The TBI test is a panel of in vitro diagnostic chemiluminescent microparticle immunoassays (CMIA) used for the quantitative measurements of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) in human plasma and serum and provides a semi-quantitative interpretation of test results derived from these measurements using the ARCHITECT i1000SR System.

The interpretation of test results is used, in conjunction with other clinical information, to aid in the evaluation of patients, 18 years of age or older, presenting with suspected mild traumatic brain injury (Glasgow Coma Scale score 13-15) within 12 hours of injury, to assist in determining the need for a CT (computed tomography) scan of the head. A negative test result is associated with the absence of acute intracranial lesions visualized on a head CT scan.

The TBI test is intended for use in clinical laboratory settings by healthcare professionals.

Device Description

The TBI test is a panel of in vitro diagnostic quantitative measurements of GFAP and UCH-L1 and provides a semi-quantitative interpretation of GFAP and UCH-L1 in human plasma and serum.

GFAP: This assay is an automated, two-step immunoassay for the quantitative measurement of GFAP in human plasma and serum using chemiluminescent microparticle immunoassay (CMIA) technology.

UCH-L1: This assay is an automated, two-step immunoassay for the quantitative measurement of UCH-L1 in human plasma and serum using CMIA technology.

Interpretation of Results: The assay cutoffs were established to be 35.0 pg/mL (35.0 ng/L) for GFAP and 400.0 pg/mL (400.0 ng/L) for UCH-L1. The GFAP and UCH-L1 results are reported separately and the software provides a TBI interpretation relative to the respective cutoff values.

AI/ML Overview

The provided text describes the TBI (Traumatic Brain Injury) test, an in vitro diagnostic device, and its performance evaluation for the ARCHITECT i1000SR system. The submission is a 510(k) for substantial equivalence to a predicate device (TBI on the Alinity i system).

Here's an analysis of the acceptance criteria and study as per your request, based on the provided text:

Acceptance Criteria and Reported Device Performance

The document does not explicitly present a "table of acceptance criteria" in the format of specific thresholds for the performance metrics. Instead, it states that the device "met the pre-defined product requirements for all characteristics evaluated in the verification studies." The performance metrics reported are for precision (20-Day and Reproducibility), Limits of Blank (LoB), Detection (LoD), Quantitation (LoQ), and Linearity, along with a comparison summary using Passing-Bablok regression against the predicate device.

Table of Reported Device Performance (Implied Acceptance through Meeting Requirements):

Performance Metric	Reported Device Performance (TBI on ARCHITECT i1000SR)
GFAP 20-Day Precision	2.2 to 6.2 %CV for samples with GFAP concentrations from 20.4 to 37,098.8 pg/mL
UCH-L1 20-Day Precision	2.2 to 4.5 %CV for samples with UCH-L1 concentrations from 187.6 to 19,645.0 pg/mL
GFAP Reproducibility	2.7 to 6.0 %CV for samples with GFAP concentrations from 23.6 to 34,087.5 pg/mL; 1.30 pg/mL SD for sample with GFAP concentration 19.1 pg/mL
UCH-L1 Reproducibility	2.4 to 3.9 %CV for samples with UCH-L1 concentrations from 193.0 to 20,363.2 pg/mL
GFAP LoB	2.0 pg/mL
GFAP LoD	3.2 pg/mL
GFAP LoQ	6.1 pg/mL
UCH-L1 LoB	9.2 pg/mL
UCH-L1 LoD	18.3 pg/mL
UCH-L1 LoQ	26.3 pg/mL
GFAP Linearity	6.1 to 42,000.0 pg/mL
UCH-L1 Linearity	26.3 to 25,000.0 pg/mL
Sample Onboard Stability	2 hours
Reagent Onboard/Calibration Curve Storage Stability	30 days
Comparison to Predicate (GFAP)	N=123, R=1.00 (95% CI: 1.00, 1.00), Intercept: -0.6 (95% CI: -1.1, -0.3), Slope: 1.03 (95% CI: 1.02, 1.05)
Comparison to Predicate (UCH-L1)	N=123, R=1.00 (95% CI: 1.00, 1.00), Intercept: -6.0 (95% CI: -7.9, -4.0), Slope: 1.06 (95% CI: 1.05, 1.07)

Study Details:

