Learn about the impact of China 's regulatory reforms for companies conducting clinical research in the country from PAREXEL Consulting experts.

1. © 2018 PAREXEL INTERNATIONAL CORP.
EFFECTIVE
REGULATORY
STRATEGIES FOR
CHINA MARKET ENTRY
Mingping Zhang
Vice President (Technical), Integrated Product
Development, PAREXEL® Consulting
April 17, 2018
PAREXEL KOREA SYMPOSIUM 2018

2. © 2018 PAREXEL INTERNATIONAL CORP. / 2
AGENDA
EFFECTIVE
REGULATORY
STRATEGIES FOR
CHINA MARKET
ENTRY
• Key Changes in China Regulatory
Reforms
• Strategies to Accelerate Drug
Development For China
• Interaction with CFDA and CDE

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WHAT IS THE OVERALL CHINA STRATEGY?
Reimbur-
sement
Pre-Approval
Hospital
Listing
Bidding
Process
PricingMAA RegistrationBridge Clinical Trials
Post-Approval
2-4 yrs 1.5 - 2 yrs 1-7 ms
Description
Stake-holders
• NDRC • Bidding committee • Hospital listing
committee
• MoHR&SS for national list
• PLSS for provincial lists
• CFDA
Registration Launch
• CFDA
1-5 yrs
1-12 ms
Happening:
• Balance price & quality,
• Broad coverage include high value drug,
• Enlist the new drug timely
MRCT Shortened and no
CPP required
Foreign company:
Integrate China into global
synchronize development
Foreign company:
Welcome to bring new
treatments into China

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WHY THE “NEW DRUG DEFINITION” MATTERS
Generic
New drug
Innovative
Improvement
Small innovation(505B2)
Drug
With Data
Exclusivity
(3~5 years)
First
generic
enjoys 1.5
year Data
Exclusivity
Previous definition
Never market in China
New definition
Never market in Anywhere
Previous definition
Meet China publish Spec.
New definition
Equivalent to originator.
Different regulatory strategy - Late entry to China will lose new drug
designation and data exclusivity
*CPP are not required for China NDA now
*Dosage form change without justifying
clinical benefit will be rejected
*The regulatory category will be fixed by the
status when the application has been accepted

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KEY CONSIDERATIONS FOR CHINA CDP (PROS)
Market Considerations:
• China forecasted to become the #2 pharmaceutical market by 2020 *
• Healthcare spending increased to 7% of total government expenditures in 2016
and it will keep increasing in near future
• Government making efforts to streamline the market access process
Development Considerations:
• The largest patient pool and fast recruitment
• Adopting ICH requirements
• Good infrastructure at clinical sites and data acceptance by US FDA/EMEA; can
be used for product registration
• Much faster CTA & NDA approval timeline compared to year 2015
• Foreign clinical data may be acceptable for China registration
*Source: McKinsey & Elsevier Business Intelligence report: <<In Search of New Growth Models for Big Pharma in China>> (2013)

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Market Considerations:
• Market access process is complicated
• National reimbursement still takes a couple of years
Development Consideration:
• Although there are 30,000 hospitals in China, only approximately 600 clinical
sites have adequate GCP capabilities and are experienced clinical trial sites
• It is mandatory to address efficacy and safety in China for China registration
– It is encouraged to use China sub-group analysis in MRCT;
– China stand-alone trial or strong scientific justification are also accepted
• China Ethics Committee (EC) approval process & requirements are not fully
aligned with the regulatory reforms
• The new HGRAC process (Dec 2017) is not fully implemented
KEY CONSIDERATIONS FOR CHINA CDP (PROS)
HGRAC: Human Genetics Resources Administration of China

