(73 days)
Not Found
No
The description details a standard Real Time PCR assay with automated extraction and detection. There is no mention of AI or ML algorithms being used for data interpretation or any other part of the process. The data interpretation is described as being performed by the instrument's software, which is typical for PCR systems and does not imply AI/ML.
No
The device is an in vitro diagnostic test intended to aid in the diagnosis of C. difficile infections by detecting specific nucleic acids, not to directly treat or prevent a disease.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "intended for use to aid in the diagnosis of toxigenic Clostridium difficile infections."
No
The device description clearly outlines the use of physical components like the bioMérieux NucliSENS easyMAG automated extractor and the Cepheid SmartCycler II instrument, which are hardware. While software is used for monitoring and interpretation, the device is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use / Indications for Use: The description explicitly states it is an "in vitro diagnostic test" and is "intended for use to aid in the diagnosis of toxigenic Clostridium difficile infections." This directly aligns with the definition of an IVD, which is used to examine specimens from the human body to provide information for diagnosis, monitoring, or treatment.
- Device Description: The description details how the device analyzes biological samples (stool specimens) to detect specific nucleic acids (Clostridium difficile toxin B gene) using laboratory techniques (nucleic acid extraction, PCR amplification, and detection). This is characteristic of an in vitro diagnostic process.
- Anatomical Site: The test is performed on "Stool specimens," which are biological samples taken from the human body.
- Summary of Performance Studies: The performance studies evaluate the device's ability to accurately detect the target in clinical samples, using metrics like sensitivity and specificity, which are standard for evaluating IVDs.
N/A
Intended Use / Indications for Use
The ProGastro™ Cd Assay is a Real Time PCR in vitro diagnostic test for the qualitative detection of toxigenic Clostridium difficile nucleic acids isolated and purified from liquid or soft stool specimens obtained from symptomatic patients. This test targets the Clostridium difficile toxin B gene (tcdB) and is intended for use to aid in the diagnosis of toxigenic Clostridium difficile infections.
Product codes (comma separated list FDA assigned to the subject device)
LLH
Device Description
The ProGastro Cd Assay detects toxigenic Clostridium difficile and an Internal Control by a process of nucleic acid extraction from patient specimens followed by PCR amplification and detection. Following collection of a soft or liquid stool sample from a symptomatic patient, a portion of the sample is diluted in Stool Transport and Recovery (S.T.A.R.) Buffer and the solids separated via centrifugation (Stool Clarification). The Internal Control is added to the sample prior to extraction to monitor for PCR inhibitors that may be present. The nucleic acids from the sample are extracted and purified using the bioMérieux NucliSENS easyMAG automated extractor. Nucleic acids are added to the C. diff Mix for subsequent PCR amplification and detection using the Cepheid SmartCycler II.
The C. diff Mix contains oligonucleotide primers and probes that target the tcdB gene of toxigenic strains of C. diff. The probes are dual-labeled with a reporter dye attached to the 5'-end and a quencher dye attached to the 3'-end (see table below). During PCR amplification the primers and probes anneal to the template (if present) followed by primer extension and template amplification. The 5'-3' exonuclease activity of the Taq polymerase cleaves the probe thus separating the reporter dye from the quencher and generating an increase in fluorescent signal. The amount of fluorescence at any given cycle is dependent on the amount of amplification product present. The SmartCycler II instrument and software monitors the process, interprets the data, and presents a report upon completion.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
patients over two years of age
Intended User / Care Setting
Not Found
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
Performance characteristics of the ProGastro Cd Assay were established during a prospective study at 3 U.S. clinical laboratories from July through October 2008. Samples used for this study were leftover raw stool specimens that were collected for routine Clostridium difficile testing from patients over two years of age by each site. The reference method was tissue culture cytotoxin assay (CTA). A total of 771 raw stool samples were tested with the ProGastro Cd Assay and by CTA.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Performance:
Study type: Prospective study
Sample size: 771 raw stool samples
Key results:
Sensitivity: 91.7% (83.0% - 96.1%) 95% CI
Specificity: 94.7% (92.8% - 96.1%) 95% CI
Discrepant analysis was performed using a predetermined algorithm including a molecular (PCR) test, bidirectional genetic sequencing, enzyme immunoassay (EIA), and culture followed by PCR and bidirectional sequencing.
Reproducibility:
Study type: Reproducibility study
Sample size: 300 (6 samples and 4 controls x 2 operators x 5 days x 3 sites)
Key results: The overall percent agreement with the expected result for the ProGastro Cd Assay was 99.0%.
