(567 days)
ORTHO T. cruzi ELISA Test System is an enzyme-linked immunosorbent assay for the in vitro qualitative detection of antibodies (Immunoglobulin G) to Trypanosoma cruzi (T. cruzi) in human adult serum (glass, plastic, or serum separator tubes) and plasma (EDTA, lithium heparin or citrate) using whole-cell lysate antigens. Reactive assay results are presumptive evidence of past infection, and in conjunction with other serological and clinical information, may be used for the laboratory diagnosis of individuals with Chagas' disease.
Definitive diagnosis of an acute phase of infection (including acute congenital infection) must be made by alternate methods, e.g., hemoculture, blood smear.
This test is not intended for use on samples of cord blood or screening blood or plasma donors.
The ORTHO T. cruzi ELISA Test System is an enzyme-linked immunosorbent assay (ELISA). ELISA technology utilizes the principle that antibodies bound to the solid phase can be detected by complementary antibodies or antigens labeled with an enzyme capable of acting on a chromogenic substrate. When substrate is applied, the presence of antigens or antibodies can be detected by development of a colored end product. The optical densities are read spectrophotometrically.
This ELISA was developed to detect human antibodies to T. cruzi in serum and plasma. The assay utilizes microwells coated with a whole-cell lysate containing T. cruzi antigens as the solid phase. The assay procedure is a three-stage test carried out in a microwell coated with lysate (antigens) prepared from T. cruzi. In the first stage, test specimen, Negative Control, and Positive Calibrator are diluted directly in the test well containing Specimen Diluent, and incubated for a specified length of time. If antibodies to T. cruzi are present, antigen-antibody complexes will form on the microwell surface. If antibodies to T. cruzi are absent, complexes will not form. Unbound antibodies in the sample will be removed during the subsequent wash step.
In the second stage, murine monoclonal antibody conjugated with Horseradish Peroxidase (Conjugate) is added to the test well. The Conjugate binds specifically to the antibody portion of the antigen-antibody complex. If complexes are not present, the unbound Conjugate is removed by the subsequent wash step.
In the third stage, an enzyme detection system composed of o-phenylenediamine (OPD) and hydrogen peroxide is added to the test well. If bound Conjugate is present, the OPD with be oxidized, resulting in a colored end product. Sulfuric acid is then added to stop the reaction. The color intensity depends on the amount of bound Conjugate and, therefore, is a function of the concentration of antibodies to T. cruzi present in the specimen. The intensity of color in the substrate solution is then determined with a microwell reader (spectrophotometer) designed to measure light absorbance in a microwell.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Device: ORTHO® T. cruzi ELISA Test System
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a separate section with specific numerical thresholds for performance metrics. However, the performance study data implicitly demonstrates the device's acceptable performance by showing strong agreement with established methods and probable T. cruzi antibody status. The key performance metrics are Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA).
Given the context of a 510(k) submission, the implicit acceptance criteria would be for the device to perform comparably to, or demonstrate a high level of agreement with, the established comparator methods and the "most probable T. cruzi antibody status."
| Metric | Implicit Acceptance Criteria (based on predicate/comparator performance expectations) | Reported Device Performance (vs. Most Probable T. cruzi Antibody Status) |
|---|---|---|
| Positive Percent Agreement (PPA) | High agreement (e.g., >90%) with probable positive cases | 98.92% (92/93) (Overall) (95% CI: 94.15% - 99.97%) |
| Negative Percent Agreement (NPA) | High agreement (e.g., >95%) with probable negative cases | 99.39% (975/981) (Overall) (95% CI: 98.67% - 99.78%) |
| Positive Percent Agreement (PPA) (Serological Presumed Positive Population) | High agreement (e.g., >95%) with probable positive cases in this specific population | 100% (662/662) (95% CI: 99.44% - 100%) |
| Negative Percent Agreement (NPA) (Serological Presumed Positive Population) | High agreement (e.g., >95%) with probable negative cases in this specific population | 98.65% (146/148) (95% CI: 95.20% - 99.84%) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- High and Low Risk Subjects Study: N = 1074 subjects
- Serological Presumed Positive Population Study: N = 810 specimens
- Data Provenance:
- Country of Origin: The "Serological Presumed Positive Population" study explicitly states specimens were obtained from endemic countries: Bolivia (17.8%), Brazil (24.7%), Chile (10.6%), Guatemala (2.2%), Mexico (32.5%), and Nicaragua (12.2%). The provenance for the "High and Low Risk" subjects is not explicitly stated, but given T. cruzi is endemic to Latin America, it's highly likely they came from similar regions or populations with risk factors associated with these regions.
- Retrospective or Prospective: Not explicitly stated, but the description of "specimens from 1074 subjects" and "specimens obtained from" suggests these were pre-collected samples, which typically implies a retrospective study design.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- The document does not specify the number of experts used to establish the ground truth.
- It refers to "a pre-specified testing algorithm" involving the ORTHO T. cruzi ELISA Test System, a comparator T. cruzi IFA (indirect immunofluorescence assay), and supplemental T. cruzi RIPA (radioimmunoprecipitation assay) testing to determine the "most probable T. cruzi antibody status." This implies a laboratory-based algorithm rather than subjective expert interpretation for each individual case ground truth.
- Qualifications of Experts: Not specified. However, the reliance on established serological methods (IFA, RIPA) suggests that interpretation would be done by qualified laboratory personnel following established protocols, though individual "experts" for ground truth adjudication are not mentioned.
4. Adjudication Method for the Test Set
The adjudication method used to establish the "most probable T. cruzi antibody status" for the test sets was a pre-specified testing algorithm rather than an expert consensus method like 2+1 or 3+1.
- For High and Low Risk Subjects:
- Specimens negative with both the ORTHO T. cruzi ELISA and the T. cruzi IFA were assigned a "most probable T. cruzi antibody status of negative" (if not tested with RIPA).
- Specimens tested with RIPA were assigned a most probable status of positive, negative, or indeterminate based on RIPA results.
- For Serological Presumed Positive Population:
- Specimens that were ORTHO T. cruzi ELISA repeatedly reactive AND positive with the T. cruzi IFA were assigned a "most probable T. cruzi antibody status of positive" without further RIPA testing.
- All specimens negative with both assays OR with discordant results between the two assays were tested with the T. cruzi RIPA, and their status was assigned "based upon the RIPA results."
This method essentially uses a hierarchical testing algorithm with RIPA as a confirmatory test for ambiguous cases, which acts as the adjudicator.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
- No, an MRMC comparative effectiveness study was not done.
- This device is an ELISA diagnostic kit, which is an in vitro diagnostic (IVD) assay to detect antibodies in serum/plasma. It is not an AI-assisted diagnostic device that would involve human readers interpreting images or data with or without AI assistance. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply here.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
- Yes, the performance presented in the report is for the device operating in a standalone capacity (algorithm only).
- The ORTHO T. cruzi ELISA Test System is an automated/semi-automated in vitro diagnostic assay. The results (optical densities) are read spectrophotometrically, and the interpretation (reactive/nonreactive) is based on a pre-defined cutoff. While human operators are involved in running the assay (pipetting, washing, loading), the diagnostic decision itself from the optical density reading is based on the device's internal algorithm/parameters, not human interpretation of a raw signal. The performance metrics (PPA, NPA) directly reflect this standalone assay performance against the established ground truth.
7. The Type of Ground Truth Used
The ground truth used was a "most probable T. cruzi antibody status" established by a pre-specified testing and interpretation algorithm involving:
- The ORTHO T. cruzi ELISA Test System itself
- A comparator T. cruzi IFA
- Supplemental T. cruzi RIPA testing (Radioimmunoprecipitation Assay) as a confirmatory assay.
This approach combines multiple serological methods, with RIPA acting as the highest tier for ambiguous results, to arrive at a "most probable" truth, which is a form of composite reference standard or multi-test algorithm ground truth.
8. The Sample Size for the Training Set
- The document does not specify any sample size for a training set.
- This is common for in vitro diagnostic (IVD) devices like ELISA kits, which are often developed and optimized using a variety of samples during their analytical validation phase, but the rigorous performance evaluation for regulatory submission typically focuses on a distinct clinical validation (test) set. The concepts of "training set" and "test set" are more explicitly separated for machine learning/AI models.
9. How the Ground Truth for the Training Set Was Established
- Since a "training set" is not explicitly mentioned or detailed in the provided document, there is no information on how its ground truth was established. If one were used in development, it would likely follow similar principles of using established serological methods and clinical information for sample characterization.
