China’s meteoric growth over the past twenty years (or so) has seen it go from strength to strength, particularly in the clinical trials sector. As the clinical trial market of the world’s most populous nation (and second largest economy) continues to mature, so does their regulatory requirements. These regulatory adjustments pose a risk to sponsors if their CROs are not agile enough to react appropriately and in a timely fashion. Indeed, the broader Asia-Pacific region has experienced similar growth in their respective clinical trials sectors. Equally, the ability to navigate this burgeoning regulatory environment, requires a CRO partner who not only has an intimate knowledge of the country and the region, but has on-the-ground experience developing and managing some of the largest clinical trials ever conducted, in the region.
The last 12 months has seen significant changes to the regulatory landscape in China, as the CFDA (Chinese Food and Drug Administration) began to reduce the significant administrative backlog of pending applications in the approval system. Early 2015, for example, saw the number of applications waiting for review reach over 2,000! This backlog had a knock-on effect to the already overburdened and under-resourced National System. CTA (Clinical Trial Authorization) approval time had stretched to anything from 12 to 24 months. This led the National State Assembly to make regulatory reform a national priority. For this move, they should be congratulated.
On 22nd July 2015, the CFDA released a list containing 1622 applications which required to be sponsor self-checked for quality of the clinical trial data. (948 of 1622 cases were new drug registration, 503 cases were generic registration, 171 were imported drug registration). Penalties, naming and shaming, would result in non-compliance with a potential 3 year ban from conducting further clinical research for institutions, sponsors and CRO’s found to be submitting deficient dossiers after self-inspection. Additionally, all other dossiers associated with those found in breach would be retrospectively inspected for quality. This initial quality clamp down resulted in over 1,400 dossiers being withdrawn or quality cited by the CFDA reducing the backlog to around 250.
Further quality and guideline revisions were subsequently released by the CFDA and Healthy China is given its own chapter in the national 13FYP document. Healthy China has become the official umbrella for healthcare issues ranging from healthcare reform to promotion of healthy lifestyles and food safety measures. The 13FYP calls for a healthcare philosophy that is based on prevention, aiming at providing fundamental healthcare services for everyone. Healthy China in the 13FYP calls to: Improve drug provision with emphasis on reforming drug review and approval processes and allowing priority listing for innovative drugs. This has resulted in a raft of new policies and guidelines from the CFDA that will be implemented by Q3 2016:
Lists of drugs for priority review released for comments
Following the CFDA’s release of priority approval procedures in February; in April, the Center for Drug Evaluation (CDE) of the CFDA released for public comment lists of drugs that will be subject to priority review, such as HCV drugs and antineoplastic drugs.
CFDA released Guiding Principles for Bioequivalence Test Waivers for public comment
On April 8, the CFDA released Guiding Principles for Bioequivalence Test Waivers for public comment. This policy indicates that the CFDA will allow some pharmaceuticals to only conduct dissolution tests for consistency evaluation.
CFDA finalized Working Procedures for Clinical Trial Data Inspection
On March 29, the CFDA finalized Working Procedures for Clinical Trial Data Inspection, following a draft released for public comment on February 24. The finalized policy standardizes the procedure of inspecting clinical trial data for drug registration applicants and CROs.
Considering all of the above, the implementation of these policies, together with increased funding for the number of inspectors, along with decentralisation of approvals to provincial CFDA offices, will significantly improve CTA approval times towards the target of 6-8 months for a multi-country regional clinical trial application.
George Clinical, China has been conducting clinical research studies for the past 8 years and was established as a separate legal entity in mid-2013. Currently 55 staff (45 in project management and Clinical Operations) work with International sponsors to conduct Phase III and Phase IV studies. Research networks in cardiology are particularly strong and we co-operated with over 260 sites in 56 cities over the last three years.
George Clinical’s experience in truly understanding trial set up and site networks is evident in China. The CANVAS-R study, is case in point, where the team managed to make their first Ethics Committee submission on the same day that approval was obtained from the CFDA. This is due to the preparation that the George Clinical China team undertook during the regulatory review period. Instead of the typical 60 days it takes to obtain approval from the Ethical Committees, it took merely 11 days. This paved the way for a total of 26 submissions within less than two months.
In order to further expedite the process of site set-up, eight sites were willing to begin contract negotiations before Ethics Committee approval was obtained. This resulted in the first contract being signed two weeks after the sponsor made the contract template available. All of this translated into 118 subjects and 92 randomised subjects over 7 sites being enrolled in one month, with an average of over 13 subjects per site per month.
As the world’s most populous region continues to expand and establish itself as a mature player in the clinical trials sector, China will lead the way in the best regulatory practice considering their size, influence and geographical spread. This process of adjustment will take time, however it is up to contract research organisations with an intimate knowledge of the Chinese regulatory environment to help sponsors navigate any changes as they occur, with ease.