The Alinity i Toxo IgM assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of IgM antibodies to Toxoplasma gondii in human serum, serum separator, and plasma tubes (lithium heparin, lithium heparin separator, and tripotassium EDTA) on the Alinity i system.

The Alinity i Toxo IgM assay is to be used as an aid in the diagnosis of acute or recent Toxoplasma gondii infection in suspected individuals including women of child-bearing age. It is recommended that the assay be performed in conjunction with a Toxoplasma gondii IgG assay.

The Alinity i Toxo IgM assay has not been cleared for use in screening blood, plasma, or tissue donors.

Device Description

The Alinity i Toxo IgM assay is an automated, two-step immunoassay for the qualitative detection of IgM antibodies to Toxoplasma gondii in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology. The kit includes Reagents (Microparticles and Conjugate), Calibrator, and Controls.

AI/ML Overview

The provided text is a 510(k) Summary for the Abbott Laboratories Alinity i Toxo IgM assay. It details the device's characteristics, intended use, and performance studies to demonstrate substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided document:

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

The document does not explicitly present a "table of acceptance criteria" with predefined thresholds that the device must meet in a comparative format. Instead, it presents various performance studies (precision, analytical specificity, cross-reactivity, matrix equivalency, class specificity, CDC panel agreement, and clinical agreement) and then summarizes the results of these studies. The implicit acceptance criteria are the successful demonstration of performance comparable to a cleared device and FDA guidance documents.

However, we can infer some "acceptance criteria" from the results presented, especially in the CDC Panel Agreement and Clinical Agreement sections. The document highlights the Percentage Positive Agreement (PPA) and Percentage Negative Agreement (NPA) as key metrics.

Here's a table focusing on the performance of the Alinity i Toxo IgM assay as tested against established benchmarks:

Table of Device Performance Metrics

Performance Metric	Acceptance Criteria (Implicit/Inferred)	Reported Device Performance
Precision	Low Coefficient of Variation (CV%) for various panels and controls, demonstrating consistent results within and across runs, days, and lots.	Within-Laboratory (20-Day):- Negative Control: SD 0.014 (NAc)- Positive Control: SD 0.104 (3.8% CV)- High Nonreactive Panel: SD 0.040 (NAc)- Low Reactive Panel: SD 0.064 (4.7% CV)- Reactive Panel: SD 0.109 (4.3% CV)Reproducibility (5-Day, Multi-Site):- Negative Control: SD 0.018 (NAc)- Positive Control: SD 0.132 (5.1% CV)- High Nonreactive Panel: SD 0.041 (NAc)- Low Reactive Panel: SD 0.067 (5.1% CV)- Reactive Panel: SD 0.136 (5.5% CV)(Overall low CVs demonstrate good precision.)
Analytical Specificity (Interfering Substances)	No significant interference from common endogenous substances, other conditions, or drugs at specified concentrations.	Endogenous Substances: No significant interference observed for Unconjugated Bilirubin (40 mg/dL), Conjugated Bilirubin (40 mg/dL), Hemoglobin (1000 mg/dL), Total Protein (15 g/dL), Triglycerides (3000 mg/dL).Other Conditions: No significant interference observed for HAMA (800 ng/mL), RF (200 IU/mL).Drugs: No significant interference observed for Ascorbic Acid (300 mg/L), Atovaquone (120 mg/L), Beta Carotene (6 mg/L), Biotin (4250 ng/mL), Clindamycin (5.1 mg/dL), Folic Acid (100 nmol/L), Pyrimethamine (15 mg/L), Spiramycine (4.2 mg/L), Sulfadiazine (25.5 mg/dL), Sulfamethoxazole (210 mg/dL), Trimethoprim (4.2 mg/dL).
Cross-Reactivity	Minimal false reactive results from individuals with other medical conditions and high titer Toxoplasmosis IgG.	Out of 177 specimens from individuals with various unrelated conditions (e.g., CMV, EBV, HSV, Flu vaccine recipients, Syphilis, etc.) and high titer Toxoplasmosis IgG, only 1 out of 10 RF (Rheumatoid Factor) specimens resulted in a false reactive result.
Matrix Equivalency	Acceptable performance across different blood collection tube types (serum, serum separator, lithium heparin plasma, lithium heparin plasma separator, and tripotassium EDTA plasma).	All tested blood collection tube types were found acceptable for use with the Alinity i Toxo IgM assay.
Class Specificity	Reactivity only to human anti-Toxoplasma IgM and no reactivity to human anti-Toxoplasma IgG.	Demonstrated reactivity only to human anti-Toxoplasma IgM, with no reactivity to human anti-Toxoplasma IgG.
CDC Panel Agreement	High positive and negative percent agreement with the CDC Toxoplasma 1998 Human Serum Panel.	PPA: 100.00% (32/32) with 95% CI (89.28%, 100.00%)NPA: 100.00% (65/65) with 95% CI (94.42%, 100.00%)
Clinical Agreement	High positive and negative percent agreement with an FDA-cleared predicate assay.	Population 1 (n=897):- PPA: 94.94% (150/158) with 95% CI (90.33%, 97.41%)- NPA: 94.44% (697/738) with 95% CI (92.55%, 95.88%)Population 2 (pregnant women, n=234):- PPA: 94.74% (18/19) with 95% CI (75.36%, 99.06%)- NPA: 100.00% (215/215) with 95% CI (98.24%, 100.00%)

