T-34: Implement Refuse to File (RTF) Mechanism on Drug Review Process to Enhance the Quality and Submission of Application Submissi
Yi Tzu Hsu
TFDA/Center For Drug Evaluation Taiwan
The goal of RTF study is to analyze and classify the deficiency of data package, promoting the communication between agency and sponsors and increasing the quality of application submission. Moreover, the agency could initiate education and training program for sponsors basic on deficiency database.
TFDA and CDE announced RTF in 2016 and implemented on January 1st, 2017. RTF is a critical regulatory process to help TFDA/CDE avoid unnecessary review for incomplete applications that are submitted as ANDA. Reviewers will check the data completeness in parts of Administration section, CMC, and pK.
So far, there are 10 applications rejected (including 4 importing drug applications) in 24 ANDAs. The most common deficiencies for these RTFs were:
(1) The technical dossier did not contain the CoA of excipients (7/10) in CMC section,
(2) The application did not contain the certificate of PIC/S GMP of manufacturers (5/10) in CMC section.
(3) The technical dossier did not contain the validation protocol or report of 3 commercial batches (4/10) in CMC section.
(4) The technical dossier does not contain the CoA of drug substance or drug product (3/10) in CMC section.
For 4 importing drug oral dosage form applications:
(1) The application does not contain the validation report of specification and analytical method (3/4),
(2) The supporting information of the manufacturer was not approved in Taiwan (3/4),
(3) The linkage data when there are more than one sources of drug substance (2/4).
(4) The evidence of the bio-batch in BE study was the same as the drug product that would be applied (2/4) in PK section.
Through this analysis sponsors can receive the significant advices from the review team, and agency can also have a better direction on education and training program for sponsors after clarify main deficiencies. This new mechanism can achieve transparency on the criteria of drug review, and more accessible communication between agency and sponsors.
As the results, RTF is a useful mechanism to provide sponsors a directive way for preparing technical dossier and increasing the quality of submission; on the other hand, the agency can control review clock to accelerate review timelines. The application submission is now being improved, while the development of biopharmaceutical industry and the public health in Taiwan are improved and getting better.