The European Medicines Agency (EMA) has developed 12 modules (I to XVI) for pharmacovigilance processes. The EMA has already covered the topics for Modules XI to XIV in other guidance documents, and thus they are null. The remaining modules play a vital role in ensuring patient safety.

Module I focuses on quality objectives for pharmacovigilance systems to comply with safety standards. It guides pharmaceutical companies on how to handle each aspect of the process to meet those objectives. Pharmacovigilance systems are used to identify if a drug has adverse effects and to track drug safety over time. Organizations can show their findings to regulatory authorities and alert the public if new adverse events are detected and verified.

Module II requires the inclusion of a pharmacovigilance system master file (PSMF) with every marketing authorization (MA) application. The PSMF must contain details on the Qualified person responsible for pharmacovigilance, organizational structure, computer system, PV processes, quality system activities, delegated activities.

Module III and IV are pharmacovigilance inspections and audits respectively, which are conducted by competent authorities to ensure compliance with EMA guidelines. Inspections ensure the availability of resources to meet pharmacovigilance requirements, while audits verify the ability of pharmacovigilance systems to perform activities effectively.

Module V involves the creation of a risk management plan (RMP) for every drug. The RMP identifies the safety profile of the drug and creates a pharmacovigilance plan to identify new adverse reactions. As more information emerges, the RMP adapts to changes in the drug’s safety profile.

Module VI provides guidance on the collection, management, and submission of reports of suspected adverse reactions to medicinal products. The reports are collected by pharmacovigilance systems and evaluated by competent authorities and MA holders.

Module VII focuses on Periodic Safety Update Reports (PSURs) which provide an overview of a drug’s risk-benefit during the post-authorization phase. The competent authorities review the PSURs within 70-90 days of the data lock point to check if the risk-benefit balance has changed.

Module VIII involves conducting Post-Authorization Safety Studies (PASS) to identify a safety hazard or confirm the safety profile of a drug. These studies are initiated by the EMA or the MA holder and reviewed by the Pharmacovigilance Risk Assessment Committee (PRAC).

Module IX refers to signal management which is about the evaluation, reporting, and timelines of drug safety issues. Pharmaceutical companies need to send a signal to the EMA within 30 days of identifying an adverse reaction.

Module X involves additional monitoring for certain drugs that may have adverse reactions emerge after authorization. The EMA maintains a list of these drugs which require additional data collection, and they are identified with an inverted equilateral black triangle ▼.

Module XV is about safety communication, and it involves disseminating information to healthcare professionals and the public about the safe use of drugs.

Module XVI focuses on the implementation of risk minimization measures to minimize risks associated with drug use. These measures are based on the RMP and are regularly reviewed and updated. Overall, these modules help in ensuring the safety of patients and the public.

China GVP on the other hand showed similar structures. China GVP is based on the “Guidelines for Adverse Drug Reaction Reporting and Monitoring” issued by the Chinese Ministry of Health, while EU GVP is developed by the European Medicines Agency (EMA) in collaboration with the EU member states.

In terms of content, both frameworks cover similar aspects as illustrated in the graph with same colour highlighted for the PV aspects covered. However, there may be differences in specific requirements and guidelines due to variations in regulatory processes and regional considerations. It is important for pharmaceutical companies operating in both regions to be familiar with and adhere to the respective GVP guidelines to ensure compliance with local pharmacovigilance requirements.

The establishment of China PSMF referenced EMA GVP Module II of PSMF as a model. Nevertheless, two additional aspects “Entrustment of Pharmacovigilance Activities” and “Full-time Personnel” are incorporated in the China PSMF as required in the Guideline for Preparation of the Pharmacovigilance System Master File published by NMPA.

The implementation of Pharmacovigilance activities in China is governed by the China (GVP), which mandates Marketing Authorization Holders (MAHs) to establish pharmacovigilance quality objectives and a comprehensive quality assurance system. To fulfill PV responsibilities, MAHs are required to introduce the concept of the Qualified Person for Pharmacovigilance (QPPV). Similarly, the European Union requires MAHs to establish a Pharmacovigilance system and appoint a QPPV. However, the United States does not have explicit requirements for Pharmacovigilance systems.

The official implementation of the China GVP is on December 1, 2021, emphasising the primary responsibilities of MAHs in Pharmacovigilance. Despite the existence of Level 3 Adverse Drug Reaction Monitoring Centres, a shortage of QPPVs has been observed in recent years in China.

The qualifications and responsibilities of QPPVs within the GVP quality management system have led to variations and confusion within MAHs. This includes differences in position designation, hierarchical level, duties, and the required knowledge and skills for QPPVs. The QPPV plays a vital role as the main contact between the MAH and Regulatory Authorities, ensuring drug safety and compliance with regulations through the establishment and maintenance of pharmacovigilance systems, monitoring and reporting adverse drug reactions, and implementing risk management strategies.

