(90 days)
The illumigene Pertussis DNA Amplification Assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direct detection of Bordetella pertussis in human nasopharyngeal swab samples taken from patients suspected of having respiratory tract infection attributable to Bordetella pertussis.
The illumigene Pertussis DNA Amplification Assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to pertussis by targeting the IS481 insertional element of the B. pertussis genome. The 18481 insertional element can also be found in B. holmesii and some B. bronchiseptica strains. Respiratory infections with B. pertussis, B. holmesii or B. bronchiseptica may yield positive test results infection may cause clinical illness similar to B. pertussis, and mixed outbreaks involving both B. pertussis and B. holmesii infection have been reported. Additional testing should be performed if necessary to differentiate B. holmesii and B. pertussis. B. bronchiseptica is a rare cause of infection in humans. When clinical factors suggest that B. pertussis may not be the cause of respiratory infection, other clinically appropriate investigation(s) should be carried out in accordance with published guidelines.
Negative results for the illumigene Pertussis DNA Amplification Assay do not precude Bordetella pertussis infection and positive results do not rule out co-infection with other respiratory pathogens. Results from the illumigene Pertussis assay should be used in conjunction with information obtained during the patient's clinical evaluation as an aid in diagnosis of B. pertussis infection and should not be used as the sole basis for treatment or other patient management decisions.
illumigene Pertussis DNA Amplification Assay is intended for use in hospital, reference or state laboratory settings. The device is point-of-care use.
The illumigene Pertussis DNA Amplification Assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direct detection of Bordetella pertussis in human nasopharyngeal swab samples. The assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to target the IS481 insertional element of the B. pertussis genome.
Here's an analysis of the provided text regarding the illumigene Pertussis DNA Amplification Assay, structured to answer your questions about acceptance criteria and the supporting study:
The provided document is an FDA 510(k) clearance letter for the illumigene Pertussis DNA Amplification Assay. It primarily outlines the device's intended use and FDA's determination of substantial equivalence. Crucially, this document does NOT contain detailed information about the acceptance criteria or the specific study results proving the device meets those criteria.
Generally, for an in vitro diagnostic (IVD) like this, acceptance criteria would involve performance metrics such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) compared to a reference standard. The study data would then quantify these metrics.
Since the provided text does not contain this information, I will indicate where the information is not provided by the document.
Acceptance Criteria and Study Details for illumigene Pertussis DNA Amplification Assay
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (from study protocol) | Reported Device Performance (from study results) |
|---|---|---|
| Sensitivity | Not provided in this document | Not provided in this document |
| Specificity | Not provided in this document | Not provided in this document |
| Positive Predictive Value (PPV) | Not provided in this document | Not provided in this document |
| Negative Predictive Value (NPV) | Not provided in this document | Not provided in this document |
| Limit of Detection (LoD) | Not provided in this document | Not provided in this document |
| Cross-Reactivity | Not provided in this document | Not provided in this document |
| Interfering Substances | Not provided in this document | Not provided in this document |
2. Sample size used for the test set and the data provenance
- Sample Size for Test Set: Not provided in this document.
- Data Provenance (e.g., country of origin of the data, retrospective or prospective): Not provided in this document. Typically, clinical studies for IVDs involve prospective collection of samples from diverse geographic locations to ensure generalizability.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is typically relevant for image-based diagnostic devices or those requiring expert interpretation. For a DNA amplification assay, the "ground truth" for the test set is established by a reference method (e.g., culture, another highly sensitive PCR method with sequencing confirmation). Therefore, the concept of "experts establishing ground truth" in the same way it would apply to imaging interpretation is not directly applicable here.
- Number of experts: Not applicable in the context of this type of diagnostic test's ground truth.
- Qualifications of experts: Not applicable.
4. Adjudication method for the test set
As the ground truth for a DNA amplification assay is typically established through laboratory reference methods (e.g., bacterial culture, validated PCR with sequencing), an "adjudication method" involving human readers (like 2+1, 3+1 for imaging) is not applicable. Discrepancies would be resolved by retesting or using a higher-level confirmatory test.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance
- MRMC Study: No, an MRMC study is not applicable for a standalone in vitro diagnostic (IVD) test like a DNA amplification assay. This type of study is designed for diagnostic tools that involve human interpretation, such as medical imaging analysis, often comparing AI-assisted performance against unassisted human performance. The illumigene Pertussis DNA Amplification Assay is a laboratory test that provides a quantitative or qualitative result directly, without requiring human "reading" in the same diagnostic sense.
