China’s CDE has told drugmakers to communicate more with them and will offer guidance for breakthrough therapy applications.
On Feb. 22, the CDE released a draft of procedures for the marketing application review for breakthrough therapies to solicit public comments. The draft’s biggest highlight is the emphasis on communication with the agency.
This came days after the FDA's Oncology Drugs Advisory Committee voted down the application by Innovent and Eli Lilly to launch their anti-PD-1 antibody sintilimab in the U.S. One of the problems the committee cited was a lack of communication with the agency to obtain regulatory advice before and during the study.
In the CDE document, the agency shared that it will assign a team made up of experts to companies at the early drug development stage. The team will be responsible for the whole process, from pre-New Drug Application (NDA)/Biologics License Application (BLA) communication to post-marketing technical review.
The CDE experts will help with the related review, compliance, acceptance and project management based on indication grouping, review task, and any conflicts of interest.
The procedures are updated based on a previous Administrative Measures for Drug Registration document that came into effect in 2020.
In the draft, the CDE said the aim is to carry out early intervention, development and review simultaneously, as well as rolling submissions, inspections and testing ahead of the emergency approval for COVID-19 vaccines and drugs.
Some companies told PharmaDJ that for breakthrough therapy designations, the key is getting priority opportunities to communicate with the CDE regulators and get their guidance on clinical trials.
It is expected that many companies would welcome the opportunity to keep communication lines open with the CDE review team and the agency.
Communication in two stages
According to the document, communication between the applicant and the CDE is divided into two stages: the pivotal clinical trial stage and the pre-NDA/BLA stage. Pre-NDA/BLA communication is the new addition to this updated version.
In the pivotal clinical trial stage, the CDE review team discusses and reaches an agreement with the applicant on the NDA/BLA submission plan. It also intervenes in advance to guide the applicant to file rolling submission as required. The application timeframe for the meeting is 30 working days.
Applicants may submit communication materials on a rolling basis. The application timeframe for the meeting is also 30 working days.
During pre-NDA/BLA communication, the CDE will conduct a preliminary review of the study data. The applicant can prepare additional information based on the feedback and submit to the rolling NDA/BLA submission.
In addition to relevant technical issues, the review team will also preliminarily review the manufacturing process information sheet, quality standards, inserts, labeling samples, and other attachments.
The document eliminates the requirement for the companies to apply certain procedures. For innovative drugs granted breakthrough therapy designation, applicants that have completed the exploratory clinical trials can automatically move on to the communication and review before and during the pivotal clinical trial without the need for a special application.
The work procedure also clarifies the time limits: the communication will be done within 30 working days after application while the review will be finished in 130 working days, which is the same as the priority review process.
To speed up the review, the CDE also encourages applicants to submit registration testing applications before the NDA/BLA submission. If not applied, the testing work will be started within 10 working days after accepting the NDA/BLA.
A communication mechanism
In July 2020, the new Administrative Measures for Drug Registration came into effect. Then in December, the CDE revised the Drug Development and Technical Review Communication Management Measures issued in 2018 to regulate communication between the applicants and the CDE in the NDA/BLA technical review.
The measures stipulated that the form of communication includes face-to-face meetings, video conferences, telephone conferences, or written responses. Applicants are encouraged to communicate with the CDE via teleconference. The meeting generally lasts for 60 to 90 minutes.
Communication meeting are divided into Type I, II, and III meetings. To hold the meeting, the applicant needs to apply first. Then a CDE regulator responsible for project management and the applicant's drug registration specialist will negotiate and reach an agreement.
Class I meetings address major safety issues encountered in clinical trials and important technical issues for BTDs, held within 30 working days after the application.
Class II meetings are held at pivotal development stages and within 60 working days from application. They cover four stages: pre-IND application, phase II end/phase III pre-launch, NDA/BLA, and risk assessment and control.
Class III meetings are held within 75 working days after an application.
More meeting requests
According to the CDE’s annual review reports, the number of communication applications has been increasing year after year. The growth is not only the result of growing NDA/BLAs but also reflects the urgent need for applicants to receive timely guidance from the regulatory agency during drug development.