was signed by Joseph A. Kotarek -S on December 11, 2024, at 14:38:36. The time zone is -05'00'. The name is written in a larger font than the digital signature.

Joseph Kotarek, Ph.D. Branch Chief Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics 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) K243498

Device Name Alinity c Benzodiazepines Reagent Kit

Indications for Use (Describe)

Chromatography/Tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method.

Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.

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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Alinity c Benzodiazepines Reagent Kit Special Premarket Notification

510(k) Summary K243498

I. Device Information

Contact Details
Sponsor:	Microgenics CorporationThermo Fisher Scientific46500 Kato RoadFremont, CA 94538, USAPhone: 925-208-7045
Correspondent Contact Information:	Nikhita TandonManager, Regulatory AffairsEmail: Nikhita.tandon@thermofisher.comPhone:925-208-7045
Device Name
Device Trade Name:	Alinity c Benzodiazepines Reagent Kit
Common Name:	Benzodiazepine Test System
Classification Name:	Enzyme Immunoassay, Benzodiazepine
Regulation Number:	21 CFR 862.3170
Product Code:	JXM
Legally Marketed Predicate Device
Predicate Premarket Notification Number:	K173963
Predicate Trade Name:	DRI Benzodiazepine Assay
Predicate Common Name:	Benzodiazepine Test System
Predicate Classification Name:	Enzyme Immunoassay, Benzodiazepine
Predicate Regulation Number:	21 CFR 862.3170
Predicate Product Code:	JXM

ll. Date Summary Prepared

November 11, 2024

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lll. Description of Device

IV. Intended Use

A. Indications for Use:
See indications for use below.

B. Intended Use:

The Alinity c Benzodiazepines Reagent Kit is a homogeneous enzyme immunoassay intended for the qualitative and/or semiquantitative determination of the presence of benzodiazepines and their metabolites in human urine at a cutoff concentration of 200 ng/mL (0.700 umol/L) on the Alinity c analyzer.

The assay is intended to be used in laboratories and provides a rapid analytical screening procedure to detect benzodiazepines in human urine. This assay is calibrated against oxazepam. This product is intended to be used by trained professionals only. The semiquantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/Tandem Mass Spectrometry (LC- MS/MS) or permitting laboratories to establish quality control

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procedures.

The assay provides only a preliminary analytical test result. A more specific alternative chemical must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method : 2 Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.

V. Comparison to Predicate Device

Characteristics	Predicate DeviceDRI Benzodiazepine Assay (K173963)	Candidate DeviceAlinity c Benzodiazepines Reagent Kit	Comparison
Indications for Use	See intended use below for indications use	See intended use below for indications use	Identical
Intended Use	The DRI® Benzodiazepine Assay is ahomogeneous enzyme immunoassayintended for the qualitative and/or semi-quantitative determination of the presence ofbenzodiazepines and their metabolites inhuman urine at a cutoff concentration of 200ng/mL. The assay is intended to be used inlaboratories and provides a rapid analyticalscreening procedure to detectbenzodiazepines in human urine. The assayis designed for use with a number of clinicalchemistry analyzers. This assay is calibratedagainst Oxazepam. This product is intendedto be used by trained professionals only.The semi-quantitative mode is for the purposeof enabling laboratories to determine anappropriate dilution of the specimen forconfirmation by a confirmatory method suchas Liquid Chromatography/tandem mass	The Alinity c Benzodiazepines Reagent Kit is ahomogeneous enzyme immunoassay intendedfor the qualitative and/or semiquantitativedetermination of the presence ofbenzodiazepines and their metabolites inhuman urine at a cutoff concentration of 200ng/mL (0.700 µmol/L) on the Alinity c analyzer.The assay is intended to be used inlaboratories and provides a rapid analyticalscreening procedure to detectbenzodiazepines in human urine. This assay iscalibrated against oxazepam. This product isintended to be used by trained professionalsonly.The semi-quantitative mode is for the purposeof enabling laboratories to determine anappropriate dilution of the specimen forconfirmation by a confirmatory method such asLiquid Chromatography/Tandem Mass	Identical with exception to thebrand name of the device andnaming of the clinicalchemistry analyzer. This doesnot impact the intended use ofdevice.

