ILLUMIGENE C. DIFFICILE, AND ILLUMIPRO-10

{0}------------------------------------------------ | Image: Meridian Bioscience, Inc. logo | Special 510(k) Application illumigene C. difficile, Performance Characteristic Extension | | |---------------------------------------|------------------------------------------------------------------------------------------|----------------------------------------| | | Description: | 510(k) Summary illumigene C. difficile | | | Identification: | Attachment 002 | | | Date: | December 31, 2010 | | 510(k) number: | K110012 | Date of preparation: | December 31, 2010 | |-----------------------|-----------------------------------------------------------------------------------------------------------------------|----------------------|-------------------| | Submitter: | Meridian Bioscience, Inc. | | | | Submitter's address: | 3471 River Hills Drive | | | | | Cincinnati, Ohio 45244 | | | | Contact: | Michelle Smith | | | | Contact number: | (513) 271-3700 | | | | Device name: | illumigene® C. difficile | | | | Common name: | C. difficile DNA Amplification Assay | | | | Classification name: | C. difficile Nucleic Acids | | | | | OMN, CFR Section 866.2660 | | | | Predicate device: | K100818: illumigene® Molecular Diagnostic Test System (illumigene C. difficile DNA Amplification Assay, illumipro-10) | | | | | Model 280050, 610172 | | | | Reference comparator: | Cytotoxic bacterial culture | | | FEB 2 4 2011# Description of the device: The illumigene Molecular Diagnostic Test System is comprised of the illumigene C. difficile DNA Amplification Test Kit, the illumigene C. difficile External Control Kit and the illumipro-10 Automated Isothermal Amplification and Detection System. The illumigene C. difficile DNA amplification assay utilizes loop-mediated isothermal amolification (LAMP) technology to detect the presence of toxigenic C. difficile in patients suspected of having C. difficile associated disease (CDAD). Each illumigene C. difficile assay is completed using an illumigene Sample Preparation Apparatus. Illumigene Reaction Buffer, illumigene C. difficile Test Device, Sample Collection Brush, and illumigene Extraction Tube. Samples are prepared using the Sample Collection Brush and the illumigene Sample Collection Apparatus, target DNA is heat extracted in the Extraction Tube and DNA amplification occurs in the illumigene C. difficile Test Device. The illumipro-10 heats each illumigene C. difficile Test Device containing prepared samples, facilitation of target DNA. When toxigenic C. difficile is present in the patient specific sequence is amplified and Magnesium pyrophosphate is formed. Magnesium pyrophosphate in the reaction mixture. The illumipro-10 detects the change in light transmission mixture created by the precipitating Magnesium pyrophosphate. Sample results are reported as Positive based on the detected change in transmission. The illumigene C. difficile External Control Kit consists of a Positive Control Reagent. External Control reagents are provided to aid the user in detection of reagent deterioration, adverse environmental or test conditions, or variance in operator performance that may lead to test errors. The illumigene C. difficile External Control Kit is required for routine Quality Control. {1}------------------------------------------------ | Image: Meridian Bioscience, Inc. logo | Special 510(k) Application illumigene C. difficile, Performance Characteristic Extension | | |---------------------------------------|------------------------------------------------------------------------------------------|----------------------------------------| | | Description: | 510(k) Summary illumigene C. difficile | | | Identification: | Attachment 002 | | | Date: | December 31, 2010 | # Intended Use: The illumigene C. difficile DNA amplification assay, performed on the illumipro-10, is a qualitative in vitro diagnostic test for the direct detection of toxigenic C. difficile in human stool specimens from pediatric and adult patients suspected of having Clostridium difficile-associated disease (CDAD). The illumigene C. difficile assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect the pathogenicity locus (PaLoc) of toxigenic Clostridium difficile Paloc is a gene segment present in all known toxigenic C. difficile strains. The C. difficile Paloc codes for both the Toxin A gene (tcdA) and the Toxin B gene (tcdB), has conserved border regions, and is found at the same site on the C. difficile genome for all toxigenic strains. The illumigene C. difficile assay detects