When Zhejiang Pharmaceutical Association organized a conference on Chinese drug approval reforms in Hangzhou, China, participation was strong. About 500 people, mostly from drug firms operating in the province, attended the one-day event in December.
“Our objective is to have a response rate faster than foreign regulatory agencies such as the U.S. FDA,” Jiaxi Xu, director of the Center for Drug Evaluation at the China Food & Drug Administration (CFDA), told attendees. Many of them left the event encouraged that profound changes are afoot.
They may be, but Xu’s statement is in sharp contrast with the current situation, in which CFDA is struggling with such a long backlog of drug approvals that even important new treatments are approved in China years behind other countries.
An overview of ongoing reforms at China’s FDA
◾ Launch a pilot project that allows the holder of a drug patent and its manufacturer to be different entities.
◾ Draft experts to temporarily help agency review drug applications.
◾ Review more quickly new drugs that might be of great benefit to Chinese patients.
◾ Sanction drug firms that provide false data.
Announced, but not yet fully implemented:
◾ Review drug applications as quickly as the U.S. FDA.
◾ Create a dedicated review channel for innovative drugs.
◾ Raise quality standards for generic drugs by requiring bioequivalency testing.
◾ Make drug review and approval process more transparent.
SOURCES: China Food & Drug Administration, other sources
Because drawn-out and complex drug approvals benefit neither Chinese patients nor China’s innovative pharmaceutical firms, the country is reforming its review procedures. The government has announced a series of policy objectives in recent months aimed at speeding up and simplifying approvals.
“Our country’s goal is to raise the ability to create innovative and effective drugs,” said Sang Guowei, president of the influential Chinese Pharmaceutical Association, at the Hangzhou event. China has moved beyond the need to stimulate the growth of its already well developed generic drug industry, he pointed out. “We must develop world-class drug review capabilities,” Sang argued.
CFDA’s effort to make China’s drug industry more innovative has support from the country’s top leaders. China’s highest decision-making body, the State Council, issued a two-page statement in August urging reforms of the approval process for pharmaceuticals and medical devices. The statement decreed that by the end of 2016, CFDA will clear the backlog of drugs awaiting approval, which number more than 20,000 and consist mostly of generics. The State Council also pledged that CFDA will improve the transparency of the drug approval process.
Some of the changes are already apparent to both local and international firms. New drug applications are being reviewed faster, according to George Baeder, a former pharmaceutical industry executive who is now a director of China Global Insight, a California-based think tank.
On the basis of his conversations with executives at both Chinese and foreign companies, Baeder has concluded that the treatments that could most benefit Chinese patients are being reviewed quickly, regardless of whether the applicants are Chinese or foreign.
In January, Baeder notes, China approved two new treatments for HIV: Johnson & Johnson’s Complera and GlaxoSmithKline’s Tivicay. “There is no discrimination against foreign companies,” he says.
Reviews are moving along largely because CFDA has brought to its headquarters in Beijing drug experts from throughout China to help clear the backlog, explains Liming Shao, a Fudan University professor who is director of the School of Pharmacy’s Shanghai Center for Drug Discovery & Development. “Even our school has contributed a few people,” he says.
To prevent a new backlog from forming once the current one is cleared and the mobilized experts return to their regular jobs, CFDA will implement new procedures that clearly separate new drugs from generics, Shao says. At present, the two follow the same procedure because a new drug is broadly defined as “never launched in China,” he says.
In the future, new drugs will be defined as “never been launched in the world.” And generic drugs will have to demonstrate bioequivalency, as is the case in the West.
Quicker review times will stimulate drug discovery and development, Shao predicts. “A slow process increases the cost of innovation,” he notes. Small firms may find themselves struggling to stay afloat while they wait for their drug candidates to be reviewed, he points out. “These changes will reduce the burden on small biotech firms.”
China’s drug discovery firms got another boost in December when CFDA announced the launch of a pilot program under which the manufacturer of a drug and the holder of its patent don’t have to be the same entity. Previously, companies that launched new drugs in China had to also be the manufacturer. “Now, any professor in China can get the approval to make and launch a drug,” Shao says.
Managers of Chinese contract research organizations report that more of their business is now coming from China-based companies. A few years back, Shanghai-based Medicilon worked almost exclusively for foreign drug firms. It now derives nearly half of its business from China, says Chunlin Chen, chief executive officer and founder of the company.
The new Chinese customers rely more heavily on Medicilon than do its foreign ones. “Our Chinese customers don’t have the know-how to implement good research practices,” Chen says. Systematic record keeping is a particular challenge, he points out. As a result, Chinese drug firms come to Medicilon for its ability to conduct research according to international protocols.
For Medicilon, the work is gratifying. “Whereas our Western customers come to us to save money, the customers from China value our know-how,” Chen says.
China still has some way to go before its drug approval system catches up to the West, Chen says. Now, a common practice for his firm’s Chinese customers is to initiate clinical trials in Australia prior to seeking authorization to do so in China. “The Chinese Center for Drug Evaluation actually encourages dual filing in China and abroad,” Chen notes. “They feel more confidence when a drug is also under the approval process in the U.S. or Australia.”
China could eventually develop a drug review and approval process that is faster and superior to those in the West, China Global Insight’s Baeder says. For instance, the system in the U.S. is unwieldy because of entrenched precedents and the legal liabilities that drug firms face when something goes wrong. China, by contrast, is freer to adopt more efficient ways of doing things.
One possibility, Baeder says, is “adaptive” trials, in which a drug’s efficacy is demonstrated by first testing it on a subset of the patient population that is most likely to respond well to it. After initial success, trials are progressively expanded to groups of patients who are measurably less certain to generate positive results or face higher risks of side effects.
Baeder sees the potential for other clinical trial innovations in China. “The massive scale and rising cost of unmet medical needs can be combined with the world’s largest relatively homogenous ethnic population and a high proportion of treatment-naive patients to make the country a particularly attractive location in which to develop large scale alternative approaches to drug development,” he says.
Given that drug approval in China has been bogged down for so long, it’s too early to suggest that the Chinese process will soon leapfrog the West’s. But for the researchers who are advancing the country’s drug discovery capabilities, any smoothing of the path to market will be most welcome.