The Alinity i Total ß-hCG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma for the early detection of pregnancy on the Alinity i analyzer.

Device Description

Alinity i Total ß-hCG Reagent Kit

The Alinity i Total ß-hCG assay is a two-step immunoassay for the quantitative and qualitative determination of ß-hCG in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology.

Alinity i System

The Alinity i System (also known as the Alinity i analyzer) uses chemiluminescent microparticle immunoassay (CMIA) detection technology to measure the concentration of analytes in samples. The modular design of the Alinity family of analyzers allows multiple processing modules, which perform all sample processing activities, to be physically joined to form a single workstation or system. The selection of processing module(s) determines the configuration of the system.

Each Alinity analyzer, regardless of type, consists of a System Control Module (SCM), Reagent and Sample Manager (RSM), and processing module.

AI/ML Overview

Here's an analysis of the provided information, structured according to your request:

Device: Alinity i Total ß-hCG Reagent Kit and Alinity i System

Intended Use: The Alinity i Total ß-hCG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma for the early detection of pregnancy on the Alinity i analyzer.

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

Performance Characteristic	Acceptance Criteria	Reported Device Performance
Within-Laboratory Precision (Total Imprecision)	≤ 10 %CV for the Low, Medium, and High Controls (target range from 25 to 5000 mIU/mL).	Panel 1 (25.35 mIU/mL): 5.1% CV (within range of 4.6-5.5%)Panel 2 (765.76 mIU/mL): 1.9% CV (within range of 1.5-2.3%)Panel 3 (4971.95 mIU/mL): 2.2% CV (within range of 1.7-2.7%)Calibrator B (5.33 mIU/mL): 7.6% CV (within range of 7.1-8.2%)Calibrator C (165.16 mIU/mL): 2.9% CV (within range of 2.7-3.3%)Calibrator D (9421.08 mIU/mL): 2.8% CV (within range of 2.2-3.5%)Calibrator E (13069.37 mIU/mL): 3.2% CV (within range of 2.8-3.6%)All reported %CV values are within the ≤10% criterion.
Linearity	The assay is linear across the measuring interval of 2.42 to 15,000 mIU/mL.	The assay was linear across the range of 2.42 to 15,000 mIU/mL.
Limit of Detection (LoD)	Implicit: LoD should be sufficiently low for early pregnancy detection. The predicate's stated analytical sensitivity is ≤ 1.2 mIU/mL. The Alinity i LoD ranged from 0.16 to 0.67 mIU/mL, with the highest observed LoD value being 0.67 mIU/mL.	The highest observed LoD value was 0.67 mIU/mL (IU/L).
Limit of Quantitation (LoQ)	LoQ is defined as the lowest concentration at which a maximum Total Error allowable (TEa) of 25% was met.	The highest observed LoQ value at 25% TEa was 2.42 mIU/mL (IU/L). The LoQ ranged from 1.10 to 2.42 mIU/mL.
Measuring Interval	Defined as the range of values in mIU/mL (IU/L) which meets the limits of acceptable performance for bias, imprecision, and linearity.	The measuring interval of the Alinity i Total ß-hCG assay is 2.42 to 15,000.00 mIU/mL (2.42 to 15,000.00 IU/L).
Analytical Specificity (Cross-Reactivity)	Cross-reactivity calculated as a percent interference for samples with a ß-hCG concentration > 25 mIU/mL (> 25 IU/L) was shown to be less than 10% for each cross-reactant.	Cross-reactivity was within or equal to ±10% for FSH (≤ 500 mIU/mL), LH (≤ 500 mIU/mL), TSH (≤ 100 μIU/mL), and hCG alpha subunit (≤ 500 mIU/mL).
Potentially Interfering Substances	Potential interference from bilirubin, hemoglobin, total protein, and triglycerides showed a difference in measured concentration of ß-hCG within or equal to ±10%.	Difference in measured concentration of ß-hCG was within or equal to ±10% for Bilirubin (≤ 20 mg/dL), Hemoglobin (≤ 500 mg/dL), Total Protein (≤ 12 g/dL), and Triglycerides (≤ 3000 mg/dL). Similar results for various exogenous substances.
Within-Assay Sample Carryover	Carryover from a sample containing 1,000,000 mIU/mL ß-hCG to an adjacent 0 mIU/mL ß-hCG sample was less than 7.5 mIU/mL ß-hCG.	The difference between the protected sample and the unprotected sample was 0.22 mIU/mL, which is well below the 7.5 mIU/mL criterion.
Method Comparison (Quantitative)	Comparison to ARCHITECT Total ß-hCG assay to show substantial equivalence, typically assessed by correlation coefficient, slope, and intercept.	Correlation Coefficient: 1.00Intercept: 0.12Slope: 1.01Concentration Range: 2.40 – 14,866.03 mIU/mLThese values demonstrate excellent agreement with the predicate.
Method Comparison (Qualitative Concordance)	High concordance with the ARCHITECT Total ß-hCG assay across different concentration categories (Positive ≥ 25.00, > 5.00 - < 25.00, Negative ≤ 5.00).	High concordance demonstrated with 201 positive, 44 indeterminate, and 132 negative samples showing agreement. Only 4 discordant specimens with concentrations very close to the cutoffs.
Verification of Auto-Dilution	The difference in mean concentration was within +/- 10% when comparing the auto diluted samples on the Alinity i system to auto diluted samples on the ARCHITECT system.	The mean % difference was 0.3%.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Within-Laboratory Precision:
- Low, Medium, High Controls: 398-399 replicates for each control across 2 instruments and reagent lots.
- Calibrators B, C, D, E: 399-400 replicates for each calibrator across 2 instruments and reagent lots.
- Additional samples for LoD/LoQ related analysis: 176 replicates for 6 samples and 400-401 replicates for 3 samples.
Linearity: The number of samples evaluated for linearity is not explicitly stated, but the study was based on CLSI document EP06-A.
Limits of Blank, Detection, and Quantitation (LoB, LoD, LoQ): n ≥ 60 replicates of zero-analyte samples for LoB; n > 60 replicates of low-analyte level samples for LoD; n ≥ 60 replicates of low-analyte level samples for LoQ.
Analytical Specificity (Cross-Reactivity): Number of samples not explicitly stated, but "samples with a ß-hCG concentration > 25 mIU/mL" were used.
Potentially Interfering Substances: Number of samples not explicitly stated, but "test samples containing potentially-interfering endogenous substances to reference samples" were used.
Within-Assay Sample Carryover: 1 sample containing high ß-hCG and 1 adjacent 0 mIU/mL ß-hCG sample tested.
Method Comparison (Quantitative): 210 serum samples.
Method Comparison (Qualitative): 381 Alinity i Total ß-hCG qualitative results.
Tube Type Equivalency (Matrix Comparison): 43 unique positive pregnant donor's serum specimens, supplemented into 45 unique female non-pregnant whole blood specimens.
Expected Values Non-Pregnant (Reference Range): 128 pre-menopausal, 140 peri-menopausal, and 137 post-menopausal human serum specimens.
Isoform Recognition: Pooled normal human female serum (ß-hCG concentrations less than 1.2 mIU/mL) supplemented with 6 different ß-hCG isoforms and 1 alpha subunit. (Number of replicates not specified).
Verification of Auto-Dilution: 25 samples created by supplementing ß-hCG stock solution into normal male serum.