the Paloc by targeting a partial DNA fragment on the Toxin A gene. The tcdA target region was selected as an intact region remaining in all known A+B+ and A-B+ toxinotypes. illumigene C. difficile is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use. | Characteristic | illumigene™ C. difficile, Revised | illumigene™ C. difficile, K100818 | |-------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Test Format | No Change | DNA Amplification Assay | | Intended Use | | | | DNA Amplification Technology | No Change | Loop-Mediated Isothermal Amplification (LAMP) | | Target Sequences Detected | No Change | Partial DNA fragment on the Toxin A gene of the<br>pathogenicity locus (PaLoc) found in all known<br>strains for toxigenic C. difficile. | | Qualitative/Quantitative | No Change | Qualitative | | Screening, Diagnostic or<br>Identification Test | No Change | Diagnostic | | Specimen Types | | | | Unformed Human Stool | No Change | Yes | | Human Stool in Cary-Blair-based<br>Media | No Change | Yes | | Reagents/Components | illumigene Sample Preparation Apparatus<br>illumigene Reaction Buffer<br>illumigene C. difficile Assay Device<br>illumigene Heat Treatment Tubes<br>Sample Collection Brushes | illumigene Sample Preparation Apparatus<br>illumigene Reaction Buffer<br>illumigene C. difficile Assay Device<br>illumigene Extraction Tubes<br>Sample Collection Brushes | | Extraction | Not Applicable.<br>Sample preparation by heat treatment. DNA<br>Extraction and purification not required. | Manual | | Amplification | No Change | Self-contained and automated | # Comparison to predicated device: {2}------------------------------------------------ | Specimen | Special 510(k) Application illumigene C. difficile, Performance Characteristic Extension | | |----------------|------------------------------------------------------------------------------------------|----------------------------------------| | Description | Description: | 510(k) Summary illumigene C. difficile | | Identification | Identification: | Attachment 002 | | Date | Date: | December 31, 2010 | # Comparison to predicated device: | Characteristic | illumigene™ C. difficile, Revised | illumigene™ C. difficile | |---------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Detection | No Change | Self-contained and automated | | Testing Time | No Change | Approximately 60 minutes | | Calibration | No Change | Not required | | Controls | | | | Inhibition, Assay | No Change | Provided<br><i>illumigene</i> Sample Preparation Apparatus:<br><i>Staphylococcus aureus</i><br><i>illumigene C. difficile</i> Assay Device: <i>Staphylococcus aureus</i> LAMP Primers<br>Adjunct Reagents<br><i>illlumigene C. difficile</i> External Control Kit<br>Catalog 279920 | | External | No Change | <i>illlumigene C. difficile</i> External Control Kit<br>Catalog 279920 | | Extraction | Not Applicable.<br>Sample preparation, including heat treatment monitored by external thermometer and interval timer. Equipment is user supplied. | User Supplied | | Equipment | | | | Instrumentation | No Change | <i>illumipro-10™</i> Automated Isothermal Amplification and Detection System | | | Micropipette 50 µL, 200 µL | Micropipette 50 µL, 200 µL | | | Dry-bath with 12mm Heat Block, 95 C | Dry-bath with 12mm Heat Block, 95 C | | | Interval Timer | Interval Timer | | General Laboratory Equipment | Vortex Mixer | Vortex Mixer | | | Digital Thermometer with Max/Min<br>Temperature Memory | | | Reading Method | No Change | Visible Light Transmission | | Results | | | | C. difficile Toxinotypes Tested | No Change | 0 (A+/B+)<br>III (A+/B+)<br>V (A+/B+)<br>VIII (A-/B+)<br>X (A-/B+)<br>XII (A+/B+)<br>IX/XXIII (A+/B+)<br>INVALID<br>POSITIVE<br>NEGATIVE | | Results Interpretation | No Change | | {3}------------------------------------------------ | Meridian<br>Bioscience, Inc. | Special 510(k) Application illumigene C. difficile, Performance Characteristic Extension | | |------------------------------|------------------------------------------------------------------------------------------|--| | Description: | 510(k) Summary illumigene C. difficile | | | Identification: | Attachment 002 | | | Date: | December 31, 2010 | | # Performance Comparison, Non-clinical Tests: Interference Testing (Reference K100818) Selected drugs and other non-microbial substances that might be present in stool samples from heathly persons or patients suspected of having C. difficile associated disease were added to a natural negative and a contrived positive sample. The natural negative and contrived positive samples were