Regulatory Highlights and Drug Development in China was presented at the 5th China Clinical Trials Outsourcing Congress March 4-5, 2013 by Xiaoxiong (Jim) Wei, MD, PhD, Medical Director at Medpace.

1. FOCUSED. TRUSTED. GLOBAL.
EXPERTS
Regulatory Highlights and Drug
Development in China
5th China Clinical Trial Outsourcing Congress March 4-5, 2013
Presented by Jim Wei, MD, PhD

2. FOCUSED. TRUSTED. GLOBAL.
Agenda
o The current status of the China regulatory environment
for conducting clinical trials in China
o Clinical facilities accredited by China SFDA to conduct
trials
o Outcomes regarding US FDA site inspections in China
o Advantages and disadvantages of conducting trials in
China
o Strategic partnership with China domestic pharma
companies

3. FOCUSED. TRUSTED. GLOBAL.
China Regulatory Highlights
o Regulatory timeline are shortened recently.
However, 6~12 months Clinical Trial Application
(CTA) approval time are still needed
o All CTA, NDA submission packages are required in
Chinese
o ICH-CTD format for application package has been
accepted
o Need source country approval of Certified
Pharmaceutical Product (CPP) to complete the
NDA process
o Predetermined minimal patient number and newly
required statistical significance

4. FOCUSED. TRUSTED. GLOBAL.
China Drug Registration
Classification and Requirement
Class 1 A NME, which has never been •Phase I – SAD: 20-30
approved and marketed in any •Phase I –MAD: 20-30
country •Phase II: >100 (test group)
Class 2 Change in administration route and •Phase III: > 300 + statistically
not yet approved to be marketed in •Significant
any country
Class 3 A drug has been approved and •PK: 20-30
market in foreign market (e.g. US and •Phase III: >200 (>100 / arm)
EU) but new to China •Multiple indications (>60 /
arm)
Class 4 Change acidic or alkaline radicals of Same as above
the salt
Class 5 Change in dosage form without Same as above
change in administration
Class 6 Generic product

5. FOCUSED. TRUSTED. GLOBAL.
Process for Approval of
Clinical Trial Applications
China SFDA
Center for
Center for Center for
Drug
Filing Drug
Evaluation
Registration
(CDE)
Admin Review
Review
Registration
90 B-days
30 B-days 30 B-days
(4.5 months)
(1.5 months) (1.5 months)
-It takes 7.5 month by default
-It takes 9-12 months when no additional information is requested
-It took shorter time in 2012

6. FOCUSED. TRUSTED. GLOBAL.
China SFDA vs. US FDA
NDA Review Process
Review Process US FDA China SFDA
Filing Review Review Team Center for Filing
Technical Review Division Center for Drug
Evaluation (CDE)
SFDA
Administrative Review Office or Division Department of Drug
Registration

7. FOCUSED. TRUSTED. GLOBAL.
China SFDA vs. US FDA
Regulatory Focus
o Type of Products: Generic vs. New Drugs
o New Drugs: Domestic/imported vs. IND/NDA
o Data Requirements: Dependent vs. Independent
o Processing Unit: Application vs. Drug/Indication
o Definition of Drug/Review Focus: CMC vs. Clinical
o Interaction: Agency-initiated vs. Sponsor-initiated
o Conditional Approval: No vs. Yes
o Ability to Minimize Risk: Limited vs. Continuous
o Approval: Manufacturing vs. Marketing
authorization

8. FOCUSED. TRUSTED. GLOBAL.
SFDA Center for Drug Evaluation (CDE)
o Has improving its functions:
 Green Channel Approach and approval time is shortened
 Pre-IND consultation
 Sponsored training workshops to promote GMP, GLP, GCP
and new drug development
 Participating in major international conferences
• - DIA, AAPS, and many regional workshops
 More harmonization with ICH
• - More ICH/FDA guidances translated in Chinese
 Established in-house statistical group
 Expanding review staff
 Implementing Good Review Practice
• More Science-based approach
• Openness, fairness, rightfulness

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Time Needed for First-Round Evaluation of Initial IND in 2012
2012年化药IND品种首轮审评结束所需时间的分析
审评中心自2012年1月1日至2012年12月10日共完成化药IND（包括化药注册分类1类和2类）品种首轮审评幵
已有结论 （结论包括会议讨论、发补、批准、不批准），按化合物计共47个。现对上述首轮审评所用时间
分析如下： 下图所示的时间为品种正式进入中心到各部门完成首轮审评幵已有结论的时间。
>9 months
9 months
8 months
7 months
6 months
<5 months
Compound [Jan. 1 – Dec. 10, 2012]

