CHINA PHARMACEUTICAL NEWSLETTER

NEWSSFDA Convenes National Meeting

on Food and Drug Supervision The State Food and Drug Administration (SFDA) held a meeting on food and drug supervision from August 1 to 3, 2010 in Zhejiang Province. There was in-depth

concept of supervision. The priorities in the reform and development of food and drug supervision were studied.

Shao Mingli, Commissioner of the State Food and Drug Administration, summed up what the SFDA had done in the first half of the year and made arrangements and deployed the work for the second half of the year. Deputy Commissioner Wu Zhen made a r r angemen t s fo r E-Supervision of essential drugs for the second half of the year. Deputy Commissioner Bian Zhenj ia made arrangements for the safety of food in the catering service, regulation of health food, cosmetics and medical devices and inspection of drugs for the second half of the year. (August 3, 2010)

W H O D i r e c t o r - G e n e r a l D r Margaret Chan visits NICPBP in the company of Shao Mingli, Commissioner of SFDA In the afternoon of July 27, 2010, Dr Margaret Chan, Director-General of the World Health Organization (WHO) and her entourage vis i ted

the National Institute for the Control of Pharmaceutical and Biological Products (NICPBP) in the company of Shao Mingli, Commissioner of the State Food and Drug Administration (SFDA).

Chan. The relevant people from NICPBP introduced their work about the prevention

cooperation with the WHO and relevant countries.

After the vis i t , Dr. Chan leaves her comments in the visitors’ book, says: “Thanks to you, the NICPBP experts for your contribution to the prevention and control of Influenza A (H1N1). Because of your efforts and those of the central leadership, China made the world's first H1N1 vaccine, which is the pride of China,

and great news for people around the world.” (July 29, 2010)

SFDA Commissioner Shao Mingli meets Vice Governor of Hubei Province Zhang Tong and his Entourage, Talked about Construction of a Demonstration Area of Food and Drug Safety in Wuhan City Area On the 8th July 2010, Shao Mingli , Commissioner of the SFDA, met Zhang Tong, Vice Governor of Hubei Province and his entourage. The

two parties exchanged their views on further promoting the construction of a demonstration area of food and drug safety in the Wuhan City Area. (July 10, 2010)

Bian Zhenjia, Deputy Commissioner of SFDA, meets Pakistani Minister of Health Shahabuddeen and his Entourage In the morning of July 6 , Mr. B ian Zhen j i a , t he Depu ty C o m m i s s i o n e r o f t h e S F D A m e t with Pakis tani Minis ter of Heal th Shahabuddeen and his entourage. The two parties exchanged their views on how to carry out cooperation in the framework of a memorandum of understanding and cooperation. (July 8, 2010)

Compilation of 2015 Version of Chinese Pharmacopoeia Started The organizing of the Tenth Pharmacopoeia Committee and the preparation of the 2015 version of the Chinese Pharmacopoeia started recently. “The symposium on the Chinese Pharmacopoeia and improvement of pharmaceutical standards” was held in Shanghai. At the conference, the National Pharmacopoeia Committee and persons from the relevant units, as well as experts, made suggestions about the formation of the Tenth Pharmacopoeia Commission and outline for the compilation of t he 2015 ve r s i on o f t he Ch inese Pharmacopoeia. (July 17, 2010)

Published byChina Center for Pharmaceutical International Exchange & Servier (Tianjin) Pharmaceutical Co., Ltd.

Volume IV 2010

2 CHINA PHARMACEUTICAL NEWSLETTER

ASFDA Warns of Serious Skin Damage and Other Risks in the Use of Sotretinoin

31A

A(2010 8 11 )

Recently, the National Adverse Drug Reaction Monitoring Center issued the 31st Adverse Drug Reaction Information Bulletin which said that sotretinoin could lead to rare but serious skin lesions. SDFA therefore reminded medical staff, the public and pharmaceutical manufacturers of serious damage and other risks when using sotretinoin. (August 11, 2010)

SFDA Calls attention to Striated Muscle Dissolution Caused by Use of Lamivudine and Telbivudine

