BACKGROUND AND INTRODUCTION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 13

outset, using a science and risk basis, as opposed to a traditional approach, where
normally end-product testing used to check quality requirements have been met.
Chapter 5 shows key steps for QbD and how to apply them.
Chapter 6 presents approaches to use and disseminate risk-based information
in making decisions related to early product development and clinical product
manufacture. It shows the integration of science and risk management to allow
for successful product development, such as basis for design and product control
strategy. It uses a block diagram for tablet manufacture, and an Ishikawa (fish-
bone) diagram, breaking the process into the 6Ms to identify risk factors that
need to be considered and possibly controlled in designing the manufacturing
and control process.
Chapter 7 discusses methods for using QRM to commission and qualify
equipment and facilities utilized in the manufacture of products, including the
evaluation and leveraging of information. It presents important considerations for
the use of QRM in making decisions needed to plan, develop, and conduct more
effective commissioning and qualification efforts. It shows some of the areas
where risk assessment can effectively be used to help develop and implement a
sound, efficient qualification program using simple but effective tools.
Chapter 8 then picks up the use of risk in developing and implementing
a sound and effective process validation life cycle. It shows how risk-based
approaches can be applied during process characterization and validation, for
the identification of CPPs for new and existing processes, risk prioritization,
technology transfer, process changes, and in defining review schedule. Cleaning
validation and cross-contamination risks are also discussed in this chapter.
The next chapters present several specific areas of product manufacture where
risk assessment can be used. Chapters 9 and 10 provide two views on the use of
risk assessment for the evaluation and improvement of one of the most challeng-
ing and complex manufacturing processes—aseptic processes. Risk assessment
in the context of aseptic pharmaceutical manufacture is the principal focus in
Chapter 9, with particular description and explanation of a quantitative, statisti-
cal tool of risk analysis permitting a more exacting evaluation of risk. It describes
aseptic processing hazards, such as intrinsic hazards, extrinsic hazards, risk of
endotoxin, and models for microbial ingress. Chapter 10 reviews contemporary
thinking relative to aseptic processing risk assessment and mitigation. Formal-
ized risk assessment described in this chapter and its essential counterpart risk
mitigation will play an increasing role in the design, operation, and maintenance
of aseptic operations.
Chapters 11 and 12 present views on the use of risk for better understanding
and operation of drug and biopharmaceutical manufacture. Chapter 11 focuses
on the areas of risk that a drug company may encounter in pharmaceutical man-
ufacturing, specifically addressing oral solid and liquid formulations. Common
risks associated with the manufacturing process for a solid tablet outlined in a
fishbone diagram are identified. A case study illustrates how to apply risk man-
agement principles to identify and mitigate risks that could affect product quality
and patient safety using the HACCP process. Chapter 12 discusses applications