10. FOCUSED. TRUSTED. GLOBAL.
2012 SFDA/CDE : Initial 47 INDs
34 Applications were 1.1 New Drug Class (72% of the total INDs)
Average Time Shortest Time
Indication Percent （%）
(Month) （Month)
适应症 所占比例
平均用时（月） 最短用时（月）
Anti-cancer
32% 6.1 4.2
抗肿瘤
Endocrine
17% 6.7 5.8
内分泌
Psychiatry/CNS
15% 7.3 5.8
精神神经
GI
13% 7.6 5.6
消化

11. FOCUSED. TRUSTED. GLOBAL.
FDA Alumni Association and China SFDA Joint Training
Annual Workshop of Science-based Regulatory Decision-making, Beijing since 2009
o FDA Alumni Association (FDAAA) and SFDA/CDE co-
sponsored a successful pilot regulatory science
educational workshop for SFDA reviewers in Beijing
in 2009
 The three lectures and group discussion topics
• Vaccine Development Issues by Florence Houn
• Science-based Decision-making for Anti-Infective Products
by Mark J. Goldberger
• New Treatment for Cancer: US Regulatory Considerations
by Robert J. DeLap
o The FDAAA International Network (FDAAA IN) will
continue to explore ways to do outreach and
provide education to China SFDA regarding
establishment and operations of regulatory
programs

12. FOCUSED. TRUSTED. GLOBAL.
Certified Institutions for Clinical Trials in China
o Site: 550 hospitals
 To certify therapeutic areas to qualify conduct of
studies
 Re-certification every 3 yeas
o Phase I Units: about 115 units with 8-24beds per
unit
o About 20 centers focus on anticancer drug
(Phase II/III),
 A few centers are capable of conducting both Phase
I and Phase II/III,
o >13500 investigators and their staffs were
trained for GCP

13. FOCUSED. TRUSTED. GLOBAL.
FDA GCP Site Inspection in China
o US FDA inspected clinical investigators in China:
 8 PIs before 2008
 10 PIs between 2009 and 2012
o Regulatory actions were not necessary
although there were a few minor problems
(Classification: Voluntary Action Indicated, VAI)
o Problems found:
 Inadequate drug accountability
 Inadequate and inaccurate records
o FDA Clinical Investigator Inspection List (CIIL)at
www.fda.gov

14. FOCUSED. TRUSTED. GLOBAL.
FDA GCP Inspection on China Sites
as of 2012
Investigator Information Inspection Information
ZIP or Deficiency
Investigator Inspection
Name Location Address City Postal Type Classification Codes
ID No. Date
Code
432986 Ding, Ju-Hong Jiangsu Family 277 Feng Huan Nanjing 210029 07-Jun-1999 DA VAI 04,06,16
Planning Institute Zi jic
487467 Lu, Zhi-meng Ruijin Hospital - Shanghai - 13-Dec-2004 DA VAI 06
486375 Li, Zhanquan Liao Ning Province 33 Wenyi rd Shenyang 110016 20-Mar-2006 DA VAI 04,06
Peoples Hosp
499597 Wang, Fengde Jilin Chemical Corp. no.32 datong Tiedong area 132022 27-Mar-2006 DA VAI 04,06
road
499599 Zhao, Ruiping Baotou Central no.61 ring road Baotou city 014040 13-Mar-2006 DA VAI 04,06
Hospital west
499748 Zheng, Liwen Shenyang Military number 171 Changchun 130062 29-Mar-2006 DA VAI 04,06
208 Hospital, Jilin xian street
prov.
500052 Zhong, Jianhon Mei County Hospital Sikeng Songkou 514755 03-Apr-2006 DA VAI 04,06
g economic
development
zone
520953 Xiu-Qing, Jiao Institute Of No. 20 Fengtai Bejing - 09-Nov-2008 DA VAI 06
Microbiology And Street
Epidemiology
519006 Shen, Keng Peking Union Med 1 Shuai Fu Yuan Beijing 100730 30-Mar-2009 DA NAI 00
Coll Hosp Wangfujing
http://www.accessdata.fda.gov/scripts/cder/CLIIL/index.cfm?fuseaction=Search.Search&SortField=EntityId&DataField=CountryCode&Keywords=CH&SortRequest=1

