The Copalis™ TORC Total Antibody Assay uses Coupled Particle Light Scattering (Copalis™) technology in a microparticle agglutinationbased immunoassay for the qualitative detection of total antibodies (IgG and IgM) to Toxoplasma gondii, rubella and cytomegalovirus (CMV) in human serum using the CopalisTM One Immunoassay System. The presence of antibodies is indicative of current or prior infection with the suspected organism. The results of this assay on a single serum specimen are used to determine the patient's immune status for rubella and to determine the patient's immunological experience for Toxoplasma gondii and CMV. When evaluating properly paired sera, the results of this assay are used to demonstrate seroconversion as evidence of recent infection. Both specimens should be tested simultaneously (see Interpretation of Results). This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

Device Description

The Copalis TORC Total Antibody Assay is based on the principle of antibodydependent particle aggregation as detected by measurement of changes in light scattering. Due to the unique measuring system, a sample can be tested for antibodies to Toxoplasma gondii, rubella and CMV using a single reagent and obtain results for the individual antibodies. Sized latex microparticles coated with inactivated Toxoplasma gondii, rubella and CMV antigens aggregate in the presence of antibodies to these infectious agents. After 10 minutes of agitation, the levels of aggregation are determined by discrimination of particle sizes and measurement of the number of reacted and unreacted particles as they flow past a detector. Reactivity is assessed by the level of aggregation per particle size relative to a cutoff value. The Copalis TORC Total Antibody Assay detects the presence of both IgM and IgG antibodies. Two levels of controls are used to monitor proficiency.

AI/ML Overview

Here's an analysis of the acceptance criteria and the study proving device performance, based on the provided text for the Copalis™ TORC Total Antibody Assay:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets in the provided text. However, the "Performance Data" section outlines the evaluated metrics and their results, which implicitly serve as the achieved performance benchmarks.

Metric	Acceptance Criteria (Implicit)	Reported Device Performance
Clinical Sample Testing
Toxoplasma gondii Relative Sensitivity	High sensitivity expected	91.4%
Toxoplasma gondii Relative Specificity	High specificity expected	98.6%
Rubella Relative Sensitivity	High sensitivity expected	98.7%
Rubella Relative Specificity	High specificity expected	100%
CMV Relative Sensitivity	High sensitivity expected	94.4%
CMV Relative Specificity	High specificity expected	100%
POL Proficiency Study
Agreement with "expected" results	100% agreement expected	100%
Reproducibility (Within-run %CV)	Low variability expected	Toxoplasma: 1.0 - 6.7%Rubella: 3.6 - 9.5%CMV: 2.1 - 11.9%
Reproducibility (Total %CV)	Low variability expected	Toxoplasma: 2.3 - 9.0%Rubella: 5.4 - 8.3%CMV: 2.4 - 15.8%

Detailed Study Information:

Sample size used for the test set and the data provenance:
- Clinical Sample Testing: A total of 250 serum samples were tested.
- POL Proficiency Study: A 14-member blinded proficiency panel was used. Each panel member was tested in triplicate (across three runs) by multiple operators.
- Data Provenance: The clinical sample testing was conducted at Sienna Biotech laboratory. The POL Proficiency Study was conducted at 3 POL sites. The text does not specify the country of origin but implies a US context given the FDA submission. Both studies appear to be prospective as they were conducted to evaluate the performance of the new device.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Clinical Sample Testing: The ground truth for this study was established by comparing the Copalis TORC Total Antibody Assay to the corresponding Abbott IMx assays. These predicate devices are established assays, implying their results serve as the reference standard. The text does not specify the number or qualifications of experts involved in running the Abbott IMx assays or in interpreting their results for ground truth determination.
- POL Proficiency Study: The "expected" results for the 14-member blinded proficiency panel were established by in-house testing on a comparator assay. Similar to the clinical sample testing, the text does not detail the number or qualifications of experts involved in establishing these "expected" results.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- The provided text does not describe an explicit adjudication method for resolving discordant results in either the clinical sample testing or the POL proficiency study. The ground truth was primarily established by comparator assays.
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:
- This document describes an immunoassay device, not an AI-powered diagnostic system. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable to this device. The POL study did involve multiple operators (human users) to assess reproducibility and proficiency, but it was not framed as an AI-assist study.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- The Copalis TORC Total Antibody Assay is a laboratory-based immunoassay system, not an algorithm that operates independently. Its performance data (sensitivity, specificity, reproducibility) are inherently "standalone" in the sense that they represent the device's analytical performance on samples, rather than human interpretation of device output. The "human-in-the-loop" aspect comes from laboratory personnel operating the system, not interpreting images or complex data in a way that AI would assist.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for both the clinical sample testing and the POL proficiency study was established by results from comparator assays (Abbott IMx assays for clinical, and an unspecified "comparator assay" for the POL study's "expected" results). This falls under the category of reference standard testing using established diagnostic methods.
The sample size for the training set:
- The provided document does not mention a training set. This is expected as the Copalis TORC Total Antibody Assay is an immunoassay, not a machine learning model that requires explicit training data. Its development would involve chemical and biological optimization, not algorithmic training.
How the ground truth for the training set was established:
- Since there is no mention of a training set or machine learning components, the concept of establishing ground truth for a training set is not applicable to this device.

Summary

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

Image /page/0/Picture/0 description: The image shows a handwritten sequence of characters, which appears to be a combination of letters and numbers. The sequence reads 'K970931'. The characters are written in a bold, somewhat stylized font, with thick strokes that give them a distinct and easily readable appearance. The overall impression is that of a code or identifier, possibly a serial number or reference code.

