Design Control and Validation of a Facility for Sterile Clinical Trial Preparations

Abstract

Our Clinical Trials Sterile manufacturing facility was designed to fulfil the requirements of product sterility, suitable batch capacity and versatility in handling varying clinical research formulations in a safe environment. As a Unit specializing in the manufacture of sterile liquid and freeze dried clinical supplies within a research environment, we have experience associated with validation of developing processes, varying batch size and the handling of toxic or costly research materials. Being restricted in size, the facility features several items of multi-cycle equipment. The special requirements for control and validation of such equipment are discussed. The construction, delineation of work areas and the air distribution/filtration system is described with an indication of the nature and regularity of maintenance and measurement of critical air flow parameters. The microbiological monitoring program is designed to give a weekly indication of the overall level of contamination during periods of nonproduction and more specifically, a daily count of contamination of critical areas and operations during manufacture of clinical supplies. Sterilizer validation is discussed in detail in conjunction with routine maintenance and control schedules and establishment of “standard cycles”. The control of the complete manufacturing process by nutrient broth evaluation is described with reference to level of challenge, contamination “acceptance” levels and changes in the process necessitating re-validation. The facility has its own water for injection ring main. Control of chemical and microbiological water purity is described together with the application of the Limulus Amebocyte Lysate Test to routine control of water quality.