ASEPTIC PROCESSING: TWO - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 242

quality and economic factors support the application of this technique to
optimize a facility design and prevent the need for post build retrofit or
modification early on in the facility's life span. These examples illustrate
that the exploitation of risk assessment in the application of QbD has a pro-
found opportunity for improving sterility assurance [20] and demands far
wider adoption. Truly quantitative risk analysis, methodically and simultane-
ously considering the multiple contributors germane to contamination risk,
realized the full potential of QbD; however, it necessitates a sophisticated
computation. QbD is further discussed in Chapter 14.
• Comparative analysis of processes and products . Understanding product and
patient risk is paramount to making the most appropriate decision regarding
the provision of aseptically manufactured products. Comparative examina-
tion, in a consistent manner, of the risks associated with multiple established
processes or products permits distinction and comprehension of inherent
strengths and vulnerabilities. Here, the application of available historical
data can be employed to execute more accurate assessments of risk and
adoption of quantitative tools and techniques, than the sole use of qualita-
tive methods. In the aseptic manufacturing environment, such an analysis
may facilitate decisions regarding the utilization or preference of available
manufacturing strategies. This underlines a much under-valued aspect of risk
assessment. Analysis and evaluation not only focuses our attention toward
vulnerabilities and jeopardy but concurrently to those beneficial elements of
processes, systems, and products permitting their further advantageous use
[21]. Comparative risk assessment may also be adopted to direct or prioritize
process improvements to focus resources to truly benefit product quality.
Optimization of monitoring, bioburden, and particulate management. In the man-
agement and monitoring of aseptic environments, it has been a historic miscon-
ception that more equates to better. Many aseptic manufacturing environments
have been driven toward increased frequency and quantity of environmental mon-
itoring and sampling, which have seemingly added little to the control of risk.
Although the application of tools such as statistical process control (SPC) has
merit in contributing to measuring and controlling risk from bioburden, [22] it
could drive to a strategy untenable in terms of sampling and control limits if
applied in the purest sense. For example, the population frequency and quantity
of microorganisms annually recovered in a clean room environmental monitoring
program will drive the program control limits when SPC is stringently adopted
in the purest Deming sense. Inevitably, year-on-year application will drive these
control limits to unobtainable levels. In terms of measuring and controlling risk, it
is far more value adding to apply risk analysis and risk evaluation tools and tech-
niques to assist the rational choice of monitoring methods, sampling locations, and
frequency. Aseptic environmental monitoring strategies benefit particularly well
from this approach. Akers and Agalloco, [23] Whyte, [5] and Whyte and Eaton
[24] have innovated effective risk analysis tools and techniques to evaluate risk
to product from bioburden and which have the additional utility to be utilized for