SFDA Deploys E-Supervision of Essential Drugs for the Second Half of the Year

30

(2010 7 26 )

8 3

2007 10

2008 11 1

2010

The 30th Adverse Drug Reaction Information Bulletin issued recently by the National Adverse Drug Reaction Monitoring Center said that Lamivudine could cause damage to the musculoskeletal system. The clinical manifestations were similar to those caused by telbivudine. Therefore SDFA reminded patients that the medication must be used in strict accordance with physicians’ guidance

O n A u g u s t 3 , W u Z h e n , D e p u t y C o m m i s s i o n e r o f S D FA , d e p l o y e d E-Supervision of essential drugs for the second half of year.

According to the principle of “step-by-step implementation and steady progress”, national drug E-Supervision is being carried out category by category, batch by batch and step by step. Phase I: A regulatory network for special drugs was basically completed in October 2007, to monitor dynamically the whole process for narcotic drugs and first-class psychotropic substances, from production to distribution to storage. Phase II: Starting from November 1, 2008, E-Supervision of blood products, vaccines, traditional Chinese medicine injections and second-class psychotropic substances

and that they must go to hospital if they feel unwell after taking such drugs. (July 26, 2010)

(collectively called the "four categories"). Those that are not included in the network

code for E-Supervision may not be sold. Phase III: E-Supervision of all varieties of essential drugs be carried out in 2010. Phase IV: Based on the work of the previous three phases, to monitor gradually all drugs on the market electronically.

On June 17, SDFA issued Notice on E-Supervision of All Varieties of Essential Drugs. It specifies clearly that successful bidders for the manufacturing of essential drugs must jo in the e lect ronic drug supervision network by March 31, 2011 and

progress of the work, SFDA has achieved a lot in financial security and personnel

Volume IV 2010 3

4-4-methylmethcathinone listed in the Administration of Psychotropic Drugs

Vice-Chairman of NPC Standing Committee Sang Guowei’s Speech on Drug Innovation in China

4-

2010 8 2

2010 9 1 4-

4-

4-4-

(2010 8 5 )

7 8 10 45

Recently, 4-methylmethcathinone has been abused in some countries. To avoid this spreading to our country and leading to social and public health problems, the State Food and Drug Administration, Ministry of Public Security and Ministry of Health jointly issued a notice on August 2, 2010 saying that starting from September 1, 2010, 4-methylmethcathinone would be listed in

substances and that no unit or individual was allowed to experiment with, produce, process, use, store, transport, import or export 4-methylmethcathinone without

On July 8 ~ 10, the 45th “New & Special Drugs Trade Fair in China” was held at the National Convention Center in Beijing. Sang Guowei, Vice-Chairman of the NPC

approval.

4-methylmethcathinone has not been approved as a drug on the Chinese market. No reports of abuse of 4-methylmethcathinone have been found. (August 5, 2010)

Standing Committee, attended the opening ceremony and delivered a speech on drug innovation in China.Sang Guowei said in his speech that

6 17

2011 3 31

(2010 8 5 )

training. Next, it will strengthen its efforts, urge progress, and focus on training so that regulators and companies will realize that the implementation of E-Supervision can enhance the effectiveness of supervision and the companies’ self-management. Demonstration sites must be constructed. A good job in technical support and services should be done and the E-Supervision system platform and services should be

at work should be answered via multiple channels using a variety of methods.

Wu Zhen said that of the four specific tasks led by the State Food and Drug A d m i n i s t r a t i o n , E - S u p e r v i s i o n o f

essential drugs was the most difficult. It is complicated and time is short. People in the system must work together to forge ahead to complete the objective successfully of monitoring all varieties of essential drugs electronically. The administrations of provinces, autonomous regions and municipalities must be brought into full play. A good job must be done in E-Supervision in the jurisdiction. He hoped that the leaders and staffs in the administration of provinces, autonomous regions and municipalities would work hard at this work. (August 5, 2010)