In China GVP it is required that the QPPV “should be a managerial position with certain responsibilities, have a background in medicine, pharmacy, epidemiology, or related fields, possess a bachelor’s degree or higher education, or have an intermediate or higher professional and technical title.” It also states that the QPPV should have “over three years of experience in pharmacovigilance-related work, be familiar with Pharmacovigilance-related laws and regulations and technical guidance principles in China, and have the knowledge and skills for Pharmacovigilance management”.

The selection requirements of EU QPPV also include similar professional background requirements, with a specific emphasis on medical knowledge or a background in medicine. The EU-GVP mentions that the EU-QPPV should possess the skills to manage the pharmacovigilance system and have the expertise or ability to acquire knowledge in relevant fields such as medicine, pharmacy, epidemiology, and biostatistics.

In China GVP, it is required that the QPPV should have “over three years of experience in pharmacovigilance-related work,” meaning that they have been dedicated to working in drug vigilance and have experience in activities related to the collection and reporting of drug safety information (such as physicians, pharmacists, CRA/CRC personnel in clinical research), as well as adverse drug reaction (ADR) handling. Similarly, in the EU-GVP, EU-QPPV applicants or MAHs are subject to qualification review and assessment before appointment, including evaluation of university education, understanding of EU pharmacovigilance requirements, and experience in pharmacovigilance.

According to Article 25 of the China GVP, the QPPV is responsible for the operation and continuous improvement of the pharmacovigilance system, ensuring its compliance with relevant laws, regulations, and the requirements of the GVP. Therefore, the responsibilities of the QPPV can be summarized as continuous improvement, compliance, risk control, information communication, and auditing.

1. The foundation of pharmacovigilance quality management work is based on the pharmacovigilance system as the main focus. The QPPV implements continuous improvement plans through the Deming cycle (Plan, Do, Check, Act), ensuring the effective operation of the pharmacovigilance system.
2. Compliance of monitoring reports is one of the quality objectives of pharmacovigilance. By setting quantifiable quality control indicators, the effectiveness of the pharmacovigilance system is measured. If the compliance indicators are not met, the QPPV should lead the analysis of errors, training, processes, and other reasons.
3. Pharmacovigilance is work based on the principle of “full-process control and risk management.” The QPPV should supervise the entire process of pharmacovigilance, conduct drug safety risk identification, assessment, and control, and ultimately ensure the effective implementation of risk control measures.
4. Channels of communication in pharmacovigilance should remain open, including multiple channels for reporting safety information (phone, fax, email, mobile applications, etc.). QPPV should be contacted (department) promptly through convenient means to provide feedback on safety issues or other work instructions, such as conducting inspections and benefit-risk assessments, and respond adequately and timely to inquiries from Regulatory Authorities.
5. Safety information is one of the important contents of pharmacovigilance work. The QPPV is responsible for the accurate and complete communication and transmission of information to ensure timely and effective communication.
6. The QPPV needs to review and issue important documents, including periodic safety update reports and post-marketing safety study protocols. These documents reflect the integrity of the pharmacovigilance system or the safety of specific products. However, it is not recommended to include Individual Case Safety Report files in the category of important documents.

There are some differences in the qualifications for QPPV positions between China and EU, mainly in terms of experience, knowledge and skills, and personnel attributes (see Table 1).

1. Education and professional background: No significant differences between China and EU. Both require a Bachelor degree or above, with a focus on relevant fields such as medicine and pharmacy. However, the EU places more emphasis on the field of biostatistics. Due to the interdisciplinary nature of Pharmacovigilance, both China and the EU face a shortage of professionals in the field, allowing individuals with relevant backgrounds to assume QPPV responsibilities.
2. Experience and qualifications of QPPV: China specifies a requirement of 3 years of relevant experience in pharmacovigilance, while the EU does not explicitly mention the years of experience.
3. Knowledge and skills: Both China and the EU require familiarity with local pharmacovigilance-related laws, regulations, and technical specifications. In China, as the initial version of GVP was just released in May 2021, it may take some time for QPPVs to acquire the necessary knowledge in the field of drug vigilance. Therefore, if Chinese pharmaceutical companies choose to hire or outsource QPPV positions, it may be possible to quickly meet legaland policy requirements.
4. Duties and place of residence: China requires QPPVs to hold management positions and expects them to influence relevant personnel and departments through these positions, which is more conducive to conducting Pharmacovigilance work. The EU-GVP does not specify management position requirements, although it emphasizes responsibilities and influence, which typically requires time accumulation in managerial roles. The EU also emphasizes that QPPVs should reside within the EU or in Norway, Iceland, or Liechtenstein. China does not mention residence requirements, but in general, it is preferable for QPPVs to be located within China, as it facilitates communication with Regulatory Authorities.
5. Personnel attributes of QPPV: The Chinese GVP does not mention the outsourcing or employment of external QPPV personnel, while the EU-GVP allows QPPVs to be employees of third-party companies to oversee and manage the pharmacovigilance system of MAHs.

