Editor's note -- BioWorld™, the daily biopharma newsletter from ThomsonReuters, attended the ChinaBio® Partnering Forum, held in Suzhou earlier this month, and produced a series of articles based on panel discussions and interviews with participants. The articles detail the insider’s sense of rapid development in China’s biopharma sector – every year seems different from the one before. The articles will be reprinted in ChinaBio® Today over the next few weeks with the gracious consent of BioWorld (www.bioworld.com).

The current article discusses China’s Center for Drug Evaluation, a part of the CFDA, and how drug developers should approach the agency to get the best results (see original Bioworld article).

The previous article focused on innovation, using as examples the China biopharmas Ruiyi, Shenogen Pharma, Suzhou Alphamab Co. and Mabspace Biosciences (see article).

Strategies for Dealing with the CFDA

Navigating the obstacle course of China's regulatory system requires strategic thinking, long-term planning and creative problem solving – and deep pockets don’t hurt, according to the experts discussing cross-border approvals at the ChinaBio Partnering Forum held in Suzhou earlier this month.

When trying to get a novel drug approved, it is important to understand that Chinese regulations are based on a legacy of manufacturing and generics, said Ling Su, life sciences regulatory expert at Sidley Austin LLP in Beijing.

That explains the importance of determining whether to seek approval for a domestic drug, which means setting up costly biologic manufacturing in China, or to shoot for an imported drug license (IDL), which has its own pros and cons, namely fewer risks but longer time frames.

An obvious hurdle is the bottleneck at the understaffed CFDA's Center for Drug Evaluation (CDE), ill-equipped to handle the challenge of approving complex innovative drugs. "The resources and expertise within the agency are quite limited," Ling said.

That's not to say the CFDA is not evolving rapidly. "We are seeing a good trend of improvement with small-molecule drugs. We were able to get an approval very fast, within eight months," said Jimmy Wei, venture partner at KCPB China. "The big challenge is for biologics, vaccines, antibodies – these can take more than two years to get approved."

Consider that reviewers have personal responsibility for their professional decisions, with potentially heavy consequences if things go wrong. In China, the responsibility for the efficacy and safety of the drug rests on the regulators' shoulders. As a result, at every step of the way, there is a need to get permission and approvals. "No other agency in the world is doing this," said Hua Mu, senior vice president of operations at Wuxi Apptec Co. Ltd., of Shanghai.

While it might seem that merely adding more reviewers would solve a lot of problems, Ling said, "If we get 600 more reviewers, then you create 600 times more problems. Where do you find the qualified people with the training and experience?"

Later this year, it is expected that the CFDA will come out with a draft Drug Administration law, that if passed by the State Council and the National People's Congress could go into effect by 2016.

Ling pointed out that the chance to reform has come around only twice before in the last 30 years. "We may not be around for the next revision so this is our opportunity to facilitate reform," Ling added.


Not Waiting for the Government

The panel agreed that the issue of meeting China's substantial unmet medical needs is a shared responsibility requiring the combined effort of regulators, society and industry. But industry can't afford to wait for government to change.

As CEO of a small biotech, Dajun Yang, of Ascentage Pharma Group Co. Ltd., of Shanghai, said he finds it is important to define a strategy from the outset. "Every year we file two INDs [investigational new drug applications] with the CDE; the CDE might be 12 or 15 months, but you put yourself in a position to de-risk with multiple shots at a target."

During the long wait to get IND approval in China, some look outside to Australia and increasingly to Taiwan to initiate phase I trials, getting a start on in-human data. With a recent cross-strait agreement, Taiwan has become an increasingly attractive option.

With phase I data in hand, time lost has the possibility of being made up during the new drug application phase. "Look at the whole process and whole value chain on your portfolio, not just the CDE IND process," Yang advised.

Taking that idea a substantial step further, KPCB's Wei announced that his firm is in the process of building two state-of-the-art identical biologic manufacturing facilities in Germany, with one shipping to Taiwan and the other to China, with "the same process, same supplier and same equipment to reduce the risk of a bridging study."

That innovative approach garnered appreciative murmurs from the audience with Mu also alluding to a similar plan in the works at his company.

The longer-term bet is that government eventually will allow biotechs to take advantage of high-quality contract manufacturing organization (CMO) facilities to safely manufacture for clinical trials. Using a reliable CMO "will save a lot of money and reduce the price for biologics product, which right now are very expensive in China," Wei said.

Nothing Reassures Like Quality

A sentiment echoed by many but perhaps said best by Peng Wang, president of R&D at Yaobao Pharmaceutical Group Co. Ltd., of Beijing, is that "It comes down to the quality; if the science is really good, it is my impression the [approval] time will be shorter."

China can deliver international standard data, assured Mu, citing his past experience with Hutchinson Medipharma, where during licensing deals with big pharma the firm's data were heavily vetted and returned with high marks.

"I don't believe there is a so-called China standard," Ascentage’s Yang said. "Maybe there are some different practices in terms of quality of product [and] standard operating procedures to run the trials, but everything we do must follow a international standard."

Nevertheless, he admits quality programs are still elusive for many traditional pharma companies, though they know they need such programs to survive, opening the doors ever wider to cross-border opportunities. "Historically speaking, there is a great window of opportunity for co-development," Yang said.

In the last seven years, Wei observed he has seen a jump in co-development deals. Within the KPCB portfolio alone, he said, there have been at least a dozen deals, leveraging innovation that was generated in the U.S. or Europe to bring to China.

In his experience, with the right science and the right indication, he found "from the day we signed the license to the day we launched the product it took two years. Actually, that never happened before, to my understanding. I foresee there will be more and more deals like this."

While hopes were expressed that the Chinese government will change the regulatory process, Yang observed, "Overall, I do not have too much hope that the regulatory process will become more predictable or transparent. We can only do our best from the scientific aspect and provide quality product."

Disclosure: none.