ASEPTIC PROCESSING: TWO - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 241

must be applied in its entirety to truly benefit the patient population. There are
many industry standards and guidelines available detailing risk management tools,
processes, and techniques. Despite the broad number of publications on risk man-
agement, the same fundamental terms, processes, and concepts apply. A cursory
glance through the risk management standard [14] generated by the Institute of
Risk Management (IRM), the Association of Insurance and Risk Managers (AIR-
MIC), and Alarm the National Forum for Risk Management in the Public Sector
will clearly illustrate to the reader the level of generic commonality. Furthermore,
the International Standards Organization (ISO) has a family of international risk
management standards that will act as a universally accepted paradigm for the
application of risk management practices [15].
10.4 MEASURING AND CONTROLLING RISK
The benefits of a formal assessment of risk to help assure product sterility or
product quality during aseptic pharmaceutical manufacture, afforded to the man-
ufacturer, are universally recognized by the regulatory agencies [16-18]. Risk
assessment and risk management are arguably facilitating the genesis of the next
phase in the continued evolution of GMPs. Risk assessment (risk analysis and
risk evaluation) as part of an integrated risk management program permits the
practitioner to adroitly measure and control risk as a common discipline within
the diverse spectrum of aseptic environments and scenarios. Tidswell and McGar-
vey [19] originally listed a number of means by which measuring and controlling
risk could be applied to achieve specific objectives benefiting product quality;
these include, but are not limited to, the following:
• Prospective analysis of designs . Analysis and evaluation of risk performed
in the early stages of any process or product design can be used to drive
specifications, design criteria, or refine attributes. Applying risk management
at the early phase or when “on the drawing board” likely means the absence
of performance data but does necessitate inclusion of a greater number of
assumptions and increased uncertainty. Understanding the magnitude and
scope of these constraints may direct choice of the most pertinent risk anal-
ysis and decision tools. Repeated and consecutive cycles of risk assessment
performed on evolving product prototypes or conceptual process models
prospectively refine the design “on the drawing board” to an acceptable level
of risk. Recently, the application of a quantitative evaluation of microbial
ingress risk into medical devices during aseptic admixing exemplifies how
this technique may be used to drive device design with contextual considera-
tion of the clinical or in-use environment [13]. In an analogous manner, any
proposed aseptic manufacturing process or facility design can be subjected
to rigorous and repeated cycles of evaluation. Here, the risk of product or
process contamination can be evaluated with cycles of refinements made
to the likes of personnel flow and process and equipment flow, with con-
textual consideration of the product and process containment. Clearly, both