Aggregate Reporting in China

Periodic Safety Update Report/Periodic Benefit Risk Evaluation Report – Requirement in China

Periodic safety update report (PSUR) provides a periodic and comprehensiveassessment of the worldwide safety data of a marketed drug. Over-time itwas recognized that the risk of the marketed drug should be assessed in the light of its benefits and change in the risk estimate overtime. Consequently, the report name was changed to Periodic Benefit-Risk Evaluation Report (PBRER).
According to China GVP,
Chapter V – Risk Identification and Assessment | Section 4 – Periodic Safety Report
Article 79 The periodic safety update report shall be based on the work carried out by the holders during the reporting period. A comprehensive and in-depth review, summary and analysis of the collected safety information shall be conducted, and the format and content shall meet the requirements of “Guidance for Writing Periodic Safety Update Reports of Drugs”.
Article 80 For innovative drugs and improved new drugs a periodic safety update report shall be submitted every 1 year from the date of obtaining the approval documents until the first re- registration, and then every 5 years. For other types of drugs, the periodic safety update report shall generally be submitted every 5 years from the date of obtaining the approval documents. If the drug regulatory authority or the adverse drug reaction monitoring agency requires otherwise, submission shall be made in accordance with the requirements.
Article 81 The data summarization time of the periodic safety update report starts from the date when the drug approval document is first obtained or starts from the first approval date for marketing of the drug around the world (i.e., the International Birth Day (IBD). Integrity and continuity should be maintained during the periodic safety update report data coverage period).
Article 82 Periodic safety update reports shall be submitted through the National Adverse Drug Reaction Monitoring System after approval by the pharmacovigilance responsible person.
Article 83 The holders shall deal with and respond to the review opinions on the periodic safety update reports in a timely manner. For analysis and assessment requirements for specific safety issues, in addition to separate submission as required by the drug regulatory authority or the adverse drug reaction monitoring agency, it should also be analyzed and evaluated in the next periodic safety update report.
Article 84 The holders may submit a periodic benefit-risk assessment report instead of a periodic safety update report. The writing format and submission requirements shall comply with the relevant guidelines of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceutical for Human Use. Other requirements are the same as those for periodic safety update reports.
Article 85 The risk assessment in the periodic safety update report shall be based on all uses of the drug.When carrying out a benefit-risk assessment, the assessment of effectiveness shall include data from clinical trials and data obtained during actual use for the approved indication. The comprehensive benefit-risk assessment should be based on the approved indications, combined with the risks in the actual use of the drug.
Article 86 Unless otherwise required by the drug regulatory authority, periodic safety update reports do not need to be submitted for the following drugs or products managed as drugs: raw materials, in vitro diagnostic reagents, Traditional Chinese medicinal materials, and Traditional Chinese medicine decoction pieces. According to NMPA Announcement on the application of the ICH – E2C(R2): PBRER2, MAH can submit PBRER following the ICH guidelines.
1. China Good Pharmacovigilance Practice Announcement of the NMPA on the Publication of China Good Pharmacovigilance Practice (No. 65 of 2021)
2. NMPA Announcement on the application of the ICH Guidelines, E2C(R2): PBRER (No. [2020]86)

Official FAQ related to PSUR in China

Which products are not required to submit a PSUR?
For APIs, excipients and in-vitro diagnostic reagents that are subject to the approval number, PSURs do not need to be submitted.
For Chinese herbal medicines, Chinese herbal drinks and imported Chinese herbal medicines that are subject to approval number control, it is not required to submit PSUR. For products that are manufactured by domestic pharmaceutical manufacturers entrusted from abroad (e.g. certified by EU/FDA and other relevant countries/regions, in compliance with the laws and regulations of the commissioning country) but have not obtained the approval documents from China, it is not required to submit PSUR.
How should an overseas pharmaceutical manufacturer of an imported drug, which does not have a drug manufacturer in China but has an office or an agency appointed by it in China and a general agent for its products in China, submit a PSUR?
The overseas pharmaceutical manufacturer of the drug should designate its office (or agent) or general agent in China as the safety representative of the drug in China, to fulfil the responsibility of reporting adverse drug reactions and submitting PSURs for the drug. After obtaining the authorisation from the overseas pharmaceutical manufacturer, the representative office (or agency) or general agent in the country will register with the Adverse Drug Reaction Monitoring Platform through the provincial centre where the safety representative is located and then submit the PSUR.
Can a marketing authorisation holder use a Periodic Benefit-Risk Evaluation Report (PBRER) to be submitted instead of a PSUR? What are the specific requirements if a PBRER is submitted?
Yes. If a PBRER is submitted, the format and timeline for submission apply to the ICH E2C (R2): Periodic Benefit-Risk Evaluation Report (PBRER), i.e. PBRERs with a reporting period of 1 year or less should be submitted within 70 days of the Data Lock Point (DLP) and within 90 days for those with a reporting period of 1 year or more. The guidelines and their questions and answers are available in the ICH section of the Centre for Drug Evaluation website. Other questions can be found in the Guidelines for Writing Periodic Safety Update Reports (PBRERs) and Frequently Asked Questions and Answers (Q&A).
The PBRER for imported medicines should be translated into Chinese and submitted together with the original English PBRER, except for the annexes to the PBRER.
Fore more questions please leave your contact emails and we will provide you the Translated version.
Reference:1. PSUR Frequent Question Answered (Q&A) answered 1 – 5
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