POINTS TO CONSIDER FOR COMMISSIONING AND QUALIFICATION OF MANUFACTURING FACILITIES AND EQUIPMENT - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 152

involves listing all of the systems and components in the process and then deter-
mining if each item has an impact on product quality. To be able to assess the
impact of a system or component to product quality, one must understand the
process, the variables inherent in the process, the source of process variation, and
the effect of variation.
The system or component is assessed as to the effect its failure may have on
the quality of the product. If the failure of the system or component affects the
quality of the product, then it should be qualified. A relative impact assessment
would determine to what level the failure would affect quality. The greater the
effect on product quality, the more important the qualification. As the concern is
ultimately patient safety, detection of process failure or loss of product quality
attribute plays a role in mitigating the risk. If the failure or its effect can be
detected and removed before reaching the patient, then the risk to patient safety
is eliminated. The risk to product quality may still remain and would result in the
loss of the product. If detection is used as a mitigating factor, then the detection
method should be qualified.
The impact on quality of a system or component will vary according to the
process step it is supporting. For illustrative purposes, let us continue to use
lighting as an example. Lighting to illuminate an area may or may not require
qualification, depending on the effect on product quality. While lighting in an
inspection booth where visible defects are inspected would likely require qualifi-
cation, lighting to strictly illuminate the packaging area floor may not. Lighting
in a stability chamber, where the product may be light sensitive, may require
qualification, while the lighting in the laboratory room may not.
Systems with functions that affect product quality are sometimes referred to as
direct impact systems, quality impact systems, or GMP impact systems . However,
some systems may affect the ability to manufacture the product, but not the
quality of the product. In other words, failure of these systems may shut down
operations or limit yields. For example, a vacuum system that transports waste
might not affect product quality and therefore not require qualification, but a
vacuum system that removes dust from a tableting operation might have an
effect on the quality of the product and would require qualification. Another
such system might be plant steam. If plant steam is lost, then production may
not be possible. However, the quality of the product is not affected. In this case,
the company could choose not to qualify the plant steam system, and rely on
commissioning to assure reliable operation.
Although it may be sound business judgment to qualify or commission these
systems in some way to ensure proper functionality and capability, it may not be
necessary to qualify these systems to assure product quality and patient safety.
However, the failure of a clean steam system, which produces steam for the
autoclave and does contact filler parts, may affect product quality if it results
in poor quality steam. A notable exception might be assurance of continued
product supply. If patient safety is an objective, the loss of product because of
the malfunction or failure of “nonimpact systems” while not affecting product
quality might still result in harm. For the purpose of this chapter, product supply