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

Cutoff Establishment (Internal Validation): 1219 samples (1053 nonreactive, 166 reactive). Data provenance not specified (likely internal laboratory samples, retrospective).
Within-Laboratory Precision (20-Day): Not directly a "test set" sample size for diagnostic accuracy, but involves 2 controls and 4 plasma panels tested multiple times (360-360 replicates per control/panel).
Analytical Specificity (Interference): Samples with target ranges of anti-Toxo IgM (0.60 to 0.99 S/CO and 1.00 to 2.00 S/CO) spiked with interferents. Specific number of samples per substance/condition not given, but refers to CLSI guidance.
Cross-Reactivity: 177 serum specimens from individuals with other medical conditions and high titer Toxoplasmosis IgG. Data provenance not specified (likely retrospective or collected for study).
Matrix Equivalency: 43 donors (20 reactive, 23 nonreactive). Samples collected in 5 different tube types. Data provenance not specified.
Class Specificity: Not specified as a separate sample set size, likely inferred from internal controls or prepared samples.
CDC Panel Agreement: 97 specimens (32 true positive, 65 true negative) from the CDC Toxoplasma 1998 Human Serum Panel. This is a retrospective, well-characterized panel.
Reproducibility (5-Day, Multi-Site): Same sample panels as within-laboratory precision (controls and 4 plasma panels) tested across 3 US sites. 360 replicates per sample.
Clinical Agreement:
- Population 1: 897 consecutively collected remnant specimens. 169 from the US and 710 from outside the US. This implies a mixture of retrospective and potentially prospective collection depending on "consecutively collected remnant specimens."
- Population 2: 207 consecutively collected remnant specimens from pregnant women in the US. This implies a mixture of retrospective and potentially prospective collection.
- Total US specimens in the clinical study: 376 (169 from Pop 1 + 207 from Pop 2).

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)

The document does not mention the use of experts (e.g., radiologists) for establishing ground truth, as this is an in vitro diagnostic (IVD) device for serological testing.
Ground Truth for IVDs: For IVDs like this, "ground truth" is typically established by:
- Reference Method/Predicate Device: The clinical agreement study uses an "FDA-cleared, commercially available anti-Toxo IgM assay" (the bioMérieux VIDAS TOXO IgM assay) as the comparator, which serves as the reference standard for clinical performance.
- Well-Characterized Panels: The CDC Toxoplasma 1998 Human Serum Panel is used, where the "true positive" and "true negative" status of specimens are established by the CDC through their own rigorous characterization processes.
- Internal Characterization: For studies like cutoff determination, samples are "characterized with a commercially available anti-Toxo IgM assay," implying the use of an existing reference method.

Therefore, the "experts" in this context are the established reference methods and panels from organizations like the CDC, rather than individual human interpretative experts for modalities like radiology.

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 imaging studies where multiple human readers interpret images, and discrepancies are resolved by an expert panel.
For an IVD assay like this, the "adjudication" is inherent in the comparison to a predefined reference standard (the predicate device or the CDC panel's established status) or by the assay's internal cutoff determination process.
The document does not describe any specific human "adjudication" process for the result of the Alinity i Toxo IgM assay beyond its comparison to the comparator assay or CDC panel.

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, an MRMC comparative effectiveness study was not done.
MRMC studies are specific to AI/CADe (Computer-Assisted Detection) or CADx (Computer-Assisted Diagnosis) devices that assist human readers in interpreting medical images.
The Alinity i Toxo IgM assay is an in vitro diagnostic (IVD) device that performs a laboratory test for antibodies; it does not involve human readers interpreting images or AI assistance for such interpretation.

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

Yes, this device inherently performs as a standalone "algorithm" in the sense that it is an automated laboratory assay. The results (S/CO values) are generated by the instrument based on its chemical reactions and detection system, and then interpreted against predefined cutoffs.
While a human operator loads samples and manages the instrument, the diagnostic detection (CMIA technology for Toxo IgM antibodies) is fully automated by the device itself, without human interpretation of the primary result (RLU or S/CO). The physician then interprets the qualitative result (Reactive, Grayzone, Nonreactive) in the context of the patient's clinical picture.
The performance metrics (precision, analytical specificity, cross-reactivity, CDC panel agreement, clinical agreement) are all measures of this standalone analytical performance.

