Post on 24-Aug-2020
“The pessimist sees difficulty in every opportunity, the optimist sees the opportunity in every difficulty”.
Churchill, Winston
Expectations are same:
Safety
Efficicacy
GMP compliance
Profile attribute
Population GDP growth
GDP per capita
Public expenditure on health
Private expenditure on health
2003 1.293 B Bln USD 4,157.8
USD $3217
1.6% of GDP 3.0%
2009 1.341B Bln USD 10,085.7
USD $7519
2.4% of GDP 2.2%
Profile attribute
Import of goods
Import of goods and service
Export of goods
Export of goods and service
2003 Bln. US$ 412.8
27.4% of GDP
Bln. US$ 438.2
29.6%
2010 Bln. US$ 1396.0
22.3% of GDP
Bln. US$ 1577.8
26.7%
Total value 1252.3 Billion RMB
Annual increase 21.3% during 10th 5 year plan
above GDP and national average level
section value billion
chemicals 240.58
Preparations 354.69
TCM 335.91
Biological Products 131.42
Medical Products 189.62
Q2 2012 CNY 405 B. = 21.1% growth
Q1 2012 24.1% growth
2012 growth rate significantly higher than Q1 and Q2 of 2011
12m MAT (moving annual total) 19.6% growth rate
compared with 18.3% in MAT Q2 2011
Hospital (100 beds or more) sales at hospital purchasing price
Domestic Application Reception Foreign
Application Reception
Chemical
Chinese
Biologic
Supplemental
Quantity 1528 105 69 2433 599
Sum 4135 2433 599
Total 4734
category 2008 2009 2010 2011 2011 renewal approvals
Chemicals 2449 1587 1003 717 581
TCM’s 1160 1706 151 143 55
Biologicals 132 67 24 38 24
Total 3741 3360 1178 898 660
Approved Drugs in 2010
Chemical Drugs Chinese Medicines Biologics
New drug
Form changed drug
Generic drug
New drug
Form changed drug
Generic drug
New drug
Form changed drug
Generic drug
103 51 640 12 59 9 9 1 2
794 80 12
886
Type Domestic Foreign Total
Chemicals 466 255 976
TCM 33 3 36
Biological 29 50 79
Total 528 308 1091
1963: Chinese MoH planned drug regulation to manage
1979: MoH and State Pharmaceutical Admn jointly published the New Drug Management Regulation
1985: first comprehensive Drug Admn. Law
1988: rule for new importation drug registration; provisions were enacted in 1991 and revised 1999
1992: US-China MOU
1993:Provisions for Drug Administrative Protection were enacted, 7.5 years of market exclusivity for patented drugs
1999: The State Pharmaceutical Admn of China: division of Drug Admn in the MoH and the Division of TCM Admn Bureau were merged
2001: Drug Admn. Law revised; requires premarket testing and approval and prohibit drug adulteration
Amendment 1; provision for New Drug Approval;
Amendment 2; provision for new Biological Drug Approval
2001: Gained membership with WTO
2002: New Drug Registration Regulation aligned with WTO
The State Food and Drug Administration (SFDA), primarily oversees drug administration
Used to be an independent authority but in 2008 incorporated into MoH because of drug safety and internal corruption scandals
Centre for drug Evaluation (CDE)
National Institute for the control of Pharmaceutical and Biological products (NICPBP)
The State Development and Reform Commission (SDRC), responsible for the drug price administration; and
The Provincial Administration for Industry and Commerce, cooperating with the Provincial Food and Drug Administration, (PFDA) to regulate drug advertisements.
Food and drug safety
Basic healthcare system
Perfect drug supply and guarantee system
Guidelines for accelerating structure adjustment of pharmaceutical industry jointly issued by MIIT, MOH, and SFDA on Oct.9,2010
Guidelines and basic principles were provided
Incentives for 2012 GMP implementation
Standards and timeline will not change
Accelerating review and approval tech and transfers among subsidiaries and M&A deals
Higher tender price for “better” products with 2010 GMP certifications
Accelerated GMP certifications of facilities with international compliance certifications
Research program listed as “state major R&D projects” will be reviewed through green channel
Encourage short supply and orphan drugs mfg.
