Page 65 - Assurance of Sterility for Sensitive Combination Products and Materials

52 Assurance of sterility for sensitive combination products and materials

manipulations or interventions should be minimized. Where interventions
are necessary, steps should be taken to minimize the risk of product con-
tamination from such actions. Interventions can be categorized as inherent
(routine) or corrective (nonroutine).
Inherent interventions are manipulations in the critical aseptic process-
ing area that are part of the process. They must be performed for the pro-
cess to proceed. These interventions include activities such as setting up of
the filler parts, installing filters, loading components, placing environmental
monitoring sensors, removing fill checks, and transferring materials.
Corrective interventions are activities that might occur but do not have
to occur. These include such activities as removing of fallen vials, removing
of jammed stoppers, clearing of broken containers, adjustments, and minor
repair and replacement of parts.
All inherent and corrective interventions should be performed using
proper aseptic technique, respecting first air and airflow principles. For
corrective interventions, additional steps may be required to reduce con-
tamination risk and reestablish aseptic conditions after the performance
of corrective interventions. These steps can be determined through a risk
assessment and may include such actions as removal of open containers
in near the intervention, disinfection of the area where the intervention
is performed, additional environmental monitoring, and/or segregation of
post-intervention product [5, 7].

4.12 First air principles

One of the most effective control measures for the prevention of microbio-
logical contamination is the use of clean airflow. Aseptic practices are those
process steps and related functions performed using aseptic techniques that
adhere to first air principles in a protected classified environment. First air
refers to an uninterrupted HEPA filtered air source traveling to the sterile
entity. The good aseptic technique involves observing first air principles
and avoids placing potentially contaminated objects in between the source
of HEPA filtered air and the sterile entity (product or product contact sur-
face). Interventions using sterilized objects that are handled correctly, such
as sterilized forceps that disrupt first air have a low risk of contaminating
the sterile product. Interventions using non-sterile objects, such as gloved
hands or gown sleeves that disrupt first air have a higher risk of contaminat-
ing the sterile product. The risk can be mitigated by designing the process