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

The ground truth for this device was established primarily through:

Reference Standard/Predicate Assay: For the clinical agreement study, the Alinity i Toxo IgM assay results were compared against an FDA-cleared, commercially available anti-Toxo IgM assay (the bioMérieux VIDAS TOXO IgM assay). This predicate device serves as the clinical "ground truth" or reference.
Well-Characterized Panel: For the CDC Panel Agreement study, the ground truth was the established status of samples within the CDC Toxoplasma 1998 Human Serum Panel (i.e., known true positive or true negative Toxoplasma specimens). This panel's characterization is highly reliable.
Internal Characterization/Comparator Assay: For cutoff establishment, samples were characterized using a "commercially available anti-Toxo IgM assay."

8. The sample size for the training set

The document does not explicitly describe a separate "training set" in the context of machine learning or AI model development.
For IVD devices, a "training set" might loosely refer to the samples used during assay development and optimization (e.g., for reagent formulation, instrument parameters, and initial cutoff setting), but this data is not typically reported as a formalized "training set" size in the same way as for AI.
The closest description of data used for internal calibration/optimization is the 1219 samples used for assay cutoff establishment (1053 anti-Toxo IgM nonreactive samples and 166 anti-Toxo IgM reactive samples). This dataset could be considered analogous to a development/training set for establishing the assay's interpretation rules, although it's crucial to understand this isn't an AI/ML context.

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

As mentioned above, there isn't a traditional "training set" for an AI model.
For the 1219 samples used to establish the assay cutoff, the ground truth (reactive/nonreactive) was established by characterizing these samples with a "commercially available anti-Toxo IgM assay." This means the existing, established methods of Toxo IgM detection were used to classify these samples, allowing the Alinity i assay to be "trained" (or its cutoff optimized) to align with those established classifications.

Summary

{0}------------------------------------------------

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. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

August 30, 2024

Abbott Laboratories Laura Fraczek Regulatory Affairs Senior Specialist 100 Abbott Park Rd. Abbott Park, Illinois 60064

Re: K233932

Trade/Device Name: Alinity i Toxo IgM Regulation Number: 21 CFR 866.3780 Regulation Name: Toxoplasma Gondii Serological Reagents Regulatory Class: Class II Product Code: LGD Dated: December 13, 2023 Received: December 14, 2023

Dear Laura Fraczek:

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.

{1}------------------------------------------------

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

{2}------------------------------------------------

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 a digital signature. The signature indicates that the document was digitally signed by JORGE L. MUNOZ -S. The date of the signature is August 30, 2024. The timestamp of the signature is 10:42:40 -04'00'.

Jorge Munoz, Ph.D. Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

{3}------------------------------------------------

Indications for Use

510(k) Number (if known) K233932

Device Name Alinity i Toxo IgM

Indications for Use (Describe)

The Alinity i Toxo IgM assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of IgM antibodies to Toxoplasma gondii in human serum separator, and plasma tubes (Ithium heparin, lithium heparin separator, and tripotassium EDTA) on the Alinity i system.

The Alinity i Toxo IgM assay has not been cleared for use in screening blood, plasma, or tissue donors.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{4}------------------------------------------------

510(k) Summary

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

I. 510(k) Number

K233932

II. Applicant Name

Abbott Laboratories Department 09AA 100 Abbott Park Road Abbott Park, IL 60064

Primary contact person for all communications:

Laura Fraczek, Senior Specialist Regulatory Affairs Abbott Diagnostics Division Telephone Number: (224) 668-8852 Fax Number: (224) 667-5810

Secondary contact person for all communications:

Jacob Richards, Associate Director, Regulatory Affairs Abbott Diagnostic Division Telephone Number: (224) 668-5877 Fax Number: (224) 667-5810

Date summary prepared: August 28, 2024

{5}------------------------------------------------

III. Device Name

Alinity i Toxo IgM

Reagents

Trade Name: Alinity i Toxo IgM Reagent Kit Device Classification: Class II Classification Name: Toxoplasma gondii serological reagents Governing Regulation: 21 CFR 866.3780 Code: LGD

Calibrator

Trade Name: Alinity i Toxo IgM Calibrator Device Classification: Class II Classification Name: Toxoplasma gondii serological reagents Governing Regulation: 21 CFR 866.3780 Code: LGD

Controls

Trade Name: Alinity i Toxo IgM Controls Device Classification: Class II Classification Name: Toxoplasma gondii serological reagents Governing Regulation: 21 CFR 866. 3780 Code: LGD

IV. Predicate Device

bioMérieux VIDAS TOXO IgM assay (K923166)

V. Description of Device

Reagents

The kit configurations of the Alinity i Toxo IgM Reagent Kit are described below.

