Parts 1 and 2 of this article will examine seven critical components of a comprehensive validation program for new and renovated manufacturing facilities. The programs and procedures explained are appropriate for all commonly manufactured dosage forms (e.g., tablets and capsules, active pharmaceutical ingredients [APIs], parenterals). Given that the design, construction, and qualification and validation of a major facility are relatively infrequent events in most corporate life cycles, some of these project components are not well known or understood. For this reason, Part 1 of this article examines the following areas:
Part 2 will continue with a discussion of the following validation-related subjects:
By definition, the construction of a new or renovated facility and the purchase and installation of mechanical equipment and process systems constitute a project. All projects have basic, common features: a logical start, a logical end, and little or no possibility of recurrence (i.e., the project will not repeat at some future time). In addition, the design process is common to all facility projects. All facilities start with a design, about which engineers, owners, scientists, and other stakeholders confer to determine how the facility will appear and operate and what equipment and systems are needed. The usual sequence starts with the development of a conceptual design by an engineering firm, from which preliminary decisions are made about facility layout and size, utilities required, and equipment capacity and material of construction. The process then continues into the preliminary and detailed engineering stages, in which costs are finalized and designs are completed and approved. It is at this point when the conceptual design transitions to preliminary engineering that formal review to verify GMP compliance begins.
In general, process equipment and utility systems affecting product quality or contacting product are the subject of design review. Typical reviewed utilities include heating, ventilation, and air-conditioning (HVAC), compendial waters (e.g., water-for-injection, purified water, clean steam), and compressed gases such as nitrogen and compressed air. At present, regulatory expectations for other utilities such as chilled water or plant steam are minimal, and these may be omitted. Design review is mandatory for highly customized or unique process equipment, particularly when the unit is custom manufactured. Equipment for critical processes such as aseptic filling and packaging, lyophilization, and final purification also requires rigorous evaluation. Because the GMP regulations are interpretive and nonspecific for equipment design and construction, the design engineer and owner are responsible for assessing compliance (1).