Implications of risk assessment on processing
When a process step or other activity is determined to be high risk, what should be done? These determinations should cause
initiation of project activities to reduce the risk level. However, if reduction is not possible, there should be additional
in-process controls, additional testing, additional training, and so on. In summary, the organization should expend additional
effort to mitigate or control the risk situation. At the same time, efforts on processes or activities that are well controlled
or do not represent risk can be minimized. For example, a new purified water (PW) supply was planned for an aseptic processing
facility. This PW supply was to be used as feed water for a water-for-injection (WFI) still, for initial rinse water for clean
in place (CIP) of formulation and filling equipment, and for make-up of wash solutions for CIP of formulation and filling
equipment. WFI was used for the final rinse of this equipment. Based on these parameters, a 3-D risk assessment was performed
on the PW system, giving the results shown in Table III.
Table III: 3-D risk assessment for purified water system.
The overall score determined by this risk assessment is 30, indicating the overall risk is low to medium. This low overall
score indicates that detailed formal risk assessment methods such as FMEA are not needed for this system. While the overall
risk score indicates few controls are needed, the distance along product stream score indicates that some engineering controls
and in-process controls are justified. Based on this analysis, the design engineer decides to add an ultraviolet (UV) system
for controlling bioburden, as well as conductivity alarms to indicate system problems. In addition, periodic monitoring and
trending of system bioburden is justified.
A contrasting example would be an aseptic filler intended for multiproduct use. This filler is designed for high-speed filling
and stoppering of several different products with rapid changeover. This filler is designed for in-line check weighing, and
for automated CIP and sterilization in place (SIP). A 3-D risk assessment of this equipment gave the results shown in Table
Table IV: 3-D risk assessment for aseptic filler.
The risk assessment clearly indicates the filler is a high risk system. Based on this assessment, design and process FMEAs
were performed on the filler to identify controls to mitigate high-risk items. Table V is a partial example of a process FMEA
used to identify design controls for the new filler.
Table V: Process FMEA example (system=aseptic filler; process=clean-in-place).
This example shows a small portion of a detailed FMEA for the CIP process for a critical system (aseptic filler). A FMEA such
as this one could be used to put additional controls into place during design of the system, as well as to identify critical
items that need to be verified during validation.