List Number (LN)	07P4740	07P4745
Tests per cartridge	100	500
Number of cartridges per kit	2	2
Tests per kit	200	1000
Microparticles	6.6 mL	27.0 mL
Conjugate	6.1 mL	26.5 mL

{6}------------------------------------------------

Microparticles: Anti-human IgM (murine, monoclonal) antibody coated microparticles in TRIS buffer with protein (bovine and goat) stabilizers, and detergent. Minimum concentration: 0.08 % solids. Preservatives: antimicrobial agents.
Conjugate: Conjugate complex consisting of acridinium-labeled anti-Toxoplasma ● p30 antigen antibody (murine, monoclonal) and native Toxoplasma gondii lysate in phosphate buffer with protein (bovine) stabilizer, and detergent. Minimum concentration: 25 µg/mL. Preservative: sodium azide.

Calibrator

The Alinity i Toxo IgM Calibrator is described below.

Calibrator 1: Contains anti-Toxoplasma p30 antigen IgM antibody (human, • monoclonal) prepared in recalcified human plasma. The calibrator is reactive for IgM antibodies to Toxoplasma gondii (anti-Toxo IgM). Preservatives: ProClin 950 and sodium azide.

Calibrator	Quantity
Calibrator 1	1 x 3.0 mL

The Alinity i Toxo IgM Calibrator is manufactured and referenced to an internal reference standard.

Controls

The Alinity i Toxo IgM Controls are described below.

Negative Control: Contains recalcified human plasma. •
Positive Control: Contains anti-Toxoplasma p30 antigen IgM antibody (human, . monoclonal) prepared in recalcified human plasma. The positive control is reactive for IgM antibodies to Toxoplasma gondii (anti-Toxo IgM).
Preservatives: ProClin 950 and sodium azide. •

{7}------------------------------------------------

		Anti-Toxo IgM
Control	Quantity	Target(S/CO)	Range(S/CO)
Negative Control	1 x 4.0 mL	-	< 0.67
Positive Control	1 x 4.0 mL	2.50	1.25 - 3.75

The targets and ranges for the controls are provided in the table below.

The Alinity i Toxo IgM Positive Control is referenced to an internal reference standard.

Biological Principles of the Procedure

Pre-diluted sample and anti-human IgM murine monoclonal antibody coated paramagnetic microparticles are combined and incubated. Together with IgM antibodies of other specificities, anti-Toxo specific IgM present in the sample binds to the anti-human IgM murine monoclonal antibody coated microparticles, forming an antibody-antibody complex. The mixture is washed. A conjugate complex consisting of an acridinium-labeled anti-Toxo p30 antigen murine monoclonal F(ab')2 fragment and native Toxoplasma gondii lysate, containing the p30 antigen, is added to create a reaction mixture and incubated. This conjugate complex is bound by anti-Toxo specific IgM that has been captured by the anti-human IgM murine monoclonal antibody coated microparticles, forming an antibody-antibody-conjugate complex. 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 anti-Toxo IgM in the sample and the RLU detected by the system optics.

{8}------------------------------------------------

The presence or absence of anti-Toxo IgM in the sample is determined by comparing the chemiluminescent RLU in the reaction to the cutoff RLU determined from an active calibration.

VI. Intended Use of the Device

The Alinity i Toxo IgM assay has not been cleared for use in screening blood, plasma, or tissue donors.

VII. Comparison of Technological Characteristics

The Alinity i Toxo IgM assay (subject device) utilizes a CMIA methodology for the qualitative in vitro detection of IgM antibodies to Toxoplasma gondii and is intended for use on the Alinity i system.

