ARCHITECT Toxo IgG

K210596 · Abbott Laboratories · LGD · May 19, 2022 · Microbiology

Device Facts

• Record ID: K210596
• Device Name: ARCHITECT Toxo IgG
• Applicant: Abbott Laboratories
• Product Code: LGD · Microbiology
• Decision Date: May 19, 2022
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3780
• Device Class: Class 2

Intended Use

The ARCHITECT Toxo IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of IgG antibodies to Toxoplasma gondii in human serum and plasma on the ARCHITECT i System. The ARCHITECT Toxo IgG assay is to be used as an aid in the determination of immune status to T gondii in individuals, including women of child-bearing age, and as an aid in the diagnosis of T gondii infection. A positive result does not distinguish between recent and past infection. Not intended for use in screening blood, plasma or tissue donors.

Device Story

The ARCHITECT Toxo IgG is a chemiluminescent microparticle immunoassay (CMIA) for quantitative detection of IgG antibodies to Toxoplasma gondii in human serum and plasma. The device uses recombinant T. gondii antigens (P30/SAG1 and P35/GRA8) coated on paramagnetic microparticles. In a two-step process, patient samples are incubated with microparticles; specific antibodies bind to the antigen. After washing, murine anti-human IgG acridinium-labeled conjugate is added. Following a second wash, Pre-Trigger and Trigger solutions are added to initiate a chemiluminescent reaction. The system optics measure the resulting relative light units (RLU), which are directly proportional to the anti-Toxo IgG concentration. The assay is performed on the ARCHITECT i System in clinical laboratory settings by trained technicians. Results are used by clinicians to assess immune status or diagnose infection. The device provides quantitative results (IU/mL) to aid clinical decision-making regarding patient management, particularly for pregnant women.

Clinical Evidence

Clinical performance was evaluated via method comparison and reproducibility studies. Method comparison (n=1614) against an FDA-cleared assay showed high agreement across routine and pregnant populations. CDC panel testing (n=100) demonstrated 97% sensitivity and 100% specificity. Precision studies (CLSI EP05-A3) showed total %CVs ranging from 2.5% to 6.7% across various concentrations. Analytical specificity testing (n=164) showed no interference from common medical conditions or substances. Linearity was established from 0.2 to 75.0 IU/mL.

Technological Characteristics

CMIA technology; uses paramagnetic microparticles coated with recombinant T. gondii antigens (P30/SAG1 and P35/GRA8). Energy source: chemiluminescent reaction (acridinium-labeled conjugate). Form factor: reagent kit for automated ARCHITECT i2000SR system. Connectivity: integrated into ARCHITECT i System. Software: automated processing. Standards: CLSI EP05-A3, EP06-A, EP07, EP12-A2, EP17-A2.

Indications for Use

Indicated for individuals, including women of child-bearing age, to determine immune status to Toxoplasma gondii and as an aid in the diagnosis of T. gondii infection. Not for blood, plasma, or tissue donor screening.

Regulatory Classification

Identification

Toxoplasma gondii serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Toxoplasma gondii in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identify Toxoplasma gondii from clinical specimens. The identification aids in the diagnosis of toxoplasmosis caused by the parasitic protozoan Toxoplasma 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.

Predicate Devices

• Vidas Toxo Igg II (txg) Assay Model 30 210 (K993319)

Submission Summary (Full Text)

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May 19, 2022

Abbott Laboratories Linda Sohn Regulatory Project Manager Dept 09AA, Bldg. Ap8-1, 100 Abbott Park Rd. Abbott Park, Illinois 60064

Re: K210596

Trade/Device Name: ARCHITECT Toxo IgG Regulation Number: 21 CFR 866.3780 Regulation Name: Toxoplasma Gondii Serological Reagents Regulatory Class: Class II Product Code: LGD Dated: February 26, 2021 Received: March 1, 2021

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. 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 located 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.

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

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

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 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 ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Ribhi Shawar, Ph.D. (ABMM) Branch Chief, General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number K210596

Device Name ARCHITECT Toxo IgG

Indications for Use (Describe) ARCHITECT Toxo IgG

The ARCHITECT Toxo IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of IgG antibodies to Toxoplasma gondii in human serum and plasma on the ARCHITECT i System.

