Application of Pharmacovigilance in post- marketing traditional Chinese medicine Hua-Wen Xin Wuhan General Hospital, Wuhan, China

Pharmacovigilance The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems

Aims of Pharmacovigilance To improve patient care and safety To improve public health and safety To contribute to the assessment of benefit, harm, effectiveness and risk of medicines To promote education and clinical training To promote effective communication to the public To promote rational and safe use of medicines

Its concerns including: herbals traditional and complementary medicine blood products biologicals medical devices vaccines

Traditional Chinese Medicine (TCM) >9000 kinds of TCM preparations have been approved to be sold approval numbers have been granted. Side effects and desired effects

Three groups raw herbal medicine(Zhong yao cai), sliced herbal medicine(zhong yao yin pian), patent medicine(zhong cheng yao)

Industrial output value of TCM during

ADR caused by TCM ADRs related to TCM were reported frequently in China 152,320 and 663 kinds of TCM were detected with ADR in the year 2001,2002,2003. The ADR due to TCM injections accounted for 77.2% of all ADR caused by TCM.

The causes of ADRs by TCM Variability in active/toxic ingredients Use of inherent toxic herbs Overdose of herbs drug-herb interactions Coexisting diseases Idiosyncratic reactions

Manufacturing and quality problems: Adulteration Misidentification Substitution of one herb with another Variability in the amount of active ingredients Improper processing and preparation contamination The causes of ADRs by TCM

546 kinds of Chinese patent medicine were recorded in the Chinese Pharmacopoeia issued in But 235 kinds did not describe the items related to pharmacovigilance.

Number ADRContraindicationsPrecaution Missing number % % % Capsule tablet Injection Granules Mixture Powder Pill Missing items about pharmacovigilance in 92 label instruction of TCM

Efforts in PV about TCM SFDA has improved its regulations on herbal medicine to implement quality control systems GAP GLP GMP

ADR monitoring in China Three stages Primal construction experimentation development

“Information bulletin for ADR monitoring” Hepatic lesion caused by Zhuanggu Guanjie pill Renal damage by Longdan Xiegan pill Serious ADR (allergic reaction and so on) by Qingkailin injection,Shuanghuanglian injection,Shenmai injection, Yuxingcao injection, Lianbizhi injection

To ensure the safety and efficacy of TCM injection, in 2000, the state launched the “Improvement of Quality Standards of TCM Injections with the Production Permission and Work on Fingerprints Chromatogram” and issued the Technological Requirements of Fingerprint Chromatogram Research of TCM Injection.

Working hard to improve the safety and quality control Fix the production areas of crude drugs of TCM injection Strictly control the quality of raw materials,intermediate production Realize overall quality control for production and processing

Aristolochic acid causes serious renal damage SFDA cancelled the pharmaceutical standards of some medicinal materials containing aristolochic acid. All TCM preparations which contain Fructus Aristolochiae,…….would be managed strictly as prescribed drugs. SFDA suspended accepting the application of these TCM preparations for variety protection, generic drug and new drug registration.

SFDA suspended using and approving Yuxingcao injection on 1 June 2006.

In May 2007,the national ADR monitoring centre informed timely some correlative manufactures of the serious adverse reactions caused by Xiangdan injection and urged them to strengthen the research on the ADR.

The drug administration departments have revised the directions for puerarin, potassium de-hydroandrograpolide succinate( 穿琥宁 ) and andrographolide sodium bisulfite （穿心莲） injections. Abolished the pharmaceutical standard for manchurian aristolochia stem. Revoked the manufacturing permission for bimolane

In order to supervise the quality of TCM, the drug monitoring authority implements the market spot checks. It is beneficial to punish the manufacturer and seller of quack and inferior drugs. Cohort study is suggested to do in future so that a further relationship between TCM and ADR can be obtained.

Conclusions The establishment of risk assessment Early-warning mechanism The interaction of TCM and chemicals The international exchange of safety information

References Wang HN, et al. China Journal of Chinese Materia Medica,2008,33: Cheng F, et al. China Journal of Chinese Materia Medica,2009,34: Wang H, et al. Pharmacoepidemiology and drug safety,2009,18: