Management System

Pharmacovigilance System Master File (PSMF)

PSMF is a comprehensive document that describes the pharmacovigilance system of a company or organization involved in the development, manufacturing, and distribution of medicinal products. The purpose of the PSMF is to provide regulatory authorities with an overview of the company’s pharmacovigilance system and to demonstrate compliance with legal requirements.

The PSMF includes information on the organizational structure, roles and responsibilities of the personnel involved in pharmacovigilance activities, the procedures and processes for collecting and evaluating safety data, risk management plans, and other relevant documents related to the company’s pharmacovigilance system. It also provides information on deficiencies in the system and non- compliance with the requirements, the action and measures that could be taken for specific pharmacovigilance activities.

PSMF is a mandatory document for companies that hold a marketing authorization for medicinal products, and it is subject to internal audits and regulatory inspections by regulatory authorities (NMPA). In addition, the PSMF should be updated regularly to reflect changes in the company’s pharmacovigilance system and to ensure compliance with evolving regulatory requirements.

In summary, the PSMF is a critical document that serves as a blueprint for the company’s pharmacovigilance activities and provides assurance to regulatory authorities that the company is actively monitoring the safety of its products and taking appropriate measures to manage any risks associated with their use.

Per the Chinese GVP1

Chapter VII Documents, Record and Data Management Section 2 Pharmacovigilance System Master File

Article 104 The holders shall create and maintain Pharmacovigilance System Master File to describe the pharmacovigilance system and activities.

Article 105 The holders shall update the Pharmacovigilance System Master File in a timely manner to ensure consistency with the current pharmacovigilance system and activities and continue to meet relevant laws, regulations and actual work needs.

Article 106 The pharmacovigilance system master file shall include at least the following contents:

Organizational structure: describe the organizational structure, responsibilities and mutual relationships related to pharmacovigilance activities;
Basic information of the pharmacovigilance responsible person: including residential region, contact information, resume, responsibilities, etc.;
Staffing of full-time personnel: including the number of full-time personnel, relevant professional backgrounds, responsibilities, etc.;
Sources of information on suspected adverse drug reactions: describe the main channels and methods of information collection on suspected adverse drug reactions;
IT tools or systems: describe IT tools or systems used to carry out pharmacovigilance activities;
Management system and operating procedures: provide a brief description of the pharmacovigilance management system, and a catalog of the pharmacovigilance management system and operating procedures;
The operation of the pharmacovigilance system: describe the monitoring and reporting of adverse drug reactions, and the identification, assessment and control of drug risks;
Entrustment of pharmacovigilance activities: specify the content and time limit of entrustment, entrusted unit, etc., and provide a list of entrustment agreements;
Quality management: describe the quality management of pharmacovigilance, including quality objectives, quality assurance systems, quality control indicators, internal audits, etc.;
Appendix: Including system and operating procedural documents, drug list, entrustment agreement, internal audit report, and master file revision log, etc.

Reference: 1. China Good Pharmacovigilance Practice Announcement of the NMPA on the Publication of China Good Pharmacovigilance Practice (No. 65 of 2021)

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Pharmacovigilance Risk Management Plan (RMP)

Pharmacovigilance Risk Management Plan (RMP) is an essential component of the risk management strategy for a medicinal product. It is a comprehensive document that outlines the potential risks associated with the use of the product and the measures that will be taken to mitigate those risks. The RMP is required to be submitted to regulatory authorities at the time of product approval, and it is periodically updated throughout the product lifecycle.

The RMP includes a description of the safety profile of the product, including known and potential risks, as well as uncertainties and gaps in knowledge. It also includes a summary of the safety data collected during the pre-clinical and clinical development of the product. The RMP outlines the risk minimization measures that will be implemented, including pharmacovigilance activities, safety monitoring, and risk communication.

The RMP also includes a plan for post-authorization safety studies (PASS), which are studies conducted after the product has been approved to further evaluate its safety profile. The PASS may be required by regulatory authorities as a condition of approval or as part of risk management plan updates. The RMP outlines the objectives, design, and timelines of the PASS.The RMP is a dynamic document that is updated throughout the product lifecycle as new safety data becomes available or as new risks are identified. It is an essential tool for ensuring the safety of the product and for meeting regulatory requirements.

According to China GVP1

Chapter VI Risk Control Section 3 Pharmacovigilance Plan

Article 96 The pharmacovigilance plan, as part of the post-marketing risk management plan, is a written document describing the post-marketing drug safety characteristics and how to manage drug safety risks.

Article 97 The holders shall formulate and implement a pharmacovigilance plan based on the results of the risk assessment if important risks are found in a marketed drug, and update the plan in a timely manner according to changes in risk perception.

Article 98 The pharmacovigilance plan includes an overview of drug safety and pharmacovigilance activities, and a description of the risk control measure to be taken and the implementation time period, etc.

Article 99 The pharmacovigilance plan shall be reported to the holder’s Drug Safety Committee for review.

Currently in China, the Post-marketing Pharmacovigilance Plan (PVP) requirement is described and incorporated in the Guidance document for writing Clinical RMP2. It is anticipated that in the future NMPA may specify the Risk Control measures and activities respectively in terms of clinical pre-phase and post-marketing phase of the products in separate guidance documents.

Reference: 1. China Good Pharmacovigilance Practice Announcement of the NMPA on the Publication of China Good Pharmacovigilance Practice (No. 65 of 2021) 2. Guidelines for Writing Clinical Risk Management Plans (Interim) Announcement by the CDR of NMPA on the publication of the Guidelines for Writing Clinical Risk Management Plans (Interim) (No. 68 of 2021)

For full PDF of Guidelines for Writing Clinical Risk Management Plans (Pharmacovigilance Plan inclusive), please contact us via online chat or email.

