POINTS TO CONSIDER FOR COMMISSIONING AND QUALIFICATION OF MANUFACTURING FACILITIES AND EQUIPMENT - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 128

systems, and components involved in the manufacturing process are suitable for
use and function properly, reliably, consistently, and predictably. The method for
doing so is to be determined by the manufacturing company. While the FDA PV
guidance does not contain specific sections on risk management and qualification,
there is an expectation that product quality and, therefore, qualification-related
decisions are made using information based on risk to product quality. The FDA
expects firms to develop programs for assuring that facilities and equipment
involved with critical process steps be qualified and that the rationale for the
qualification program should be based on risk to product quality.
While the FDA position on the use of formal risk assessments is not manda-
tory (at the time of this writing), regulators do expect companies to use a logical
approach, taking into consideration risk to product quality, when making deci-
sions related to regulated product manufacture and release. Therefore, the use of
risk assessment and risk management in decision making is considered important,
useful, and expected.
FDA citations reinforce the expectation of using risk assessment results as
decision-making criteria in facility design. In a 2006 warning letter, the FDA
noted: “Regardless of how often any product is manufactured, because of the

potential risk of cross-contamination, a risk assessment is necessary to determine
whether you need separate and defined areas for manufacturing potent and nonpo-
tent products.” And further states “ ... , your firm provides no risk assessment to
determine the hazard classification of your products [4].” It is interesting to note
that the firm did not appear to get the warning letter because it failed to do a risk
assessment; rather, the warning indicated a lack of clear decision-making criteria
linked to patient safety. In other words, performing formal risk assessment may
not be a requirement, but making sound decisions based on maintaining product
quality is and risk assessments help to achieve that.
The drug industry has presented its views on risk-based qualification. To help
industry clarify the relationship between proper design and the necessity of risk-
based qualification, the ASTM published its Standard Guide for Specification,
Design, and Verification of Pharmaceutical and Biopharmaceutical Manufactur-
ing Systems and Equipment (E2500-07) in July 2007. The document presents
an industry standard guidance, written to help people understand the relation-
ship between risk to product quality, process design, and having equipment and
facilities that work in a reliable manner. The ASTM E2500 Standard Guide states:

...

“ Product and process information, as it relates to product quality and patient safety,
should be used as the basis for making science and risk-based decisions that ensure
that the manufacturing systems are designed and verified to be fit for their intended use.
Further, the Guide reinforces the need for sound engineering and design as the key
to effective facility and equipment qualification — good engineering practice (GEP)
should underpin and support the specification, design, and verification activities by
stating that quality by design concepts should be applied to ensure that critical aspects
are designed into systems during the specification and design process [5].”