Data Provenance: The document does not specify the country of origin of the data or explicitly state whether the studies were retrospective or prospective, though the nature of laboratory studies often implies prospective data collection for the specific tests being performed. The samples used for method comparison and expected values are "human serum specimens."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)

This device is an in-vitro diagnostic (IVD) assay that measures the concentration of a biomarker (ß-hCG). The "ground truth" for such assays is typically established by reference methods, certified calibrators, and well-characterized samples, rather than human experts interpreting images or complex clinical scenarios.

Calibrators: Manufactured gravimetrically and referenced to the World Health Organization (WHO) 4th International Reference Standard 75/589 for ß-hCG. This WHO standard serves as the "ground truth" or reference, established by an international consensus of experts in biochemistry and endocrinology related to hCG.
Predicate Device: The ARCHITECT Total ß-hCG assay (K983424) and ARCHITECT i System (K983212) serve as the comparator ("ground truth" for method comparison studies), implying their performance has been previously validated and accepted.
Precision and LoD/LoQ samples: These are laboratory-prepared samples or characterized controls with known concentrations.
Reference Intervals: Based on human serum specimens from specific demographic groups.

Therefore, direct "human experts" for establishing ground truth in the context of diagnostic interpretation (like radiologists for imaging) are not applicable here. The ground truth is rooted in established metrological traceability to international standards and performance against a cleared predicate device.

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

Adjudication methods like 2+1 or 3+1 are typically used in studies where human readers provide subjective interpretations (e.g., in medical imaging) and disagreements need to be resolved. This is not applicable to an automated IVD assay where results are quantitative or qualitative based on pre-defined cutoffs and analytical measurements. The assay itself provides a numerical result or a positive/negative/indeterminate classification, which is then compared against established reference values or a predicate device.

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

No, a multi-reader, multi-case (MRMC) comparative effectiveness study was not done. MRMC studies are relevant for evaluating improvements in human reader performance (e.g., radiologists, pathologists) when assisted by an AI system. The Alinity i Total ß-hCG assay is an automated diagnostic test that directly measures a biomarker concentration. There is no human "reader" in the loop needing assistance from the device in the way an AI would assist in image interpretation.