4 CHINA PHARMACEUTICAL NEWSLETTER

China has made gratifying achievements in some areas in new drug innovation and development. For example, a drug screening system based on target tumors was established; development of the butylphthalide chiral drug (L-butylphthalide) was in the second phase of clinical trials; and trials have been completed with over 5000 subjects of China's first genetically-engineered vaccine, which is the world's first stomach disease vaccine. The results showed that the protection ratio of the vaccine agains t Hel icobacter pylor i infection is greater than 72.1% and it has a good preventive effect on gastritis, gastric ulcers, duodenal ulcers and other upper gastrointestinal diseases. In addition, the world's first Hepatitis E vaccine will be

II of the clinical trials of the world's first vaccine for hepatitis B have ended and the third phase trial is upcoming. Antofloxacin

independently created by Chinese scientists, came on the market in 2009.

Mr. Sang pointed out: “Our expected outcome is to set up a national drug innovation system. Our integrated capacity for new drug research and development is close to international advanced levels. China is becoming powerful in new drug development. Enterprises have become the principal component in technological innovation. The pharmaceutical industry is developing by leaps and bounds - the majority of their products have changed from generic drugs to innovative drugs, making a significant contribution to deepening the health care system, protecting

the health of our people, and promoting the development of our national economy.”

In addition, Sang Guowei divided the construction of China’s pharmaceutical innovation system into three stages in his report. From 2008 to 2010 is the innovative transformation stage, when the national drug innovation system takes its basic shape. From 2011 to 2015 will be the rapid growth phase, when the main technical specifications of drug research and development will be up to international standards, and R & D capacity will increase significantly, narrowing the gap with the developed countries. From 2016 to 2020 will be the stage of making strides in development. Integrated capacity and new drug research and development will be close to international advanced levels.

Sang Guowei further pointed out that new drug innovation and development should foster the features of the strategic emerging industries, highlight the characteristics of independent innovation, focus on increasing the country's core competitiveness, grasp the new trends in international drug development, and strive to enter the international advanced level in a number of areas, so that new drugs are safer, more

In the meantime, Sang Guowei put forward

companies in the new situation of health care reform. Chinese enterprises should "make big pharmaceutical companies

and should establish a technologically c o m p e t i t i v e s t r a t e g y f o r n e w d r u g innovation and development. In this regard, Sang Guowei recommended that they could focus on the following aspects. Firstly, an industrialization strategy, namely developing new preparations of products and re-developing existing long-lasting, immediate-release, and controlled-release preparations and fixed-dose combinations. Secondly, a centralized strategy, creating a substantial union of industry, university and research to extend the research and development of new drugs. Thirdly, a brand and cost-

5000

72.1%

2009

20082010

2011 2015

2016 2020

Volume IV 2010 5

Seven Ministries and Commissions Jointly Issue Centralized

Supervision and Administration of Centralized Drug Purchasing

(2010 7 21 )

Centralized Medical Institution Drug Purchasing Specifications and Supervision and Administration of Centralized Drug Purchasing, which were jointly issued by the

for Rectifying, the National Development and Reform Commission, the Ministry of Supervision, the Ministry of Finance, the State Administration of Industry & Commerce, and the State Food and Drug Administration were formally promulgated and implemented recently. The following principles are clearly laid out in the new regulat ions: led by the government;

is insisted upon; price must be reasonable; the conduct of medical institutions is monitored continuously.

Centralized Medical Institution Drug Purchasing Specifications points out that the centralized medical institutions drug purchasing system which is led by the government and uses province as the unit must be established. The p e o p l e s g o v e r n m e n t o f p r o v i n c e s , autonomous regions and municipalities shall be responsible for the establishing centralized drug purchasing leadership and administration agency which is made up of the relevant departments, and shall set up working organ and centralized, non-profit drug purchasing and trading platform. When medical institutions and pharmaceutical producing and trading enterprises want to purchase or sell drugs, transactions must be made on the centralized non-profit drug purchasing and trading platform established by the provinces, autonomous regions or municipalities. The transactions should be

organized and monitored, and concentrated and conducted on the same platform. The

of the centralized purchasing agencies, medical institutions and pharmaceutical companies concerning malpractices arising in the purchasing and selling of drugs. It also makes some necessary adjustments to the criteria and processes of bidding and purchasing.