Sample sizes used for the test set and the data provenance:
- Test Set (Method Comparison): N=123 for both GFAP and UCH-L1 assays in the comparison study against the predicate device.
- Data Provenance: The document does not specify the country of origin of the data or whether the data was retrospective or prospective. It refers to "verification studies" and "studies were performed based on guidance from CLSI EP09c, 3rd ed." These are typically laboratory-based analytical performance studies. The clinical utility of the test (used to aid in evaluation of patients with suspected mild TBI to determine need for CT scan) suggests that patient samples were likely used for the comparison study, but details about their collection (retrospective/prospective, patient demographics, clinical context) are not provided in this summary.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not applicable and not provided in the document. The TBI test is an in vitro diagnostic (IVD) quantitative measurement of biomarkers (GFAP and UCH-L1). The "ground truth" for its performance is established by comparison to a legally marketed predicate device (K223602, TBI for Alinity i) and internal analytical performance studies using known concentrations or reference methods. The "interpretation of test results" for the TBI test (positive/negative) is based on established cutoff values for GFAP and UCH-L1, which are compared to CT scan results (absence of acute intracranial lesions). There is no mention of human experts directly establishing "ground truth" for the device's output itself in this context.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. This is an IVD device measuring biomarkers. Adjudication methods like 2+1 or 3+1 are typically used in image-based diagnostic studies where human readers interpret images, and consensus is sometimes needed to establish ground truth or resolve discrepancies.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. This is an in vitro diagnostic (IVD) test, not an AI-assisted imaging device that impacts human reader performance. Therefore, an MRMC study and effect size on human readers are not applicable.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, in a sense. The TBI test is a standalone device (a panel of immunoassays interpreted by defined cutoffs). Its performance is evaluated analytically (precision, linearity, LoD/LoQ) and by direct comparison of its measurements to those of a predicate device, which is also a standalone IVD. The interpretation of the test results (positive/negative) is an automated process based on the measured biomarker levels and predefined cutoffs. While the "interpretation of test results is used, in conjunction with other clinical information, to aid in the evaluation of patients... to assist in determining the need for a CT (computed tomography) scan," the device itself provides the result as an algorithm-driven interpretation (based on raw measurement data).
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For the quantitative measurements (GFAP, UCH-L1), the "ground truth" in the comparative study is the performance of the legally marketed predicate device (TBI on Alinity i system, K223602). Analytical performance metrics (LoB, LoD, LoQ, linearity, precision) are established using reference materials or samples with known or characterized concentrations.
- For the clinical context of determining the "need for a CT scan of the head," the ground truth stated for a negative test result is its association with "the absence of acute intracranial lesions visualized on a head CT scan." This implies that CT scan findings serve as the clinical ground truth for evaluating the negative predictive value of the test, though this specific performance characteristic is not detailed in the provided summary. For the positive result, the test aids in determining the need for a CT scan, but the summary doesn't explicitly state the ground truth for a positive result (e.g., presence of lesions, clinical outcome).
The sample size for the training set:
- No information about a "training set" is provided. This is an IVD device based on established immunoassay technology and predefined cutoffs, not a machine learning or AI algorithm that typically requires a distinct training phase with labeled data. The cutoffs (35.0 pg/mL for GFAP and 400.0 pg/mL for UCH-L1) are stated as "established," but the method and data used for their establishment are not described in this summary.
How the ground truth for the training set was established:
- Not applicable as no "training set" is mentioned in the context of this 510(k) summary.

Summary

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Image /page/0/Picture/0 description: The image shows the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.

September 29, 2023

Abbott Laboratories Lisa Kelly Associate Director Regulatory Affairs 100 Abbott Park Road Dept.09AA, Building CP1 Abbott Park, Illinois 60064

Re: K232669

Trade/Device Name: TBI Regulation Number: 21 CFR 866.5830 Regulation Name: Brain trauma assessment test Regulatory Class: Class II Product Code: QAT Dated: August 31, 2023 Received: September 1, 2023

Dear Lisa Kelly:

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.

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.

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).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part

Page 2

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 OS 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 (OS) 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.

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-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,

Ying Mao -S

Ying Mao, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

Submission Number (if known)	K232669
Device Name

TBI

Indications for Use (Describe)

The TBI test is intended for use in clinical laboratory settings by healthcare professionals.

