(113 days)
The ImmunoCard Toxin A enzyme immunoassay (EIA) is a rapid in vitro qualitative procedure for detecting Clostridium difficile toxin A in human stool. The test can be used to aid in the diagnosis of C. difficile-associated disease. The test may also be used to determine the production of toxin A by C. difficile in BHI broth culture.
The ImmunoCard Toxin A assay system is a card based EIA for toxin A of C. difficile. Each kit contains the following components: Toxin A ImmunoCards (50), Positive Control (0.5ml), Enzyme Conjugate (7.5ml), Sample Diluent (10.0ml), Wash Reagent (28ml), Substrate Reagent (13ml), Transfer Pipets (50). In brief, the assay is performed by preparing a 1/15 dilution of stool in a mixture of Sample Diluent and Enzyme Conjuqate. Using a transfer pipet, 150pl of diluted specimen are then added to each of the lower (sample application) ports on an ImmunoCard. The sample is allowed to enter the card for 5 minutes. Three drops of Wash Reagent are added to each of the upper (Reaction) ports and allowed to enter the card. Three drops of Substrate Reagent are then added and the card is viewed for visible blue color development after 5 minutes.
The provided 510(k) summary for Meridian Diagnostics, Inc.'s ImmunoCard Toxin A describes the device's intended use and performance characteristics based on a comparison to a predicate device and reference methods. Here's a breakdown of the requested information:
Acceptance Criteria and Reported Device Performance
| Criteria | Reported Device Performance |
|---|---|
| Comparison to Cytotoxin Test (Predicate) | |
| Relative Sensitivity (>80% implied) | 82.7% |
| Relative Specificity (>95% implied) | 98.2% |
| Relative Agreement (>95% implied) | 96.2% |
| Comparison to 3 Reference Methods (Toxin A EIA, Cytotoxin, and Toxigenic Culture) | |
| Sensitivity (>80% implied) | 85.2% |
| Specificity (>95% implied) | 97.5% |
| Agreement (>95% implied) | 96.0% |
| Analytical Sensitivity (Limit of Detection) | |
| Toxin A Detection Limit (pg) | Approximately 32 pg of toxin A (equates to 3.2 ng toxin A/ml of stool after dilution and assay volume considerations). |
| Reproducibility | No incorrect results were obtained with any test or procedural control (evaluated using strong positive, weak positive, and negative stools, tested in triplicate on 3 different days at 3 different locations). |
| Specimen Stability (Fresh vs. Frozen) | Toxin A is stable in stool for at least 3 days when stored at 4°C. Freezing (≤ -20°C) does not appreciably alter performance. |
Note regarding acceptance criteria: The document doesn't explicitly state quantitative acceptance criteria for sensitivity, specificity, and agreement. However, based on the reported values generally seen in diagnostic device submissions, typical implied thresholds of >80% sensitivity and >95% specificity/agreement are used in the table above. The "Equivalent relative performance" statement indicates the reported values were deemed acceptable for substantial equivalence.
Study Information:
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Sample Size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective):
- Sample Size: Not explicitly stated for either the comparison to the cytotoxin test or the 3-reference method comparison. The document mentions "clinical data" but does not quantify the number of patient samples.
- Data Provenance: Not specified (e.g., country of origin, retrospective or prospective). The use of "clinical data" implies human stool samples, but details are lacking.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable as the ground truth was established by laboratory methods (cytotoxin assay and other reference methods), not by expert human readers.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. The ground truth was established by laboratory tests. For the "3 reference methods" ground truth, it implies a consensus or agreement among those three methods, but the specific adjudication rules are not detailed (e.g., if 2 out of 3 had to agree).
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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:
- Not applicable. This device is an in-vitro diagnostic (IVD) assay, not an AI-assisted imaging device that involves human readers.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance presented is for the ImmunoCard Toxin A assay as a standalone diagnostic test. It's a laboratory test, and its results are interpreted directly (visible blue color development), not requiring human-in-the-loop for result generation beyond the initial sample preparation and visual reading.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For the primary comparison: The predicate tissue culture cytotoxin assay with neutralization using specific anti-toxin was used as the ground truth.
- For the more robust comparison: A combination of 3 reference methods (Toxin A EIA, cytotoxin, and toxigenic culture) was used. This represents a "composite reference standard" or "gold standard" based on established laboratory methods for C. difficile toxin detection and pathogenicity.
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The sample size for the training set:
- Not explicitly stated. As this is an in-vitro diagnostic assay rather than an AI/ML algorithm requiring a distinct "training set," the concept of a training set in that sense does not apply. The development and optimization of the ImmunoCard Toxin A would have involved various experimental samples, but these are not typically categorized as a "training set" in the context of AI/ML.
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How the ground truth for the training set was established:
- Not applicable for the reason stated above. If there were any development samples, their "ground truth" would have been established by similar reference laboratory methods.
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APR 1 8 1996 510 (k) Summary
Meridian Diagnostics, Inc. Cincinnati, Ohio 45244
APPENDIX A - 510(k) Summary
Identification Information E.
