The deadline is coming: will the schedule of conformity assessment be adjusted? Will the standards be relaxed?

Recently, more and more attention has been paid to the consistency evaluation schedule of quality and efficacy of generic drugs or the news of adjustment in the industry Caixin quoted Liu Pei, inspector of the Department of policies and regulations of the State Drug Administration, as saying at the academic annual meeting of the National Center for drug policy and Economic Research of the pharmaceutical industry, "the drug administration will adjust the schedule of consistency evaluation" The news has not been officially confirmed However, whether the message is true or not, it can be clear that the debate about whether the consistency evaluation is postponed is indeed the most concerned topic in the current industry On May 26, 2016, the former CFDA's announcement on the implementation of the opinions of the general office of the State Council on the evaluation of the consistency of quality and efficacy of generic drugs pointed out that in principle, the consistency evaluation of the chemical generic oral solid preparations approved for listing before October 1, 2007 and listed in the national basic drug catalog should be completed by the end of 2018 Now, it's less than half a month from this "big limit" Obviously, for the vast majority of varieties, it is basically impossible to complete the consistency evaluation on schedule by the end of 2018 According to the data published by CDE and the report of industry research institutions, as of November 30, 2018, including 289 varieties within and outside the catalog, the cumulative acceptance number of CDE's generic drug conformity assessment is 615, involving 223 varieties of 234 enterprises Among them, the total number of products passing the conformity evaluation is only 121, and the varieties in the 289 catalogue are even less According to the notice previously published by CFDA, there are 17740 approval numbers of varieties that need to be evaluated for consistency only in the 289 catalog 1 Will consistency evaluation relax standards? In fact, as early as March 4, 2018, at the Symposium of CPPCC members of the National People's Congress of the "voice responsibility" pharmaceutical industry, 25 industry associations (academies) such as China Pharmaceutical Enterprise Management Association jointly issued a proposal on improving the conformity evaluation policy of generic drugs, in which several opinions were clearly put forward, including the completion of the appropriate relaxation of the conformity evaluation of basic drugs It is suggested to set a principle completion time limit for non base drug consistency evaluation But for enterprises, it must be noted that even if the consistency evaluation is really delayed, it does not mean that they can relax From the perspective of the implementation work of consistency evaluation that has been carried out in various regions, the standard requirements for consistency evaluation will not be reduced For example, Shanghai In September, Shanghai food and drug administration clearly put forward in the implementation opinions on deepening the reform and optimization of administrative examination and approval of "release and administration service", that "the oral preparations in the national essential drug catalog that fail to pass the consistency evaluation shall not be registered again" and "the drugs in the national essential drug that fail to meet the requirements of the oral solid preparations shall be eliminated" Jiangxi, Zhejiang, Sichuan and other provinces have also taken similar measures They have strictly implemented the policy of "suspend the online procurement qualification of products that have passed the conformity evaluation if there are three products that have passed the conformity evaluation" Another key point is whether the requirement of not re registering within the time limit will change with the time limit If the time limit for conformity evaluation is given, but the enterprise still does not complete the conformity evaluation before the product is re registered, then even if the subsequent products pass the conformity evaluation, they can only re apply for registration, which is not the expected situation for the enterprise On the other hand, objective reasons such as clinical resources and extreme shortage of subjects will not improve with time Chen Hongying and Wang Jiansong, senior engineers of Guangzhou Baiyunshan Pharmaceutical Group Co., Ltd and Baiyunshan Pharmaceutical General Factory, published in the Journal of Chinese clinical pharmacology, showed that at present, there are about 150 medical institutions that are qualified to carry out bioequivalence test in China, while there are about 70 medical institutions that are willing to undertake bioequivalence test, because each project has to be opened Two groups of fasting and postprandial trials were conducted in four cycles, with each project occupying a ward for at least one month on average Therefore, the maximum number of bioequivalence trials that can be carried out in a clinical hospital within one year is no more than 20 Based on this calculation, the number of projects completed each year is no more than 1500 varieties In the next few years, there will be tens of thousands of approvals for consistency evaluation Therefore, the battle for clinical resources will reach the stage of white fever from 2017 to 2019 As a result, rescheduling the consistency evaluation schedule and giving appropriate grace on the existing basis may be able to alleviate the urgent needs of enterprises to a certain extent But on the whole, even if it is really delayed, enterprises still can not relax, and it is still an urgent task to promote the completion of product conformity evaluation as soon as possible In addition, how to balance the relationship between consistency evaluation and current