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

{9}------------------------------------------------

	Subject Device	Predicate Device
Characteristics	Alinity i Toxo IgMK233932	VIDAS TOXO IgM AssayK923166
Intended Use andIndications for Use	The Alinity i Toxo IgM assay is achemiluminescent microparticle immunoassay(CMIA) used for the qualitative detection ofIgM antibodies to Toxoplasma gondii in humanserum, serum separator, and plasma tubes(lithium heparin, lithium heparin separator, andtripotassium EDTA) on the Alinity i system.The Alinity i Toxo IgM assay is to be used asan aid in the diagnosis of acute or recentToxoplasma gondii infection in suspectedindividuals including women of child-bearingage. It is recommended that the assay beperformed in conjunction with a Toxoplasmagondii IgG assay.The Alinity i Toxo IgM assay has not beencleared for use in screening blood, plasma, ortissue donors.	The VIDAS® TOXO IgM (TXM) assay is intendedfor use on the instruments of the VIDAS® family(VITEK® ImmunoDiagnostic Assay System) as anautomated enzyme-linked fluorescent immunoassay(ELFA) for the presumptive qualitative detection ofanti-Toxoplasma gondii IgM antibodies in humanserum, as an aid in the diagnosis of acute, recent, orreactivated Toxoplasma gondii infection. This assaymust be performed in conjunction with an anti-Toxoplasma gondii lgG antibody assay. VIDAS®TOXO IgM (TXM) assay performance has not beenestablished for prenatal screening or newborntesting. This assay has not been cleared by the FDAfor blood/plasma donor screening.
	Calibrator(s)	1 Calibrator	1 Calibrator
	Control(s)	2 (Negative and Positive)	2 (Negative and Positive)
		Subject DeviceAlinity i Toxo IgM	Predicate DeviceVIDAS TOXO IgM Assay
	Characteristics	K233932	K923166
	Antigen andAntibody Used	• Anti-Toxoplasma p30 antigen antibody(murine, monoclonal) and nativeToxoplasma gondii lysate• Anti-human IgM murine monoclonalantibody	• Immunocomplex of T. gondii antigen (RH Sabinstrain)• Mouse monoclonal anti-P30 antibodies
	Type of Specimen	Serum and Plasma	Serum
	Methodology	Chemiluminescent microparticle immunoassay	Enzyme-linked fluorescent immunoassay
	Interpretation ofResults	Nonreactive: < 0.83 S/COGrayzone/Equivocal: 0.83 to < 1.00 S/COReactive: ≥ 1.00 S/CO	Negative: < 0.55 Test ValueEquivocal: ≥ 0.55 to < 0.65 Test ValuePositive: ≥ 0.65 Test Value
	Components	Microparticles – Anti-human IgM (murine,monoclonal) antibody coated microparticles inTRIS buffer with protein (bovine and goat)stabilizers, and detergent. Minimumconcentration: 0.08 % solids. Preservatives:antimicrobial agents.Conjugate - Conjugate complex consisting ofacridinium-labeled anti-Toxoplasma p30antigen antibody (murine, monoclonal) andnative Toxoplasma gondii lysate in phosphatebuffer with protein (bovine) stabilizer, anddetergent. Minimum concentration: 25 µg/mL.Preservative: sodium azide.	Solid Phase Receptacle (SPR) – SPR coated goatanti-μ chain antibodiesReagent Strip – Strip consists of 10 wells coveredwith labeled, foil seal. The wells contain the variousreagents required for the assay including:• Sample diluent: 300 µL of TRIS buffered saline(0.05 mol/L, pH 7.4) with protein and chemicalstabilizers and 1 g/L sodium azide.• Pre-wash: 600 µL of TRIS buffered saline(0.05 mol/L, pH 7.4) with protein and chemicalstabilizers and 1 g/L sodium azide.• Wash buffer: 600 µL of TRIS buffered saline(0.05 mol/L, pH 7.4) with protein and chemicalstabilizers and 1 g/L sodium azide.• Conjugate: 400 µL of immunocomplex ofT. gondii antigen (RH Sabin strain) grown in mice(9) and mouse monoclonal anti-P30 antibodies
	Subject DeviceAlinity i Toxo IgMK233932	Predicate DeviceVIDAS TOXO IgM AssayK923166
Characteristics		conjugated to alkaline phosphatase withgentamycin 0.02% and 0.9 g/L sodium azide.• Reading cuvette with substrate: 4-Methyl-umbelliferyl phosphate (0.6 mmol/L) +diethanolamine (DEA) (0.62 mol/L or 6.6%,pH 9.2) + 1 g/L sodium azide (300 µL).
Calibration Storage	Maximum of 30 days	14 days

Assay Similarities

{10}------------------------------------------------

Assay Differences

{11}------------------------------------------------

{12}------------------------------------------------

VIII. Summary of Nonclinical Performance

A. Assav Cutoff

The cutoff for the Alinity i Toxo IgM assay was established using samples characterized with a commercially available anti-Toxo IgM assay. A total of 1219 samples (1053 anti-Toxo IgM nonreactive samples and 166 anti-Toxo IgM reactive samples) were included. A receiver-operating characteristic analysis showed a clear separation of the nonreactive and reactive results using a cutoff of 1.00 S/CO (with a grayzone from 0.83 to < 1.00 S/CO).

B. Within- Laboratory Precision (20-Day)

A 20-day within-laboratory precision study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 3 lots of the Alinity i Toxo IgM reagents, 3 lots of the Alinity i Toxo IgM Calibrator, 3 lots of the Alinity i Toxo IgM Controls, and 1 instrument. Two controls and 4 recalcified human plasma panels (representing serum matrix) were tested in 3 replicates at 2 separate times per day on 20 days using 3 reagent lot/calibrator lot combinations, where a unique reagent lot and a unique calibrator lot are paired. The performance is shown in the following table.