Centralized Medical Institution Drug Purchasing Specifications and Supervision and Administration of Centralized Drug purchasing were formulated according to the principles of standardized procedures, transparent operations and restricted powers. Its purpose is to encourage medical institutions to centralize purchasing of

responsibility to ensure implementation; to strengthen supervision to prevent collective corruption; and to clarify objectives to control purchasing prices. In the new regulations, the subjects monitored include all those who participate in drug purchasing. The subjects monitored cover all aspects of purchasing. The method of supervision is real-time network monitoring. Monitoring links are involved in the whole process of the purchasing of drugs. (July 21,2010)

(2010 7 14 )

leading strategy, making great innovations

in the production processes of old products with modern, new technology. Fourthly, a

drugs, research and develop matching drugs, genes and biological markers, etc.

(July 14, 2010)

6 CHINA PHARMACEUTICAL NEWSLETTER

SFDA Issues Announcement on Drug Clinical Trial Agency

SFDA Issues Notice on the Conversion of Prescription Drugs Switch to OTC

7 15

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(2010 7 15 )

6 30

2004 101

www.cdr.gov.cn 1

In accordance with the Drug Administration Law of the People’s Republic of China and Accreditation of Drug Clinical Trial Agency (trial version), after a review of the data and site inspection, SFDA issued Announcementon Accreditation of Drug Clinical Trial Agencies (No.23). The Guangdong Second Provincial Traditional Chinese Medicine Hospital and another 12 medical institutions

they were granted Clinical Trials Agency .

The medical institutions in the announcement

Guangdong Second Provincial Traditional Chinese Medicine Hospital, First Affiliated Hospital of Guangzhou Medical College,

In order to switch prescription drugs to OTCsmoothly, ensure safe and effective use of drugs and promote rational drug use, SFDA, in line with Prescription and OTC Category Administration (trial version), issued a notice on July 30 on the conversion of prescription drugs switch to OTC, as follows:

I . Acco rd ing t o t he p r i nc ip l e s and

administration of prescription drugs and OTC, SFDA organized the selection and announced the list of OTC. Moreover, f o l l o w i n g t h e d r u g m a n u f a c t u r e r ' s application and proposal, it may organize evaluation of the conversion of prescription drugs switch to OTC.

II. Pharmaceutical manufacturers may apply for or propose the conversion of prescription drugs switch to OTC in accordance with Notice on Evaluation of Conversion of Prescriptions Drugs switch to OTC (Guo Shi Yao Jian An No. 101[2004]) and Information

Second Hospital of Hebei Medical University, Affiliated Hospital of Bengbu Medical

College, Guangzhou Psychiatric Hospital, Fujian Provincial Tumor Hospital, Fuzhou Infectious Disease Hospital, First Affiliated Hospital of Anhui Medical University, Jiangxi Medical College Hospital, He’s Eye Hospital of Shenyang, Tianjin An Ding Hospital and Wuxi TCM Hospital. (July 15, 2010)

Prescription Drugs switch to OTC. The relevant materials should be submitted directly to the Center for Drug Reevaluation, SFDA.

III. The Center for Drug Reevaluation of SFDA organizes technology assessment according to the relevant technical principles

passed technical evaluation and are to be converted will be publicized on www.cdr.gov.cn for one month.

IV. According to the views of the technical e v a l u a t i o n o f t h e C e n t e r f o r D r u g Reevaluation of SFDA will review and announce the names of the drugs that will be switched to OTC drugs and the model directions for the OTC.

