China Food and Drug Administration (CFDA) is facing increasing pressure as a backlog of pharmaceutical marketing and clinical trial applications grow, though trial standards there are approaching those of international standards, according to a perspective published in Nature Reviews Clinical Oncology on Tuesday.
At least part of the problem stems from the fact that CFDA uses “an overly strict approach” for approving clinical trial applications, which contrasts with an “overly lax approach” to approving marketing applications, the authors say, noting that the policies have resulted in a “notable widening of the gap between domestic and international clinical research, resulting in China falling many years behind other countries in terms of the approval of new drugs.
“A severe backlog of pending approval decisions has accumulated for novel agents,” the authors, two of whom work for CFDA's Center for Drug Evaluation (CDE), note. “Furthermore, vast numbers of generic drugs remain on the waiting list for approval, owing to delays in examination and approval of each case by the CFDA. This backlog arose, in part, from a lack of trained staff.”
In 2015, more than 21,000 applications awaited review by the CDE, most of which were for generic drugs. For clinical trials, the article says that between 2013 and 2015, the average delay for an application to register a clinical trial of an innovative drug was 14 months.
CFDA’s clinical trial registration and approval process differs from the US Food and Drug Administration’s (FDA) process in that FDA uses an investigational new drug (IND) filing system, whereas CFDA uses a clinical trial approval (CTA) process whereby the CDE reviews each trial protocol individually, even if the trial is for a generic drug.
The applicant in China must obtain an approval letter from the CDE before a trial can be initiated, and after all approved clinical trials are completed, a new drug application (NDA) must be submitted to the CDE.
“Several steps of this approval process are repetitive,” the authors write. “Both the heavy workload involved in obtaining a CTA and the duplication of several aspects of this work in submission of the NDA are major reasons for the severe backlog of applications and the major delays in the processing of new drug approvals in China.”
However, despite the issues associated with clinical trial registration and drug-approval processes in China, clinical trials of innovative cancer agents conducted in China have been published in high-profile oncology journals.
To further improve its drug approval process, China has implemented what’s known as a “four-colour-light” strategy where different drugs are classified into redefined categories of innovative and generic drugs, with priority given to the innovative drugs.
CFDA has also updated the categories of chemical drug registration and redefined the definition of “innovative drug” from nationally innovative drugs (drugs not listed in China) to “globally innovative drugs,” which are those not listed in China or elsewhere.
“Drugs that are optimized versions of previously approved agents (with a known structure and active ingredient), which are, therefore, often similar in terms of structure, dosage, route of administration, indication and/or use as a combination therapy, and often also treatment outcome, are no longer eligible for classification as ‘new’ drugs,” the authors say.
Other strategies are also being implemented to fight these backlogs and inefficiencies, including the development of a new clinical trial approval system and several measures designed to encourage more participation by Chinese researchers and research centers in international clinical trials.
The changing landscape of clinical trial and approval processes in China