Table of Contents

China’s Good Pharmacovigilance Practices (GVP)

An essential Guide to China’s Good Pharmacovigilance Practices (GVP)

China’s National Medical Products Administration (NMPA), formerly known asCFDA, released the China Good Pharmacovigilance Practice (GVP) guidelines in May 2021. These China GVP guidelines are designed to improve and align China’s pharmacovigilance regulations and practices with international standards set by the International Council for Harmonization (ICH).
The China GVP guidelines consist of nine chapters and 134 articles, providing a comprehensive framework for marketing authorization holders (MAHs) and drug registration applicants in China to establish and implement a robust pharmacovigilance (PV) system. These guidelines cover important aspects such as reporting adverse drug reactions (ADRs), signal detection, PV master files, and strengthening of passive monitoring.
By adhering to the China GVP guidelines, MAHs and clinical drug trial sponsors can ensure compliance with China’s PV regulations, enhance drug safety for patients, and minimize risks associated with adverse drug reactions. Implementing a comprehensive PV system in accordance with global standards not only promotes patient safety but also contributes to the overall quality and credibility of the pharmaceutical industry in China.
The China Good Pharmacovigilance Practices (GVP) guidelines contain the following table of content:
Chapter 1 – Overview
Chapter 2 – Quality Management
  • Section 1 Basic Requirement
  • Section 2 Internal audit
  • Section 3 Entrusting Management
Chapter 3 – Institutional Personnel and Resources
  • Section 1 Organisation/Institutions
  • Section 2 Personnel training
  • Section 3 Facility and Resources
Chapter 4 – Monitoring and Reporting
  • Section 1 Information Collection
  • Section 2 Report Assessment and Processing
  • Section 3 Report Submission
Chapter 5 – Risk Identification and Assessment
  • Section 1 Signal Detection
  • Section 2 Risk Evaluation
  • Section 3 A Post-Authorisation Safety Study (PASS)
  • Section 4 Periodic Safety Update Report
Chapter 6 – Risk Control
  • Section 1 Risk Control Measures
  • Section 2 Risk Communication
  • Section 3 Pharmacovigilance Plan
Chapter 7 – Management of Documents, Records and Data
  • Section 1 Policy and Procedural Documents
  • Section 2 Pharmacovigilance System Master File (PSMF)
  • Section 3 Record and Data
Chapter 8 – Pharmacovigilance during Clinical Trial
  • Section 1 Basic Requirement
  • Section 2 Risk Monitoring, Identification, Evaluation and Control
Chapter 9 – Supplementary Provisions

China Pharmacovigilance History

Pharmacovigilance in China: Milestones and Advancements

China pharmacovigilance regulatory reform has a history dating back to 1980’s with the building of ADR monitoring networks in China to more significant evolution after China joined ICH in 2017 which is now the foundation and commitment towards an internationally harmonised PV system. China strengthened pharmacovigilance policies with the introduction of Drug Administration Law in 2019 which set out the framework for developing China Good Pharmacovigilance Practices (GVP) in 2021.
  • 1950 to 1998: Building of ADR monitoring network in China.
  • 1988: Ministry of Health initiates a pilot project on ADR monitoring involving 10 hospitals in China.
  • 1994: 66 hospitals in 26 provinces in China designated as key hospitals for ADR monitoring, marking a significant step towards a comprehensive system.
  • Pre-2017: Regulations and implementation of pharmacovigilance in China not mature nor systematic.
  • September 2018: China NMPA releases Announcement No. 66 mandating MAHs to report ADRs through NADRMS based on the principle of reporting on suspicion in CHina.
  • 2019: China Drug Administration Law released, requiring pharmaceutical companies to establish pharmacovigilance and annual reporting systems in China.
  • 2020: China GCP revised with the release of the fourth edition by NMPA and NHC.
  • May 2021: China GVP 2021 is officially released and comes into force on December 1st, marking a new chapter for PV in China.
  • 2022: Official China guidance document on writing pharmacovigilance systems is published, further standardizing the framework and reducing the difficulty of building PV systems.

China PV Policy Trend

In the near to medium term, the Chinese authorities is expected to continue to accelerate and enforce GVP and pharmacovifilance regulations to improve drug safety and patient outcomes.

CIOMS and PV

China Pharmacovigilance and CIOMS: Building a Strong Framework for Drug Safety

Revised for SEO: CIOMS plays a crucial role in the field of pharmacovigilance by coordinating and publishing guidelines on drug safety, working with representatives from the global biomedical scientific community. The organization’s programs focus on key areas of biomedicine, including bioethics, health policy, ethics, human values, drug development and use, and international nomenclature of diseases. Since the 1980s, CIOMS has been running projects that address drug safety, and its working groups have published several guidelines for practice. These guidelines are influential in shaping pharmacovigilance practice worldwide and are widely used, although they have no legal or regulatory mandate. CIOMS also developed the CIOMS Form I, a standard format for reporting suspected adverse reactions to medical products that has proved valuable in practice and is still widely used.
The organisation was founded by the WHO and UNESCO, the United Nations Educational, Scientific and Cultural Organisation, in 1949. It is an independent not-for-profit body which is not affiliated to, or funded by, any single government or nation. The organisation brings together representatives from the “biomedical scientific community” worldwide, aiming to encourage and facilitate international biomedical scientific activities whilst maintaining a relationship with the United Nations organisation (particularly WHO and UNESCO)
The CIOMS working groups have published a number of practice guidelines, including
  • I – Internatonal reporting form (also known as CIOMS I Form)
  • II – Periodic Safety Update Reports (PSUR)
  • III – Guideline for Preparing Core Clinical Safety Information (CCSI) on Drugs
  • IV – Benefit-risk assessments for marketed drugs
  • VI – Management of Safety Information from Clinical Trials
  • VII – Development safety update reports (DSUR)
  • VIII -Signal Detection(Publication: Practical Aspects of Signal Detection in Pharmacovigilance)
In addition, CIOMS was involved in publishing an initiative to standardise the use of medical terms associated with adverse drug reactions. However, this has not been widely accepted in pharmacovigilance practice.