prepared from donor samples and were confirmed negative by cytotoxic bacterial culture. The contrived positive sample was prepared by spiking a confirmed negative sample with toxinogenic C. difficile strain VPI 10463 to 18 CFU/test, slightly above the 16 CFU assay limit of detection for this organism. Potentially interfering substances were added at final concentrations of 5% V/V or greater. Dilution Controls for each sample were prepared by adding a phosphatebuffered saline solution in place of the potentially interfering substance. Each sample was tested in triplicate. The following substances, at the specified saturated solvent/diluents concentrations, do not interfere with illumigene C. difficile test results in the final concentrations listed: Barium sulfate (5 mg/ml), fecal fat (equivalent to 2.65 mg palmitic acids per mL), hemoglobin (as methemoglobin) (3.2 mg/mL), Imodium AD® (0.00667 mg/mL), Kaopectate® (0.87 mg/mL), Metronidazole (12.5 mg/ml, mucin (3.33 mg/mL), Pepto-Bismol® (0.87 mg/mL), Prilosec® (0.5 mg/mL), Tagamet® (0.5 mg/mL), TUMS® (0.5 mg/mL), Vancomycin (12.5 mg/mL), white blood cells (5%V/V), whole blood (5% V/V). # Cross-reactivity Study (Reference K100818) Potentially cross-reactive microorganisms that might be present in stool samples from healthy suspected of having C. difficile associated disease were added to a natural negative and a contrived positive sample. The natural negative and contrived positive samples were prepared from donor samples and were confirmed negative by cytore. The contrived positive sample was prepared by spiking a confirmed negative sample with toxinogenic C. difficile strain VPI 10463 to 18 CFU/test, slightly above the 16 CFU assay limit of detection for this organism. Potentially cross-reactive microorganisms were added at concentrations of 1.2 x 10 / ml (bacteria and fungi) or 1 x 10 / 9 / ml (viruses). Dilution Controls for each sample were prepared by adding a phosphate-buffered saline solution in place of the potentially cross-reactive microorganisms. Each sample was tested in triplicate. The following microorganisms, at the indicated concentrations, do not interfere with illumigene C. difficile test results: Aeromonas hydrophila, Bacteroides fragilis, Campylobacter fetus, Campylobacter jejuni, Candida albicans, Citrobacter frendii, Clostridium perfringens, Enterobacter cloace, Enterococcus faeadis, Escherichia coli, Escherichia coli 0157:H7, Escherichia hermannii, Helicobacter pylori, Klebsiella pneumoniae, Lactococcus lactis, Listeria monocytogenes, Peptostreptococus anaerobius, Plesiomonas shigelloides, Proteus vulganoso, Pseudomonas fluorescens, Salmonella Groups B-E, Serratia marcescens, Shigella boydi, Shigella flexneri, Shigella sonnei, Staphylococus aureus, Staphylococus epidermidis, Yersinia enterocolitica, Adenovirus Types 40 and 41, Coxsackievirus, Echovirus, Rotavirus. #### Performance Comparison, Clinical Tests: Clinical trials for the illumigene C. difficile assay, including the illumipro-10 Automated Isothermal amplification and detection system, were conducted in 2010. Performance characteristics of the illumigene C. difficile assay were determined by comparison to cytotoxic bacterial culture in two separate studies: (1) Patients 2 years of age and above and (2) Patients less than 2 years of age. (1) Patients 2 years of age and above: Independent clinical test sites located in the Midwestern and Southern regions of the United States and the manufacturer evaluated a total of 697 qualified patient samples were collected from 274 (39.3%) males and 419 (60.1%) females. In the case of 4 (0.6%) of the patients, sex was not known. The age groups of patients range from 2 years of age to 96 years. No differences in test performance were observed based on patient age, gender or geographical location. Overall Sensitivity was determined to be 95.2% (95% Cl: 89.2% - 97.9%). Overall Specificity was determined to be 95.3% (95% Cr: 93.2% -96.7%). Subsequent tables show overall assay performance by clinical site and patient age. {4}------------------------------------------------ | | Special 510(k) Application illumigene C. difficile, Performance Characteristic Extension | | |--|------------------------------------------------------------------------------------------|----------------------------------------| | | Description: | 510(k) Summary illumigene C. difficile | | | Identification: | Attachment 002 | | | Date: | December 31, 2010 | #### Table 1. Performance data (Patients 2 years of age and above) | Cytotoxic bacterial<br>culture | illumigene