【正文】 luding new chemical entity (NCE) can be filed independent of a drug product application for new drug, generic drug or imported drug (including international multicentered clinical trial). ? Submission Status – To protect proprietary information contained in a DMF, only administrative information, ., DMF , DMF holder/manufacturer and name of the submission (APIs and intermediate chemical names, etc.) should be listed on SFDA website (or the website of an anization designated by SFDA, ., CDE) after a DMF is accepted. – Open part information is shared only among DMF holder, DMF user and SFDA (or an anization designated by SFDA, ., CDE), and should not be disclosed to the public 42 RDPAC Proposal for DMF in China ? Review Trigger – Submission of an application for new drug, generic drug or imported drug (including international multicentered clinical trial), which has a letter of authorization for referring to a DMF. – A DMF already reviewed will not be reviewed again for a new cross reference unless it is scientifically warranted for its application in a referenced application for new drug, generic drug, or imported drug (including international multicentered clinical trial). ? Review Criteria – Sciencebased (., ICH guidelines) criteria same as those for NDA in China 43 RDPAC Proposal for DMF in China ? Variation/Supplement/Revision – DMF holder to amend the DMF and notify each of the affected new drug, generic drug and imported drug (including international multicentered clinical trial) applicants, who then submit variation applications to crossreference to the DMF amendment. ? Maintenance Responsibility – A DMF holder should provide annual report to CDE, which describes changes to a DMF and authorized usage of a DMF. CDE may terminate a DMF if its DMF holder fails to provide annual report for two consecutive years. 44 RDPAC Proposal for DMF in China ? Communication of Deficiencies – Specific deficiencies should be municated between CDE and the DMF holder. – Applicants referring to DMFs are informed only with general information regarding deficiencies by CDE. ? Sample Testing – Sample testing by SFDA is unnecessary. ? DMF holders are responsible for their products to meet appropriate quality requirements ? The applicants referring to DMFs are responsible for ensuring that those products by DMFs are appropriate for their intended uses. 45 RDPAC Proposal for DMF in China ? Excipients – Since a product application may involve many excipients, it is more practical to differentiate the level of details required for a DMF depending upon different types of excipients and associated risks. ? Compendial excipients can be effectively managed with the basic information about manufacturer, route of administration and specifications that can be readily provided by the excipient manufacturers. ? For those excipients that have been widely used but have not been collected in a pharmacopeia, abbreviated information about manufacturing process, residual solvents, batch analysis and stability, in addition to the basic information, should be sufficient. ? For novel excipients, a plete CMC and toxicological information package should be submitted in either an NDA or a DMF. 46 RDPAC Proposal for DMF in China ? Remarks – Information about the various ponents of a drug product may be submitted (optionally) in the format of DMFs to support review, approval and management of the post approval changes of the drug product. – DMF system is still under development. Suggest that a DMF system be rolled out in a staged manner for different types of materials, ., novel excipient, API and intermediate. – It is important to consider potential practical problems that may be encountered when using DMF to establish an information management system for APIs, intermediate, excipients and packaging materials. – It is necessary to use science/risk based approaches when establishing such a system to ensure regulatory oversight of the drug product quality while retaining regulatory flexibility when associated risks are manageable . 47 Acknowledgement ? Chiwan Chen (Pfizer Inc.) ? Victoria Wei (Jamp。J) ? Cornelia NopitschMai (BfArM) ? RDPAC DMF Task Force ? IPECChina 48 Thank You!