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difficile, the FDA has issued a draft guidance entitled, “Draft Guidance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.
References
- 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
Yes, you are right, quality control is quite important in the supporting guidance for industry.
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