DIRK J. SPIELVOGEL
Global Drug Substance Project Coordinator, Small Molecules Technical Development, MSAT

F. Hoffmann-La Roche, Ltd.
Grenzacherstrasse, CH-4070 Basel, Switzerland

Co-authors: 

SERGIO BACCHI – Global Drug Substance Project Coordinator, Small Molecules Technical
Development, MSAT 

MICHAEL E. PIERCE – Head Drug Substance Manufacturing Science and Technology
Small Molecules Technical Development

Abstract

Continued process verification (CPV), as the third stage of the validation life cycle, can now be considered an established practice since its introduction by the FDA in 2011. This perspective aims to provide feedback on managing CPV of outsourced pharmaceutical manufacturing operations. Four illustrative collaboration models are used to describe general aspects, benefits and drawbacks. Independent of the collaboration mode it is concluded that CPV is not only a regulatory and quality requirement. CPV serves as a valuable tool to assess manufacturing data and allows and aids unbiased decision making across organizations to maintain manufacturing processes in a validated state, improve operability and secure safe products for patients.

INTRODUCTION

Since the 2011 publication of the FDA guidance for industry “Process Validation: General Principles and Practices” numerous articles (1) have assessed the intent and implementation of the outlined three staged approach consisting of Process Design (PD), Process Qualification (PQ) and Continued Process Verification (CPV). Organizations active in the field of pharmaceutical manufacturing have implemented processes to satisfy this FDA guidance as well as other pertaining relevant guidelines and standards (2). In this perspective, specific focus is given to stage 3 of the process validation life cycle, that is Continued Process Verification and in particular upon its execution and impact in the context of outsourced operations for small molecules manufacturing. In doing so, the aim is to share experiences on working models, lessons learned while considering the pro’s and con’s for both contracting parties.

CPV is more than just a regulatory requirement. CPV intends to allow detection of non-common cause variation in the manufacturing process and potential impact to product, ahead of irreparable ...