Control system validation in multipurpose biopharmaceutical facilities

Abstract

In the biopharmaceutical industry, validation requirements have significant implications in almost every engineering aspect of the production process. Strict demands from the US Food and Drug Administration (FDA) and from the European Commission regulatory authorities for validated systems in bulk pharmaceutical manufacturing facilities have raised both the profile and the importance of this aspect of the design and production process. Successive rulings, particularly by the US FDA, have served to focus an increased amount of time and energy on the development of validation strategies in most manufacturing sites. In some areas, such as the validation of the manufacturing process itself and of the associated production equipment, the requirements have tended to concentrate on the formal documentation of many aspects of the commissioning and production processes which previously were typically checked but not necessarily recorded in detail. The validation of vessel cleaning has, on the other hand, generated a large amount of work (and documentation) which was, in many cases, not previously required such as for example, swab testing or the cleaning of vessels between campaigns of the same product. The validation of computer systems has tended to set a requirement for documentation and verification somewhere in between. In many areas of the validation process there is simply a formal recording of work which would also be completed for an unvalidated computer system. In other areas, new and extensive verification is required above that which would be completed otherwise. In this paper, the details of the validation requirements for computer control systems are reviewed. Particular emphasis is placed on the implications for a multipurpose biopharmaceutical facility. Each step is discussed, from the development of a validation plan, through the definition and design of the software and hardware, to the installation and qualification of the complete system.