		Mean	Repeatability(Within-Run)		Between-Run		Between-Day		Between-Lot a		Overall WithinLaboratory b
Sample ID	N	(S/CO)	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Negative Control	360	0.14	0.012	NAc	0.000	NAc	0.004	NAc	0.008	NAc	0.014	NAc
Positive Control	360	2.72	0.077	2.8	0.034	1.3	0.031	1.2	0.051	1.9	0.104	3.8
True NonreactivePanel	358d	0.14	0.013	NAc	0.000	NAc	0.005	NAc	0.006	NAc	0.015	NAc
High NonreactivePanel	360	0.81	0.028	NAc	0.006	NAc	0.009	NAc	0.027	NAc	0.040	NAc
Low Reactive Panel	359d	1.34	0.047	3.5	0.000	0.0	0.007	0.5	0.042	3.2	0.064	4.7
Reactive Panel	359d	2.54	0.078	3.1	0.000	0.0	0.023	0.9	0.073	2.9	0.109	4.3

Almity i Toxo IgM reagent lot and Alinity i Toxo IgM callbrator lot are confounding effect is represented by betweenlot.

b Overall within-laboratory variability contains repeatability (within-run), between-day, and between-lot variance components.

ు Not applicable

d In cases where n < 360, replicate(s) were excluded due to an instrument error and no results were reported.

* Clinical and Laboratory Standards Institute (CLSI). Evaluation of Quantitative Measurement Procedures: Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.

{13}------------------------------------------------

C. Analytical Specificity

Potentially Interfering Endogenous Substances

The Alinity i Toxo IgM assay was evaluated for potential interference caused by endogenous substances based on guidance from CLSI EP07, 3rd ed. * and CLSI EP37, 1st ed. * Each substance was evaluated using samples containing anti-Toxo IgM at the target ranges of 0.60 to 0.99 S/CO and 1.00 to 2.00 S/CO.

No significant interference (interference ≤ +0.10 S/CO for samples < 1.00 S/CO and ≥ -10% for samples ≥ 1.00 S/CO) was observed at the following concentrations.

No Significant Interference
Potentially Interfering Substance	Interferent Level
Unconjugated Bilirubin	40 mg/dL
Conjugated Bilirubin	40 mg/dL
Hemoglobin	1000 mg/dL
Total Protein	15 g/dL
Triglycerides	3000 mg/dL

Potentially Interfering Other Conditions

The Alinity i Toxo IgM assay was evaluated for potential interference caused by HAMA and RF based on guidance from CLSI EP07, 3rd ed.16. Each condition was evaluated using samples containing anti-Toxo IgM at the following target range: 1.00 to 1.40 S/CO.

No significant interference (interference ≤± 10%) was observed at the following concentrations.

Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.

* Clinical and Laboratory Standards Institute (CLSI). Supplemental Tables for Interference Testing in Clinical Chemistry. 1st ed. CLSI supplement EP37. Wayne, PA: CLSI; 2018.

{14}------------------------------------------------

No Significant Interference
Potentially Interfering Other Condition	Interferent Level
HAMA	800 ng/mL
RF	200 IU/mL

Potentially Interfering Drugs and Other Substances

The Alinity i Toxo IgM assay was evaluated for potential interference caused by exogenous substances based on guidance from CLSI EP07, 3rd ed. and CLSI EP37, 1 st ed. Each substance was evaluated using samples containing anti-Toxo IgM at the target ranges of 0.60 to 0.99 S/CO and 1.00 to 2.00 S/CO.

No significant interference (interference ≤ +0.10 S/CO for samples < 1.00 S/CO and ≥ -10% for samples ≥ 1.00 S/CO) was observed at the following concentrations.

No Significant Interference
Potentially Interfering Substance	Interferent Level
Ascorbic Acid	300 mg/L
Atovaquone	120 mg/L
Beta Carotene	6 mg/L
Biotin	4250 ng/mL
Clindamycin	5.1 mg/dL
Folic Acid	100 nmol/L
Pyrimethamine	15 mg/L
Spiramycine	4.2 mg/L
Sulfadiazine	25.5 mg/dL
Sulfamethoxazole	210 mg/dL
Trimethoprim	4.2 mg/dL

{15}------------------------------------------------

Potential Cross-Reactivity

Potential cross-reactivity for the Alinity i Toxo IgM assay was determined by testing a total of 177 serum specimens from individuals with other medical conditions unrelated to Toxoplasmosis infection, in addition to individuals with high titer Toxoplasmosis IgG. Out of 10 RF specimens, one resulted in a false reactive result with the Alinity i Toxo IgM assay.

