Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description details a standard ELISA assay based on antigen-antibody binding and enzymatic color development, with no mention of AI or ML components.

Therapeutic

No.
The device is intended for the qualitative detection of Measles IgM antibodies to aid in the diagnosis of a current or recent measles infection, not for treatment.

Diagnostic

Yes

Explanation: The device is intended for use "as an aid in the diagnosis of a current or recent measles (rubeola) infection," which directly indicates its role as a diagnostic tool.

SaMD (Software as a Medical Device)

No

The device description clearly outlines a physical ELISA kit with reagents, solid phases, and a requirement for a spectrophotometer or ELISA microwell plate reader, indicating it is a hardware-based diagnostic test, not software only.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states it's for the "qualitative detection of Measles IgM antibodies in human serum of patients suspected of measles (rubeola) infection." This involves testing a sample taken from the human body (serum) in vitro (outside the body) to provide information about a medical condition (measles infection).
Device Description: The description details an "Enzyme-Linked Immunosorbent Assay (ELISA)," which is a common laboratory technique performed in vitro to detect the presence of specific substances in a sample.
Performance Studies: The performance studies involve testing human serum samples using the device and comparing the results to other laboratory methods. This is characteristic of evaluating the performance of an IVD.
Predicate Device: The mention of a "Predicate Device" (K904083; Gull Rubeola IgM ELISA kit) is a strong indicator that this device is being submitted for regulatory review as an IVD, as predicate devices are used to demonstrate substantial equivalence for new IVDs.

All these elements align with the definition and characteristics of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Trinity Biotech Captia™ Measles IgM Enzyme-Linked Immunosorbent Assay (ELISA) is intended for the qualitative detection of Measles IgM antibodies in human serum of patients suspected of measles (rubeola) infection. This assay is intended for use as an aid in the diagnosis of a current or recent measles (rubeola) infection in conjunction with other clinical information and laboratory findings.

Performance characteristics have not been evaluated in immunocompromised or immunosuppressed individuals. This test is not intended for use in neonatal screening or for use at a point of care. This test is not intended for use in screening blood and plasma donors.

Product codes (comma separated list FDA assigned to the subject device)

PCL

Device Description

The Trinity Biotech Captia™ Measles IgM test is an Enzyme-Linked Immunosorbent Assays (ELISA). When measles antigen (Edmonston strain) is bound to the solid phase and brought into contact with a patient's serum, antigen specific antibody, if present, will bind to the antigen on the solid phase forming antibody complexes. Excess antibody is removed by washing. This is followed by the addition of goat anti-human IgM globulin conjugated with horseradish peroxidase which will bind to the antibody-antigen complexes. The excess conjugate is removed by washing, followed by the addition of Chromogen/Substrate tetramethylbenzidine (TMB). If specific antibody to the antigen is present in the patient's serum, a blue color develops. When the enzymatic reaction is stopped with 1N H2SO4. The contents of the wells turn yellow. The color, which is indicative of the concentration of antibody in the serum, can be read on a suitable spectrophotometer or ELISA microwell plate reader.

Each kit contains the following components in sufficient quantities to perform the number of tests indicated on the package label.

1. Purified measles antigen coated microassay plate: 96 wells, configured in twelve 1x8 strips stored in a foil pouch with desiccant. (96T: one plate)
1. Calibrator: Human serum or defibrinated plasma. Sodium azide (= 500 mg/dL) and bilirubin (unconjugated) (>= 20 mg/dL). No adverse results or significant change in results occurred.
Interference with red cells, cholesterol, gamma globulin, triglycerides, beta carotene, protein, ascorbic acid, and anticoagulants has not been tested.

Assay Cut-off Determination:

228 Measles IgM negative sera were assayed.
Cut-off determined by Mean + 4 Standard Deviations of optical density readings (0.105 + 4(0.070) = 0.385).
Immune Status Ratio (ISR) values: = 1.10 are positive, 0.91 to 1.09 are equivocal.

