Challenges, trends and
Strategies in TCM
Development
May 17th 2011 | Beijing, China
Unique Potential for Innovation in China
Traditional Chinese Medicine
Jing’an, Shanghai, March 2011
Translational Medicine
TCM is One of Fastest Growing Therapy Areas
Kanpo Medicine: System of herbal medicine practiced in Japan by both herbalists and practitioners of modern medicine. Kampo originated in China and is based on Chinese herbal medicine
TCM Rx Is Mostly For CV, Oncology, Gynecology
What is Modernised TCM?
Good Agriculture Practice (GAP) certificate:
•Ensures TCM herbs and raw ingredients are clean
and fit for human consumption and that they
contain the effective ingredients
•TCM medicine manufacturers usually do not need
this certificate, but suppliers may be chosen
according to whether or not they have this
certificate
•>99 GAP bases in 22 provinces covering 49 different
herbs.
“Modern
Quality
TCM”
Good Laboratory Practice (GLP) certificate:
•Beginning in 2007, all non-clinical drug research
must be carried out in a GLP certified facility
Good Manufacturing Practice (GMP)
certificate:
•The requirement for all drug manufacturers to
have this certificate came into effect at the
beginning of 2004
•All TCM makers must have this certificate or
they are subject to suspension.
Good Supply Practice (GSP) certificate:
•Introduced in 2001, it is necessary if a company seeks
to develop an internal distribution and supply
network
•Foreign companies generally are not able to attain
this certificate, but domestic subsidiaries can.
Good Clinical Practice (GCP) certificate:
•Since 1999, GCP certifications are necessary to perform
clinical trials on a drug to determine its quality and
efficacy
Good Extraction Practice (GEP) certificate:
•This covers the first step of the TCM manufacturing
process, which ensures quality and use of TCM
products
5
Protect Innovation: Patent Law & Regulations
Before 1st amendment to Chinese
Patent Law in 1993, there was no
patent protection for pharma
product or food
 Chinese Patent Law recognises
composition of matter, method & use
claims
 Can be easy to design around (e.g.
change composition mix, change
extraction method)
 Difficult to enforce (e.g. difficult to
prove infringer used same method)
patent applns
12000
10000
patent grants
8000
4000
2000
Year
2009
2007
2005
2003
2001
1999
1997
1995
0
1993
No of TCM Patents
6000
2007: A New TCM Standard for Registration
TCM
NCE
Pre-clinical safety
GLP for short term tox required
GLP for long term tox preferred
Use of existing data permissible
GLP required
Pre-clinical
pharmacology
GLP should be applied “as much as
possible”
GLP required
CMC
1 batch tested for CT
3 batches tested for NDA
1 batch tested for CT
3 consecutive batches tested for NDA
Phase I*
20-30 patients for toleration
20-30 patients for toleration & PK
Phase II/III/IV*
Ph II = 100
Ph III = 300
Ph IV = 2,000
Ph II = 100
Ph III = 300
Ph IV = 2,000
Endpoints
Western (primary) + TCM (secondary) Western
Primary endpoint must be met
Primary endpoint must be met
*number given/trial group
SFDA Regulations Revised in 2007
Pre-2007
8000
Marketing applns
Marketing approval
7000
6000
5000
4000
3000
2000
1000
2011
2010
2009
2008
2007
2006
2004
2005
New TCM drug approvals:
2009:
72
2010:
10
Since 2007
0
A New Era of Evidence Based TCMs
 Development attrition risk likely lower than NCE :



Many promising new chemical drugs have failed to deliver efficacy
Efficacy for TCMs based on many years of (anecdotal) clinical experience,
Many years of non-controlled clinical use = low risk of unexpected safety issues
 Regulatory



Clear regulatory pathway for TCM in China and major markets
(SFDA Guidance 2007, FDA Guidance 2004, EU Directive 2004)
New requirements for evidence represent significant barrier for most TCM companies
Competitors who choose to develop same/similar TCMs must produce data to support
their claims to the same standard as the innovator
Similar to biosimilars, represents major barrier to entry
 Government: 2007 Party Congress support increased role for TCM in
healthcare



Encouraged private sectors investment, TCM heritage protection
TCM innovation/modernization
More TCM use for Primary care, Essential Drug List, National Reimbursement Drug
List
 Global market is an aspiration
TCM/Botanicals: A Global Opportunity
 US & EU have regulatory guidelines for botanical drugs


US: FDA Guidance for Industry: Botanical Drug Products, June 2004
EU: Directive 2004/24/EC, amending Directive 2001/83/EC, April 30, 2004
•
Guideline On Declaration Of Herbal Substances And Herbal Preparations In Herbal Medicinal
Products/Traditional Herbal Medicinal Products (EMA/HMPC/CHMP/CVMP/287539/2005 Rev 1),
March 11, 2010
•
List of Questions and Answers (Q&A) Received During the HMPC Assessors Training on
Quality Issues Emerging for Herbal Medicinal Products (EMEA/531300/2008, November 6, 2008
•
Guideline on Selection of Test Materials for Genotoxicity Testing for Traditional Herbal
Medicinal Products/Herbal Medicinal Products (EMEA/HMPC/67644/2009) November 12, 2009
•
Reflection Paper on Markers used for Quantitative and Qualitative Analysis of Herbal Medicinal
Products and Traditional Herbal Medicinal Products (EMEA/HMPC/253629/2007) July 15, 2008
•
Guideline on the Quality of Combination Herbal Medicinal Products/Traditional Herbal
Medicinal Products (EMEA/HMPC/CHMP/CVMP/214869/2006) June 23, 2008
Guideline on Quality of Herbal Medicinal Products/Traditional Herbal Medicinal Products
(CPMP/QWP/2819/00 Rev 1, EMEA/CVMP/814/00 Rev 1), March 30, 2006
•
•
Guideline on specifications: Test Procedures And Acceptance Criteria For Herbal Substances,
Herbal Preparations And Herbal Medicinal Products/Traditional Herbal Medicinal Products
(CPMP/QWP/2820/00, EMEA/CVMP/815/00) March 30, 2006
 Early experience

Veregen is the only botanical approved in US (MediGene AG, 2006)
•


Green tea extract for condyloma acuminata
Hutchinson Pharma’s HMPL-004 for IBD completed Phase II in US
Tasly’s Danshen Dripping pill has completed Ph II
1st May 2011: A Watershed for TCM in EU
TCM: Drug Development Challenges
Right Patient
Right Drug
Right Dose
Western or
Chinese
concepts of
disease?
Traditional
combinations
or select herbs
based on
pharmacology
Recipe?
Maximum
tolerated dose?
Dose ranging?
Placebo control?
Randomised?
Double blind?
Active control?
Individualised?
Clinical Research: 10 Challenges
Evidence Based TCMs
Evidence Based TCMs: Individualised
Evidence Based TCMs: Dementia
Evidence Based TCMs: Stroke
2011 and Beyond………
Backup
Evidence Based TCMs: Rhinitis