Access Toxo IgM II

K242095 · Beckman Coulter, Inc. · LGD · Oct 11, 2024 · Microbiology

Device Facts

• Record ID: K242095
• Device Name: Access Toxo IgM II
• Applicant: Beckman Coulter, Inc.
• Product Code: LGD · Microbiology
• Decision Date: Oct 11, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3780
• Device Class: Class 2

Indications for Use

The Access Toxo IgM II assay is a paramagnetic-particle chemiluminescent immunoassay for the qualitative detection of Toxoplasma gondii-specific IgM antibody in adult human serum and plasma using the Access Immunoassay Systems. The Access Toxo IgM II assay is presumptive for the diagnosis of acute, recent, or reactivated Toxoplasma gondii infection in males and pregnant or non-pregnant females. It is recommended this assay be performed in conjunction with a Toxoplasma gondii-specific IgG antibody assay. Note: This assay has not been cleared/approved by the FDA for the screening of blood or plasma donors in the United States.

Device Story

Access Toxo IgM II is a paramagnetic-particle chemiluminescent immunoassay for qualitative detection of Toxoplasma gondii-specific IgM antibodies. Input: human serum or plasma samples. Operation: 2-step sandwich chemiluminescence immunoassay performed on the DxI 9000 Access Immunoassay Analyzer. The system uses anti-human IgM capture antibodies and inactivated T. gondii antigen conjugated to alkaline phosphatase. Output: qualitative result (Reactive, Equivocal, or Non-Reactive) based on signal-to-cutoff (S/CO) ratio. Used in clinical laboratory settings by trained personnel. Healthcare providers use results in conjunction with IgG testing to diagnose acute, recent, or reactivated toxoplasmosis. Benefits include standardized, automated diagnostic support for infection management.

Clinical Evidence

Bench testing only. Precision studies (within-laboratory and between-instrument) conducted over 20 days and 5 days respectively, showing consistent performance across reagent lots and analyzers. Method comparison study (n=152) between DxI 9000 and Access 2 system showed 100% PPA (95% CI: 91.43%–100%) and 100% NPA (95% CI: 96.53%–100%).

Technological Characteristics

Paramagnetic-particle chemiluminescent immunoassay. Capture: sheep anti-human IgM polyclonal antibody. Detection: alkaline phosphatase-conjugated mouse monoclonal antibody (P30-specific). Substrate: Lumi-Phos PRO. Instrument: DxI 9000 Access Immunoassay Analyzer. Automated, 2-step sandwich format. Calibration: stored curve, 28-day frequency. Storage: 2-10°C.

Indications for Use

Indicated for qualitative detection of Toxoplasma gondii-specific IgM antibody in adult human serum and plasma. Presumptive diagnosis of acute, recent, or reactivated T. gondii infection in males and pregnant or non-pregnant females. Recommended for use with T. gondii-specific IgG antibody assay. Not for blood/plasma 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

• Access Toxo IgM II Assay (K003259)

Submission Summary (Full Text)

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FDA

U.S. FOOD & DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY AND INSTRUMENT

## I Background Information:

A 510(k) Number

K242095

B Applicant

Beckman Coulter Inc.

C Proprietary and Established Names

Access Toxo IgM II

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| LGD | Class II | 21 CFR 866.3780 - Toxoplasma Gondii Serological Reagents | MI - Microbiology |

## II Submission/Device Overview:

A Purpose for Submission:

Clearance of new device

B Measurand:

IgM antibodies to Toxoplasma gondii

C Type of Test:

Chemiluminescent Immunoassay

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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III Intended Use/Indications for Use:

A Intended Use(s):
See Indications for Use below.

B Indication(s) for Use:
The Access Toxo IgM II assay is a paramagnetic-particle chemiluminescent immunoassay for the qualitative detection of Toxoplasma gondii-specific IgM antibody in adult human serum and plasma using the Access Immunoassay Systems.

The Access Toxo IgM II assay is presumptive for the diagnosis of acute, recent, or reactivated Toxoplasma gondii infection in males and pregnant or non-pregnant females. It is recommended this assay be performed in conjunction with a Toxoplasma gondii-specific IgG antibody assay.

Note: This assay has not been cleared/approved by the FDA for the screening of blood or plasma donors in the United States.

C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only

Performance has not been established for the use of bodily fluids other than human serum or plasma.

D Special Instrument Requirements:
DxI 9000 Access Immunoassay Analyzer

IV Device/System Characteristics:

A Device Description:
The Access Toxo IgM II assay is a paramagnetic-particle chemiluminescent immunoassay for the qualitative detection of Toxoplasma gondii-specific IgM antibody in adult human serum and plasma using the Access Immunoassay Systems.

The Access Toxo IgM II assay consists of the reagent pack, calibrators, and quality controls (QCs), packaged separately. Other items needed to run the assay include substrate and wash buffer.

B Principle of Operation:
The Access Toxo IgM II assay is an immunoenzymatic assay and uses the immunocapture principle. The sample to be tested is added to a reaction vessel with paramagnetic particles coated with human IgM-specific sheep polyclonal antibody as capture antibody. After incubation in a reaction vessel, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then a complex formed with T. gondii antigen and T.

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gondii (P30)-specific monoclonal antibody that has been labeled with alkaline phosphatase is added to the reaction vessel. After a second incubation and a second washing, the chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The photon production is a function of the amount of enzyme conjugate present at the end of the reaction. The light quantity measured for a sample allows a determination of the presence of T. gondii-specific IgM antibody, by comparison with a cut-off value defined during the assay calibration on the instrument. If the light production is equal or greater than the cut-off value, the sample is considered reactive in the Access Toxo IgM II assay.

The cutoff for non-reactivity is 0.8 S/CO and reactivity is 1.00 S/CO. Results between 0.8 – 1.0 S/CO (equivocal zone) should be confirmed by testing a new sample 10 to 20 days later. The Access Toxo IgM II assay results interpretation is presented in Table 1.

Table 1: Access Toxo IgM II Results Interpretation

| Readout in S/CO | Interpretation |
| --- | --- |
| S/CO < 0.8 | Non-Reactive |
| 0.8 ≤ S/CO < 1.0 | Equivocal |
| S/CO ≥ 1.0 | Reactive |

V Substantial Equivalence Information:

A Predicate Device Name(s):

Access Toxo IgM II Assay

B Predicate 510(k) Number(s):

K003259

C Comparison with Predicate(s):

| Device & Predicate Device(s): | K242095 Candidate Device | K003259 Predicate |
| --- | --- | --- |
| Device Trade Name | Same | Access Toxo IgM II |
| General Device Characteristic Similarities | | |
| Intended Use/Indications for Use | Same | The Access Toxo IgM II assay is a paramagnetic-particle chemiluminescent immunoassay for the qualitative detection of Toxoplasma gondii-specific IgM antibody in adult human serum and plasma using the Access Immunoassay Systems.
The Access Toxo IgM II assay is presumptive for the diagnosis of acute, |

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| Device & Predicate Device(s): | K242095 Candidate Device | K003259 Predicate |
| --- | --- | --- |
| | | recent, or reactivated Toxoplasma gondii infection in males and pregnant or non-pregnant females. It is recommended this assay be performed in conjunction with a Toxoplasma gondii-specific IgG antibody assay.
Note: This assay has not been cleared/approved by the FDA for the screening of blood or plasma donors in the United States. |
| Analyte | Same | IgM antibody to T. gondii |
| Technology | Same | 2-step (sandwich) chemiluminescence immunoassay |
| Format | Same | Chemiluminescent |
| Method | Same | Automated |
| Calibration | Same | Utilizes a stored calibration curve |
| Calibration frequency | Same | 28 days |
| Sample Type | Same | Serum and plasma |
| Results Interpretation | S/CO < 0.8 Non-Reactive
0.8 ≤ S.CO < 1.0 Equivocal
S/CO ≥ 1.0 Reactive | S/CO < 1.0 Non-Reactive
0.8 ≤ S.CO < 1.0 Grey Zone
S/CO ≥ 1.0 Reactive |
| Capture Antibody | Same | Anti-human IgM antibody (sheep) |
| Detection Antibody | Same | Inactivated T. gondii Ag - T. gondii (P30)-specific mouse monoclonal antibody conjugated to alkaline phosphatase (bovine) complex |
| Stability | Same | 28 days after opening, 2-10°C |
| | | |
| General Device Characteristic Differences | | |
| Substrate | Lumi-Phos PRO substrate | Access Substrate |
| Instrument | DxI 9000 Access Immunoassay Analyzer | Access Immunoassay System |

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# VI Standards/Guidance Documents Referenced:

The following Clinical and Laboratory Standards Institute (CLSI) guidelines were used:

- CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline
- CLSI EP12-Ed 3: Evaluation of Qualitative Binary Output Examination Performance; Approved Guideline

# VII Performance Characteristics (if/when applicable):

# A Analytical Performance:

# 1. Precision/Reproducibility:

a) Within-Laboratory Precision: A 20-day within-laboratory precision study was conducted using 3 lots of the Access Toxo IgM II reagents, three lots of the Access Toxo IgM II calibrators and 3 DxI 9000 Access Immunoassay Analyzer systems. Four human serum samples were tested in 2 replicates at 2 runs per day over 20 days using 3 reagent lot/calibrator lot combinations, where a unique reagent lot and calibrator lot are paired. The data were analyzed for repeatability (within-run), between-run, between-day, and within-laboratory precision. Within-laboratory precision data summary is shown in Table 2.