Seroconversion Study:

BIOMEX Rubeola IgG and IgM Antibody Seroconversion Panel (SCP-MEA-001) with 15 samples from one individual over 55 days was used.
Tested on four (4) different lots of the device.
Demonstrated IgM response consistent with seroconversion.
Seroconversion was demonstrated at Day 20 on the Captia™ Measles IgM ELISA.
Remained positive until Day 22 for Captia™ Measles IgM ELISA.
Comparator 1 showed seroconversion at Day 22 and was positive only at that bleed date.
Comparator 2 showed seroconversion earlier (Day 13) and remained positive for the remainder of the timeframe.

Clinical Studies (Studies 1 and 2):

Sample Size: 188 samples from individuals suspected of measles infection in outbreak settings (Texas Department of Health, North Carolina State Laboratory of Public Health).
All samples tested on the Captia™ Measles IgM ELISA.
All but one sample tested by a comparator algorithm (including comparator Measles IgM ELISA, IFA, Complement Fixation (CF), Hemagglutination Inhibition (HI), and Captia™ Measles ELISA IgG test kit).
When considering indeterminate results from the comparator algorithm:
- % Positive Agreement: 88/97 = 90.7% (95% CI: 83.3-95.0%)
- % Negative Agreement: 70/87 = 80.5% (95% CI: 70.9-87.4%)
Percent of Captia™ Measles IgM Results that are Equivocal = 8.6% (16 of 187).

Clinical Study (Study 3):

Sample Size: 8 samples from Kansas Department of Health and Environment Laboratory.
All samples tested on Captia™ Measles IgM and Captia™ Measles IgG ELISA test kits, and compared to the institution's comparator algorithm (RNA polymerase chain reaction (PCR) on urine, nasopharyngeal swab (NPS), and/or throat swab (TS)).
When considering indeterminate results from the comparator algorithm:
- % Positive Agreement: 3/4 = 75.00% (95% CI: 30.1-95.4%)
- % Negative Agreement: 4/4 = 100.00% (95% CI: 39.8-100.0%)
One sample tested NPS negative at two sites, urine positive at one site, and urine indeterminate at one site by PCR.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Clinical Sensitivity: Not Applicable
Clinical Specificity: Not Applicable
% Positive Agreement (Clinical Studies 1 & 2): 90.7% (95% CI: 83.3-95.0%)
% Negative Agreement (Clinical Studies 1 & 2): 80.5% (95% CI: 70.9-87.4%)
% Positive Agreement (Clinical Study 3): 75.00% (95% CI: 30.1-95.4%)
% Negative Agreement (Clinical Study 3): 100.00% (95% CI: 39.8-100.0%)
Percent of Captia™ Measles IgM Results that are Equivocal (Studies 1 & 2 combined): 8.6% (16 of 187)

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K904083

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.3520 Rubeola (measles) virus serological reagents.

(a)
Identification. Rubeola (measles) virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to rubeola virus in serum. The identification aids in the diagnosis of measles and provides epidemiological information on the disease. Measles is an acute, highly infectious disease of the respiratory and reticuloendothelial tissues, particularly in children, characterized by a confluent and blotchy rash.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.

Summary

0

Trinity Biotech Captia™ Measles IgM 510(k) Summary

Trinity Biotech hereby submits this 510(k) summary for the Captia™ Measles IgM Test in accordance with the requirements of 21CFR 807.92(C)

| Submitter's

ldentification:
Name &	Trinity Biotech
Address	2823 Girts Road
		Jamestown, NY 14701, USA
Contact:		Bonnie B. DeJoy, Corporate Vice President of Regulatory Affairs
		Email: bonnie.dejoy@trinityusa.com
	Phone:	716-483-3851 x 1030
	Fax:	716-488-1990

A. 510(k) Number:

K140455

B. Purpose for Submission:

Traditional 510(k) in accordance with the requirements of 21CFR 807.92(C)

C. Measurand:

Measles-specific IgM antibodies in human serum

D. Type of Test:

Enzyme-Linked Immunosorbent Assay (ELISA)