ICH and PV

Understanding the Role of ICH in Drug Safety and Pharmacovigilance

Revised for SEO: The International Council for Harmonisation (ICH) was established in 1990 as a collaboration between regulatory authorities and industry professionals to ensure the safety, quality, and efficacy of medicines intended for human use. The need for greater uniformity in testing and safety regulations across regions led to the formation of ICH, which has been able to develop practice guidelines that meet global standards through working groups comprised of representatives from regulatory authorities, pharmaceutical industries, and organizations such as the World Health Organization.
The ICH has established numerous documents outlining safety standards for both pre-clinical and clinical stages of drug development. Pre-clinical guidelines are identified with an “S” designation, while clinical safety guidelines are marked as “E” for “Efficacy.” Each clinical safety guideline has a unique identifying code, which is periodically revised to reflect updated standards. The ICH has developed several clinical safety guidelines that have reached “step 4” status and provide detailed expectations for reporting clinical data to regulatory authorities.
E2A Clinical Safety Data Management provides definitions and standards for the expedited reporting of adverse drug reactions (ADRs) to regulatory authorities to ensure patient safety. E2B (R2) Maintenance of the Clinical Safety Data Management including Data Elements for Transmission of Individual Case Safety Reports provides a standardized format for the maintenance and transmission of individual case safety reports (ICSRs) to regulatory authorities to ensure timely and accurate reporting of ADRs. E2B (R3) Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports updates and expands on the previous E2B (R2) guideline, providing a more comprehensive list of data elements to be included in ICSRs.
E2C (R1) Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs provides guidance on the content, format, and frequency of periodic safety update reports (PSURs) for marketed drugs, with the aim of ensuring ongoing assessment of drug safety.
E2C (R2) Periodic Benefit-Risk Evaluation Report provides guidance on the preparation and submission of periodic benefit-risk evaluation reports (PBRERs) for marketed drugs, with the aim of ensuring ongoing assessment of the balance between drug efficacy and safety.
E2D Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting provides definitions and standards for the expedited reporting of ADRs that are identified post-approval, with the aim of ensuring ongoing monitoring and assessment of drug safety.
E2E Pharmacovigilance Planning provides guidance on the development of pharmacovigilance plans for new drugs, with the aim of ensuring proactive monitoring and assessment of drug safety.
E2F Development Safety Update Report provides guidance on the preparation and submission of development safety update reports (DSURs) for drugs in clinical development, with the aim of ensuring ongoing assessment of drug safety during the clinical trial process.
Please note that this page cannot provide detail on the full scope of the ICH guidelines and the interested reader is referred instead to the source material which can be found online at the ICH website, detailed in the references below. Please note that this page should not be considered as professional pharmacovigilance advice

Application of ICH in China Pharmacovigilance

According to CFDA Announcement on the Application of Secondary Guidelines of International Conference on Harmonization Technical Requirement for Registration of Pharmaceuticals for Human Use (No.10, 2018)
  • From 1 May 2018, E2A, M1, E2B(R3) applied for SUSAR in Clinical studies of medicinal products
  • From 1 July 2018, E2D applied for the reporting of post-marketing ADR
  • From 1 July 2019, the requirement of M1 and E2B (R3) can be applied for post-marketing ADR and from 1 July 2022, above technical guidelines (M1 and E2BB (R3)) applied to the reporting of post-marketing ADR.
According to Announcement by NMPA on the Application of 15 ICH Guidelines, including “E1: Exposure Levels in Populations: Assessing the Clinical Safety of Drugs for the Long-Term Treatment of Non-Life-Threatening Diseases” and others (No. [2019] 88)
  • E2F will be applicable from the Announcement date (12 Nov 2019)
  • E2E: will be applicable to NDA accepted 3 months after the Announcement date & NDA approved 6 months after the Announcement date

China’s Phamacovigilance Regulators: A Closer Look at NMPA, CDE, and CDR

Exploring the responsibilities of NMPA, CDE, and CDR in China’s PV system

SAMR – State Administration for Market Regulation The SAMR is a full ministry agency reporting directly to the State Council of the People’s Republic of China. Under the SAMR is the NMPA, which regulates clinical trials and pharmaceutical market industry.
NMPA – National Medical Products Administration China NMPA (Formerly CFDA) is the regulatory authority responsible for China’s drug surpervision and management, which includes implementing regulations and guidelines for ensuring drug safety in clinical trials, marketing authoritisations and pharmacovigilance policies in China.
Other responsibilities:
  • Management and supervision of drugs, cosmetics, and medical devices.
  • Establishing standards for drugs, cosmetics, and medical devices.
  • Managing registration of drugs, cosmetics, and medical devices.
  • Handling quality management for all regulated products.
  • Risk management of regulated products after listing.
  • Managing qualification and registration of licensed pharmacists.
  • Inspection and supervision of drugs, cosmetics, and medical devices.
  • Handling foreign exchanges and other interactions with international parties.
  • Guiding drug supervision and administration departments under government jurisdiction.
China CDE (Centre for Drug Evaluation) NMPA’s Center for Drug Evaluation (CDE) is responsible for the evaluation of drug clinical trial applications, drug marketing authorization applications, supplementary applications, and overseas drug production registration applications. China’s Centre for Drug Evaluation (CDE) is also responsible for pharmacovigilance reporting pre-marketing Adverse Events, including Serious Adverse Events and Unintended Serious Adverse Events in China.
CDR-Centre for Drug Reevaluation, NMPA | National Center for ADR Monitoring</strong > China’s Centre for Drug Reevaluation (CDR) is responsible for the regulation of China’s pharmacovigilance, post-marketing pharmacovigilance, and colleagues are responsible for issuing some technical standards and guidelines.

