PHARMACEUTICAL PRODUCT MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 270

• determining what areas need process improvements; and
• increasing product and process understanding.
11.1 ROLE OF QUALITY RISK MANAGEMENT
Risk assessment as part of an effective risk management program directs the
product and process knowledge gathering process [1-11]. Decisions are made
about how to assess, control, monitor, and/or accept risk based on predicted
benefits and possible consequences. It determines through a systematic approach
the product attributes and process parameters that are truly critical to the final
product quality and safety and which are not critical. The value of this approach is
that time, money, and other resources are not wasted on controlling, monitoring,
or validating parameters that do not ensure final product quality.
Regulators are encouraging the use of risk assessment in the beginning during
product development where the expected aim is to build quality into the product
by design [12-16]. ICH Q8 (R2), Pharmaceutical Development, recognizes risk
assessment as a tool to be used early on and throughout the development process
to determine at a minimum, those aspects of drug substances, excipients, con-
tainer closure systems, and manufacturing processes critical to product quality
and to define their control strategy. Through a series of planned and designed
experiments, these different aspects and any interactions between them can be
examined. The end result is the creation of a comprehensive product profile that
not only provides confidence that the final product will be safe and efficacious
but also provides a foundation on which the impact of future changes can be
predicted.
Although the critical product attributes and process parameters and their con-
trol strategy are best determined during the drug development stage, the risk
assessment process can be applied at any point in the product's life cycle.
Regulators are expecting that the pharmaceutical manufacturer knows the risks
associated with their product and manufacturing process, which could result in
product quality or safety issues whether the drug product is in development or
already on the market.
Pharmaceutical manufacturers have been practicing some form of risk man-
agement, formally or informally, for some time to improve process efficiencies
or investigate product quality issues. Historically, the risk management practices
have been deductive in nature and performed through an informal process. A
formal process is not always appropriate or necessary and informal processes are
acceptable as long as the rationale is logical, documented, and the process follows
company policy. What should be avoided is an “I made the decision in the coffee
room” type of process where decisions may not be documented. Otherwise, the
risk decision-making process may be too subjective rather than empirical and
may not be well documented. Inadequate documentation and justification of risk
decisions could open the door for questions by regulators. Proper documentation
of the decision-making process and decision justification are essential to provide