E. Applicant:

Trinity Biotech

F. Proprietary and Established Names:

Captia™ Measles IgM

G. Regulatory Information:

1. Regulation section:

21 CFR 866.3520 Rubeola (measles) virus serological reagents

1

1. Classification:
  Class I
1. Product code:
  PCL
1. Panel:
  83 (Microbiology)

H. Intended Use:

l. Intended use(s):
The Trinity Biotech Captia™ Measles IgM Enzyme-Linked Immunosorbent Assay (ELISA) is intended for the qualitative detection of Measles IgM antibodies in human serum of patients suspected of measles (rubeola) infection. This assay is intended for use as an aid in the diagnosis of a current or recent measles (rubeola) infection in conjunction with other clinical information and laboratory findings.

Performance characteristics have not been evaluated in immunocompromised or immunosuppressed individuals. This test is not intended for use in neonatal screening or for use at a point of care. This test is not intended for use in screening blood and plasma donors.

1. Indication(s) for use:
  Same as Intended Use
1. Special conditions for use statement(s):
  For prescription use only
1. Special instrument requirements:
  Not applicable

I. Device Description: .

The Trinity Biotech Captia™ Measles IgM test is an Enzyme-Linked Immunosorbent Assays (ELISA). When measles antigen (Edmonston strain) is bound to the solid phase and brought into contact with a patient's serum, antigen specific antibody, if present, will bind to the antigen on the solid phase forming antibody complexes. Excess antibody is removed by washing. This is followed by the addition of goat anti-human IgM globulin conjugated with horseradish peroxidase which will bind to the antibody-antigen

2

complexes. The excess conjugate is removed by washing, followed by the addition of Chromogen/Substrate tetramethylbenzidine (TMB). If specific antibody to the antigen is present in the patient's serum, a blue color develops. When the enzymatic reaction is stopped with 1N H2SQ2. The contents of the wells turn yellow. The color, which is indicative of the concentration of antibody in the serum, can be read on a suitable spectrophotometer or ELISA microwell plate reader.

Each kit contains the following components in sufficient quantities to perform the number of tests indicated on the package label.

1. Purified measles antigen coated microassay plate: 96 wells, configured in twelve 1x8 strips stored in a foil pouch with desiccant. (96T: one plate)
1. Calibrator: Human serum or defibrinated plasma. Sodium azide ( 1380 mg/dL. The highest titer of RF+ tested (1: 1280; 500 IU/mL) did not adversely affect the performance of the assay.

5

Precision/Reproducibility: C.

The Trinity Biotech Captia™ Measles IgM ELISA Test Kit was evaluated for interassay precision. This study consisted of six (6) blinded proficiency panel members, varying in reactivity: Four (4) low to moderate Positive samples and two (2) Negative samples run in triplicate at three (3) separate facilities. Testing at each site was done over 10 days by two (2) operators at each site resulting in a total number of 180 data points. The results are summarized below:

| Sample
ID | ISR
Site 1
N=60 | ISR
Site 2
N=60 | ISR
Site 3
N=60 | MEAN | STD
DEV | % CV |
|--------------|-----------------------|-----------------------|-----------------------|------|------------|-------|
| 1 | 1.30 | 1.34 | 1.23 | 1.29 | 0.055678 | 4.3% |
| 2 | 0.57 | 0.68 | 0.67 | 0.64 | 0.060828 | 9.5% |
| 3 | 1.16 | 1.26 | 1.07 | 1.16 | 0.095044 | 8.2% |
| 4 | 1.92 | 1.84 | 1.76 | 1.84 | 0.08000 | 4.3% |
| 5 | 0.67 | 0.82 | 0.84 | 0.78 | 0.092916 | 12.0% |
| 6 | 1.28 | 1.18 | 1.01 | 1.16 | 0.136504 | 11.8% |

Precision Between All Sites.

