China's generic pharmaceutical industry ushers in an opportunity period: to replace and not replace

Source: China Science Daily, October 8, 2014, "more than 80% of the drugs used in China are generic drugs." Hu Shanlian, director of Shanghai health development center and professor of School of public health of Fudan University, proposed at the recent Shanghai round table meeting on health policy that "between 2014 and 2018, there will be 295 patents of original research drugs expire, which creates a great opportunity for China's generic drugs." China is a big country of generics, but not a big country of generics Jin Shaohong, senior consultant of international cooperation of CFDA, pointed out that although the quality consistency evaluation system of generic drugs needs to be improved, the expiration of patents creates conditions for the development of generic drugs "In the next five years, China's generic drug industry will usher in an opportunity period." In the World Health Organization (who) quality description of generic drugs, innovative drugs and generic drugs can be interchanged, especially after the patent period; the US Food and Drug Administration (FDA) definition of generic drugs also specifically mentions that they should be consistent with brand drugs in terms of dosage, safety, administration method, quality and effect "Therefore, quality is very important in the definition of generic drugs The key to substitute generic drugs for original drugs is equivalence." Hu Shanlian said The quality of generic drugs should be in line with bioequivalence and clinical equivalence "Only through the pharmacokinetic and pharmacodynamic tests, as well as necessary clinical and in vitro tests, can generic drugs have the same bioequivalence as the original drugs The more important clinical equivalence is to pass the long-term clinical trial " "Large scale safety clinical trials are essential, and the current generic pharmaceutical standards in China are still at a relatively primary level," Hu said In addition, there is a big gap between China and the world in terms of pharmacokinetic parameters "For example, Cmax (peak concentration of blood drugs), the EU concentration standard is much narrower than that of China." Jin Shaohong introduced In view of this, in order to improve the quality of generic drugs, China has proposed to carry out drug consistency evaluation since 2012, issued the work plan for quality consistency evaluation of generic drugs (Draft for comments), and proposed to complete the quality consistency evaluation of some varieties in 2014, and basically complete the quality consistency evaluation of all solid oral preparations by 2015, From 2015 to 2020, the quality consistency evaluation of injection and other dosage forms will be carried out "If this evaluation is done well, the quality of generic drugs in China will be greatly improved." Hu Shanlian took out some documents collected for example, "comparing the dissolution curves of Sanofi's irbesartan and three domestic generic drugs, it is obvious that the dissolution rate of generic drugs is low, and the quality of generic drugs is far from the original drugs In addition, the dissolution curve of different drugs in the same category is high or low, which shows that the quality of generic drugs in our country is worthy of attention " The consistency evaluation needs to be carried out "the quality consistency evaluation of generic drugs is not a surprise and phased task." "First of all, we need to fully understand the characteristics of drug quality consistency evaluation and closely integrate it with the clinical practice It is not a requirement to conduct clinical trials again, but to understand the differences in clinical effectiveness and safety between generic drugs and original research drugs, with specific reference targets," Jin Shaohong reminded At the same time, it should be clear whether the generic drugs and the original research products have the same chemical structure, the same dosage form and the same route of administration It is understood that the main body of drug consistency evaluation is the manufacturer, and actively participate in the whole process of the project together with the clinical use Department of the drug inspection institute and the pharmaceutical industry research department Before research and evaluation, it is necessary to find out the clinical inconsistencies between the generic drug and the original research drug According to this key point and the specific analysis of the specific situation, a specific scheme for the quality consistency evaluation of the generic drug is developed, rather than using a unified method to evaluate the quality consistency of different generic drugs Jin Shaohong also said that the role of clinical institutions in the evaluation of quality consistency of generic drugs should be given full play "Through the retrospective analysis of the risk assessment of the evaluated works, we can provide accurate clinical medicine and pharmaceutical information, summarize and summarize the specific manifestations of clinical inconsistencies." In addition, clinical institutions should also participate in the examination and approval of the experimental scheme of the quality conformance evaluation of generic drugs, and check whether the experimental scheme is aimed at the problems found in clinical practice; participate in the evaluation and acceptance of the experimental results of the quality conformance evaluation of generic drugs, and check whether the submitted materials solve the existing problems, and formulate new indicators; For generic drugs that have passed the quality consistency evaluation, continue to carry out clinical evaluation "When drug production and research institutions carry out consistency evaluation, they should pay attention to strategies, analyze varieties scientifically and clarify the attributes of re evaluated varieties." "Generics should be combined with clinical practice to conduct research on the production process, select the target and control drugs, formulate the test plan according to the information, and implement it according to the designed plan," said Jin Shaohong The idea of quality management throughout the whole process is that drug quality depends on inspection As long as the standards are in line, the quality will be assured "However, with all kinds of problems encountered in the supervision, we realize that the quality of the whole drug comes from the management of all links, and we need to work together." Zhou Qun, chief engineer of Shanghai food and drug administration, believes that generic quality management runs through the whole life cycle of products "Drug quality (including original research drug and generic drug) comes from whether it is reasonable in design and research, whether the R & D process is standard and scientific, whether the production process can ensure the stability of product quality, and whether the test meets the standards." Zhou Qun said, "the quality of drugs also comes from supervision It is not possible to rely on the main responsibility of enterprises." According to the introduction, the management of drugs after being put on the market is also very important Once the industrial mass production changes, it may cause deviation to the quality and affect the curative effect China's new version of GMP (compulsory standards for pharmaceutical, food and other industries) has been in line with international standards such as the European Union New requirements have been put forward in product risk management, change control and deviation analysis, which is also the basis for ensuring the stability of product quality after being put on the market As a very important part of product life cycle management, generic drug quality conformance evaluation is actually a re evaluation work "This link is cyclical and constantly improving." Jin Shaohong said that the criteria for evaluating the clinical safety and effectiveness of drugs sometimes change with the change of technology and clinical application "For example, if we approve an anti-tumor drug in the early stage, when myrrh is available, maybe 30% of its curative effect will be considered as effective, but in the future work, if we find that the curative effect of the new drug reaches 70%, at this time, the first 30% Therapeutic products will be eliminated through re evaluation, so the whole life cycle process of drugs is a process of risk-benefit balance selection, and re evaluation of generic drugs is also a part of this process " Jin Shaohong analyzed In view of the fact that the level of generic drugs in China is still in the primary stage, and the quality consistency evaluation of generic drugs is still groping forward, "how to improve the overall quality of generic drugs, so that generic drugs are not only temporary substitutes in clinical drugs, but also permanent substitutes, which has become the biggest problem faced by the opportunity period of generic drugs in China." Zhou Qun said