1. WHO Projects Organized in Cooperation with SFDA in China Christina Foerg-Wimmer, PhD Pharmaceutical Advisor WHO China Office May 18, 2011 | Beijing, China

2. WHO Projects Organized in Cooperation with SFDA in China 2 Current projects focusing on quality and safety of pharmaceutical products, sponsored by Bill and Melinda Gates Foundation (BMGF) –To substantially improve TB control in China by increasing national capacity to produce fixed-dose combination (FDC) anti-TB medicines of assured quality and to regulate TB FDC drugs (WHO TA over 18 months, WHO budget US$ 1.5 million, SFDA US$ 0.5 million) Global Fund to Fight HIV/AIDS, TB and Malaria (GFATM) –To improve the quality of anti-TB, HIV/AIDS and malaria medicine produced in China to ensure improved accessibility and patient outcomes. (Initial 3-year program of work approved including US$ ~ 4.2 million for WHO TA, total consolidated HSS budget US$ ~25.5)

3. BMGF projects on TB control in China 3 China MoH – Gates Foundation TB project: Use of Innovative Tools and Delivery Approaches to Improve TB control in China (5 years) SFDA – Gates Foundation Subproject: China anti-tuberculosis FDC drug quality assurance (2 years) WHO – Gates Foundation Project: To substantially improve TB control in China by increasing national capacity to produce fixed-dose combination (FDC) anti-TB medicines of assured quality and to regulate TB FDC drugs (18 months)

4. 4 TB FDCs in China According to MoH/CDC guideline, the predicted consumption of TB FDCs will increase approximately 10 times in the years 2010 -2013 (MoH/CDC guideline). Additionally, there will be also considerable demand from non-CDC users, once TB FDCs are available. *Pacific Health Summit, USA, June 2009. 4Estimated from self-reported sales numbers by FDC manufacturers (Huangban, Hongqi, Nanyang). Source: Interviews and Global TB Control 2009

5. 5 BMGF – Project activities 1.GMP: Support 4 manufacturers of FDC anti-TB drugs in implementing WHO GMP standards, and in meeting requirements for participating in WHO PQ program 2.Post-market surveillance: Provide technical support to quality control testing labs for TB FDC drugs in China.. 3.Pharmacopeia: Support the Chinese Pharmacopeia Committee (CPhC) in revising or drafting monographs of TB FDC drugs and of their respective APIs for inclusion in the Chinese Pharmacopeia.

6. 6 BMGF - GMP part No direct financial support to manufacturers through this project but Technical Assistance (TA), including free of charge support to: achieve quality assured production of TB FDC drugs and thus, strengthen their role on domestic market and increase export opportunities implement new GMP standards move towards WHO prequalification. WHO prequalification functions as a gate-keeping mechanism to enter international tenders and procurement is growing better understand GMP and data requirements for FDCs which is of benefit not only for FDC but all other drug production

7. 7 BMGF - GMP part Manufacturers participating in the project commit themselves to: Produce or develop TB FDCs (in line with WHO recommended formulations) Produce or develop TB FDCs (in line with WHO recommended formulations) Submit these medicines for WHO Prequalification Submit these medicines for WHO Prequalification Accept informal audits and follow expert advice on how to upgrade GMP and dossier standards to meet WHO requirements Accept informal audits and follow expert advice on how to upgrade GMP and dossier standards to meet WHO requirements Cooperate with expert external and internal of WHO such as on gap analysis and remediation plan Cooperate with expert external and internal of WHO such as on gap analysis and remediation plan Make financial investments for quality upgrade, if needed Make financial investments for quality upgrade, if needed

8. 8 GFATM complex project HIVTB Malaria HSS HSS Cross Cutting Interventions are described under TB part of proposal Project overall objective Reducing the morbidity and mortality from M/XDR-TB in China HSS cross-cutting intervention: Improving the quality of anti-TB, HIV/AIDS and malaria medicine produced in China to ensure improved accessibility and patient outcomes. 2010 – Signature of project agreement Resources planned for 3 years with possible extension until 2015 (total 5 years)

9. 9 GFATM HSS project components Objective 1: GMP – implement revised GMP standards, – strengthen GMP inspection system, – promote WHO Prequalification Objective 2: Strengthen the national quality control system by – prequalification of reference quality control laboratory, – implementation of quality system in the network of official QCLs – widening the scope of NIS field controls Objective 3: Chinese Pharmacopoeia – revision of existing or development of new pharmacopoeial monographs for selected anti-HIV/AIDs, TB and malaria medicines

