Aseptic processing involves handling sterile products in a controlled environment to minimize contamination, with critical emphasis on filling and sealing containers to maintain sterility. Terminal sterilization processes, such as heat or irradiation, are applied to product containers, which must be done under high-quality environmental conditions due to the lack of sterilization for the final product in its container. The document highlights the significance of controlling microbial contamination, including bacterial spores and endotoxins, and outlines quality control measures such as the LAL assay for endotoxin testing.

1. Aseptic Processing
Operation
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2. Aseptic Processing
Aseptic processing is defined as “handling of
sterile product, containers, and/or devices in
a controlled environment, in which the air
supply, materials, equipment, and personnel
are regulated to maintain sterility”
(ISO 13408-1, 2008)

3. Producing Drug Products By
Terminal sterilization
• Product containers are filled and sealed
under high-quality environmental
conditions designed to minimize
contamination, but not to guarantee sterility.
• Product in its final container is subject to a
sterilization process such as heat or
irradiation.
Aseptic processing
• Drug product, container, and closure are
subject to sterilization separately, and then
brought together.
• Because there is no process to sterilize the
product in its final container, it is critical
that containers be filled and sealed in an
extremely high –quality environment.

4. Terminal
Sterilization
Drug
Product
Container
/ Closure
Excipiants
Sterilization
Process
Sterile
Drug
Product !

5. Aseptic Processing
Drug
Product
Sterilization
Process
Container
Closure
Excipient
Sterilization
Process
Sterilization
Process
Sterilization
Process
Sterile
Closure
Sterile
Excipient
Aseptic
Processing
Sterile
Drug
Product
Sterile
Container
Sterile
Final
Product
Can use multiple sterilization processes each optimized for the individual component

6.  Bacteria, virus, fungi and other viable microbes
 Bacterial spores and endotoxins
 Non viable Particles like dust, fibers, glass and other
visible and sub-visible particulates suspended in the air
and may contaminate product.
Contaminating
Agents

7. Extremely heat stable – recommended conditions for
inactivation are 180 0
C for 3 hours.
Endotoxin: a pyrogenic (fever inducing) substance (e.g. lipopolysaccharide)
present in the bacterial cell wall. Endotoxin reactions range from fever to death.
Endotoxin Testing
LAL Assay (Limulus amoebocyte lysate)
ENDOTOXIN LIMIT FOR WFI IS
0.25 EU/ml
Quality Control

8. References
EU GMP Annex 1: Manufacture of Sterile Medicinal
Products – Draft revision 2020

9. Thanks