(569 days)
Not Found
No
The description details a standard immunofluorescence assay with digital imaging and software interpretation, but there is no mention of AI or ML algorithms being used for image analysis or result interpretation.
No.
This device is an in vitro diagnostic test intended to aid in the diagnosis of C. difficile infection by detecting toxins, not to directly treat or prevent a disease.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "intended as an aid in the diagnosis of C. difficile infection (CDI)".
No
The device description clearly states that the SensiTox C. difficile Toxin Test is an immunofluorescence assay performed on the proprietary MultiPath Analyzer, which is a hardware component that processes the sample, heats the cartridge, splits aliquots, mixes with particles, incubates, and uses magnets for imaging. While software is used for interpretation, the core functionality relies on dedicated hardware.
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 Clostridioides difficile toxins A and/or B in human stool specimens" and is "intended as an aid in the diagnosis of C. difficile infection (CDI)". This clearly indicates it's used to examine specimens derived from the human body to provide information for diagnostic purposes.
- Specimen Type: The device analyzes "human stool specimens," which are biological specimens from the human body.
- Method: It uses an "immunofluorescence assay," which is a laboratory technique performed outside the body.
- Clinical Context: The test is intended for use in a "clinical laboratory" and is evaluated in a "prospective clinical study" for its performance in diagnosing CDI.
All these points align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The SensiTox C. difficile Toxin Test is an immunofluorescence assay intended for the qualitative detection of Clostridioides difficile toxins A and/or B in human stool specimens. The test is intended as an aid in the diagnosis of C. difficile infection (CDI) in patients exhibiting symptoms of CDI. Negative results do not preclude toxigenic C. difficile infection. The SensiTox C. difficile Toxin Test should not be used as the sole basis for treatment or other management decisions. The test can only be used with the MultiPath platform.
Product codes (comma separated list FDA assigned to the subject device)
LLH
Device Description
The SensiTox C. difficile Toxin Test detects toxins A and B in stool samples using an immunofluorescence assay and the proprietary MultiPath detection technology. The assay is performed on the proprietary MultiPath Analyzer.
A stool sample, collected in a dry, clean, and leakproof collection media, is used for the test. The stool sample is added to Stool Specimen Diluent containing Protessed manually through a spin column to remove particulates. The stool filtrate is added to the SensiTox C. difficile Cartridge, a single use consumable that contains all the reagents required to run a single test. The Cartridge is loaded onto the MultiPath Analyzer for processing through the steps of the assay.
Once loaded onto the Analyzer, the barcodes on the Cartridge that identify the test type and associated test specific information (manufacturer installed barcode) and sample (laboratory affixed barcode) are read. The cartridge is moved to the fluidics station where it is first heated to 35°C. The sample is then split into 6 equal aliquots in 6 distribution wells within the cartridge, 3 wells specific to toxin B. The sample aliquots flow from the distribution wells to the reagent wells containing target specific antibody conjugated fluorescent and magnetic particles in the form of lyophilized beads. Upon contact with the sample, the lyophilized beads rehydrate and the reaction mixtures flow into the imaging wells, the bottoms of which are coated with a dye cushion reagent. Upon contact with the reagents, the dyecushion dissolves forming a dense opaque aqueous layer that separates the sample and reagents from the bottom optical surface of the Imaging Well. In the upper assay layer, the toxins, if present, bind to the magnetic and fluorescent particles tethering them together. The cartridge is incubated for 28 minutes to allow the reaction to take place and then is moved to the magnetics station. At the magnetics station, the imaging well is placed over permanent magnets that draw the magnetic particles and any fluorescent particles that are tethered to them via the target molecules through the dyecushion layer, depositing them on the bottom imaging surface. The captured fluorescent particles are imaged and quantified using non-magnified digitalimaging.
The Analyzer can be run in batch mode or by random access. Up to 20 cartridges can be loaded onto the Analyzer in parallel. The first result is reported in approximately 35 minutes of loading the Analyzer with subsequent results being reported in 2.5 minute increments. The results are interpreted using the MultiPath applications software as valid or invalid, and if valid, the results are reported as toxin detected if either toxin A or B or both toxins are present or toxin not detected if neither toxin is present. Results are displayed on the instrument touch screen and can be printed.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Immunofluorescence, Digital Imaging
Anatomical Site
Human stool specimens
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Clinical laboratory
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
- Limit of Detection (LoD): LoD for C. difficile toxins A and B was determined by spiking negative pooled stool with purified toxins A and B. Tested 5 dilutions of toxins A and B with 3 lots of reagents and 20 replicates per lot (total 60 replicates per concentration). LoD for toxin A is 3.5 ng/mL and for toxin B is 50 ng/mL.
