Page 245 - Assurance of Sterility for Sensitive Combination Products and Materials

222 Assurance of sterility for sensitive combination products and materials

9.1 Labeling products as sterile
One of the most challenging hurdles for combination products or products
sensitive to standard sterilization processes is understanding the require-
ments for making a claim in the labeling of the product that it is sterile and
the regulatory pathway to making such a claim. The broad assumption in
the industry is that if a combination or sensitive product cannot be steril-
−6
ized to a maximal sterility assurance level (SAL) of 10 using traditional
sterilization processes, it automatically must be manufactured using aseptic
processing. Several standards, such as International Standards Organization
(ISO) 13408-1 and European Agency for the Evaluation of Medicinal
Products (EMA) guidance of the sterilization of medicinal products, state
that terminal sterilization is preferred for providing sterile product, with
aseptic processing being an option if terminal sterilization is not possible.
To that end, new guidelines are available that facilitate the understanding
of and provide guidance in situations when terminal sterilization at an SAL
−6
other than 10 might be acceptable.
There are several standards and guidance documents that provide op-
tions for achieving a sterile label claim, including Pharmacopeias, European
Standards (EN) and EMA documents, United States (US) standards and US
Food and Drug Administration (FDA) ISO guidance documents. The EN
documents that are utilized in many countries around the world are EN
556-1 and EN 556-2. The central US document is AAMI ST67. In addi-
tion, in the ISO arena, ISO TS 19930 provides guidance for meeting the
requirements of EN 556 and AAMI ST67, whereas the ISO 13408 series
provides comprehensive guidance for achieving a sterile claim using aseptic
processing. A current list of FDA-recognized, consensus standards is avail-
able at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/
search.cfm.

9.1.1 Communicating with regulatory authorities
Regardless of the choice of a sterile label claim or the means by which it is
achieved, regulatory bodies for specific countries have the authority to ap-
prove the processes chosen for supporting that claim. Therefore, it is critical
to understand the regulatory pathway that pertains to a particular country
or region for supporting and obtaining approval for a label claim that the
product is sterile.
Each country’s regulatory authority has a system for submitting a prod-
uct for approval. Integral to that approval is the sterile label claim and