BIOPHARMACEUTICAL MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 350

product and a robust product formulation that is able to withstand slight excur-
sions in temperature. The former is demonstrated via validation exercises, while
the latter is demonstrated through stability studies that challenge the product at
temperature extremes.
12.3.9.2 Quality Risk Management in Distribution The major risks associated
with distribution and supply chain are discussed in the following section.
While biopharmaceutical products share many of the same distribution risks
as pharmaceutical products, their primary risk is associated with temperature
excursions beyond acceptable ranges. This risk is controlled through careful
qualification of packaging and shipping containers as well as a thorough charac-
terization of the distribution chain to ensure that product temperatures are well
maintained and excursions are minimized.
12.4 SUMMARY AND CONCLUSIONS
Risks are associated with biopharmaceutical manufacturing processes from the
acquisition of raw materials and excipients through distribution of the final prod-
uct (Table 12.4). The identification (Table 12.5) and analysis of risks at each step
of the process facilitates better process knowledge, resulting in a more robust
process and a product of more uniform quality. A variety of tools are available
to help the practitioner complete this task. Examples of these tools have been
provided in this chapter and elsewhere in this topic.
The overall control of process risks begins with the identification of the prod-
uct's critical quality attributes and the critical process parameters by which they
are controlled. Given this information, appropriate control strategies can be estab-
lished to mitigate the potential for process shifts and subsequent product quality
issues.
Raw material and excipient supplies must be carefully assessed and controlled
to assure consistency and safety of the incoming material. The microbiological
attributes of raw materials are of particular importance and must be carefully
controlled to preclude the possibility of contamination. Excipient variability and
its impact on product quality must be well defined.
Cell banks must be adequately characterized and maintained. Cell banks carry
a risk of introducing adventitious agents into the process stream, or changing
genetically or biochemically, and thereby altering the characteristics of the prod-
uct produced. These risks need to be addressed and mitigated through appropriate
cell bank handling, characterization, and storage.
Biopharmaceutical manufacturing risks can be similar at several stages of
the process, a fact that can be advantageous for manufacturers. For example,
cell culture and downstream purification processes carry common risks including
that of microbial contamination and unsuitability of growth media. Improper
resins, cleaning failures, or changes in process parameters may also adversely
impact product quality. Robust process characterization analyses through either