Page 56 - Assurance of Sterility for Sensitive Combination Products and Materials

44 Assurance of sterility for sensitive combination products and materials

is typically implanted or injected, the patient risk profile is similar between
the various microbial sources. This makes the controls for all levels of con-
tamination a high concern.
Based on the standard definition of process risk where risk is the rela-
tionship of severity of a hazard (in this case loss of sterility), probability of
the hazard occurring, and ability to detect the hazard, the severity would be
high, occurrence inconclusive, and detection relatively poor. Therefore, the
overall risk is high.
Because the current detection technology and the correlation between
what can be observed, and the desired outcome is not strong, significantly
reducing this risk through detection is not likely. The best way to control an
aseptic process failure and reduce the aseptic processing risk is by reducing
the likelihood of occurrence through sound risk and science-based process
control strategies and design.

4.4 Aseptic process design
Proper design and planning of the aseptic process are essential to ensuring a
compliant and effective sterile combination product manufacturing process.
One of the first steps is to understand the objective of the process and its
relationship to product quality and output. The objective of the aseptic pro-
cess is preventing contamination during the manufacturing of the product.

4.5 Sterility by design

To provide effective process control, it is essential to identify all process vari-
ables that impact the product output. Attaining primary confidence in the
process should happen during the design of the process, rather than during
final process qualification testing or continued process verification. It is this
confidence that enables the company to commit to the process design [8].

4.6 Line of sight [9]

One method of identifying critical process parameters early in the develop-
ment stages is to use the line of sight (LOS) approach, as noted in Fig. 4.1.
In a LOS approach, the objective of the aseptic process design is kept in
sight. All actions are focused on achieving this objective. The objective is
the establishment and maintenance of a critical quality attribute (CQA), in
this case, product sterility. All actions taken in the design should be able to