The ARCHITECT Toxo IgG assay is to be used as an aid in the detection of immune status to Toxoplasma gondii in individuals, including women of child-bearing age, and as an aid in the diagnosis of Toxoplasma gondii infection.

Not intended 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)

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# Section 5: 510(k) Summary (Summary of Safety and Effectiveness)

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. Applicant Name

Abbott Diagnostics Department 09AA, Building AP8A, 100 Abbott Park Road Abbott Park, IL 60064

Primary contact person for all communications:

Linda Sohn, Project Manager Regulatory Affairs Abbott Diagnostics Division Telephone Number: [phone] Fax Number: [phone] Date Summary prepared: May 18, 2022

Karen Weaver, Director of Regulatory Affairs Abbott Diagnostic Division Telephone Number: [phone] Fax Number: [phone]

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# II. Device Name

# ARCHITECT Toxo IgG

### Reagents

Trade Name: ARCHITECT Toxo IgG Reagent Kit Device Classification: Class II Classification Name: Toxoplasma gondii serological reagents Governing Regulation: 21 CFR § 866.3780 Code: LGD

#### Calibrator

Trade Name: ARCHITECT Toxo IgG Calibrator Device Classification: Class II Classification Name: Toxoplasma gondii serological reagents Governing Regulation: 21 CFR § 866.3780 Code: LGD

### Controls

Trade Name: ARCHITECT Toxo IgG Controls Device Classification: Class II Classification Name: Toxoplasma gondii serological reagents Governing Regulation: 21 CFR § 866.3780 Code: LGD

Predicate Device:

BioMérieux VIDAS TOXO IgG II (TXG) assay (k993319)

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# III. Description of Device

### Reagents

The ARCHITECT Toxo IgG reagent kit contains:

- . Microparticles: (1 bottle x 6.6 mL per 100-test / 1 bottle x 27.0 mL per 500-test) Recombinant Toxoplasma gondii antigen coated microparticles in MES buffer with protein (bovine). Minimum concentration: 0.03% solids. Preservative: ProClin 300.
- . Conjugate: (1 bottle x 5.9 mL per 100-test / 1 bottle x 26.3 mL per 500-test). Murine acridinium-labeled anti-human IgG in MES buffer with protein (bovine) stabilizer. Minimum concentration: 0.05 µg/mL. Preservatives: antimicrobial agents.
- Assay Diluent: (1 bottle x 10.0 mL per 100-test / 1 bottle x 50.9 mL per 500-test). • TRIS buffer with protein (murine) and protein (bovine). Preservative: ProClin 300.

# Calibrators

The ARCHITECT Toxo IgG Calibrators:

- . Calibrator A - 1 Bottle (4.0 mL); an aqueous solution with protein (bovine) stabilizer. Preservative: ProClin 300.
- Calibrators B through F 5 bottles (4.0 mL each); contain anti-Toxo IgG in an . aqueous solution with protein (bovine) stabilizer. Preservative: ProClin 300.

Calibrators cover the calibration range of the assay (0.0 - 200.0 IU/mL). The calibrators are at the following anti-Toxo IgG concentrations:

| Calibrator | Target Anti-Toxo IgG Concentration (IU/mL) |
|------------|--------------------------------------------|
| A | 0.0 |
| B | 5.0 |
| C | 25.0 |
| D | 50.0 |
| E | 100.0 |
| F | 200.0 |

The ARCHITECT Toxo IgG Calibrators are referenced to the World Health Organization (WHO) First International Standard (01/600) for anti-Toxoplasma IgG.

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# Controls

The ARCHITECT Toxo IgG Controls:

- . Negative Control - 1 Bottle (8.0 mL); contains recalcified human plasma with protein (ovine) stabilizer. Preservatives: ProClin 950 and sodium azide.
- . Positive Control 1 - 1 Bottle (8.0 mL); contains anti-Toxo IgG in aqueous solution with protein (bovine) stabilizer. Preservative: ProClin 300.

