SHANGHAI – The verdict is in. The regulatory reforms that China kicked off in 2015 have opened the floodgates to an unprecedented number of early phase clinical trials being conducted in China.

This year to date, 838 clinical trials are underway in China, according to data presented by Jason Zhu, CEO for contract research organization PPC, at the ChinaTrials 11 event. Back in 2015, when the State Council gave the CFDA (now the National Medicinal Products Administration, or NMPA) permission to conduct wholesale reforms of the regulatory system, there were only 338 trials ongoing.

In the five years before the reforms, from 2009 to 2015, the number of trials inched up by a third. But compared to the two years following the reforms, the number of trials has more than doubled.

It follows that the vast majority of those new studies are early stage trials. In 10 years, the number has gone from 134 phase I studies to more than 400.

Not so long ago, multinational corporations (MNCs) dominated the IND clinical trial category. In 2009, the top three were Novartis AG, Bayer AG and Pfizer Inc. The first local pioneers to enter the top 10 were Hutchison Medipharma, a subsidiary of Hutchison China Meditech Ltd., and Jiangsu Hansoh Pharmaceutical Co. Ltd. in 2014.

But today, the list of top 10 clinical trials sponsors is led by local firms. Jiangsu Hengrui Medicine Co. Ltd. is the most dominant, with more than 40 trials ongoing.

In second place, Novartis lags far behind with fewer than 20 trials. Going down the list, companies from spots three to seven are largely tied: Beigene Ltd., Chia Tai Tianqing Pharmaceuticals Holdings Co. Ltd., Lee's Pharmaceuticals Ltd. and Sichuan Kelun Pharmaceutical Co. Ltd., with more than 15 trials each.

Rounding out the bottom of the list are Astrazeneca plc, Roche Holding, Qilu Pharmaceutical Co. Ltd. and Luye Pharma Group.

The increasing number of trials, and shift from foreign to domestic sponsors, illustrates the dramatic changes that the regulatory reforms have wrought.

Some of the more significant changes Zhu outlined are as follows:

• Improved quality, after instituting clinical trial data self-assessments and on-site inspections

• Faster timelines due to streamlined review and approval procedures such as a pre-IND meeting with the Center for Drug Evaluation (CDE), a 60-day notification-based CTA review, an expedited pathway for unmet medical needs and rare disease and conditional approvals

• More clinical trial sites, after permitting hospitals to do an online filing with the NMPA (and removing the CCP accreditation step)

• Global integration following International Council of Harmonization (ICH) membership and acceptance of overseas data

And the changes keep on coming. Nearly every Friday, the NMPA announces changes to the regulations, leaving regulatory affairs experts to pore over the details each weekend.

During a panel, local Chinese executives working for MNCs lamented how difficult but necessary it is to provide context to headquarters about the weekly regulatory announcements. Difficulties arise when those at HQ rely on Google translate to keep up to speed. But translations fail to capture the gray areas the authorities intentionally leave open to interpretation – so that they can test different ways to actually execute changes on the ground.

Hurdles still remain

While many of the changes are welcomed by the industry, other issues have cropped up as well.

Attendees recounted that they struggle to find talent that can manage early stage clinical trials. Mabspace Biosciences Co. Ltd.'s CEO, Xueming Qian, said salaries for chief medical officers working in China can be 30 percent to 40 percent higher than similar counterparts in the U.S.

"You have to entice the experienced people to bring their careers and families to China," said Qian.

Fangning Zhang, a McKinsey consultant, reiterated that "the talent war is top of mind for everyone. The biggest pain is retention." But she said not enough attention is being paid to tackle that problem.

The result is salaries that are spiraling ever upward. Where once the benefit to doing clinical development in China was lower costs, higher salaries are eroding that advantage.

Timelines are another area where further improvement is needed. While the time it takes to initiate clinic trials has been whittled down to seven months (vs. 12 months-plus in the past), China still takes far longer than other markets such as Australia.

For the 60-day notification process to be successful, sponsors find it is crucial to have a pre-IND meeting first to communicate with the authorities. One panelist shared that asking for a face-to-face meeting can take a very long time, but written responses have been quick.

"You cannot rely on rounds of comments from the NMPA," said Jason Yang, chief medical officer and senior vice president of clinical development at Cstone Pharmaceuticals Co. Ltd. "You need to have an executable protocol for pre-IND. Few companies have the talent capable of doing that. A lot of companies will be washed out. Many will not be competitive in this process, which might be the intention of regulators."

Other pain points continue to beleaguer the industry. Many experts view the two-stage requirement to obtain approval from a hospital ethics committee and the NMPA as a cumbersome process. Few hospitals are equipped to have an independent ethics review of a clinical trial and sorely lack capacity. That can lead hospital ethic committees to drag their feet until more experienced government reviewers weigh in.

"An [ethics committee, or EC] will issue approval after the NMPA says they have no comments or wait until all comments have been received. If the EC issues approval but the drug authorities do not, they feel awkward," shared Limin Wen, head of clinical development at Fosun Kite Biotechnology Co. Ltd.

Helen Jiang, vice president and chief medical officer at Qingfeng Medicine, added, "I hope the NMPA will be more aggressive and we can do the EC and NMPA review in parallel like other countries."

Lastly, China's strict rules governing the collection and usage of human genetic resources remains a thorny problem, especially for MNCs. One audience member asked how China continues to have those regulations, unlike other countries, even though they are a signatory to the global rules such as the ICH. The response was swift from the moderator: ICH admittance does not preclude following existing domestic laws.