ADR Reporting in China: Official System explained

National Adverse Drug Reactions Monitoring System (NADRMS)</strong > NADR Monitoring System is used for Adverse Events Reporting and Management:
  • Medicinal
  • Medical Device
  • Cosemetics
  • Drug Abuse
Reference: https://www.adrs.org.cn/</a >
China Direct ADR Reporting System for MAH, NCADRM Reference: https://daers.adrs.org.cn/#/login?_k=mi0b3p</a >
National Medical Device Adverse Event Monitoring Information System, NCADRM</strong > Reference: https://maers.adrs.org.cn/console/login.ftl</a >
Cosmetic Adverse Reaction Monitoring System Reference:https://caers.adrs.org.cn/adrcos/</a >
Inserting regulations like the following format (scrolling)?

Clinical Pharmacovigilance (PV) in China

CDE – Regulatory Authority Responsible for China Clinical Pharmacovigilance Activities

The Clinical Trials Management Office, which is subordinated to China Center for Drug Evaluation (CDE), is specifically responsible for the reception, analysis and evaluation of suspected and unexpected serious adverse reactions (SUSAR) during clinical trials conducted in China, as well as development safety update reports (DSURs) during the research and development of relevant drugs. Following the guidelines of ICH E2A, E2B and E2F, among others, China CDE has published a series of technical standards and normative documents based on the actual situation in China which includes an electronic reporting system for SUSAR cases during clinical trials.
Pharmacovigilance in clinical trials is the process of monitoring and assessing the safety of investigational drugs or therapies during the clinical trial. This is essential to ensure that the benefits of the treatment outweigh any potential risks or adverse effects. The principle goal of China pharmacovigilance systems in clinical trials is to identify and prevent any adverse reactions or unexpected events related to the investigational product.
China Clinical Pharmacovigilance activities typically include the following:
  • Design and implementation of a China pharmacovigilance plan: This plan outlines the strategies for collecting and reporting adverse events (AEs) and serious adverse events (SAEs) during the clinical trial.
  • China pharmacovigilance adverse event reporting and management: All AEs and SAEs that occur during the clinical trial must be reported and managed according to regulatory requirements.
  • Safety monitoring: Regular safety monitoring is conducted to identify any potential safety issues that may arise during the clinical trial.
  • Risk management: Strategies are implemented to mitigate the risks associated with the investigational product and to ensure the safety of the trial participants.
  • Safety reporting in China: All safety data and analyses are compiled and reported to regulatory authorities, ethics committees, and other relevant stakeholders.
China pharmacovigilance in clinical trials plays a crucial role in ensuring the safety of study participants and in providing reliable safety data for regulatory approval of new drugs or therapies. It also helps to build trust between the pharmaceutical industry, regulatory agencies, and the general public.

Navigating SUSAR Reporting in China

China CDE began to receive SUSAR reports from drug registration sponsors on May 1, 2018. In China SUSAR reporting stands for “Suspected Unexpected Serious Adverse Reaction” reporting. It refers to the requirement for sponsors of clinical trials to report any serious adverse reactions that occur during the trial to the relevant regulatory authorities.
In China serious adverse reaction is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is a congenital anomaly/birth defect.
If such an adverse reaction is considered to be unexpected (i.e. not consistent with the product’s known safety profile), the sponsor is required to report it to the China regulatory authorities as a SUSAR. The purpose of SUSAR reporting is to ensure that the safety of trial participants is monitored and that any potential risks associated with the investigational product are identified and communicated to the relevant authorities.

China SUSAR Reporting

The specific guideline for China SUSAR reporting is “The Standards And Procedures for Expedited Reporting of Safety Data during Clinical Trials</strong >” which serves as the official guidline document published on 27 Apr 2018, Effective date 1st May 2018.
The applicant must report any unexpected and serious adverse reactions that are assessed as certain or suspected to be related to the investigational drug. If the applicant and investigator cannot come to an agreement on the causality assessment between the adverse event and the drug, and neither party can rule out a relationship to the investigational drug, then a expediated reporting should proceed.
The following scenarios generally do not need to be reported as expediated reporting:
  1. non-serious adverse events,
  2. serious adverse events that are not related to the investigational drug
  3. serious adverse reactions that are expected, and
  4. when the primary efficacy endpoint is a serious adverse event, the applicant is not advised to report it as a case safety report (ICSR) to the national drug regulatory agency.
The applicant is responsible for determining whether to report serious adverse reactions related to a positive control drug to other drug manufacturers and/or directly to the China drug regulatory agency. The applicant must report such events to the drug manufacturer or directly to the regulatory agency. Adverse events related to a placebo generally do not meet the criteria for an adverse reaction and do not need to be reported.

Adaptation to ICH-E2B(R3)

The content of case safety reports for unexpected serious adverse reactions should follow the requirements outlined in the ICH “E2B(R3): Management of Clinical Safety Data – Data Elements for Transmission of Individual Case Safety Reports” and use the ICH “M1: MedDRA” to code relevant terms.
The applicant is responsible for monitoring the safety information of clinical trials and reporting serious adverse events. The applicant must appoint a dedicated person to be responsible for clinical trial safety information monitoring and serious adverse event report management, establish standard operating procedures for clinical trial safety information monitoring and serious adverse event reporting, and train all relevant personnel. The applicant must also be aware of the latest safety information during the clinical trial process, conduct timely safety risk assessments, inform relevant trial stakeholders of relevant information, and be responsible for reporting unexpected serious adverse reactions in a timely manner.

China SUSAR Reporting Deadlines

After learning of a serious adverse event, the applicant should immediately conduct a comprehensive analysis, evaluation, and judgment of the event. According to the nature (category) of the serious adverse event, the applicant should report it to the Center for Drug Evaluation (CDE), NMPA quickly within the following time limits:
  • For unexpected serious adverse reactions that cause death or endanger life, the applicant should report as soon as possible after learning of it, but no later than 7 days, and report and improve follow-up information within the following 8 days.
Note: The day the applicant first learns of the event is Day 0.
  • For unexpected serious adverse reactions that do not cause death or endanger life, the applicant should report as soon as possible after learning of it, but no later than 15 days.
The start time for quick reporting is the approval date of the clinical trial/national drug regulatory authority’s implicit permission start date, and the end time is the date of the last follow-up of the last subject in the country. Serious adverse events that occur between the end of the clinical trial or follow-up and obtaining the evaluation and approval conclusion should be reported by the investigator to the applicant, and if they are unexpected serious adverse reactions, quick reporting should also be conducted.
After the first report, the applicant should continue to track serious adverse reactions and report new information or changes to the previous report in a timely manner in the form of follow-up reports. The reporting time limit is 15 days from obtaining new information.