Type of Use (Select one or both, as applicable)

| Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary

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

I. Applicant Name

Date summary prepared: September 29, 2023

Abbott Diagnostics Department 09AA, Building CP01 100 Abbott Park Road Abbott Park, IL 60064

Primary contact person for all communications:

Lisa Kelly, Associate Director of Regulatory Affairs Abbott Laboratories lisa.kelly(@abbott.com Phone (224) 668-8849 Fax (224) 280-2358

Secondary contact person for all communications:

Noah Lermer, PhD, Director of Regulatory Affairs Abbott Laboratories noah.lermer@abbott.com Phone (224) 214-7838 Fax (224) 667-1221

II. Device Name

TBI

Reagents

Trade Name: Glial fibrillary acidic protein (GFAP) Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) Device Classification: Class II (Special controls) Classification Name: Brain trauma assessment test Governing Regulation: 21 CFR § 866.5830 Product Code: QAT

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III. Predicate Device

TBI K223602

IV. Description of Device

The TBI test is a panel of in vitro diagnostic quantitative measurements of GFAP and UCH-L1 and provides a semi-quantitative interpretation of GFAP and UCH-L1 in human plasma and serum.

GFAP:

This assay is an automated, two-step immunoassay for the quantitative measurement of GFAP in human plasma and serum using chemiluminescent microparticle immunoassay (CMIA) technology.

Sample, anti-GFAP coated paramagnetic microparticles, and assay specific diluent are combined and incubated. The GFAP present in the sample binds to the anti-GFAP coated microparticles. The mixture is washed. Anti-GFAP acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added.

The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a direct relationship between the amount of GFAP in the sample and the RLU detected by the system optics.

UCH-L1:

This assay is an automated, two-step immunoassay for the quantitative measurement of UCH-L1 in human plasma and serum using CMIA technology.

Sample, anti-UCH-L1 coated paramagnetic microparticles, and assay specific diluent are combined and incubated. The UCH-L1 present in the sample binds to the anti-UCH-L1 coated microparticles. The mixture is washed. Anti-UCH-L1 acridinium-labeled conjugate is added to create a reaction mixture and incubated.

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Following a wash cycle, Pre-Trigger and Trigger Solutions are added.

The resulting chemiluminescent reaction is measured as an RLU. There is a direct relationship between the amount of UCH-L1 in the sample and the RLU detected by the system optics.

Interpretation of Results

The assay cutoffs were established to be 35.0 pg/mL (35.0 ng/L) for GFAP and 400.0 pg/mL (400.0 ng/L) for UCH-L1.

The GFAP and UCH-L1 results are reported separately and the software provides a TBI interpretation relative to the respective cutoff values as shown in the following table.

Specification for Constituent Assay Results	TBI Result	TBI Interpretation
GFAP and UCH-L1 below (<) cutoff	0	Negative
GFAP and/or UCH-L1 above (≥) cutoff	1	Positive

The following table provides a detailed summary of the TBI interpretation based on potential results.

GFAP Assay Result(Relative to Cutoff of35.0 pg/mL [35.0 ng/L])*	UCH-L1 Assay Result(Relative to Cutoff of400.0 pg/mL[400.0 ng/L])*	TBI Interpretation**
Below	Below	Negative
Below	Above	Positive
Above	Below	Positive
Above	Above	Positive
No result	Below	Not reportable***
No result	Above	Positive***
Below	No result	Not reportable***
Above	No result	Positive***
No result	No result	Not reportable***

Above means greater than or equal to the cutoff. Below means less than the cutoff.

** The GFAP and UCH-L1 results can be found on the Result Details screen under Constituent Information on the User Interface.

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*** An automated TBI interpretation will not be reported for specimens without a result for GFAP and/or UCH-L1. The GFAP and/or UCH-L1 assay(s) may be retested if needed to obtain a result and a manual TBI interpretation may be required. The TBI interpretation for a specimen is considered positive if the result for either constituent assay (GFAP or UCH-L1) is greater than or equal to the cutoff and no result is obtained for the other assay. The TBI interpretation for a specimen is not reportable if the result for either constituent assay is less than the cutoff and no result is obtained for the other assay.
In the case of a flagged ">" or "<" result for either assay, the TBI interpretation should be evaluated manually. A result flagged ">" should be considered above the cutoff and a result flagged "<" should be considered below the cutoff.

