Mid year inventory: self inspection and verification of MAH three policies progress

Source: the first half of 2016-07-05 medical economic report has ended For the pharmaceutical R & D industry, this half year is a relatively frequent year for the introduction of policies Successive policy releases are both challenges and opportunities In the first half of the year, the three policy focuses are self-examination and verification, chemical drug registration and listing license system, while the three key points are difficult to obtain approval documents, few registration applications and new changes in technology transfer 1 From clinical verification to process verification? On July 22, 2015, CFDA announced to carry out self inspection and verification of drug clinical trial data, involving 1622 drug acceptance numbers This is just the beginning In the first half of 2016, the withdrawal announcements of related drugs were issued successively As of June 2016, there were 317 acceptance numbers of registration applications voluntarily withdrawn by enterprises through self inspection on the date specified by CFDA, 193 registration applications that did not need to be submitted to apply for relief of clinical trials, 40 applications that were not approved by announcement, 876 applications that were withdrawn by announcement, and 17 approval numbers of products listed in CFDA database In 2016, in order to promote the landing of import registration related applications as soon as possible, CFDA launched two major moves 1、 To promote the long-term non submission of drug registration inspection report and relevant data, samples and relevant reference materials for drug registration as soon as possible That is, the announcement of the General Administration on matters related to drug registration and inspection (2016 No 36), which was released on February 5, CFDA has no further information disclosure temporarily 2、 Process on-site verification According to the notice of the General Administration on printing and distributing the working procedures of drug clinical trial data verification (Provisional) (sfjyhg [2016] No 34), CFDA food and drug audit and inspection center publicizes the on-site verification plan on its website for 10 working days, and the applicant who fails to submit the withdrawal application within 10 working days after the publicity shall be deemed to accept the on-site verification After the end of the online publicity period, the inspection center will notify the drug registration applicant, the clinical trial institution and the provincial food and drug regulatory authority where it is located of the date of on-site inspection of the varieties that have not submitted the withdrawal application, and will no longer accept the withdrawal application of the drug registration applicant On April 1, 2016, the announcement of the General Administration on the application for self inspection and verification of drug clinical trial data (No 81 in 2016) decided to receive 256 new drug registration applications that have completed the production or import of clinical trial declaration after Announcement No 117 in 2015, excluding 75 applications that have been voluntarily withdrawn by drug registration applicants For the remaining 181 registration applications, the data of drug clinical trials were checked one by one On June 13, 2016, the announcement on the open drug clinical trial data self-examination report filling system required 181 drugs with Announcement No 81 in 2016 to fill in the drug clinical trial data self-examination report from June 13 to 27 This means that the clinical self-examination and verification will soon enter the process After the application for production registration of drugs in the future, all those who have done clinical trials must submit the self-examination report for clinical verification The author believes that the self-examination and verification process of clinical trials will promote drug companies to fully consider the success probability of the effectiveness and safety of clinical trials when setting up drug projects, and products with clear clinical efficacy will be more popular It is reported that CFDA intends to conduct self-examination and verification on the production process, mainly for the products whose actual production process is inconsistent with the approved production process and which have an impact on the safety and effectiveness of drugs CFDA will take this opportunity to standardize the supplementary application process of process change, which is also conducive to enterprises to propose process change according to the actual situation in the consistency evaluation research From the experience of CFDA in 2007 and 2010 in verifying the production process of injections and essential drugs respectively, the author believes that products with high adverse reaction rate and sales price, especially the bid winning price lower than the market average cost, are the products most likely to be subject to strict inspection by flight inspection, and biochemicals, sterile drug injections and proprietary Chinese drugs are the focus of CFDA 2 Is the new classification and consistency evaluation policy clear? The work plan for the new classification reform of chemical drugs was finally implemented in March 2016, and the detailed rules for the implementation of application materials were issued in May This is expected to improve the current situation of sluggish drug registration in the first half of 2016, especially the "cliff" decline in generic drug applications in 2016 The low declaration of chemical generic drugs is also related to the consistency evaluation, because in the future, chemical generic drugs must pass the consistency evaluation In the first half of 2016, CFDA set a special column for "generic drug consistency evaluation" As a project launched in the 12th