Parameter-finding studies of photodynamic therapy for approval in Japan and the USA

Objective: The purpose of this study is to investigate methods of evaluating therapeutic parameters used in the premarket evaluation of photodynamic therapy (PDT) drugs that have previously been approved in Japan and the United States, in order to establish a methodology that allows optimization of the therapeutic parameters of PDT, and to analyze current issues. Materials and Methods: We examined the details of premarket evaluation of drug dose, drug-light intervals, as well as wavelengths, power density, and energy density of illumination sources used for the PDT drugs that have been approved in Japan the United States. Results: There was a tendency for optimal drug dose and light energy density to be assessed in clinical studies. Drug-light intervals were assessed in the United States in clinical studies, and in Japan only in non-clinical studies. For various drugs, drug-light intervals were assessed based on fluorescence. For most drugs, the wavelength at which the drug can be photo-activated was determined in non-clinical studies. We found only few examples regarding the optimization of light power density as compared to the other therapeutic parameters. Conclusions: Drug dose, drug-light interval, and light energy density are particularly important parameters with regard to the efficacy and safety of PDT drugs. In order to determine the optimal therapeutic parameters of PDT more effectively, appropriate clinical studies need to be designed. Also the use of biomedical engineering, such as fluorescence measurement, is effective for optimizing PDT therapeutic parameters. We believe that in the future there will be a greater number of regulatory science related studies like ours will lead to the further spread of PDT.