PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 218

As it is used throughout the process lifecycle, QRM documents are living and
should be maintained in the current state through timely review and update.
This chapter presents QRM application in PV, typical tools, risk factors, and
challenges in applying risk-based validation. PV activities at all three stages of
PV lifecycle are discussed, along with examples of QRM application in process
design, PPQ and continued process verification. It shows risk-based validation in
study designs, such as univariable and multivariable studies, and mixing and hold
time studies. QRM tools can be utilized in determining CPPs, identifying high risk
areas, defining controls and risk control strategies, determining the significance
of process changes and the periodic review schedule. Considering the higher cost
of running experiments at the commercial scale, the risk prioritization tool can be
used to identify areas that pose the highest risk, design space, and control range
for CPPs. Integration of QRM in technology transfer would ensure successful
process transfer.
CV is an integral part of successful licensure and commercial manufacturing.
This chapter also discusses risk factors for CV and multiproduct operations.
Finally, a list of applicable regulatory guidances for CV and PV was provided.
DISCLAIMER
The information provided in this paper reflects the authors' view and is not
intended to represent the official position of our companies. Actual processes
previously or currently implemented by the company may differ from those dis-
closed in this paper. Author makes no representations or warranties regarding
these processes as may be implemented by readers of this chapter.
REFERENCES
1. 21 CFR 210 and 211: Current Good Manufacturing Practice In Manufacturing, Pro-
cessing, Packing, or Holding of Drugs: General. April 1, 2009 (revised).
2. EudraLex by the European Commission, Volume 4—Medicinal Products for Human
and Veterinary Use: Good Manufacturing Practice; Annex 15 to the EU Guide, Qual-
ification and Validation, July 2001.
3. FDA Guideline on General Principles of Process Validation, May 1987.
4. FDA Guideline on General Principles of Process Validation, January 2011.
5. Q8 (R2) Pharmaceutical. Development, ICH Harmonised Tripartite Guideline, August
2009.
6. Supplementary guidelines on good manufacturing practices: Validation, Annex 4,
WHO Technical Report Series, No. 937, 2006.
7. PIC/S Guide to Good Manufacturing Practice for Medicinal Products Annexes,
September 2009.
8. CMC Biotech Working Group, Product Development and Realisation Case Study:
A-Mab, Version 2.1, 30th October 2009.