The controls are at the following proposed target Toxo IgG concentrations and ranges:

| Control | Control Range IU/mL |
|---------------------------------|---------------------|
| Negative Control (Control –) | $\leq$ 0.5 |
| Positive Control 1 (Control +1) | 3.0 to 9.0 |

# Principles of the Procedure

This assay is a two-step immunoassay for the quantitative determination of IgG antibodies to Toxoplasma gondii in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology.

Pre-diluted sample, recombinant Toxoplasma gondii antigen (containing recombinant antigens P30[SAG1] and P35[GRA8]) coated paramagnetic microparticles, and assay diluent are combined and incubated. The Toxoplasma gondii specific antibodies present in the sample bind to the recombinant Toxoplasma gondii antigen (containing recombinant antigens P30[SAG1] and P35[GRA8]) coated microparticles. The mixture is washed. Murine anti-human IgG 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 anti-Toxo IgG in the sample and the RLU detected by the system optics.

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### IV. Intended Use of the Device

The ARCHITECT Toxo IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of IgG antibodies to Toxoplasma gondii in human serum and plasma on the ARCHITECT i System.

The ARCHITECT Toxo IgG assay is to be used as an aid in the detection of immune status to Toxoplasma gondii in individuals, including women of child-bearing age, and as an aid in the diagnosis of Toxoplasma gondii infection.

Not intended for use in screening blood, plasma, or tissue donors.

# V. Comparison of Technological Characteristics

The ARCHITECT Toxo IgG assay (subject device) utilizes a chemiluminescent microparticle immunoassay (CMIA) methodology for the quantitative in vitro determination of IgG antibodies to Toxoplasma gondii and is intended for use on the ARCHITECT i System.

The similarities and differences between the subject device and the predicate assay are presented in the Assay Similarities table.

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| Assay Similarities | | |
|-----------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Characteristics | Subject Device<br>ARCHITECT Toxo IgG | Predicate Device<br>VIDAS TOXO IgG II Assay<br>(K993319, Package Insert 30 210-01 [March 2019]) |
| Intended Use and<br>Indications for Use | The Toxo IgG assay is a chemiluminescent<br>microparticle immunoassay (CMIA) for the<br>quantitative determination of IgG antibodies to<br><i>Toxoplasma gondii</i> in human serum and plasma on<br>the ARCHITECT i System.<br>The Toxo IgG assay is to be used as an aid in<br>the detection of immune status to <i>Toxoplasma gondii</i><br>in individuals including women of child-bearing age<br>and as an aid in the diagnosis of <i>Toxoplasma gondii</i><br>infection.<br>Not intended for use in screening blood, plasma, or<br>tissue donors. | VIDAS TOXO IgG II is an automated quantitative<br>test for use on a VIDAS analyzer for the measurement<br>of anti- <i>Toxoplasma gondii</i> IgG in human serum.<br>It is intended for use as an aid in determination of<br>immune status. It is not intended for use in testing<br>(screening) blood donors. |
| Controls | 2 (Negative and Positive) | 2 (Negative and Positive) |
| Standardization | The ARCHITECT Toxo IgG Calibrators are<br>referenced to the World Health Organization (WHO)<br>First International Standard (01/600) for<br>anti- <i>Toxoplasma</i> IgG. | The VIDAS TXG calibrator consists of Human serum<br>containing anti- <i>Toxoplasma</i> IgG and is calibrated<br>against the WHO standard. |
| Assay Protocol | 2-step | 2-step |

