The background information to be considered in an IND application mainly includes four parts: the structural source of the compound, the pharmacological classification, the current status of research/marketing of similar drugs at home and abroad, and the basic status of the application project. Among them, the structure source mainly analyzes whether the compound is a new structure, an existing core structure modification, or a salt or ester of a marketed drug; the pharmacological classification is mainly combined with the research information provided by the applicant to determine whether it is a new mechanism, a new target or a new target. There is a mechanism or target of a drug. The above two points can be used to make preliminary judgments on its druggability and risk. For example, compounds with new structures, new mechanisms and new targets, the hidden development risk is much higher than the salt or ester formation of the marketed drugs. The possibility of being a medicine is also relatively low.
On the one hand, it may be to increase the availability of medicines, and on the other hand, it may be to solve the problems of existing medicines. Therefore, it is necessary to fully understand the target indications, including epidemiological evidence, disease severity and prognosis, current treatment methods and their shortcomings, and the development trend and experience of target indication drugs. In addition, it is necessary to understand the relevant diagnosis and treatment guidelines, drug development trends and the potential of the varieties under application, etc.
The main concern is whether the applicant has formulated the overall plan of the human trial research path, at which stage the applied research is in the planning, or there is no overall or phased research plan, only the application project itself has put forward the research questions/plans at a specific stage .
Understand the basic information of the application project, such as which phase/phase of human clinical trials to be carried out, including the amount of the sample, the duration of the trial, the dosing plan, the research scale (location), etc., to provide for the follow-up technical evaluation Reference basis.
Pay attention to the basis for supporting the current application, mainly considering the basis of validity. These supporting evidences mainly come from clinical trials (in the process of clinical trials of a certain compound, new clinical applications may be discovered, and new clinical applications may be discovered. Applications are often far from the original expected indications), basic research (basic research starting from the laboratory is still the standard path for most drug development, if the supporting information comes from basic research, you need to pay attention to the evidence of this information Intensity) or other relevant information (in some cases, especially when drugs with the same mechanism of action have been successfully marketed and there is no reasonable model, bridging information can be used to obtain supporting information for the application, such as mechanism research, drug metabolism Distribution of research information, etc.).
Judging from the current international research trends, the development of new drugs is a research evaluation model dominated by clinical trial programs. The staging of traditional clinical trials is becoming more and more obscure. Whether a drug can be marketed depends on whether the data obtained can support the evaluation of its safety and effectiveness, rather than whether complete clinical trials have been carried out. The content and schedule of non-clinical and pharmaceutical research should be determined according to the content of the clinical trial to be carried out, and research and evaluation are accompanied by research and evaluation while making decisions. The overall and scientific evaluation of the research program is mainly to evaluate the proposed clinical program. The content includes basic research hypothesis, research population, efficacy indicators, research cycle, drug delivery method and basis, control bias means, data management, Applicant’s risk control measures, etc.
Based on the proposed clinical trial plan, evaluate the compound’s own research data, the research data of similar compounds or drugs with the same mechanism of action, and the safety information related to the preparation, and judge whether the existing data (self + literature) can support the safety of the clinical trial , And put forward the risk control points that may need attention. The risk mainly comes from research on the compound itself, similar compounds, and similar mechanisms.
Whether the quality of the test substance used in early clinical trials is comparable to the quality of the test substance used in non-clinical trials, and whether the quality of the test substance used in subsequent clinical trials is comparable to the quality of the test substance used in the previous clinical trials, pay attention to the test substance The nature and content of impurities.
Based on the above evaluation of the proposed clinical trial plan and safety information, analyze whether there are sufficient risk control measures in the clinical trial plan. The specific content includes: whether the subjects in the clinical trial design are healthy volunteers or select the corresponding patient group based on the safety risk signals and the clinical trial itself; for the known potential risks, whether the monitoring procedures are complete, whether the exposure can be effectively exposed and can be identified Safety signals, whether there are unacceptable system risks; whether the clinical trial plan has formulated the necessary risk control methods based on risk analysis; whether there is a mechanism for evaluating and improving the risk control methods.
In the development of innovative drugs, pharmacy-related changes are almost inevitable, especially in the early development stage, where changes occur more frequently. Generally, in the pre-clinical and early clinical research stages, pharmaceutical research is mainly to provide quality-guaranteed research samples for the above research; with the advancement of clinical research, pharmaceutical research is committed to definite, stable, reproducible, and industrialized production Process and build a complete drug quality control system; combined with clinical research/treatment needs, scale-up production needs, and continuous deepening of drug understanding, the dosage form, specifications, prescription process, analysis methods, quality standards, etc. are adjusted and optimized.
Summarize the aforementioned background information and evaluative information, and judge whether the evidence currently obtained supports the research plan drawn up by the applicant. If it is supported, it is necessary to clarify the scope of clinical exploration supported, the corresponding risk prompts, the supportive research that needs further follow-up and other related aspects such as the work of PI, CRO, and ethics committee. If the existing evidence does not support the proposed clinical trial protocol, it is necessary to clarify the deficiencies and follow-up issues that should be paid attention to.
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