再生醫療製劑安全監視管理辦法

These Regulations are enacted pursuant to Paragraph 3, Article 17 of the Regenerative Medicinal Products Act (hereinafter referred to as “the Act”).

The safety surveillance period designated by the central competent authority pursuant to Paragraph 1, Article 17 of the Act shall correspond to the valid period of the drug license or the conditional approval.

1The central competent authority may designate specific regenerative medicinal products (“the Products”) and announce the mandatory and prohibited components of the Safety Surveillance Plan.

2The Marketing Authorization Holder (MAH), as the holder of a product license or conditional approval, shall develop a Product Safety Surveillance Plan in accordance with the announcement and retain it for inspection.

3For the items designated pursuant to Paragraph 1, the central competent authority may require the MAH to prepare all or part of the Safety Surveillance Plan for the Products and submit it for approval.

1The Product Safety Surveillance Plan referred to in Paragraphs 2 and 3 of the preceding Article shall contain the following elements:

21. The planning, operation, and management of the safety surveillance process.

32. The sources and methods for collecting safety information.

43. The assessment and analysis of the safety information referred to in the preceding item.

54. The risk control measures to be applied to Products for which safety concerns have been identified.

65. The responsibilities of internal personnel involved in safety surveillance.

76. The planning and implementation of safety surveillance training.

1In any of the following circumstances, the MAH shall report the event through the online system established by the central competent authority within three days from the date on which it becomes aware of the situation:

21. Unexpected serious adverse reactions, or serious adverse reactions occurring at a frequency exceeding expectation.

32. Circumstances requiring an evaluation of new or modified contraindications or restrictions on use.

43. The Products have been suspended or withdrawn from the market due to adverse reactions in any of the A10 countries, which include Germany, the United States, the United Kingdom, France, Japan, Switzerland, Canada, Australia, Belgium, and Sweden.

54. The Products have been suspended or withdrawn from the market due to adverse reactions in countries other than those listed in the preceding subparagraph, and such events are determined to require reporting.

6The term “serious adverse reactions” in Subparagraph 1 of the preceding paragraph shall refer to those defined in Article 2 of the Regulations for Reporting Severe Adverse Reactions of Medicaments.

1When any condition described in Paragraph 1 of the preceding Article occurs, the central competent authority may require the MAH to take one or more of the following measures:

21. Issue a safety alert or take other actions achieving the same purpose.

32. Submit a Safety Assessment and Analysis Report.

43. Revise the product information (package insert).

54. Develop and implement a Risk Evaluation and Mitigation Plan/ Risk Management Plan (REMP/RMP).

65. Take other necessary measures.

1The MAH shall continuously collect safety data during the validity period of the drug license or conditional approval and submit a Periodic Safety Update Report (PSUR as per Appendix 1 to the central competent authority within ninety (90) days after each data lock point (DLP).

2The periodicity shall be every six months during the first and second year following the issuance of the license or conditional approval, and annually thereafter. The DLP for each period shall be the last day of such period.

3The MAH may, within three months from receiving notification of the issuance of the license or conditional approval, apply for re-determination of periodicity by submitting:

41. The International Birth Date (IBD) or the start date of the Periodic Safety Update Report (PSUR) approved in any of the A10 countries.

52. Proposed DLPs for each period, provided that the interval between periods does not exceed one year.

1Based on the risk level of the Products, the central competent authority may require the MAH to prepare a Risk Evaluation and Mitigation Plan / Risk Management Plan (REMP/RMP) (Appendix 2) and submit it for approval within the following timelines:

21. For Products containing specified types or ingredients announced by the authority, submission shall be made within 90 days after the announcement; for Products licensed after the announcement, submission shall be made within 90 days of receiving the license or conditional approval.

32. For Products not included in the preceding subparagraph, where deemed necessary by the central competent authority, the MAH shall submit the REMP/RMP as part of the review documents prior to issuance of the license or conditional approval.

4The REMP/RMP shall include risk evaluation and control methods, timelines for submitting performance reports, and other implementation items.

5Any modification to the REMP/RMP shall be subject to approval by the central competent authority before implementation, except for the following changes:

61. Name, address, contact information, telephone number, or fax number of the MAH or manufacturer.

72. Name or address of the distributor.

1The MAH shall designate units or personnel to perform the following tasks and maintain records for inspection:

21. Reporting pursuant to Article 5.

32. Collection of safety data and submission of periodic safety reports pursuant to Article 7.

43. Preparation, implementation, and reporting of the REMP/RMP pursuant to Article 8.

If the MAH suspends or terminates business operations and is therefore unable to complete the submission of PSURs under Article 7 or the implementation of the REMP/RMP under Article 8, it shall submit a report covering the portion already completed within sixty (60) days from the occurrence of such suspension or termination. If business operations resume, the MAH shall continue to fulfill outstanding obligations.

1The MAH shall retain all safety surveillance-related materials for at least ten (10) years after expiration of the drug license or conditional approval; for gene therapy products, materials shall be retained for at least twenty (20) years.

2The preceding materials include all original data, records, documents, and literature underlying such plans or reports.

3Where a drug license or conditional approval is transferred with approval of the central competent authority, the transferring MAH shall deliver all safety-surveillance materials to the transferee, who shall continue surveillance and retention obligations in accordance with these Regulations.

1The central competent authority may dispatch personnel to inspect the MAH’s safety surveillance operations or require submission of relevant materials. The MAH shall not evade, obstruct, or refuse such inspection.

2The authority may invite experts, scholars, or relevant agencies or organizations to participate in the inspections or provide opinions.

All plans and reports required under these Regulations shall be prepared in Traditional Chinese or English. Attachments not originally in Traditional Chinese or English shall be accompanied by a translated version in either language.

If the MAH needs to collect, process, or use personal data for implementing safety surveillance of the Product, such actions shall comply with the Personal Data Protection Act and other relevant laws and regulations.

These Regulations shall enter into force on the date the Act is implemented.