The Trinity Biotech Captia™ Measles IgM ELISA Test Kit was evaluated for lot to lot precision. This study consisted of six (6) blinded proficiency panel members, varying in reactivity: four (4) low to Moderate Positive samples and two (2) Negative samples run in triplicate on three (3) separately manufactured kit lots. The results are summarized below:

| Sample
ID | ISR's
Lot 1 | ISR's
Lot 2 | ISR's
Lot 3 | Mean | Std Dev | % CV |
|--------------|----------------|----------------|----------------|------|----------|-------|
| 1 | 1.22 | 1.43 | 1.36 | 1.34 | 0.120773 | 9.02 |
| 2 | 0.57 | 0.42 | 0.46 | 0.48 | 0.108972 | 22.55 |
| 3 | 1.19 | 1.31 | 1.24 | 1.25 | 0.103253 | 8.27 |
| 4 | 2.13 | 1.96 | 1.56 | 1.88 | 0.27924 | 14.83 |
| 5 | 0.79 | 0.75 | 0.56 | 0.7 | 0.109545 | 15.72 |
| 6 | 1.27 | 1.32 | 1.3 | 1.29 | 0.041265 | 3.19 |

Inter-lot Reproducibility

A separate precision/reproducibility study was performed internally (Trinity Biotech, Jamestown) using one (1) lot of the Captia™ Measles IgM ELISA Test Kit. The study compared the consistency between two (2) Operators. This study consisted of six (6) blinded proficiency panel members, varying in reactivity: Four (4) Low to

6

moderate Positive samples, and two (2) Negative samples run by each of the Operators over 10 days. The results are summarized below:

| Sample
ID | ISR's
Operator
1 N=30 | ISR's
Operator
2 N=30 | MEAN
ISR | STD
DEV | % CV |
|--------------|-----------------------------|-----------------------------|-------------|------------|-------|
| 1 | 1.26 | 1.33 | 1.3 | 0.0495 | 3.80% |
| 2 | 0.58 | 0.55 | 0.57 | 0.02121 | 3.80% |
| 3 | 1.14 | 1.17 | 1.16 | 0.02121 | 1.80% |
| 4 | 1.92 | 1.91 | 1.92 | 0.00707 | 0.40% |
| 5 | 0.69 | 0.65 | 0.67 | 0.02828 | 4.20% |
| 6 | 1.32 | 1.23 | 1.28 | 0.06364 | 5.00% |

Intra-run Precision/Reproducibility Between users: Total Precision at Site 1 with Two Operators Over Ten Days

d. Linearity/assay reportable range:

Not Applicable

Traceability, Stability, Expected values (controls, calibrators, or methods): ૯.
Traceability - The Controls and Calibrators are traceable against frozen internal Quality Control standard panels consist of patient samples whose values span the assay range.

Stability - Real time stability studies support the shelf life of the Reagents. Controls and Calibrators at 2 - 8° C up to the stated expiration date on the labeling.

Expected Values - The ISR (Immune Status Ratio) Values for the Positive and Negative Controls should be in their respective ranges printed on the vial labels. If the Control values are not within their respective ranges, the test should be considered invalid and should be repeated.

f. Detection limit:
Not Applicable
g. Analytical specificity:
Cross Reactivity

47 samples were used for establishing the potential cross reactivity of the Trinity Biotech Captia™ Measles IgM ELISA Test Kit. The samples were selected as confirmed positive by Trinity Biotech Captia™ CMV IgM, HSV1 IgM, HSV2 IgM, Rubella IgM, VZV IgM and

7

Mumps IgM test kits, for each of the following potentially cross-reacting agents. CMV, HSV-1. HSV-2. Rubella. VZV. Mumps and Parvo-B19. Fourteen (14) of the suspected cross reactive samples tested as measles IgM antibody tested positive or equivocal (12 positive and 2 equivocal) with the Trinity Biotech Captia™ Measles IgM ELISA test kit. These 14 samples were then run on a comparator Measles IgM IFA test kit and a comparator Measles IgM ELISA test kit. A sample was determined as measles IgM antibody positive if the results on two (2) measles IgM tests were positive. A sample was determined as measles IgM antibody negative if the results on two (2) measles IgM tests were negative. The results are presented in the table below:

