Translational research requires the high scientific and ethical quality throughout clinical trails according to the ICH-GCP guideline. Cell therapy includes blood transfusion, stem cell transplantation, adoptive immunotherapy, gene therapy, and regenerative therapy. GMP (Good Manufacturing Practice)-graded cell processing such as cell preparation, culture, manipulation, labeling, storage, and shipping is mandatory for the progress of such advanced cell therapy. One of the first steps in cGMP conversion from bench to clinic is designing facility for preparation of clinical material to be used in human trials. However, cGMP-graded cell processing has a number of different points compared with the conventional GMP for drugs. Since we have no definite and detailed rules yet in Japan how to prepare cell products for advanced cell therapy and how to design these cell processing facilities, we have to establish these rules as soon as possible in collaboration with physicians, technicians, engineers, pharmacists, GMP consultants, and government officials in order to make an appropriate progress of translational research for cell therapy. Considerations important for the development of cGMP-graded cell processing are discussed.
Conformity of drug products to their specifications alone is not sufficient to assure the quality of drugs to be administered to human subjects. In many European and North American countries, the necessity of validation of the drug manufacturing processes has been discussed and these countries have incorporated such validation into their regulation of drug products. Validation is now recognized as a global standard and has become an essential requirement for drug manufacture. For sterile drug products, specific methodology for conducting the validation has been established and accepted internationally. Regarding solid drug products for oral administration, however, there have been only a small number of studies on the validation of manufacturing processes and many drug manufacturers have difficulty in deciding how to carry out validation for oral solid preparations. Based on experience in GMP (Good Manufacturing Practice) inspection, the author investigated suitable methodology for the validation of ethical drugs, OTC (over-the-counter) drugs, and natural drug preparations/extract products in oriental medicine formulation. The results of the study were published as Osaka Prefecture's “Guidelines for Validation by Individual Drug Formulatron Groups,” which have facilitated the spread of validation without imposing a great burden on manufacturers. In this report, the author would like to explain the administrative background and the fundamental concept of the study.
As any kind of dryer has its own drying speed, freeze-dryer also has a drying speed as capacity in addition to total shelf surface and ice condensation load to be designed and validated. The drying speed, i.e. sublimation speed and desorption speed mainly depends on the conductance of pipe between drying chamber and ice condenser and the ice condensation speed in addition to heat transfer from shelves to product. Such drying speeds of freeze-dryers should be validated as time-based capacity with full load of water at a required control pressure for the purpose of checking max. allowable set values for operation parameter, challenge tests, reduction in cycle time and future improvement in design and drying performance.
A temperature multiplication chemical indicator must change color by a temperature multiplication condition step-by-step. The chemical indicator of new development inspected performance evaluation with Steam CIER (Chemical indicator Evaluator Resistometer) Vessel. In addition, I let change of color performance of a chemical indicator and a change of central temperature of a standardized test pack used a normal steam sterilizer, and air exclusion rate change and inspected it. As a result, a thing having the performance that a chemical indicator changed color in a processing condition of 121°C and 134°C step-by-step of new development was inspected. I suggested that the system, which supposed an approximate sterility assurance level, used color-difference meter with this chemical indicator and could build it.