Category	n	Number of Alinity i Toxo IgMFalse Reactive Results
Anti-dsDNA Antibodies	10	0
Anti-nuclear Antibody (ANA)	10	0
Cytomegalovirus (IgM)	10	0
Epstein-Barr Virus (EBV) IgM	9	0
Herpes Simplex Virus Types 1/2 (IgG/IgM)	18	0
Human anti-mouse antibody	10	0
Hyper IgG	10	0
Hyper IgM	10	0
Influenza vaccine recipients	10	0
Measles (IgM)	10	0
Parvovirus B19 (IgG)	6	0
Parvovirus B19 (IgM)	4	0
Rheumatoid Factor	10	1a
Rubella (IgM)	10	0
Samples from immunocompromised patients	10	0
Syphilis	10	0
Toxoplasmosis High Titer (IgG)	10	0
Varicella Zoster Virus	10	0
Total	177	1

a One out of 10 RF specimens was falsely reactive with the Alinity i Toxo IgM assay.

{16}------------------------------------------------

D. Matrix Equivalency

A study was performed to evaluate whether specific blood collection tube types are suitable for use with the Alinity i Toxo IgM assay. The matrix collection tube type equivalency study was conducted including 43 donors of reactive (20 donors) and nonreactive (23 donors) samples in 5 types of blood collection tubes (serum, serum separator, lithium heparin plasma, lithium heparin plasma separator, and tripotassium EDTA plasma) for use with the Alinity i Toxo IgM assay. Data was analyzed using regression analysis comparing numerical S/CO results of all matrices to serum to evaluate any potential bias. All of the blood collection tube types tested are acceptable for use with the Alinity i Toxo IgM assay.

E. Class Specificity

Class specificity testing of the Alinity i Toxo IgM assay demonstrated reactivity only to human anti-Toxoplamsa IgM. No reactivity to human anti-Toxoplasma IgG was observed.

F. CDC Panel Agreement

The Centers for Disease Control and Prevention (CDC) Toxoplasma 1998 Human Serum Panel was tested using the Alinity i Toxo IgM assay. The Alinity i Toxo IgM assay results were submitted to the CDC for data analysis and for the result interpretation for each sample. The panel consisted of 32 true positive Toxoplasma specimens and 65 true negative Toxoplasma specimens. The Alinity i Toxo IgM assay detected the 32 positive specimens as reactive and the 65 negative specimens as nonreactive. The CDC performed kit sensitivity (positive percent agreement [PPA]) and kit specificity (negative percent agreement [NPA]) analyses and sent the results to Abbott.

The percent agreement of the Alinity i Toxo IgM assay relative to the CDC results was calculated. The PPA was 100% with a 95% confidence interval (CI) of 89.28% to 100.00%. The NPA was 100% with a 95% CI of 94.42% to 100.00%.

{17}------------------------------------------------

The results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. This does not imply endorsement of the assay by the CDC.

Alinity i Toxo IgM Interpretation	CDC Interpretation		Positive % Agreement (95% CI)ª	Negative % Agreement (95% CI)ª
	Positive	Negative
Reactive	32	0	100.00(32/32)	100.00(65/65)
Grayzone/Equivocal	0	0
Nonreactive	0	65

a The 95% CI for negative percent and positive percent agreement were estimated using the Wilson score method.

IX. Summary of Clinical Performance

A. Expected Values

Representative performance data are provided in this section. Results obtained in individual laboratories may vary.

The Alinity i Toxo IgM results from the clinical method comparison study for each category in the US intended use population are summarized in the following table.

Category	Number ofReactive (%)	Number ofNonreactive (%)	Total
Population 1	1 (0.6)	168 (99.4)	169
Population 2	1 (0.5)	206 (99.5)	207
Total	2 (0.5)	374 (99.5)	376

Note: Population 1 are consecutively collected remnant specimens sent to a laboratory for anti-Toxo IgM testing. Population 2 are consecutively collected remnant specimens from pregnant women sent to a laboratory for anti-Toxo IgM testing.

{18}------------------------------------------------

The Alinity i Toxo IgM assay was reactive in 2 (0.5%) of the collected specimens in the US intended use population (n = 376).

B. Reproducibility Study (5-Day)

A 5-day reproducibility study was conducted at 3 US sites, using the same sample panels used in the within-laboratory precision study, in addition to one positive and one negative control based on the guidance from CLSI EP05-A3. Four replicates per sample were evaluated in 2 runs per day over 5 days. Testing was conducted using 3 lots of the Alinity i Toxo IgM reagents, 2 lots of the Alinity i Toxo IgM Calibrator, and 1 lot of the Alinity i Toxo IgM Controls at each of the 3 testing sites.

