(70 days)
VIDAS® C. difficile Toxin A & B (CDAB) assay is an automated test for use on the VIDAS instruments for the qualitative detection of Clostridium difficile toxin A and toxin B in stool specimens using the ELFA technique (Enzyme-Linked Flurorescent Assay). The VIDAS C. difficile toxin A & toxin B (CDAB) assay is an aid for diagnosing Clostridium difficile associated disease (CDAD).
VIDAS® C. difficile Toxin A & B (CDAB) assay is an automated test for use on the VIDAS instruments for the qualitative detection of Clostridium difficile toxin A and toxin B in stool specimens using the ELFA technique (Enzyme-Linked Fluorescent Assay). The assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR), a pipette tip-like device, serves as the solid phase as well as the pipetting device for the assay. The assay reagents are ready-to-use and pre-dispensed in the sealed reagent strips (STRs). Each of the four reaction steps are performed automatically by the VIDAS instrument. The reaction medium (sample/conjugate mixture) is cycled in and out of the SPR several times. Each step is followed by a wash cycle which eliminates unbound components. At the end of the VIDAS CDAB assay, results are automatically calculated by the VIDAS instrument. A test value as well as the qualitative result (positive, negative or equivocal) are provided on the result sheet for each sample.
Here's a breakdown of the acceptance criteria and study information for the VIDAS® CDAB Assay based on the provided text, structured according to your request:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document describes a 510(k) submission for a device claim extension of the VIDAS® CDAB Assay, not an initial submission where acceptance criteria would be explicitly detailed. Therefore, explicit "acceptance criteria" for the new claim extension are not clearly laid out as distinct pass/fail thresholds in the document.
Instead, the performance data is presented comparatively against a predicate device (the original VIDAS CDAB Assay, K072138, and Premier Toxins A&B) and a "gold standard" (CTA - Cytotoxicity Assay). The implication is that the new claim extension is acceptable if its performance is comparable to or better than the predicate and clinically acceptable as an aid in diagnosis.
Given this, I will infer the "acceptance criteria" from the predicate device's performance, as the purpose of a 510(k) is to demonstrate substantial equivalence.
| Performance Metric | Acceptance Criteria (Inferred from Predicate/Clinical Acceptability) | Reported Device Performance (VIDAS® CDAB Assay) |
|---|---|---|
| Non-clinical/Analytical | ||
| Precision/Reproducibility | Comparable to predicate | Total precision: 7.4 – 37.6% CV |
| Inter-assay precision: 6.8 – 26.8% CV | ||
| Intra-assay precision: 2.9 – 26.3% CV | ||
| C. difficile strain types (A+/B+) | 100% detection for A+/B+ strains | 100% (23/23) |
| C. difficile strain types (A-/B+) | High detection rate for A-/B+ strains | 83% (15/18*) *Note: 3 equivocal results |
| Limit of Detection (stool) | Comparable to predicate | Toxin A at ≥ 7.73 ng/mL; Toxin B at ≥ 4.55 ng/mL |
| Drug Interference | No significant interference from common drugs | Evaluated (Vancomycin, Metronidazole, Loperamide, Bismuth subsalicylate, Salicylate, Barium sulfate, Imodium, Pepto-Bismol) - specific results not quantified/detailed in summary |
| Clinical Studies (vs. CTA) | ||
| Sensitivity | Clinically acceptable for diagnostic aid (e.g., >80-85%) | 88.3%; 95% CI: 81.2 – 93.5% |
| Specificity | High (e.g., >95-98%) | 99.8%; 95% CI: 99.2 – 99.9% |
| Positive Predictive Value (PPV) | High (e.g., >90%) | 98.1%; 95% CI: 93.5 – 99.8% |
| Negative Predictive Value (NPV) | High (e.g., >90%) | 98.4%; 95% CI: 97.3 – 99.1% |
| Clinical Studies (vs. Predicate) | ||
| Positive Agreement | High agreement with predicate (e.g., >80%) | 81.3%; 95% CI: 73.4 – 87.6% |
| Negative Agreement | Very high agreement with predicate (e.g., >95%) | 99.5%; 95% CI: 98.8 – 99.9% |
| Global Agreement | High overall agreement with predicate (e.g., >90%) | 97.1%; 95% CI: 95.9 – 98.1% |
| Additional Site Performance | ||
| Sensitivity (vs. CTA) | Clinically acceptable | 88.0%; 95% CI: 68.8 – 97.5% |
| Specificity (vs. CTA) | High | 95.1%; 95% CI: 86.3 – 99.0% |
| Total Agreement (vs. CTA) | High | 93.0%; 95% CI: 85.4 – 97.4% |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 1011 specimens
- Data Provenance: Clinical study conducted in the USA and Europe. The document states it's a "summary of the non-clinical and clinical test results," implying that these are the results from the specific studies conducted to support the device. The term "retrospective or prospective" is not explicitly stated, but clinical studies for diagnostic devices typically involve prospective sample collection or the use of remnant/archived samples. Given the nature of a 510(k) for a claim extension, it's highly likely to be a combination, potentially including data from the original submission (K072138) and new data for the extension, though this is not explicitly clarified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth for the clinical studies was primarily established using a "CTA" (Cytotoxicity Assay). This is a laboratory-based method, not dependent on human expert interpretation in the same way as, for example, a radiologist reading an image. Therefore, information about the "number of experts" or their specific "qualifications" for establishing this type of ground truth is not applicable and not provided in the document.
4. Adjudication Method for the Test Set
Not applicable. The ground truth (CTA) is a laboratory assay result, not subject to human interpretation discrepancies that would require an adjudication method.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is more common for imaging diagnostics where human interpretation is a primary component of the diagnostic process. The VIDAS® CDAB Assay is an automated immunoassay.
6. Standalone (Algorithm Only) Performance
Yes, the performance data presented (Sensitivity, Specificity, PPV, NPV, and agreement rates) is the standalone performance of the VIDAS® CDAB Assay. It's an automated test, meaning its output is directly compared to the ground truth (CTA) without human intervention in its result generation or interpretation for the purpose of primary performance calculation. The "aid in diagnosing" phrasing implies a human-in-the-loop for final clinical decision-making, but the performance metrics themselves are standalone.
7. Type of Ground Truth Used
The primary ground truth used for the clinical studies was the Cytotoxicity Assay (CTA). This is a laboratory-based assay considered a reference standard for detecting C. difficile toxins.
8. Sample Size for the Training Set
The document does not explicitly mention "training set" or "validation set" sizes, which are typically associated with machine learning or algorithmic development. For an immunoassay like VIDAS, the "development" or "optimization" process involves various analytical studies (e.g., reagent optimization, buffer formulations) and may use smaller, targeted panels of positive and negative samples, but these are not typically referred to as a "training set" in the context of large-scale clinical data for algorithmic learning. The clinical performance data presented refers to the test set used for validation.
9. How the Ground Truth for the Training Set Was Established
Since an explicit "training set" is not mentioned in the context of an algorithm or machine learning for this immunoassay device, the method for establishing its ground truth is not applicable. The device's underlying principles are based on biochemical reactions (ELFA) and not learned from large datasets in the same way an AI algorithm would be.
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Korn931
JUN 1 1 2008
510(k) SUMMARY
VIDAS® CDAB Assay
A. Submitter Information Submitter's Name: bioMérieux, Inc. 595 Anglum Road Address: Hazelwood, MO 63042 Contact Person: Nikita S. Mapp Associate Staff Regulatory Affairs Specialist Phone Number. 314-731-7474 314-731-8689 Fax Number. Date of Preparation: April 1, 2008 B. Device Name Trade Name: VIDAS® CDAB Clostridium difficile Enzyme Immunoassay Common Name: 21 CFR 866.2660, Product Code LLH Classification Name: Reagents, Clostridium Difficile Toxin C. Predicate Device Name VIDAS® C. difficile Toxin A & B (CDAB) assay [K072138] Trade Name:
D. Device Description
VIDAS® C. difficile Toxin A & B (CDAB) assay is an automated test for use on the VIDAS instruments for the qualitative detection of Clostridium difficile toxin A and toxin B in stool specimens using the ELFA technique (Enzyme-Linked Fluorescent Assay).
The assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR), a pipette tip-like device, serves as the solid phase as well as the pipetting device for the assay. The assay reagents are ready-to-use and pre-dispensed in the sealed reagent strips (STRs). The individual kit components are described in detail on the following pages.
Each of the four reaction steps are performed automatically by the VIDAS instrument. The reaction medium (sample/conjugate mixture) is cycled in and out of the SPR several times. Each step is followed by a wash cycle which eliminates unbound components.
- Toxin A and/or toxin B present in the sample binds with the anti-toxin A antibodies Step 1: (rabbit polyclonal) and anti-toxin B antibodies (mouse monoclonal) coated on the interior wall of the SPR.
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- Binding between toxin A and anti-toxin A antibodies (mouse monoclonal) Step 2: conjugated with biotin. Binding between toxin B and anti-toxin B antibodies (mouse monoclonal) conjugated with biotin.
- The presence of biotin is detected by incubation with streptavidin conjugated with Step 3: alkaline phosphatase.
- Two detection steps are performed successively Alkaline phosphatase catalyzes Step 4: the hydrolysis of the substrate (4-Methyl-umbellifery) phosphate) into a fluorescent product (4-Methyl-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence is proportional to the quantity of toxin A and/or toxin B present in the sample.
At the end of the VIDAS CDAB assay, results are automatically calculated by the VIDAS instrument. A test value as well as the qualitative result (positive, negative or equivocal) are provided on the result sheet for each sample.
E. Intended Use
VIDAS® C. difficile Toxin A & B (CDAB) assay is an automated test for use on the VIDAS instruments for the qualitative detection of Clostricium difficile toxin A and toxin B in stool specimens using the ELFA technique (Enzyme-Linked Fluorescent Assay). The VIDAS C. difficile toxin A & toxin B (CDAB) assay is an aid for diagnosing Clostridium difficile associated disease (CDAD).
| Item | Device[VIDAS CDAB Assay - Claim Extension] | Predicate[VIDAS CDAB Assay - K072138] |
|---|---|---|
| Intended Use | An automated test for use on the VIDASinstruments for the qualitative detection ofClostridium difficile toxin A and toxin B instool specimens using the ELFA technique(Enzyme-Linked Fluorescent Assay). TheVIDAS C. difficile toxin A & toxin B (CDAB)assay is an aid for diagnosing Clostridiumdifficile associated disease (CDAD). | An automated test for use on theVIDAS instruments for thequalitative detection of Clostridiumdifficile toxin A and toxin B in stoolspecimens using the ELFAtechnique (Enzyme-LinkedFluorescent Assay). |
| Indications for Use | Interpretation of test results should bemade taking into consideration the patienthistory and any other tests performed. | Same |
| Specimen | Stool | Same |
| Assay Principle | Enzyme immunoassay | Same |
| Automated | Automated assay | Same |
| Assay Technique | Enzyme-Linked Fluorescent Assay (ELFA) | Same |
| Antibodies | capture Anti-Toxin A (rabbit polyclonal)Anti-Toxin B (mouse monoclonal) | Same |
| detection Anti-Toxin A (mouse monoclonal)Anti-Toxin B (mouse monoclonal) |
F. Technological Characteristics Summary
A comparison of the similarities and differences of the assays is presented in the table below.
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| Item | Device[VIDAS CDAB Assay – Claim Extension] | Predicate[VIDAS CDAB Assay – K072138] |
|---|---|---|
| Conjugate | Mouse monoclonal anti-toxin A and anti-toxin B antibodies conjugated with biotin | Same |
| Sample Volume | 200 µl (liquid stool)200 mg (semi-solid & solid stools) | Same |
| Assay Time | ~75 minutes | Same |
G. Performance Data
.