| Cross
Reacting
Agents | Number
of
Samples | Trinity Biotech Captia™
Measles IgM
Result | | | Consensus Comparator
Result* | |
|-----------------------------|-------------------------|--------------------------------------------------|-----|-------|---------------------------------|-----|
| | | Neg | Pos | Equiv | Neg | Pos |
| Mumps IgM | 4 | 4 | 0 | 0 | NT | NT |
| VZV IgM | 4 | 4 | 0 | 0 | NT | NT |
| Rubella IgM | 4 | 4 | 0 | 0 | NT | NT |
| CMV IgM | 7 | 3 | 3 | 1 | 3 | 1 |
| HSV1 IgM | 16 | 9 | 7 | 0 | 5 | 2 |
| HSV 2 IgM | 10 | 7 | 2 | 1 | 2 | 1 |

NT = Not tested

Tested only if Captia™ Measles IgM result was positive.

Potential cross reactivity was observed with CMV IgM, HSV1 and HSV2 IgM. Potential cross-reactivity with Parvovirus, Respiratory Syncytial Virus (RSV) and parainfluenza has not been ruled out, as either specimens were not tested or a limited number were tested.

Interfering Substances

Interfering substance testing was conducted using three (3) characterized samples for measles IgM, spiked with recommended interfering substances according to the quidance in the CLSI document EP7-A2 (Interference Testing in Clinical Chemistry: Approved Guideline 2nd Ed). Results from the three (3) samples tested as spiked with the interfering substance and unspiked (as a control) were favourable. No adverse results or significant change in results occurred with these samples tested with the following:

Potential Interferent	Concentration
Hemoglobin	$\ge$ 500 mg/dL
Bilirubin (unconjugated)	$\ge$ 20 mg/dL

Interference with substances such as red cells, cholesterol, gamma globulin, triglycerides, beta carotene, protein, ascorbic acid and anticoagulants have not been tested.

8

h. Assay cut-off:

The obiective of this study was to demonstrate the performance of the Trinity Biotech Captia™ Measles IgM ELISA Test Kit; specifically to generate data to demonstrate determination of the cut-off. The results are summarized below:

228 Measles IgM negative sera were assayed on the Trinity Biotech Captia™ Measles IgM ELISA Test Kit. Four (4) samples were disqualified as they were in the equivocal range on Trinity IgM ELISA or indeterminate on a comparator Measles IFA test kit (due to non-specific staining most likely due presences of ANA antibodies). The mean and standard deviation of the optical density readings for the sera were 0.105 and 0.070 respectively. The positive threshold for the assay was determined by adding the mean and 4 standard deviations (0.105 + 4(0.070) = 0.385). Positive sera were titrated to give a constant ratio of the threshold value to obtain a Cut-off Calibrator serum. On all subsequent assays, this serum was run and the assay was calibrated by multiplying the OD value for the calibrator by the ratio to the cut-off calibrator value. This value was then divided into the O.D. for the patient sera to obtain an Immune Status Ratio (ISR). By definition the Cut-off ISR is equal to 1.00. To account for inherent variation in immunoassay, values of 0.91 to 1.09 were considered equivocal. Therefore ≤ 0.90 are considered negative and values ≥ 1.10 are considered positive. values

i. Seroconversion study:

The BIOMEX Rubeola IgG and IgM Antibody Seroconversion Panel (Cat No. SCP-MEA-001) contained 15 samples depicting the onset and decline of IgG and IgM antibodies to Rubeloa (Measles) from one individual over a period of 55 days. The 15 member panel demonstrated an IgM response consistent with an antibody response for seroconversion when tested on four (4) different lots of the Trinity Biotech Captia™ Measles IgM ELISA Test Kit.

