Biomedical Engineering Reference
In-Depth Information
identifies variables (e.g., raw material variability, process parameters) that may
influence product quality. All of these can be explored via designed experi-
ments to elaborate the effects of the variables and any parameter interactions.
Risk assessment and management during process development helps companies
identify the process parameters and attributes that will impact the quality of the
product. It also allows companies to confidently validate only the parameters and
attributes that are critical to the manufacturing process. This enhanced under-
standing of the process parameters and quality attributes eventually leads to a
more thorough understanding of the product and its quality and safety profile.
In recent years, the trade-offs between achieving optimal supply chain efficien-
cies and management of supply chain risk has created some major problems for
companies because they have jeopardized patient safety. Global supply chains
are even more risky than domestic supply chains because of numerous links
interconnecting a wide network of firms and communication and cultural gaps.
Therefore, supply chain risk assessment is absolutely essential for biotech prod-
ucts and should begin with incoming raw materials and excipients and extend
through the distribution chain to the patient. Information gained from experience
and product development can be used to identify potential risks and establish mit-
igations to minimize their occurrence and increase the ability to detect failures
should they occur.
Finally, risk assessments should become a living part of the product life cycle.
Specifically, as the product/process design matures, technology content improves,
and patient needs and safety concerns are better defined or regulatory require-
ments change, the risk assessment plan should be maintained and updated as new
knowledge is gained about the product and process.
This chapter briefly discusses the process steps traditionally used for manu-
facturing biopharmaceutical products and identifies areas of risk associated with
this process step. The reader should note that, while this chapter provides a list
of risks that are associated with the process steps outlined, it is not exhaustive
or all inclusive. This chapter also does not address risks associated with the
preparation of finished dosage forms, for example, prefilled syringes. These risks
are addressed elsewhere in this topic (see Chapter 9 for a complete discussion
of aseptic processing risks). A detailed case study is provided at the end of
the chapter, which illustrates how a risk assessment tool can be applied in the
manufacturing process to identify, mitigate, and control risk. Finally, this text is
based on the opinion and experience of the authors and is not meant to replace
regulatory guidances or regulations.
12.2 UNDERSTANDING CRITICAL QUALITY ATTRIBUTES
AND CRITICAL PROCESS PARAMETERS
All products have a set of characteristics or attributes by which they may be
defined. Frequently, such attributes are included in specifications and product
release tests and are thought of as quality attributes. When a quality attribute
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