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510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirement of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K072732
l Submitter Name, Address, and Contact
Ortho-Clinical Diagnostics, Inc. 1001 US Highway 202 Raritan, NJ 08869-0606
Contact Person: Laura C. Vellucci (908) 218-8532
2 Preparation Date
Date 510(k) prepared: September 20, 2007
3 Device Name
Trypanosoma cruzi (T. cruzi) Whole Cell Lysate Antigen, ORTHO® T. cruzi ELISA Test System
Common Name: Trypanosoma cruzi (T. cruzi) Whole Cell Lysate Antigen ORTHO® T. cruzi ELISA Test System Trade Name: Classification Name: Trypanosoma spp. Serological reagents (21 CFR 866.3870)
Assay Class: I (general controls)
4 Predicate Device
The ORTHO T. cruzi ELISA Test System is substantially equivalent to K930272 Hemagen Chagas' Kit (EIA Method) - Hemagen Diagnostics, Inc., and/or K023889 Enzyme Linked Immunosorbent Assay, T. cruzi - Wiener Laboratories and the T. cruzi indirect immunofluorescence assay, IFA, performed by Focus Diagnostics, Cypress, CA is the comparator method.
5 Device Description
The ORTHO T. cruzi ELISA Test System is an enzyme-linked immunosorbent assay (ELISA). ELISA technology utilizes the principle that antibodies bound to the solid phase can be detected by complementary antibodies or antigens labeled with an enzyme capable of acting on a chromogenic substrate. When substrate is applied, the presence of antigens or antibodies can be detected by development of a colored end product. The ontical densities are read spectrophotometrically.
Ortho-Clinical Diagnostics, Inc.
APR 1 5 2009
.
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This ELISA was developed to detect human antibodies to T. cruzi in serum and plasma. The assay utilizes microwells coated with a whole-cell lysate containing T. cruzi antigens as the solid phase. The assay procedure is a three-stage test carried out in a microwell coated with lysale (antigens) prepared from T. cruzi. In the first stage, test specimen, Negative Control, and Positive Calibrator are diluted directly in the test well containing Specimen Diluent, and incubated for a specified length of time. If antibodies to 7. cruzi are present, antigen-antibody complexes will form on the microwell surface. If antibodies to T. cruzi are absent, complexes will not form. Unbound antibodies in the sample will be removed during the subsequent wash step.
In the second stage, murine monoclonal antibody conjugated with Horseradish Peroxidase (Conjugate) is added to the test well. The Conjugate binds specifically to the antibody portion of the antigen-antibody complex. If complexes are not present, the unbound Conjugate is removed by the subsequent wash step.
In the third stage, an enzyme detection system composed of o-phenvlenediamine (OPD) and hydrogen peroxide is added to the test well. If bound Conjugate is present, the OPD with be oxidized, resulting in a colored end product. Sulfuric acid is then added to stop the reaction. The color intensity depends on the amount of bound Conjugate and, therefore, is a function of the concentration of antibodies to T. cruzi present in the specimen. The intensity of color in the substrate solution is then determined with a microwell reader (spectrophotometer) designed to measure light absorbance in a microwell.
Special Instrumentation Requirements
There are no special ELISA instrument requirements for the device. All 510(k) performance testing was conducted using semi-automated instrumentation defined as:
- . Ortho Summit Sample Handling System or
- Fixed or Adjustable Single-Channel Micropipette .
- . AutoWash 96 (multichannel aspirator-washer device)
- . AutoReader IV (dual wavelength microwell reader)
- Model 120 Incubator .
- Ortho Assay Software (OAS) .
- (instrumentation process and data management software)
- . Ortho T. cruzi CT (Clinical Trial) OAPD (Ortho Assay Protoco| Disk)
The instructions for use call for:
- Adjustable multichannel micropipettes, or equivalent reagent dispenser capable of . delivering 50 uL and 200 uL with at least ± 5% accuracy
- Fixed or adjustable single channel micropipettes or equivalent pipetter-dilutor capable of . delivering 20 µL and 200 µL with at least ± 5% accuracy
- . 50 uL to 300 uL disposable pipette tips or equivalent
- . 20 uL disposable pipette tips or equivalent
- Appropriately sized serological pipette or graduated cylinder .
