(444 days)
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.
The ARCHITECT Toxo IgG reagent kit contains:
- Microparticles: Recombinant Toxoplasma gondii antigen coated microparticles in MES buffer with protein (bovine). Minimum concentration: 0.03% solids. Preservative: ProClin 300.
- Conjugate: Murine acridinium-labeled anti-human IgG in MES buffer with protein (bovine) stabilizer. Minimum concentration: 0.05 µg/mL. Preservatives: antimicrobial agents.
- Assay Diluent: TRIS buffer with protein (murine) and protein (bovine). Preservative: ProClin 300.
The ARCHITECT Toxo IgG Calibrators:
- Calibrator A - an aqueous solution with protein (bovine) stabilizer. Preservative: ProClin 300.
- Calibrators B through F - contain anti-Toxo IgG in an aqueous solution with protein (bovine) stabilizer. Preservative: ProClin 300.
The ARCHITECT Toxo IgG Controls:
- Negative Control - contains recalcified human plasma with protein (ovine) stabilizer. Preservatives: ProClin 950 and sodium azide.
- Positive Control 1 - contains anti-Toxo IgG in aqueous solution with protein (bovine) stabilizer. Preservative: ProClin 300.
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.
The provided text describes the Abbott ARCHITECT Toxo IgG assay, a chemiluminescent microparticle immunoassay for the quantitative determination of IgG antibodies to Toxoplasma gondii. This document is a 510(k) premarket notification summary, which means it aims to demonstrate substantial equivalence to a legally marketed predicate device, not necessarily to prove its own absolute effectiveness against a clinical ground truth like disease outcome or pathology.
Therefore, the acceptance criteria are primarily demonstration of analytical performance that is substantially equivalent to the predicate device and supports the stated indications for use. The "study that proves the device meets the acceptance criteria" refers to the nonclinical and clinical laboratory studies presented in the 510(k) summary that support this substantial equivalence.
Here's an analysis of the requested information based on the provided text:
1. A table of acceptance criteria and the reported device performance
The document doesn't explicitly list "acceptance criteria" as a separate table. Instead, it presents performance data from various studies. The implicit acceptance criteria are the successful demonstration of performance characteristics typically required for an in vitro diagnostic device to be found substantially equivalent to a predicate.
Below is a table summarizing key performance metrics and the reported results. The "Acceptance Criteria" column reflects the generally expected performance for such assays or thresholds implicitly met by the reported data, rather than specific numerical targets stated in the document.
| Performance Metric (Implicit Acceptance Criteria) | Reported Device Performance (ARCHITECT Toxo IgG) |
|---|---|
| Within-Laboratory Precision (Low %CV, repeatability) | - Negative Control: Mean 0.0 IU/mL, SD 0.01 IU/mL (N/A %CV) - Positive Control 1: Mean 6.4 IU/mL, SD 0.16 IU/mL (2.5 %CV) - Other Panels: %CVs for Panels 3, 4, 5 were 3.8%, 2.8%, 2.5% respectively. |
| Lower Limits of Measurement (LoB, LoD, LLoQ within acceptable ranges) | - LoB: 0.1 IU/mL - LoD: 0.2 IU/mL - LLoQ: 0.2 IU/mL (at 20% CV) |
| Linearity (Assay measures concentrations accurately across a range) | Linear across 0.2 to 75.0 IU/mL. |
| Analytical Specificity / Interference (No significant interference from common substances or cross-reacting conditions) | - No significant interference observed from listed endogenous substances (e.g., Bilirubin, Hemoglobin, Triglycerides) and drugs (e.g., Ascorbic Acid, Atovaquone). - Zero reactive results (0/164) from specimens with various potentially interfering medical conditions (e.g., other viral infections, autoimmune markers, rheumatoid factor). |
| CDC Panel Agreement (High agreement with a well-characterized reference panel) | - Sensitivity (Positive Agreement): 97% (68/70 positive specimens detected as reactive) - Specificity (Negative Agreement): 100% (30/30 negative specimens detected as nonreactive) |
| System Reproducibility (Multi-site) (Consistent performance across different sites/operators) | - Negative Control: Mean 0.0 IU/mL, SD 0.02 IU/mL (N/A %CV) - Positive Control 1: Mean 6.4 IU/mL, SD 0.22 IU/mL (3.5 %CV) - Other Panels: Reproducibility %CVs for Panels 3, 4, 5 were 5.6%, 5.9%, 6.7% respectively. |
| Percent Agreement with Predicate Device (High agreement with a legally marketed comparator) | - Routine Order Samples: - Negative % Agreement: 98.54% (1082/1098) - Positive % Agreement: 94.87% (148/156) - Preselected Positive Samples: - Negative % Agreement: 100.00% (1/1) - Positive % Agreement: 96.73% (148/153) - Pregnant Females Samples: - Negative % Agreement: 100.00% (186/186) - Positive % Agreement: 93.33% (14/15) |
2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
- Precision and Reproducibility Studies:
- Within-Laboratory Precision: 120 replicates per panel/control (e.g., Positive Control 1 N=120, Panel 3 N=120). Data provenance implicitly laboratory-based from Abbott.