Multilateral cooperation: WHO, ICH, APEC, DCVRN, FHH, IRCH and PIC/S
Bilateral cooperation: signed MOU with USA, Canada, Cuba, Brazil, Australia, EU, Russia, UK, France, Denmark, Italy, Latvia, Pakistan, Singapore, South Korea, Japan and Thailand etc.
ICH Chinese focus study teams:
Formulated work specifications
Regular work meeting
Positive advancements:
Publication of the translated version of ICH guidelines
Established research achievement online disc
2010 annual report
Complete logo design of ICH Chinese team
Expanded study team size
WHO vaccine pre-authentication
System authentication
Signed negotiation cooperation mechanism with EC’s DG Enterprise and Industry in Oct.2007
First annual high level working group meeting between SFDA and EU was in Bejing in April 2009
Commissioner Mr. John Dalli visited China and both parties renewed MOU in Oct.2010
In August 2007, US FDA Commissioner visited SFDA
In Dec.2007 signed safety agreement of Pharmaceuticals and Medical Devices with DHHS of USA
In Dec.2010 annual Sino-USA pharmaceutical regulatory meeting was organized and discussed mutual points of interest and collaboration
FDA exchanges
Generic Drug Forum
Annual meeting and conferences (BIO Chinese and JCCT framework)
New Drug Application
Drug standardized by the State (ANDA/ANDS)
Import Drug Application
Supplementary Application
“New Drug” never been marketed in China
Old regulation; produced in China for the first time
Chinese manufacturer who produce imported drugs on
Chinese market should submit the application accordingly to
the requirements for “the drug standardized by the State”
Class 1: NCE’s are true NCE that have not been marketed in the world
Class 2: NCE’s marketed abroad but not part of foreign pharmacopoeia and have not been imported to China
Class 3: new combinations of already approved drugs
Class 4: NCE’s listed in foreign pharmacopoeia or previously imported into China; new dosage forms of approved drugs; new route of administration of approved drugs
Class 5: New indications for approved NCE’s
China accounts for 20% of world’s population and only 1.5% of global drug market
World’s third largest prescription drug market and likely to grow for sometime
Basic health insurance is not available for all therefore low cost and ability to cost effectively follow innovations
Currently has about 4000 drug companies and most focused on generic business
2010 SFDA approved 886 applications and 651 were generics (73%)
No “branded drug” concept like in USA
Amended regulation for drug registration uses “new” drugs that has not been previously marketed in China. “Generic” drugs has an existing national drug standard and was previously approved by SFDA
Generic chemical drugs need BE studies to be conducted on 18-24 subjects
Generic drugs based on TCM or natural drug injections CT on not less than 100 pairs of cases are required
Biosimilars subject to full phase III CT
Establish Regulations: measures for drug research supervision and management
Establish Systems: scientific registration management system with technical review, audit, inspection etc.
Establish the teams: internationalized professional inspector teams
Establish the mechanisms: uniform, coordinated, flexible efficient dynamic audit and inspection mechanisms
Establish the institution: grading and classification management institution for drug R&D units, CT, contract study and registration applicants and commissioners
Article 11:
Applicant to submit documents explaining the China Patent Status and ownership rights. Assume liability of patent infringement
Article 12:
If an infringement dispute occurs after the registration parties negotiate or resolve through judicial organs to patent admn institutions
Article 13:
Under patent protection another sponsor can apply for registration within 2 years prior to expiry
Current Provision was promulgated on Oct.30, 2002
Put into force on Dec.1, 2002
More reasonable and suitable, particularly with regard to China’s entry into WTO
Qualification of the applicant has been clearly stipulated
Applicant should be a legal entity such as corporation, pharmaceutical firm, government agency and/or scientific institution
Import drug registration require branch in China or China’s authorized agency
Assigned person should have sufficient knowledge and proficient in admns of regulations
China’s membership in WTO:
Within 6 years of approval of drug with NCE the regulatory authority will not approve use of proprietary data to apply for NCE
Required to submit patent information, ownership, non-infringement and promise to assume all the infringement responsibilities
Allowed to submit within 2 years of patent deadline so as to allow to be in market immediately after patent expiry
Application to be filed with the provincial FDA (PFDA)
PFDA determines whether application dossier is in proper order
PFDA provides notification of acceptance or reasons for rejection and opportunity to reapply
Within 5 days of acceptance, the PFDA will conduct an on-site inspection and take samples of 3 consecutive batches to send to Drug Control Institute for inspection
