PHARMACEUTICAL PRODUCT MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 290

11.3.4 HACCP Process
The HACCP process consists of seven principles:
• Principle 1: Conduct a hazard analysis.
• Principle 2: Determine the CCPs.
• Principle 3: Establish critical levels at each CCP.
• Principle 4: Establish a system to monitor control at each CCP.
• Principle 5: Establish the corrective actions to be taken when monitoring
indicates that a particular CCP is not under control.
• Principle 6: Establish procedures for verification.
• Principle 7: Establish documentation.
A case study is used to work through the seven HACCP principles to show
how a pharmaceutical manufacturer could apply the HACCP approach to review
operations. The case study involves the manufacture of a solid tablet as illustrated
in Figure 11.2 where incoming materials are granulated, milled, blended, com-
pressed into the final tablet, and packaged. The tablet has a bioburden requirement
to safeguard its preservative system and ensure product quality, but it is manufac-
tured in a nonsterile manufacturing environment. The objective in the case study
is to perform a risk-based assessment of the nonsterile manufacturing process to
identify the microbial hazards and ensure that they are adequately controlled so
the product meets its bioburden requirements.
Before the application of the HACCP principles to a specific product or pro-
cess, there are preliminary to be accomplished. These tasks are as follows:
• Assemble the HACCP team.
• Describe the product and raw materials.
• Construct a process flow diagram.
• Verify the process flow diagram.
11.3.4.1 Assemble the HACCP Team The team selected in the case study con-
sisted of four to six individuals with specific knowledge and expertise relative to
the product and process. The members were from multiple disciplines:
• facilitator (knowledgeable in HACCP process);
• production personnel (including local operators who know the variations
and limitations of the operations);
• microbiologist(s);
• quality control/assurance personnel;
• engineering; and
• other expertise (external experts knowledgeable in microbial hazards).