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

Yes, the studies described are, by nature, standalone performance evaluations of the algorithm/device. The Alinity i Total ß-hCG assay and Alinity i System operate without human intervention once the samples are loaded and the test is initiated. The "performance" refers to the analytical accuracy, precision, linearity, and other parameters of the automated system itself, comparing its output to expected values or to a predicate device.

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

The ground truth for this device is based on several elements:

International Reference Standards: The calibrators are traceable to the World Health Organization (WHO) 4th International Reference Standard 75/589 for ß-hCG.
Predicate Device: The ARCHITECT Total ß-hCG assay and ARCHITECT i System serve as the established "ground truth" comparator for method comparison studies, demonstrating substantial equivalence.
Known Concentrations: For precision, linearity, LoD, LoQ, cross-reactivity, and interference studies, the ground truth is samples with known or spiked concentrations of ß-hCG or interfering substances.
Clinical Groupings: For "Expected Values Non-Pregnant," the ground truth is the categorization of individuals (pre-menopausal, peri-menopausal, post-menopausal) based on their clinical status.

There is no "pathology" or "outcomes data" as a direct ground truth in these analytical performance studies.

8. The sample size for the training set

The document describes premarket notification (510(k)) studies for a diagnostic assay, primarily focused on analytical validation and comparison to a predicate. It does not mention a "training set" in the context of machine learning or AI development. The device is a "chemiluminescent microparticle immunoassay (CMIA)" system, meaning its principles are based on established biochemical reactions, not on learning from a dataset in the way an AI algorithm would be "trained."

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

As there is no "training set" for an AI algorithm mentioned for this device, a ground truth for a training set was not established. The device operates based on the inherent chemical and biological characteristics of the assay and the optical detection system, calibrated against known standards.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 October 23, 2017

ABBOTT LABORATORIES LINDA SOHN REGULATORY AFFAIRS SENIOR SPECIALIST DEPT. 9AA. BLDG AP8 100 ABBOTT PARK ROAD ABBOTT PARK, IL 60064

Re: K170317

Trade/Device Name: Alinity i Total ß-hCG Reagent Kit Alinity i System Regulation Number: 21 CFR 862.1155 Regulation Name: Human chorionic gonadotropin (HCG) test system Regulatory Class: II Product Code: DHA, JJE Dated: September 19, 2017 Received: September 20, 2017

Dear Linda Sohn:

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 Parts 801 and 809); 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

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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Kellie B. Kelm -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 (if known) K170317

Device Name Alinity i Total ß-hCG Reagent Kit Alinity i System

Indications for Use (Describe) Alinity i Total ß-hCG Reagent Kit

Alinity i System

The Alinity i System is a fully automated immunoassay analyzer allowing random and continuous access, as well as priority and automated retest processing using chemiluminescent microparticle immunoassay (CMIA) technology. CMIA technology is used to determine the presence of antibodies, and analyte in samples.

Type of Use (Select one or both, as applicable)
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Representation Use (Part 201, CERCLA, Subject Property)	On-Site Service Use (21E, CERCLA)
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Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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K170317

510(k) Summary (Summary of Safety and Effectiveness)

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

Abbott Laboratories Dept. 09AA, AP8-1 100 Abbott Park Road Abbott Park, IL 60064

Primary contact person for all communications:

Linda Sohn, ADD, Project Manager, Regulatory Affairs Phone: (224) 667-4846 Fax: (224) 667-4836 E-mail: Linda.Sohn@abbott.com

Secondary contact person for all communications:

Amy Ghering, Associate Director, Regulatory Affairs Phone: (224) 668-6934 Fax: (224) 667-4836 E-mail: Amy.Ghering@abbott.com

Date Summary Prepared: January 31, 2017.

Date Summary Revised: October 23, 2017.

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II. Device Name

Alinity i Total β-hCG Reagent Kit Alinity i System

Alinity i Total β-hCG Reagent Kit

Device Classification: Class II Classification Name: Human chorionic gonadotropin (HCG) test system Governing Regulation: 862.1155 Product Code: DHA

Alinity i System

Device Classification: Class I Classification Name: Discrete photometric chemistry analyzer for clinical use Governing Regulation: 21 CFR 862.2160 Product Code: JJE

III. Predicate Device

Reagents

ARCHITECT Total β-hCG (K983424)

Instrument

ARCHITECT i System (K983212)

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IV. Description of Device

A. Reagents

Kit Contents

Volumes (mL) listed in the table below indicate the volume per cartridge:

REF	07P5120	07P5130
Tests per cartridge	100	600
Number of cartridges per kit	2	2
Tests per kit	200	1200
Microparticles	6.6 mL	32.1 mL
Conjugate	4.2 mL	9.0 mL

. Microparticles: Anti-ß-hCG (mouse, monoclonal) coated microparticles in TRIS buffer with protein (bovine) stabilizers. Minimum concentration: 0.06% solids. Preservatives: antimicrobial agents.
Conjugate: Anti-ß-hCG (mouse, monoclonal) acridinium-labeled conjugate in . MES buffer with protein (bovine) stabilizers. Minimum concentration: 2.9 µg/mL. Preservative: antimicrobial agent.