The seroconversion panel consisted of one patient with 15 draws during an approximately two month period from May 315 to July 250", 1994. Seroconversion was demonstrated at Day 20 on the Trinity Biotech Captia™ Measles IgM ELISA Test Kit. and remained positive until Day 22Comparator 1 demonstrated seroconversion at Dav 22 and was positive only at that bleed date. Comparator 2 sero-conversion happened earlier than the Trinity kit by 2 days and remained positive for the remainder of timeframe. The results are summarized below:

9

						Comparator		Comparator
Trinity Biotech Captia™ Measles IgM ELISA						1		2
Lot		Lot	Lot
Lot 027		28	29	Lot 030		Rubeola IgM		Rubeola IgM
Bleed
Day	ISR	Result	ISR	Result	ISR	Result	ISR	Result	S/CO	Result	S/CO	Result
Day1	0.22	Neg	0.29	Neg	0.2	Neg	0.12	Neg	NT	NT	0.429	Neg
Day 6	0.29	Neg	0.33	Neg	0.24	Neg	0.15	Neg	0.02	Neg	0.449	Neg
Day 8	0.25	Neg	0.31	Neg	0.21	Neg	0.14	Neg	-0.04	Neg	0.389	Neg
Day 13	0.26	Neg	0.34	Neg	0.27	Neg	0.21	Neg	0.28	Neg	1.101	Pos
Day 15	0.44	Neg	0.51	Neg	0.54	Neg	0.43	Neg	0.46	Neg	3.045	Pos
Day 20	1.53	Pos	1.71	Pos	1.77	Pos	1.28	Pos	0.92	Neg	7.332	Pos
Day 22	1.36	Pos	1.4	Pos	1.49	Pos	1.24	Pos	1.09	Pos	5.919	Pos
Day 27	0.84	Neg	0.92	equiv	0.96	equiv	0.71	Neg	0.5	Neg	3.785	Pos
Day 29	0.59	Neg	0.8	Neg	0.89	Neg	0.54	Neg	0.33	Neg	3.296	Pos
Day 35	0.54	Neg	0.63	Neg	0.62	Neg	0.47	Neg	0.61	Neg	2.449	Pos
Day 37	0.44	Neg	0.53	Neg	0.53	Neg	0.79	Neg	0.24	Neg	2.113	Pos
Day 43	0.44	Neg	0.6	Neg	0.54	Neg	0.38	Neg	0.17	Neg	2.04	Pos
Day 45	0.37	Neg	0.5	Neg	0.5	Neg	0.31	Neg	0.15	Neg	1.802	Pos
Day 49	0.34	Neg	0.59	Neg	0.39	Neg	0.28	Neg	0.04	Neg	1.471	Pos
Day 54	0.38	Neg	0.5	Neg	0.42	Neg	0.29	Neg	0.27	Neg	1.47	Pos

j. Specificity in a Normal Population

A total of 200 random serum samples were tested to establish the expected values in a population of individuals between the ages 18-65 with no known clinically apparent Measles infection. The table below summarizes the distribution of Trinity Biotech Measles IgM assay ISR Values observed for the population.

Distribution of Trinity Biotech Captia™ Measles IgM Assay ISR Values from a Normal Population

| Measles IgM
ISR Range | Number of
Specimens
(Frequency) | Percent of
Total |
|--------------------------|---------------------------------------|---------------------|
| 0.00-0.20 | 65 | 32.5% |
| 0.21-0.40 | 91 | 45.5% |
| 0.41-0.60 | 29 | 14.5% |
| 0.61-0.80 | 8 | 4.0% |
| 0.81-0.90 | 4 | 2.0% |
| 0.91-1.10 | 1 | 0.5% |
| 1.11-1.20 | 0 | 0.0% |
| 1.21-1.40 | 1 | 0.5% |
| >2.00 | 1 | 0.5% |

1 0

10

Image /page/10/Figure/0 description: This bar graph shows the specificity in a normal population of 200 people. The x-axis shows the ISR values, and the y-axis shows the frequency. The bar graph shows that the highest frequency is in the 0.21-0.40 range, with a frequency of approximately 90. The 0.00-0.20 range has a frequency of approximately 65.