Fatal or life-threatening SUSAR for China

In China for fatal or life-threatening SUSAR, the applicant should report as soon as possible but no later than 7 days after the first report is made and submit a follow-up report with as much information as possible within 8 days of the first report. For subsequent reporting of new information in the form of a follow-up report or changes to the previous report, the time limit for reporting is 15 days from the date the new information was obtained.
The Center for Drug Evaluation (CDE), NMPA receives the individual case safety reports submitted by the applicant during the drug clinical trial period in an e-submission format that complies with ICH E2B (R3), and conducts analysis and evaluation. When necessary, opinions on modifying the trial plan, suspending or terminating the drug clinical trial, etc. will be put forward according to relevant standards.
In addition to individual safety reports of unexpected serious adverse reactions, the applicant should also report other potential serious safety risk information to the national drug regulatory authority as soon as possible, and make medical and scientific judgments on each situation.
Generally speaking, information that obviously affects the drug risk-benefit assessment or may consider changing the drug use, or affects the overall drug development process, belongs to this category, such as:
  1. The occurrence rate of known serious adverse reactions has increased, and it is judged to be clinically important;
  2. There is a significant harm to the exposed population, such as the drug being ineffective in treating life-threatening diseases;
  3. Significant safety findings (such as carcinogenicity) in recently completed animal experiments.
The applicant should also report unexpected serious adverse reactions related to the trial drug and other potential serious safety risk information obtained from other sources to the Chinese drug regulatory authority quickly.

SUSAR Report in Chinese Language

Both domestic and foreign individual safety reports and reports of other potential serious safety risks should be reported in Chinese.
The acceptance number of the drug application clinical trial should be clearly marked in both individual safety reports and reports of other potential serious safety risks.
Reference: 1.The Standards And Procedures for Expedited Reporting of Safety Data during Clinical Trials Announcement of the publication of the Standards and Procedures for Expedited Reporting of Safety Data during Drug Clinical Trials
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China DSUR Reporting

In China, DSUR also stands for Development Safety Update Report. China CDE opened the DSUR reporting submission channel on its official website to receive DSUR reports from drug registration sponsors on April 26, 2019,.
In 2020, overall 1775 copies of DSUR reports were submitted to CDE by the sponsors.
DSUR in China is a required regulatory document that provides a comprehensive summary of the safety profile of a drug under investigation during a clinical trial. The DSUR is submitted at regular intervals to the CDE and is intended to be a tool for ensuring that the safety of trial subjects is being appropriately monitored and that any emerging safety concerns are being addressed.
The China DSUR includes a description of any adverse events or safety issues that have been identified during the reporting period, along with an assessment of their severity and potential impact on the study or the overall safety profile of the drug. It also includes information on any changes that have been made to the trial protocol or study design, as well as any actions taken to address safety concerns or manage risks to study participants.
The DSUR is typically required for all clinical trials of investigational drugs, and may be requested by regulatory authorities at any stage of the clinical trial process. The contents are reviewed by the Chinese authorities as part of their ongoing assessment of the safety and efficacy of the drug, and may be used to inform decisions about whether to allow the clinical trial to continue or whether to require additional safety measures.

RMP (Risk Identification, Evaluation & Control) in China

RMP outlines the potential risks associated with a medicinal product and the measures that are in place to minimize or manage those risks. The purpose of an RMP is to identify, characterize, and assess the known and potential risks of a medicinal product, and to determine whether additional measures are necessary to mitigate these risks.

The Origin and Implementation of Pharmacovigilance Planning in China

As early as 12 November, 2019, the NMPA published a notice on 15 ICH guidelines (No. 88 of 2019), requiring that new drug marketing applications (NDAs) accepted three months after the date of publication, and new drug marketing applications approved six months after the date of publication starting to implement the ICH E2E: Pharmacovigilance Planning. The ICH E2E Guidelines focus on the submission of a Safety Specification and Pharmacovigilance Planning by the Regulatory Authority at the time of application for marketing authorization.

Safety Specification

The safety specification for China should be “a synopsis of important identified risks, important potential risks, and important missing information about the drug” and should begin with a summary of epidemiological information about the target indication.
Regardless of the indication and target population, a risk should be classified as important if it has the following characteristics:
  1. The risk leads to serious consequences when it occurs. such as death, disability or a serious impact on the quality of life of the person using the drug.
  2. requires a high proportion of clinical 1000 precautions.
  3. presents a significant challenge to current clinical practice. Significant risks may not affect all drug-using populations but are only highly prevalent in drug-users with certain characteristics. Applicants are advised to assess the risk causation scale, preventability and its impact on the benefit-risk balance and as an important reference for the development of risk control measures.
On July 1, 2020, the CDE published the “M4 Module 1 Administrative Document and Drug Information”, which explicitly requires applicants to submit NDA information “1.8.3 Risk Management Plan (RMP)”, including Pharmacovigilance Plan and Risk minimization Measures.
In the ICH E2E Guidelines and relevant Chinese laws, regulations, and guidelines, the terms “Pharmacovigilance Plan”, “Risk Management Plan”, and “Risk Analysis and Management Plan” are considered as one concept due to the refinement of laws and translation.