B. Calibrators

Cal A through Cal F prepared in human serum. Preservative: Sodium azide.

		Total β-hCGConcentration
Calibrator	Quantity	(mIU/mL)	(IU/L)
A	1 x 3.0 mL	0	0
B	1 x 3.0 mL	10	10
C	1 x 3.0 mL	250	250
D	1 x 3.0 mL	1000	1000
E	1 x 3.0 mL	7500	7500
F	1 x 3.0 mL	15,000	15,000

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Standardization Statement

The calibrators are manufactured gravimetrically and referenced to the World Health Organization (WHO) 4th International Reference Standard 75/589 for β-hCG at each concentration level.

C. Controls

The controls recommended for use with the Alinity i Total ß-hCG assay were cleared under K983424 with the name ARCHITECT Total β-hCG Controls. The Total ß-hCG assay on the Alinity i System uses the same ARCHITECT Total ß-hCG Controls with no change to formulation or container. Therefore, Abbott is not seeking a new clearance for the Alinity i Total ß-hCG Controls in this submission because only the branding has changed.

Control L. Control M. and Control H contain hCG prepared in human serum. Preservative: Sodium azide.

The following target concentration ranges may be used for individual replicate control specifications on the Alinity i analyzer:

Control	Quantity	Total ß-hCGConcentration(mIU/mL)(IU/L)	Range(mIU/mL)(IU/L)
Control L	1 x 8.0 mL	25	16 – 34
Control M	1 x 8.0 mL	750	488 - 1013
Control H	1 x 8.0 mL	5000	3250 - 6750

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D. Alinity i System

Each Alinity analyzer, regardless of type, consists of a System Control Module (SCM), Reagent and Sample Manager (RSM), and processing module.

E. Principles of the Procedure

The Alinity i analyzer processes Total ß-hCG test orders as follows:

1. Sample and anti-ß-hCG coated paramagnetic microparticles are combined and incubated.
1. The ß-hCG present in the sample binds to the anti-ß-hCG coated microparticles.
1. The mixture is washed.
1. Anti- B-hCG acridinium-labeled conjugate is added to create a reaction mixture and incubated.
1. Following a wash cycle, Pre-Trigger and Trigger Solutions are added.
1. The resulting chemiluminescent reaction is measured as relative light units (RLUs). There is a direct relationship between the amount of ß-hCG in the sample and the RLUs detected by the system optics.

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V. Intended Use of the Device

The Alinity i Total β-hCG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma for the early detection of pregnancy on the Alinity i analyzer.

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VI. Comparison of Technological Characteristics

The Alinity i Total β-hCG assay (candidate assay) utilizes a chemiluminescent microparticle immunoassay (CMIA) methodology for the quantitative and qualitative determination of Total ß-hCG and is intended for use on the Alinity i analyzer.

The similarities and differences between the candidate assay and the predicate assay and the candidate instrument and the predicate instrument are presented in Tables 1 through 4 starting on page 8.

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Comparison of Candidate Alinity i Total β-hCG to Predicate ARCHITECT Total β-hCG

Table 1: Reagent Similarities

	Candidate Assay	Predicate Assay (K983424)
Characteristics	Alinity i Total β-hCG	ARCHITECT Total β-hCG
Technical Characteristics
Methodology	Chemiluminescent Microparticle Immunoassay(CMIA)	Same
Intended Use/Indications for Use	The Alinity i Total β-hCG assay is achemiluminescent microparticle immunoassay(CMIA) used for the quantitative and qualitativedetermination of beta-human chorionic gonadotropin(β-hCG) in human serum and plasma for the earlydetection of pregnancy on the Alinity i analyzer.	The ARCHITECT Total β-hCG assay is aChemiluminescent Microparticle Immunoassay(CMIA) for the quantitative and qualitativedetermination of beta human chorionic gonadotropin(β-hCG) in human serum and plasma for the earlydetection of pregnancy.
Specific AnalyteDetected	Total β-hCG	Same
Formulation	Microparticles – Anti-β-hCG (mouse, monoclonal)coated microparticles in TRIS buffer with protein(bovine) stabilizers. Minimum concentration: 0.06%solids. Preservatives: antimicrobial agents.Conjugate - Anti-β-hCG (mouse, monoclonal)acridinium-labeled conjugate in MES buffer withprotein (bovine) stabilizers. Minimum concentration:2.9 µg/mL. Preservative: antimicrobial agent.	Same
Assay Protocol	2-step	Same

