From knowledge to risks
Once each unit operation is related to CQAs through a cause-and-effect matrix and the process parameters and attributes are documented, an initial risk assessment to determine the potential impact of each process parameter is performed. Prior to process characterization experiments, this risk assessment may be more high level using primarily prior knowledge and scientific principles. However, a more formal FEMCA may also be considered.
Table II is an example of an initial risk assessment for a single unit operation. Included in the justification is the expected relationship with CQAs and how the parameter may be influenced during scale-up. Fixed parameters are set to non-critical as they do not impact process variability. For the initial process characterization experiments, process parameters with medium to high impact will be included.
Table II: Example of initial risk assessment of process parameters
In Part I of this series, the author looked at criticality as a continuum to apply risk analysis during process design, and to relate process unit operations to quality attributes using a cause-and-effect matrix.
In Part II, the continuum of criticality for parameter and attributes will be used to design process characterization studies using DOE. From the initial risk assessment of critical parameters, experimental data from formal studies will confirm the criticality assignment—critical or not—and help to assess the level of impact to CQAs.
References
1. FDA, Guidance for Industry, Process Validation: General Principles and Practices, Revision 1 (Rockville, MD, January 2011).
2. ICH, Q8(R2) Harmonized Tripartite Guideline, Pharmaceutical Development, Step 4 version (August 2009).
3. ICH, Q9 Harmonized Tripartite Guideline, Quality Risk Management (June 2006).
4. ICH, Q10, Harmonized Tripartite Guideline, Pharmaceutical Quality System (April 2009).
5. ICH, ICH Quality Implementation Working Group Points to Consider (R2), ICH-Endorsed Guide for ICH Q8/Q9/Q10 Implementation (6 December 2011).
6. ISO/IEC Guide 51: Safety Aspects-Guidelines for their inclusion in standards, 2nd ed. (1999).
7. IEC 60812, Analysis Techniques for System Reliability-Procedure for Failure Mode and Effects Analysis (FMEA), Edition 2.0 (January 2006).
8. ISPE, Product Quality Lifecycle Initiative (PQLI) Good Practice Guide, Overview of Product Design, Development, and Realization: A Science- and Risk-Based Approach to Implementation (October 2010).
9. ISPE, Product Quality Lifecycle Initiative (PQLI) Good Practice Guide, Part 1-Product Realization using QbD, Concepts and Principles (2011).
10. Parenteral Drug Association, Technical Report 60, Process Validation: A Lifecycle Approach (2013).