Read Announcement No. 230 carefully to see the focus of recent policy trends of CFDA

Source: Dandelion 2015-11-25 recent CFDA action frequency, in addition to the most concerned about the clinical verification, but also a one-off release of four drafts and a Notice No 230 From the consultation and implementation time, it can be seen that CFDA is very urgent in the policy change, and it is in line with the mood of the insiders who are eager to know the follow-up policy change Although the draft for comment of priority review was released after Announcement No 230, it can be seen from the announcement number that four draft for comment should be in the front and one comprehensive announcement should be in the back (Announcement No 227 for priority review) It can also be judged that CFDA wants to answer the industry's doubts about the four drafts through announcement 230 It is not known whether more drafts or guidance will be released after announcement 230, but it is rumored that more detailed rules will be issued by CFDA in December Rome wasn't built in a day To launch so many reform policies within two months, it must be that CFDA has been brewing demand, which has not been published before There are two rumours in the anecdote: 1 There is no strong leadership to make decisions, and the opinions of all parties are debated, which cannot be finally formed; 2 Many technical details are hard to be determined, and the competition of multiple forces hinders the implementation and release of the policy No matter what happened inside CFDA, the industry finally ushered in the biggest change in the history of China's pharmaceutical industry, which also caused a strong shock, concern and praise in the industry As the announcement of No 230 has been put together with many announcements, and has been submerged in a number of drafts for comments, enterprises and institutions that have been stunned by clinical verification have no intention to carefully read the profound meaning and good intentions of No 230 And let the author according to their own understanding, to help you analyze 12, is also to remind peers to pay enough attention to the importance of this document Announcement No 230 contains ten major points, including quality improvement of generic drugs, improved new drugs, optimization of clinical trial application, centralized review, active withdrawal of registered varieties, strict inspection of safety and effectiveness, approval of clinically urgent drugs, falsification of clinical trial data, guidance of rational application and appeal review Now I'm going to speculate on the intention of CFDA one by one 1、 Improving the approval standard of generic drugs is another emphasis on "consistency" The scope of this emphasis is no longer the consistency evaluation of listed varieties, but the whole "generic drugs" scope Although the quality and efficacy of generic drugs have been mentioned in many places before, it is the first time to officially appear in the announcement and interpret it However, the whole content, from the perspective of discussion, is more logical, seems to have no focus, and covers a wide range I feel like I want to cover all aspects, but due to space limitations, the description is relatively superficial According to the normal logic, the first paragraph should describe the content of "implementing classification processing", and then emphasize "among them, the generic drug registration application that has been listed outside China but has not been listed in China should be further emphasized and highlighted" But this announcement put the latter in the first paragraph, and after the emphasis, we will talk about how to classify and deal with things I don't know if it's intentional, or if the writer's thinking is not too clear, or if it indicates that there are any targeted documents to be issued in the future In the content of "implementing classified treatment", i.e., "there are approved listed original research drugs in China" and "there are listed original research drugs outside China but not approved in China" are taken as (I) and (II) However, the "application for registration of generic drugs to be listed" was added as a separate line, emphasizing that only when the pharmaceutical research is consistent, other research materials will be reviewed This logical sequence should be to show that if the pharmaceutical parts are inconsistent, there is no need to waste human and material resources to review other research materials, which can save a lot of time and manpower for CDE However, there are some contradictions between this and the current way of main examination + auxiliary examination Often, the speed of auxiliary examination of other materials is faster than that of main examination of pharmacy I believe that many enterprises have experienced this CDE teachers call first to ask for materials of pharmacology and toxicology, and then ask for materials of pharmacy for examination and evaluation If this announcement is carried out, surely we will not ask for the pharmacological and toxicological data in the review of a project in the future? Secondly, standardizing the review and approval of new improved drugs is the most strange place in the announcement The documents about the new drug classification have been circulated in the early days Earlier, master zero pointed out that the "three categories" were policy doting on many occasions Prior to the release of the announcement, a draft for comments on the new drug registration classification has been officially released, in which the content of "improved new drugs" has been clearly defined In the announcement, the review and approval of improved new drugs was specifically proposed as a big point, presumably CFDA should further strengthen the concept of improved drugs, and also answer some doubts of the public However, the content of this article is only a short paragraph! Most of the content of this paragraph is just repeating the definition of "improved new drug" At the end of the article, it is specially mentioned that "except for the application for registration of drug use for children whose dosage forms and specifications are changed", the real purpose of this article must be that "children's drug use" is not approved only when it has technological innovation and clinical value has obvious advantages " In other words, if the development of