V. Pharmaceutical manufacturers should s tandardize OTC specif icat ions and labels, and promptly make supplementary applications to the local provincial food

Volume IV 2010 7

2009

TCM Internationalization Follows Six Principles

Adjustment of Some Drug Names and Forms in the NDRL (2009 version)

8 7

(2010 8 12 )

6 28

18AA --2a -2b

(2010 7 10 )

Health and Director General of the State Administration of Traditional Chinese Medicine pointed out, at the “Fifth TCM Deve lopment Forum” on Augus t 7 , that there was a long road ahead before the world accepted TCM and that six principles must be followed. The six principles are as follows: First, “From China to the World”. Before the world can accept TCM, its curative effects and normative standards must be improved in domestic practice; Second, “Chinese Culture First”. Let the world know the culture of TCM so that there is a cultural foundation for TCM in the process of introducing Traditional Chinese Medicine to the world; Third, “From Medicine to

On June 28, the Ministry of Human Resources and Social Security issued a notice adjusting and standardizing some drug names and the fo rms o f some medicines in the National Drug Reimbursement List (NDRL) for Basic Medical, Work-related and Maternity Insurance. The drugs that have been adjusted include the Western medicines: A d e f o v i r D i p i v o x i l , C o m p o u n d

Practice”. Introduce good TCM products to the world and then more people would like to know about TCM diagnosis and treatment methods. Fourth, “From Easy to Difficult”. Let more people know about acupuncture, massage and other non-drug therapies, and then it will be easier for them to accept the complicated diagnosis and treatment methods; Fifth, “From Point to Surface”. Find new ways of international cooperation to bring TCM to the world by example; Sixth, “From Private to Official”. In the progress of TCM “going out”, private enterprises should go first, to lay the foundation for the government to gain access to the legal systems and mechanisms.

(August 12, 2010)

Risperidone, Salmeterol/Fluticasone, B i f i d o b a c t e r i u m , L a c t o b a c i l l u s A c i d o p h i l u s , E n t e r o c o c c u s Tr i p l e Viable Preparations, Iopromide, and the Traditional Chinese Medicines: Feilike

Capsule and Xuhanting Capsule.

(July 10, 2010)

and drug administrations according to Provisions for Drug Registration and relevant regulations and with reference to the model directions for the OTC publicized by SFDA. Approval should be obtained before use.VI. SFDA will further study the management

(2010 6 30 )

pattern of "double cross" type drugs (drugs that are both prescription drugs and OTC). The related work of conversion of the “double cross” type drugs will be carried out

(June 30, 2010)

8 CHINA PHARMACEUTICAL NEWSLETTER

Meeting Brief

8 6

2011 7

31

(2010 8 6 )

S F D A C o n v e n e s S y m p o s i u m o n Revision of the Implementation Plan for Drug Safety Inspection and Assessment

On Augus t 6 , SFDA Drug Sa fe ty Remediation Leadership Group Office held a symposium on revision of the Implementation Plan for Drug Safety Inspect ion and Assessment and an expert seminar. They discussed the implementation plan and relevant tandards of Assessment .

The Implementation Plan for Drug Safety Inspection and Assessment will be used for inspection and evaluation of drug safety remediation in 31 provinces, autonomous regions and municipalities, conduc ted by SFDA and re levan t

authorities after the end of drug safety remediation in July 2011. The purpose is to evaluate the effectiveness of drug safety work, encourage local governments to further strengthen drug safety supervision and to get them to consider drug safety as an important project for livelihood, and, on this basis, to form the drug safety evaluation system. (August 6, 2010)

Ministry of Health Reiterates Severe Punishment for Commercial Bribery in Drug Sales and Procurement, Requiring the Establishment of Record-keeping Systems for Commercial Bribery within the Year

6 30

(2010 7 3 )

On June 30, the Minis t ry of Heal th i s s ued a no t i c e c a l l i ng fo r f u r t he r s t r e n g t h e n i n g t h e m a n a g e m e n t o f c o m m e r c i a l b r i b e r y i n d r u g s a l e s and procurement and for expansion of e ffor t s to inves t iga te cases . The p r o v i n c i a l h e a l t h a d m i n i s t r a t i v e d e p a r t m e n t s m u s t s e t u p r e c o r d -keeping systems for commercial bribery wi thin the year. For the enterpr ises producing or trading pharmaceuticals l is ted in the record-keeping system,

the provincial heal th administrat ive depar tments must f i rmly cancel the

centralized drug purchasing and must not accept their applications for any of their products for participation in centralized purchasing for two years. Medical institutions of local provinces, autonomous regions and municipalities may not purchase their drugs, medical

any name for two years. (July 3, 2010)

