The risk to contamination associated with personnel is such that the contributions for these factors must be weighted more
heavily than those derived from the contributing factors that are not human-related. An extra weighting of 10× has been assigned
to those process steps in which personnel presence and close interaction with sterilized products, materials, and equipment
is mandated: aseptic compounding, aseptic setup, and aseptic filling.
The risk for the overall process is the sum of the contributions from all of the relevant process factors, weighted according
to the effects of various practices. Determination of the individual factors varies and includes simple multiplications that
reflect the combined influence of variables within an individual process step. Weighting factors are included in the lyophilization
and aseptic filling parameters to provide a more balanced consideration of these process steps. Addition is used as the primary
means of calculation for the following reasons:
- It substantially simplifies the calculations once the individual contributions have been determined.
- It is consistent with the sense that adding an activity (e.g., lyophilization) to a process adds risk to that process (e.g., solution filling). This allows the elements of a larger activity to be addressed individually and directly and optimized
from a risk perspective more easily.
As in the other risk-assessment models, a low score in the present model suggests a low potential for contamination. The risk
contributions for the various process elements of the overall aseptic process are described below and quantified in the tables
that accompany this text.
The risk assessment relies heavily on the environmental technology used in the aseptic process. The authors have applied a
corrective factor that is based on the individual contributions of the various process steps to the final score. If aseptic
compounding and aseptic filling are not performed using the same environmental technology, then the contribution risks for
each should be calculated separately, on the basis of the technology used.
Facility contributions depend on the types of environments provided for the supporting tasks associated with aseptic processing,
including sterilization unloading and personnel gowning, and the background environment for the fill zone. Additional contributions
from the facility derive from the sanitization method used and the frequency of treatment (see Table IIa).
Table IIa: Facility considerations for cleanrooms.
Similar parameters relate to using isolators, but the factors and weighting are adjusted to suit the differences in technology
(see Table IIb). The authors have included RABS within the cleanroom category because this is the technology that it most
resembles. The model for facility contributions can be expressed as:
cleanroom contribution = sanitization interval factor × sanitization process factor × background classification factor
isolator contribution = decontamination interval factor × decontamination factor × background classification factor
The intervals between sanitization and the type of process applied are multiplied and added to the contribution from the background
environments. Smaller facilities where one room serves multiple purposes (e.g., filling and unloading) receive a lower score because of their simplicity.
Table IIb: Facility considerations for isolators.