- System Reproducibility: 360 replicates per control/panel (e.g., Positive Control 1 N=360). Conducted at 3 clinical sites (US based: New York City and Farmingdale, New York, and Palo Alto, California).
- Lower Limits of Measurement: N ≥ 60 replicates per analyte level. Data provenance implicitly laboratory-based from Abbott.
- Analytical Specificity:
- Interfering Endogenous Substances, Drugs, and Other Substances: Not specified exact number of replicates per interferent, but tested at 2 analyte levels.
- Potentially Interfering Other Conditions: 164 specimens.
- CDC Panel Agreement: 100 specimens (70 true positive, 30 true negative) from the CDC Toxoplasma 1998 Human Serum Panel (implies retrospective, pre-characterized samples).
- Percent Agreement (Method Comparison Clinical Study):
- Total N = 1414 specimens.
- Routine Order: 777 specimens (US) and 482 specimens (outside US). Total 1259.
- Preselected Positive: 84 specimens (US) and 71 specimens (outside US). Total 155.
- Pregnant Females: 200 specimens (US).
- Data Provenance: The document explicitly states the clinical study was performed in the US (at 3 clinical testing sites located in New York City and Farmingdale, New York and Palo Alto, California) and with samples collected in the US and outside of the US. The study is described as a "clinical study," implying prospective collection and testing, but the use of "preselected positive" specimens indicates some retrospective sample selection.
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 specify the number or qualifications of experts used to establish the ground truth for the test sets.
- For the CDC Panel, the "gold standard" was the Dye Test. This test itself is highly specialized and would have been performed by experts at the CDC, but their specific qualifications are not detailed here. The panel itself is a "masked, characterized serum panel," implying its ground truth was established prior to this study.
- For the Percent Agreement (Method Comparison) study, the "ground truth" was established by a "current FDA cleared commercially available anti-Toxo IgG assay" (the comparator device). For discordant samples from this study, the Dye Test was used as a reference. Again, the experts performing these comparator or Dye Tests are not detailed.
- For the Precision, Linearity, and Analytical Specificity studies, the samples are either manufactured/spiked or are pre-screened based on other assays or clinical categories. The ground truth here is analytical rather than clinical, and is established by the methods of sample preparation and characterization typically done by laboratory scientists.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The document does not describe a formal reader (e.g., radiologist) adjudication method (like 2+1 or 3+1) because this is an in vitro diagnostic (IVD) assay, not an image-based AI device. The "reading" or determination of results is done by the automated ARCHITECT i System based on chemiluminescent reactions, not human interpretation of complex images.
For discordant results in the method comparison study, the Dye Test was used as an arbitration method for clarification. For example, in the routine order comparisons, 24 discordant samples were tested using the Dye Test.
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 MRMC comparative effectiveness study was done. This type of study (MRMC) is relevant for diagnostic imaging systems, particularly those that incorporate Artificial Intelligence (AI) to assist human readers (e.g., radiologists interpreting medical images).
The ARCHITECT Toxo IgG assay is an in vitro diagnostic immunoassay. Its "reader" is the ARCHITECT i System, an automated instrument. There is no human "reader" in the loop interpreting results in the same way a radiologist interprets an image. Therefore, questions about human reader improvement with AI assistance are not applicable to this device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance of the ARCHITECT Toxo IgG assay is presented as standalone (algorithm/instrument only) performance. The ARCHITECT i System automatically processes samples and yields quantitative results (IU/mL) and qualitative interpretations (reactive, grayzone/equivocal, nonreactive). There is no "human-in-the-loop" affecting the primary measurement or interpretation by the device itself after it has been loaded.
The various precision, linearity, analytical specificity, and agreement studies (including the CDC panel agreement) demonstrate the standalone performance of the device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for evaluating this IVD device employed a combination of methods:
- Well-characterized Reference Panels: Specifically, the CDC Toxoplasma 1998 Human Serum Panel, which was characterized using the Dye Test (a highly regarded serological reference method for Toxoplasma IgG).
