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Regulatory pathway for labeling combination products as sterile 229

Information in Premarket Notification (510(k)) Submissions for Devices Labeled
as Sterile” (“510(k) sterile devices guidance”). This guidance is intended
to provide a summary of the information that the Agency recommends
applicants include in 510(k) submissions to CDRH and CBER for de-
vices intended to be labeled as sterile. The guidance is available at: https://
www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/
guidancedocuments/ucm109897.pdf.
The 2016, 510(k) sterile devices guidance updates and clarifies the in-
formation in its 2002 predecessor, “Updated 510(k) Sterility Review Guidance
K90-1” and it provides expanded guidance related to recent advances in
sterilization technology. Until established to be otherwise, such sterilization
technology innovations are considered to have the potential of increasing
human health risks. One of these is the risk of infection, if a new technol-
ogy does not provide adequate sterility assurance. This guidance provides
clarification regarding the Agency’s concerns and expectations.
It is worth noting at the onset that the scope of this guidance includes
medical devices that are intended to be labeled sterile as a result of being
subjected to “industrial terminal sterilization processes based on microbial inactiva-
tion” rather than microbial exclusion. Accordingly, methods such as filtration
and aseptic processing are outside of the scope of this guidance.
Should an applicant wish to impart a specific sterility assurance to a de-
vice using a unique sterilization method as part of an innovative approach
to processing a sensitive device, the following summary of the 2016, 510(k)
sterile devices guidance is provided to help identify concerns associated
with the development of unique sterilants, unique combinations of steril-
ants, and/or unique sterilization methods. (For other submission types such
as PMAs and IDEs for devices that raise similar issues, industry should to
reach out to the Agency to obtain case-by-case, relevant guidance.)

9.4.1 Methods of sterilization

One area of clarification provided by this guidance is the refined definitions
of the three categories of industrial sterilization methods. The basis of these
definitions is multifactorial, and the category designation of any given tech-
nology has the potential to change as the Agency’s knowledge of the process
increases with experience.
• Established A methods are those for which there is a well-established
and extensive history of safe and effective use, and extensive litera-
ture, including the existence of dedicated, FDA-recognized, consensus
standard(s).