PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 174

PROCESS LIFECYCLE VALIDATION

A. HAMID MOLLAH AND SCOTT BOZZONE

8.1 INTRODUCTION

Process validation (PV) is a requirement of the Current Good Manufacturing
Practices Regulations for Finished Pharmaceuticals (21 CFR Parts 210/211 and
EU GMPs) [1,2]. Since 1987, when the U.S. FDA issued guidance [3], the
pharmaceutical industry approach to PV has typically been to evaluate three
consecutive, prospective batches. This approach was used regardless of risks
associated with aspects such as complexity of the process or dosage form, type
of unit operation, or development history. There has historically been limited
application of risk management in defining the amount of data or number of
batches required for PV studies. In contrast, a science- and risk-based approach
applied throughout the process lifecycle is a more holistic and robust approach.
Table 8.1 shows a comparison between traditional, and science- and risk-based
process approaches.
Risk management can be applied in several areas of PV, from early process
design/development through maintenance of validated states during commercial
manufacturing [4]. Some of the benefits of applying a science- and risk-based
approach during PV are as follows:

• improves process understanding by proactive identification of failure modes
(hazards), and managing the identified risks as early on in the product life-
cycle as possible;