Analysis of the Policy Signals in the 2016 Drug Review Annual Report of CDE

CDE (Center for Drug Evaluation, CFDA) issued 2016 Drug Review Annual Report on March 17, 2017. The introduction of this report was very interesting itself: CDE had issued a review report one week earlier, but emergently withdrew it as some parts involved leaking of the commercial interests of some applicants. The present review report formally issued is a document the pharmaceutical product R&D, registration and production personnel are very concerned about. CDE does not only introduce the data and trend analysis of review of various pharmaceutical products in 2016, but also generally introduce the work to do in 2017 in the last part. The original text is as follows: firstly, further solve the pharmaceutical product review backlog to make sure the solution of the registration application backlog in the year, and achieve review according to the specified deadline in 2018; secondly, center on improving review quality, encouraging innovation, increasing review transparency, and continuing to deepen, refine and achieve priority review, communication, project management, indication team, expert consulting, information disclosure, and filing review system, etc.; thirdly, accelerate the establishment and improvement of the review quality control system, technical guideline system, and compliance management system; fourthly, accelerate the pharmaceutical product production process registration and checking, establish the process registration platform, introduce the process change guidelines, and regulate the process change management; fifthly, create pharmaceutical product variety files, and establish and improve databases containing pharmaceutical product processes, prescriptions, packaging materials of raw materials and excipients, quality standards, package inserts, safety information after marketing, and production process changes, etc.; sixthly, establish the pharmaceutical product Electronic Common Technical Document (eCTD) system and strive to receive chemical generic applications and conduct review according to eCTD requirements by the year end; seventhly, further optimize the internal organizations, improve the scientific management level, be strict with the review personnel management, strengthen confidential system construction and supervision and management, and optimize the career development system of reviewers.

The above closing remarks can be said to be highly summarized and refined, but they raise clear requirements for the pharmaceutical product registration and production management in 2017 and even the future work in the next years. Here I take the liberty of analyzing and interpreting the above policy signals based on my own perception to present the followings to the readers.

Firstly, further solve the pharmaceutical product review backlog to make sure the solution of the registration application backlog in the year, and achieve review according to the specified deadline in 2018.

Policy analysis: The main reason why the CDE has been much criticized by the pharmaceutical industry is the long-term backlog of the pharmaceutical product registration applications. This work has gained significant attention and progress improvement since the pharmaceutical product review system reform. If the solution of the review backlog issue in 2018 mentioned in the review report refers to solution by the end of 2018, this will mean that CDE should complete the review of the varieties having been applied and those newly applied in 2 years, meaning that CDE will continue to increase the recruitment and construction of the review force. The pharmaceutical industry needs to pay more attention to the strong personnel in own R&D and registration departments to avoid them from poaching by CDE, resulting in passiveness in own work.

Secondly, center on improving review quality, encouraging innovation, increasing review transparency, and continuing to deepen, refine and achieve priority review, communication, project management, indication team, expert consulting, information disclosure, and filing review system, etc.

Policy analysis: All the above work has been in progress, seen from the work progress of CDE in last year. Pharmaceutical enterprises shall do the following work in response to the above policy information:

---Concerning product establishment, deeply and accurately grasp the clinical value and treat it as the main consideration.

---Perfect the information gathering mechanism, and frequently track information of CDE website and CFDA associated websites, to make sure timely grasping of any change.

---Establish a project management system similar to or stricter than the filing review system, to make sure the application data quality.

---Timely communicate with CDE regarding major R&D project issues, to avoid policy risk.

Thirdly, accelerate the establishment and improvement of the review quality control system, technical guideline system, and compliance management system.

Policy analysis: Quite a number of guidelines have been established by CDE over the past decade or so, but those guidelines are to be revised or reestablished because they are too old, conflict with each other in the content, conflict with current laws in the content, or their technical requirements are contrary to the prevailing international practices. With regard to the revision of those guidelines, pharmaceutical enterprises should timely conduct following up, mastery and learning, and then establish the internal SOPs on the one hand, and actively participate in the revision and drafting by using the status in the industry, to establish industry status for enterprise development on the other hand.

Fourthly, accelerate the pharmaceutical product production process registration and checking, establish the process registration platform, introduce the process change guidelines, and regulate the process change management.

Policy analysis: This work may be the work pharmaceutical enterprises are most concerned about and also the work they have to face. The issuance of the Announcement on the Implementation of Drug Production Process Checking Work (Draft for Comment) by CFDA in 2016 could be said to have caused a big splash. It was not supported by pharmaceutical enterprises and even each provincial administration due to the high requirements and heavy tasks, and eventually the completion deadline mentioned in the document was put on hold by CFDA. However, it is certain that this work will be continued, judging from CFDA’s determination and efforts in promoting the pharmaceutical product reform. CDE has successively issued draft of guidelines for process change of marketed chemical pharmaceutical products and draft of guidelines for process change of marketed TCM products (both are seeking for opinions) at the beginning of 2017 to cooperate with this work. Predictably, the draft of guidelines for process change of marketed biological products will soon start to seek for opinions.

I estimate that the new document on process checking will be introduced in May-July 2017 according to the present practices of each work of CDE and CFDA. Therefore, pharmaceutical enterprises, especially those with many varieties and specifications, are reminded to prepare in advance.

Fifthly, create pharmaceutical product variety files, and establish and improve databases containing pharmaceutical product processes, prescriptions, packaging materials of raw materials and excipients, quality standards, package inserts, safety information after marketing, and production process changes, etc.

Policy analysis: This work is in fact closely related to the 4^th work. By rights, the drug administration at different levels is supposed to master relevant information when each enterprise is applying for each variety and conducting subsequent supplementary applications and filing. However, the processes actually implemented by enterprises deviate from the information grasped by the drug administration due to inadequate efforts or intentional or unintentional negligence in the past. The creation of the variety files brought up again this time is in fact a kind of work that closely cooperates with the process checking. Pharmaceutical enterprises are reminded to pay high attention to the impacts of the 4^th and 5^th work on own products.

Sixthly, establish the pharmaceutical product Electronic Common Technical Document (eCTD) system and strive to receive chemical generic applications and conduct review according to eCTD requirements by the year end.

Policy analysis: Currently CTD-format application data are only implemented for chemical drugs according to CFDA’s requirements for CTD application data, and such format has not been mandatory for TCM and biological products. Seen from CTD implementation way, the implementation of eCTD will also begin with chemical drugs. For the pharmaceutical industry, this work can reduce the difficulty in managing the application data but will increase the concern about technology leakage. Such concern is linked to the worries about the internal technicians and also the worries about the drug administration information management.

In my opinion, there will be many difficulties in implementing eCTD applications for chemical generics by the end of 2017 in China, seen from the roadmap of European and American drug administration agencies in implementing eCTD. Pharmaceutical enterprises are reminded here that it is now necessary to establish the position of electronic data management personnel in the R&D department.

Seventhly, further optimize the internal organizations, improve the scientific management level, be strict with the review personnel management, strengthen confidential system construction and supervision and management, and optimize the career development system of reviewers.

Policy analysis: This work can be said to be CDE’s requirements for itself. Seen from the incident of the said annual review report that was issued and then withdrawn, it is very necessary to establish and regulate the relevant systems. The industry practitioners know well the meaning of the strengthening of confidential system construction mentioned above, therefore, I will not go into details here.

In a word, the work arrangement and prospects for 2017 in CDE’s review annual report have sent a very clear signal to the pharmaceutical industry that 2017 will be a challenging and busy year.