A summary of the non-clinical and clinical test results are presented in the table below.
| Item | Device[VIDAS CDAB] | Predicate[Premier Toxins A&B] |
|---|---|---|
| Non-clinical (Analytical) Comparison | ||
| Precision/Reproducibility | 6 pools of samples tested in duplicate over6 daystotal precision: 7.4 – 37.6% CVinter-assay precision: 6.8 – 26.8% CVintra-assay precision: 2.9 – 26.3% CV | Same |
| C. difficile strain types | A+/B+ 100% (23/23) | Same |
| A-/B+ 83% (15/18*) | ||
| *3 of the A-/B+ strains gave equivocalresults | ||
| Limit of Detection (stool) | Toxin A at level of ≥ 7.73 ng/mL; | Same |
| Toxin B at level of ≥ 4.55 ng/mL | ||
| Drug Interference | Vancomycin; Metronidazole; Loperamide; | Not evaluated in K072138 |
| Bismuth subsalicylate; Salicylate; Barium | ||
| sulfate; Imodium tablet & liquid; Pepto-Bismol tablet & liquid | ||
| Clinical Studies Comparison | ||
| Number of specimen | 1011 specimens | Same |
| Study Site(s) | USA and Europe | Same |
| Results | versus CTA (all sites) | Submitted in K072138 |
| Sensitivity: 88.3%; 95% CI: 81.2 – 93.5% | ||
| Specificity: 99.8 %; 95% CI: 99.2 – 99.9% | ||
| PPV: 98.1%; 95% CI: 93.5 – 99.8% | ||
| NPV: 98.4 %; 95% CI: 97.3 – 99.1% | ||
| additional testing w/external site | N/A | |
| Sensitivity: | 88.0%; 95% CI: 68.8 – 97.5% | |
| Specificity: | 95.1%; 95% CI: 86.3 – 99.0% | |
| Total Agreement: | 93.0%; 95% CI: 85.4 – 97.4% | |
| Results | versus Predicate (all sites) | Same |
| Positive Agreement: 81.3%; 95% CI: 73.4 – 87.6% | ||
| Negative Agreement: 99.5%; 95% CI: 98.8 – 99.9% | ||
| Global Agreement: | 97.1%; 95% CI: 95.9 – 98.1% |
:
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H. Conclusion
The VIDAS® CDAB Assay is substantially equivalent to the VIDAS CDAB Assay [K072138].
The 510(k) summary includes only information that is also covered in the body of the 510(k). The summary does not contain any puffery or unsubstantiated labeling claims. The summary does not contain any raw data, i.e., contains only summary data. The summary does not contain any trade secret or confidential commercial information. The summary does not contain any patient identification information.
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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The eagle is black, and the text is also black. The background is white.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUN 1 1 2008
Ms. Nikita S. Mapp Associate Staff Regulatory Affairs Specialist bioMérieux, Inc. 595 Anglum Road Hazelwood, MO 63042
K080931 Trade/Device Name: VIDAS® CDAB Assay Regulation Number: 21 CFR § 866.2660 Regulation Name: Microorganism Differentiation and Identification Device Regulatory Class: I Product Code: LLH Dated: April 1st, 2008 Received: April 2nd, 2008
Dear Ms. Mapp:
Re:
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 idications 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 Federall Food, Dr to 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, isting 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 additions FDA may publish further announcements concerning your device in the Federal Depister.
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 practive requirements as set forth in the quality systems (QS) regulation (21 CFR Party 200).
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Page 2 -
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 yours,
Sally attayma
Sally A. Hoivat, 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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Indications for Use
K080931 510(k) Number (if known):
Device Name: VIDAS® C. difficile Toxin A & B (CDAB) Assay
Indications For Use: VIDAS® C. difficile Toxin A & B (CDAB) assay is an automated test for use on the VIDAS instruments for the qualitative detection of Clostridium difficile toxin A and toxin B in stool specimens using the ELFA technique (Enzyme-Linked Flurorescent Assay). The VIDAS C. difficile toxin A & toxin B (CDAB) assay is an aid for diagnosing Clostridium difficile associated disease (CDAD).
Prescription Use X (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Ludlow W. Poole
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K08093/
§ 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.