March 6, 1997

SUMMARY OF SAFETY AND EFFECTIVENESS

SUBMITTED BY:

Judith J. Smith Sienna Biotech, Inc. 9115 Guilford Rd. Suite 180 Columbia, MD 21046

NAME OF DEVICES:

Trade Name:

Common Names/Descriptions:

Copalis TORC Total Antibody Assay

APR 2 4 1997

Immunoassay for the Detection of Total Antibodies to Toxoplasma gondii, Rubella and Cytomegalovirus

Classification Names:

Toxoplasma gondii serological reagents; Rubella virus serological reagents; Cytomegalovirus serological reagents

PREDICATE DEVICES:

Abbott IMx Toxo IgG 2.0, Rubella IgG 2.0, CMV IgG

DEVICE DESCRIPTION:

INTENDED USE: The Copalis™ TORC Total Antibody Assay uses Coupled Particle Light Scattering (Copalis™) technology in a microparticle agglutinationbased immunoassay for the qualitative detection of total antibodies (IgG and IgM) to Toxoplasma gondii, rubella and cytomegalovirus (CMV) in human serum using the CopalisTM One Immunoassay System. The presence of antibodies is indicative of current or prior infection with the suspected organism. The results of this assay on a single serum specimen are used to determine the patient's immune status for rubella and to determine the patient's immunological experience for Toxoplasma gondii and CMV. When evaluating properly paired sera, the results of this assay are used to demonstrate seroconversion as evidence of recent infection. Both specimens should be tested simultaneously (see Interpretation of Results). This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

KIT DESCRIPTION: Coupled Particle Light Scattering (Copalis) technology provides a rapid method for the measurement of antibodies to specific viral or protozoal pathogens.

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

SUMMARY OF SAFETY AND EFFECTIVENESS (cont.)

PERFORMANCE DATA:

Clinical Sample Testing: Clinical sample testing was conducted at Sienna Biotech laboratory to evaluate the performance of the Copalis TORC Total Antibody Assay (TORC) compared to the corresponding Abbott IMx assays.

A total of 250 serum samples were tested. In initial testing, relative sensitivity of the Toxoplasma gondii antibody component of the assay was 91.4%; relative specificity was 98.6%. Relative sensitivity of the rubella antibody component of the assay was 98.7%; relative specificity was 100%. Relative sensitivity of the CMV antibody component of the assay was 94.4%; relative specificity was 100%.

Physician Office Laboratory (POL) Proficiency Study:

A study was conducted at 3 POL sites to evaluate the proficiency and reproducibility of different operators with the Copalis TORC Total Antibody Assay (TORC). The 3 sites represented POLs ranging from small to large group practices; 4 operators participated in the study, representing high school to 4-year educational levels.

A 14-member blinded proficiency panel was tested by each operator in each of three runs. Proficiency among operators was determined by comparison of Copalis TORC assay results for each panel member with the "expected" results as established by in-house testing on a comparator assay. The study showed 100% agreement between Copalis results from all operators and expected results.

Reproducibility was determined based on the 7 samples run in duplicate within each run. Within-run and total percent coefficient of variation (%CV) were calculated among operators for each sample. See the following table for a summary of %CV ranges.

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

SUMMARY OF SAFETY AND EFFECTIVENESS (cont.)

SAMPLE	RANGE	TOXO	RUBELLA	CMV
#1	CTR	131	190	215
	WITHIN-RUN %CV	5.9	6.0	11.9
	TOTAL %CV	7.7	8.2	13.9
#2	CTR	151	189	100
	WITHIN-RUN %CV	6.7	7.9	2.4
	TOTAL %CV	9.0	7.6	2.4
#3	CTR	134	188	127
	WITHIN-RUN %CV	6.6	9.5	6.5
	TOTAL %CV	8.0	8.3	6.0
#4	CTR	101	201	223
	WITHIN-RUN %CV	1.5	6.0	6.3
	TOTAL %CV	2.3	7.4	13.2
#5	CTR	101	150	101
	WITHIN-RUN %CV	1.7	5.2	2.1
	TOTAL %CV	2.3	5.4	2.8
#6	CTR	100	133	250
	WITHIN-RUN %CV	1.6	4.1	8.2
	TOTAL %CV	2.4	6.7	15.8
#7	CTR	101	141	140
	WITHIN-RUN %CV	1.0	3.6	2.2
	TOTAL %CV	2.5	7.0	7.5

Physician Office Laboratory Reproducibility;
Total Precision - All Sites, All Operators

Regulation Number and Section

§ 866.3510 Rubella virus serological reagents.

(a)
Identification. Rubella virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to rubella virus in serum. The identification aids in the diagnosis of rubella (German measles) or confirmation of a person's immune status from past infections or immunizations and provides epidemiological information on German measles. Newborns infected in the uterus with rubella virus may be born with multiple congenital defects (rubella syndrome).(b)
Classification. Class II. The special controls for this device are:(1) National Committee for Clinical Laboratory Standards':
(i) 1/LA6 “Detection and Quantitation of Rubella IgG Antibody: Evaluation and Performance Criteria for Multiple Component Test Products, Speciment Handling, and Use of the Test Products in the Clinical Laboratory, October 1997,”
(ii) 1/LA18 “Specifications for Immunological Testing for Infectious Diseases, December 1994,”
(iii) D13 “Agglutination Characteristics, Methodology, Limitations, and Clinical Validation, October 1993,”
(iv) EP5 “Evaluation of Precision Performance of Clinical Chemistry Devices, February 1999,” and
(v) EP10 “Preliminary Evaluation of the Linearity of Quantitive Clinical Laboratory Methods, May 1998,”
(2) Centers for Disease Control's:
(i) Low Titer Rubella Standard,
(ii) Reference Panel of Well Characterized Rubella Sera, and
(3) World Health Organization's International Rubella Standard.