V. Intended Use of the Device

The TBI test is intended for use in clinical laboratory settings by healthcare professionals.

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VI. Comparison of Technological Characteristics

The similarities and differences between the subject device and the predicate device are presented in the following table.

Characteristics	Cleared Predicate Device:TBI for Alinity i(K223602)	Subject Device:TBI for ARCHITECT
General Device Characteristic Similarities
Intended Use andIndications forUse	The TBI test is a panel of in vitrodiagnostic chemiluminescentmicroparticle immunoassays (CMIA)used for the quantitativemeasurements of glial fibrillary acidicprotein (GFAP) and ubiquitincarboxyl-terminal hydrolase L1(UCH-L1) in human plasma andserum and provides a semi-quantitative interpretation of testresults derived from thesemeasurements using the Alinity isystem.The interpretation of test results isused, in conjunction with otherclinical information, to aid in theevaluation of patients, 18 years of ageor older, presenting with suspectedmild traumatic brain injury (GlasgowComa Scale score 13-15) within12 hours of injury, to assist indetermining the need for a CT(computed tomography) scan of thehead. A negative test result isassociated with the absence of acuteintracranial lesions visualized on ahead CT scan.The TBI test is intended for use inclinical laboratory settings byhealthcare professionals.	The TBI test is a panel of in vitrodiagnostic chemiluminescentmicroparticle immunoassays (CMIA)used for the quantitativemeasurements of glial fibrillary acidicprotein (GFAP) and ubiquitincarboxyl-terminal hydrolase L1(UCH-L1) in human plasma andserum and provides a semi-quantitative interpretation of testresults derived from thesemeasurements using theARCHITECT i1000SR System.The interpretation of test results isused, in conjunction with otherclinical information, to aid in theevaluation of patients, 18 years of ageor older, presenting with suspectedmild traumatic brain injury (GlasgowComa Scale score 13-15) within12 hours of injury, to assist indetermining the need for a CT(computed tomography) scan of thehead. A negative test result isassociated with the absence of acuteintracranial lesions visualized on ahead CT scan.The TBI test is intended for use inclinical laboratory settings byhealthcare professionals.
Intended UseSetting	Clinical Laboratory	Same
Measurands	GFAP and UCH-L1	Same
Specimen Type	Plasma and serum	Same
AssayTechnology	CMIA	Same
Characteristics	Cleared Predicate Device:TBI for Alinity i(K223602)	Subject Device:TBI for ARCHITECT
ReportableResult	Quantitative results for GFAP andUCH-L1 and semi-quantitativeinterpretation for TBI	Same
Calibrators	GFAP: 6 levelsUCH-L1: 6 levels	Same
Controls	GFAP: 3 levels (25.0, 500.0, and30000.0 pg/mL)UCH-L1: 3 levels (250.0, 2000.0, and15000.0 pg/mL)	Same
Assay Format	Two separate test kits – one for GFAPand one for UCH-L1	Same
Sample Volume	GFAP kit: 200 μLUCH-L1 kit: 150 µL	Same
ReportableInterval(pg/mL, ng/L)	Analytical Measuring Interval:GFAP: 6.1 – 42,000.0UCH-L1: 26.3 – 25,000.0Reportable Interval:GFAP: 3.2 - 42,000.0UCH-L1: 18.3 - 25,000.0	Same
GFAP Cutoff	35.0 pg/mL (35.0 ng/L)	Same
UCH-L1 Cutoff	400.0 pg/mL (400.0 ng/L)	Same
Reagentformulation	GFAP Reagent Kit• Microparticles: Anti-GFAP (rabbit, monoclonal) coated microparticles in TRIS buffer with protein (bovine) stabilizer. Minimum concentration: 0.05 % solids. Preservative: ProClin 300.• Conjugate: Anti-GFAP (mouse, monoclonal) acridinium-labeled conjugate in MES buffer with protein (bovine) stabilizer. Minimum concentration: 0.2 mg/L. Preservative: ProClin 300.• Assay Specific Diluent: TRIS buffer with protein (bovine) stabilizer. Preservative: ProClin 300.	Same
Characteristics	Cleared Predicate Device:TBI for Alinity i(K223602)	Subject Device:TBI for ARCHITECT
Reagentformulation(continued)	UCH-L1 Reagent Kit• Microparticles: Anti-UCH-L1(mouse, monoclonal) coatedmicroparticles in TRIS buffer withprotein (bovine) stabilizer. Minimumconcentration: 0.05% solids.Preservative: sodium azide.• Conjugate: Anti-UCH-L1 (mouse,monoclonal) acridinium-labeledconjugate in MES buffer with protein(bovine) stabilizer. Minimumconcentration: 0.2 mg/L.Preservative: ProClin 300.• Assay Specific Diluent: TRIS bufferwith protein (bovine) stabilizer.Preservative: sodium azide.	Same
General Device Characteristic Differences
InstrumentPlatform	Alinity i system	ARCHITECT i1000SR System
ReagentPackagingConfiguration	GFAP Reagent Kit2 Cartridges x 100 Tests• 1 cartridge (7.1 mL) Microparticles• 1 cartridge (6.4 mL) Conjugate• 1 cartridge (6.4 mL) Assay SpecificDiluentUCH-L1 Reagent Kit2 Cartridges x 100 Tests• 1 cartridge (7.1 mL) Microparticles• 1 cartridge (12.5 mL) Conjugate• 1 cartridge (10.5 mL) Assay SpecificDiluent	GFAP Reagent Kit100 Tests• 1 bottle (7.4 mL) Microparticles• 1 bottle (6.7 mL) Conjugate• 1 bottle (6.7 mL) Assay SpecificDiluentUCH-L1 Reagent Kit100 Tests• 1 bottle (7.4 mL) Microparticles• 1 bottle (12.0 mL) Conjugate• 1 bottle (10.9 mL) Assay SpecificDiluent

