FDA Pushes Back on Drug Approval Based on 100% Clinical Data from China
(Thursday, February 10, 2022)
FDA is strongly pushed back on attempts by a Chinese company seeking approval for a new cancer drug based on clinical data from one Phase 3 study conducted in its entirety in China. While this decision may seem contrary to earlier statements by FDA leaders that were interpreted to mean that FDA would accept pivotal data from single foreign countries, this is consistent with the regulatory history of FDA decisions and common sense. There are several reasons why this market approval application was doomed from the get-go. Clinical data from foreign countries have always been accepted in support of market approval applications so long as the trials meet FDA standards and can be audited by FDA. The ICH E5 guidance from 1998 describes conditions under which data from one region can be used for market approval in another region. However, the intent of the guidance was to encourage multiregional trials to evaluate applicability of the data to all regions where approval was being sought. Even ICH E5 recommends bridging studies to extrapolate data from one region to another in the absence of multiregional data. The regulatory requirements were further clarified in the ICH E17 guidance released in 2017 that emphasized the importance of multiregional clinical data for applying data across multiple regions. The only times single nation clinical trials have been successfully used for market approval is when the data is used for approval in the country where the clinical trial was conducted. Single country trials are also permitted for determining bioequivalence of generic drugs but in those cases the safety and effectiveness of the drug is not in question. In this case, the applicant tried to selectively use ICH E5 and ignored ICH E17 guidance. FDA based its primary objection on non-compliance to ICH E17 that strongly recommends multiregional clinical trials over foreign data from a single country. In addition, the trial in China was not conducted under an IND application so FDA was never consulted about the trial design or any other aspect of the trial. FDA was consistent in its opposition to the company’s intent to apply for a BLA with data solely from China from the very first time the company approached FDA with its plan. The company submitted the application anyway hoping for a political discussion for a regulatory outcome, which it got. The company’s intent to make this a political debate is evident from all it has done since filing its application. First, it promised a post-market study in the US about 6 months after its application sensing the strong resistance from FDA. Second, it promised charging lower price for its drug, if approved, knowing well that FDA cannot hold it accountable for pricing decisions post approval and that regulatory decisions cannot be based on pricing or competition considerations. It launched a publicity campaign trying to label this issue as an anti-China bias at the FDA. All these attempts should not influence the Advisory Committee or the FDA. The company had ample opportunities to meet FDA in the middle by at least doing a bridging study. And it is trying to set a precedence for other Chinese companies. More than 25 Chinese companies are seeking similar FDA approvals based solely on Chinese clinical trials and FDA is seriously concerned about that. The vote by the FDA advisory committee about this issue and the FDA decision following it would have long-term effect on applications seeking FDA approval based on clinical trials conducted in a single foreign country. It is not about China but about scientific credibility and logic of the regulatory decisions. A reverse situation would never work in China or any other country and this should be true for the US too.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC