PHARMACEUTICAL PRODUCT MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 293

• equipment (cleaning and storage);
• utilities;
• personnel; and
• facility (material flow, cleaning and sanitation, environmental controls).
Not all of these processes mentioned are covered in the example. The example
will cover an analysis of the compression step to show how the HACCP process
works. The compression step occurs after the raw materials are granulated, milled,
and blended. In the compression step, a tablet press compresses the granulation
material into the size and shape of the finished tablet. The process flow map
created for the compression step is illustrated in Figure 11.3.
Each processing step was assigned a sequential number on the process flow
diagram. Next, the team conducted a hazard analysis of the identified hazards.
The challenge that the team faced was to prepare a list of steps in the process
where significant microbiological hazards could occur and determine what are
truly significant versus insignificant hazards. Significant microbial hazards are of
such a nature that their elimination or reduction to acceptable levels is essential
to meeting the bioburden requirement for product quality.
Each potential hazard was assessed on the basis of the severity of the con-
sequences of the exposure to the potential hazard (e.g., magnitude and duration
of illness) and its likely occurrence. It is helpful to consider the likelihood of
exposure and severity of the potential consequences if the hazard is not properly
controlled.

11.3.4.7 Identify Preventive Measures If a microbial hazard exists, preventive
measures must be identified. Preventive measures would include the following:
• effective cleaning and sanitization procedures;
• temperature control;

8.0 Tablets exit
into white
containers without
any plastic liner

1.0 Inspection of
module

5.0 Take samples
of tablets at
machine chute
during start-up
using gloved hands

2.0 Tablet press
cleaned and
assembled

9.0 Take in-process
tablet samples
using gloved hands
at exit chute

6.0 Run tablet
machine

3.0 Bring in active
blend and osmotic
blend

7.0 Tablets pass
through de-duster
and metal detector

4.0 Charge tablet
press using drum
inverter or clean
scoops

10.0 Transfer tablets
from unlined white
containers when full
to 11 kg containers
with 2 plastic liners

Figure 11.3 Process flow diagram example. Process flow diagram for tablet compression
process step.