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Supplement to K170317 Alinity i Total β-hCG 510(k) October 2017	Cha CalTyp Spe Per WitPre
-----------------------------------------------------------------	-------------------------------------------	--	--	--	--	--

Table 1: Reagent Similarities

	Candidate Assay	Predicate Assay (K983424)
Characteristics	Alinity i Total β-hCG	ARCHITECT Total β-hCG
Calibration CurveType	6-point4 Parameter Logistic Curve fit data reduction method(4PLC, Y-weighted)	Same
Specimen Type	Serum and plasma	Same
Performance Characteristics
Within-LaboratoryPrecision (20-Day)	The within-laboratory (total) imprecision (within-run,between-run, and between-day) was ≤ 10 %CV forthe Low, Medium, and High Controls (target rangefrom 25 - 5000 mIU/mL).	Same
Linearity	This assay is linear across the measuring interval of2.42 to 15,000 mIU/mL (2.42 to 15,000 IU/L).	The assay range is 1.2 to 15,000 mIU/mL.
Measuring Interval	The measuring interval is 2.42 to 15,000.00 mIU/mL(2.42 to 15,000.00 IU/L).Note: The measuring interval is defined as the rangeof values in mIU/mL (IU/L) which meets the limits ofacceptable performance for bias, imprecision, andlinearity. The inputs to the measuring interval includeprecision, linearity, and the quantitation limit.	The ARCHITECT Total β-hCG assay was designedto have an analytical sensitivity of ≤ 1.2 mIU/mL,with an Assay Range of 1.2 mIU/mL to 15,000mIU/mL.
Detection Limit:Limit of Detection(LoD) andLimit ofQuantitation (LoQ)	• The highest observed LoD value was0.67 mIU/mL (IU/L).• The highest observed LoQ value at 25% TEawas 2.42 mIU/mL (IU/L).	The analytical sensitivity is ≤ 1.2 mIU/mL.Note: The LoQ was not measured for ARCHITECT.

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Table 1: Reagent Similarities
-------------------------------

Characteristics	Candidate AssayAlinity i Total β-hCG	Predicate Assay (K983424)ARCHITECT Total β-hCG
AnalyticalSpecificity (CrossReactivity, FSH,LH, TSH, hCGalpha subunit)	The cross reactivity was calculated as a difference inthe measured concentration of β-hCG and was shownto be within or equal to ±10% for each cross reactant.	Same
PotentiallyInterferingSubstances(Bilirubin,Hemoglobin,Triglycerides, andTotal Protein)	Potential interference from bilirubin, hemoglobin,total protein, and triglycerides showed a difference inmeasured concentration of β-hCG within or equal to±10% at the levels indicated below:• Bilirubin ≤ 20 mg/dL• Hemoglobin ≤ 500 mg/dL• Total Protein ≤ 12 g/dL• Triglycerides ≤ 3000 mg/dL	Same
Within-AssaySample Carryover	Carryover from a sample containing1,000,000 mIU/mL β-hCG to an adjacent 0 mIU/mLβ-hCG sample was less than 7.5 mIU/mL β-hCG.	Same

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Characteristics	Candidate AssayAlinity i Total β-hCG	Predicate Assay (K983424)ARCHITECT Total β-hCG
Tube Types	Serum• Serum• Serum Separator	Human Serum• Serum• Serum Separator
	Plasma• Dipotassium EDTA• Tripotassium EDTA• Lithium heparin• Lithium heparin plasma separator• Sodium heparin	Plasma• Lithium Heparin• Sodium Heparin• Potassium EDTA
Use of Calibrators	Yes	Same
Use of Controls	Yes	Same

Table 1: Reagent Similarities

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Characteristics	Candidate AssayAlinity i Total β-hCG	Predicate Assay (K983424)ARCHITECT Total β-hCG
Container and Closure Materials
Container	Polypropylene (PP)Black colorant	High Density Polyethylene (HDPE)• Natural (microparticles)• Black colorant (conjugate only)
Closure Material(contact only)	Sealed integrated black polyolefin elastomer septumand moved the product contact from the cap to the septum.	F217 cap liner, Polyethylene Foam betweenLow-Density Polyethylene liners, within PP cap;white polyolefin elastomer septum (customer-placedupon first use)

Table 2: Reagent Differences

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Comparison of the Candidate Alinity i System to the Predicate ARCHITECT i System

