Generic shuffle is on the way: how to improve be success rate? What risks should strategic investment guard against?

Source: medical economics Daily, April 14, 2016“ Now, for the sake of technical confidentiality, many original manufacturers will hide the most differentiated internal control methods The open quality standards are mostly obtained by using high-speed or high-concentration surfactants, or high-solubility media without differentiated dissolution test conditions Such dissolution methods can not reflect the difference of internal quality of preparations, that is, the lack of differentiation " On April 8, at a seminar on "BD (Business Development) opportunities and risks under the situation of consistency evaluation" jointly sponsored by ChBD and Zhengzhong pharmaceutical, Dr Liao Wensheng, President of Shanghai Mabu pharmaceutical science and Technology Co., Ltd., pointed out the industry confusion on how to carry out consistency evaluation At present, the consistency evaluation of 292 varieties has been launched In addition to most basic drug varieties, some non basic drug varieties, enteric coated tablets, slow-release capsules and other special dosage forms are also included Considering that many varieties will eventually give up evaluation, bioequivalence (be) exemption and pharmaceutical cost fluctuation, the generic pharmaceutical industry will face a big reshuffle Consistency evaluation is like sailing against the current It is a pain point for the industry to explore the differences in its internal quality The dissolution method must have the distinguishing force be, which is the bridge connecting pharmacy and curative effect On April 8, the guidelines for exemption of human bioequivalence test (Draft for comments) was put on the Internet for comments There is a big direction for generics to exempt from be test However, the reporter learned that only about 5% of the varieties do not need to change the process at present Moreover, it is difficult for be test to be successful at one time Whether it can pass the consistency evaluation on schedule is a test for every enterprise "It has become a new standard for listed drugs to conduct a comprehensive consistency evaluation, but the procedures and materials are almost the same as those of the new generic drugs, and further requirements are required," said Liao As a result, the workload and cost of developing a new project is greater than in the past " He suggested that enterprises should give priority to the selection of key varieties, and leave enough time for process change, be, supplementary application and queuing for review "In order to improve the success rate, we should first study the dissolution curve in vitro," he said Note that the dissolution method and conditions must be differentiated FDA recognizes that a specific drug has its dissolution / release curve in vitro, allowing for the existence of different release mechanisms, as long as bioequivalence is sufficient In my opinion, the in vivo predictive power of dissolution method can be established by pre be (the sponsor conducts pre test in a few subjects before formal be study), and the prescription and process can be adjusted continuously to make the dissolution behavior consistent Therefore, whether the prescription and process need to be changed or be exemption will greatly speed up the progress For projects that cannot be exempted from be, the key is to improve the success rate of be " In principle, generic drugs need to be evaluated for consistency through be, and the in vitro dissolution method is used for the varieties that meet the be exemption Liao Wensheng suggested that "in combination with pre be to obtain in vivo and in vitro correlation data, the dissolution method should be modified so that it has both differentiation and in vivo prediction By adjusting the prescription and process, the dissolution of self-made and reference preparations in the dissolution method with differentiation and in vivo prediction is consistent Pre be is not only a touchstone to test the predictive power of dissolution method in vivo, but also an effective means to improve the success rate of be " "It is urgent to carry out the consistency evaluation, whether the excipients are in line with the route of administration used, and the key characteristics related to the performance of the preparation, especially the excipients which have a great impact on disintegration and dissolution For example, the quality testing standards of simvastatin excipients in Europe, America, Japan and other countries are different, and the impurities and dissolution are also different " He Lize, vice president of Guangzhou Renheng Pharmaceutical Research Institute, said that more efforts should be made to study the content uniformity and batch quality stability of related substances In the next few years, when generic drugs enter the era of high quality, "activate stock, optimize increment" may need to be realized in the way of M & A and restructuring to support industrial upgrading and structural adjustment Experts believe that in the future, for the varieties with clear policy risk and easy to determine reference products, or the injection with lower difficulty and the varieties exempt from be, the risks brought by immature process can be avoided, and there will be no confusion about the shortage of be resources, so the concentration of generic drugs will be higher and higher The industry generally believes that under the background that capital and time risk become the key to consistency evaluation, resources in the industry will accelerate the flow, such as technology transfer, entrusted development, joint development, establishment of joint venture, etc., which will be the means to achieve the upgrading of varieties and models For example, Zheng traditional Chinese medicine has been actively seeking suitable targets for enterprise merger and acquisition and introducing new special drug R & D projects However, in the policy tide of consistency evaluation, on the one hand, we should consider how to optimize the allocation of resources efficiently in the industry, on the other hand, we should pay special attention to the value trend and potential risks of pharmaceutical projects under the new policy How to grasp the BD opportunities and risks brought by the consistency evaluation? Duan Feng, deputy general manager of Shenzhen xinlitai pharmaceutical investment department, thinks that there are two factors for the success of M & A: first, the value judgment, whether the product matches the enterprise's marketing resources, that is, the selection of the product that matches its own marketing team Second, valuation For example, xinlitan was purchased by xinlitai, and the valuation of the project was revised 7-8 times Finally, the domestic original hypertension drug completed the M & A with 339 million yuan "M & A doesn't have to worry about the gains and losses In the long run, whether the project is suitable for the team is the key, and the real confidence to the boss is the sales team " As he shehui, director of R & D of Zhengzhong pharmaceutical, said: "we should also pay attention to risks in the investment of bio generic drugs For example, the therapeutic hepatitis B vaccine introduced by Fudan Haitai Pharmaceutical Co., Ltd has entered phase III clinical trials, and the investment has taken 22 years In addition, the risk of clinical data verification, no re registration of unproductive varieties, and revocation of drug production license are all worthy of attention " From the perspective of the whole industry, Chen zhouquan, senior pharmaceutical research engineer of China Resources Sanjiu Pharmaceutical Co., Ltd., said frankly from the perspective of traditional Chinese medicine: "first of all, there is no long-term plan to adhere to, traditional Chinese medicine injection is not easy to touch, and injection is a good product After in-depth research, it is the second choice to better meet the clinical needs Secondly, it is necessary to dig gold from classics For example, formula granules have theory and future policy basis worthy of further study In my opinion, it is the most important to be able to solve the practical clinical problems New technologies, new methods and new processes may not be able to make good new Chinese medicine, and matching is the most important "