Churchill, Winston Expectations are same: Safety Efficicacy GMP - PowerPoint PPT Presentation

“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 Population GDP GDP per Public Private attribute growth capita expenditure expenditure on health on health 2003 1.293 B Bln USD USD 1.6% of GDP 3.0% 4,157.8 $3217 2009 1.341B Bln USD USD 2.4% of GDP 2.2% 10,085.7 $7519

Profile Import of Import of Export of Export of attribute goods goods and goods goods and service service 2003 Bln. US$ 27.4% Bln. US$ 29.6% 412.8 of GDP 438.2 2010 Bln. 22.3% Bln. 26.7% US$ 1396.0 of GDP US$ 1577.8

 Total value 1252.3 Billion RMB  Annual increase 21.3% during 10 th 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 Chemical Chinese Biologic Supplemental Reception 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 Form Generic New Form Generic New Form Generic drug changed drug drug changed drug drug changed drug drug drug 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