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- . Multichannel micropipette reservoirs or equivalent containers
- . OCD microwell plate or strip washer or equivalent multichannel microwell aspiratorwasher device capable of at least 5 cycles of wash by dispensing and aspirating at least 700 uL of fluid per well and leaving a full well of fluid to soak at least 20 seconds.
- . OCD microwell plate or strip reader or equivalent dual wavelength microwell reader capable of reading at 490 or 492 nm with a reference filter of 620 or 630 nm. A 610 nm filter is required for performing Sample Omission Monitoring (SOM) reads. Linearity of the microwell reader must range from at least 0 to 2.5 absorbance units.
- . 37℃ ± 1℃ microwell incubator (dry)
Users are instructed, when using semi-automated instruments, to follow the procedures that are contained in the operator's manual provided by the device manufacturer. Lahoratories must follow their approved validation procedures to demonstrate compatibility of this product on semi-automated and automated systems.
6 Device Intended Use
ORTHO T. cruzi ELISA Test System is an enzyme-linked immunosorbent assay for the in vitro qualitative detection of antibodies (Immunoglobulin G) to Trypanosoma cruzi (T. cruzi) in human adult serum (glass, plastic, or serum separator tubes) and plasma (EDTA, lithium heparin or citrate) using whole-cell lysate antigens. Reactive assay results are presumplive evidence of past infection, and in conjunction with other serological and clinical information, may be used for the laboratory diagnosis of individuals with Chagas' disease.
Definitive diagnosis of an acute phase of infection (including acute congenital infection) must be made by alternate methods, e.g., hemoculture, blood smear.
This test is not intended for use on samples of cord blood or screening blood or plasma donors.
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7 Comparison to Predicate Device
The ORTHO T. cruzi ELISA Test System is substantially equivalent to K930272 Hemagen Chagas` Kit (EIA Method) - Hemagen Diagnostics, Inc., and/or K023889 Enzyme Linked Immunosorbent Assay, 7. cruzi -Wiener Laboratories and the 7. cruzi indirect immunofluorescence assay, IFA, performed by Focus Diegnostics, Cypress, CA is the comparator method.
Comparison of the ORTHO T. cruzi ELISA Test System to the K930272 Hemagen Chagas' Kit (EIA Method) - Hemagen Diagnostics, Inc., and K023889 Enzyme Linked Immunosorbent Assay, T. cruzi - Wiener Laboratories
| New Device | Predicate Device | Predicate Device | ||
|---|---|---|---|---|
| DeviceCharacteristic | ORTHO T. cruzi ELISA TestSystem | K930272Hemagen Chagas' Kit(EIA Method) -Hemagen Diagnostics, Inc. | K023889Enzyme LinkedImmunosorbent Assay,T. cruzi -Wiener Laboratories | |
| Intended Use | ... for the in vitro qualitativedetection of antibodies((Immunoglobulin (G) toTrypanosoma cruzi (T. cruzi) | ... for the detection ofcirculating antibodies toTrypanosoma cruzi, thecausative agent of Chagas'disease | Qualitative detection ofantibody to Trypanosoma cruzi,the causative agent for Chagas'disease in human serum orplasma. | |
| Indications for Use | Reactive assay results arepresumptive evidence of pastinfection, and in conjunctionwith other serological andclinical information, may beused for the laboratorydiagnosis of individuals withChagas' disease. | When used according toinstructions, the kit is useful inexhibiting prior exposure to T.cruzi and as an aid in thediagnosis of Chagas' disease. | When using according toinstructions, the kit is useful inestablishing prior exposure to T.cruzi and as an aid in thediagnosis of Chagas' disease. | Deleted: A |
| Basic Principle | Enzyme-linked immunosorbentassay, ELISA | Enzyme-linked immunosorbentassay, ELISA | Enzyme-linked immunosorbentassay, ELISA | |
| Where used | CLIA Certified ClinicalLaboratory | CLIA Certified ClinicalLaboratory | CLIA Certified ClinicalLaboratory | |
| Sample Type | Serum or Plasma(EDTA, lithium heparin orcitrate) | Serum | Serum or Plasma(heparin, EDTA, and citratebased anticoagulants) | |