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	Predicate DeviceCharacteristics DRI Benzodiazepine Assay (K173963)	Candidate DeviceAlinity c Benzodiazepines Reagent Kit	Comparison
	spectrometry (LC-MS/MS) or permittinglaboratories to establish quality controlprocedures.The assay provides only a preliminaryanalytical test result. A more specificalternative chemical method must be used toobtain a confirmed analytical result. Gaschromatography/ mass spectrometry(GC/MS) or Liquid chromatography/tandemmass spectrometry (LC-MS/MS) is thepreferred confirmatory method.Clinical and professional judgment should beapplied to any drug of abuse test result,particularly when preliminary results are used.For In Vitro Diagnostic Use Only.	Spectrometry (LC-MS/MS) or permittinglaboratories to establish quality controlprocedures.The assay provides only a preliminaryanalytical test result. A more specificalternative chemical method must be used toobtain a confirmed analytical result. GasChromatography/Mass Spectrometry (GC/MS)or Liquid Chromatography/Tandem MassSpectrometry(LC-MS/MS) is the preferred confirmatorymethod.Clinical and professional judgment should beapplied to any drug of abuse test result,particularly when preliminary results are used.For In Vitro Diagnostic Use Only.
FDA ProductCode	JXM	JXM	Identical
DeviceClassificationand Name	21 CFR 862.3170, ENZYMEIMMUNOASSAY, BENZODIAZEPINEBenzodiazepine test system, 91 - Toxicology	21 CFR 862.3170, ENZYME IMMUNOASSAY,BENZODIAZEPINEBenzodiazepine test system, 91 - Toxicology	Identical
OperatingPrinciple(Technology)	Homogeneous Enzyme Immunoassay	Homogeneous Enzyme Immunoassay	Identical
	Predicate Device	Candidate Device
Characteristics	DRI Benzodiazepine Enzyme Immunoassay(K173963)	Alinity c Benzodiazepines Reagent Kit	Comparison
Analyte	Benzodiazepines	Benzodiazepines	Identical
Measured Analyte	Benzodiazepines and their metabolites	Benzodiazepines and their metabolites	Identical
Test Matrix	Human Urine	Human Urine	Identical
Cut-off Levels	200 ng/mL	200 ng/mL	Identical
Methodology	Homogeneous Enzyme Immunoassay	Homogeneous Enzyme Immunoassay	Identical
Materials	Antibody/Substrate Reagent containsactive ingredients: sheep polyclonal anti-benzodiazepine antibodies, glucose-6-phosphate (G6P) and nicotinamide adeninedinucleotide (NAD) and Inactive ingredients:TRIS buffer, bovine serum albumin (BSA).Preservative: sodium azide	Antibody/Substrate Reagent containsactive ingredients: Anti-benzodiazepine sheeppolyclonal antibodies, glucose-6-phosphate(G6P) and nicotinamide adenine dinucleotide(NAD) and Inactive ingredients: TRIS buffer,bovine serum albumin (BSA). Preservative:sodium azide	Identical
	Enzyme Conjugate Reagent contains activeingredients: benzodiazepine derivative labeledwith glucose-6-phosphate dehydrogenase(G6PDH) and Inactive ingredients: TRISbuffer, BSA. Preservative: sodium azide	Enzyme Conjugate Reagent contains activeingredients: benzodiazepine derivative labeledwith glucose-6-phosphate dehydrogenase(G6PDH) and Inactive ingredients: TRIS buffer,BSA. Preservative: sodium azide
Reagent Form	Liquid ready-to-useReagents are sold in three sizes, 18 mL, 100mL and 500 mL kits.	Liquid ready-to-useReagents are sold as 2 cartridges per kit with250 tests per cartridge and 500 tests per kitVolume of R1 per cartridge: 32.2 mLVolume of R2 per cartridge: 31.8 mL	Identical Formulation. Kitavailable in different sizes
Antibody	Sheep Polyclonal Anti-benzodiazepineantibodies	Sheep Polyclonal Anti-benzodiazepineantibodies	Identical
Storage	2-8°C until expiration date	2-8°C until expiration date	Identical
Principal Operator	Trained professionals	Trained professionals	Identical
Instrument	Beckman Coulter AU680 Clinical ChemistryAnalyzer	Alinity c Analyzer System	Different analyzers, but bothmeet the followingrequirements: Automatedclinical analyzers capable ofmaintaining a constanttemperature, pipetting, mixingreagents, measuringenzymatic rates at 340 nm andtiming the reaction accurately.