Internal Audit

See Pharmacovigilance Audit and Inspections in China (Linked to the corresponding section upon clicking)

Entrustment Management

According to China GVP,

Chapter II Quality Management Section 3 – Entrustment management

Article 15 Holders are the main body responsible for pharmacovigilance, and if pharmacovigilance related work needs to be entrusted based on business needs, the corresponding legal responsibility shall be borne by holders.

Article 16 When holders entrust pharmacovigilance-related work to another party, both parties shall sign an entrustment greement to ensure that the information is true, accurate, complete and traceable, and compliant with the requirements of relevant laws and regulations during the entire process of pharmacovigilance activities.

Signed pharmacovigilance entrustment agreements, or written agreements can be used between the holders of a Group and between the headquarters and the holders, to define the corresponding responsibilities and working mechanisms. The corresponding legal responsibilities shall be borne by the holders.

Article 17 Holders shall examine and select entrusted parties who have appropriate pharmacovigilance conditions and capabilities. The entrusted parties should be legal persons within the territory of China that can guarantee the effective operation of relevant pharmacovigilance work, have corresponding working capabilities, and have the professional personnel, management system, equipment resources and other working conditions to undertake the entrusted pharmacovigilance activities. The entrusted parties should coordinate the holder to accept the extended inspection by the drug regulatory authorities.

Article 18 Holders shall perform periodic audit to the entrusted parties and require the entrusted parties to fully understand the quality objectives of their pharmacovigilance and ensure that the pharmacovigilance activities continue to meet the requirements.

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Pharmacovigilance System

The China GVP indicted the requirement that MAH are obligated when using IT system to support the PV activities1:

Chapter III Organization Personnel and Resources Section 3 Equipment and Resources

Article 29 The holders shall be equipped with the equipment and resources required for pharmacovigilance activities, including office areas and facilities, a safe and stable network environment, paper and electronic data storage space and equipment, literature resources, medical dictionaries, IT tools or systems, etc.

Article 30 When using an IT system to carry out pharmacovigilance activities, the following requirements should be met:

Define the management requirements for the design, installation, configuration, validation, testing, training, use, maintenance and other processes of the system, and record the above processes in a standardized manner;
Define the security management requirements of the system, and select control methods such as access control, authority allocation, audit trail, authorization change, and electronic signature, etc. according to different levels to ensure the security of the system and its data;
The system shall have complete data security and confidentiality functions to ensure that electronic data is not damaged, lost, leaked. Proper verification or validation shall be carried out to prove that it meets the intended purpose.

Signal Detection

See Signal Management in China: An Overview of Regulatory Requirements (Linked to the corresponding section upon clicking)

Aggregate Report

See Aggregate Reporting in China (Linked to the corresponding section upon clicking)

Post-Authorisation Safety Study (PASS)

According China GVP1,

Article 71 The holders shall take the initiative to carry out drug post-marketing safety studies based on the risk of the drug, or carry out drug post-marketing safety studies in accordance with the requirements of the provincial or higher drug regulatory authority. Post-marketing safety studies and activities of drugs shall not be aimed at product promotion.

Article 74 The holders shall select appropriate post-marketing safety study methods based on the study objectives, drug risk characteristics, clinical use, etc. Post-marketing safety studies of drugs can be based on primary data collected directly from medical staff or patients in this study, or based on secondary data that has occurred before this study and been collected for other research purposes.

Article 75 The holders shall formulate a written study protocol for post-marketing safety studies. The study protocol shall be formulated by personnel with appropriate academic background and practical experience, and reviewed and approved by the pharmacovigilance responsible person.

The study protocol shall stipulate the procedures for the collection, assessment and reporting of the information on suspected adverse drug reactions during the study period, and shall be summarized in the study report.

During the study process, the study protocol can be revised or updated as needed. After the start of the study, any substantial revisions to the study protocol (such as study endpoints and study population changes) shall be recorded in the protocol in a traceable and reviewable manner, including the reason, content, and date of the change.

Article 76 For drug post-marketing safety studies required by the drug regulatory authority, the study protocol and report shall be submitted according to the requirements of the drug regulatory authority.

Article 77 The holders shall monitor the safety information during the study period, and when discovering any new information that may affect the benefit-risk balance of the drug, it shall conduct an assessment in a timely manner.

An official response to Recommendation No. 9017 of the Fifth Session of the 13th National People’s Congress of NMPA explained the current challenges that have been encountered2:

In order to guide holders to standardize the conduct of post-marketing safety studies on drugs, NMPA issued the GVP in May 2021. The GVP fully draws on international regulatory experience regarding post-marketing safety studies of drugs, and clarifies the scope, purpose, ethical requirements, research methods, data sources, research protocols, research reports and other ten normative requirements for holders to conduct post-marketing safety studies of drugs, so that holders have rules to follow in conducting post-marketing safety studies of drugs. Since the release of the GVP, NMPA has organised several training sessions to disseminate and guide the holders and continuously promote them to improve the capability and level of post-marketing safety studies.

In the next step, the NMPA will continue to support the research and development of innovative drugs driven by clinical value, and continue to improve the relevant working mechanism in collaboration with relevant departments to better meet public demand for medicines.

Reference: 1. China Good Pharmacovigilance Practice Announcement of the NMPA on the Publication of China Good Pharmacovigilance Practice (No. 65 of 2021) 2. Response to Recommendation No. 9017 of the Fifth Session of the 13th National People’s Congress

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