- Reproducibility: Evaluated at 3 sites over 5 days by 2 operators each day. Randomized and blinded samples of Stool Specimen Diluent spiked with varying concentrations of toxins A and B (low positive, moderate positive, high positive, negative) were prepared. Total of 376 samples (95 negative, 281 positive) were run with an overall reproducibility of 99.2%. One false positive result from negative samples and one false negative result each from low and moderate positive samples were generated.
- Analytical Reactivity (Inclusivity): Tested multiple ribotypes of toxins A and B. Pooled stool samples negative for toxins A and B were spiked with purified toxin from clinically important ribotypes. Six ribotypes of toxin A (15 ng/mL) and 8 ribotypes of toxin B (300 pg/mL) were tested. Positive controls (toxins A and B from wildtype strain 087) also tested. All toxin A and B ribotypes tested were detected.
- Analytical Specificity: Evaluated by testing cultured organisms (bacteria, yeast, viruses) in negative pooled stool or contrived stool containing 15 ng/mL of toxin A and 300 pg/mL of toxin B. Organisms were tested at 1x10^6 CFU/mL (bacteria, yeast) or 1x10^5 PFU/mL (viruses), in triplicate. None of the organisms cross-reacted or negatively interfered with toxin detection.
- Interfering Substances: Negative pooled stool and contrived pooled stool with toxins A (15 ng/mL) and B (300 pg/mL) were spiked with potential interferents. None of the interferents negatively impacted performance, except Vancomycin at 50 mg/mL, which negatively impacted detection of toxins A and B (not inhibitory at 40 mg/mL).
- Clinical Performance Evaluation: Prospective clinical study at three geographically diverse sites in the US using de-identified, unpreserved, stool specimens from patients suspected of C. difficile infection. Performance compared to cellular cytotoxicity neutralization assay (CCNA). Overall clinical performance: Sensitivity 90.6%, Specificity 95.7%.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Overall Reproducibility: 99.2%
- Clinical Performance:
- Sensitivity: 90.6% [95% CI: 83.1% - 95.0%]
- Specificity: 95.7% [95% CI: 94.2% - 96.8%]
- Positive Predictive Value: 68.0% [95% CI: 59.5% - 75.4%]
- Negative Predictive Value: 99.0% [95% CI: 98.1% - 99.5%]
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.
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
§ 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.
0
Image /page/0/Picture/0 description: The image contains the logos of the Department of Health and Human Services and the Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
July 8, 2021
First Light Diagnostics, Inc. % Fran White President, Regulatory Affairs MDC Associates, LLC 180 Cabot Street Beverly, Massachusetts 01915
Re: K193490
Trade/Device Name: SensiTox C. difficile Toxin Test Regulation Number: 21 CFR 866.2660 Regulation Name: Microorganism Differentiation And Identification Device Regulatory Class: Class I Product Code: LLH Dated: December 16, 2019 Received: December 17, 2019
Dear Fran White:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part
1
801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ribhi Shawar, Ph.D. (ABMM) Chief. General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K193490
Device Name SensiTox C. difficile Toxin Test
Indications for Use (Describe)
The SensiTox C. difficile Toxin Test is an immunofluorescence assay intended for the qualitative detection of Clostridioides difficile toxins A and/or B in human stool specimens. The test is intended as an aid in the diagnosis of C. difficile infection (CDI) in patients exhibiting symptoms of CDI. Negative results do not preclude toxigenic C. difficile infection. The SensiTox C. difficile Toxin Test should not be used as the sole basis for treatment or other management decisions. The test can only be used with the MultiPath platform.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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Page 1 of 7
2.0 510(k) SUMMARY
| Date of Summary: | June 30, 2021 |
|---|---|
| Product Name: | SensiTox™ C. difficile Toxin Test |
| Sponsor: | First Light Diagnostics |
| 2 Omni Way | |
| Chelmsford, MA 01824 | |
| Correspondent: | MDC Associates, Inc. |
| Fran White, President Regulatory Affairs | |
| 180 Cabot Street | |
| Beverly, MA 01915 | |
| Phone: (978) 927 3808 | |
| Fax: (866) 540 3448 | |
| Email: regulatory@mdcassoc.com | |
| Common Name: | Microorganism differentiation and identification device |
| Regulation Number: | 866.2660 |
| Classification: | LLH, Class I |
Substantial Equivalency
| Description | First Light Diagnostics
Subject Device
SensiTox C. difficile Toxin Test | Meridian Bioscience, Inc.