| Antigen | Trypanosoma spp.(T. cruzi Tulahuen) | Trypanosoma spp. | Recombinant T. cruzi antigensfrom the trypomastigoteparasite stage: #1, #2, #13,#30, and #36) | |
| Antigen Prep | Whole cell lysate coated ontoplastic microwells | Purified antigens from culturedT. cruzi organisms | Recombinant technology | |
| Sample Volume | 20 $ μL $ | 10 $ μL $ | 10 $ μL $ | |
| Procedure | Diluted sample is incubatedwith the antigen prep. After anappropriate time the serumdilution in removed, and theantigen prep is washed. The | Diluted sample is incubatedwith the antigen prep. After anappropriate time the serumdilution in removed, and theantigen prep is washed. The | Diluted sample is incubatedwith the antigen prep. After anappropriate time the serumdilution in removed, and theantigen prep is washed. The | |
| antigen prep is overlaid with | antigen prep is overlaid with | antigen prep is overlaid with |
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| New Device | Predicate Device | Predicate Device | |
|---|---|---|---|
| antibody labeled with anchromogenic substrate | antibody labeled with anchromogenic substrate | antibody labeled with anchromogenic substrate | |
| ConjugateAntibody | Anti-human IgG | Anti-human IgG | Anti-human IgG |
| Tracer | Horseradish peroxidase with aSubstrate Solution made fromSubstrate Buffer and OPDTablets | Horseradish peroxidase withsubstrate 3, 3', 5, 5' -tetramethylbenzidine (TMB) | Horseradish peroxidase withsubstrate 3, 3', 5, 5' -tetramethylbenzidine (TMB) |
| AntibodiesDetection | The antibody-HRP bound to thewhole cell lysate-antibodycomplex reacts with the OPDproducing a colored endproduct. The OD is readspectrophotometrically | The antibody-HRP bound to thewhole cell lysate-antibodycomplex reacts with the TMBproducing a colored endproduct. The OD is readspectrophotometrically | The antibody-HRP bound to therecombinant antigens-antibodycomplex reacts with the TMBproducing a colored endproduct. The OD is readspectrophotometrically |
Performance
ORTHO T. cruzi ELISA and T. cruzi IFA Results among High Risk and Low Risk Subjects
Specimens from 1074 subjects at high or low risk for T. cruzi infection were tested with a comparator T. cruzi IFA and with the ORTHO T. cruzi ELISA Test System. The results are presented in the following table.
| ORTHO T. cruzi ELISA | T. cruzi IFA Result | ||
|---|---|---|---|
| Result | Positive | Negative | Total |
| Repeatedly Reactive | 82 | 162 | 98 |
| Nonreactive | 31 | 973 | 976 |
| Total | 85 | 989 | 1074 |
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The table below summarizes the percent agreement he ORTHO T. cruzi ELISA and the T. cruzi IFA. Data are listed by population and overall, with positive and negative percent agreement and 95% exact confidence intervals (CI).
| Population | Positive PercentAgreement | 95% ExactConfidenceInterval | Negative PercentAgreement | 95% ExactConfidenceInterval |
|---|---|---|---|---|
| High Risk | 96.47%(82/85) | 90.03% - 99.27% | 96.93%(474/489) | 94.99% - 98.27% |
| Low Risk | 100%(300/300) | 98.78% - 100% | ||
| PregnancyLow Risk | 99.50%(199/200) | 97.25% - 99.99% | ||
| Total | 96.47%(82/85) | 90.03% - 99.27% | 98.38% (973/989) | 97.39% - 99.07% |
ORTHO T. cruzi ELISA Results and Most Probable T. cruzi Antibody Status among High Risk and Low Risk Subjects
Because the T. cruzi IFA is a non-reference standard for detection of antibodies to T. cruzi, the most probable T. cruzi antibody status of the high and low risk study subjects was determined by ORTHO T. cruzi ELISA Test System, comparator T. cruzi IFA and supplemental T. cruzi RIPA testing according to a pre-specified testing algorithm. Specimens not tested with RIPA that were negative with both the ORTHO T. cruzi ELISA and the T. cruzi IFA were assigned a most probable T. cruzi antibody status of negative. Specimens tested with the RIPA were assigned a most probable T. cruzi antibody status of positive, negative or indeterminate based on the RIPA results.