ExcipactIPEC GMP

GDP

Special Focus

Authentication System will lead into Excipient Regulation in Europe

Europe i s developing a voluntary certification standard for excipients. The standard will be based on existing GMP and GDP standards, under the guidance of

a recognized third-party.EU leaders seem to have agreed to further strengthen efforts to build a strong

Volume IV 2010 9

certification system for excipients in Europe.

IPEC-Europe is cooperating with EFCG and other trade associations to develop a voluntary certification standard called Excipact. The standard will enable accessory manufacturers and suppliers

products. Certification will be based on current GMP and GDP standards under the guidance of IPEC and will be examined

Europe is expected to approve the relevant Acts combating counterfeit drugs in 2011. As part of the decree, the European Commission may be authorized to release

manufacturers and suppliers to comply with GMP and GDP guidelines.

Increasing attention is being paid to the safety of excipients

In the summer of 2009, the European Commission decided not to include excipients in the new Act, as it believed

that the cost of implement ing the excip ients cer t i f ica t ion s tandards

industry generally expected that the new Act would only focus on the production and distribution of finished and bulk drugs.

Now, however, the members of European Parl iament and the EU Council of Ministers representing the EU member governments have realized the importance of excipients complying with GMP and GDP standards.

Excipact strives to be recognized

At the end of last year, the EU Council of Ministers decided that certain excipients, identified by the principles of risk consideration, should be included in the corresponding decrees cracking down on counterfeit drugs. Therefore, in the words of the draft amendments to the Act, the

excipients are as important as those for bulk drugs. (July 19, 2010)

IPEC-Europe EFCG

Excipact

IPEC GMP GDP

2011

GMP GDP

2009

GMP GDP

Excipact

GMP GDP(2010 7 19 )

FDA cGMPFDA Plans to Revise the cGMP Guidelines:Outsourcing and Raw Materials Become Focus

FDA

FDA Hasselbalch FDA

cGMP

2001 2007

1

W i t h t h e g l o b a l i z a t i o n o f t h e pharmaceutical industry, the contract outsourcing business is developing rap id ly. The U.S . Food and Drug Administration (FDA) is facing serious challenges: more and more products on the U.S. market come from areas outside the United States. At a recent meeting at Xavier University in the United States, Brian Hasselbalch, an FDA official, said that the FDA would revise the cGMP guidelines to further strengthen market supervision.

Brian Hasselbalch cited a series of data showing changes in the U.S. pharmaceutical market. From 2001 to 2007, the number of pharmaceutical production bases outside the U.S. has doubled (see Figure 1). In particular, India and China are exporting more and more pharmaceutical products and bulk drugs to the United States (see Figure 2). Over 80% of bulk drugs in the United States are imported. Most pharmaceutical manufacturing facilities are not in the United States either. The production and

10 CHINA PHARMACEUTICAL NEWSLETTER

2 80%

FDA

FDA cGMP

FDA cGMP

2010 FDA

FDA

cGMP

cGMP

OTC

FDA

cGMP

upstream and downstream supply chains are complicated. The level of market regulation at the origin of the goods is

FDA to monitor, and higher supervising

After listing the problems caused by raw products including heparin, diethylene glycol and melamine, Hasselbalch stressed that FDA would manage cGMP in an up-to-date way.

Brian Hasselbalch listed FDA plans to revise the cGMP guidelines. In the

top priority for FDA in 2010 is to increase its understanding of the supply chain, especially knowledge of the original manufacturers, and follow-up procedures, and strengthen the auditing of the original manufacturers. Moreover, transport containers should be checked one by one in each time. The system whereby contaminated goods are reported to FDA should be implemented strictly. It is taken

The contents of cGMP that will be improved may inc lude some new

o f " m a n a g e m e n t r e s p o n s i b i l i t y " to ensure consistency with cGMP, including supply of resources and

t h e a b i l i t y o f s e l f -inspection and recovery; I n c r e a s i n g r e s p o n s e s to defec ts or problems in exist ing regulations, i n c l u d i n g d e f e c t investigation and follow-up and data evaluat ion of the problems checked;

i n c o n t r o l p r o c e s s e s ; Tra in ing of documents a n d i m p r o v e m e n t o f effectiveness; Conducting tests on ingredients of pure water and drinking water;

Revocation of exemption of expired OTC drugs, etc.