Table 3: Instrument Similarities

	Candidate Device	Predicate Device
Category	Alinity i System	ARCHITECT i System (K983212)
IntendedUse/Indication forUse	The Alinity i System is a fully automated,random/continuous access, immunoassay analyzer,which utilizes chemiluminescent microparticleimmunoassay (CMIA) detection technology for bothlarge and small molecular weight analytes.	Same
DetectionTechnology	Chemiluminescent microparticle immunoassay(CMIA)	Same
Sample Handling	Robotic sample handler (RSH) transport system thathas random and continuous access to samples.Autoretest Capability	Same
	Priority and batch sample loading	Same
Reagent Handling	The on-board storage area cooler and the septum capprovide evaporation control. Continuous ReagentAccess.	Same
User Interface	Continuous access to Trigger and Pre-Trigger andreconstituted Wash Buffer solutions are storedon-board.	Same

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	Table 4: Instrument Differences
--	---------------------------------	--

Characteristics	Candidate DeviceAlinity i System	Predicate DeviceARCHITECT i System (K983212)
DedicatedPretreatment Lane	Includes dedicated pretreatment lane	N/A
Dedicated WashStation	Dedicated wash cups for sample pipettor and reagentpipettors	Sample pipettor and reagent pipettors do not havededicated wash cups

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VII. Summary of Nonclinical Performance

Within-Laboratory Precision (20-Day)

Precision was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP05-A2.

A summary of results is presented below:

			Within-Run(Repeatability)		Within-Laboratory (Total)a
PanelMember	n	MeanmIU/mL(IU/L)	SD	%CV	SD (Rangeb)	%CV(Rangeb)
1	398	25.35	0.844	3.3	1.293(1.154-1.416)	5.1(4.6-5.5)
2	399	765.76	11.099	1.4	14.809(11.542-17.734)	1.9(1.5-2.3)
3	399	4971.95	73.079	1.5	110.173(85.849-131.611)	2.2(1.7-2.7)
B	400	5.33	0.269	5.0	0.408(0.357 - 0.463)	7.6(7.1 - 8.2)
C	400	165.16	3.680	2.2	4.583(4.386-5.639)	2.9(2.7 - 3.3)
D	399	9421.08	194.693	2.1	265.152(2.14698 - 339.368)	2.8(2.2 - 3.5)
E	400	13069.37	314.717	2.4	412.842(372.088 - 484.306)	3.2(2.8 - 3.6)

ª Includes within-run, between-run, and between-day variability.

b Minimum and maximum SD or %CV for each reagent lot and instrument combination.

The precision of the Alinity i Total ß-hCG assay was considered acceptable if the within laboratory (total) imprecision (within run, between run, and between day) was ≤ 10 %CV for the Low, Medium, and High Controls (target range from 25 to 5000 mIU/mL).

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Nine samples were assayed in replicates of at least 22 on 2 runs in a single day on 2 instruments and reagent lots. The number of replicates within negative and positive concentrations are shown in the table below.

MeanConcentration(mIU/mL)(IU/L)	n	Negative≤ 5 mIU/mL(IU/L)	> 5 and< 25 mIU/mL(IU/L)a	Positive≥ 25 mIU/mL(IU/L)
0.01	176	176	0	0
3.15	176	176	0	0
4.06	176	176	0	0
6.57	176	0	176	0
8.47	176	0	176	0
21.10	176	0	176	0
24.00	176	0	139	37
28.41	176	0	0	176
29.94	176	0	0	176
*2.32b	401	401	0	0
*5.33b	400	106	294	0
*25.35b	398	0	173	225

a Status not determined. Redraw is recommended after 48 hours to determine status.

b These samples are from the 20-day precision study.

The Alinity i Total β-hCG assay demonstrated acceptable precision.

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Linearity

Linearity was evaluated based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP06-A.

The assay was linear across the range of 2.42 to 15,000 mIU/mL.

Limits of Blank, Detection, and Quantitation (LoB, LoD, and LoQ)

The LoB, LoD, and LoQ study was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP17-A2.

Across the instruments and reagents lots, the LoB ranged from 0.00 to 0.20 mIU/mL, the LoD ranged from 0.16 to 0.67 mIU/mL, and the LoQ ranged from 1.10 to 2.42 mIU/mL.

The LoB represents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.

The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n > 60 replicates of low-analyte level samples.

The LoQ was determined from n ≥ 60 replicates of low-analyte level samples and is defined as the lowest concentration at which a maximum TEa (Total Error allowable) of 25% was met.

Measuring Interval

The measuring interval of the Alinity i Total ß-hCG assay is 2.42 to 15,000.00 mIU/mL (2.42 to 15,000.00 IU/L).