C. difficile | | | | |--------------------------------|-------------------------|----------|--------------|-------| | | Positive | Negative | Invalid*** | Total | | Positive | 99 | 5** | 4 | 108 | | Negative | 27* | 546 | 16 | 589 | | Total | 126 | 551 | 20 | 697 | | | | | 95% CI | | | Sensitivity | 99/104 | 95.2% | 89.2 - 97.9% | | | Specificity | 546/573 | 95.3% | 93.2 - 96.7% | | | Correlation | 645/677 | 95.3% | 93.4 - 96.6% | | | Invalid Rate | 20/697 | 2.9% | | N/A | 15/27 false positive results were positive by another FDA cleared molecular assay. Of the remaining 12 false positive by a FDA cleared assay for the detection of GDH. * * 2/5 false negative results were negative by another FDA cleared molecular assay, *** Invalid results were obtained for 20/697 (2.9%) samples tested. Eleven (1.6%) of the invalids observed were categorized as Assay Invalids, indicative of improper sample preparation, reagent failure, instrument failure. One of the eleven specimens remained invalid after repeat testing from the original sample. | Site | Positive Samples | | | Negative Samples | | | |--------|--------------------------------------------------|---------------|--------------|--------------------------------------------------|---------------|--------------| | | illumigene/<br>Cytotoxic<br>bacterial<br>culture | Sensitivity % | 95% CI | illumigene/<br>Cytotoxic<br>bacterial<br>culture | Specificity % | 95% CI | | Total | 99/104 | 95.2% | 89.2 – 97.9% | 546/573 | 95.3% | 93.2 – 96.7% | | Site 1 | 4/5 | 80.0% | 37.6 – 96.4% | 58/60 | 97.6% | 88.6 – 99.1% | | Site 2 | 12/12 | 100% | 75.7 – 100% | 62/67 | 92.5% | 83.7 – 96.8% | | Site 3 | 20/20 | 100% | 83.9 – 100% | 87/92 | 94.6% | 87.9 – 97.7% | | Site 4 | 8/8 | 100% | 67.6 – 100% | 36/39 | 92.3% | 79.7 – 97.3% | | Site 5 | 55/59 | 93.2% | 83.8 – 97.3% | 303/315 | 96.2% | 93.5 – 97.8% | (2) Patients less than 2 years of age: Independent clinical test sites located in the Midwestern and Southern regions of the United States and the manufacturer evaluated a total of 193 qualified patient samples were collected from 103 (53.4%) males and 90 (46.6%) females. The age groups of patients tested ranged from 0 months. No differences in test performance were observed based on patient age, gender or geographical location. Overall Sensitivity was determined to be 93.3% (95% Cl. 78.7 -98.2%). Overall Specificity was determined to be 96.3% (95% Cl: 92.2% - 98.3%). Subsequent tables show overall assay performance as well as performance by clinical site and patient age. {5}------------------------------------------------ | Image: Meridian Bioscience, Inc. logo | Special 510(k) Application illumigene C. difficile, Performance Characteristic Extension | | |---------------------------------------|------------------------------------------------------------------------------------------|----------------------------------------| | | Description: | 510(k) Summary illumigene C. difficile | | | Identification: | Attachment 002 | | | Date: | December 31, 2010 | #### Table 3. Performance data (Patients less than 2 years of age) | Cytotoxic bacterial<br>culture | illumigene C. difficile | | | | |--------------------------------|-------------------------|----------|--------------|-------| | | Positive | Negative | Invalid*** | Total | | Positive | 28 | 2** | 1 | 31 | | Negative | 6* | 156 | 0 | 162 | | Total | 34 | 158 | 1 | 193 | | | | | 95% CI | | | Sensitivity | 28/30 | 93.3% | 78.7 - 98.2% | | | Specificity | 156/162 | 96.3% | 92.2 - 98.3% | | | Correlation | 184/192 | 95.8% | 92.0 - 97.9% | | | Invalid Rate | 1/193 | 0.5% | N/A | | * 3/6 false positive results were positive by another assay. Of the remaining 3 false positive results, all were positive by a FDA cleared assay for the detection of GDH. ** 1/2 false negative results were negative by another FDA cleared molecular assay. - *** Invalid results were obtained for 1/193 (0.5%) samples tested. The invalid observed was an Assy Invalid, indicative of improper sample preparation, reagent failure, instrument failure. The specimen remained invalid after repeat testing from the original sample, #### Table 4. Performance characteristics by site (Patients less than 2 years of age) | Positive Samples | | | Negative Samples | | | | |------------------|---------------------------------------------------|---------------|------------------|---------------------------------------------------|---------------|--------------| | Site | illumigene /<br>Cytotoxic<br>bacterial<br>culture | Sensitivity % | 95% CI | illumigene /<br>Cytotoxic<br>bacterial<br>culture | Specificity % | 95% CI | | Total | 28/30 | 93.3% | 78.7 - 98.2% | 156/162 | 96.3% | 92.2 - 98.3% | | Site 1 | 8/8 | 100% | 67.6 - 100% | 48/49 | 98.0% | 89.3 - 99.6% | | Site 2 | 20/22 | 90.9% | 72.2 - 97.5% | 105/109 | 96.3% | 90.9 - 98.6% | | Site 4 | 0/0 | N/A | N/A | 2/3 | 66.7% | 20.8 - 93.9% | | Site 5 | 0/0 | N/A | N/A | 1/1 | 100% | 20.7 - 100% | #### Table 5. Overall results by patient age | | Positive Samples | | | Negative Samples | | | |------------------|--------------------------------------|---------------|--------------|--------------------------------------|---------------|--------------| | Patient age | illumigene /<br>Toxigenic<br>culture | Sensitivity % | 95% CI | illumigene /<br>Toxigenic<br>culture | Specificity % | 95% CI | | < 2 years | 28/30 | 93.3% | 78.7 - 98.2% | 156/162 | 96.3% | 92.2 - 98.3% | | ≥ 2 to 12 years | 10/11 | 90.9% | 62.3 - 98.4% | 75/79 | 94.9% | 87.7 - 98.0% | | > 12 to 21 years | 5/5 | 100% | 56.6 - 100% | 53/56 | 94.6% | 85.4 - 98.2% | | > 21 years | 83/87 | 95.4% | 88.8 - 98.2% | 417/437 | 95.4% | 93.0 - 97.0% | | Age Unknown | 1/1 | 100% | 20.7 - 100% | 1/1 | 100% | 20.7 - 100% | {6}------------------------------------------------ | Image: Meridian Bioscience, Inc. logo | Special 510(k) Application illumigene C. difficile, Performance Characteristic Extension | | |---------------------------------------|------------------------------------------------------------------------------------------|----------------------------------------| | | Description: | 510(k) Summary illumigene C. difficile | | | Identification: | Attachment 002 | | | Date: | December 31, 2010 | # Analytical Sensitivity (Reference K100818) The analytical sensitivity of this assay for C. difficile was based on 20 replicates for each measurand and with a stated probability (e.g., 95% or 19/20 positive replicates) of obtaining positive responses at the following levels of the measurands: | Strain ID | Toxinotype | Phenotype | LoD/Test | |-----------|------------|-----------|-------------| | VPI 10463 | 0 | A+/B+ | 4 CFU/test | | 2007431 | III (NAP1) | A+/B+ | 32 CFU/test | | CF1 | VIII | A-/B+ | 64 CFU/test | | 2006240 | V (NAP7) | A+/B+ | 32 CFU/test | | B18 | III | A+/B+ | 64 CFU/test | | 2007858 | IX/XXIII | A+/B+ | 32 CFU/test | | 8864 | X | A-/B+ | 64 CFU/test | Additional C. difficile stock cultures from different sources were tested and produced positive reactions at 64 CFU/test with illumigene C. difficile. Strains and toxinotypes tested were as follows: Type 0 Strains: 10463, 2005070, 2005257, 2008029, 2008162, 2008341, 2008351, 2009099, B1, G1, J7, K12, Y1; Type III Strains: 2004052, 2004118, 2007431, B17, Bl8; Type V Strains: 2005325, 2006240, 2009018, 2009065, BK6; Type VIII Strains: 43598, 2008016, CF1; Type X Strains: 8864; Type XII Strains: 2007435; Type IX/XIII Strains: 2007858; Unknown Strains: 2009132, 2009277. ### Reproducibility (Reference K100818) Blind coded panels of 10 samples were supplied to three independent laboratories for precision studies. Samples were randomly sorted within each panel to mask sample included contrived samples manufactured at the assay limit of detection (n = 3) and just below the limit of blank (i.e., high negative sample, n = 3). The panels also included uncharacterized positive (n = 2) and negative (n = 2) samples. Testing was performed by different operators at each site on the same day (intra-assay variability) for five days (inter-assay variability). Three lots of illumigene C difficile were used in this study. The results are given in the table below: | | Site 1<br>Percent agreement | | Site 2<br>Percent agreement | | Site 3<br>Percent agreement | | Total<br>Percent agreement | | |---------------|-----------------------------|------|-----------------------------|------|-----------------------------|------|----------------------------|------| | Sample Type | | | | | | | | | | Negative | 20/20 | 100% | 20/20 | 100% | 19/19**** | 100% | 59/59 | 100% | | High Negative | 25/30 | 83% | 29/30 | 97% | 28/30 | 93% | 82/90 | 91% | | Low Positive | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 90/90 | 100% | | Positive | 20/20 | 100% | 20/20 | 100% | 20/20 | 100% | 60/60 | 100% | **** 1 specimen generated an instrument invalid test result. # Conclusions The illumigene C. difficile assay used in conjuntion with the illumipro-10 can be used to detect toxigenic C. difficile in human stool samples from pediatric and adult patients. The test is diagnostic for toxigenic C. difficile infection. {7}------------------------------------------------ Image /page/7/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 emblem featuring a stylized representation of three human profiles facing to the right, with flowing lines suggesting movement or connection. Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 Meridian Bioscience, Inc. c/o Ms. Michelle L. Smith Director Quality Systems 3471 River Hills Drive Cincinnati, OH 54244 FEB 2 4 2011 Re: K110012 Trade/Device Name: illumigene™ C. difficile DNA Amplification Assay Regulation Number: 21 CFR § 866.2660 Regulation Name: Microorganism differentiation and identification device Regulatory Class: Class I Product Codes: OMN Dated: December 31, 2010 Received: January 3, 2011 Dear Ms. Smith: We have reviewed your Section 510(k) premarket notification of intent to market the indication indication we nave reviewed your becally be device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate 101 use stated in the encreation to togals annual date of the Medical Device American on to comments provided 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). and Cosment Act (Act) that do not require subject to the general controls provisions of the Act. The Tou may, therefore, market the 80 ress, and include requirements for annual registration, listing of general controls provisions a ractice, labeling, and prohibitions against misbranding and adulteration. If your device is classified (see above) into class II (Special Controls), it may be subject to such If your device is Classified (see acove) nike one affecting your device can be found in Title 21, 2011 in Title 21, 2011 additional collions. Existing major regulations are 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 Please be advised that FDA s issualic of a sudentify with other requirements of the Act that FDA has made a determination that your device only of the Foreles. You must that FDA has made a decemination and regulations administered by other Federal and listing or any Federal statures and regulations connisting, but not limited to: registration and listing (21 comply with all the Act's requirements, 201 - 1000 - adject device report comply with all the Act 3 requirements morams) of in the reporting (reporting of CFR Part 807); labeling (21 CFR Parts (21 and 809); and monufacturing practice CFK Part 807), labeling (21 CFR 803); and good manufacturing practice {8}------------------------------------------------ # Page 2 - Ms. Smith requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter requirements as see gin 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 Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance. 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 (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html. Sincerely yours, 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 {9}------------------------------------------------ # Indication(s) for Use Form # 510(k) Number (if known): K-1 0 D I Z Device Name: illumigene Molecular Diagnostic Test System (illumigene® C. difficile DNA Amplification Assay, illumipro-10™) # Indications for Use: The illumigene C. difficile DNA amplification assay, performed on the illumipro-10, is a qualitative in vitro diagnostic test for the direct detection of toxigenic C. difficile in human stool specimens from pediatric and adult patients suspected of having Clostridium difficile-associated disease (CDAD). The illumigene C. difficile assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect the pathogenicity locus (PaLoc) of toxigenic Clostridium difficile PaLoc is a gene segment present in all known toxigenic C. difficile strains. The C. difficile PaLoc codes for both the Toxin A gene (tcdA) and the Toxin B gene (tcdB), has conserved border regions, and is found at the same site on the C. difficile genome for all toxigenic strains. The illumigene C. difficile assay detects the Paloc by targeting a partial DNA fragment on the Toxin A gene. The tcdA target region was selected as an intact region remaining in all known A+B+ and A-B+ toxinotypes. illumigene C. difficile is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use. Prescription Use _____________________________________________________________________________________________________________________________________________________________ (Part 21 CFR 801 Subpart D) Over-The-Counter Use _ (21 CFR 801 Subpart C) AND/OR (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED) Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD) Led Poly on Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety 510(k) K110012