Comparison studies: 2.

a. Method comparison with predicate device:
See Clinical Studies.
b. Matrix comparison:
Not Applicable. The kit is for use with Human Serum only.
1. Clinical studies:
- a. Clinical Sensitivity:

Not Applicable

b. Clinical specificity:
Not Applicable
c. Other clinical supportive data (when a. and b. are not applicable):
Three (3) studies were conducted to evaluate the performance of the Trinity Biotech Captia™ Measles IgM ELISA test kit.

11

Studies 1 and 2

188 samples were collected from individuals in whom a measles IgM test was ordered (suspected of measles infection in outbreak settings by the Texas Department of Health, Austin, Texas (66 samples) and the State Laboratory of Public Health in Raleigh, North Carolina (122 samples)). All serum samples were tested on the Trinity Biotech Captia™ Measles IgM ELISA test kit. All but one (1) sample was tested by a comparator testing algorithm used at each institution to determine the presence of current or recent measles infection, referred to as "comparator algorithm" in the performance tables. The algorithms used consisted of the results of other laboratory confirmation methods including comparator Measles IgM ELISA test kit, a comparator Measles IgM IFA test kit, Complement Fixation (CF), Hemagglutionation Inhibition (HI) and the Trinity Biotech Captia™ Measles ELISA IgG test kit. See Table below for results.

Comparator Algorithm

	+	Indeterminate
+	88		6
Equivocal	ನಿ	ನ	10
	ನ		70

# Agree	Total	Result	95% CI
88	તેર્ભ	91.67%	84.2-96.3
70	86	81.40%	71.6-89.0

Percent of Captia M Measles IgM Results that are Equivocal = 8.6% (16 of 187)

Performance with the indeterminate results from the comparator algorithm calculated against the performance of the Captia™ Measles IgM:

Comparator Algorithm

	+	Indeterminate	-
+	88	1	6
Trinity Biotech
Captia™ Measles IgM	Equivocal	3	3	10
-	5	1	70
	# Agree	Total	Result	95% CI
% Positive Agreement	88	97	90.7%	83.3-95.0%
% Negative Agreement	70	87	80.5%	70.9-87.4%

Percent of Captia 100 Measles IgM Results that are Equivocal = 8.6% (16 of 187)

12

Study 3

Eight (8) samples were submitted for testing at the Kansas Department of Health and Environment Laboratory (KDHE), Topeka, Kansas. All samples were tested on the Captia™ Measles IgM and Captia™ Measles IgG ELISA test kits as well ascompared to the method used by the testing institution to determine the presence of current or recent measles infection, referred to as "comparator algorithm" in the performance table. The comparator algorithm included RNA polymerase chain reaction (PCR) on urine, nasopharyngeal swab (NPS) and/or throat swab (TS) samples. The final % agreement is presented in the table below:

		Comparator Algorithm
		+	Indeterminate	-
Trinity Biotech CaptiaTM
Measles IgM	+	3	0	0
	Equivocal	0	0	0
	-	0	1*	4
	# Agree	Total	Result	95% CI
% Positive Agreement	3	3	100.00%	29.2-100.0%
% Negative Agreement	4	4	100.00%	39.8-100.0%

This sample tested NPS negative at two sites, urine positive at one site and urine . indeterminate at one site (all testing done by PCR).

Performance with the indeterminate results from the comparator algorithm calculated against the performance of the Captia™ Measles IgM:

	Comparator Algorithm
	+	Indeterminate	-
Trinity Biotech Captia™
Measles IgM	+	3	0	0
	Equivocal	0	0	0
	-	0	1*	4
	# Agree	Total	Result	95% CI
% Positive Agreement	3	4	75.00%	30.1-95.4%
% Negative Agreement	4	4	100.00%	39.8-100.0%

1. Clinical cut-off:
  Refer to Assay Cut-off above.

13

5. Expected values/Reference range:

IgM antibodies appear in the first week of infection and usually peak within a month. Although uncommon, low levels of IgM may persist for one (1) year or longer. The annual incidence rates are reported to vary in different geographical areas.

Recent reports (2004-2011) from the Centers for Disease Control and Prevention (CDC) indicate that annual measles incidence is