PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 202

risk, commercial-scale experiments are not required. Here are the steps for exper-
imental design and execution.
1. Collect input from SME(s) to identify input parameters that may impact
product quality attributes.
2. Identify potential interactions between two or more parameters.
3. Define preliminary operating ranges for each mechanical parameter.
4. Design and execute specific experiments (e.g., DoEs) to study parameter
interactions and their impact on product quality.
5. Use the DoE results to define key mechanical parameter operating windows
for optimal equipment set points.
Benefits of commercial-scale mechanical DoE study include the following:
• improved understanding of production processes and equipment through
hands-on experimentation;
• identification of high risk activities;
• definition of optimal process windows (parameter operating ranges);
• discovery of equipment issues/mismatches;
• more reliable production output; and
• more consistent product quality.
Step 6: Risk Control Strategy and its Effectiveness Develop and document a
risk control strategy. It should include a summary of the results obtained from
the RA, the actions that were or need to be taken to control the identified risks,
any risk acceptance decisions, and the estimation of the residual risk remaining
in the product/process, together with the rationale as to why this level of risk is
acceptable.
The effectiveness of the risk reduction strategies developed and implemented
as a result of the QRM process needs to be monitored on an ongoing basis
following its implementation. This monitoring can take the form of changes to
existing production documentation to ensure the appropriate testing implemented
becomes part of the standard manufacturing process for the product. The follow-
ing tools, data and information can be used to determine the effectiveness of a
control strategy:
• inputs process variables—statistical process control (SPC) and process capa-
bility indices for critical input parameters;
• outputs (quality control assay results)—SPC and process capability indices
for critical and key quality attributes; and
• discrepancies, CAPA (corrective and preventive action), deviations, and
product complaints.