Table 2: Access Toxo IgM II Within-Laboratory Precision

| Sample | N | Mean (S/CO) | Within-Run (Repeatability) | | Between-Run | | Between-Day | | Between -Lot and Instrumenta | | Overall Precisionb | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 1 | 240 | 0.14 | 0.004 | 2.8 | 0.005 | 3.6 | 0.003 | 1.9 | 0.006 | 4.7 | 0.009 | 6.8 |
| Sample 2 | 240 | 1.03 | 0.040 | 3.9 | 0.024 | 2.3 | 0.010 | 0.9 | 0.038 | 3.7 | 0.061 | 5.9 |
| Sample 3 | 240 | 5.58 | 0.151 | 2.7 | 0.083 | 1.5 | 0.160 | 2.9 | 0.230 | 4.1 | 0.329 | 5.9 |
| Sample 4 | 240 | 8.76 | 0.207 | 2.4 | 0.169 | 1.9 | 0.213 | 2.4 | 0.368 | 4.2 | 0.502 | 5.7 |

a Access Toxo IgM II reagent lot, Access Toxo IgM II calibrator lot and DxI 9000 instruments are confounded, and the confounding effect is represented by between-lot and instrument.
b Overall within-laboratory variability includes within-run, between-run, between-day, and between-lot variance components.

b) Reproducibility (between-Instrument Precision): An additional precision study was conducted over 5-day by testing four serum samples on 3 DxI 9000 Access Immunoassay Analyzers in an internal site. The samples were tested with 3 lots of Access Toxo IgM II reagents, and 1 lot of Access Toxo IgM II calibrator on each instrument with 5 replicates per run and 1 run per day over 5 days. Between-instrument reproducibility data is shown in Table 3.

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Table 3: Access Toxo IgM II Assay Reproducibility (Between-Instrument Precision)

| Sample | N | Mean (S/CO) | Within-Run (Repeatability) | | Between-Day/Runsa | | Between Instrument | | Between Reagent lot | | Reproducibilityb | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 1 | 225 | 0.14 | 0.004 | 3.2 | 0.005 | 4.0 | 0.004 | 2.8 | 0.005 | 3.5 | 0.009 | 6.8 |
| Sample 2 | 225 | 1.10 | 0.034 | 3.1 | 0.044 | 4.0 | 0.008 | 0.7 | 0.015 | 1.4 | 0.057 | 5.3 |
| Sample 3 | 225 | 4.83 | 0.117 | 2.4 | 0.154 | 3,2 | 0.000 | 0.004 | 0.047 | 1.0 | 0.199 | 4.1 |
| Sample 4 | 225 | 9.26 | 0.210 | 2.3 | 0.316 | 3.4 | 0.081 | 0.9 | 0.170 | 1.8 | 0.410 | 4.6 |

a Days and runs are confounded.
b Reproducibility includes within-run, between-run, between-day, and between-lot variance components.

c) Reproducibility (between-site precision): Refer to K002453 and K031506.

2. Linearity:

Not applicable

3. Analytical Specificity/Interference:

Refer to K002453.

4. Assay Reportable Range:

Not applicable

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

Not applicable

6. Detection Limit:

Not applicable

7. Assay Cut-Off:

Refer to K002453.

8. Carry-Over:

Not applicable

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# B Comparison Studies:

1. Comparison of Access Toxo IgM II assay on the Access 2 Immunoassay Analyzer to the DxI 9000 systems:

A method comparison study was conducted to compare the performance of the Access Toxo IgM II assay on DxI 9000 Access Immunoassay Analyzer to the Access Toxo IgM II assay on the Access 2 Immunoassay System. A total of 152 native serum samples were tested. Positive percent agreement (PPA) and negative percent agreement (NPA) between the DxI 9000 Immunoassay Analyzer and the Access 2 Immunoassay system was calculated for the Access Toxo IgM II assay and shown in Table 4.

Table 4: Performance Agreement of Access Toxo IgM II assay on the Access 2 Immunoassay Analyzer to the DxI 9000 System (n=152)

| Access Toxo IgM II | Access 2 Immunoassay Analyzer | | | | |
| --- | --- | --- | --- | --- | --- |
| | | Reactive | Grey Zone | Non-reactive | Total |
| DxI 9000 System | Reactive | 41 | 0 | 0 | 41 |
| | Equivocal | 0 | 4 | 0 | 4 |
| | Non-Reactive | 0 | 0 | 107 | 107 |
| | Total | 41 | 4 | 107 | 152 |
| Positive Percent Agreement (PPA) | | 100.00% (41/41) | 95% CI^{a} = 91.43% to 100.00% | | |
| Negative Percent Agreement (NPA) | | 100.00% (107/107) | 95% CI^{a} = 96.53% to 100.00% | | |

a95% CI for PPA and NPA were estimated using the Wilson score method.

2. Matrix Comparison:

Refer to K003259.

# C Clinical Studies:

1. Clinical Sensitivity: Not applicable
2. Clinical Specificity: Not applicable

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3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):

For clinical agreement study refer to K002453.

D Clinical Cut-Off:

Not applicable

E Expected Values/Reference Range:

Not applicable

VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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