Since April, the State Food and Drug Administration has issued two guiding principles in a row, which has aroused the attention of the industry.
On April 18, the CDE's official website released a draft for comments on the Technical Guidelines for The Study of Clinical Dependence of Drugs, which aims to further check drug dependence. Just four days ago, the official website of the State Food and Drug Administration also issued the "Guidelines for Pharmacovigilance Inspection" to strengthen the domestic pharmacovigilance examination.
Details of drug safety, such as pharmacovigilance and clinical dependence, have not been paid enough attention by the Chinese pharmaceutical industry in the past. In the United States, it is also after major events such as "Purdue Pharmaceutical PainKiller New Drugs" that it has gradually been paid attention to by the FDA, requiring strengthening clinical efficacy studies and post-marketing adverse reaction monitoring.
The Health Bureau noted that although the above two documents point to different points, there is one thing in common: the focus of observation is innovative drugs.
In fact, for innovative drugs, novel targets and mechanisms only mean the starting point of the long march of research and development, and the "long run" of clinical trials and adverse reaction monitoring is the conscience to verify the efficacy.
The FDA has repeatedly rejected Chinese drugs, and China is also strengthening regulation
The trend at the regulatory level may be related to the frequent "going to sea" of China's innovative pharmaceutical companies.
On the morning of December 2, 2021, Hengrui Pharmaceutical, the "first brother" of the domestic innovative drug, issued an announcement that the listing application of the innovative drug Punabulin in Dalian Wanchun, which was invested in, was rejected by the FDA for the reason that the clinical data was insufficient.
This drug has previously attracted much attention in China, and in the second half of 2020, it was awarded "Breakthrough Treatment Varieties" and "Breakthrough Therapy Identification" in China and the United States respectively. In the two interim analyses of the phase III clinical trial, the data of punabulin were also surprising enough. In February 2021, Huang Lan, founder of Wanchun Pharmaceutical, said bluntly in an interview: "2021 will be the year when Punabulin shows its anti-cancer effects." ”
The anti-cancer effect has not been shown, and the clinical trial data has been stamped with "unqualified".
Cinda is even more lamentable. On the evening of February 10, 2022, the U.S. FDA Oncology Drug Information Committee held a review meeting to discuss whether Innovent Biologics' PD-1 monoclonal antibody could be approved for marketing in the United States. The final review meeting rejected the listing application of Cinda PD-1 by a vote of 14:1, and the problem remained in the clinical trial. The FDA expert committee noted that the clinical aspects of Innovent PD-1 do not meet the principle of diversity in the trial population.
In fact, the FDA is not specifically for Chinese pharmaceutical companies, but the requirements for all clinical trials are relatively high. In January, a clinical trial of a CD47 monoclonal antibody owned by Gilead Sciences was halted by the FDA because the clinical trial could produce unexpected adverse reactions.
Clinical trials are the only way to verify the efficacy of innovative drugs, and various investment institutions are eagerly awaiting a good outcome. Judging from the current trend, the State Food and Drug Administration's regulatory requirements for drug approval are becoming stricter.
One of the reasons for the tightening of approvals may be the current global target pile. Taking PD-1 as an example, in the case of merck, BMS, Roche and other pharmaceutical giants entering the market, and the domestic listing has exceeded 6 models, the latecomers are still full of momentum in such targets. According to the clinicaltrials.gov's official website, there are 762 PD-1 product projects that are "in the recruitment".
Capital-intensive investment results in waste of resources; regulators raise clinical trial requirements, promote the survival of the fittest, and maintain an innovative environment. This is the current game between capital and regulation, and this is true in both China and the United States.
More than 20 documents have been issued consecutively, and domestic innovative drugs are under pressure
To some extent, FDA actions have always been regarded as a weather vane. Since officially joining the International Association for the Registration of Medicinal Substances for Human Use (ICH) in June 2017, the technical specifications related to the quality, safety and efficacy of Chinese drugs have gradually moved closer to the world.
One of the conveniences brought by ICH is the mutual recognition of clinical research data between China and foreign countries. Therefore, joining ICH kicked off the prelude to the domestic wave of innovative drugs. Objectively speaking, China's drug regulatory system has been gradually improved with the vigorous development of innovative drugs.
The Technical Guidelines for The Study of Clinical Dependence of Drugs (Draft for Comment) released on 18 April point out that the guidelines are mainly applicable to innovative drugs and improved new drugs with potential for abuse developed in mainland China. Previously, "there is no technical requirement for the mainland to standardize the management of such research", which is the first time that the technical principles of relevant research have been clarified in China.
Just over three months this year, CDE has successively issued more than 20 clinically related documents, such as the Technical Guidelines for Food Impact Research in the Process of New Drug Research and Development, the Guidelines for Statistical Supervision of Drug Clinical Trial Centers (Trial Implementation), and the Technical Guidelines for Clinical Pharmacology Research of Biosimilar Drugs.
Whether it is to provide guidance on the research and development of corresponding drug categories or to publicize the technical principles of relevant supervision work, CDE intends to promote the efficient promotion of drug research and development through the guidance and interference of clinical trials.
In addition to the clinical stage, the supervision of adverse reactions of post-marketing products is also an important path to be responsible for drug efficacy.
On April 15, the State Food and Drug Administration issued the Guiding Principles for Pharmacovigilance Inspection, which aims to further implement the main responsibility of the listed pharmacovigilance and improve the pharmacovigilance management norms. According to the document, drugs with large sales volumes or limited alternative drugs, drugs with additional safety conditions at the time of approval, innovative drugs, and improved new drugs are the main categories considered in pharmacovigilance inspection.
According to this standard, vaccines, exclusive varieties, various types of innovative drugs and other drugs that once lived in the "outlet" will become the key observation objects of monitoring.
Whether it is the strengthening of supervision at the clinical trial stage or the continuous monitoring of post-market products, it means that drug research and development will face more, more detailed and longer tests of efficacy. For innovative pharmaceutical companies, pharmaceutical companies that are accustomed to rubbing concepts without real skills may face a "clearance crisis".
Text | Nicotinamide operating | 23 Figure | Visual China
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