- Comparison to a Legally Marketed Predicate/Comparator Device: For the method comparison studies, the results of the ARCHITECT Toxo IgG assay were compared against a "current FDA cleared commercially available anti-Toxo IgG assay." This serves as a practical ground truth for demonstrating substantial equivalence within regulatory frameworks for IVDs.
- Arbitration with Reference Method: For discordant results in the method comparison study, the Dye Test was used as an arbitration method to resolve discrepancies and provide a more definitive "ground truth" for those specific samples.
- Analytical Ground Truth: For studies like linearity, precision, LoB/LoD/LLoQ, and analytical specificity, the "ground truth" is established by precisely prepared samples (e.g., known concentrations, spiked interferents, samples verified to be negative).
8. The sample size for the training set
The document describes premarket studies for a commercial IVD kit, not an AI/ML algorithm development. Therefore, there is no explicit "training set" in the context of machine learning model development.
The studies described are for validation and verification of the device's performance characteristics. For an IVD assay like this, the "training" aspect would relate to the assay's biochemical development, reagent formulation, and calibration curve generation, which are usually proprietary development processes and not "data sets" in the AI/ML sense.
9. How the ground truth for the training set was established
As there is no explicit "training set" for an AI/ML model described for this IVD assay, this question is not directly applicable.
The development and internal optimization of an immunoassay typically involve extensive laboratory work where known standards and characterized samples are used to optimize reagent concentrations, reaction conditions, and calibration algorithms. The "ground truth" during such development would be based on reference methods, gravimetric/volumetric preparations, and established scientific principles of immunology and chemistry.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the FDA name on the right. The symbol on the left is a stylized image of a human figure, while the FDA name on the right is written in blue letters. The words "U.S. FOOD & DRUG ADMINISTRATION" are written in a clear, sans-serif font.
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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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: (224) 667-4846 Fax Number: (224) 667-4836 Date Summary prepared: May 18, 2022
Karen Weaver, Director of Regulatory Affairs Abbott Diagnostic Division Telephone Number: (224) 668-9286 Fax Number: (224) 667-4836
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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 DeviceARCHITECT Toxo IgG | Predicate DeviceVIDAS TOXO IgG II Assay(K993319, Package Insert 30 210-01 [March 2019]) |
| Intended Use andIndications for Use | The Toxo IgG assay is a chemiluminescentmicroparticle immunoassay (CMIA) for thequantitative determination of IgG antibodies toToxoplasma gondii in human serum and plasma onthe ARCHITECT i System.The Toxo IgG assay is to be used as an aid inthe detection of immune status to Toxoplasma gondiiin individuals including women of child-bearing ageand as an aid in the diagnosis of Toxoplasma gondiiinfection.Not intended for use in screening blood, plasma, ortissue donors. | VIDAS TOXO IgG II is an automated quantitativetest for use on a VIDAS analyzer for the measurementof anti- Toxoplasma gondii IgG in human serum.It is intended for use as an aid in determination ofimmune status. It is not intended for use in testing(screening) blood donors. |
| Controls | 2 (Negative and Positive) | 2 (Negative and Positive) |
| Standardization | The ARCHITECT Toxo IgG Calibrators arereferenced to the World Health Organization (WHO)First International Standard (01/600) foranti- Toxoplasma IgG. | The VIDAS TXG calibrator consists of Human serumcontaining anti- Toxoplasma IgG and is calibratedagainst the WHO standard. |
| Assay Protocol | 2-step | 2-step |
Assay Similarities
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| Assay Differences | ||
|---|---|---|
| Characteristics | Subject DeviceARCHITECT Toxo IgG | Predicate DeviceVIDAS TOXO IgG II Assay(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/mLGrayzone/Equivocal: 1.6 to < 2.7 IU/mLReactive: ≥ 2.7 IU/mL | Negative: < 4 IU/mLEquivocal: From ≥ 4 to < 8 IU/mLReactive: ≥ 8 IU/mL |
