Taiwan Clinical Trials | 台灣臨床試驗資訊平台

Q11

How much is the extension fee for DMF after the 5-year expiration time?

Please refer to the latest “Fee-Charging Standards for the Registration of Western Medicines and Medical Devices” released by the TFDA.

Q12

Is there any relevance between the API licenses and DMF certificates for the imported APIs? Could the DMF certificate replace the import certificate of the APIs for own use, so that an application for an import certificate can be omitted?

API licenses: According to Article 39 of the Pharmaceutical Affairs Act, it is required to apply for registration, for the imported or manufactured drugs, to the central competent health authority. Drugs can only be imported or manufactured after the licenses are approved and issued. In addition, the drugs indicated in the Pharmaceutical Affairs Act include APIs and pharmaceutical preparations. Drugs with DMF certificates indicate that the API technical documents have been reviewed and approved by the TFDA. The DMF certificate could replace the part of technical documents required for registration of the API.
The API could be imported or exported with a valid API license. The API could also be imported with import certificate for own use according to Article 16 of the Pharmaceutical Affairs Act. However, a DMF certificate could not replace the API license and the import certificate.

Q13

Is a pharmaceutical preparation needed to apply for DMFs? Is the document required for submission and review for imported APIs with valid API licenses?

According to the announcement DOH 1021402886 released on May 21, 2013, new applications submitted for approval containing new chemical entities or containing the ten ingredients listed in the announcement curtaining those ten ingredients need to include their DMFs started July 1, 2013. The DMF applications should be submitted prior to June 30, 2014 for existing drug products.
If the applicant intends to apply for a DMF certificate for imported APIs registration and granted licenses before June 30, 2013, the relevant information should be provided as indicated in the announcement DOH 1021401257 released on February 21, 2013.

Q14

The DMF is divided into the closed part and the open part. Which part of documents should be submitted? Should all the technical documents be submitted together? Could the applicant submit the open part first, and the closed part submitted afterwards to the TFDA from overseas?

(1).When applying for a DMF review, the applicant must enclose both the closed part and open part for review.

(2).If the closed part could not be provided in the submission, the applicant may submit the open part to the TFDA for DMF application and annotate in the official letter that the foreign API manufacturer will submit the closed part later. After receiving the TFDA application number, the applicant could contact the foreign API manufacturer and mail the closed part to the Division of Medicinal Product Section 3 of the TFDA, and annotate the TFDA application number clearly on the package. When mailing the closed part to the TFDA, the foreign API manufacturer should notify the applicant of the TFDA application number or the CDE case number to facilitate the process.
An example is shown as follows:
Name: Division of Medicinal Products, Food and Drug Administration, Ministry of Health and Welfare, Taiwan.
Address: No. 161-2, Kunyang St., Nangang District, Taipei 115-61, Taiwan (R.O.C.).

(3).Before or after 7 days of the package being delivered, the applicant in Taiwan should send a letter to inform the agency with the relevant information, including the delivery company, package number, delivered date, and the name of the original manufacturer. If the open part submitted by the applicant and the closed part submitted by the foreign API manufacturer are sent out at the same day, the applicant should track the packages and make sure the officer receiving both closed part and open part.

Q15

What documents should be submitted for DMF applications?

The documents should be submitted based on types of DMF application as followings:

Standard or General Application
- Cover Letter (The name of the API, and the name and address of the API manufacturer must be included.)
- Application Form (Application category for full dossiers must be confirmed, and exchange from full dossiers to abbreviated dossiers is not acceptable.)
- Checklist for DMF technical documents (Please refer to the Announcement DOH1021401257 released on February 21, 2013.)
- DMF technical documents (The open part and the closed part should both be included. This document can be exempted if the domestic API license has been issued after 1996 and is still effective.)
Abbreviated Application
- Cover Letter (The name of the API, the name and address of the API manufacturer should be included.)
- Application Form (Application category for abbreviated dossiers must be confirmed, and exchange from abbreviated dossiers to full dossiers is not acceptable.)
- Official certificate (This is to certify the API had been reviewed and approved by EDQM, EMA, or any one of the A10 countries* listed in the Regulations for Registration of Medicinal Products. The certificate, indicating the API being used in pharmaceutical preparations issued from any one of the A10 countries, is also satisfied.)
- Technical documents for abbreviated dossiers are as follows (please refer to the Announcement DOH1001403285 released on June 21, 2011):
  - Information on starting material (including the source, specification, and CoA)
  - Flow diagram and description of manufacturing process (including the actual quantities of raw materials and the yields of intermediates and the API)
  - All organic solvents, catalysts, and reagents used during the manufacturing process.
  - Specifications, analytical procedures (reference of the method), and CoAs of intermediates and API
  - Stability data including storage condition and results of stability studies
Application for verification-The application is reviewed based on the CEP/COS issued by EDQM
- Not applicable to biologics, sterile products, fermentation products, and herbal products
- Cover Letter (The name of the API, and the name and address of the API manufacturer should be included.)
- Application Form (Application category for abbreviated dossiers must be confirmed, and exchange from abbreviated review to full review is not acceptable.)
- Technical documents required are listed as follows (please refer to the Announcement MOHW1031413560 released on February 12, 2015):
  - Letter of Authorization for TFDA to asssess the CEP/COS information.
  - Statement of no variations after EDQM assessment
  - CoAs of at least three batches of an API
  - Current manufacturing process approved by EDQM

*A10 countries: Germany, US, UK, France, Japan, Switzerland, Canada, Australia, Belgium, and Sweden

Q16

What are the acceptable official documents qualified for abbreviated dossiers?

The official documents include CEP/COS, CPP, FSC, EIR (Establishment Inspection Report), and GMP certificate. CEP/COS has an effective period of 5 years, and it should be the latest version as shown on the EDQM website. Nevertheless, the effective period of others is 2 years. The requirements are listed as follows:

The official certificate for the pharmaceutical preparations has been approved issued from any one of the A10 countries, in which the name of the API, and the name and address of the API manufacturer should be included.
The official certificate or the certificate copy notarized by ministry of foreign affairs should be submitted. The copy should be authenticated with the original one and the listed items should meet the Regulations for the Registration of Medicinal Products. The official certificate may be required if necessary.
The copy of the CEP/COS issued by the EDQM is accepted. However, the CEP/COS should be valid, and the original CEP/COS may be required if necessary.

Q17

What are the DMF review time, the period and the number of times allowed for submission of the requested supplementary information?

The review time required for processing applications for DMF can be found in the latest "Ministry of Health and Welfare Food and Drug Administration Application Processing Timetables" released by the TFDA. In principle, twice supplements for insufficient information are permitted for an application, and the supplement must be submitted in two months. One-month extension is allowed in one of the two supplement submissions during the process. If the supplementary information is not received by the due date, the TFDA will reject the application based on insufficient dossier. The applicant may file an appeal for a rejected application within 4 months. The appeal may only be filed once.

Q18

What are the TFDA procedures for handing DMF applications submitted without the closed part?

If the closed part is not submitted in the DMF application, the TFDA will issue an official letter to request the closed part.

Q19

Can a domestic agent file two DMF applications for the same API manufactured by two different manufacturers? Is one DMF application acceptable or would two applications be required?

The domestic agent can file DMF applications for the same API manufactured by two different manufacturers at the same time, but two DMF applications must be filed separately.

Q20

According to “the DMF Technical Document Checklist” announced by the TFDA on February 21, 2013, process validation documents required in Checklist 3.2.S.2.5 may be replaced by the process validation protocol and batch production record. The batch production record provided should be of at least one representative batch. Does the batch production record provided have to be one of the three batches for process validation?

The batch production record provided is not necessary to be one of the three batches for process validation.

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