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Image /page/10/Picture/1 description: The image displays the logo for Thermo Fisher Scientific. The words "Thermo Fisher" are in red, with "Scientific" in black underneath. The font is bold and sans-serif, giving the logo a modern and corporate appearance. The logo is simple and recognizable.

Characteristics	Predicate DeviceDRI Benzodiazepine Enzyme Immunoassay(K173963)	Candidate DeviceAlinity c Benzodiazepines Reagent Kit	Comparison
Package Insert	Header and footer	Header and footer	Different, candidate device'sheader and footer has beenmodernized to reflect presentlabeling regulation andpractices and branding

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Characteristics	Predicate DeviceDRI Benzodiazepine Enzyme Immunoassay(K173963)	Candidate DeviceAlinity c Benzodiazepines Reagent Kit	Comparison
	Additional Material	Additional Material
	Ref Kit Description 1664 DRI Negative Calibrator, 10 mL 1388 DRI Negative Calibrator, 25 mL 1588 DRI Multi-Drug Urine Calibrator 1, 10 mL 1589 DRI Multi-Drug Urine Calibrator 1, 25 mL 1591 DRI Multi-Drug Urine Calibrator 2, 10 mL 1592 DRI Multi-Drug Urine Calibrator 2, 25 mL 1594 DRI Multi-Drug Urine Calibrator 3, 10 mL 1595 DRI Multi-Drug Urine Calibrator 3, 25 mL 1597 DRI Multi-Drug Urine Calibrator 4, 10 mL 1598 DRI Multi-Drug Urine Calibrator 4, 25 mL DOAT-4 MAS® DOA Total-Level 4 DOAT-5 MAS® DOA Total-Level 5																											Ref Kit Description 08P6306 Alinity c DOA MC NegativeCalibrator Kit 09P5201 Alinity c Benzodiazepines QualCalibrator Kit 09P5202 Alinity c BenzodiazepinesSemiquant Calibrator Kit 08P6318 Alinity c DOA MC I Controls											Calibrators and Controls areIdentical in formulation butassigned different Ref.numbers.DOA MC Cals/controls containOxazepam and are traceableto the Oxazepam drugpurchased from a commercialsource which is established at98% purity.

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Alinity c Benzodiazepines Reagent Kit Special Premarket Notification