15. FOCUSED. TRUSTED. GLOBAL.
FDA GCP Inspection on China Sites
as of 2012 - cont’d
Investigator Information Inspection Information
ZIP or Deficiency
Investigator Inspection
Name Location Address City Postal Type Classification Codes
ID No. Date
Code
463257 Zeng, Bingfang Shanghai Baotou 600 Yi Shan Rd Shanghai 200233 16-Feb-2009 DA VAI 05,06
Hospital
509832 Yang, Renchi Hemat & Blood 288 Nanjing Rd Tianjin 300020 12-Aug-2009 DA NAI 00
Diseases Hosp Inst
521447 Sun, Aining The First Affiliated Hosp 188# Shizi St Suzhou 215006 10-Aug-2009 DA NAI 00
Of Soochow Univ
519006 Shen, Keng Peking Union Med Coll 1 Shuai Fu Yuan Beijing 100730 30-Mar-2009 DA NAI 00
Hosp Wangfujing
524066 Shen, Zhixiang Rui Jin Hospital 197 Rui Jin Er Rd Shanghai 200025 03-Aug-2009 DA NAI 00
Hematology
Department
534903 Xiao, Rui Lianong Angang No. 32 Liaoning 014040 15-Aug-2011 DA NAI 00
Lishan Hospital Shuangshan Rd,
Lishan District
534904 Lou, Fengyun Jilin Province Jilin City No. 4 Nanjing Jilin City 132001 26-Jul-2011 DA VAI 05,18
Central Hospital Street
525437 Jing, Zhicheng Shanghai Pulmonary 507 Zhengmin Shanghai 200433 24-Sep-2012 DA NAI 00
Hosp Univ Rd, Yangpu Dist
538295 Jin, Zimeng Peking Union Medical No. 1 Shuai Fu Beijing 100730 11-Apr-2012 DA VAI 03,03,05,15
College Hospital Yuan Wan Fu
Jing
http://www.accessdata.fda.gov/scripts/cder/CLIIL/index.cfm?fuseaction=Search.Search&SortField=EntityId&DataField=CountryCode&Keywords=CH&SortRequest=1

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US FDA Clinical Investigator Inspection List
(CIIL) - Deficiency Code
 00: No deficiencies noted
 03: Inadequate informed consent form (21 CFR 50.25)
 04: Inadequate drug accountability (21 CFR 312.60,
312.62)
 05: Failure to follow investigational plan (21 CFR
312.60)
 06: Inadequate and inaccurate records(21 CFR
312.62)
 15: Failure to notify IRB of changes, failure to submit
progress reports (21 CFR 312.66)
 16: Failure to report adverse drug reactions(21 CFR
312.64, 312.66)

17. FOCUSED. TRUSTED. GLOBAL.
Advantages to Conducting Clinical
Trials in China
o Large patient populations
o Patient enrollments are rapid
o Experienced investigators are increasing
o Sites and clinical investigators are motivated
o Competitive cost compared to US and EU
 Relatively lower expenses for travel, monitoring,
project management fees, clinical investigator fees,
and procedural fees for diagnostic and therapeutic
interventions
o Large market for new drug products

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Disadvantages
o Ethnic differences
o Ethical issues
 Placebo
o GCP and protocol training is a must and may take
longer time to implement
 Take long time to Initiate a clinical trial
o A clinical trial application must be approved with a
written notice by SFDA
 it can be long time
o Investigator:
 Clinical investigators must be in the therapeutic
departments that are certified by China SFDA
o Clinical trials vs. marketing in China

19. FOCUSED. TRUSTED. GLOBAL.
China Pharma Industry
o Revenue: 10 millions – 1 billion US$ for most firms
o In-house pipelines for new drug development
 Increasing interest in acquiring new drug candidates
from R&D firms
 Increasing co-development for drug products with
foreign firms for China market

20. FOCUSED. TRUSTED. GLOBAL.
China Pharma Industry - cont’d
o State-owned:
 Sinopharm, Shanghai Pharm Group, Harbin Pharma
Group
o API-focused:
 Hisun pharma, Huahai Pharma
 Shifting to new drug development:
 HengRui, HEC Pharma
 Specialty:
 Fudan-Zhangjiang Biopharma
 Biotech:
 Hutchison MediPharma

21. FOCUSED. TRUSTED. GLOBAL.
Chinese Government Initiatives for New Drug
Development (Invented in China)
o Central Government
 Flood of Funding
• Billion US$ government grants in the 5-year plan starting
2012
o Provincial and local governments
 Matching funds to the projects funded by the central
government
o Incubators for new drug development in Economic
Development Zones in every province and major
metropolitan areas:
 Shanghai
 Taizhou
 Suzhou
 Beijing

22. FOCUSED. TRUSTED. GLOBAL.
Summary
o China regulatory environment is improving
o Clinical trial infrastructure is getting more mature
o Patient population, good drug compliance, faster
enrollment are rewards
o Ethnic difference, placebo issues, long regulatory
approval and language are obstacles.
o Planning, training and close monitoring are essential
for success in conducting clinical trials in China
o China domestic pharma firms are ready for
acquiring or co-developing drug candidates in
China market

23. FOCUSED. TRUSTED. GLOBAL.
Thank You!
Medpace
www.medpace.com