PHARMACEUTICAL PRODUCT MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 294

• moisture control;
• bioburden testing of raw materials;
• in-process microbial reduction steps (e.g., pasteurization);
• control of storage conditions; and
• in-process filtration.
The team identified any preventive measures required. Preventive measures
already in place and those that need to be put in place were considered. It is
important to remember that more than one preventive measure may be required
for each hazard or one preventive measure may address more than a single hazard.
The team initiated a hazard analysis chart to record the results of the haz-
ard analysis. Table 11.1 provides an example. The team recorded the following
information:
• each step, with an assigned a reference number;
• the determination whether or not there could be a microbial hazard associ-
ated with the step along with the rationale for the determination; and
• any preventive measure(s).
For process steps 1.0, 3.0, and 4.2, no microbial hazards were identified.
For process step 2.0, purified water is used to clean the equipment. The water
quality is tested to ensure it meets quality specifications before use. This measure
ensures that the microbial burden in the water is being controlled, which reduces
the risk that high levels of microbial contamination is being introduced during the
cleaning process. For process step 4.0, the room air is filtered by high efficiency
particulate air (HEPA) filters and the personnel are gowned. These measures help
reduce the risk of microbial contamination being introduced into the product
container during its exposure to the manufacturing environment and personnel.
For process step 4.1, the equipment is set to sound an alarm when the correct
air temperature (300 ◦ F) for drying is reached. Once the alarm is sounded, the
operator can start the 30-min drying step. This measure helps reduce the risk that
the air temperature is not sufficient to dry the equipment in 30 min, resulting in
wet equipment. In addition, procedural controls are in place and personnel are
trained to ensure that the equipment is dry because moisture supports the growth
of microorganisms. For process step 5.0, contamination of the equipment or
finished product from operator contact during the sampling process is controlled
with the use of gloves. Operators are trained in the proper sampling techniques
to don the gloves properly, keep them clean and dry, and avoid product contact.
Going forward, not all of the process steps included in Table 11.1 will be
covered. Steps 4.0 and 4.1 will be used to demonstrate how the HACCP approach
continues.
11.3.4.8 Principle 2: Determine the Critical Control Points (CCPs) Although
other approaches may be used, an effective tool to help determine where the
CCPs should be in the process is a decision tree. The CCP decision tree is based