Page 53 - Assurance of Sterility for Sensitive Combination Products and Materials

Aseptic processing 41

former actively seeks to destroy all viable microorganisms from the product
while the latter attempts to prevent product contamination by carefully
controlling the conditions and actions designed prior to sealing, comple-
tion, and final packaging.
Another strategy is to combine aseptic processing and sterilization. Here
aseptic processing principles and methods are used to reduce the bioburden
or level of microbiological contamination in the product to very low levels
and a final sterilization treatment is employed to increase the level of steril-
ity assurance. This is sometimes referred to as post-aseptic lethal treatment.
This chapter will primarily focus on aseptic processing of the drug
product part of the combination product. The chapter will not present all
aspects or requirements for aseptic processing but will discuss some of the
points to consider for manufacturing sterile combination products using
aseptic processing.
Where all parts of the combination product can be terminally sterilized,
it is required that they be. However, not all components or products can
withstand terminal sterilization. Components may lose functionality and
product may lose potency or purity because of exposure to heat, radiation,
or other methods of sterilization. When one or more of the components or
products of a combination product cannot be terminally sterilized, aseptic
processing is typically used for that part or the entire combination product.
There are three options for manufacturing a sterile combination product
using aseptic processing:
1. Manufacture and assemble all components—drug, device, and packag-
ing aseptically.
2. Manufacture and assemble some of the components aseptically and then
assemble with sterilized components.
3. Manufacture and assemble all components aseptically and subject prod-
uct to post-aseptic lethal or decontamination treatment.

4.3 Aseptic processing
Aseptic processing is a set of process steps, conditions, and actions taken to
render product and components sterile and prevent microbiological con-
tamination of that product and those components prior to final assembly
and sealing. The Parenteral Drug Association (PDA) Technical Report 22,
Process Simulations for Aseptically Filled Products, defines aseptic pro-
cessing as the handling of sterile materials in a controlled environment
in which the air supply, facility, materials, equipment, and personnel are