Characteristics	Predicate Device	Candidate Device	Comparison
	DRI Benzodiazepine Enzyme Immunoassay(K173963)	Alinity c Benzodiazepines Reagent Kit
	Precautions and Warnings	Precautions and Warnings	Different, candidate deviceprecautions and warnings havebeen modernized to reflectpresent safety regulations.
	The reagents are harmful if swallowed.
		• [IVD]
	DANGER:	• For In Vitro Diagnostic Use
	1. The reagents contain ≤ 0.2% bovine serumalbumin (BSA) and ≤0.5% Drug-specific	• [Rx Only]Safety Precautions
	antibody (Sheep). Avoid contact with skin and	CAUTION: This product requires the handling
	mucous membranes. Avoid inhalation.May cause skin or inhaled allergic reaction.	of human specimens. It is recommended thatall human-sourced materials and all
	2. In the case of accidental spill, clean and	consumables contaminated with potentially
	dispose of material according to your	infectious materials be considered potentially
	laboratory's Standard Operating Procedure,	infectious and handled in accordance with the
	local, and state regulations.	OSHA Standard on Bloodborne Pathogens.
	3. In the case of damaged packaging on	Biosafety Level 2 or other appropriate regional,
	arrival, contact your technical support	national, and institutional biosafety practices
	representative.	should be used for materials that contain, are
	4. Reagents used in the assay components	suspected of containing, or are contaminated
	contain ≤0.09% sodium azide. Avoid contact	with infectious agents.5-8
	with skin and mucous membranes. Refer to
	Safety Data Sheet for additional precautions,
	handling instructions, and accidental exposure	The following warnings and precautions
	treatment.	apply to: [R1]
	H317 - May cause allergic skin reaction.	Contains sodium azide.
	H334 - May cause allergy or asthma	EUH032 Contact with acids liberates very
	symptoms or breathing difficulties if inhaled.	toxic gas.
	Avoid breathing mist or vapor. Contaminated	P501 Dispose of contents / container inaccordance with local regulations.
	work clothing should not be allowed out of the
	workplace. Wear protective gloves/eye
	protection/face protection. In case of	The following warnings and precautions apply
	inadequate	to: [R2]
Characteristics	Predicate Device	Candidate Device	Comparison
	DRI Benzodiazepine Enzyme Immunoassay(K173963)	Alinity c Benzodiazepines Reagent Kit
	ventilation wear respiratory protection. If onskin: Wash with plenty of soap and water. IFNHALED: If breathing becomes difficult,remove victim to fresh air and keep at rest in apositioncomfortable for breathing. If skin irritation orrash occurs: Get medical advice/attention. Ifexperiencing respiratory symptoms: Call aPOISON CENTER or doctor/physician. Washcontaminated clothing before reuse. Disposeof contents/container to location in accordancewith local/regional/national/internationalregulations.	WARNING Contains tromethaminehydrochloride* and sodium azide.H316* Causes mild skin irritation.EUH032 Contact with acids liberates verytoxic gas.ResponseP332+P313* If skin irritation occurs: Get medicaladvice / attention.DisposalP501 Dispose of contents / container inaccordance with local regulations.* Not applicable where regulation EC1272/2008 (CLP) or OSHA HazardCommunication 29 CFR 1910.1200 (HCS)2012have been implemented.Follow local chemical disposal regulationsbased on your location along withrecommendations and content in theSafety Data Sheet to determine the safedisposal of this product.For the most current hazard information, seethe product Safety Data Sheet.Safety Data Sheets are available atwww.corelaboratory.abbott or contact yourlocal representative

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					ThermoFisher
		S C I E N T I F I C

	Predicate Device	Candidate Device
Characteristics	DRI Benzodiazepine Enzyme Immunoassay(K173963)	Alinity c Benzodiazepines Reagent Kit	Comparison
	Specimen Collection and Preparation	Specimen Collection and Preparation	Different, candidate device specimen collection and preparation has been modernized to reflect present guidelines and provide clearer handling instructions.
	Collect urine specimens in plastic or glass containers. Care should be taken to preserve the chemical integrity of the urine sample from the time it is collected until the time it is assayed.	The specimen type used for this assay is human urine only.The specimen type listed below was verified for use with this assay.
	Specimens kept at room temperature that do not receive initial test within 7 days5 of arrival at the laboratory may be placed into a secure refrigeration unit at 2-8°C for two months.6 For longer storage prior to analysis or for sample retention after analysis, urine specimens may be stored at -20°C.6, 7	Specimen Collection Vessel SpecialType Conditions Urine Clean plastic or glass containerTesting of fresh urine specimens is suggested. Samples within a pH range of 3 to 11 are suitable for testing with this assay.
	Laboratories following the SAMHSA mandatory guidelines should refer to SAMHSA “Short- Term Refrigerated Storage” and “Long-Term Storage” requirements.4	The instrument does not provide the capability to verify specimen types. It is the responsibility of the operator to verify that the correct specimen types are used in the assay. Specimen Conditions Analyze fresh specimens if possible. To prevent cross contamination, use of disposable pipettes or pipette tips is recommended. Preparation for Analysis
	To protect the integrity of the sample, do not induce foaming and avoid repeated freezing and thawing. An effort should be made to keep pipetted samples free of gross debris. It is recommended that grossly turbid specimens be centrifuged before analysis. Frozen samples should be thawed and mixed prior to analysis. Adulteration of the urine sample may cause erroneous results. If adulteration is

