Editor’s Notes: This article was originally published on January 25, 2024, and was updated on April 24, 2024, as per the latest developments.
On April 23, 2024, the National Medical Products Administration (NMPA) of China published the Notice on Optimizing Marketing Authorization Applications for Transferring Manufacturing Sites of Approved Overseas Drugs to China.
The notice outlines the following three points.
1. In the case of drugs that have already received approval in China but are currently manufactured outside of China, if the applicant intends to transfer the manufacturing site to China, they must adhere to the requirements and procedures for submitting drug marketing authorization applications.
2. For drugs mentioned in Point 1, the applicant is permitted to submit the original overseas marketing authorization dossier along with the research dossiers related to transfer of the manufacturing site as supporting documentation for the marketing authorization application in China.
The dossier requirements will be published by the Center for Drug Evaluation (CDE).
3. In the case of originator chemical drugs and biological products mentioned in Point 1, their marketing authorization applications will be admitted into the priority review process by the NMPA.
With the new requirements, it is expected that the review process will be expedited for drugs that have been approved in China but are manufactured outside China, as their overseas dossiers can possibly be recognized by the NMPA.
On January 24, 2024, the National Medical Products Administration (NMPA) of China issued a draft of the Notice on Optimizing Marketing Authorization Applications for Transferring Manufacturing Sites of Approved Overseas Drugs to China.
The term "approved overseas drugs" refers to drugs that have been previously approved by China but are manufactured outside of China.
The draft brings encouraging news as it suggests that China may accept the original registration application dossier, including documents related to chemistry, manufacturing, and controls, non-clinical and clinical studies, if they remain applicable.
However, specific studies on the transfer of manufacturing sites will still be required, and the dossier requirements on these studies will be issued by the Center for Drug Evaluation (CDE).
Another positive aspect mentioned in the draft is that the NMPA acknowledges that such applications for originator chemical drugs and biological products are eligible for priority review.
Previously, in March 2023, CDE released a draft outlining the dossier requirements for such documents, which included waivers or simplifications for certain submission documents.
The table below provides an overview of the notable requirements for each module of the application dossier.
Notable Requirements for the Marketing Authorization Applications of Approved Overseas Drugs Transferring Manufacturing Sites to China
Module | Requirements |
Module 1 | Following the M4 Module 1: Administrative Information and Prescribing Information Required documents for special attention: - Copy of the certification documents and their appendices proving marketing authorization, including the drug import registration certificate, the approval document for supplemental application, the approval document for registration renewal, quality standards, a table specifying the manufacturing process, medication package inserts, etc. Reasons should be specified if no relevant documents under this item are provided. … |
Module 2 | Following the CTD format. The quality overall summary (QOS) should include a table showing the general comparison between the situations before and after the change of the manufacturing site, and the main results and conclusion of the studies comparing the pre- and after-change situations under each item. If there are associated changes apart from changes of MAH and the manufacturing site, studies on the other changes should also be summarized under each item. |
Module 3 | Following the CTD format. The applicant shall also pay attention to the following documents based on the specific situations of the manufacturing site transferred from overseas to China. 1) Formulation and manufacturing process research documents; 2) API & excipient research documents; 3) Quality research & trial documents; 4) Research documents on packaging materials in direct contact with the drug; 5) Drug stability research documents; 6) Consideration for related changes. |
Module 4 | Except for oral dosage forms, the applicant should provide the safety trial documents of all drugs whose manufacturing are transferred from overseas to China to show the pre- and after-change comparison between the samples.
If CMC study is insufficient to prove the equivalence between the samples before and after the change, more non-clinical studies may be required, e.g., dosage form safety trial, toxicity trial for repeated doses, and/or non-clinical pharmacokinetic study. If non-clinical trial is required, the applicant should submit the documents in CTD format. If not required, the applicant has no need to submit the documents for this item. |
Module 5 | For drugs whose manufacturing site is transferred from overseas to China, the applicant can refer to the principle of generic drug’s equivalence evaluation—not doing in vivo study if the CMC study is sufficient to show the comparison.
For some drugs which cannot be proved to be equivalent to the previous situation after the manufacturing site changes, the applicant can consider comparing the equivalence through BE study, which may involve PK-BE, PD-BE, or clinical endpoint bioequivalence (CEP-BE) study. The requirements for in vivo BE study are consistent with those for the registration of class 4 chemical drugs.
For clinical endpoint equivalence study, the applicant shall submit clinical trial documents in CTD format. If in vivo study is not required, the applicant has no need to submit the documents for this item. |
Contact BaiPharm if you would like to learn more about drug registration in China.
