Cara N. Wilder, Ph.D.
Section 510(k) of the Food, Drug, and Cosmetic Act requires device manufacturers to notify the Food and Drug Administration (FDA) of their intent to market a medical device. This process, known as Premarket Notification, allows the FDA to determine if an equivalent legally marketed device already exists, ensures that the new device is properly identified and classified, and that the device is cleared for use1. For devices that pose a serious level of risk of illness or injury to the user, such as those that are used internally or to sustain life, a Premarket Approval (PMA) submission is required. This is the most stringent type of approval application required by the FDA, and requires information on how the medical device was designed and manufactured as well as any preclinical and clinical studies on the device. For a medical device to acquire PMA, it must be backed by sufficient valid scientific evidence assuring that it is safe and effective for its intended use.
As part of the requirements for 510(k) clearance or PMA, medical devices must be examined using appropriate FDA guidances; the recommended guidance documents depend on the classification and the intended use of the device. For example, for the development of a 510(k) in vitro diagnostic (IVD) device intended for the detection of Clostridium difficile, the FDA has issued a draft guidance entitled, “Draft Guidance for Industry and Food and Drug Administration Staff – Establishing the Performance Characteristics of In Vitro Diagnostic Devices for the Detection of Clostridium difficile.”2 This particular guidance recommends various analytical, clinical, and cross-contamination studies for establishing the performance characteristics of IVDs developed for the detection of C. difficile in stool samples via antigen-, antibody-, or nucleic acid-based tests.
One of the key features of this guidance, and those similar to it, is the recommendation for determining the analytical sensitivity and cross-reactivity through the use of authenticated, characterized strains. For determining the analytical sensitivity of a C. difficile detection assay, the FDA recommends the use of a variety of strains that represent the various known C. difficile toxinotypes (0; IIIb; IIIc; tcdA- , tcdb-; V; VIII, XII, and XXII). To analyze cross-reactivity, the FDA recommends the use of medically-relevant viruses and bacteria of varying species such as Bacillus cereus, Citrobacter freundii, and Clostridium tetani.
To support the need for highly characterized strains, ATCC has fully authenticated and described microbial strains that are recommended in guidances for industry. For the aforementioned C. difficile guidance, ATCC offers a number of C. difficile strains that have been genotypically and phenotypically authenticated as well as functionally characterized for toxinotype, binary toxin, and ribotype. These defined characteristics, along with the provided isolation history, allows for the easy selection of strains recommended for testing the analytical sensitivity of novel medical devices. Moreover, the expansive breadth of the ATCC collection allows for the easy obtainment of representative strains for cross-reactivity testing.
ATCC similarly supports a number of other guidance documents, such as the “Draft Guidance for Industry and Food and Drug Administration Staff - Establishing the Performance Characteristics of Nucleic Acid-Based In vitro Diagnostic Devices for the Detection and Differentiation of Methicillin-Resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (SA)” 3. In this latter guidance, characterized S. aureus strains with known SCCmec type and PFGE type are needed for establishing analytical sensitivity, and pathogenic and commensal flora found in the nares should be tested to analyze cross-reactivity. To aid in the development of these diagnostic devices, ATCC has fully characterized a majority of the S. aureus strains in the collection for both SCCmec type and PFGE type, and have confirmed the presence of the mecA gene in methicillin-resistant strains.
Overall, when developing a novel medical device, it is important to ensure that the device is properly evaluated and verified based on FDA guidance recommendations prior to submitting it for 510(k) clearance or PMA. Using authenticated, fully characterized strains from an ISO accredited and certified standards development organization, such as ATCC, can help ensure the reliability and reproducibility of analytical sensitivity and cross-reactivity data, thus confirming the efficacy and validity of the device in question.
- Food and Drug Administration. Premarket Notification (510k). Available online: http://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/premarketsubmissions/premarketnotification510k/default.htm
- Food and Drug Administration. Draft Guidance for Industry and Food and Drug Administration Staff - Establishing the Performance Characteristics of In Vitro Diagnostic Devices for the Detection of Clostridium difficile. Available online: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm234868.htm.
- Food and Drug Administration. Draft Guidance for Industry and Food and Drug Administration Staff - Establishing the Performance Characteristics of Nucleic Acid-Based In vitro Diagnostic Devices for the Detection and Differentiation of Methicillin-Resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (SA). Available online: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm237235.htm