Additional Reproducibility Study:
Study type: Reproducibility study
Sample size: 90 (intermediate concentration samples)
Key results: The percent positive for the intermediate member across all sites was 42.2%.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity 91.7% (83.0% - 96.1%) 95% CI
Specificity 94.7% (92.8% - 96.1%) 95% CI
Overall percent agreement with the expected result for reproducibility: 99.0%
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
Prodesse, Inc. ProGastro Cd Assay 510(k) Submission
K0906239
Page 1 of 4
Date: April 14, 2009
Attachment D 510(k) SUMMARY
CONTACT
Kristine Schraufnagel Prodesse, Inc. W229 N1870 Westwood Dr. Waukesha, WI 53186
APR 1 6 2009
NAME OF DEVICE
| Trade Name: |
|---|
| Regulation Number: |
| Classification Name: |
ProGastro Cd Assay 21 CFR 866.2660 reagents, Clostridium difficile toxin
PREDICATE DEVICE
K923463 - TechLab C. difficile toxin/Antitoxin Kit K081920 - BD Geneohm CDiff Assay
INTENDED USE
The ProGastro™ Cd Assay is a Real Time PCR in vitro diagnostic test for the qualitative detection of toxigenic Clostridium difficile nucleic acids isolated and purified from liquid or soft stool specimens obtained from symptomatic patients. This test targets the Clostridium difficile toxin B gene (tcdB) and is intended for use to aid in the diagnosis of toxigenic Clostridium difficile infections.
PRODUCT DESCRIPTION
The ProGastro Cd Assay detects toxigenic Clostridium difficile and an Internal Control by a process of nucleic acid extraction from patient specimens followed by PCR amplification and detection. Following collection of a soft or liquid stool sample from a symptomatic patient, a portion of the sample is diluted in Stool Transport and Recovery (S.T.A.R.) Buffer and the solids separated via centrifugation (Stool Clarification). The Internal Control is added to the sample prior to extraction to monitor for PCR inhibitors that may be present. The nucleic acids from the sample are extracted and purified using the bioMérieux NucliSENS easyMAG automated extractor. Nucleic acids are added to the C. diff Mix for subsequent PCR amplification and detection using the Cepheid SmartCycler II.
The C. diff Mix contains oligonucleotide primers and probes that target the tcdB gene of toxigenic strains of C. diff. The probes are dual-labeled with a reporter dye attached to the 5'-end and a quencher dye attached to the 3'-end (see table below). During PCR amplification the primers and probes anneal to the template (if present) followed by primer extension and template amplification. The 5'-3' exonuclease activity of the Taq polymerase cleaves the probe thus separating the reporter dye from the quencher and generating an increase in fluorescent signal. The amount of fluorescence at any given cycle is dependent on the amount of amplification product present. The SmartCycler II instrument and software monitors the process, interprets the data, and presents a report upon completion.
1
| ProGastro Cd Assay 510(k) Submission |
|---|
| Analyte | Gene Targeted | Probe
Fluorophore | Absorbance
Peak | Emission
Peak | Instrument
Channel |
|-----------------------|---------------|----------------------|--------------------|------------------|-----------------------|
| Clostridium difficile | tcdB, Toxin B | FAM | 495 nm | 520 nm | FAM |
| Internal Control | NA | Quasar 670 | 647 nm | 667 nm | Cy5 |
SUBSTANTIAL EQUIVALENCE Clinical Performance
Performance characteristics of the ProGastro Cd Assay were established during a prospective study at 3 U.S. clinical laboratories from July through October 2008. Samples used for this study were leftover raw stool specimens that were collected for routine Clostridium difficile testing from patients over two years of age by each site. The reference method was tissue culture cytotoxin assay (CTA). Demographic details for this patient population are summarized in the following table:
| Age | Number of Subjects
(Percentage of Total) |
|---------------|---------------------------------------------|
| 2 - 5 years | 60 (7.8 %) |
| 6 - 21 years | 163 (21.1%) |
| 22 - 59 years | 292 (37.9%) |
| ≥ 60 years | 256 (33.2%) |
A total of 771 raw stool samples were tested with the ProGastro Cd Assay and by CTA. None of the 771 samples were inhibited when tested with the ProGastro Cd Assay.
| CTA | |||||
|---|---|---|---|---|---|
| Positive | Negative | Total | Comments | ||
| ProGastro | |||||
| Cd Assay | Positive | 66 | 37a | 103 | Sensitivity 91.7% |
| (83.0% - 96.1%) 95% CI | |||||
| Negative | 6b | 662 | 668 | Specificity 94.7% | |
| (92.8% - 96.1%) 95% CI | |||||
| Total | 72 | 699 | 771 |
Discrepant analysis for samples where ProGastro Cd Assay and CTA results were in disagreement was performed using a predetermined algorithm including a molecular (PCR) test (which targeted a different region of the tcdB gene than that of the ProGastro Cd Assay) followed by bidirectional genetic sequencing, enzyme immunoassay (EIA), and culture followed by PCR and bidirectional sequencing.