improved children's medicine, even if it can not prove the "advantage", it is possible to be approved However, the scope of approval for children's drug use is limited to "changing dosage forms and specifications", rather than all the improved new drugs for children So, are the improved new drugs that "change the acid radical, base and route of administration" excluded? This should also put an end to some enterprises' attempts to drill the loophole of "children's drug use" and avoid some meaningless "improved new drugs" breaking through under the guise of "children's drug use" However, there are still some problems If we change the acid radical, the base and the way of administration, will it not be suitable for children's drug registration? Especially for changing the way of administration For example, would it also be of great value to change oral administration into nasal administration, rectal administration and local administration? Of course, it can also be understood as the obvious advantage of "clinical value", which improves the compliance of children's medication In a word, this is a bit abrupt 3、 Optimizing the review and approval of clinical trial application mainly includes two parts The first paragraph is about the clinical application of new drugs, and the second paragraph is about the filing of generic be In the first paragraph, clinical applications for new drugs will not be reviewed and approved in stages, but will be approved once Industry insiders believe that innovative drugs should be approved in phase I, II and III clinical at the same time, and keep communication with CFDA and CDE at any time during clinical development Those in the industry engaged in the development of innovative drugs should know that before the release of this announcement, the operation mode of phase III clinical continuous batch has begun to be implemented, of course, more in the hands of review teachers This time, this practice was clearly defined from the policy level through the way of writing, which is also a full affirmation of this practice The implementation of this policy, for innovative drug research enterprises, is very good, can greatly shorten the R & D cycle, avoid the repeated application and approval process waste a lot of human and material resources Of course, this also puts forward higher requirements for the clinical trials of innovative drugs That is to say, when we carry out phase I clinical trials, even before that, we should comprehensively consider the three stages of clinical trials, and design a more complete and continuous clinical trial scheme Under the background of cracking down on clinical fraud, there is no doubt that higher requirements are put forward for the quality of some clinical staff in enterprises In the second paragraph, regarding the be filing system of generic drugs, this should be a further emphasis on the draft for comments on be filing system, and it should be reiterated once again: it will be implemented from December 1, 2015 It highlights the urgency of the filing system, and also enables some enterprises that are still confused to wake up as soon as possible and make layout in advance There is nothing new in this paragraph Most of the descriptions and regulations can be found in the draft Therefore, the third point is to highlight the "one-time approval of clinical application for innovative drugs", and the generic be filing is just mentioned incidentally 4、 The implementation of centralized evaluation of the same variety is only a short paragraph, all of which are only 85 words However, this paragraph is very important What's important? It is to correct the name of "centralized evaluation" from the policy level It is believed that "centralized review" is no longer a strange word, and the industry has defaulted to this mode of centralized review Peers who have worked for more than ten years should also remember the centralized review before and after 2007 However, this centralized review is unprecedented in terms of quantity, speed, strength of disapproval and human and material resources invested (not necessarily "after the end") In fact, the wind of centralized review began to blow as early as 2014 However, the date when the centralized review of CDE started, which varieties are included in the centralized review, how to classify them, and how to carry out them in order have always been a mystery We can only capture some information from various wechat and QQ groups, and also feel that the wind of centralized review is stronger and faster from the reports of several data analysis companies This time, "centralized review" was formally put forward in the announcement, which should be a "proper name" The reason why it is just a short paragraph of text, personal understanding should be for the follow-up of more detailed rules to do a foreshadowing Although there are few words in this paragraph, there are many key information mentioned: (1) the same varieties accepted before the announcement date The content of this sentence is very rich! In 2014, the closing event of rumor centralized review was from March to may 2015 Now, it seems that the closing time is limited to November 2015, which is to define the time node to enter the centralized review "The same varieties that have been accepted" does not mean that there are 6 categories, 3 categories or 3 + 6 categories Does it indicate that no matter how many categories, they will be subject to centralized review? But the order is different From the perspective of "the same variety", the exclusive variety should not be included in the centralized evaluation (2) In case of non-compliance, the decision of disapproval shall be made in a timely manner The expression of "non-compliance" is vague What is the "regulation"? Personal understanding should be the "Filing review" that has appeared before However, it is also learned from many channels that there are more operable review standards and processes in the hands of review teachers, which are unknown to the public Perhaps, before the end of December, there will be some documents about the "centralized review" standard released? (3) if they meet the requirements, the approval decisions will be made in order of application and the approval certificates will be prepared and issued In the document "Comment No 230", questions have been raised about "approval in order of declaration" Forget it