Page 63 - Assurance of Sterility for Sensitive Combination Products and Materials

50 Assurance of sterility for sensitive combination products and materials

4.10 Aseptic practices
The sterile drug product aseptic manufacturing process includes steps that
expose surfaces or materials to potential sources of microbiological contam-
ination. These sources can include people, the environment, equipment or
facility surfaces, utilities, gases, water, or raw material inputs such as com-
ponents, parts, ingredients, other materials, etc. The protection of the sterile
product and product contact surfaces is essential to the reliable performance
of the aseptic process and is the objective of good aseptic practices. This
objective should be captured in the validation approach.
Monitoring and detecting contamination could be easy, as might be
the case with bioburden of materials, or difficult, as might be the case with
environmental contamination. Sporadic or intermittent contamination, as
might be the case with biofilm, or human intervention-related contamina-
tion tends to be particularly challenging.
Aseptic practices are designed to protect the product from microbiolog-
ical contamination and include controls such as:
• Clean room design and operation
• smooth and cleanable clean room surfaces to reduce the potential for
contamination in seams and openings;
• clean room equipment design to allow for accessibility and workflow;
• clean room equipment cleanable surfaces;
• positioning of equipment and functions with minimal first air
interference;
• clean room high-efficiency particulate air (HEPA) filtered air supply
with adequate velocity,
• clean room differential air pressure for correct flow from clean to less
clean areas;
• clean room HVAC temperature and humidity controls to minimize
operator discomfort, particulate static charge, and microbiological
growth;
• clean room air changes to remove contaminated air;
• design of adjacent clean room spaces and areas to allow for work and
personnel flow and protect cleaner areas; and
• work, personnel, equipment, materials, and component flow to re-
duce the risk of contamination of cleaner areas and materials from
contact with less clean items;
• Material/product preparation and handling
• sterilization and decontamination of product contact materials and
surfaces;