Risk identification, analysis, and evaluation
A multidisciplinary team made up of representatives from the Quality, Safety, Engineering, and Manufacturing divisions reviewed
possible room designs, containment techniques, and operator-protection strategies. Some options reviewed included cleanable/controlled
rooms, general purpose processing rooms, pressure differentials between zones, airlocks, packout booths, continuous liners,
and dust-tight direct connect technology with the bulk container. As part of the exercise, various risks were identified for
the packout process. Identification, definition, and documentation of the risks are crucial to the process. Examples of the
potential risks are:
- Foreign-material contamination
- Contamination of packaging material with other chemicals and foreign materials
- Operator exposure.
Two approaches for determining ways to cost effectively manage the above risks are:
- Minimize the environment around the package to facilitate control
- Use pressure differentials to help prevent the airborne migration of powder and foreign material. Four possible pressure differential
zones around the package are packout booths, rooms, airlocks, and the general processing floor. Each zone can either be positive,
negative, or equal to adjacent zones depending upon the hygiene/control strategy.
The assessment process first involved using the predeterimined risk factors to determine whether a respective packaging room
or packout strategy would be appropriate. A risk level of high, medium, or low was assigned to each risk factor. If the risk
level was determined to be "medium" or "high," then actions to mitigate the identified risk were considered and reviewed to
determine their impact to reduce the identified risk level.
The scenario below involves the use of a general purpose processing room for API packaging. This type of room is typical for
many API plants. It is designed to segregate critical processing activities from the general manufacturing floor. Considerations
when evaluating this type of room include:
- The presence of rough surfaces or ledges make the room difficult to clean.
- The room is typically not designed for easy maintenance.
- The air in this type of room may not be HEPA-filtered but the air is normally filtered to some degree to remove dust.
In this example, an initial assessment was performed on the general purpose processing room regarding the risk factors. The
risk levels were determined to be "medium" for all factors except "exposure to the operator in the room" which was assigned
a "high" risk level. This assessment required mitigation for all factors.
Instituting a strict cleaning and maintenance program along with a positive pressure differential protects the API being packaged
and the packaging materials being used for packaging. There were three options that pertained to mitigation of the remaining
factors that could protect other compounds outside the room and operators inside or outside the room. After the mitigation,
a follow-up assessment was performed and the new risk level is "none to low" for all factors.
After reviewing the adjusted control strategy against the risk factors, additional solutions can be considered—if needed—until
the risk is at least reduced to a "low" level.
Risk documentation and communication
The packaging control strategy for each packaging room and product should be documented using the risk assessment table and
approved by both Quality and Safety. A copy of the approved control strategy is then sent to Quality, Safety, Engineering,
and Manufacturing for implementation.
The packaging room and the packaging strategy should be reviewed annually to assess potential changes to facilities, equipment
and systems to assess cumulative impact of changes upon cross contamination, foreign material, and hygiene control.
Ted Frank is with Merck & Co; Stephen Brooks, Kristin Murray,* and Steve Reich are with Pfizer; Ed Sanchez is with Johnson
& Johnson; Brian Hasselbalch is with the FDA Center for Drug Evaluation and Research; Kwame Obeng is with Bristol Myers Squibb;
and Richard Creekmore is with AstraZeneca.
*To whom all correspondence should be addressed, at email@example.com