Specificity (Cross-Reactivity)

Potential interference was evaluated based on guidance from the Clinical Laboratory and Standards Institute (CLSI) document EP07-A2. The cross-reactivity was calculated as a percent interference for samples with a ß-hCG concentration > 25 mIU/mL (> 25 IU/L) and was shown to be less than 10% for each cross-reactant.

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The Alinity i Total ß-hCG assay is not susceptible to interference from the cross-reactants when evaluated at the levels presented in the table below:

Cross-Reactant	Cross-Reactant Level
TSH	≤ 100 μIU/mL
LH	≤ 500 mIU/mL
FSH	≤ 500 mIU/mL
hCG alpha subunit	≤ 500 mIU/mL

Potentially Interfering Substances – Bilirubin, Hemoglobin, Triglycerides, and Total Protein

Potential interference was evaluated based on guidance from the Clinical Laboratory and Standards Institute (CLSI) document EP07-A2. Interference effects were assessed by comparing test samples containing potentially-interfering endogenous substances to reference samples. The percent interference for Total ß-hCG samples was shown to be less than or equal to 10% for each potentially interfering endogenous substance.

The Alinity i Total ß-hCG assay is not susceptible to interference effects from the following interferents at the interferent levels listed in the table below:

Interferent	Interferent Level
Conjugated Bilirubin	≤ 20 mg/dL
Unconjugated Bilirubin	≤ 20 mg/dL
Hemoglobin	≤ 500 mg/dL
Triglycerides	≤ 3000 mg/dL
Total Protein	≤ 12 g/dL

Potentially Interfering Exogenous Substances - Drugs

Potential interference was evaluated based on guidance from the Clinical Laboratory and Standards Institute (CLSI) document EP07-A2. The percent interference for Total ß-hCG samples was shown to be less than or equal to 10% for each potentially interfering exogenous substance.

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Interferent	Target Interferent Level
Acetaminophen	≤ 20 mg/dL
Acetylcysteine	≤ 167 mg/dL
Acetylsalicylic Acid	≤ 66 mg/dL
Ampicillin	≤ 53 mg/L
Ascorbic Acid	≤ 6 mg/dL
Atropine	≤ 20 mg/dL
Ca-Dobesilate	≤ 200 mg/L
Caffeine	≤ 20 mg/dL
Cyclosporine	≤ 5 mg/L
Cefoxitin	≤ 660 mg/L
Doxcycline	≤ 30 mg/L
Ethanol	≤ 1%
EDTA	≤ 80 mg/dL
Ibuprofen	≤ 50 mg/dL
Levodopa	≤ 20 mg/L
Methyldopa	≤ 15 mg/L
Metronidazole	≤ 120 mg/L
Phenylbutazone	≤ 400 mg/L
Rheumatoid Factor (RF)	≤ 194 IU/L
Rifampicin	≤ 64 mg/L
Sodium Heparin	≤ 3000 U/L
Sodium Salicylic Acid	≤ 70 mg/dL
Theophylline	≤ 40 mg/L
Gentisic Acid	≤ 20 mg/dL

The Alinity i Total ß-hCG assay is not susceptible to interference effects from the following interferents at the interferent levels listed in the table below:

Method Comparison

Quantitative

A study was performed using serum specimens based on guidance from CLSI EP09-A3 using the Weighted Deming regression method.

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The data summary below presents that data with all outliers included.

	SampleType	Units	N	CorrelationCoefficient	Intercept	Slope	ConcentrationRange
Alinity i Totalβ-hCG vsARCHITECTTotal β-hCG	Serum	mIU/mL(IU/L)	210	1.00	0.12	1.01	2.40 – 14,866.03

Qualitative

A total of 381 Alinity i Total ß-hCG qualitative results were analyzed for concordance with the ARCHITECT Total ß-hCG assay. Samples below the lower limit of the measuring interval were included in the analysis.

	ARCHITECT Total β-hCGmIU/mL (IU/L)
Alinity i Total β-hCGmIU/mL (IU/L)	Positive≥ 25.00	> 5.00 - < 25.00 a	Negative≤ 5.00
Positive ≥ 25.00	201	0	0
> 5.00 - < 25.00a	1	44	3
Negative ≤ 5.00	0	0	132

a Status not determined. Redraw is recommended after 48 hours to determine status.

Concentration Values of Discordant Specimens
Alinity i Total β-hCGmIU/mL (IU/L)	ARCHITECT Total β-hCGmIU/mL (IU/L)
24.42	26.41
5.25	4.58
5.06	4.62
5.16	4.80

The method comparison data for the investigational method, Alinity i Total ß-hCG and the comparator method, ARCHITECT Total ß-hCG was acceptable.

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Within-Assay Sample Carryover

The difference between the protected sample and the unprotected sample was 0.22 mIU/mL. The Alinity i Total B-hCG assay is not susceptible to within-assay sample carryover.

