PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 175

TABLE 8.1 Traditional versus Science and Risk-Based Lifecycle Approach
Traditional Approach Science and Risk-Based Lifecycle Approach

• One time activity focuses on
final product testing
• Demonstrates process based
on current understanding
• Process runs at established
set points

• Facilitates increased process understanding
• Proactive and iterative activities throughout the
process lifecycle
• Process monitoring is tied to process validation
through the control strategy

• Arbitrarily selecting three
batches for initial validation
(e.g., qualification batches)
• Selecting three batches
typically for process changes

• Uses scientific rationale to determine number of
batches/amount of data required
• Determines scope of validation by analyzing
data and significance of change
• Uses statistical tools during development, initial
validation, and process monitoring
• Considers all potential risk factors in designing
process validation studies
• Prioritizes critical aspects and reduces effort on
aspects that are not important

• Study design is based on
template and/or existing
practice

• Leverages historical knowledge and experience
• Determines extent of validation testing/sampling
• Analyzes validation data and determine controls

• Deviation is seen as a
setback

• Deviation may provide an opportunity to
increase process understanding and avoid
failures during commercial manufacturing

• enables science-, data-, and risk-based discussions by a team of subject
matter experts (SMEs) so that decisions and outcomes are sound and robust;
• ensures that high risk, critical aspects of the process are well understood by
appropriately designed studies;
• reduces product and process failures;
• saves cost and time by focusing on the pertinent components of process and
establishing priorities that separate essentials from “nice to haves.”

The risk-based approach does not mean doing less, but doing the right amount
at the right time and avoiding non-value-added activities. While equipment and
systems are qualified before the start of qualification (also known as validation,
demonstration, and consistency) batches, commercial-scale PV, and cleaning val-
idation (CV) are performed during the qualification campaign. There are many
similarities between PV and CV: both include a process development phase and
have regulatory requirements to be qualified at the commercial scale, both have
potential critical process parameters (CPPs), utilize a continued verification phase
during commercial manufacturing, and are a significant aspect in establishing