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- Submitter's Information:
- Submitter's Name and Address: a)
Meridian Diagnostics, Inc. 3471 River Hills Dr. Cincinnati, OH 45244
- b) Phone Number: 1-800-543-1980
- Contact Person: Allen D. Nickol, PhD C) Director Scientific & Regulatory Affairs
- Date Summary Prepared: December 22, 1995 d)
- Name of Device: ImmunoCard Toxin A. The ImmunoCard Toxin 2) A enzyme immunoassay (EIA) is a rapid in vitro qualitative procedure for detecting Clostridium difficile toxin A in human stool. The test can be used to aid in the diagnosis of C. difficile-associated disease. The test may also be used to determine the production of toxin A by C. difficile in BHI broth culture. Classification Name unknown.
- Tissue culture cytotoxin Predicate Equivalent Device: 3) assay with neutralization using specific anti-toxin.
- Description of Device: The ImmunoCard Toxin A assay system 4 ) is a card based EIA for toxin A of C. difficile. Each kit contains the following components:
- Toxin A ImmunoCards (50) a)
- Positive Control (0.5ml) b)
- Enzyme Conjugate (7.5ml) C)
- Sample Diluent (10.0ml) d )
- Wash Reagent (28ml) e )
- Substrate Reagent (13ml) f)
- Transfer Pipets (50) ਕੇ )
the assay is performed by preparing a In brief, 1/15 dilution of stool in a mixture of Sample Diluent and Enzyme 150pl of diluted Using a transfer pipet, Conjuqate. specimen are then added to each of the lower (sample application) ports on an ImmunoCard. The sample is allowed Three drops of Wash to enter the card for 5 minutes. Reagent are added to each of the upper (Reaction) ports and
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allowed to enter the card. Three drops of Substrate Reagent are then added and the card is viewed for visible blue color development after 5 minutes.
- The ImmunoCard Toxin A enzyme immunoassay 5) Intended Use: is a rapid in vitro qualitative procedure (EIA) for detecting Clostridium difficile toxin A in human stool. The test can be used to aid in the diagnosis of C. difficile-associated disease. The test may also be used to determine the production of toxin A by C. difficile in BHI broth culture.
- Comparison ର) Predicate Devices: with The following comparison of the use, technology, function and performance supports the Statement of Equivalence between the ImmunoCard Toxin A test and cytotoxin testing.
- a) Both assays detect toxins of C. difficile in patient stools. The ImmunoCard Toxin A test detects enterotoxin (toxin A), the etiologically important toxin. The cytotoxin assay detects toxin B, which is associated with disease through coproduction with toxin A.
- b) Both assays are in vitro immunoassays. The ImmunoCard Toxin A test is an EIA, while the cytotoxin assay is an antibody-dependent toxin neutralization bioassay.
- C) Both tests are performed directly on stool extracts. The ImmunoCard Toxin A test utilizes a Sample Diluent and Enzyme Conjuqate, while the cytotoxin assay requires sample dilution, centrifugation and filtration.
- Both assays yield qualitative results (i.e. positive or d) negative). The cytotoxin assay can be performed using higher than standard (1/40) dilutions, although the diagnostic significance of this has yet to be determined.
- Equivalent relative performance was recorded relative e) sensitivity 82.7%, relative specificity 98.2%, relative agreement 96.2%) when comparing the ImmunoCard Toxin A and cytotoxin tests. When ImmunoCard Toxin A results were compared with concordant result of 3 reference methods (Toxin A EIA, cytotoxin and toxigenic culture), sensitivity, specificity and agreement were 85.2%, 97.5% and 96.0%.
- These clinical data demonstrate the correlation between f)
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510 (k) Summary
the two methods, supporting the ImmunoCard Toxin A EIA as being substantially equivalent to the reference cytotoxin method.
Additional Information/Nonclinical Test Results: F.
- The sensitivity of the ImmunoCard 1) Sensitivity Limits: Toxin A is approximately 32 pg of toxin A. Allowing for the 1/15 dilution of sample and 150µl assay volume, this equates to 3.2ng toxin A/ml of stool as the ImmunoCard Toxin A limit of detection.
- Reproducibility: Reproducibility of the ImmunoCard Toxin A 2) test was evaluated by running strong positive, weak positive, and negative stools. Ten specimens were tested in triplicate on each of 3 different days at 3 different No incorrect results were obtained with any locations. test or procedural control.
- Fresh versus Frozen Stools: The data indicated toxin A is 3) stable in stool for at least 3 days when stored at 4°C. If specimen cannot be tested within this period, freezing the specimen is recommended (≤ -20°C) and does not appreciably alter performance.
§ 866.2660 Microorganism differentiation and identification device.
(a)
Identification. A microorganism differentiation and identification device is a device intended for medical purposes that consists of one or more components, such as differential culture media, biochemical reagents, and paper discs or paper strips impregnated with test reagents, that are usually contained in individual compartments and used to differentiate and identify selected microorganisms. The device aids in the diagnosis of disease.(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 § 866.9.