10. 10 GFATM – Strengthening of GMP standards in China Support to 400 selected API and FPP manufacturers producing HIV/AIDS, TB and Malaria medicines to implement revised GMP standards and achieve international acceptability and to pass WHO PQ –Indicator: 200 manufacturers of selected ARVs, TB and Malaria medicines compliant with revised GMP Training of GMP inspectors –Indicator: Number of inspectors passed post training competency evaluation (GMP and QMS for GMP) - 1816 trained, 80% pass Development and implementation of QMS for SFDA inspectorates –Indicator: 2 out of 32 inspectorates established QMS for GMP according to international standards

11. 11 GFATM – Strengthening of GMP standards in China Activities to strengthen GMP standards include: Extensive trainings by international experts (for GMP inspectors and manufacturers) Seminars and workshops such as to resolve difficulties in implementation of revised GMP and develop an implementation strategy Regional meetings such as on GMP implementation status, impact assessment, WHO PQ Joint inspections to manufacturers by SFDA and international experts

12. 12 GFATM – Quality Control part Building a reliable network of Quality Control labs in China 386 QC labs across China are included Development of QMS for quality control laboratories (NIFDC and network of QC labs) –Indicator: 6 QC labs implemented Quality Management Systems according to international standards Trainings of lab personnel on QMS and QC testing –Indicator: Number of QC lab staff trained and passed final competency examination - 540, 90% pass Prequalification of national reference quality control laboratory (NIFDC) Audits of QC labs and development of CAPA plans. Strengthening of post-marketing surveillance by mobile testing units.

13. 13 GFATM – Pharmacopeia part Revision of selected monographs in Chinese Pharmacopeia Collection and evaluation of data from manufacturers on synthetic methods and manufacturing processes Harmonization of monographs with major Pharmacopeias (i.e. PhEur, USP, BP, PhInt), reflecting ICH quality guidelines Monographs of APIs and FPPs are included, focus on anti- HIV/AIDS, malaria and TB medicines –Indicator: 50 monographs reviewed in Chinese/International pharmacopoeia and SFDA standards

14. 14 Industry situation Current status of China’s pharmaceutical industry: ~4700 manufacturers of APIs and FPPs Mainly small to medium scale manufacturers Number of international certifications and participation in international tenders is low Consolidation of pharmaceutical industry expected after implementation of new Chinese GMP Countries where prequalified medicines are manufactured (July 2009)

15. 15 WHO PQ in China (April 2011) Therapeutic area INNFormulationApplicantManufacturing sitePackagingReference HIVNevirapineTabletsHuahai US Inc.Zhejiang Huahai Pharmaceutical Co. Ltd, Zhejiang, P.R. China HDPE bottle 60USFDA2 MAAmodiaquineFilm-coated tablets Guilin Pharmaceutical Co. Ltd Guilin, Guangxi, ChinaPVC/Alu blisters 6; Cardboard box 2 x 6 MA045 MAAmodiaquine + Artesunate TabletsGuilin Pharmaceutical Co. Ltd Guilin, Guangxi, ChinaPVC/Alu blister 3x(4+4), 3+3, 6+6, 12+12 MA046 MAArtemether + Lumefantrine TabletsNovartis PharmaBeijing, China; Suffern, USA Blister 6, 12, 18, 24MA026 MAArtesunateTabletsGuilin Pharmaceutical Co. Ltd Guilin, Guangxi, ChinaBlister 12MA044 MAArtesunatePowder for Injection Guilin Pharmaceutical Co., Ltd. Guilin, Guangxi, P.R. ChinaVial (glass) 60mg.MA051 Challenges in availability of WHO prequalified essential medicines, such as paediatric formulations, e.g. FDCs for HIV/AIDS and malaria, Artemisinin based FDCs for malaria treatment, Second line treatment for TB, medicines for neglected diseases (e.g. praziquantel for schistosomiasis)

16. 16 Links WHO website http://apps.who.int/prequal/ WHO Prequalification website also provides information in Chinese MoH website: GFATM R9 TB project kick-off meeting on 29 July, 2010. http://www.moh.gov.cn/publicfiles/business/htmlfiles/mohjbyfkzj/s10 768/201007/48285.htm Gates project kick-off meeting on 1 April, 2009. http://www.moh.gov.cn/publicfiles/business/htmlfiles/chenz/pldhd/20 0904/39806.htm

17. 17 Thank you for your attention! Contact: Christina Foerg-Wimmer, PhD Pharmaceutical Advisor WHO China Office Tel: (+86 10) 6532 7189 FoergWimmerC@wpro.who.int