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重大专项
（National Major List）
特殊审评
（Special Review Procedure/
SRP）
抗HIV与抗 耐药结核/抗感染
(HIV, TB)
临床急需和可及性需求
（Medical needs, include
Orphan drugs）
儿童用药
（Pediatric drugs）
加快品种
（fast review）
血液制品
(Blood product)
CTD
PRIORITY REVIEW & ACCELERATE APPROVAL
AFTER REFORMBEFORE
REFORM Significant
clinical value
Demonstrate
superiority in treatment
of certain disease
Others
Category I application HIV Generic quality re-evaluation
projects which need to raise
supplemental application for
major changes;
Innovative drug transfer to
China local manufacturing
Tuberculosis (TB) GCP inspection withdraw
projects which can meet
Generic quality re-evaluation
requirements;
Innovative technology with
significant clinical improvement
Antibiotic
The CTA 3 years before patent
expire or NDA 1 year before
patent expire
Viral hepatitis Un-med medical needs
product (the list will be
published by government)
* The first application
acceptance will block the
other similar product got
“priority review”
Local companies conducting
global synchronized
development or local
companies with drugs
successfully registered and
launched in US/EU market
Rare diseases
Traditional medicine which has
clear defined role in major
disease treatment/prevention
Geriatrics drugs In public medical emergency,
compulsory license product;
National major projects Pediatrics with unmet
medical needs
For products for life-threatening
conditions & unmet medical needs
a meeting with CDE can be
requested anytime and conditional
approval (e.g. Phase II) can be
discussed/granted Foreign clinical data is
accepted directly

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SHORTENED REGULATORY TIMELINE
- CDE 2017 ANNUAL REVIEW REPORT
Day
Completeness
IND
timeline summary
 Red line is year 2017; the other color line stand for year 2012~2016
 “Completeness” means the approval/rejection decision can be made in regulation
define timeline(IND-110 WD; NDA – 140 WD)
Day
Completeness
NDA
timeline summary

9. © 2018 PAREXEL INTERNATIONAL CORP. / 9
For Innovative DrugsFor Innovative Drugs
AFTER CHANGEBEFORE CHANGE
Before
Aug 2015
Chem.CTA 20 m
Chem.NDA 30 m
Bio. CTA 34 m
Bio. NDA 34 m
After 2018**
Chem. CTA 60 WD*
Chem. NDA 7~13 m*
Bio. CTA 60 WD*
Bio. NDA 7~13 m*
Root cause:
(1) CDE Significantly increasing number of reviewers from about 90 to 800 in
2018
(2) Significantly decrease the application by improve the acceptance/approval
criteria, and change the BE to filing procedure
(3) 2017 finished review 9680; new application 4837
*Clock stop period is not counted
** After new DRR is implemented
SHORTENED REVIEW TIMELINE

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<< CDE COMMUNICATION GUIDANCE (DRAFT) >>
MARCH. 13. 2018
CDE
F2F
VC
Written
TC
Scope
• Innovative Drugs
• Category II
(505B2) products
• Biosimilars
• Complex
Generics
• GCE products

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TYPES OF CDE CONSULTATION MEETINGS
<< CDE COMMUNICATION GUIDANCE (DRAFT) >>MARCH. 13. 2018
Type I – Significant Development Issue : e.g., key issues of innovative
drug development or significant safety issues
• Held within 30 days of request; Briefing book (BB) must submit with the
meeting application
Type II – Entitled meetings: pre-IND*, end of Phase I*, end of Phase II,
pre-NDA/BLA meeting, PMS meeting
• Held within 60 days of request; Briefing Book (BB) due 30 days before the
meeting
Type III – Any other meeting: meeting to discuss the general
development of a drug; e,g, Category II, III, IV or V
• Held within 75 days of request; Briefing Book (BB) due 30 days before the
meeting
*May or may not be granted

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RECOMMENDED STRATEGY: GLOBALLY SYNCHRONIZED
DEVELOPMENT - NEW DRUG DEVELOPMENT
MRCT Pivotal trial in China & US, EU, ROW
• China (if no significant ethnical difference concern)
• Global MRCT – minimum 15% to 20% subjects
• Regional MRCT – minimum 50% subjects
• China, US, EU & ROW
• Protocol amendment/confirmation with different HA
Additional indication & Phase IV study
• China & RoW
• Leverage other country & Area?
 China KoL meeting & EC submission
 Pre-IND meeting with CDE
 CTA sub. & Approval
 Phase I PK in China
 《guidance of China CFDA NCE phase I application
requirements, CFDA, 2018 Jan》

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RECOMMENDED STRATEGY: GLOBALLY SYNCHRONIZED
DEVELOPMENT - BIOSIMILARS
KEY CONSIDERATIONS:
1) Similar: Step-wise & total evidence
2) Difference: RLD accepted in another country; limited indications
Scenario I: China Joins Global Pivotal
Study
Scenario II*: China Bridge Study
* Without CPP, it is not allowed to apply for a China stand alone study for Biosimilars

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THANK YOU
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