Predicate Device
K041003
ImmunoCard® Toxins A & B |
|--------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Regulation | 866.2660 | Same |
| Product Code | LLH | Same |
| Device Class | Class I | Same |
| Panel | 83 Microbiology | Same |
| Intended Use | The SensiTox C. difficile Toxin Test is an
immunofluorescence assay intended for the
qualitative detection of Clostridioides difficile
toxins A and/or B in human stool specimens.
The test is intended as an aid in the diagnosis
of C. difficile infection (CDI) in patients
exhibiting symptoms of CDI. Negative results
do not preclude toxigenic C. difficile infection.
The SensiTox C. difficile Toxin Test should not
be used as the sole basis for treatment or
other management decisions. The test can
only be used with the MultiPath platform. | ImmunoCard® Toxins A & B is a rapid, qualitative,
horizontal-flow enzyme immunoassay (EIA) for
detecting Clostridium difficile toxins A and B in
human stool. This assay is used as an aid in the
diagnosis of C. difficile-associated disease. |
4
| Page 2 of 7 | |||
|---|---|---|---|
| Description | First Light Diagnostics | ||
| Subject Device | |||
| SensiTox C. difficile Toxin Test | Meridian Bioscience, Inc. | ||
| Predicate Device | |||
| K041003 | |||
| ImmunoCard® Toxins A & B | |||
| Similarities | |||
| Sample Type | Human Stool | Same | |
| Analyte | Toxin A and B | Same | |
| Prescription Required? | Prescription use only | Same | |
| Setting | Clinical laboratory | Same | |
| Differences | |||
| Technology | Immunofluorescent assay | Enzyme immunoassay | |
| Antibodies | Detection & Capture: Mouse monoclonal | ||
| anti-toxin A and B | Goat polyclonal anti-toxin B | ||
| Test format | Fluidic cartridge with direct digital imaging | Lateral flow with visual interpretation |
Intended Use
The SensiTox C. difficile Toxin Test is an immunofluorescence assay intended for the qualitative detection of Clostridioides difficile toxins A and/or B in human stool specimens. The test is intended as an aid in the diagnosis of C. difficile infection (CDI) in patients exhibiting symptoms of CDI. Negative results do not preclude toxigenic C. difficile infection. The SensiTox C. difficile Toxin Test should not be used as the sole basis for treatment or other management decisions. The test can only be used with the MultiPath platform.
Limitations
For prescription use only. Please refer to the SensiTox C. difficile Toxin Test labeling for a more complete list of warnings, precautions, and contraindications.
Methodology
The SensiTox C. difficile Toxin Test detects toxins A and B in stool samples using an immunofluorescence assay and the proprietary MultiPath detection technology. The assay is performed on the proprietary MultiPath Analyzer.
A stool sample, collected in a dry, clean, and leakproof collection media, is used for the test. The stool sample is added to Stool Specimen Diluent containing Protessed manually through a spin column to remove particulates. The stool filtrate is added to the SensiTox C. difficile Cartridge, a single use consumable that contains all the reagents required to run a single test. The Cartridge is loaded onto the MultiPath Analyzer for processing through the steps of the assay.