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Characteristics	Predicate Device	Candidate Device	Comparison
	DRI Benzodiazepine Enzyme Immunoassay(K173963)	Alinity c Benzodiazepines Reagent Kit
	suspected, obtain another sample and forwardboth specimens to the laboratory for testing.	Adulteration of the urine specimen may causeerroneous results. If adulteration is suspected,obtain another specimen and forward bothspecimens to the laboratory for testing.
	Handle all urine specimens as if they werepotentially infectious.	An effort should be made to keep pipettedspecimens free of gross debris. It is recommendedthat highly turbidspecimens be centrifuged before analysis.Stored specimens must be inspected forparticulates. If present, mix with a low speed vortexor by inversion andcentrifuge the specimen to remove particulatesprior to testing.Prepare frozen specimens as follows:• Frozen specimens must be completelythawed before mixing.• Mix thawed specimens thoroughly.• Visually inspect the specimens. If layering orstratification is observed, mix until specimensare visibly homogeneous.• If specimens are not mixed thoroughly,inconsistent results may be obtained.Specimen StorageAnalyze fresh specimens if possible.
		SpecimenTypeTemperature	Maximum Storage Tim
Characteristics	Predicate Device	Candidate Device	Comparison
	DRI Benzodiazepine Enzyme Immunoassay(K173963)	Alinity c Benzodiazepines Reagent Kit
		UrineRoom Temperature2 to 8°C
		24 hours930 days10
		If analysis will not be completed within the maximum storage recommendations, the urine should be frozen at or below -20°C.11 Repeated freeze/thaw cycles should be avoided to minimize analyte deterioration.
		It is the responsibility of the individual laboratory to determine specific specimen stability criteria for their laboratory per their laboratory workflow.
		For additional information on sample handling and processing, refer to CLSI C52-ED3.11 The storage information provided here is based on references maintained by the manufacturer.
		Stored specimens must be inspected for particulates. If present, mix with a low-speed vortex or by inversion and centrifuge the specimen to remove particulates prior to testing.
		Specimen ShippingPackage and label specimens in compliance with applicable state, federal, and international regulations covering the transport of clinical specimens and infectious substances.
Characteristics	Predicate DeviceDRI Benzodiazepine Enzyme Immunoassay(K173963)	Candidate DeviceAlinity c Benzodiazepines Reagent Kit	Comparison
		Do not exceed the storage limitations listed above.

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				ThermoFisher
S C I E N T I F I C