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VII. Performance Summary:

The TBI test using the GFAP assay and UCH-L1 assay, evaluated on the ARCHITECT i1000SR System, met the pre-defined product requirements for all characteristics evaluated in the verification studies.

VerificationActivity	TBI on ARCHITECT i1000SR
GFAP 20-DayPrecision	2.2 to 6.2 %CV for samples with GFAP concentrations from20.4 to 37,098.8 pg/mL
UCH-L1 20-DayPrecision	2.2 to 4.5 %CV for samples with UCH-L1 concentrationsfrom 187.6 to 19,645.0 pg/mL
GFAPReproducibility	2.7 to 6.0 %CV for samples with GFAP concentrations from23.6 to 34,087.5 pg/mL1.30 pg/mL SD for sample with GFAP concentration 19.1 pg/mL
UCH-L1Reproducibility	2.4 to 3.9 %CV for samples with UCH-L1 concentrationsfrom 193.0 to 20,363.2
GFAPLoB, LoD, LoQ	LoB – 2.0 pg/mLLoD – 3.2 pg/mLLoQ – 6.1 pg/mL
UCH-L1LoB, LoD, LoQ	LoB - 9.2 pg/mLLoD – 18.3 pg/mLLoQ – 26.3 pg/mL
GFAP Linearity	GFAP 6.1 to 42,000.0 pg/mL
UCH-L1 Linearity	UCH-L1 26.3 to 25,000.0 pg/mL
Sample Onboard	2 hours
Reagent Onboard/Calibration CurveStorage	30 days

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Comparison Summary

Studies were performed based on guidance from CLSI EP09c, 3rd ed. using the Passing-Bablok regression method.

		ARCHITECTi1000SR(pg/mL)		Alinity i(pg/mL)		CorrelationCoefficient (r)		Intercept		Slope
Assay	N	Min	Max	Min	Max	R	95% CI	Estimate	95% CI	Estimate	95% CI
GFAP	123	7.9	32359.2	6.5	32548.6	1.00	(1.00,1.00)	-0.6	(-1.1, -0.3)	1.03	(1.02,1.05)
UCH-L1	123	48.7	23763.7	51.5	24127.7	1.00	(1.00,1.00)	-6.0	(-7.9, -4.0)	1.06	(1.05,1.07)

VIII. Conclusion

The results presented in this Special 510(k) demonstrate that the performance of the subject device (TBI on the ARCHITECT i1000SR) is substantially equivalent to the performance of the predicate device (TBI on the Alinity i system, K2223602).

