Pharma firms deal with clinical trial complexity

The China Food and Drug Administration (CFDA)'s draft Guidance on Multi-Regional Clinical Trials (MRCTs) raises the requirements for MRCTs, spurring concern at foreign pharmaceutical companies over potential problems with the launch of new products as well as a lack of procedural guidance.

Issued on November 21 2014, the draft encourages drug makers to use MRCTs to develop products for medical needs that haven't been met yet, and for serious life-threatening diseases. It also suggests conducting additional clinical trials in China or tailoring regional studies for local patients, which creates another step for companies seeking market authorisation.

Multinational companies (MNCs) may now also have to go through an additional filing of MCRT data before getting final new drug approval.

“The changes could further delay product entry for two to three years,” said Chen Yang, who leads the PRC life sciences practice at Sidley Austin. "It seems that the CFDA may want MNCs to reapply with the regular drug import procedure, which would be repetitive in terms of practice.” Some MNCs have pending applications that have been put on hold for over a year purely for procedural reasons.

Technical issues, such as how an MRCT proceeds to a new drug application, need to be addressed. An MRCT is a single clinical trial conducted simultaneously in multiple regions under a common protocol. This is an increasingly popular way for multinational pharmaceutical companies to carry out development.

A number of MNCs have been arguing against the proposed changes since 2013, as over the past 10 years they have been allowed to use data from multi-centre trials to support registration in China. Doing so provided the Chinese population access to innovative drugs much sooner than through regular import drug registration. It is understood that local pharmaceutical companies have complained to the CFDA that this created a shortcut for MNCs. Manufacturers could earlier only apply for MRCTs after receiving approval overseas. Now MNCs may need to use Chinese patients and the related dataset for local approval.

“The guidance clarifies under what circumstances companies can use MRCT data sets, which is important because there have been no substantive criteria before,” said Katherine Wang of Ropes & Gray. “These include how they should analyse multi-centre data, present safety and efficacy in Chinese patients and whether trials have been consistent and monitored from all sides.”

The waiting period for the clearance of a local clinical study can range from 10 to 18 months, and once the company runs the study, it has to apply for product registration and wait for approval, which can take another 12 to 30 months.

The industry has been lobbying for a solution. While the draft guidance provides a starting point for the CFDA in regulating MRCTs in China, it falls short of resolving procedural issues. Practitioners raised another concern: the CFDA is under-resourced and may not have the capacity to handle the increased administration and supervision that comes with the change.

“Companies with pending applications for innovative drug MRCTs don't know what they have to do, so they are just waiting,” said one lawyer who did not want to be named. “They are actively working with the CFDA to find a solution but are not aware of one just yet. Nobody knows what the answer to the riddle is."

Despite its silence on procedural requirements, the draft offers technical guidance for companies on how to structure clinical studies, said Yang. It is open to public comment until December 21 2014.


By Katherine Jo