Page 254 - Assurance of Sterility for Sensitive Combination Products and Materials

Regulatory pathway for labeling combination products as sterile 231

and directs the reader to FDA’s, “Requests for Feedback on Medical Device
Submissions: The Pre-Submission Program and Meetings with Food and Drug
Administration Staff” guidance document (previously cited).
4. A description of the pyrogenicity testing, if applicable. Guidance is sig-
nificantly expanded in this section, which identifies the general cate-
gories of devices for which pyrogenicity testing should be performed,
and cites relevant references to guidance and standards. In addition, it
recommends that the submission should include information on the test
method and acceptance criteria. Finally, it recommends that the submis-
sion should include more extensive information on alternatives to batch
testing, if that route is intended.
5. A description of the sterile barrier system(s). This should be provided,
as well as a simple description of any simulation methods (e.g., distri-
bution, accelerated aging) and test methods (e.g., dye penetration, seal
strength) used to validate package integrity and shelf life claims.

9.5 Documents pertaining to terminal sterilization and SAL
9.5.1 Guidance from the Association for the Advancement
of Medical Instrumentation
The Association for the Advancement of Medical Instrumentation (AAMI)
has had a standard in place since 2006, which has been recognized by FDA
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and which addresses SALs other than 10 . The current edition is titled
AAMI ST67: 2019: Sterilization of health care products—Requirements and guid-
ance for selecting a sterility assurance level (SAL) for products labeled “sterile.”
However, a revision is in process, most likely due to be published in 2019.
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AAMI ST67 allows for SALs other than 10 , such as 10 , 10 , and
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10 , depending on whether the product can tolerate traditional steriliza-
tion processes. Historically, alternative SALs have been more accepted in the
United States because the North American medical device industry and the
CDRH of the FDA have applied two SALs to describe assurance of prod-
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uct sterility—an SAL of 10 for products intended to contact breached
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or compromised tissue, and 10 for products not intended to come into
contact with breached skin or compromised tissue.
As in ISO TS 19930, everything presented in AAMI ST67 is based
on the premise that a manufacturer will pursue sterilization to a maximal
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SAL of 10 before considering other options. However, AAMI ST67 pro-
vides more in-depth guidance into what a manufacturer should consider
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when evaluating whether sterilization to a 10 SAL is feasible/reasonably