# Assay Similarities

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| Assay Differences | | |
|---------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Characteristics | Subject Device<br>ARCHITECT Toxo IgG | Predicate Device<br>VIDAS TOXO IgG II Assay<br>(K993319, Package Insert 30 210-01 [March 2019]) |
| Antigen Used | P30 (SAG1) and P35 (GRA8) | Cytoplasmic Toxoplasma antigen (RH Sabin strain) |
| Type of Specimen | Serum and plasma | Serum |
| Methodology | Chemiluminescence Immunoassay | Enzyme-linked fluorescent immunoassay (ELFA) |
| Interpretation of Results | Nonreactive: < 1.6 IU/mL<br>Grayzone/Equivocal: 1.6 to < 2.7 IU/mL<br>Reactive: ≥ 2.7 IU/mL | Negative: < 4 IU/mL<br>Equivocal: From ≥ 4 to < 8 IU/mL<br>Reactive: ≥ 8 IU/mL |
| | Assay Differences | |
| | Subject Device<br>ARCHITECT Toxo IgG | Predicate Device<br>VIDAS TOXO IgG II Assay<br>(K993319, Package Insert 30 210-01 [March 2019]) |
| Characteristics | | |
| Components | Microparticles – Recombinant Toxoplasma gondii<br>antigen coated microparticles in MES buffer with<br>protein (bovine). Minimum concentration: 0.03%<br>solids. Preservative: ProClin 300.<br>Conjugate - Murine acridinium-labeled anti-human<br>IgG in MES buffer with protein (bovine). Minimum<br>concentration: 0.05 µg/mL. Preservatives:<br>antimicrobial agents.<br>Assay Diluent – TRIS buffer with protein (murine)<br>and protein (bovine). Preservative: ProClin 300. | Solid Phase Receptacle (SPR®) – PR coated with<br>membrane and cytoplasmic Toxoplasma antigen (RH<br>Sabin strain) grown in mice<br>Reagent Strip – Strip consists of 10 wells covered<br>with labeled foil seal. The wells contain the various<br>reagents required for the assay including:<br>Serum diluent: TRIS buffer (50 mmol/l) pH 7.4 +<br>protein and chemical stabilizers + 1 g/L of sodium<br>azide.<br>Pre-washing buffer: TRIS (50 mmol/l) pH 7.4 +<br>protein and chemical stabilizers + 1 g/L of sodium<br>azide<br>Washing buffer: TRIS (50 mmol/L) pH 7.4 + protein<br>and chemical stabilizers + 1g/L of sodium azide<br>Conjugate: Alkaline phosphatase labeled monoclonal<br>anti-human IgG antibodies (mouse) + 1 g/L of sodium<br>azide<br>Serum diluent: TRIS buffer (50 mmol/L) pH 7.4 +<br>protein and chemical stabilizers + 1 g/L of sodium<br>azide<br>Reading cuvette with substrate: 4-Methyl-<br>umbelliferyl phosphate (0.6 mmol/L) +<br>diethanolamine (DEA) (0.62 mol/L or 6.6%, pH9.2) +<br>1 g/L sodium azide |
| Calibrators | 6 (Calibrators A to F) | 1 Calibrator |
| Calibration Storage | Maximum of 30 days | 14 days |

#### . Diffe .

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# Assay Differences

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# VI. Summary of Nonclinical Performance

# A. Within- Laboratory Precision (20-Dav)

A study was performed based on guidance from CLSI EP05-A3. Testing was conducted using 3 lots of the ARCHITECT Toxo IgG reagents, 3 lots of the ARCHITECT Toxo IgG Calibrators, and 3 lots of the ARCHITECT Toxo IgG Controls and 1 instrument. Two controls and 5 human serum panels were assayed in a minimum of 2 replicates at 2 separate times per day on 20 days on 3 reagent lot/calibrator lot combinations, where a unique reagent lot and a unique calibrator lot are paired. The performance from a representative combination is shown in the following table.

| | | | Within-Run<br>(Repeatability) | | Within-Laboratorya<br>(Total) | |
|--------------------|-----|-----------------|-------------------------------|------|-------------------------------|--------------------|
| Sample | N | Mean<br>(IU/mL) | SD | %CV | SD<br>(Rangeb) | %CV<br>(Rangeb) |
| Negative Control | 118 | 0.0 | 0.01 | N/Ac | 0.01<br>(0.01 - 0.02) | N/Ac |
| Positive Control 1 | 120 | 6.4 | 0.16 | 2.5 | 0.16<br>(0.15-0.19) | 2.5<br>(2.4-3.1) |
| Panel 1 | 118 | 0.1 | 0.03 | N/Ac | 0.04<br>(0.04 - 0.05) | N/Ac |
| Panel 2 | 120 | 1.5 | 0.06 | N/Ac | 0.06<br>(0.06 - 0.06) | N/Ac |
| Panel 3 | 120 | 4.2 | 0.16 | 3.8 | 0.18<br>(0.11-0.18) | 3.8<br>(2.9 - 4.5) |
| Panel 4 | 120 | 8.9 | 0.25 | 2.8 | 0.26<br>(0.23 - 0.26) | 2.9<br>(2.7 - 2.9) |
| Panel 5 | 119 | 69.3 | 1.76 | 2.5 | 1.91<br>(1.78 - 1.93) | 2.8<br>(2.6-2.8) |

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

b Minimum and maximum SD or %CV across all reagent lot/calibrator lot combinations.

C Not applicable

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

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# B. Lower Limits of Measurement

A study was performed based on guidance from CLSI EP17-A2. * Testing was conducted using 3 lots of the ARCHITECT Toxo IgG reagents on each of 2 instruments over a minimum of 3 days. The maximum observed limit of blank (LoB), limit of detection (LoD), and lower limit of quantitation (LLoQ) values are summarized below.

| | IU/mL |
|-------|-------|
| LoBa | 0.1 |
| LoDb | 0.2 |
| LLoQc | 0.2 |

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

b 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.

C The LLoQ is defined as the lowest concentration at which a maximum allowable precision of 20 %CV was met and was determined from n ≥ 60 replicates of low-analyte level samples.

^{^} Clinical and Laboratory Standards Institute (CLSI). Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition. CLSI Document EP17-A2. Wayne, PA: CLSI; 2012.

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# C. Linearity

A study was performed based on guidance from CLSI EP06-A.*

This assay is linear across the analytical measuring interval of 0.2 to 75.0 IU/mL.

^* Clinical and Laboratory Standards Institute (CLSI). Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approved Guideline. CLSI Document EP06-A. Wayne, PA: CLSI; 2003.

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# D. Analytical Specificity

# Potentially Interfering Endogenous Substances, Drugs, and Other Substances

A study was performed based on guidance from CLSI EP07, 3rd ed. * and CLSI EP37, 1st ed. * Each substance was tested at 2 levels of the analyte (approximately 2.0 IU/mL and 4.0 IU/mL). No significant interference (interference within ± 0.3 IU/mL for samples < 2.7 IU/mL and within ± 10% for samples ≥ 2.7 IU/mL) was observed at the following concentrations.

| Potentially Interfering Endogenous Substance | Interferent Level |
|----------------------------------------------|-------------------|
| Bilirubin (Conjugated) | 40 mg/dL |
| Bilirubin (Unconjugated) | 40 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Total Protein | 15 g/dL |
| Triglycerides | 3000 mg/dL |

| Potentially Interfering Drug and Other<br>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 |

^* 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.

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# Potentially Interfering Other Conditions

A total of 164 specimens from individuals with medical conditions unrelated to T gondii infection and specimens containing potentially interfering substances were evaluated. No tested specimens resulted in Reactive Results.

| Clinical Category | | Number of ARCHITECT Toxo IgG |
|-------------------------------------------|-----|------------------------------|
| Potentially Interfering Condition | N | Reactive Results |
| Anti-dsDNA Antibodies | 10 | 0 |
| Anti-nuclear Antibody | 10 | 0 |
| Cytomegalovirus (CMV) IgG | 10 | 0 |
| Epstein-Barr Virus (EBNA-1 IgG) | 10 | 0 |
| Epstein-Barr Virus (VCA IgG) | 10 | 0 |
| Influenza Vaccine Recipients (IgG or IgM) | 10 | 0 |
| Human Anti-Mouse Antibody | 10 | 0 |
| Herpes Simplex Virus Types 1 (IgG) | 9 | 0 |
| Herpes Simplex Virus Types 2 (IgG) | 10 | 0 |
| Hyper IgG (polyclonal) | 10 | 0 |
| Measles (IgG) | 10 | 0 |
| Hyper IgG (monoclonal) | 4 | 0 |
| Parvo-B19 virus (IgG) | 10 | 0 |
| Rheumatoid Factor | 10 | 0 |
| Rubella (IgG) | 7 | 0 |
| Syphilis (IgG) | 10 | 0 |
| Toxoplasmosis (High titer IgM) | 5 | 0 |
| Varicella Zoster Virus | 9 | 0 |
| Total | 164 | 0 |

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### E. CDC Panel Agreement

The CDC Toxoplasma 1998 Human Serum Panel was obtained from the Centers for Disease Control and Prevention (CDC) and tested on the ARCHITECT Toxo IgG assay. The results were submitted to the CDC for data evaluation. The panel consisted of 70 true positive toxoplasma specimens and 30 true negative toxoplasma specimens as defined by the Dye Test.

The ARCHITECT Toxo IgG assay detected 68 out of the 70 positive specimens as reactive and 2 out of the 70 positive specimens as grayzone/equivocal (both grayzone/equivocal results were aliquots of the same specimen). Of the 30 negative specimens, the ARCHITECT Toxo IgG assay detected all 30 specimens as nonreactive.

The ARCHITECT Toxo IgG assay demonstrated 97% agreement with the positive specimens (sensitivity) and 100% agreement with the negative specimens (specificity).

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.

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### VII. Summary of Clinical Performance

# A. Expected Values

Due to geographic locations or demographics, assay results obtained in individual laboratories may vary from data presented.

Of the 1614 specimens tested in the ARCHITECT Toxo IgG clinical study, 977 were from the intended use population in the US. Either age or sex was not reported for 14 specimens. Of the remaining 963 specimens, 763 (79.2%) were routine order (384 female and 379 male, 0 to 88 years old) and 200 (20.8%) were pregnant females (19 to 53 years old). The mean age the 963 specimens was 40 years.

The ARCHITECT Toxo IgG assay was reactive in 115 (11.9%) of the collected specimens in the intended use population in the US (n = 963). Testing of the specimens was performed at 3 clinical testing sites located in New York City and Farmingdale, New York and Palo Alto, California.

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The distribution of ARCHITECT Toxo IgG reactive, grayzone/equivocal, and nonreactive results of the 963 US intended use population specimens by age and sex is summarized in the following table.

| Age Range<br>(Years) | Sex | ARCHITECT Toxo IgG Result | | | |
|----------------------|--------|---------------------------|-------------------------------------|------------------------------|-------|
| | | Number of<br>Reactive (%) | Number of<br>Grayzone/Equivocal (%) | Number of<br>Nonreactive (%) | Total |
| 0 to 12 | Female | 2 (11.1) | 0 (0.0) | 16 (88.9) | 18 |
| | Male | 0 (0.0) | 0 (0.0) | 36 (100.0) | 36 |
| 13 to 21 | Female | 2 (3.9) | 0 (0.0) | 49 (96.1) | 51 |
| | Male | 3 (8.8) | 0 (0.0) | 31 (91.2) | 34 |
| 22 to 29 | Female | 12 (9.2) | 0 (0.0) | 118 (90.8) | 130 |
| | Male | 2 (5.6) | 0 (0.0) | 34 (94.4) | 36 |
| 30 to 39 | Female | 12 (6.6) | 2 (1.1) | 167 (92.3) | 181 |
| | Male | 5 (12.2) | 0 (0.0) | 36 (87.8) | 41 |
| 40 to 49 | Female | 5 (9.1) | 1 (1.8) | 49 (89.1) | 55 |
| | Male | 7 (12.7) | 0 (0.0) | 48 (87.3) | 55 |
| 50 to 59 | Female | 5 (9.1) | 0 (0.0) | 50 (90.9) | 55 |
| | Male | 12 (19.4) | 1 (1.6) | 49 (79.0) | 62 |
| 60 to 64 | Female | 8 (25.0) | 0 (0.0) | 24 (75.0) | 32 |
| | Male | 7 (15.9) | 0 (0.0) | 37 (84.1) | 44 |
| 65 to 100 | Female | 23 (37.1) | 1 (1.6) | 38 (61.3) | 62 |
| | Male | 10 (14.1) | 4 (5.6) | 57 (80.3) | 71 |
| | Total | 115 (11.9) | 9 (0.9) | 839 (87.1) | 963 |