Pharmacovigilance Plan

Pharmacovigilance plans should include both:
  1. Routine pharmacovigilance activities
  2. Additional pharmacovigilance activities
If not specifically requested by the CDE, it is recommended that the first post-marketing evaluation of the pharmacovigilance programme/RMP be conducted approximately 2 years after the product is launched and may include, but is not limited to:
  1. The implementation of the pharmacovigilance plan and RMP.
  2. Whether the cumulative post-marketing data obtained influenced the judgement of product risk
  3. Whether the pharmacovigilance activities undertaken are adequate or no longer applicable
  4. The evaluation of the effectiveness of risk minimisation measures;
  5. Whether the pharmacovigilance plan and RMP affects the accessibility of the product or places an unnecessary burden on the healthcare system.
China Pharmacovigilance Plan China referencing ICH E2E as follows: Routine Pharmacovigilance Practices Routine pharmacovigilance should be conducted for all medicinal products, regardless of whether or not additional actions are appropriate as part of a Pharmacovigilance Plan. This routine pharmacovigilance should include the following:
  • Systems and processes that ensure that information about all suspected adverse reactions that are reported to the personnel of the company are collected and collated in an accessible manner;
  • The preparation of reports for Chinese regulatory authorities: Expedited adverse drug reaction (ADR) reports Periodic Safety Update Reports (PSURs)
  • Continuous monitoring of the safety profile of approved products including signal detection, issue evaluation, updating of labeling, and liaison with regulatory authorities;
  • Other requirements, as defined by local regulations.
Action Plan for Safety Issues The Plan for each important safety issue should be presented and justified according to the following structure:
  • Safety issue;
  • Objective of proposed action(s);
  • Action(s) proposed;
  • Rationale for proposed action(s);
  • Monitoring by the sponsor for safety issue and proposed action(s);
  • Milestones for evaluation and reporting.
Summary of Actions to be Completed, Including Milestones An overall Pharmacovigilance Plan for the product bringing together the actions for all individual safety issues should be presented. Whereas section 3.1.3 suggests presenting an action plan by ongoing safety issue, for this section the Pharmacovigilance Plan for the product should be organised in terms of the actions to be undertaken and their milestones. The reason for this is that one proposed action (e.g., a prospective safety cohort study) could address more than one of the identified issues.
It is recommended that milestones for completion of studies and other evaluations, and for submission of safety results, be included in the Pharmacovigilance Plan. In developing these milestones one should consider when:
  • Exposure to the product will have reached a level sufficient to allow potential identification/characterisation of the AEs/ADRs of concern or resolution of a particular concern; and/or
  • The results of ongoing or proposed safety studies are expected to be available.
These milestones might be aligned with regulatory milestones (e.g., PSURs, annual reassessment and license renewals) and used to revise the Pharmacovigilance Plan.

Post-marketing PV in China

Definition Post-marketing pharmacovigilance (PV) refers to the collection, monitoring, assessment, and reporting of adverse drug reactions (ADRs) that occur after a drug has been approved and marketed for use in the general population. Post-marketing PV activities are carried out by regulatory authorities, pharmaceutical companies, and healthcare professionals to ensure that drugs remain safe for use in the general population. The ultimate goal of post-marketing PV is to identify and minimize the risks associated with the use of medicinal products, thereby ensuring the safety and well-being of patients.
ADR Monitoring Network in China and Main Responsible Competent Authority</strong >
China’s drug adverse reaction monitoring network is divided into four levels, including the National Centre for Drug Re-evaluation (CDR), 34 provincial drug adverse reaction monitoring centres, and hundreds of municipal and county-level institutions responsible for adverse drug reaction monitoring.1 These institutions monitor and evaluate medical device-related adverse events, cosmetic adverse reactions, and drug abuse, in addition to adverse drug reactions. The role of China’s adverse drug reaction monitoring agencies has gradually been shifted to pharmacovigilance management.
At present, CADRMS incorporates a direct reporting system for ADRs for MAHs, a reporting system for ADRs for medical institutions and enterprises, a monitoring system for medical device-related adverse events, a monitoring system for adverse cosmetic reactions and a reporting system for drug abuse.2 In addition, CADRMS has functional modules for data analyses, signal detection, potential alert management and periodic safety update report management.3 In recent years, CDR has explored and constructed an active monitoring system for drug safety based on electronic medical records from medical institutions.
In 2010, the Ministry of Health and the National Medical Products Administration formulated the National Guideline for the Surveillance of Suspected Adverse Events following Immunization, which clearly outlines the reporting requirements for Adverse Events Following Immunization (AEFI) for post-approval vaccines. According to this guideline, responsible reporting units and reporters are required to report suspected AEFI to their local county-level Centre for Disease Control and Prevention agency where the vaccine recipients reside.4 China has gradually established and enhanced its AEFI monitoring information management system, and the AEFI case reporting network was completed on a national level in 2008.5 The Chinese Centres for Disease Control and Prevention established the AEFI Monitoring System, which shares information with the Drug Adverse Reaction Monitoring Agency.
Reference: 1. Zhao Y, Wang TS, Li GY, Sun S. Pharmacovigilance in China: Develop- ment and challenges. Int J Clin Pharmacol. 2018;40(4):823-831. 2. National Center for ADR Monitoring of China. The Chinese Adverse Drug Reaction Monitoring System. Available at http://www.adrs.org.cn/. 3. Song HB, Shen C. Thoughts on the use of electronic health data in the safety research of marketed drugs. China Food Drug Administrat Mag. 2020;36-47. 4. National Surveillance Program for Suspected Abnormal Response of Vaccination. Chin J Vacc Immun. 2011;17:72-81. 5. Liu DW, Wu WD, Li KL, et al. Surveillance of adverse events following immunization in China: Past, present, and future. Vaccine. 2015; 33(32):4041-4046.
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Individual Adverse Drug Reactions Reporting and Monitoring in China

What is an Individual Case Safety Report (ICSR) in China?

