Normalized Design On The New Drug Substance Research

Research on the synthesis of the potential new drug substance is one of the most important parts in the new drug research process. One of the main objectives of the synthesis research is to provide qualified drug substance for pharmacological, toxicological, pharmaceutical and clinical research; another one is to guarantee the stability, availability and feasibility of the synthesis technology. There is still a big gap in this research area between China and the developed countries, for example, the lack of scientific reasonable design and normalized regulations during the screening and synthesis of the potential medicinal molecule, the definitive chemical and physical characterization, as well as the quality control are the most draw-back factors in the synthesis research now. The absence of a scientific, objective and strict reviewing system is also a bottle-neck for the discovery and development of new drugs.Scientific research design, normalized research process, authentic and complete applying data are very important to ensure the quality of the new drug. Normalized design of new drug substance helps to improve the quality of applying materials for registration by dividing the whole research process into a series steps which including the determination of target-molecule, the design and study of preparation process, the selection of organic solvent and residual solvent analysis, the chemical structure elucidation of target-molecule, and the impurity analysis etc. 1 Screening and determination of target compound Screening and determination of the target compound from the active leading compounds is the premise and the foundation in the process of drug discovery and development. The leading compound may be derived from natural products, me-too of existing drugs, and screening of various intermediates.2 Design and research on the synthesis process The purpose of preparation-process research is to find a feasible and stable method to synthesize the target-compound. The main contents include the design of the synthesis process, the selection of the onset raw material and the necessary agents, the analysis of the intermedium, foreign substance and the residual solvents, and the optimization of the synthesis method. To meet such goal, a throughout literature investigation is necessary in order to get a complete knowledge of the target compound, the general synthesis methods of the target compound, and the intellectual property rights about the compound. Then a series of synthesis routes were designed basing on the knowledge from the literatures. An preliminary evaluation on the synthesis method and the process should be made and the following factors should be considered: the availability of starting reagent, the toxicity of solvent, the feasibility of experiment condition, the yield, and the requirement of environment protection etc.3 Structure identification of the target molecule A study protocol should be made based on the structural characteristics of the target compound. Instruments often used in molecular structure analysis include UV-Vis, IR, NMR, MS, XRSD, and/orXRPD, DSC, and TG etc. The structure identification of a new chemical entity is more complicated and difficult because there is no literature information and standard contrast as a reference.4 The quality control and the quality criteria To control the quality of the new drug, related research including the characteristics, identification, examination and the content determination is very important. A systemic quality control research is requireted in order to specify the structural feature, the physico-chemical property and the stability of the new drug. The routine item may be determined according the relative methods in the Pharmacopeia and the feasibility of the methods needs to be verified in detail and completely.Basing on the results of the quality control research, the quality criteria are formulated to maintain the drug quality and the stability of the synthesis method. To ensure the rationality and the feasibility of the quality criteria, all the effective factors such as the safety and the efficacy of the drug, the manufacture, supply and utilization of the drug should be considered carefully. The items and the limits involved in the quality criteria are set as initial drug standards, included here are standards pertaining to development, production, quality assurance, quality control, detection of defective products, and other issues, such as product safety and liability. 5 Experiment record and applying material Experiment record should be authentic and precise. All kinds of data such as numerical data, character, graph, table and images obtained by experiments, observation or analysis during the new drug research process belong to the experiment record. Good and complete experiment record can truthfully reflect the whole research process and it is a useful material during the on-site examination and review of the drug research from SFDA. The application materials are the materials submitted to SFDA to apply the permit for drug clinical research or marketing. Scientific normalized and complete applying material is the premise and basis of technical review.Conclusion and significance of this researchA step-by-step discussion of preparation process of new drug substance was presented in this thesis by analyzing the problems and defaults in the drug research process in our country. With reference to the SFDA and the developed country's registration guideline, the thesis proposed the basis principles on the design of synthetic route, the selection of reagent and starting materials, impurity analysis, optimization of preparation process, and elucidation of the target molecule. These discussions will have positive effects on the improvement and normalization of new drug research and production of our pharmaceutical enterprise.