This paper is the first report on research conducted by the Kansai Study Group GMP Inspection Case Study Group of the Japan PDA Pharmaceutical Manufacturers Association on GMP inspections of pharmaceutical manufacturing facilities. The theme of this study is “Unfavorable microbial control of pharmaceutical water and quality assurance of non-sterile drug products”. We recognized that while conventional deliverables often indicate the direction and approach to improvement for issues raised, they often do not go into the practical methods to be used in the field, so in this study we focused on providing specific countermeasures.

Information gathered by the FDA has revealed that, in order to prevent microbial contamination of pharmaceutical water, it is necessary to focus not only on the total number of microorganisms, but also on the types of microorganisms. The FDA refers to microorganisms that may cause serious infections or other health problems in patients as “objectionable microorganisms”. In order to reduce the risk of contamination by objectionable microorganisms in non-sterile drug products, it is important to identify the types of objectionable microorganisms detected in pharmaceutical water and to establish a contamination control strategy (CCS) that minimizes biofilm formation. We identified the risks in the four elements of hardware design, operation, monitoring, and maintenance of pharmaceutical water systems, and considered measures to mitigate them.