So, what is an ICSR? According to the ICH E2 series of related guideline documents ICSRs are complete information provided by the reporter at a point in time to describe an event or incident of concern. The report may include information relating to a subject or a group of subjects.
According to Chinese Guidelines for the Collection and Reporting of Individual Adverse Drug Reactions1 A valid report is defined to be consisted of following four elements:
  • Identifiable patient
  • Identifiable reporter
  • Suspected drug
  • Adverse reaction.
If all four elements are incomplete, the report is considered invalid and should be added before reporting. “Identifiable” means that the presence of the patient and the reporter can be confirmed. A patient is considered identifiable when one or more of the following are available: name or initials, sex, age (or age group, e.g., adolescent, adult, elderly), date of birth, other identifying code for the patient. The initial reporter who provided the case information or the relevant person contacted to obtain the case information should be identifiable. For case reports from the Internet, the identifiability of the reporter depends on the ability to verify the existence of the patient and the reporter, e.g., by providing a valid email address or other contact information.
Reference: 1. Guidelines for the Collection and Reporting of Individual Adverse Drug Reactions, Announcement by the NMPA on the Issuance of Guidelines for the Collection and Reporting of Individual Adverse Drug Reactions (No. [2018] 131)
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Sources & Collection of Adverse Events in China

According to China GVP1, cases are collected from different sources:
Medical Institutions
Approach like visits, email, telephone, and fax to collect information on AE occurring in clinical settings from medical personnel on a regular basis, keep detailed records, and establish and maintain an adverse drug reaction information file. Doctors could also inform the AE information collected from the patients to the Medical representative who subsequently inform the MAH.
Drug Distributors
The holder or its distributor should ensure that the pharmaceutical retailer is aware of the effective ways to report AE to it, develop an AE collection plan, and train the pharmacist or other personnel based in the pharmacy, I.e., Pharmacist received AE information feedbacked from the patient that purchased drug on this pharmacy. The pharmacy then send email to PV public mail or call the hotline number for AE complaint.
Phone calls & Complaints
Calls from the patient that saw the hotline indicated in either Package Insert or outer packaging of the drug or on the MAH websites.
Academic Literature
AE information identified through literature filtered in literature databases (from literature screening process)
Internet Relevant Channels
MAH should regularly visit the websites they sponsor or manage to collect possible cases of AE. In principle, MAH are not required to search external websites, but if MAH are informed of AE in external websites, they should assess whether to report them.
The MAH should use the company website/portal to collect information on AE, i.e., by creating a dedicated pathway for ADR reporting on the website, providing guidance on how to report, reporting forms and reporting content, and publishing complete and up-to-date product instructions. Graphic media, digital media, social media/platforms initiated or managed by the MAH are also a source of individual adverse drug reactions, i.e., collected using corporate social medial (i.e. Instagram or WeChat public accounts, microblogs, forums, etc.
Post-marketing Research & Projects
Individual AE identified in post-marketing studies (including those conducted outside of China) or organised data collection projects initiated by the company should be reported as required, such as clinical trials, non-interventional epidemiological studies, focused drug monitoring, patient support projects, market research or other marketing projects, etc. AE identified in post-marketing studies or projects should, in principle, be reported by the MAH to the regulatory authority, but the holder shall not interfere with the reporting behaviour of the study or project collaborators for any reason or by any means.
Regulatory Authority
If consumer or healthcare professional directly report adverse events to regulatory authority (i.e., FDA, EMA etc..) not to marketing holder (pharmaceutical company), then those reports will be shared to marketing holders by regulatory authorities. This type of cases which were received by companies from regulatory authority are to be handled as regulatory authority cases. Feedback cases downloaded from the ADR monitoring system.
Reference:
1. China Good Pharmacovigilance Practice Announcement of the NMPA on the Publication of China Good Pharmacovigilance Practice (No. 65 of 2021)Should you have any queries or seeking for consultation, please contact us via online chat or email.

Spontaneous AE Reporting in China

A spontaneous report is a direct communication of adverse event information by healthcare professionals or consumers to a company, regulatory authority, or other organization (e.g., WHO, Regional Centres, Poison Control Centre).
Reporting to Pharmaceutical companies: We can even report events directly to manufacturer of product by sending emails/fax or by telephone (details are available in google), some companies have call centres to collect adverse events.
The Call centre personnel received reporting of an AE/AEs from call or an email from a patient’s relative. After an initial confirmation of the case authenticity and validity assessment i.e., the report has identifiable reporter information, an identifiable patient, suspect product/s and AEs, the report will be triaged to PV personnel for further processing.
PV team collect the reported events and perform below assessments (using global sponsor’s database for processing and manual submission to RA):
  • Initial seriousness of the event was evaluated
  • Assess the reason for event occurrence
  • Understanding if it is new event or already known information
  • The source document that includes all the communication contents and reporting information will be translated (if necessary)
  • Input collected report information in the PV safety database and attaching the source doc + exercise due diligence schedule to collect missing if necessary
  • Fill out the information collected as shown below (ArisG System database used for example)
  • General information, patient information, protocol/project information (for Research and clinical trial products), product information, adverse event, reporter information
  • After initial review of the case processing workflow, the report will be going to next workflow where it is further reviewed and narrative will be written in medical format, the events are coded using Medical Dictionary for Regulatory Activities (MedDRA), causality is assessed, eventually releasing completed CIOMS I form.
  • Submitting information to regulatory authority based on the translated CIOMS form
  • Save the receipt of submission report (pdf) in local file for inspection/audit purposes.
  • Update the tracker.
Should you have any queries or seeking for consultation, please contact us via online chat or email.

Feedback Case Reporting in China

Log in the ADR monitoring system.
Click the feedback data button and download the feedback data in excel form
Translate into English to generate an ICSR with all the safety information (if applicable), Input in the PV Safety database and then following the process the same as that of Spontaneous case reporting until the submission to RA completed.
Should you have any queries or seeking for consultation, please contact us via online chat or email.

