China Pharma Innovation Hinges On Participation Of Medical Experts – SFDA Drug Registration Director

China approves less than 10 new chemical entities annually, according to SFDA Director of Drug Registration Wei Zhang, who has urged healthcare professionals to join China’s innovation efforts.

BEIJING – Pharmaceutical innovation not only rests on the shoulders of pharmaceutical companies and researchers, it also involves medical facilities and healthcare professionals, according to China State FDA Director of Drug Registration Wei Zhang.

“I think, to further innovation in pharmaceuticals, more hospitals and medical experts should get involved in new drug research and development.” Zhang told participants at China Health Forum’s panel on chronic disease prevention and treatment Aug. 18.

To that end, the regulatory agency has enhanced capacity in good clinical practice certification and improved regulations on Phase I clinical trials and ethical committee guidelines (Also see "China Issues New Guidelines On Phase I Trials – Will It Speed Up Approvals?" - Scrip, 5 Jan, 2012.).

SFDA has cleared 333 facilities around the country to conduct clinical trials. These sites are located mainly in Beijing, Shanghai and Guangzhou, and Jiangsu and Zhejiang provinces. Overall, researchers in China conduct 1,000 to 1,500 clinical trials each year. In the past five years, a total of 6,000 trials were conducted in China, Zhang noted.

These facilities have obtained a good clinical practices certification, covering roughly 2,400 categories of clinical studies, and some of the facilities received certifications from the European Medicines Agency and U.S. FDA.

Equally notable, SFDA established a professional GCP inspection team to oversee the facilities. The agency previously relied solely on third-party experts to conduct GCP inspections, but now it employs a team of 208 fulltime inspectors.

With international training, these inspectors are expected to carry out inspections outside China as well as domestic facilities, Zhang said. The agency already conducts good manufacturing practices inspections overseas – seven inspections in seven countries since 2011.

New R&D Focus On Prevalent Diseases

In its 12th Five-Year Plan, China set goals for supporting pharmaceutical innovation, upgrading infrastructure, reducing low-grade products and curtailing growth in medical expenditures.

The ratio of new drugs to generics has increased, reflected in new drug applications and registration approvals, Zhang said. New drugs now account for 37% of all approval applications in China, and new drug approvals increased from 115 in 2010 to 124 in 2011 (Also see "China Drug Approvals Up 26%, Mostly Due To Generics" - Scrip, 19 Oct, 2011.).

However, China has a broader definition for a new drug than in Western markets, Zhang acknowledged. In China, a product that has not been launched domestically is considered new, which differs from the Western definition of a new chemical entity. In terms of NCEs, China approves less than 10 per year, significantly lower than a rough estimate of 30 in the U.S., Zhang said.

The situation has not been helped by China’s restrictions on multi-regional clinical trials (MRCTs). In particular, SFDA allows imported drugs to participate in MRCTs in China only if they have reached Phase II elsewhere. The rule, which is meant to protect clinical trial participants, has resulted in a limited number of MRCTs in China, Zhang noted.

Nevertheless, Zhang said the government still encourages development of new drugs with high clinical value that target common and prevalent diseases in China, including hypertension, hyperlipidemia, liver disease, diabetes, cancer and chronic lung diseases.

According to SFDA data, 305 million people in China are overweight, 120 million suffer from obesity, 236 million have high blood pressure, 96.8 million are diabetic and 32.9 million have hyperlipidemia.

“We hope more researchers and enterprises, especially Chinese domestic firms, will develop new drugs centered on these high-prevailing conditions in China,” Zhang said.

At least one domestic company has heeded the call. Zhejiang’s Beta Pharma Inc. recently launched Conmana (icotinib), a reformulation of EGFR inhibitors Iressa (geftinib) from AstraZeneca PLC and Tarceva (erlotinib) from Roche. The non-small cell lung cancer treatment gained fast-track approval as a national-level innovative drug (Also see "Meet China’s New Innovators: Beta Pharma Redefines Innovation With “Me-Too, Me-Better” Strategy" - Scrip, 3 Aug, 2012.).

Like Iressa and Tarceva, Conmana is not yet listed on China’s National Drug Reimbursement List (NDRL), meaning most patients must pay out-of-pocket. But icotinib is priced 30-40% lower than its imported competitors, according to Beta Pharma VP Fenglai Tan, who spoke during a press briefing July 24.

In China, getting SFDA approval is just the beginning of a lengthy market-access process. According to a recent study from IMS Health, a market research firm, China lags the U.S. by up to 11 years for a new drug to obtain reimbursement coverage (Also see "Lost In Reimbursement? Innovative Drugs Encounter Lengthy Delays In China – IMS Study" - Scrip, 13 Aug, 2012.).

The Clinical And Social Value Of New Drugs

Zhang highlighted several new drug approvals, both imported and domestically developed, to illustrate the clinical and social value of pharmaceuticals. In terms of clinical value, first-in-class drugs by definition offer a new treatment option and meet unmet medical need, he said.

Zhang cited the importance of the launch of Esbriet (pirfenidone), a treatment for idiopathic pulmonary fibrosis in adults, a progressive and fatal lung disease designated as an orphan disease in the U.S. In September 2011, pirfenidone became the first approved treatment for IPF in China, which affects an estimated 182,000-550,000 patients. In China, pirfenidone is manufactured and marketed by Shanghai Genomics Inc., the wholly owned subsidiary of Tokyo-based GNI Ltd. The drug is also approved in Japan, where it is marketed by Shionogi & Co. Ltd., and in Europe, where it is marketed by InterMune Inc. (Also see "China Could Be Third Entry For Idiopathic Pulmonary Fibrosis Drug Pirfenidone" - Scrip, 8 Jan, 2010.).

Domestic manufacturers that develop new drugs – at least new in the sense of China – also bring social value, Zhang noted. Such is the case of hepatitis B treatment entecavir. Although approved in China in 2005, the original drug, Bristol-Myers Squibb Co.’s Baraclude, wasn’t added to the NDRL until 2009, as its patent was expiring and domestic generics were about to enter the market (Also see "As China Shakes Up The Global Market, Big Pharma Needs A New Approach To Compete (Part 2 of 2)" - Scrip, 13 Dec, 2011.). The low cost of generic entecavir reduces annual treatment expenses from up to RMB 30,000 for the original drug to RMB 10,000 for generics, Zhang said. The price differential is particularly important given that China has the world’s largest population of hepatitis B patients.

Meanwhile, SFDA is also looking to expedite development of treatments for rare diseases. The agency is considering whether to implement regulations similar to U.S. orphan drug policies to encourage R&D for rare diseases. However, Zhang noted the process is complicated by the need to coordinate policies among various government departments that oversee taxation, pricing, central bidding and procurement.

China’s complex regulatory system falls under the purview of different ministries, often with conflicting priorities, and has been cited as a major obstacle to pharmaceutical innovation in China (Also see "China’s Drive For Innovation Stymied By “Nightmare” Pharma Policies" - Scrip, 23 Mar, 2012.).

[Editor’s note: Want to know more about how China is changing the global pharma industry? Don’t miss the PharmAsia Summit Shanghai Sept. 24-26. Click here for details.]