ABSTRACT
INTRODUCTION Validation is a requirement for USP/EP/JP Purified Water and Water for Injection systems. Many pharmaceutical water purification systems have also established internal “qualification” programs, with the same general structure as a validation program. Qualification as a non compendial system has been discussed in chapters 11 and 12. Throughout this text, numerous references have been made to the fact that validation (or qualification) is “woven” throughout any pharmaceutical water purification system project. Beginning with the Basis of Design/ Validation Master Plan and proceeding through PQ with Summary Report, validation clearly demonstrates that the system performs and meets all of the stated objectives outlined in the Basis of Design/User Requirement Specification (URS) (Collentro and Angelucci, 1992). It has been suggested that proper validation of a water purification system involves integrating specific requirements throughout the project. The validation process will vary with the type and nature of the system, installation, and facility as well as “format/procedures” established by the “owner.” A summary of milestones that may be considered for this process could include but not be limited to the following:
l Basis of Design/URS l Risk Assessment l Validation Master Plan l Conceptual design l Conceptual design review l Preparation of detailed specification l Review of detailed specification l Final revision of detailed specification and associated drawings, such as a P&ID l Request for water purification equipment supplier’s proposals l Review of water purification equipment supplier’s proposals l Formal documentation of proposal review l Water purification equipment supplier “kickoff” meeting l Review of water purification equipment supplier’s “submittal package” l Periodic inspection, with meetings, of water purification equipment supplier’s
progress at indicated “milestones” l Final inspection of equipment at water purification equipment supplier’s facility
including Factory Acceptance Test (FAT) l Receipt of equipment and “turnover package” from water purification equipment
supplier l Review of turnover package, including drawings and Bill of Materials for components l Equipment installation l Performance of Site Acceptance Test l Preparation of IQ l Execution of IQ l Preparation and approval of OQ, training manual, and maintenance manual l OQ execution l System start-up l Preparation of PQ l Initiation of PQ l Ongoing review of data generated during PQ execution l Compilation of data generated during PQ execution l Preparation of a validation Summary Report l Preparation of a suggested “perpetual” analytical monitoring program for the system
It is extremely important to consider the fact that validation (or qualification) of a pharmaceutical water system cannot commence once the water purification equipment is received at a facility, installed, and started up. The process begins during preparation of the Basis of Design, the initial step in defining the requirements for the system, and proceeds throughout the project, with specified definition of required documentation. Further, it is important to remember that multiple disciplines from a pharmaceutical manufacturing firm, such as facility engineering, quality control/assurance, validation, maintenance, analytical laboratory, controls and instrumentation, administration, manufacturing, and other appropriate disciplines, must be involved throughout the project. The input of each discipline is extremely important during execution of a successful project.
