Date post: | 23-Dec-2015 |
Category: |
Documents |
Upload: | lauren-morton |
View: | 215 times |
Download: | 0 times |
Challenges, trends and Strategies in TCM Development
May 17th 2011 | Beijing, China
Unique Potential for Innovation in China
Jing’an, Shanghai, March 2011
Traditional Chinese Medicine 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?
5
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.
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 Laboratory Practice (GLP) certificate:
•Beginning in 2007, all non-clinical drug research must be carried out in a GLP certified facility
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 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 Extraction Practice (GEP) certificate:
•This covers the first step of the TCM manufacturing process, which ensures quality and use of TCM products
“ModernQualityTCM”
0
2000
4000
6000
8000
10000
12000
1993
1995
1997
1999
2001
2003
2005
2007
2009
Year
patent applns
patent grants
No
of T
CM
Pat
ents
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)
2007: A New TCM Standard for Registration
TCM NCE
Pre-clinical safety GLP for short term tox required GLP for long term tox preferredUse of existing data permissible
GLP required
Pre-clinical pharmacology
GLP should be applied “as much as possible”
GLP required
CMC 1 batch tested for CT3 batches tested for NDA
1 batch tested for CT3 consecutive batches tested for NDA
Phase I* 20-30 patients for toleration 20-30 patients for toleration & PK
Phase II/III/IV* Ph II = 100Ph III = 300Ph IV = 2,000
Ph II = 100Ph III = 300Ph IV = 2,000
Endpoints Western (primary) + TCM (secondary)Primary endpoint must be met
WesternPrimary endpoint must be met
*number given/trial group
0
1000
2000
3000
4000
5000
6000
7000
8000
2004
2005
2006
2007
2008
2009
2010
2011
Marketing applns Marketing approval
SFDA Regulations Revised in 2007P
re-2007S
ince 2007New TCM drug approvals:
2009: 722010: 10
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 innovatorSimilar 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?
Active control?
Randomised?
Individualised?
Double blind?
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