PFDA will submit the dossier with its examination recommendation, verification report, results of inspection to the SFDA CDE within 30 days
CDE will organize pharmaceutical, medical and other technical staff to examine the application dossier and verification recommendations
May request supplemental information if necessary
Drug control institute provide the sample test report to the CDE. PFDA and the sponsor (30 days)
CDE prepares a general examination recommendation and submit to SFDA along with the related data (160 days)
SFDA makes the approval decision and issue a Drug Approval Number (if no CT needed) or Clinical Trials approval (10 days)
Applicant to submit the CT data to CDE for final approval
CDE conduct technical examination of CT report
SFDA makes approval decision based upon technical examination recommendations. (30 days)
Issue DAN and Notification of Approval Opinion (10 days)
Time to approval 205/245 working days (50 weeks) provided everything move as planned
For drugs not meeting safety requirements the Amended Regulation grants SFDA authority to suspend acceptance or approval of generic drug application
wide quality and efficiency gaps existed before 2007
BE studies for such products in next 5-10 years
Level of generic drugs to raise to international standards
Start with essential drugs and commonly used drugs
Initiatives will begin with essential drugs with large population, high consumption volume, multiple mfg.
Oral drugs first and later on injectables
BE guidelines and product selection
RLD identification
All required studies to be fully initiated by 2014
Injectable and other dosages from 2015-2020
SFDA and Guangdong provincial government joined to develop capacities on experimental basis
MOU signed in March 2012 reform exploration and trial for drug evaluation and approval system
To organize technical evaluation and approve new drugs tech transfer and drug production TT application
Decisions will be filed with SFDA and SFDA will issue drug approval numbers
Review and approve for CMO except TCM and biologicals
MAA specified in certificate of pharmaceutical product (CPP) can be holder and applicant of IDL
Fees CNY 45300+ CNY 50000 (sample testing)
Clinical trials may be required for registration and may cost to the order of US$ 4-5 millions
IDL application dossier is accepted
Centre for drug evaluation (CDE) will issue a deficiency letter within 160 working days
Applicant will have 4 months to prepare and submit the supplementary data required
CDE will send its evaluation report to the SFDA within 54 working days
The SFDA will issue the final decision within 25 working days
Total 359 days or 71 weeks
Intellectual property environment
1993:
Patent law to include API rather than process only
Invention protection term from 15 to 20 years
Joined the Patent Cooperation Treaty to allow multi-jurisdictional filing
2002:
Adopted data exclusivity for 6 years term
Added provisions on patent linkage
The system institution and legislation construction of drug registration management can not be fully adaptable to the demand of the new drug
innovative production and industrial development changes in China
The relevant management regulation in the drug R&D field (especially to CT) are still to be completed and the complete system still needs to be constructed for
technical guidance principles
The whole-process supervision and inspection system of drug registration is not complete, and there is a lack of professional and full time inspection teams, shortage of admn resources while continuous increase of supervision and
management demands
The risk control capacity in the drug R&D and registration process is insufficient capacity of communicate and supervise before, during and after study to be
improved; excessive emphasis on post hoc supervision and management does not resolve the earlier croped issues
Generic IDL applications with clinical data, CDE will need another 90 working days to evaluate the dossier
Certificate of good sales practice (CGSP) is required to distribute and sell pharmaceuticals in China
Should have an inspected warehouse (at least 500 sm), registered pharmacists and documentation system
Small agent employ the CGSP to do the business but it is prohibited by the SFDA
Generic name should be in national’s reimbursement drug list (NRLD)
Ministry of Human Resources and Social Security updates the list every 4 years
National Development and Reform Commission (NDRC) controls the retail price of drugs listed under NRDL
Exceptional retail price approval if proven that quality, safety and efficacy are better
Such sponsors have little competition and higher margin to support their promotion campaign
Agents can be blacklisted by the hospitals if they can not provide according to the signed agreement
Often use “money promotion” rather than academic detailing. Illegal step and getting legal actions
Annual pharmacovigilance report so as to re-register after 5 years