" 34 samples positive by discrepant analysis. Of these 33 were positive by sequencing, and one (1) was positive by culture followed by sequencing.
6 Four (4) samples positive by discrepant analysis. Of these, one (1) was positive by seguencing, one (1) was positive by EIA, and two (2) were positive by culture followed by sequencing.
2
Reproducibility
The reproducibility of the ProGastro Cd Assay was evaluated at 3 laboratory sites. Reproducibility was assessed using a panel of 6 simulated samples that included medium positive, low positive (near the assay limit of detection) and "high negative" samples. Panels and controls were tested at each site by 2 operators for 5 days (6 samples and 4 controls X 2 operators X 5 days X 3 sites = 300). The overall percent agreement with the expected result for the ProGastro Cd Assay was 99.0%.
| Site 1 | Site 2 | Site 3 | Total | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Panel | |||||||||||||
| Member ID | Agreement | ||||||||||||
| with | |||||||||||||
| expected | |||||||||||||
| result | AVE CT | %CV | Agreement | ||||||||||
| with | |||||||||||||
| expected | |||||||||||||
| result | AVE CT | %CV | Agreement | ||||||||||
| with | |||||||||||||
| expected | |||||||||||||
| result | AVE CT | %CV | Agreement | ||||||||||
| with expected | |||||||||||||
| result (%) | 95% | ||||||||||||
| Confidence | |||||||||||||
| Interval | Overall | ||||||||||||
| Average CT | |||||||||||||
| Value | Overall | ||||||||||||
| %CV | |||||||||||||
| High Negatives1 | 19/20 | 35.2 | 1.52 | 20/20 | 35.3 | 1.05 | 20/20 | 35.5 | 1.30 | 59/60 | |||
| (98.3%) | 91.1% - | ||||||||||||
| 99.7% | 35.3 | 1.35 | |||||||||||
| Low | |||||||||||||
| Positives | 19/20 | 36.2 | 1.04 | 20/20 | 36.2 | 1.30 | 20/20 | 36.3 | 0.75 | 59/60 | |||
| (98.3%) | 91.1% - | ||||||||||||
| 99.7% | 36.2 | 1.05 | |||||||||||
| Medium | |||||||||||||
| Positives | 19/20 | 34.1 | 0.99 | 20/20 | 33.8 | 0.89 | 20/20 | 33.9 | 1.07 | 59/60 | |||
| (98.3%) | 91.1% - | ||||||||||||
| 99.7% | 33.9 | 1.04 | |||||||||||
| Positive | |||||||||||||
| Control | 10/10 | 36.7 | 3.45 | 10/10 | 34.6 | 1.03 | 10/10 | 34.1 | 1.22 | 30/30 | |||
| (100%) | 88.7% - | ||||||||||||
| 100% | 35.1 | 3.88 | |||||||||||
| Positive | |||||||||||||
| Matrix Control | 10/10 | 26.8 | 1.26 | 10/10 | 26.5 | 0.43 | 10/10 | 26.4 | 0.76 | 30/30 | |||
| (100%) | 88.7% - | ||||||||||||
| 100% | 26.6 | 1.05 | |||||||||||
| Negative | |||||||||||||
| Control1 | 10/10 | 35.0 | 0.98 | 10/10 | 35.0 | 1.44 | 10/10 | 35.4 | 1.46 | 30/30 | |||
| (100%) | 88.7% - | ||||||||||||
| 100% | 35.1 | 1.38 | |||||||||||
| Negative | |||||||||||||
| Matrix Control1 | 10/10 | 35.1 | 1.06 | 10/10 | 35.2 | 1.03 | 10/10 | 35.6 | 2.62 | 30/30 | |||
| (100%) | 88.7% - | ||||||||||||
| 100% | 35.3 | 1.80 | |||||||||||
| Total | |||||||||||||
| Agreement | |||||||||||||
| All | 97/100 (97%) | 100/100 (100%) | 100/100 (100%) | 297/300 | |||||||||
| (99.0%) | 97.1% - | ||||||||||||
| 99.7% |
1 Average Ct value is calculated for the Internal Control (IC).
3
Prodesse, Inc. ProGastro Cd Assay 510(k) Submission
An additional reproducibility study was performed to assess samples that were at an intermediate concentration, below the assay's LoD but above the "high negatives" tested during the original reproducibility study. The percent positive for the intermediate member across all sites was 42.2%. This result was expected as the intermediate concentration should be positive in the range of 5 - 95% as the samples were lower concentration than the LoD concentration (≥ 95% positive) and higher than the "high negative" concentration (