Once loaded onto the Analyzer, the barcodes on the Cartridge that identify the test type and associated test specific information (manufacturer installed barcode) and sample (laboratory affixed barcode) are read. The cartridge is moved to the fluidics station where it is first heated to 35°C. The sample is then split into 6 equal aliquots in 6 distribution wells within the cartridge, 3 wells specific to toxin B. The sample aliquots flow from the distribution wells to the reagent wells containing target specific antibody conjugated fluorescent and magnetic particles in the form of lyophilized beads. Upon contact with the sample, the lyophilized beads rehydrate and the reaction mixtures flow into the imaging wells, the bottoms of which are coated with a dye cushion reagent. Upon contact with the reagents, the dyecushion dissolves forming a dense opaque aqueous layer that separates the sample and reagents from the bottom optical
5
Page 3 of 7
surface of the Imaging Well. In the upper assay layer, the toxins, if present, bind to the magnetic and fluorescent particles tethering them together. The cartridge is incubated for 28 minutes to allow the reaction to take place and then is moved to the magnetics station. At the magnetics station, the imaging well is placed over permanent magnets that draw the magnetic particles and any fluorescent particles that are tethered to them via the target molecules through the dyecushion layer, depositing them on the bottom imaging surface. The captured fluorescent particles are imaged and quantified using non-magnified digitalimaging.
The Analyzer can be run in batch mode or by random access. Up to 20 cartridges can be loaded onto the Analyzer in parallel. The first result is reported in approximately 35 minutes of loading the Analyzer with subsequent results being reported in 2.5 minute increments. The results are interpreted using the MultiPath applications software as valid or invalid, and if valid, the results are reported as toxin detected if either toxin A or B or both toxins are present or toxin not detected if neither toxin is present. Results are displayed on the instrument touch screen and can be printed.
Performance Data: Bench Studies
-
l. Limit of Detection (LoD)
The limit of detection (LoD) for C. difficile toxins A and B was determined by spiking negative pooled stool with commercially available purified toxins A and B. For each toxin, the LoD is defined as the lowest concentration of target that can be detected at a rate of ≥95%. The LoD was established by testing 5 dilutions of toxins A and B with 3 lots of reagents and 20 replicates per lot for a total of 60 replicates per concentration. The data from the 3 lots were combined to determine the positive hit rate. The LoD established for toxin A is 3.5 ng/mL and for toxin B is 50 ng/mL. -
II. Reproducibility
The reproducibility of the SensiTox C. difficile Toxin Test was evaluated at 3 sites over the course of 5 days by 2 operators each day. Randomized and blinded samples comprised of Stool Specimen Diluent spiked with varying concentrations of both toxins A and B – low positive (1-2x LoD), moderate positive (2-4x LoD), high positive (5-8x LoD), and negative (unspiked) were prepared and provided to each participating site. Each operator mixed the designated sample with pooled stool prescreened and known to be negative for toxins A and B and processed the sample using the C. difficile test procedure. A total of 376 samples comprised of 95 negative samples and 281 positive samples was run with an overall reproducibility of 99.2% (Table 2.1). As shown in Table 2.2, the negative sample generated one false positive result and the low and moderate positive samples each generated one false negative result.
| Site | Total Samples Run | # Correct Results | # Miscalls | # Invalids | % Accuracy | % Invalid |
|---|---|---|---|---|---|---|
| Site 1 | 123 | 123 | 0 | 3 | 100% | 2.4% |
| Site 2 | 128 | 127 | 1 | 8 | 99.2% | 6.3% |
| Site 3 | 125 | 123 | 2 | 5 | 98.4% | 4.0% |
| Total | 376 | 373 | 3 | 16 | 99.2% | 4.3% |
Table 2.1 Summary of reproducibility study data
6
| Sample
| Description | Site 1 | Site 2 | Site 3 | Total | ||||
|---|---|---|---|---|---|---|---|---|
| # | % | # | % | # | % | # | % | |
| Negative | 30/30 | 100% | 30/30 | 100% | 29/30 | 96.7% | 89/90 | 98.9% |
| Low | 30/30 | 100% | 29/30 | 96.7% | 30/30 | 100% | 89/90 | 98.9% |
| Moderate | 30/30 | 100% | 30/30 | 100% | 29/30 | 96.7% | 89/90 | 98.9% |
| High | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 100/100 | 100% |
Table 2.2 Reproducibility data by sample type
III. Analytical Reactivity (Inclusivity)
Analytical reactivity testing was conducted to ensure that the SensiTox C. difficile Toxin Test can detect multiple ribotypes of toxins A and B. Pooled stool samples that were prescreened and confirmed to be negative for toxins A and B were spiked with purified toxin from clinically important ribotypes and tested in the SensiTox C. difficile Toxin Test. Six ribotypes of toxin A were tested at 15 ng/mL and 8 ribotypes of toxin B were tested at 300 pg/mL. Positive controls comprised of toxins A and B purified from the wildtype strain 087 also were tested. The results, summarized in Table 2.3, demonstrate that all toxin A and B ribotypes tested in the SensiTox C. difficile Toxin Test.