The ARCHITECT Toxo IgG results for each category in the intended use population are summarized in the following table.

| | | ARCHITECT Toxo IgG Result | | | |
|----------------------|---------------------------|----------------------------------------|------------------------------|-------|--|
| Specimen<br>Category | Number of Reactive<br>(%) | Number of<br>Grayzone/Equivocal<br>(%) | Number of<br>Nonreactive (%) | Total | |
| Routine<br>Order | 101 (13.2) | 9 (1.2) | 653 (85.6) | 763 | |
| Pregnant<br>Females | 14 (7.0) | 0 (0.0) | 186 (93.0) | 200 | |
| Total | 115 (11.9) | 9 (0.9) | 839 (87.1) | 963 | |

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# B. System Reproducibility

A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 3 lots of the ARCHITECT Toxo IgG reagents, 2 lots of the ARCHITECT Toxo IgG Calibrators, and 2 lots of the ARCHITECT Toxo IgG Controls and 1 instrument at each of the 3 clinical sites. Two controls and 5 human serum panels were assayed in 4 replicates at 2 separate times per day on 5 different days.

| | | Mean | Within-Run<br>(Repeatability) | | Within-Laboratorya<br>(Total) | | Reproducibilityb | |
|--------------------|-----|---------|-------------------------------|------|-------------------------------|------|------------------|------|
| Sample | N | (IU/mL) | SD | %CV | SD | %CV | SD | %CV |
| Negative Control | 360 | 0.0 | 0.02 | N/Ac | 0.02 | N/Ac | 0.02 | N/Ac |
| Positive Control 1 | 360 | 6.4 | 0.15 | 2.3 | 0.18 | 2.8 | 0.22 | 3.5 |
| Panel 1 | 360 | 0.0 | 0.04 | N/Ac | 0.04 | N/Ac | 0.05 | N/Ac |
| Panel 2 | 360 | 1.4 | 0.06 | N/Ac | 0.06 | N/Ac | 0.08 | N/Ac |
| Panel 3 | 360 | 4.2 | 0.12 | 2.8 | 0.12 | 2.9 | 0.23 | 5.6 |
| Panel 4 | 360 | 9.0 | 0.21 | 2.4 | 0.25 | 2.8 | 0.53 | 5.9 |
| Panel 5 | 360 | 69.4 | 2.02 | 2.9 | 2.20 | 3.2 | 4.68 | 6.7 |

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

b Includes within-run, between-run, between-day, between-lot and the site-lot interaction variability.

6 Not applicable

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

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# C. Percent Agreement

A clinical study (method comparison) was performed in the US based on guidance from CLSI EP12-A2, 2nd ed. to evaluate the percent agreement between the ARCHITECT Toxo IgG investigational assay and a current FDA cleared commercially available anti-Toxo IgG assay with routine order and preselected positive specimens collected in the US (n=777 for routine order and n=84 for preselected positive) and outside of the US (n=482 for routine order and n=71 for preselected positive) and specimens collected from pregnant females in the US (n=200).

# Routine Order

| Specimen<br>Category | ARCHITECT<br>TOXO IgG<br>Result | Comparator Result | | | Negative %<br>Agreement<br>(95% Confidence<br>Interval)a | Positive %<br>Agreement<br>(95% Confidence<br>Interval)a |
|----------------------|---------------------------------|-------------------|-----------|----------|----------------------------------------------------------|----------------------------------------------------------|
| | | Positive | Equivocal | Negative | | |
| Routine Order | Reactive | 148 | 4 | 8 | 98.54<br>(1082/1098)<br>(97.65, 99.10) | 94.87<br>(148/156)<br>(90.21, 97.38) |
| | Equivocal | 5 | 5 | 4 | | |
| | Nonreactive | 1 | 2 | 1082 | | |

a The 95% confidence interval (CI) for negative percent agreement and positive percent agreement were estimated using the Wilson Score method.

