The Chinese government has announced plans that will allow drug or medical device manufacturers to apply for approval in the country using clinical trial data generated overseas, a move heralded as a departure from the notably strict rules regarding the generation of data for Chinese approval. International media outlets have been quick to assert that this will lead to faster patient access to new products and a significant increase in revenues for the companies behind these. Any efforts to increase pharmaceutical access in China, a market estimated to reach a value of $160 billion by 2020, are welcome for the industry. However, a deeper analysis of the current pharmaceutical and health care dynamics in China is required to substantiate these claims.
Currently, pharmaceutical companies have two options when deciding on a launch strategy for the Chinese market. The first of these is to conduct the entire clinical development program in China prior to any other market. This route allows for manufacturers to apply for a Category I New Drug Application (NDA) and can result in products being quickly approved. However, this route is only an option if the product in question has not been approved in any other country, and is generally only taken by domestic pharmaceutical companies. The second route for products developed outside of China or that have already been approved in other markets involves applying for a Category III Imported Drug License (IDL).
Gaining Study Approval in China, a Lengthy Process
Currently, applying for an IDL still requires Chinese clinical trial data to be submitted, but does not require the entire development process to have taken place in the country. International pharmaceutical companies often take this route when seeking approval in China, and theoretically, this allows for simultaneous submissions for approval across international markets. This should mean that patients in China could have access to these pharmaceutical products at a similar time as patients in other markets; however, realistically, this is not the case. For example, Genentech’s Avastin (bevacizumab) was approved for use in non-small cell lung cancer (NSCLC) by the US in 2006, but did not become available to patients with NSCLC in China until 2015. Despite the approximately 10 million hepatitis C sufferers in China, Gilead’s Sovaldi (sofosbuvir), which was approved in the US in 2013, only became available in China this year.
Getting approval to conduct a trial in China, whether it is a separate trial or part of a multicenter investigation, can take many years due to the review and inspection requirements of the Chinese Food and Drug Administration (CFDA). This process is partially responsible for the lengthy delays in drug access in China. The delays in trial registration have also discouraged companies from including China when conducting multicenter trials, as delays in the inspection or approval could potential impact the development timelines of the product in other markets. However, this is not the only bottleneck delaying patient access. Another major source of delay is the review and approval process of the CFDA following evidence submittal.
Details of New Plan Remain Unclear
Upon submitting an NDA for a China-developed drug, the evidence is reviewed by the CFDA. This review is often completed within a 6–12 month timeframe. Assuming that trial data has also been generated for overseas markets, this generally allows for a China launch date approximately 12 months after a U.S. or EU launch. For international companies submitting for approval via an IDL, the delay between a products’ U.S./EU launch and its China launch is usually four to six years. The vastly longer review process timelines in China, especially for IDL submissions, are a key factor delaying the availability of products in the Chinese market, alongside delays associated with the requirement to conduct a trial in China.
The details of the plan to allow clinical trial data from overseas centers to be used have not been released yet, but are likely to stipulate that such trials must have a certain amount of ethnically Chinese patients enrolled to be used in a submission. The removal of the requirement for China-based trials will allow for a side-stepping of the time consuming inspection and approval of clinical trial sites, as well as other protocols that companies currently have to contend with in China. This will allow data to be generated in multicenter trials without the risk of delays, and will speed the submission of evidence to the CFDA. However, barring fundamental changes in the drug registration process, this data will still be used as evidence in an IDL submission and will therefore suffer from long delays in CFDA review. Unless this change is coupled with a speeding up of the review process, pharmaceutical products are still unlikely to become available in China at the same time as other major markets.
Real-world Impact of Changes Need to be Assessed
To allow for a faster entry of imported pharmaceutical products into the Chinese market, the regulatory approval process must be quickened. To this end, the CFDA has announced efforts to prioritize the review of innovative products for the treatments of various therapies areas, such as cancer, acquired immune deficiency syndrome (AIDS), and viral hepatitis. These revised timelines are ambitious compared to the current Chinese standards, and future analyses will be needed to ascertain whether they are successfully reached.
In 2015, the CFDA also announced that it had plans to increase its number of reviewers, with the aim of tackling the backlog of applications that has arisen. While this was seen as a positive step at the time, the impact of these hires may be limited if the CFDA struggles to retain its staff, as seems to be the case amid reports of CFDA staff leaving to seek significantly higher salaries offered by the private sector. The CFDA has announced intentions have also been announced to remove the requirement for the inspection and approval of clinical trial sites prior to the initiation of a trial, proposing a later inspection, or no inspection at all at certain sites, instead.
Notably, it must be considered that the current situation is to the benefit of domestic pharmaceutical companies that are able to get their products to market in China much earlier than foreign competitors. While demand for patient access to new products is pushing calls for reform, the real-world impact of changes to the Chinese system will need to be assessed in the future.