As medical devices are sterilized with novel and sometimes risky new methods and chemical combinations, the US Food and Drug Administration (FDA) announced Wednesday that it will begin inspecting companies' manufacturing facilities before clearing their 510(k) applications.
The shift in FDA’s thinking comes as the agency says in Wednesday’s final guidance, issued more than seven years after the draft document was released, that it’s received “an increasing number of 510(k)s for devices labeled as sterile that use sterilization methods other than the traditionally used methods of steam, dry heat, ethylene oxide (EO), and radiation.”
And although the agency has experience with other sterilization methods -- such as with hydrogen peroxide, ozone and flexible bag systems, and now considers those to be established methods -- there “may be alterations to the more recently developed methods, as well as original, innovative sterilization technologies, which are being developed and proposed for use in the manufacture of class I and class II devices. FDA considers these to be novel methods.”
Established Sterilization Methods
FDA considers there to be two categories of sterilization methods for medical devices: established and novel.
On the established front, these are methods with a history of safe and effective use as demonstrated through literature, clearances of 510(k)s or approvals of premarket approval (PMA) applications, and satisfactory quality system inspections.
“For established methods such as dry heat, EO, steam, and radiation, there are voluntary consensus standards for development, validation, and routine control that are recognized by FDA,” the agency says.
Examples of established sterilization methods include: dry heat, EO with devices in a fixed, rigid chamber, moist heat or steam and radiation (e.g., gamma, electron beam).
In cases where FDA has previously evaluated sterilization development and validation data for specific sterilizers and determined the methods to be adequate, the agency says other established methods include: hydrogen peroxide, ozone and flexible bag systems (e.g., EO in a flexible bag system, diffusion method, injection method).
Novel Sterilization Methods
Methods FDA has not reviewed and determined to effectively sterilize a device for its intended use are considered novel and can include using chemical(s) that have not been previously approved by FDA as a chemical sterilant or that have not been identified in the scientific literature as a chemical sterilant.
And the agency notes that even if a sterilization method uses a combination of chemicals made up of individual chemicals previously approved independently, FDA would consider such a method as novel.
Examples of novel sterilization methods include: vaporized peracetic acid; high-intensity light or pulse light; microwave radiation; sound waves; and ultraviolet light.
The guidance goes on to outline what sponsors should be sure to include in their 510(k) submission, as well this additional information for all novel sterilization methods:
- A comprehensive description of the sterilization process;
- The method used to validate the sterilization cycle (e.g., the half-cycle method);
- The validation protocol;
- The sterilization validation data. The submission should also identify any applicable published scientific literature. For novel sterilization methods, FDA may also request additional information based on the specific device submitted for review.
The agency also makes clear to note what should be excluded from this guidance, including: sterilizers that are themselves medical devices subject to 510(k); processes that rely on microbial exclusion, rather than microbial inactivation; processes intended to sterilize medical devices that incorporate materials of animal origin (i.e., human or animal tissues); processes that incorporate the use of liquid chemical sterilants; and processes intended to be used by reprocessors of single-use devices.
The guidance also provides details about the pyrogenicity information that FDA recommends sponsors include in a 510(k) submission.
On Thursday 11 February, FDA will hold a webinar to help
manufacturers understand the information provided in this final guidance
document. The agency says it will respond to
Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile