There are various academic associations related to pharmaceutical sciences and technology, most of which are dealing with pharmaceuticals themselves. The focussed areas are to synthesize new chemical entities, to find new pharmacological or therapeutic effects, and to develop new dosage forms. Relatively few researches have been reported on the area of manufacturing process, although there have been various researches and studies have been performed, particularly since the time of introduction of the concept of validation. This would be attributed to the lack of appropriate JOURNAL which enables the active information exchange possible. The journal newly published by Japan PDA would encourage persons who are engaging manufacturing plant, development engineering, quality laboratory and also who are engaging in regulatory inspections. As some examples of subjects which are expected to be contributed to the Japan PDA Journal relating to the future concept of manufacturing plant and manufacturing control, several topics are introduced. In the future manufacturing plant, 1) environment controlled area would become limited area which is as small as necessary, which becomes possible by applying isolator system or barrier system. Even the classification of cleanliness would become different one in future, along with the study of air flow dynamics as well as the application of isolator system. 2) Application of Luciferin-Luciferase-Chemo-luminance, method of microbial control would make the current air borne microbes control method different one and to make more quick in getting result and feed back to the process. 3) Continuous and automatic monitoring of air borne particulate would make more strict control and more quick action possible. 4) Systematic analysis of various data obtained from the monitoring of water would make correlation among various specifications more clear. As the results, continuous automatic in-line monitoring of water system by using conductivity, TOC, pH, and particulate matter might be enough to assure the quality of water, after the accumulation of quality data. As an example, it might be revealed that TOC value of 25 ppb or less shows endotoxin of 0.25 EU/ml or less. UF membrane would be used more frequently, since it endures high pressure steam sterilization. 5) Hydrogen peroxide sterilization would be more frequently be used according to the development and application of gas monitoring system. Submission of such papers and active discussion would make the pharmaceutical industry active and regulatory agencies would be able to have sound scientific basis on each operation.
Harmonization of requirements for the regulation of drugs in the world is essential in order to make newly developed pharmaceuticals available all over the world as quickly as possible. For such purpose, ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) has been organized and actively promoted by 6 parties from three regions (Japan: MHW & JPMA, USA: FAD & PhRMA, EU: CPMP & EFPIA). Quality topics on “Stability Testing, ” “Validation of Analytical Procedures” and “Impurities Testing” has already been finalized among three regions and implemented as the domestic guidelines by the regulatory authority of each member country. Other quality topics on “Specifications,” “GMP on Active Pharmaceutical Ingredients” and “Common Technical Documents” are now under discussion in ICH. In Japan, Revision of General Notices in Japanese Pharmacopoeia is proposed to cope with the concepts of “periodical/skip testing, ” in-process testing” and “parametric release” included in the Step 2 Draft of ICH Speicification Guideline. This article describes the concepts of ICH quality guidelines and their impacts on the regulation for drugs in Japan.
A novel dual-chamber Bag (O-IN-Bag) was designed using a film which is a blend of polyethylene and polypropylene. The Bag is divided into by welding two chambers by an easy-to-peel seal (EPS). The upper chamber is filled with an injectable powder or lyophilized drug and the lower chamber is filled with 100 ml of diluent such as 0.9% sodium chloride. In the present report, we describe the characteristics of this O-IN-Bag product. The generation of particulate matter at the breakage of the EPS, stability of cefazolin sodium (CEZ), strength of the Bag container, and sterility of the inside of the container were studied. The results were compared with those of a conventional injectable system wherein antibiotics in glass vials are reconstituted with diluent using a double-ended transfer needle or a syringe. Reportedly, the O-IN-Bag system significantly reduces the time required to reconstitute drugs and storage space, and is easy to dispose. The system could retain the sterility and stability of its contents, and generated less particulate matter than the conventional system. In addition, the Bag proved physically strong enough as a container.
Maintaining the room pressure is essential for preventing contamination during pharmaceutical operations. Among the factors affecting the room pressure, the control functions were discussed. We stressed that in order to improve the quality of room pressure control, a constant air volume unit of higher accuracy and stability should be employed; the pressure control should not be sensitive to over-integration even after a long lasting deviation; the necessary facility design is such that the air balance in the room should not be drastically changed; special considerations should be given when determining the position of louvers, the definition of reference pressure, and duct geometry; and a computer-based integral management for the entire parts of automatic controls should be employed.
Process validation is necessary to assure the quality of product and is required for approval of manufacture. Appropriate process validation is achieved by appropriate development of manufacturing process, in-process control and end-point of each process, based on the appropriate design. The development of the manufacturing process, in-process parameter and the end-point must be achieved based on the scientific approach. The sieving method using sonic filtration mechanism could achieve the evaluation of wet granulation progression in a short time and with small sampling amount. This sieving method of wet granule progression was also effective method to determine end-point of the wet-granulation process in a various production scale. Thus, the scientific approach with in-process product seems to be effective to determine the end-point of each process.