A comparison of the ORTHO T. cruzi ELISA results to most probable T. cruzi antibody status is presented in the following table.
| ORTHO T. cruzi ELISA Results and Most Probable T. cruzi Antibody Statusin the High Risk and Low Risk Populations (N=1074) | ||||
|---|---|---|---|---|
| ORTHO T. cruzi ELISAResults | Most Probable T. cruzi Antibody StatusPositive | Negative | Indeterminate1 | TOTAL |
| Repeatedly Reactive | 92 | 6 | 0 | 98 |
| Nonreactive | 1 | 975 | 0 | 976 |
| TOTAL | 93 | 981 | 0 | 1074 |
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The table below summarizes the percent agreement between the ORTHO T. cruzi ELISA and most probable T. cruzi antibody status. Data are listed by population and overall, with positive and negative percent agreement and 95% exact confidence intervals.
| Positive and Negative Percent Agreement of the ORTHO T. cruzi ELISA withMost Probable T. cruzi Antibody Status by High Risk and Low Risk Study Population (N=1074) | ||||
|---|---|---|---|---|
| Population | Positive PercentAgreement | 95% ExactConfidenceInterval | Negative PercentAgreement | 95% ExactConfidenceInterval |
| High Risk | 98.92%(92/93) | 94.15% - 99.97% | 98.96%(476/481) | 97.59% - 99.66% |
| Low Risk | 100%(300/300) | 98.78% - 100% | ||
| PregnancyLow Risk | 99.50%(199/200) | 97.25% - 99.99% | ||
| Total | 98.92%(92/93) | 94.15% - 99.97% | 99.39% (975/981) | 98.67% - 99.78% |
Specimens Presumed Positive for Antibodies to T. cruzi by Serological Methods ORTHO T. cruzi ELISA versus T. cruzi IFA
A total of 810 specimens were included in the T. cruzi scrological presumed positive population based upon two positive serological tests for T. cruzi antibodies in use in the countries of origin (i.e., ELISA, IFA, hemagglutination, or complement fixation). The comparator T. cruzi IFA was not used to admit specimens to the study. The specimens were obtained from the endemic countries of Bolivia (17.8%), Brazil (24.7%), Chile (10.6%), Gualemala (2.2%), Mexico (32.5%) and Nicaragua (12.2%). ORTHO T. cruzi ELISA testing was performed at two testing sites in Camp Hill, PA and Newark, NJ. Direct comparison of the ORTHO T. cruzi ELISA with the T. cruzi IFA is presented in the following table.
| ORTHO T. cruzi ELISA vs. T. cruzi IFA Results in Specimens Presumed Positive by SeMethods (N=810) | |||
|---|---|---|---|
| ORTHO T. cruzi ELISAResult | T. cruzi IFA Result | Total | |
| Repeatedly Reactive | 565 | 992 | 664 |
| Nonreactive | 51 | 1413 | 146 |
| Total | 570 | 240 | 810 |
All 141 specimens were negative with the 7. cruzi RIPA.
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Positive, negative and overall percent agreement of the ORTHO T. cruzi ELISA with the T. cruzi IFA and 95% exact confidence intervals are shown in the following table.
| Positive, Negative and Overall Percent Agreement of the ORTHO T. cruzi ELISA with the T. cruzi IFAin the Serological Presumed Positive Population (N=810) | ||||||
|---|---|---|---|---|---|---|
| Population | PositivePercentAgreement | 95% ExactConfidenceInterval | NegativePercentAgreement | 95% ExactConfidenceInterval | OverallPercentAgreement | 95% ExactConfidenceInterval |
| SerologicalPresumedPositive | 99.13%(565/570) | 97.96% -99.71% | 58.75%(141/240) | 52.24% -65.04% | 87.16%(706/810) | 84.66% -89.39% |
ORTHO T. cruzi ELISA versus Most Probable T. cruzi Antibody Status
Because the T. cruzi IFA is a non-reference standard for detection of antibodies to T. cruzi, the most probable T. cruzi antibody status of the study subjects presumed positive by serologic methods was determined by ORTHO T. cruzi ELISA Test System, comparator T. cruzi IFA and supplemental T. cruzi RIPA testing according to a pre-specified testing and interpretation algorithm. Specimens that were ORTHO T. cruzi ELISA repeatedly reactive and positive with the T. cruzi IFA were assigned a most probable T. cruzi antibody status of positive and were not tested with the T. cruzi RIPA. All specimens negative with both assays or with discordant results between the two assays were tested with the T. cruzi RIPA and assigned a most probable T. cruzi antibody status based upon the RIPA results. A comparison of ORTHO T. cruzi ELISA results and most probable 7. cruzi antibody status is presented in the following table
| ORTHO T. cruzi ELISA Results | Most Probable T. cruzi Antibody Status | TOTAL | ||
|---|---|---|---|---|
| Positive | Negative | Indeterminate1 | ||
| Repeatedly Reactive | 662 | 2 | 0 | 664 |
| Nonreactive | 0 | 146 | 0 | 146 |
| TOTAL | 662 | 148 | 0 | 810 |
probable T. cruzi antibody status of indeterminate among the serological presumed positive specimens tested with RIPA.