| Toxin
| Target | Ribotype | Toxin A | Toxin B |
|---|---|---|---|
| A | 001 | Detected | Not Detected |
| A | 002 | Detected | Not Detected |
| A | 014 | Detected | Not Detected |
| A | 027 | Detected | Not Detected |
| A | 078 | Detected | Not Detected |
| A | 106 | Detected | Not Detected |
| A | 087 (control) | Detected | Not Detected |
| B | 001 | Not Detected | Detected |
| B | 001 | Not Detected | Detected |
| B | 014 | Not Detected | Detected |
| B | 017 | Not Detected | Detected |
| B | 027 | Not Detected | Detected |
| B | 036 | Not Detected | Detected |
| B | 078 | Not Detected | Detected |
| B | 106 | Not Detected | Detected |
| B | 087 (control) | Not Detected | Detected |
Table 2.3 Analytical reactivity of the SensiTox C. difficile Toxin Test
Analytical Specificity IV.
The analytical specificity of the SensiTox C. difficile Toxin Test was evaluated by testing cultured organisms (bacteria, yeast, viruses) in negative pooled stool or contrived stool containing 15 ng/mL of toxin A and 300 pg/mL of toxin B. Bacteria and yeast were tested at a concentration of 1x10 CFU/mL and each virus was tested at a concentration of 1x10 PFU/mL unless otherwise indicated in Table 2.4. All organisms were tested in triplicate in each study.
None of the organisms cross-react when tested in the SensiTox C. difficile Toxin Test. None of the organisms tested in the presence of contrived pooled stool negatively interfere with the detection of toxins A or B.
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Page 5 of 7
| Species | Concentration
Tested | Species | Concentration
Tested |
|-------------------------------------------|-------------------------|--------------------------------------|-------------------------|
| Adenovirus | 1x105 PFU/mL | Enterovirus | 1x105 PFU/mL |
| Aeromonas hydrophila | 1x106 CFU/mL | Escherichia coli | 1x106 CFU/mL |
| Bacillus cereus | 1x106 CFU/mL | Escherichia coli sero:0157 | 1x106 CFU/mL |
| Bacillus subtilis | 1x106 CFU/mL | Escherichia coli type 026:H4 | 1x106 CFU/mL |
| Bacteroides fragilis | 1x106 CFU/mL | Helicobacter pylori | 1x106 CFU/mL |
| Campylobacter jejuni | 1x106 CFU/mL | Klebsiella oxytoca | 1x106 CFU/mL |
| Campylobacter coli | 1x106 CFU/mL | Norovirus | 7x104 PFU/mL |
| Candida albicans | 1x106 CFU/mL | Peptostreptococcus
anaerobius | 1x106 CFU/mL |
| Clostridium difficile (non-
toxigenic) | 1x106 CFU/mL | Proteus vulgaris | 1x106 CFU/mL |
| Clostridium haemolyticum | 1x106 CFU/mL | Pseudomonas aeruginosa | 1x106 CFU/mL |
| Clostridium novyi | 1x106 CFU/mL | Rotavirus | 1x105 PFU/mL |
| Clostridium perfringens | 1x106 CFU/mL | Salmonella enterica
(typhimurium) | 1x106 CFU/mL |
| Clostridium septicum | 1x106 CFU/mL | Serratia liquefaciens | 1x106 CFU/mL |
| Clostridium sordellii | 1x106 CFU/mL | Shigella dysenteriae | 1x106 CFU/mL |
| Clostridium sporogenes | 1x106 CFU/mL | Shigella flexneri | 1x106 CFU/mL |
| Coxsackie-virus | 1x105 PFU/mL | Shigella sonnei | 1x106 CFU/mL |
| Cytomegalovirus | 1x105 PFU/mL | Staphylococcus aureus | 1x106 CFU/mL |
| Echovirus | 4x104 PFU/mL | Staphylococcus epidermidis | 1x106 CFU/mL |
| Enterobacter aerogenes | 1x106 CFU/mL | Vibrio cholera | 1x106 CFU/mL |
| Enterobacter cloacae | 1x106 CFU/mL | Vibrio parahaemolyticus | 1x106 CFU/mL |
| Enterococcus faecalis | 1x106 CFU/mL | | |
Table 2.4 Organisms tested for analytical specificity
4 The potential for purified Clostridium sordellii toxin to cross-react was not evaluated. It is unknown if C. sordellii toxin concentration in the 106 CFU/mL preparation that was tested falls below the limit of detection for the SensiTox C. difficile Toxin Test.