| Assay Differences | ||
| Subject DeviceARCHITECT Toxo IgG | Predicate DeviceVIDAS TOXO IgG II Assay(K993319, Package Insert 30 210-01 [March 2019]) | |
| Characteristics | ||
| Components | Microparticles – Recombinant Toxoplasma gondiiantigen coated microparticles in MES buffer withprotein (bovine). Minimum concentration: 0.03%solids. Preservative: ProClin 300.Conjugate - Murine acridinium-labeled anti-humanIgG in MES buffer with protein (bovine). Minimumconcentration: 0.05 µg/mL. Preservatives:antimicrobial agents.Assay Diluent – TRIS buffer with protein (murine)and protein (bovine). Preservative: ProClin 300. | Solid Phase Receptacle (SPR®) – PR coated withmembrane and cytoplasmic Toxoplasma antigen (RHSabin strain) grown in miceReagent Strip – Strip consists of 10 wells coveredwith labeled foil seal. The wells contain the variousreagents required for the assay including:Serum diluent: TRIS buffer (50 mmol/l) pH 7.4 +protein and chemical stabilizers + 1 g/L of sodiumazide.Pre-washing buffer: TRIS (50 mmol/l) pH 7.4 +protein and chemical stabilizers + 1 g/L of sodiumazideWashing buffer: TRIS (50 mmol/L) pH 7.4 + proteinand chemical stabilizers + 1g/L of sodium azideConjugate: Alkaline phosphatase labeled monoclonalanti-human IgG antibodies (mouse) + 1 g/L of sodiumazideSerum diluent: TRIS buffer (50 mmol/L) pH 7.4 +protein and chemical stabilizers + 1 g/L of sodiumazideReading cuvette with substrate: 4-Methyl-umbelliferyl phosphate (0.6 mmol/L) +diethanolamine (DEA) (0.62 mol/L or 6.6%, pH9.2) +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(Repeatability) | Within-Laboratorya(Total) | |||||
|---|---|---|---|---|---|---|
| Sample | N | Mean(IU/mL) | SD | %CV | SD(Rangeb) | %CV(Rangeb) |
| Negative Control | 118 | 0.0 | 0.01 | N/Ac | 0.01(0.01 - 0.02) | N/Ac |
| Positive Control 1 | 120 | 6.4 | 0.16 | 2.5 | 0.16(0.15-0.19) | 2.5(2.4-3.1) |
| Panel 1 | 118 | 0.1 | 0.03 | N/Ac | 0.04(0.04 - 0.05) | N/Ac |
| Panel 2 | 120 | 1.5 | 0.06 | N/Ac | 0.06(0.06 - 0.06) | N/Ac |
| Panel 3 | 120 | 4.2 | 0.16 | 3.8 | 0.18(0.11-0.18) | 3.8(2.9 - 4.5) |
| Panel 4 | 120 | 8.9 | 0.25 | 2.8 | 0.26(0.23 - 0.26) | 2.9(2.7 - 2.9) |
| Panel 5 | 119 | 69.3 | 1.76 | 2.5 | 1.91(1.78 - 1.93) | 2.8(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 OtherSubstance | 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(Years) | Sex | ARCHITECT Toxo IgG Result | |||
|---|---|---|---|---|---|
| Number ofReactive (%) | Number ofGrayzone/Equivocal (%) | Number ofNonreactive (%) | 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 | |||||
|---|---|---|---|---|---|
| SpecimenCategory | Number of Reactive(%) | Number ofGrayzone/Equivocal(%) | Number ofNonreactive (%) | Total | |
| RoutineOrder | 101 (13.2) | 9 (1.2) | 653 (85.6) | 763 | |
| PregnantFemales | 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(Repeatability) | Within-Laboratorya(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
| SpecimenCategory | ARCHITECTTOXO IgGResult | Comparator Result | Negative %Agreement(95% ConfidenceInterval)a | Positive %Agreement(95% ConfidenceInterval)a | ||
|---|---|---|---|---|---|---|
| Positive | Equivocal | Negative | ||||
| Routine Order | Reactive | 148 | 4 | 8 | 98.54(1082/1098)(97.65, 99.10) | 94.87(148/156)(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
| ARCHITECTTOXO IgGResult | Comparator Result | Negative %Agreement(95% ConfidenceInterval)a | Positive %Agreement(95% ConfidenceInterval)a | |||
|---|---|---|---|---|---|---|
| SpecimenCategory | Positive | Equivocal | Negative | |||
| PreselectedPositive | 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
| SpecimenCategory | ARCHITECTTOXO IgGResult | Comparator Result | Negative %Agreement(95% ConfidenceInterval)a | Positive %Agreement(95% ConfidenceInterval)a | ||
|---|---|---|---|---|---|---|
| Positive | Equivocal | Negative | ||||
| PregnantFemales | Reactive | 14 | 0 | 0 | 100.00(186/186)(97.98, 100.00) | 93.33(14/15)(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.
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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 | ||
| ARCHITECTTOXO IgGResult | 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.
§ 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).