BACKGROUND AND INTRODUCTION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 4

risk. The objective of risk management, as discussed later, is not just to identify
risk, but to mitigate and reduce risk, thus improving the manufacturing process.
The outcome of the 2005 meeting was an initiative by the PDA Science Advi-
sory Board to create a task force of industry professionals to investigate and
develop a model for the use of risk management for aseptic processes. This
would later become the basis of PDA Technical Report No. 44 Quality Risk Man-
agement for Aseptic Processes , as well as later efforts on companion documents
and reports. The task force was made up of 15 individuals from sterile drug
manufacturing within 15 different organizations and companies. Only a few had
direct experience with formal risk management and that experience had largely
come from the medical device industry. The use of formal risk assessment and
management techniques for pharmaceutical and biopharmaceutical manufacturing
appeared to be a work in progress at best.
In 2008, the PDA published Technical Report No. 44. The technical report
presented concepts and a program for evaluating the risk of process failure in
making decisions for the manufacture of sterile drug products using aseptic pro-
cessing. One point presented in TR 44 was that aseptic processing was not
necessarily risky. The hazards associated with aseptic processing were signif-
icant. However, if well controlled, the risk should not necessarily be high. In
other words, determining the risk was the objective of risk management—rather,
process improvement through control and mitigation were the key objectives [9].
Since 2004, more and more FDA guidance has included recommendations for
risk management and assessments. In the 2008 draft version of the FDA Guidance
for Industry on the General Principles of Process Validation, the FDA included
a modest level of references to risk assessments in the text. Some industry com-
ments questioned the apparent “lack” of focus on risk in the document. When
asked, FDA representatives responded that they felt risk management principles
and methodology were so prevalent in the fabric of industry operation that it was
not necessary to emphasize it in the guidance. The number of references to risk
management and assessment nearly doubled in the 2011 final version [10-12].
Throughout the next several years, industry standards, guidance, and techni-
cal reports were prepared to address risk-based decision-making. In 2001 through
2011, the ISPE (International Society of Pharmaceutical Engineering) published a
series of industry guides, employing risk-based methods for design and qualifica-
tion of pharmaceutical manufacturing facilities and processes, including Volume
5 of its Facilities Baseline Guides: Commissioning and Qualification (with revi-
sions in progress) and the ISPE Guide : Science and Risk-Based Approach for the
Delivery of Facilities, Systems, and Equipment . These guides presented meth-
ods for qualifying pharmaceutical manufacturing facilities incorporating risk to
product-quality-based decision criteria. The baseline guide introduced the concept
of evaluating systems based on their relative impact to product quality [13].
In 2007, the ASTM (American Society for Testing and Methodology) issued
E2500-07, the Standard Guide for Specification, Design, and Verification of
Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment .
E2500-07 discussed a risk- and science-based approach to the qualification or