Another issue worth being concerned about i s outsourcing and contract manufacturing. There are different descriptions of the regulatory framework for outsourcing in U.S. Acts concerning food and drugs. However, as problems arising from contract or commissioned manufacturing have increased year by year, t h e n u m b e r o f w a r n i n g letters issued b y t h e F D A has increased signif icantly. B r a i n H a s s e l b a l c h stressed that the main problem o f c o n t r a c t manufacturing w a s t h e d i v i s i o n o f responsibility. Contract manufacturers should be responsible for their produced products t o c o m p l y w i t h c G M P. C o n t r a c t manufacturers employed should bear the specific responsibilities provided by relevant laws, and so should private label distributors. An important part

3000

2500

2000

1500

1000

500

02001 2002 2003 2004 2005 2006 2007

Num

ber o

f Act

ive

Site

Foreign Facilities Foreign Inspection

Fiscal Year

1255

249 211 189 280 285 212 325

1462

1729

1973

2263

2543

2782

1 2001 2007 1

Figure 1: The number of pharmaceutical production bases outside the U.S. hasdoubled from 2001 to 2007

3500

3000

2500

2000

1500

1000

500

02001 2007

China

India

2 2001 2007 4 7

Figure 2: Drugs from China and India increased by 4 times in 2001 and 7 times in 2007

Volume IV 2010 11

Procoralan(R)PROCORALAN® REDUCES RISK OF DEATH AND HOSPITALISATION FOR HEART FAILURE IN CHRONIC HEART FAILURE PATIENTS BY

MORE THAN A QUARTER

The largest-ever morbi-mortality study of treatments for chronic heart failure has shown that adding the specific heart rate lowering agent Procoralan® (ivabradine) to standard therapy significantly reduces the risk of death and hospitalisation for heart failure.1 Results from this new study, SHIFT (Systolic Heart Failure Treatment with the If

Inhibitor Ivabradine Trial), were presented today at the European Society of Cardiology Congress1 in Stockholm and published in The Lancet.2

SHIFT involved over 6,500 patients from 37 countries with moderate to severe heart failure and heart rate above 70 bpm who were followed up for an average of 23 months. The results showed that Procoralan® reduces the primary endpoint, a composite of cardiovascular death or hospitalisation for worsening heart failure, by 18% (p<0.0001). Procoralan® also reduced the likelihood of death from

p=0.014) and the risk of hospitalisation

Special column

Provided by Servier (Tianjin) Pharmaceutical Co., Ltd.

due to worsening heart failure by the same amount (26%, p<0.0001). These benefits were evident in just three months of treatment with Procoralan® and despite the fact that patients were already receiving guideline recommended therapy (beta-blockers, angiotensin converting enzyme (ACE) inhibitors, diuretics or aldosterone

Procoralan®

in these fragile patients.

“Twenty years after Angiostensin Converting Enzyme Inhibitors and ten years after beta-blockers, we now have a new life-saving drug available for our patients”, pointed out SHIFT executive committee co-chairman Professor Michel Komajda, Professor of Cardiology, University Pierre et Marie Curie Paris 6, France.

Chronic heart failure is a common and growing problem affecting 15 million patients in Europe (2% to 3% of the overall population).