Regulatory Submission

Per the GVP requirement, Spontaneous and feedback case reports can be submitted through ADR monitoring system either manually or through the National Safety Database that is completed interface with the ADR monitoring system.
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Medical Review & Narrative Writing

Medical review and narrative writing are crucial components of pharmacovigilance. Medical review involves analysing the safety data generated from clinical trials or post-marketing surveillance to identify potential safety signals and assess the overall benefit-risk profile of a drug. This process requires a deep understanding of the drug’s mechanism of action, clinical pharmacology, and the medical condition it is intended to treat. Medical reviewers must be able to critically evaluate adverse event reports and determine their causality, seriousness, and expectedness. They also need to assess the impact of the adverse event on the patient’s health and well-being and determine if any additional monitoring or risk minimization measures are necessary.
Narrative writing involves summarizing the relevant clinical and safety information in a concise and coherent manner to provide a clear picture of the patient’s medical history and the circumstances surrounding the adverse event. A well-written narrative should provide a chronological account of the patient’s medical history, including any relevant comorbidities, concomitant medications, and previous drug exposure. It should also describe the onset and progression of the adverse event, including the time to onset, duration, and severity, as well as any interventions or outcomes. The narrative should be clear, concise, and free of ambiguity or unnecessary detail.
Effective medical review and narrative writing are critical for identifying and managing potential safety risks associated with drugs. Medical reviewers and writers must be highly trained professionals with a strong background in pharmacology, clinical medicine, and data analysis. They play a vital role in ensuring the safety of patients and the continued success of drug development programs.
Should you have any queries or seeking for consultation, please contact us via online chat or email.

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 comprehensive assessment of the worldwide safety data of a marketed drug. Over-time it was 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 GVP1,
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.
Reference: 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)
Should you have any queries or seeking for consultation, please contact us via online chat or email.</strong >

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?</strong > 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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Signal Management in China: An Overview of Regulatory Requirements

Overview of Signal Management

Signal Management is a set of activities performed to determine whether, based on an examination of individual case safety reports (ICSRs), aggregated data from active surveillance systems or studies, scientific literature information or other data sources, there are new risks associated with an active substance or a medicinal product or whether known risks have changed, as well as any related recommendations, decisions, communications, and tracking.The Signal Management consists of
  • Signal Detection
  • Signal Validation
  • Signal Prioritization
  • Signal Assessment

Regulatory Guidance of Signal Management

According to China GVP1, the scope and requirement for signal management is listed below:
Chapter V Risk Identification and Assessment Section 1 Signal Detection
Article 55 The holders should carry out signal detection on the suspected adverse drug reaction information collected through various channels to discover new drug safety risks in a timely manner.
Article 56 The holders should select an appropriate, scientific, and effective signal detection method according to its own situation and product characteristics. The signal detection methods can be manual detection methods such as individual adverse drug reaction report review, case series evaluation, and case report summary analysis, or computer-aided detection methods such as data mining.
Article 57 The frequency of signal detection shall be reasonably determined according to relevant factors such as the time of drug marketing, drug characteristics, and risk characteristics. For newly marketed innovative drugs, improved new drugs and other varieties that attention required by the drug regulatory authorities or drug adverse drug reaction monitoring authority, at or above the provincial level, the frequency of signal detection shall be increased.
Article 58 When carrying out signal detection, the holders should pay special attention to the following signals:
  1. Adverse drug reactions not mentioned in the drug package insert, especially serious adverse drug reactions.
  2. Adverse drug reactions mentioned in the drug package insert, but the frequency of occurrence、 severity,etc. have increased significantly.
  3. Suspected new adverse drug reactions caused by drug-drug, drug-device, and drug-food interactions.
  4. Suspected new medications in special populations or changes of medications in known special populations.
  5. Suspected adverse reactions show clustering characteristics, and the correlation with drug quality cannot be ruled out.
Article 59 The holders shall determine the priority of signals, and prioritize the evaluation of signals that may affect the benefit-risk balance of the product or have an impact on public health. The following factors can be considered for signal priority determination:
  1. The seriousness, severity, outcome, reversibility, and preventability of adverse drug reactions;
  2. Patient exposure status and expected frequency of adverse drug reactions;
  3. Patient exposure in high-risk populations and populations with different medication modes;
  4. The impact of interruption of treatment on patients and the availability of other treatment options;
  5. Anticipated risk control measures that may be taken;
  6. Signals applicable to other same class drugs.
Article 60 The holders shall comprehensively summarize relevant information, evaluate the detected signals, and comprehensively determine whether the signals constitute a new drug safety risk. Relevant information includes individual adverse drug reaction reports ((including feedback reports from adverse drug reaction monitoring agency), clinical study data, literature reports, epidemiological information on adverse drug reactions or diseases, non-clinical study information, medical database information, relevant information released by drug regulatory authority or adverse drug reaction monitoring agency, etc. If necessary, the holders can obtain more information by conducting drug post-marketing safety studies, etc.
Article 61 If the holders aware of or discovers that multiple suspected adverse reactions with similar clinical manifestations in the same batch of the same drug (or adjacent batches) in a short period of time, presenting clustering characteristics, a case analysis and investigation shall be carried out in a timely manner.
Reference: 1. China Good Pharmacovigilance Practice Announcement of the NMPA on the Publication of China Good Pharmacovigilance Practice (No. 65 of 2021)
Should you have any queries or seeking for consultation, please contact us via online chat or email.

Responsible Person for PharmacoVigilance (RPPV)

The Qualified Person for Pharmacovigilance (QPPV) is a key role in the field of drug safety and regulatory compliance. The QPPV is responsible for overseeing the pharmacovigilance system of a pharmaceutical company or a marketing authorization holder, ensuring that all adverse events and safety issues related to their products are effectively monitored, evaluated, reported and managed in compliance with relevant regulations.
The QPPV acts as the main point of contact between the company and regulatory authorities, providing oversight and guidance to their team of pharmacovigilance professionals. They are responsible for ensuring the safety of the company’s products throughout their lifecycle, from clinical trials to post-marketing surveillance.
The QPPV must have a thorough understanding of the company’s products and the regulations governing their use, as well as the ability to effectively communicate safety information to both internal and external stakeholders. They must also maintain a continuous monitoring of safety data and emerging safety concerns, and ensure that appropriate actions are taken in a timely manner to protect patient safety.
In China the similar role is named Responsible Person for Pharmacovigilance (RPPV). The main scope, responsibility, and regulatory requirement of RPPV is illustrated in China GVP.
See also Comparison of EU-QPPV and China RPPV Section for more detailed China RPPV requirement.
Should you have any queries or seeking for consultation, please contact us via online chat or email.