6. If a standalone (i.e. algorithm only, without human-in-the-loop performance) was done
Yes, for an IVD like the illumigene Pertussis DNA Amplification Assay, the performance data presented to the FDA always represents the standalone performance of the device (i.e., "algorithm only" in the context of an automated assay). The device generates a result which is then interpreted by a healthcare professional in conjunction with clinical information, but the core performance characteristics (sensitivity, specificity) are intrinsic to the assay itself.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
For molecular diagnostic assays like the illumigene Pertussis DNA Amplification Assay, the ground truth is typically established using:
- Reference Culture: For bacterial infections, culture is often considered the gold standard, although its sensitivity for Bordetella pertussis can be low, especially in later stages of infection.
- Another highly sensitive and specific molecular method (e.g., a validated laboratory-developed PCR test or a previously cleared FDA PCR test), often with Sanger sequencing confirmation: This is frequently used as a composite reference standard when culture sensitivity is a concern.
The specific ground truth method used for this device is not provided in this document.
8. The sample size for the training set
- Training Set Sample Size: Not provided in this document. For molecular diagnostic assays, there isn't a "training set" in the machine learning sense. Instead, there are often development and validation phases where different sets of samples (sometimes called analytical and clinical validation sets) are used to establish performance. The term "training set" is more applicable to AI/ML devices.
9. How the ground truth for the training set was established
As mentioned in point 8, the concept of a "training set" with ground truth in the AI/ML context doesn't directly apply here. For the various validation studies (analytical and clinical), ground truth would be established by the reference methods described in point 7. The specific methodology for establishing ground truth for any development or validation samples is not provided in this document.
In summary: The provided FDA 510(k) clearance document confirms the device's legal market entry based on substantial equivalence for its stated Indications for Use. However, it does not detail the specific performance acceptance criteria or the comprehensive study design and results (e.g., sample sizes, ground truth methodology, actual sensitivity/specificity values) that were submitted to justify that equivalence. Such detailed information would typically be found in the full 510(k) summary or the device's instructions for use.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
MERIDIAN BIOSCIENCE, INC. SUSAN ROLIH EVP, REGULATORY AND QUALITY SYSTEMS 3471 RIVER HILLS DR CINCINNATI OH 45244
November 9, 2015
Re: K152285
Trade/Device Name: Illumigene Pertussis DNA Amplification Assav Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: II Product Code: OZZ Dated: August 11, 2015 Received: August 12, 2015
Dear Ms. Rolih:
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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Kristian M. 2015.11.09 Roth -S | | | 15:13:24 -05'00'
For: Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K152285
Device Name illumigene Pertussis DNA Amplification Assay
Indications for Use (Describe)
INTENDED USE
The illumigene Pertussis DNA Amplification Assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direct detection of Bordetella pertussis in human nasopharyngeal swab samples taken from patients suspected of having respiratory tract infection attributable to Bordetella pertussis.
The illumigene Pertussis DNA Amplification Assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to pertussis by targeting the IS481 insertional element of the B. pertussis genome. The 18481 insertional element can also be found in B. holmesii and some B. bronchiseptica strains. Respiratory infections with B. pertussis, B. holmesii or B. bronchiseptica may yield positive test results infection may cause clinical illness similar to B. pertussis, and mixed outbreaks involving both B. pertussis and B. holmesii infection have been reported. Additional testing should be performed if necessary to differentiate B. holmesii and B. pertussis. B. bronchiseptica is a rare cause of infection in humans. When clinical factors suggest that B. pertussis may not be the cause of respiratory infection, other clinically appropriate investigation(s) should be carried out in accordance with published guidelines.
Negative results for the illumigene Pertussis DNA Amplification Assay do not precude Bordetella pertussis infection and positive results do not rule out co-infection with other respiratory pathogens. Results from the illumigene Pertussis assay should be used in conjunction with information obtained during the patient's clinical evaluation as an aid in diagnosis of B. pertussis infection and should not be used as the sole basis for treatment or other patient management decisions.
illumigene Pertussis DNA Amplification Assay is intended for use in hospital, reference or state laboratory settings. The device is point-of-care use.
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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§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.
(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.