Table 1 Comparison of QPPV Qualification between China and EU.

There are differences in job responsibilities between QPPV positions in China and the European Union, including compliance management, communication management, government-enterprise communication, as well as management and legal responsibilities. The initial version of GVP in China provides a relatively concise and clear description of QPPV responsibilities. In Article 25, under “Personnel and Training,” it briefly outlines the responsibilities of QPPV, such as compliance,supervision, communication management, government-enterprise communication, and review and issuance. The Pharmacovigilance System Master File (PSMF) also requires basic information about the QPPV, including residence area, contact information, resume, and responsibilities. On the other hand, the European Union’s GVP provides a more detailed introduction to the responsibilities and role of the QPPV. The supervisory responsibilities include standard operating procedures, contract arrangements, database operations, compliance data related to quality, regular updates and auditing reports, completeness and timeliness of expedited reporting, training on pharmacovigilance, and contracted management. Please refer to Table 2 for more details.

Regarding the management responsibilities of the PSMF, the Chinese GVP does not mention or emphasize the QPPV’s authority over PSMF management or specify the personnel responsible for reviewing and issuing the PSMF. However, as a system description document, the European Union particularly emphasizes the QPPV’s management authority over the PSMF. In terms of legal responsibilities, there are differences between China and the European Union in terms of specific legal obligations. In China, the QPPV is primarily responsible for technical guidance, specifically for the technical aspects of drug vigilance,without mentioning the need to assume corresponding legal responsibilities and risks. On the other hand, the European Union QPPV has legal responsibilities, meaning that the position carries certain risks, and it is necessary to ensure compliance with legal requirements to avoid personal and company penalties. Therefore, based on the practical experience of QPPVs in the European Union in terms of quality improvement, management responsibilities, and legal regulations, as well as the early stage of establishing the drug vigilance system in China, it is necessary for China to develop more detailed specifications for QPPV job responsibilities. These specifications can be used by pharmaceutical companies and MAHs to implement QPPV selection from the perspectives of risk management and compliance management.

Currently, there are no specific laws and guidelines in China that explicitly state whether MAHs can outsource QPPV or whether QPPV should assume legal responsibilities. Possible reasons for this could be based on the experience of implementing Good Manufacturing Practices (GMP) and Good Supply Practices (GSP), where key personnel responsible for quality management should be full-time employees of the company, without precedents for outsourcing or hiring third-party personnel. At the same time, considering the current status of practicing pharmacists and Risk Management of MAH in China, no sufficient QPPVs who truly meet regulatory requirements to meet market demand. It may also be considered that most companies can initially meet transitional standards, and regulations and norms only explicitly state that the entity’s responsibility lies with the legal entity or the primary person in charge, without requiring the QPPV to assume legal responsibilities.

When implementing outsourcing for a company’s pharmacovigilance program, it is possible to consider engaging third-party personnel to assume the responsibilities of QPPV on behalf of the MAH. In this case, there is no labor contract between the MAH and the QPPV, but rather a service contract that binds them. This method of outsourcing QPPV hiring can draw lessons from the QPPV system in the European Union.

With the advancement of GVP learning and exchange both domestically and internationally, as well as the gradual maturity of MAH outsourcing business, QPPV entrusting may become an important component of MAH’s quality system outsourcing. In the second chapter of China’s GVP, titled “Entrustment Management,” MAH is required to “entrust pharmacovigilance-related work based on job needs,” but responsibilities are not transferred, and “corresponding legal responsibilities are borne by the holder.” In 2020, the National Medical Products Administration issued the “Guidelines for Writing Pharmacovigilance Agreements (Trial),” but the document does not mention entrustment related to QPPV.

Reference: 1. Discussion and Thoughts on the Job Responsibilities and Selection of QPPV between China and EU, XU Juping, HU Jun, WAN Bangxi, WEI Xiaofei, WANG Guangping

Submit the valid ICSR (EEA and non-EEA serious within 15 days, and EEA non-serious ICSR within 90 days to EudraVigilance (EV)). Non-serious non-EEA ICSRs should not be submitted to EV.

Must report adverse drug experience that is both serious and unexpected, whether foreign or domestic, as soon as possible but no later than 15 calendar days from initial receipt of the information and must submit follow-up reports within 15 calendar days of receipt of new information by the applicant.

The applicant must report each adverse drug experience involving serious listed, non-serious unlisted and listed events at quarterly intervals, for 3 years from the date of approval of the application, and then at annual intervals. The applicant must submit each quarterly report within 30 days of the close ofthe quarter (the first quarter beginning on the date of approval of the application) and each annual report within 60 days of the anniversary date of approval of the application. Follow-up information to adverse drug experiences submitted in a periodic report may be submitted in the next periodic report.