Page 40 - Assurance of Sterility for Sensitive Combination Products and Materials

28 Assurance of sterility for sensitive combination products and materials

provides a specific SAL for the product. Terminally sterilized devices usually
eliminate the need for product tests for sterility since the validation of the
process provides a higher confidence level of product sterility than product
sterility testing. The major sterilization processes of EO, radiation, and moist
heat have well-developed standards and will be discussed to provide an in-
sight into the validation of other novel sterilization methodologies.

3.2.1 Product qualification

Product specifications and associated processes of sterilization must be defined
before moving into the validation of a terminal sterilization process. Material
compatibility and ranges of conditions in the sterilization process must be un-
derstood to select the terminal sterilization method for a combination product.
For example, radiation creates free radicals and cross-linking that can be de-
structive to things such as an active ingredient or the device itself. Similarly, EO
reacts with materials and can change the performance of an active ingredients
or device. For these reasons, maximum conditions—that is, maximum dose or
maximum temperatures and concentrations—for product functionality must
be determined. Minimum process conditions that could impact the effective-
ness of inactivating microbes are addressed through the validation of the ster-
ilization process—or the ability of the process to render the product sterile.

3.2.2 Equipment qualification
The qualification of the equipment used to deliver the sterilization process
is typically broken into two categories: installation qualification and op-
erational qualification. Installation qualification allows for a documented
review of equipment location, utilities required, safety, instrumentation and
calibration, and proper operation of the equipment and ancillary systems.
Operational qualification documents must show that the system (equip-
ment, ancillary equipment, controls) can deliver the required process within
defined tolerances. The operational qualification is usually executed after
the process has been defined, and the installation and operational qualifi-
cations can be executed without product loading as the qualifications are
focused on equipment operation and performance.

3.2.3 Sterilization validation approaches

Microbial validation of the terminal sterilization process determines the
minimum conditions required to render the product free of viable organ-
isms. Since it is impossible to prove absolute sterility, the terminal ster-
ilization industry has defined this as an SAL. The SAL is defined as “the