Author: Shun Jin Date: 05/Apr/2016 Version: 1.0 China EU Pharmaceutical Forum EFPIA’s view on China regulatory reform

2 Overview of the reform for the drug review and approval system Major regulatory updates since 2015 Positive aspects of recent regulatory updates Areas requiring clarification and improvement Agenda

3 Overview of the Reform for the drug review and approval system With the aim of improving drug safety and quality and encouraging innovation Improve the quality of review and approval Resolve registration backlog Improve the quality of generic drugs Encourage the R&D of innovative drugs Enhance the transparency of review and approval Major goals Aug

4 Major regulatory updates since 2015 (1) Announcement on Promulgating the Guidance for International Multicenter Clinical Trials (IMCT) (Trial Implementation) - Jan 2015 Guidance on the Research and Development of Biosimilars (Trial for Implementation) - Feb 2015 Regulations for the Administration of Human Genetic Resources - Jul 2015 (draft)/ Oct 2015 (implemented) Working Plan for the MAH Pilot Program (Draft for Comments) - Nov 2015 Guidelines on Clinical Trials for Use of Drugs in Pediatric Population - Mar 2016 Research and development

5 Major regulatory updates since 2015 (2) Raised registration fee - May 2015 Streamlined administration and delegation of power to lower-level governments - Jun 2015 (CFDA opinion) / Mar 2016 (State Council decision) Clinical trial data inspection - Since Jul 2015 Review and approval of new excipients/ new immediate container linked to the review and approval of new drug products - Aug 2015 (State Council opinion), Jan 2016 (draft dossier requirements for comments) New registration categories for chemical drugs - Nov 2015 (draft)/ Mar 2016 (final) Priority review and approval - Nov 2015 (draft)/ Feb 2016 (final) BE study: changed from approval to notification - Dec 2015 The Administrative Measures for the Communication and Exchange of Drug Technical Evaluation (for Trial Implementation) Dec 2015 (draft)

6 Major regulatory updates since 2015 (3) ChP 2015 implementation - since Dec 2015 Consistency evaluation on generic drugs (started)/ Nov 2015 (draft)/ Feb 2016 (final) Guidance on the Reporting and Monitoring of Adverse Drug Reactions (Trial for Implementation) - Jul 2015 Drug traceability system suspended - Feb 2016 Manufacturing Post-marketing

7 Positive aspects of recent regulatory updates (1) Encouraged research and development of innovative drugs -Improve clinical trial approval and review should focus on clinical value and subject protection -Accelerate the review and approval process for drugs with urgent clinical demand -Optimization of the priority review and approval system -Strengthened communication and supervision during review and after CTA approval JK-05: China self-developed recombinant Ebola vaccine, CTA approved through Special Review Procedure in 2015 China self-developed Enterovirus Type 71 Vaccine, Inactivated (Human Diploid cell), approved through Special Review Procedure in Dec 2015

8 Positive aspects of recent regulatory updates (2) Alglucosidase Alfa for Injection: an orphan drug for Pompe disease, approved in Oct 2015 Pasireotide Diaspartate Injection: an orphan drug for Cushing’s disease, approved in May 2015 Expected improvements in drug quality and availability -Accelerated review and approval of drugs satisfying highly unmet clinical need -Encouraged development and manufacturing of drugs in shortage -Encourage pediatric drugs development and speed up the review/approval process.

9 Positive aspects of recent regulatory updates (3) Improved drug review process and increased review efficiency -Seriously investigate and punish fraudulent activities of registration application -Intention to improve CDE review quality control system (GRP) -Hire of additional review resources -One-time approval of different phases of clinical trials for locally developed innovative drugs -Notification of BE studies for generic applications -Simplification of procedures for technical transfer between local drug manufacturers Increased transparency of review and approval process -Encouraged communication between applicants and regulatory agencies

10 Positive aspects of recent regulatory updates (4) Review tasks completed by CDE Accepted new registration applications Reduced backlog of drug registration applications -Implement centralized review for the backlogged applications -Non-approval of registration renewal for drugs which have not been marketed within the validity period of the license * CDE annual report 2015

11 Positive aspects of recent regulatory updates (5) Greater clarity on clinical trial requirements -Guidelines on Clinical Trials for Use of Drugs in Pediatric Population -Guidance on the Research and Development of Biosimilars (Trial for Implementation) Expected improvement in clinical trial data integrity -Strengthened supervision over clinical trials -Severe punishment on fraudulent activities -Temporary procedure of clinical trial data inspection

12 Positive aspects of recent regulatory updates (6) Expected improvement in the quality of generic drugs -Reinforce the equivalence evaluation of generic products (comparing with innovative drug) -Control low-level applications (release the catalogues of drugs restricted for approval) -Improved supervision through frequent unannounced inspections Guidance on generic applications -Strict control on the manufacturing and approval of generic drugs which are developed with outdated manufacturing process and have been over-supplied -Publication of generic drugs for which approval is restricted

13 Areas requiring clarification (1) Priority review and approval -Connection to the existing Special Review Procedure -Details about the pediatric clinical data waiver/extrapolation requirements -Implementation details -Review timeline Biosimilars -Sourcing of reference products outside China -Manufacturing process and analytical procedures of reference products -Number of batches for the comparability exercise -Indication extrapolation

14 Areas requiring clarification (2) Implementation of ChP Availability of the official English translation and relevant materials Excipient requirements for imported products Delegation of power to lower-level governments -Need more clarity on the list of supplementary applications that can be approved by provincial FDA

15 Areas need improvement Human genetic resource management -Additional review/approval step before the new drug clinical trial can start -Prolonged clinical trial execution and finalization timeline -Delayed access of Chinese patients to innovative drugs MAH pilot program -Participation of foreign innovative drug manufacturers Consider different dossier requirements for CTA/NDA applications Alignments with internationally recognized pharmacopoeias especially for excipient and packaging materials Implementation window and implementation details

16 Summary  EFPIA appreciate the efforts by CFDA to better shape the current regulatory system  Positive trend has been captured with encouraging improvement  Further clarification and development is still needed  EFPIA is willing to support regulatory reform in Chinese market

Thanks EFPIA Brussels Office Leopold Plaza Building * Rue du Trône 108 B-1050 Brussels * Belgium Tel: + 32 (0) *