Tube Type Equivalency (Matrix Comparison)

The study used 43 unique positive pregnant donor's serum specimens to supplement the concentration of 45 unique female non-pregnant whole blood specimens to achieve concentrations across the measuring interval. The whole blood, after supplementing, was aliquoted into 7 tube types. The samples were processed according to the blood collection tube manufacturer's instructions and evaluated for ß-hCG compared to the serum control.

The following blood collection tube types are acceptable for use with the Alinity i Total ß-hCG assay:

Evaluation Tube Types
Serum (separator tube)
Dipotassium EDTA
Tripotassium EDTA
Lithium heparin
Lithium heparin (separator tube)
Sodium heparin

Expected Values Non-Pregnant (Reference Range)

Because hCG is normally synthesized and secreted by cells of the placenta or its precursor, levels of the hormone in normal, non-pregnant individuals are low to undetectable. Concentrations of ß-hCG measured in the sera of non-pregnant individuals, as reported in the literature, are < 5 mIU/mL. The concentration of ß-hCG in maternal serum rises rapidly during early pregnancy. ß-hCG levels between 5 mIU/mL and 25 mIU/mL may be indicative of early pregnancy. Values for ß-hCG generally peak during the first trimester and decline slowly throughout the remainder of the pregnancy.

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Human serum specimens were collected from non-pregnant, pre-menopausal, peri-menopausal, and post-menopausal females and were evaluated using the Alinity i Total ß-hCG assay. The results are summarized in the following table.

Age (years)	n	MenopausalStatus	ReferenceInterval(mIU/mL)(2.5 - 97.5percentile)
18 – 41	128	pre-menopausal	< 2.42
42 – 55	140	peri-menopausal	< 2.42 - 4.87
> 55	137	post-menopausal*	< 2.42 - 7.60

Post-menopausal is defined as female subjects who had not had a menstrual period for 12 months or more.

Isoform Recognition

Seven ß-hCG isoforms were evaluated by comparing test and reference samples of pooled normal human female serum (ß-hCG concentrations less than 1.2 mIU/mL). Test samples were supplemented with stock solutions of each isoform. Reference samples were unsupplemented.

The results are presented in the table below:

Isoform	WHO Code	IsoformConcentration(nmol/mL)	% Recovery
Chorionic Gonadatrophin, intact, Human	99/688	0.0001128	103.5
Chorionic Gonadatrophin, beta subunit, Human	99/650	0.0011	86.3
Chorionic Gonadatrophin, nicked, Human	99/642	0.0001326	95.0
Chorionic Gonadatrophin, nicked beta subunit, Human	99/692	0.002244	85.8
Chorionic Gonadatrophin, beta subunit, Human (purified)	75/551	0.0011256	93.7
Chorionic Gonadatrophin, beta core fragment, Human	99/708	0.00225	N/A*

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Isoform	WHO Code	IsoformConcentration(nmol/mL)	% Recovery
Chorionic Gonadatrophin,alpha subunit, Human(purified)	99/720	0.0001428	N/A*

The beta core fragment and alpha subunit are not detectable by the assay as the Test Mean is less than the Limit of Quantitation of the assay.

Verification of Auto-Dilution

A total of 25 samples were created by supplementing ß-hCG stock solution into normal male serum. An aliquot of each sample was tested using the 1:15 automated dilution protocol on both the Alinity i analyzer and the ARCHITECT instrument.

The performance of the Alinity i Total ß-hCG automated dilution protocol was considered acceptable if, the difference in mean concentration was within +/- 10% when comparing the auto diluted samples on the Alinity i system to auto diluted samples on the ARCHITECT system.

The mean % difference was 0.3%.

VIII. Summary of Clinical Performance

The section does not apply.

IX. Conclusion Drawn from Nonclinical Laboratory Studies

The results presented in this 510(k) premarket notification demonstrate that the candidate assay (Alinity i Total B-hCG. List No. 07P51) performance is substantially equivalent to the predicate assay (ARCHITECT Total β-hCG, K983424) and that the candidate instrument (Alinity i System) is substantially equivalent to the predicate instrument (ARCHITECT i System, K983212).

The similarities and differences between the candidate assay and predicate assay and the candidate instrument and predicate instrument are presented in the tables starting on page 5-8. The results presented in this 510(k) provide reasonable assurance that the

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candidate Alinity i Total β-hCG assay and the candidate Alinity i System are safe and effective for the stated intended use. Any differences between the candidate assay and the predicate assay and the candidate instrument and the predicate instrument shown in the tables do not affect the safety and effectiveness of the candidate assay and instrument.

Regulation Number and Section

§ 862.1155 Human chorionic gonadotropin (HCG) test system.

(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.