	Predicate Device	Candidate Device
Characteristics	DRI Benzodiazepine Enzyme Immunoassay	Alinity c Benzodiazepines Reagent Kit	Comparison
	(K173963)
	References4. Department of Health and Human Services.Notice of Mandatory Guidelines For FederalWorkplace Drug Testing Programs: Finalguidelines. Federal Register, SubstanceAbuse and Mental Health Administration(SAMHSA), (1994) 110 (June 9): 11983.5. Zaitsu K, Miki A, Katagi M, Tsuchihashi H.Long-term stability of various drugs andmetabolites in urine, and preventive measuresagainst their decomposition with specialattention to filtration sterilization. ForensicScience Intl 174 (2008) 189-196.6. Gonzales E, Ng G, Pesce A, West C, West R, Mikel C, Llaatyshev, S, Almazan P. Stabilityof pain-realted medications, metabolites andillicit substances in urine. Clinica Chimca Acta416: (2013) 30-35.7. C52-A2, Toxicology and Drug Testing in theClinical Laboratory; Approved Guideline –Second Edition, Clinical and LaboratoryStandards Institute (CLSI) (April 2007).	References9. Dahlin JL, Palte MJ, LaMacchia J, PetridesAK. A Rapid Dilute-and-Shoot UPLC-MS/MSAssay to Simultaneously Measure 37 Drugsand Related Metabolites in Human Urine forUse in Clinical Pain Management. J Appl LabMed 2019;3(6):974-992.10. Dixon RB, Mbeunkui F, Wiegel JV. Stabilitystudy of opioids and benzodiazepines in urinesamples by liquid chromatography tandemmass spectrometry. J Anal Sci Technol 2015;6(17).11. Clinical and Laboratory Standards Institute(CLSI). Toxicology and Drug Testing in theMedical Laboratory; Approved Guideline–Third Edition. CLSI Document C52. Wayne,PA: CLSI; 2017.	Different, candidate devicelists citations/referencesmodernized to representaccurate and presentguidelines.
Characteristics	Predicate DeviceDRI BenzodiazepineEnzymeImmunoassay(K173963)	Candidate DeviceAlinity c Benzodiazepines ReagentKit	Comparison
PerformanceCharacteristics	**Data on the IFU is representative. Actual values collected on the 2 devices à PredicateDevice (Beckman Coulter AU680 Clinical Chemistry Analyzer) and on the Candidate Device(Alinity c Analyzer System), are not expected to be identical as they have been collected ondifferent instruments, with different lots of reagents and samples.As demonstrated below, the results on both devices are proven to be substantially equivalent.
Characteristics	Predicate DeviceDRI BenzodiazepineEnzymeImmunoassay(K173963)	Candidate DeviceAlinity c Benzodiazepines ReagentKit
	Precision (Within-Laboratory Precision)	Precision (Within-LaboratoryPrecision and Reproducibility)	Predicate Device and CandidateDevice performance data aresubstantially equivalent indemonstrating precision (Within-Laboratory Precision)Additional reproducibility data isadded to reflect the presentguideline.
			For Within-Laboratory Precision≥95% of samples spiked at levels -25%, -50%, -75%, and -100% belowthe 200 ng/mL cutoff read asnegative and ≥95% of samplesspiked at levels +25%, +50%,+75%, +100% above the 200 ng/mLcutoff read as positive in bothqualitative and semi-quantitativemodes.
			For ReproducibilityIn both qualitative andsemiquantitative applications, 100%of samples at levels less than 200ng/mL read as negative, and 100%of samples at levels higher than 200ng/mL read as positive.Alinity c Benzodiazepines ReagentKit meets the acceptance criteria forprecision (reproducibility)performance on multiple Alinity c
Characteristics	Predicate DeviceDRI BenzodiazepineEnzymeImmunoassay(K173963)	Candidate DeviceAlinity c Benzodiazepines ReagentKit	Comparison
	Accuracy and Methodcomparison	Accuracy and Method Comparison	Predicate Device and CandidateDevice are substantially equivalentin demonstrating Accuracy when theimmunoassay method (predicatedevice or candidate device at 200ng/mL cutoff) is compared to thereference confirmatory method LC-MS/MS in measuring patientsamples. Both devices showed≥90% negative sample, positivesample and overall percentagreement with LC-MS/MS.
	Accuracy byRecovery and DilutionLinearity	Accuracy by Recovery and DilutionLinearity	Predicate Device and CandidateDevice are substantially equivalentin demonstrating dilution linearitythroughout the calibration range.For both devices. the %Recovery ofMean Observed Concentration inrelative to Expected (Target)Concentration for each sample metacceptance criterion (± 20% fromthe expected concentration).
	Onboard Stability -N/A because thedevice is designed foruse with a number ofclinicalchemistry analyzers.	Onboard stability- 56 days, becausethe device is designed for use onspecific clinical chemistry analyzer-the Alinity platform	Candidate Device achieved on-board reagent stability of 56 days.

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Image /page/19/Picture/1 description: The image shows the logo for Thermo Fisher Scientific. The words "Thermo Fisher" are in red, and the word "SCIENTIFIC" is in black. The logo is simple and modern.

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Image /page/20/Picture/1 description: The image contains the logo for Thermo Fisher Scientific. The words "Thermo Fisher" are in red, bold font on the top line. The word "SCIENTIFIC" is in a smaller, black, bold font on the second line.

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Image /page/21/Picture/1 description: The image contains the logo for Thermo Fisher Scientific. The words "Thermo Fisher" are in red, stacked on top of the word "SCIENTIFIC" which is in black. The logo is simple and modern.

