BACKGROUND AND INTRODUCTION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 3

that to best serve public interest, decisions on resource allocation, focus, and
prioritization should be based on risk to patient safety and public safety. Those
in the industry are impacted by the approach. For instance, a firm manufacturing
over-the-counter (OTC) oral dosage products and having a relatively clean com-
pliance record would likely be inspected less often or receive less attention than a
firm aseptically manufacturing sterile injectables and having a more problematic
compliance record.
The prioritization of resources based on risk to public safety make sense and it
led to better productivity and effectiveness. It was logical that the agency would
expect the industry to employ similar approach to make resource- and focus-
related decisions. Firms are encouraged to use risk to product quality and patient
safety as a criterion for decision making.
Risk management and assessment are not new. People use risk assessment as
a way to help make decisions every day. When you walk across the street, drive
through a yellow light, or order a meal—you employ a level of risk assessment,
weighing the impact of a hazard and the likelihood of the hazard happening
against anticipated benefit. Companies do the same in many aspects of corpo-
rate functioning from financial decisions, to investments, to plant locations, and
product development. If their objective is to serve their customer, then it makes
sense that they would employ this type of decision making to manufacturing and
response to patient needs and safety.
In 2005, the ICH (International Conference for Harmonization) issued Q9
Guidance on quality risk management. ICH Q9 was later issued in 2006 as
Guidance for Industry by the FDA and adopted by the EU as Annex 20 of
the European GMPs in 2011. The guidance remains optional for pharmaceutical
product manufacturers in the United States and Europe [7]. However, references
to risk assessments and criticism for not employing such measures have appeared
in FDA warning letters dating back to 2006 [8]. Regulatory citations indicated that
companies face questions on how decisions related to product quality were made,
if assessments of the risk of process steps and changes to product quality were
not employed. If a company's obligation is product quality and patient safety, it
should take such risks into account when making manufacturing decisions. How
else could it make these decisions?
In the spring of 2005, at the PDA (Parenteral Drug Association) annual meet-
ing in Chicago, the leaders of the Process Validation Interest Group asked its
members for their topic of most interest or concern. The overwhelming answer
was risk management. The leaders then asked how many of those individuals
were currently utilizing or were aware of efforts within their respective orga-
nizations to utilize risk management. Only a few raised their hands. This was
not unexpected. ICH Q9 was being issued and reviewed. Papers presented at the
PDA annual meeting spoke about the need for risk management.
One person in the meeting noted that their risk assessment efforts were unsuc-
cessful, as they were subject to criticism from local regulators, because of the
misuse of the risk management. The misuse apparently involved using risk assess-
ment to identify process-related risk, but then failing to take steps to mitigate that