policies such as volume purchasing may be the biggest test to the wisdom of relevant competent departments It should be said that under the current procurement policy, it may be a question mark whether enterprises still have the motivation to spend a lot of money on consistency evaluation Under the policy of consistency evaluation of quality and efficacy of generic drugs, enterprises take the lead in passing the consistency evaluation What they have will be the same quality level as the original research drugs, corresponding to the more advantageous pricing power and market access ability Market space is an ideal state However, the current policy of "4 + 7" volume purchase is a single source commitment based on consistency evaluation, which means that even if the consistency evaluation is passed, it is only in exchange for a qualification to enter the market, and the specific who can get the "volume" promised by volume purchase still needs to see the extent of their product price Whether the consistency evaluation, which takes a lot of time and energy to complete, can occupy a place in the future market, may be a big problem in front of the relevant enterprises at present 2 It has been a general trend for a long time to postpone or postpone There has been a debate on whether the consistency evaluation should be postponed or not Those who support the extension think that under the current practical difficulties including the shortage of clinical resources, unclear reference preparations and high requirements for capital investment, the requirements for completion by the end of 2018 are too high, and once implemented according to this, a series of follow-up problems will arise; while those who do not support the extension think that the national policy-making has its own timetable and roadmap, which should be strictly followed and imitated The consistency evaluation of pharmaceutical industry itself is the process of survival of the fittest, so it is more strict in time and does not constitute a problem From the current work progress, it seems to be the general trend to postpone the evaluation of the consistency of quality and efficacy of generic drugs There are three main reasons First, the introduction of the new version of the base drug catalogue may make the variety that needs to complete the consistency evaluation within the time limit no longer be 289 According to the documents previously issued by CFDA, the varieties that need to complete the consistency evaluation before the end of 2018 are the chemical generic oral solid preparations approved for marketing before October 1, 2007, which are listed in the national base drug catalog At that time, there were 289 that met these three conditions, so the "289" catalog was established However, with the release of the new national essential drug catalogue 2018 by the national health and Health Commission, the total varieties of the essential drug catalogue have increased from 520 to 685 Accordingly, there are no 289 that meet the above three conditions For the expansion of the consistency evaluation list, the corresponding time may also need to be appropriately extended However, how long the grace period is, and how much convenience it will provide for the progress of conformity assessment, will still be in question Second, once the previous provisions are general, the varieties that fail to pass the consistency evaluation within the time limit will not be registered again, then the current centralized procurement policy based on the consistency evaluation is likely to be greatly affected Recently, the "4 + 7" volume procurement policy, which has also attracted the general attention of the industry, is an important premise for its implementation, which is that the varieties participating in the bidding must be the ones that pass the consistency evaluation of the quality and efficacy of generic drugs This also means that for the varieties that have not passed the consistency evaluation, if you want to participate in the competition of drug volume purchase, you must speed up the consistency evaluation, even for non 289 varieties However, according to the current process of consistency evaluation, only a small number of varieties have passed the evaluation successfully, and a large number of varieties are still on the way of consistency evaluation Only a few of them are qualified to compete in volume procurement Therefore, with the further promotion of volume procurement policies and the increase of pilot varieties, the round of centralized procurement based on consistency evaluation will be greatly affected It is likely that there will be no qualified bidding products for some varieties Third, the consistency evaluation of products outside the 289 catalog is also an important area for enterprises to lay out, which is also an important way for enterprises to seek their own product transformation and upgrading However, according to the current regulations, a lot of resources may be wasted According to the current regulations, after the first non base drug has passed the consistency evaluation, it will not accept the consistency evaluation application of the same variety from other drug manufacturers three years later, and if there are more than three manufacturers that have passed the consistency evaluation of the same variety of drugs, it will no longer select the varieties that have failed the consistency evaluation in the centralized purchase of drugs The starting point is naturally to urge enterprises to speed up the implementation of consistency evaluation However, in the actual implementation process, due to the unclear reference preparation, the shortage of clinical resources, the difficulty in implementing supporting policies and other situations, a considerable proportion of enterprises may not be able to meet the requirements of the existing regulations, and these already invested resources may be wasted.