Characteristics	Predicate DeviceDRI Benzodiazepine EnzymeImmunoassay (K173963)	Candidate DeviceAlinity c BenzodiazepinesReagent Kit	Comparison
	Specimen storage andstability	Specimen storage and stability	Compared to Predicate Device,Specimen storage and stability hasbeen modernized in the CandidateDevice to reflect accurate presentguidelines and provide clearerhandling instructions for specimenstorage and stability claim whencompared to the predicate device.Refer to the specimen collection andpreparation comparison under"package insert" section above forsupporting literature references.
	Specificity (crossreactivity -structurally relatedand unrelated) Interference Specific Gravity Shelf-life Stability Traceability	Specificity (crossreactivity - structurallyrelated and unrelated) Interference Specific Gravity Shelf-life Stability Traceability	Identical, as these performancestudies are not instrument dependent
ProductLabeling	Kit Labeling ComponentLabeling	Kit Labeling ComponentLabeling	Different, candidate device kit andcomponent labeling have beenmodernized to reflect present thecurrent labeling regulation, safetypractices and branding.

VI. Summary of Performance Testing

A. Accuracy and Method Comparison: CLSI Guideline: EP09-A3 and CLSI EP12-A2.

The Alinity c Benzodiazepines Reagent Kit demonstrated equivalent performance on the Alinity c analyzer when compared to the reference LC-MS/MS when using the qualitative and semiquantitative applications at a cutoff of 200 ng/mL. cutoff assay, the positive agreement was 100.00%, negative agreement was 96.96%, and overall agreement was 98.41% in both qualitative and semiquantitative applications.

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B. Accuracy by Recovery and Dilution Linearity: CLSI Guideline: EP06-A

The Alinity c Benzodiazepines Reagent Kit underwent an Accuracy by Recovery and Dilution Linearity study to assess its dilution linearity and accuracy by recovery. The test mode used was semi- quantitative. A series of samples with expected concentrations ranging from 0.5 ng/mL to 1051.5 ng/mL were analyzed. The % recovery range for these samples was between 92.5% and 108.3%, indicating that the assay's accuracy by recovery was within the acceptable criteria of ± 20% from the expected concentration of each sample.

C. On-Board Reagent Stability: CLSI Guideline: EP25-A

The study was conducted to determine if sample results were susceptible to drift when the reagents were stored for 56 days for qualitative application and stored for a minimum of 7 days for semiquantitative application on board the Alinity c analyzer while the instrument was in continuous running mode. Reagent On-Board stability studies for one lot stored on-board clinical analyzer (Alinity c) supports the claim of 56 days for qualitative and semi-quantitative modes.

D. Precision: CLSI Guideline: EP05-A3

a. Within-Laboratory Precision Study

The Alinity c Benzodiazepines Reagent Kit demonstrated acceptable precision for both qualitative and semi-quantitative applications.

Greater than or equal to 95% of samples spiked at levels -25%, -50%, -75%, and -100% below the cutoffs read as negative and greater than or equal to 95% of samples spiked at levels +25%, +50%, +75%, +100% above the cutoffs read as positive in both Qualitative and Semi-quantitative modes.

b. Reproducibility Study

Alinity c Benzodiazepines Reagent Kit meets the acceptance criteria for precision (reproducibility) performance on multiple Alinity c clinical chemistry analyzers. In both qualitative and semiquantitative applications, 100% of samples at levels less than 200 ng/mL read as negative, and 100% of samples at levels higher than 200 ng/mL read as positive.

VII. Conclusion

The information supports a determination of substantial equivalence between the candidate device Alinity c Benzodiazepines Reagent Kit and the predicate device DRI Benzodiazepine Assay (K173963).

Regulation Number and Section

§ 862.3170 Benzodiazepine test system.

(a)
Identification. A benzodiazepine test system is a device intended to measure any of the benzodiazepine compounds, sedative and hypnotic drugs, in blood, plasma, and urine. The benzodiazepine compounds include chlordiazepoxide, diazepam, oxazepam, chlorzepate, flurazepam, and nitrazepam. Measurements obtained by this device are used in the diagnosis and treatment of benzodiazepine use or overdose and in monitoring levels of benzodiazepines to ensure appropriate therapy.(b)
Classification. Class II (special controls). A benzodiazepine 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).