		Mean		Repeatability		Between-Run		Between-Day		Between-Site		Between-Lota		Reproducibilityb
Sample	N	S/CO	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
NegativeControl	360	0.13	0.013	NAc	0.002	NAc	0.001	NAc	0.009	NAc	0.008	NAc	0.018	NAc
PositiveControl	360	2.62	0.074	2.8	0.031	1.2	0.022	0.8	0.056	2.1	0.075	2.9	0.132	5.1
TrueNonreactivePanel	360	0.11	0.013	NAc	0.000	NAc	0.004	NAc	0.006	NAc	0.008	NAc	0.017	NAc
HighNonreactivePanel	360	0.76	0.030	NAc	0.009	NAc	0.006	NAc	0.000	NAc	0.023	NAc	0.041	NAc
LowReactivePanel	360	1.3	0.042	3.2	0.017	1.3	0.000	0.0	0.016	1.3	0.040	3.1	0.067	5.1
ReactivePanel	360	2.49	0.077	3.1	0.032	1.3	0.019	0.8	0.059	2.4	0.080	3.2	0.136	5.5

Alinity i Toxo IgM reagent lot and Alinity i Toxo IgM calibrator lot are confounding effect is represented by betweena lot.

b Reproducibility contains repeatability, between-day, between-lot, between-site, and site-lot interaction variance components.

c Not applicable

{19}------------------------------------------------

C. Clinical Agreement

A clinical method comparison study was conducted to evaluate the clinical performance of the Alinity i Toxo IgM assay based on guidance from CLSI EP12-A2, 2nd ed. * , to evaluate the percent agreement between the Alinity i Toxo IgM investigational assay and a current FDA-cleared, commercially available anti-Toxo IgM assay with specimens collected from 2 populations. Population 1 was comprised of 897 consecutively collected remnant specimens sent to a laboratory for anti-Toxo IgM testing including specimens collected in the US (n = 169) and outside of the US (n = 710), and Population 2 was comprised of 207 consecutively collected remnant specimens from pregnant women sent to a laboratory for anti-Toxo IgM testing in the US.

Demographic information for specimens collected in the US from Population 1 and 2 is shown in the table below (n=376).

Specimen	Age	Female (n)	Male (n)	Unknown (n)	Total (n)
Population 1(n=169)	≤ 5 years	2	2	0	4
	6 to 21 years	5	7	0	12
	22 to 59 years	75	36	1	112
	≥ 60 years	20	19	0	39
	Unknown	0	2	0	2
	Total	102	66	1	169
Population 2(n=207)	≤ 5 years	0	0	0	0
	6 to 21 years	8	0	0	8
	22 to 59 years	196	0	0	196
	≥ 60 years	0	0	0	0
	Unknown	3	0	0	3
	Total	207	0	0	207
Total	≤ 5 years	2	2	0	4
	6 to 21 years	13	7	0	20
	22 to 59 years	271	36	1	308
	≥ 60 years	20	19	0	39
	Unknown	3	2	0	5
	Total	309	66	1	376

* Clinical and Laboratory Standards Institute (CLSI). User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline-Second Edition. CLSI Document EP12-A2. Wayne, PA: CLSI; 2008.

{20}------------------------------------------------

SpecimenCategory	Alinity i Toxo IgMResult	Comparator Result			Positive %Agreement(95% CI)a	Negative %Agreement(95% CI)a
Population 1(n=897)	Reactive	150	16	11	94.94(150/158)(90.33, 97.41)	94.44(697/738)(92.55, 95.88)
	Grayzone/Equivocal	1	1	14
	Nonreactive	6	1	697
	Total	157	18	722
SpecimenCategory	Alinity i Toxo IgMResult	Comparator Result			Positive %Agreement(95% CI)a	Negative %Agreement(95% CI)a
Population 2b(n=234)	Reactive	18	0	0	94.74(18/19)(75.36, 99.06)	100.00(215/215)(98.24, 100.00)
	Grayzone/Equivocal	0	0	0
	Nonreactive	1	0	215
	Total	19	0	215

PPA and NPA between the Alinity i Toxo IgM assay and an FDA-cleared assay was calculated for each population separately and are shown in the tables below.

a The 95% CI for PPA and NPA were estimated using the Wilson score method.

b Twenty-seven specimens from Population 1 were from pregnant females and therefore, were also included in Population 2.

X. Conclusion Drawn from Nonclinical and Clinical Laboratory Studies

The results presented in this 510(k) premarket notification demonstrate that the subject device (Alinity i Toxo IgM) performance is substantially equivalent to the predicate assay (bioMérieux VIDAS TOXO IgM assay, K923166).

Regulation Number and Section

§ 866.3780

Toxoplasma gondii serological reagents.(a)
Identification. Toxoplasma gondii serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies toToxoplasma gondii in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identifyToxoplasma gondii from clinical specimens. The identification aids in the diagnosis of toxoplasmosis caused by the parasitic protozoanToxoplasma gondii and provides epidemiological information on this disease. Congenital toxoplasmosis is characterized by lesions of the central nervous system, which if undetected and untreated may lead to brain defects, blindness, and death of an unborn fetus. The disease is characterized in children by inflammation of the brain and spinal cord.(b)
Classification. Class II (performance standards).