Regulation Number and Section

§ 866.5830 Brain trauma assessment test.

(a)
Identification. A brain trauma assessment test is a device that consists of reagents used to detect and measure brain injury biomarkers in human specimens. The measurements aid in the evaluation of patients with suspected mild traumatic brain injury in conjunction with other clinical information to assist in determining the need for head imaging per current standard of care.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The 21 CFR 809.10(b) compliant labeling must include detailed descriptions of and results from performance testing conducted to evaluate precision, accuracy, linearity, analytical sensitivity, interference, and cross-reactivity. This information must include the following:
(i) Performance testing of device precision must, at minimum, use one unmodified clinical specimen from the intended use population with concentration of the brain injury biomarker(s) near the medical decision point. Contrived specimens that have been generated from pooling of multiple samples or spiking of purified analyte to cover the measuring range may be used, but the contrived samples must be prepared to mimic clinical specimens as closely as possible. This testing must evaluate repeatability and reproducibility using a protocol from an FDA-recognized standard.
(ii) Device performance data must be demonstrated through a clinical study and must include the following:
(A) Data demonstrating clinical validity including the clinical sensitivity and specificity, and positive and negative predictive value of the test in the intended use population of patients with suspected mild traumatic brain injury (
i.e., Glasgow Coma Score (GCS) of 13-15), or equivalent standard of care for determination of severity of traumatic brain injury (TBI).(B) Study must be performed using the operators and in settings that are representative of the types of operators and settings for which the device is intended to be used.
(C) All eligible subjects must meet the well-defined study inclusion and exclusion criteria that define the intended use population. The prevalence of diseased or injured subjects in the study population must reflect the prevalence of the device's intended use population, or alternatively, statistical measures must be used to account for any bias due to enrichment of subpopulations of the intended use population.
(D) All eligible subjects must have undergone a head computerized tomography (CT) scan or other appropriate clinical diagnostic standard used to determine the presence of an intracranial lesion as part of standard of care and must also be evaluated by the subject device. All clinical diagnostic standards used in the clinical study must follow standard clinical practice in the United States.
(E) Relevant demographic variables and baseline characteristics including medical history and neurological history. In addition, head injury characteristics, neurological assessments, and physical evidence of trauma must be provided for each subject. This information includes but is not limited to the following: Time since head injury, time from head injury to CT scan, time from head injury to blood draw, GCS score or equivalent, experience of loss of consciousness, presence of confusion, episodes of vomiting, post-traumatic amnesia characteristics, presence of post-traumatic seizures, drug or alcohol intoxication, mechanism of injury, acute intracranial lesion type, neurosurgical lesion, and cranial fracture.
(F) Each CT scan or other imaging result must be independently evaluated in a blinded manner by at least two board-certified radiologists to determine whether it is positive or negative as defined by the presence or absence of acute intracranial lesions. This independent review must be conducted without access to test results of the device. Prior to conducting the review, the criteria and procedures to be followed for scoring the images must be established, including the mechanism for determining consensus.
(G) All the clinical samples must be tested with the subject device blinded to the TBI status and the neurological-lesion-status of the subject.
(H) Details on how missing values in data are handled must be provided.
(I) For banked clinical samples, details on storage conditions and storage period must be provided. In addition, a specimen stability study must be conducted for the duration of storage to demonstrate integrity of archived clinical samples. The samples evaluated in the assay test development must not be used to establish the clinical validity of the assays.
(iii) Performance testing of device analytical specificity must include the most commonly reported concomitant medications present in specimens from the intended use population. Additionally, potential cross-reacting endogenous analytes must be evaluated at the highest concentration reported in specimens from the intended use population.
(iv) Expected/reference values generated by testing a statistically appropriate number of samples from apparently healthy normal individuals.
(2) The 21 CFR 809.10(a) and (b) compliant labeling must include the following limitations:
(i) A limiting statement that this device is not intended to be used a stand-alone device but as an adjunct to other clinical information to aid in the evaluation of patients who are being considered for standard of care neuroimaging.
(ii) A limiting statement that reads “A negative result is generally associated with the absence of acute intracranial lesions. An appropriate neuroimaging method is required for diagnosis of acute intracranial lesions.”
(iii) As applicable, a limiting statement that reads “This device is for use by laboratory professionals in a clinical laboratory setting.”