Procoralan®

(1)

(European Society ofCardiology Congress) SHIFT

I(f)(1) The

Lancet (2)

SHIFT 37 6,50070 / bpm

23 Procoralan®

18% p<0.0001Procoralan®

26% p=0.014

26% p<0.0001 Procoralan®

3-

Procoralan®

S H I F T M i c h e l

the two parties is that pharmaceutical companies no longer monitor only their own part of the process, they also need to address the followings: Provide the contract manufacturing address, plant,

and services/raw materials; Contract manufacturing drugs and description of their use, including all specifications; Provide regular cGMP audit reports and details of the contract; Be committed to sharing test results of supervision,

in main personnel, the changes of SOP and test methods; Full disclosure of all the errors, deviations, changes, shortages, investigations and adverse events that may affect the drugs.

Brain Hasselbalch said that FDA would continue to follow the development trend that there were more and more outsourced and bought-in raw materials in the pharmaceutical industry. Regulatory organs should pay special attention to the outsourced products and raw materials procured from countries without appropriate GMP supervision. (July 12, 2010)

/ /

cGMP

SOP

FDA

GMP

(2010 7 12 )

12 CHINA PHARMACEUTICAL NEWSLETTER

China Center for Pharmaceutical International Exchange (CCPIE)

Address: Room 1106, 11th Floor, Office Building B, Maples International Center, No. 32, Xizhimen North Street, Haidian District, Beijing, 100082, P.R.C.

32 B 11 1106100082

Tel: 010-8221 2866 ext.6006Fax: 010-8221 2857Email: zr@ccpie.orgWebsite: www.ccpie.org

Servier (Tianjin) Pharmaceutical Co., Ltd.

Address: Unit 2001, 20 Floor, Tower 2, Prosper Center, No. 5 Guanghua Road, Chaoyang District, Beijing, 100020, P.R.C.

5 2 20 2001100020

Tel: 010-6561 0341Fax: 010-6561 0348E-mail: julie.zhang@cn.netgrs.comWebsite: www.servier.com.cn

Notes: All Chinese information in Newsletter extracted from Newspapers and Internet.Newsletter

Procoralan® is an innovative treatment that is currently used in angina patients as it relieves symptoms, myocardial ischemia and reduces the risk of coronary events. The SHIFT study has now also demonstrated the

® in chronic heart failure patients.

The SHIFT study is also the first study to ®,

isolated heart rate reduction reduces the risk of death or hospitalisation for heart failure.

key role in the progression of disease.

SHIFT Trial Design

SHIFT is a randomised, double-blind study that compares Procoralan® with placebo on outcomes in patients with moderate to severe chronic heart failure (most commonly caused by ischaemia), poor left-ventricular ejection function and heart rate above 70 bpm. The study was designed to

Komajda20 - 10

Michel Komajda UniversityPierre et Marie Curie Paris 6

15002% 3%

Procoralan®

SHIFTProcoralan®

SHIFT Procoralan®

SHIFTSHIFT Procoralan®

70 /

I(f)

SHIFT (Servier)SHIFT

SHIFT

Procoralan®*

I(f)

Procoralan® Coralan®

Coraxan® Corlentor®

assess whether the If inhibitor can improve cardiovascular outcomes and symptoms

therapy in patients with CHF and systolic dysfunction.

SHIFT was funded by Servier, France’s leading independent pharmaceut ical company with a long history of successful drug development for cardiovascular diseases, and coordinated by the SHIFT executive committee, an international group of heart failure experts.

Procoralan®* was developed by Servier and is indicated for the treatment of angina. It is the first agent of a new therapeutic

inhibitors.*Depending on the country, ivabradine is available as Procoralan®, Coralan®,Coraxan®, or Corlentor®

Source: PR NEwsWire Asia STOCKHOLM, Sweden,

August 29th 2010

References

1. 29th August 2010, Hotline 1, European Society of Cardiology Congress, Stockholm

Treatment with the If Inhibitor Ivabradine Trial (SHIFT). Lancet. Online 29th August 2010

1. 29th August 2010, Hotline 1, European Society of Cardiology Congress, Stockholm2. Swedberg K, et al. Bene cial effects of ivabradine on outcomes in chronic heart failure. The Systolic

Heart Failure Treatment with the I(f) Inhibitor Ivabradine Trial (SHIFT). Lancet. Online 29th August2010