Conducting clinical trials in China
pharmafile | October 26, 2010 | Feature | Research and Development |Â Â China, Jim Wei, Medpace, clinical trials, clinical trials in Chaia, regulatory affairsÂ
As industry pressure to conduct successful global clinical trials on time and on budget continue, tapping emerging global markets will be crucial to deliver sustained growth to the pharmaceutical industry.
Conducting studies in China can generate a real benefit by allowing pharmaceutical companies to access a mix of sites domestically and internationally, and leverage efficiencies by running trials simultaneously in multiple countries – while enjoying patient enrollment for faster development using emerging markets. In China, where clinical development is rapidly growing but challenges remain, best practice would dictate choosing development partners with deep expertise in local regulatory requirements and solid experience navigating the local Chinese waters. In a recent presentation, Jim Wei, the director of clinical pharmacology at Medpace gave insight into issues surrounding the conduct of clinical trials in China. Careful planning with these issues in mind is necessary to avoid regulatory delays in study start-up.
Different structure for review – FDA and the China State Food and Drug Administration (SFDA)
In the US FDA, we know that the drug submissions and Investigational New Drug (IND) new drug approval (NDA) are related to the particular division. Administrative review is conducted in the division office level at FDA and the technical review is finished by clinical division. And also, the initial filing review is completed by a review team within the division. However, within the China SFDA, the structure is very different with the approval process driven by different divisions.
Administrative review is handled by the Center for Drug Filing which is a different centre under SFDA. The technical review is finished by the Center for Drug Evaluation (the equivalent to CDER at FDA).
The final approval is handled by a third centre called the Center for Registration. There can be administrative time overlap between the centres causing inefficiencies compared to the US.
ICH and FDA guidance
The regulatory perspective of the SFDA has significantly improved in the last five years with the adoption of more ICH and FDA guidance. Previously, the SFDA modified and combined their standards, developing China SFDA guidance. Now, global trials are forcing the China SFDA to adopt more ICH guidance.
New acceptance of pre-IND meetings and consultations
A new openness exists between the sponsor and the SFDA to ask questions, and discuss strategies. Historically the SFDA was a private body – limiting public discussion. Now they are involved in international conferences such as the DIA meetings, AAPS, and many regional workshops. They are building in-house expert review teams such as the statistician review team in 2009, resulting in shortened regulatory timelines. They are also implementing good review practice according to US FDA standards. They now have a more science-based approach to handle the review applications. Sponsors have more training workshops inside China to promote ICH, GMP, GLP, and GCP guidelines respecting therapeutic guidelines.
Contrasting regulatory focus
A different perspective exists between the China SFDA and the US FDA. China’s focus has been on generics and manufacturing versus new drug applications which is the opposite of the US FDA’s major focus on new drug applications. China SFDA is used to focusing on the import of drug and the domestic development in very small scope; and the US FDA is handling all of the IND/NDAs. China’s SFDA is relying on existing data. The US FDA is focused on the new data collected from the new clinical trials.
Plan for differences in review timelines
For the centre to file, it takes 30 days. But 30 days is not the US FDA 30 days where no news good news. China’s 30 days is 30 business days. That means one and a half months for the filing plus for review, 90 business days – and then finally for the trial registration, it takes another 30 days. The total time for the review of a protocol takes seven and a half months, the shortest time without requesting additional information. However, if there is additional data or information requested in general, in reality, it takes about nine to twelve months to receive approval for the clinical trial protocol.
New spirit of regulatory collaboration
There has been recent collaboration between the China SFDA/CDE and the US FDAAA (FDA Alumni Association) members, having invited colleagues to train their staff. In June 2009, SFDA invited FDA Alumni Association to conduct a science-based review process in training workshop. Three former FDA office directors gave a one-day workshop. SFDA/CDE required all review staff to attend. In May 2010, the SFDA and FDAAA held the second workshop in Beijing again. Such activities significantly boost the China SFDA’s capacity and awareness for the global regulatory environment, exhibiting their efforts to take more steps to train their staff and adopt more ICH and US FDA guidance.
Access to government certified investigator sites for favourable recruitment
In the US, the sponsor can choose individual investigator sites. In China, sites are in hospitals and must be GCP certified by the SFDA. So far, they have 430 hospitals certified GCP clinical trial sites. Twenty centres actually focus on oncology drug development and there are 115 phase I units. Most of the sites are very small, eight to 24 beds. But now, as of last year, there are two phase I units. The bed size increased to 72 beds per unit. With over 30,000 clinical investigators in China across the country, now the government invests in what is called the drug development platforms across the regions. In every major city, there are clinical development platforms which are organised clinical centres, investigators, ethical committees. All are ready to take global trials.
Favourable FDA inspections
The US FDA conducted eight clinical site inspections. It came out with a very similar finding to the US, no significant error or misconduct with only minor findings. Therefore, the clinical sites in China are capable of conducting GCP standard and reinforcing them by the US FDA or EMEA.
Dr Jim Wei is the director of clinical pharmacology at Medpace.
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