Twenty-three of the 24 discordant samples from routine order were tested using the Dye Test resulting in either negative, low positive, or inconclusive interpretation. Two of the 3 ARCHITECT Toxo IgG nonreactive samples were negative by Dye Test, and 1 was inconclusive. One of the 11 ARCHITECT Toxo IgG reactive samples was low positive by Dye Test, 9 were negative, and 1 was inconclusive. Seven of the 9 ARCHITECT equivocal samples were negative by Dye Test, and 2 were low positive.

^* 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.

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# Preselected Positive

| | ARCHITECT<br>TOXO IgG<br>Result | Comparator Result | | | Negative %<br>Agreement<br>(95% Confidence<br>Interval)a | Positive %<br>Agreement<br>(95% Confidence<br>Interval)a |
|-------------------------|---------------------------------|-------------------|-----------|----------|----------------------------------------------------------|----------------------------------------------------------|
| Specimen<br>Category | | Positive | Equivocal | Negative | | |
| Preselected<br>Positive | Reactive | 148 | 0 | 0 | 100.00 | 96.73 |
| | Equivocal | 3 | 1 | 0 | (1/1) | (148/153) |
| | Nonreactive | 2 | 0 | 1 | (20.65, 100.00) | (92.58, 98.60) |

a The 95% confidence interval (CI) for negative percent and positive percent agreement were estimated using the Wilson Score method.

Five discordant samples from preselected positive were tested using the Dye Test resulting in either negative, low positive, or inconclusive interpretation. One of the 2 ARCHITECT Toxo IgG nonreactive samples was negative by Dye Test, and 1 was low positive. One of the 3 ARCHITECT equivocal samples was negative by Dye Test, 1 was low positive, and 1 was inconclusive.

#### Pregnant Females

| Specimen<br>Category | ARCHITECT<br>TOXO IgG<br>Result | Comparator Result | | | Negative %<br>Agreement<br>(95% Confidence<br>Interval)a | Positive %<br>Agreement<br>(95% Confidence<br>Interval)a |
|----------------------|---------------------------------|-------------------|-----------|----------|----------------------------------------------------------|----------------------------------------------------------|
| | | Positive | Equivocal | Negative | | |
| Pregnant<br>Females | Reactive | 14 | 0 | 0 | 100.00<br>(186/186)<br>(97.98, 100.00) | 93.33<br>(14/15)<br>(70.18, 98.81) |
| | Equivocal | 0 | 0 | 0 | | |
| | Nonreactive | 1 | 0 | 186 | | |

a The 95% confidence interval (CI) for negative percent agreement and positive percent agreement were estimated using the Wilson Score method.

Note: One pregnant female specimen from routine order collection was included.

One discordant sample with ARCHITECT Toxo IgG nonreactive interpretation

from pregnant females was negative by Dye Test.

{22}------------------------------------------------

Negative percent agreement and positive percent agreement from the specimen categories above were calculated according to the formulas below:

| | | Comparator Toxo IgG Result | | |
|---------------------------------|-------------|----------------------------|-----------|----------|
| | | Positive | Equivocal | Negative |
| ARCHITECT<br>TOXO IgG<br>Result | Reactive | A | B | C |
| | Equivocal | D | E | F |
| | Nonreactive | G | H | I |

Positive Percent Agreement = A/(A+D+G+H) x 100%

Negative Percent Agreement = I/(C+F+I+B) x 100%

# VIII. Conclusion Drawn from Nonclinical and Clinical Laboratory Studies

The results presented in this 510(k) premarket notification demonstrate that the subject device (ARCHITECT Toxo IgG) performance is substantially equivalent to the predicate assay (VIDAS TOXO IgG II assay, k993319).

The similarities and differences between the subject device and the predicate assay are presented in the Assay Similarities table. The results presented in this 510(k) provide reasonable assurance that the subject ARCHITECT Toxo IgG assay is safe and effective for the stated intended use. Differences between the subject device and the predicate assay shown in the tables do not affect the safety and effectiveness of the subject device.

There is no known potential adverse effect to the operator when using this in vitro device according to the ARCHITECT Toxo IgG reagent package insert.