PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 182

5. Consider and document all the risk factors, not prematurely ruling out
while identifying risks because they may appear negligible.
6. Ensure management support for risk management program, with adequate
resources and investment at the beginning.
7. Have a process for ensuring communication of risks to appropriate stake-
holders including decision makers at various stages of the risk manage-
ment process.
8. Ensure that the RA establishes connections between process monitoring
and the initial validation as appropriate.
9. Ensure RA documents are usable at multiple sites.
10. Maintain RA documents current.
8.6 LIFECYCLE APPROACH
With the issuance of the FDA guide on PV, the activities of PV should be
viewed from a lifecycle approach [4]. The three applicable stages are process
design (e.g., process development, characterization, and validation), performance
qualification (e.g., equipment/utilities qualification and process performance qual-
ification), and maintenance of validated state (e.g., process monitoring, change
evaluation, and verification) (Table 8.2). Note that the FDA guide includes both
system (equipment and utility) qualification and PV. (Refer to Chapter 7 for QRM
application for system commissioning and qualification.) This chapter discusses
process development, characterization and validation, process performance qual-
ification (PPQ), and process monitoring as well as CV and cross-contamination
risks. Examples of QRM application in this chapter encompass process design
through continued process verification stages, including cleaning. PV studies add
to the knowledge throughout the lifecycle.
8.7 PROCESS DESIGN
Process design, such as process development, scale-up and characterization, starts
with the identification of the properties of a target molecule or new chemical
entity. As the product moves through preclinical and clinical studies (Phase I to
III), scale-up and manufacturing process optimization takes place. The process is
finalized before qualification batches at the commercial scale (also known as PPQ
batches). Before the start of PPQ, studies supporting commercial-scale manufac-
turing can be performed at any scale as long as it is representative of commercial-
scale manufacturing. Scaled-down models are used in process development and
characterization to increase process knowledge through increasing the number of
conditions tested. Any planned, documented study that adds process knowledge
and supports product licensure is considered part of PV in this chapter (e.g.,
development, characterization, validation, comparability, and compatibility).