V. Interfering Substances
Negative pooled stool and contrived pooled stool containing 15 ng/mL of toxin A and 300 pg/mL of toxin B were spiked with potential interferents that can be found in stool. The interferents and the concentrations tested are listed in Table 2.5. None of the potential interferents negatively impact the performance of the SensiTox C. difficile Toxin Test, with the exception of Vancomycin. Vancomycin is not inhibitory at 40 mg/mL but was found to negatively impact the detection of toxins A and B at 50 mg/mL.
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| Potential Interfering Substance | Highest Concentration Tested and Shown
to Not Interfere |
|------------------------------------------------------------|------------------------------------------------------------|
| Nystatin | 500 U/mL (5% w/v) |
| Barium Sulphate | 50 mg/mL(5% w/v) |
| Hydrocortisone | 0.5 mg/mL (5% w/v) |
| Phenylephrine (Preparation H) | 0.1 mg/mL (5% w/v) |
| Calcium Carbonate (Tums) | 10.4 mg/mL (5% w/v) |
| Aluminum Hydroxide / Magnesium Hydroxide (Sunmark antacid) | 1 mg/mL (5% v/v) |
| Loperamide Hydrochloride (Imodium) | 3.3 µg/mL (5% v/v) |
| Bismuth Subsalicylate (Pepto Bismol) | 0.2 mg/mL (5% v/v) |
| Sennosides (Senokot) | 0.6 mg/mL (5% w/v) |
| Metronidazole in DMSO | 50 mg/mL (5% w/v) |
| Vancomycin | 40 mg/mL (4% w/v) |
| Mucin | 50 mg/mL (5% w/v) |
| DMSO | 10% v/v |
| Whole Blood | 40% v/v |
Table 2.5 Interferents and concentrations shown to not interfere with test
Clinical Performance Evaluation
The performance of the SensiTox C. difficile Toxin Test was evaluated in a prospective clinical study performed at three geographically diverse sites in the US using left over de-identified, unpreserved, stool specimens from patients suspected of having C. difficile infection. The performance of the test was evaluated in comparison to the cellular cytotoxicity neutralization assay (CCNA).
The overall clinical performance of the SensiTox C. difficile Toxin Test is summarized in Table 2.6 with the data broken down by clinical study site in Table 2.7. The sensitivity of the SensiTox C. difficile Toxin Test is 90.6% and the specificity is 95.7%.
| Cellular Cytotoxicity Neutralization Assay (CCNA) | ||||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| MultiPath C. | ||||
| difficile Assay | Positive | 87 | 41 | 128 |
| Negative | 9 | 909 | 918 | |
| Total | 96 | 950 | 1046 | |
| Sensitivity [95% CI] | 90.6% [83.1% - 95.0%] | |||
| Specificity [95% CI] | 95.7% [94.2% - 96.8%] | |||
| Positive Predictive Value [95% CI] | 68.0% [59.5% - 75.4%] | |||
| Negative Predictive Value [95% CI] | 99.0% [98.1% - 99.5%] |
Table 2.6 Summary of clinical performance of SensiTox C. difficile Toxin Test
9
| SITE | Samples (%) | CCNA Positive (%) | Percent
(95% Score Confidence Interval) | |
|--------|-------------|-------------------|--------------------------------------------|-----------------------|
| | | | Sensitivity | Specificity |
| Site 1 | 343 (32.8%) | 28 (8.2%) | 89.3% [72.8% - 96.3%] | 95.2% [92.3% - 97.1%] |
| Site 2 | 449 (42.9%) | 42 (9.4%) | 85.7% [72.2% - 93.3%] | 96.1% [93.7% - 97.6%] |
| Site 3 | 254 (24.3%) | 26 (10.2%) | 100% [87.1% - 100%] | 95.6% [92.1% - 97.6%] |
| Total | 1046 | 96 (9.2%) | | |
Table 2.7 Summary of clinical performance by participating clinical study site
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