Five Year Plan, CFDA has issued 28 relevant document announcements, including 14 in 2016, excluding the documents of one-time import of reference drugs However, from the information published in the current clinical trials and the CFDA's work meeting on generic drug consistency evaluation held on June 24, which encouraged enterprises to carry out the consistency evaluation tests as soon as possible, it is revealed that the enterprises that actually started the consistency evaluation tests are very limited Most enterprises are still on the sidelines The author believes that there are three reasons: first, which products should be selected by enterprises for consistency evaluation, and the final evaluation can only be conducted after the launch of the catalogue of generic drug consistency evaluation varieties by the end of 2018 in May 2、 In terms of project price, the cost of each cro for consistency evaluation ranges from RMB 500000 to RMB 15 million, while the time node in 2018 is only 2 years How to choose a reliable third-party enterprise with high success rate and high cost performance for consistency evaluation is uncertain 3、 In terms of project methodology, although a lot of policy documents have been issued, enterprises will feel that the consistency evaluation project is still at the stage of crossing the river by feeling the stones when it is really implemented It took more than half a year for the "in vitro dissolution test group" and the "in vivo bioequivalence group" to reach a final conclusion However, whether the four dissolution curves are exactly the same as the original research is still in dispute Most of the domestic enterprises that are used to follow expect the "first crab eater" to confirm the relevant information and then copy it CFDA plans to adopt the method of centralized review and approval for horizontal comparison scheme If the project is reviewed according to the strict standards of existing clinical verification, the success rate can refer to the current clinical verification project In view of this, the author believes that the short and medium-term benefits of the consistency test are the domestic enterprises that have already exported the relevant products of European, American and Japanese enterprises, as well as the production enterprises that have been authorized by European, American and Japanese enterprises to make real estate in China 3 Is the listing Licensor a pilot to reduce the steps of technology transfer? June 2016 In June, the pilot areas were Beijing, Tianjin, Hebei, Shanghai, Jiangsu, Zhejiang, Fujian, Shandong, Guangdong and Sichuan The pilot drugs included: new drugs approved for listing after the implementation of the program, generic drugs approved for listing according to the new standards consistent with the quality and efficacy of the original drugs, and some drugs approved for listing before the implementation of the program 。 Drug listing license holder system is a common regulation in drug regulatory field in developed countries and regions such as Europe, the United States and Japan The system adopts the management mode of separating drug listing license and production license, and allows drug listing license holders (the holders of drug listing license documents can be drug manufacturers, research and development institutions or scientific researchers) To produce drugs by oneself or entrust other enterprises to produce drugs The pilot program allows the change of holders and production enterprises before and after the approval of clinical trial application or listing license application, and has formulated corresponding change application procedures The pilot scheme stipulates that the change of holder shall be handled in the form of supplementary application, which is equivalent to the approval of technology transfer in the original laws and regulations The change from the original independent administrative license to the supplementary application of listing license is an important embodiment of simplifying the administrative license However, the supplementary application for changing the production enterprise belongs to the scope of production site change, which is equivalent to the original entrusted production approval It is a bright spot to allow cross pilot regions to commission production In the pilot scheme, the applicant is explicitly allowed to optimize the allocation of production resources in 10 pilot areas, and the applicant is allowed to entrust the entrusted production enterprise to produce drugs without new drug certificate, which means that the drug approval documents of the factories in the pilot area without the new GMP certificate in 2010 can be extended through the listing Licensor system, and there is no need to rush to 2016 The approval documents of relevant drugs were released before the second half of the year This will help to cultivate some pharmaceutical manufacturers with perfect quality system, good social reputation and focus on entrusted production In addition, the phenomenon of repeated construction of resources in the past is expected to be solved Under the condition of limited drug manufacturing enterprises and limited growth of drug market, the price of drug production approval will return to rationalization In the past, the R & D enterprises that applied for a large number of old chemicals classification 3.1 drugs will also reduce the listing application of duplicate drugs There will be a reduction in the number of repeat drug applications in the pilot area For R & D of new drugs, the holder is no longer limited by his own production qualification, and can industrialize the drugs as soon as possible through entrusted production Therefore, the listing Licensor system is more conducive to new drug R & D institutions that have previous experience in the application and listing of new drugs in Europe and the United States.