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Positive, negative and overall percent agreement of the ORTHO T. cruzi ELISA with most probable T. cruzi antibody status and 95% exact confidence intervals are shown in the following table.
| Positive, Negative and Overall Percent Agreement of the ORTHO T. cruzi ELISA with Most ProbableT. cruzi Antibody Status for the Serological Presumed Positive Population (N=810) | ||||||
|---|---|---|---|---|---|---|
| Population | PositivePercentAgreement | 95% ExactConfidenceInterval | NegativePercentAgreement | 95% ExactConfidenceInterval | OverallPercentAgreement | 95% ExactConfidenceInterval |
| SerologicalPresumedPositive | 100%(662/662) | 99.44% -100% | 98.65%(146/148) | 95.20% -99.84% | 99.75%(808/810) | 99.11% -99.97% |
8 Conclusions
The ORTHO T. cruzi ELISA Test System is substantially equivalent to K930272 Hemagen Chagas' Kit (EIA Method) . Hemagen Diagnostics, Inc., and/or K023889 Enzyme Linked Immunosorbent Assay, T. cruzi - Wiener Laboratories
The data presented in the Premarket notification provide a reasonable assurance the ORTHO T. cruzi ELISA Test System is safe and effective for the stated intended use and is substantially equivalent to the predicate device.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/9/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three stylized, curved lines.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ortho-Clinical Diagnostics, Inc. Laura C. Vellucci 1001 US Highway 202 Raritan, NJ 08869-0606
APR 1 5 2009
Re: K072732
Trade/Device Name: ORTHO® T. cruzi ELISA Test System Regulation Number: 21 CFR 866.3870 Regulation Name: Trypanosomma spp. Serological reagents Regulatory Class: Class I Product Code: MIU Dated: September 29, 2008 Received: October 1, 2008
Dear Ms. Vellucci:
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. 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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely vours,
Sally attignto
Sally A. Hojvat. M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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510(k) Number (if known): K072732
Device Name:
Trypanosoma cruzi (T. cruzi) Whole Cell Lysate Antigen, ORTHO® T. cruzi ELISA Test System
Indications for Use:
ORTHO T. cruzi ELISA Test System is an enzyme-linked immunosorbent assay for the in vitro qualitative detection of antibodies (Immunoglobulin G) to Trypanosoma cruzi (T. cruzi) in human adult serum (glass, plastic, or serum separator tubes) and plasma (EDTA, lithium heparin or citrate) using whole-cell lysate antigens. Reactive assay results are presumptive evidence of past infection, and in conjunction with other serological and clinical information, may be used for the laboratory diagnosis of individuals with Chagas' disease.
Definitive diagnosis of an acute phase of infection (including acute congenital infection) must be made by alternate methods, e.g., hemoculture, blood smear.
This test is not intended for use on samples of cord blood or screening blood or plasma donors.
Prescription Use ਮ (Per 21 CFR 801 Subpart D) AND/OR
Over -The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnos of Marces
Ortho-Clinical Diagnostics, Inc.
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Office of In Vitro Diagnostir Device Evaluation and Sately
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§ 866.3870
Trypanosoma spp. serological reagents.(a)
Identification. Trypanosoma spp. serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies toTrypanosoma spp. in serum. The identification aids in the diagnosis of trypanosomiasis, a disease caused by parasitic protozoans belonging to the genusTrypanosoma. Trypanosomiasis in adults is a chronic disease characterized by fever, chills, headache, and vomiting. Central nervous system involvement produces typical sleeping sickness syndrome: physical exhaustion, inability to eat, tissue wasting, and eventual death. Chagas disease, an acute form of trypanosomiasis in children, most seriously affects the central nervous system and heart muscle.(b)
Classification. Class I (general controls).