Pharmacovigilance Audit and Inspections in China

Internal Audit

Pharmacovigilance audit is a vital process that reviews the drug safety system to ensure it meets regulations, guidelines, and standard operating procedures. It involves internal or external auditors who are independent of the system. Internal auditors, part of the safety or quality assurance team, conduct periodic reviews, while external auditors provide an objective assessment.
The audit evaluates various aspects, including the organizational structure, standard procedures, safety database, signal detection, risk management, and adverse event reporting. It assesses data quality, identifies system gaps, and provides recommendations for improvement.
Compliance with regulations and guidelines is a key focus of pharmacovigilance audits. The audit team ensures adherence to Good Pharmacovigilance Practice (GVP) and International Council for Harmonization (ICH) guidelines, ultimately enhancing drug safety. China GVP also described the audit requirement1:
Chapter II Quality Management Section 2 Internal Audits
Article 11 Holders shall conduct periodic internal audits (hereinafter referred to as “internal audits”) to review various systems, procedures, and their implementation status, and to assess the suitability, adequacy, and effectiveness of the pharmacovigilance system. When any significant changes occur to the pharmacovigilance system, internal audits should be carried out in a timely manner. The internal audit can be carried out independently, systematically, and comprehensively by the holder’s designated personnel, or by external personnel or experts.
Article 12 An audit plan shall be developed before the internal audit. The plan should include internal audit objectives, scope, methods, standards, auditors, audit records and reporting requirements, etc… While developing the plan, key pharmacovigilance activities, key positions, and previous audit results, etc. should be considered.
Article 13 Records shall be kept for internal audits, including the basic information, content and results of the audit, and a written report shall be formed.
Article 14 For the findings identified in the internal audit, holders shall investigate the root cause and take corresponding corrective and preventive actions. The corrective and preventive actions should be followed-up and assessed.
Reference: 1. China Good Pharmacovigilance Practice Announcement of the NMPA on the Publication of China Good Pharmacovigilance Practice (No. 65 of 2021)
Should you have any queries or seeking for consultation, please contact us via online chat or email.

Regulatory Inspections

The overarching authority responsible for drug and pharmacovigilance inspections is China’s National Medical Products Administrations (NMPA). The pharmacovigilance audit and inspection work are conducted in groups formed by the Drug Inspection Institutions. The complete inspection is fulfilled with the support of the following four institutions:
  • Drug Testing Institutions
  • Centre for Drug Evaluation (CDE)
  • Centre for Drug Reevaluation (CDR)
  • National Centre for ADR Monitoring.
In addition, the legal departments will be involved upon legal issues.

Authority for Supervision of Drugs

  • NMPA and Local MPA including Provincial, Municipal, and County level are responsible to set up and designate pharmaceutical and pharmacovigilance inspection institutions in accordance with law.
  • NMPA shall be responsible for forming annual supervision and inspection plan, arranging inspection tasks, or organizing inspections, and work according to the Report on Comprehensive Evaluation of Drug Inspection and relevant evidence materials.
  • NMPA shall set up a professional team of specialized drug inspectors, implement multi-level & classification system for inspectors, formulate the standards of duties and duties of inspectors at different levels as well as requirements for comprehensive capability, and establish strict criteria for relevant positions.
  • NMPA and the drug inspection institution is responsible for establishing inspector database and inspector information platform to realize the information sharing and coordination of inspectors at all levels from national to county-level.

Institutions for Drug Inspection

  • Drug inspection institutions carry out inspections according to China’s laws and regulations on drug supervision before issuing the Comprehensive Evaluation Report on Drug Inspection and be responsible for daily management of professional inspector team and implementation of inspection plans and tasks.
  • Other departments such as drug inspection, review, evaluation, and adverse drug reaction (ADR) monitoring established shall provide technical support during the inspection.
  • Drug inspection institutions shall establish a quality management system to continuously improve the quality of drug inspection work.
  • The drug supervision authority or drug inspection institution is responsible for establishing inspector database and inspector information platform to promote the information sharing and coordination of inspection within national, provincial, and county levels.

Drug Inspection Group

  • The inspection group should be set up by the pharmacovigilance inspection team to carry out the audit.
  • Usually, an inspection group consists of more than 2 qualified inspectors
  • The team leader is responsible for the inspection team. When necessary, experts in relevant fields can be selected to participate in the inspection

Authority Inspection Key Points

According to Guidelines for Pharmacovigilance Inspections1 released by the NMPA, a total of 100 checking items are listed. 12 of which are critical and 40 are major points.
This is the 5 key points for authority inspection.
  • Institution, personnel and resources, refers to 22 articles from GVP
  • Quality management, documentation and record, refers to 28 articles
  • Monitor and report, refers to 17 articles.
  • Risk identification and evaluation, refers to 19 articles.
  • Risk control, refers to 14 articles.
Throughout the first year of 2022, the authorities overseeing drug testing, review, evaluation, and adverse drug reaction (ADR) monitoring focused their attention primarily on the first two points. These areas were given priority due to their direct accessibility and evaluative nature. In addition, the authorities made efforts to understand the operational practices within pharmaceutical companies. As we enter 2023, inspection groups have gained valuable experience, which will be reflected in their increased emphasis on activities such as signal detection, reporting, and risk control, among others.
The following is part of Pharmacovigilance Inspection Check Points in the official Guidelines for Pharmacovigilance Inspections.
For full PDF (original Chinese and English translated version) of Guidelines for Pharmacovigilance Inspections and the Annex – Pharmacovigilance Inspection Check Points Table, please contact us via online chat or email.
Reference: 1. Guidelines for Pharmacovigilance Inspections, Announcement by the NMPA on the issuance of the Guidelines for Pharmacovigilance Inspections No. [2022] 17

Literature Screening

Definition

Literature report is any adverse drug reactions reported in
  • Published abstracts or
  • Articles in medical/scientific journals
  • Unpublished manuscripts involving case reports
  • Important safety findings or clinical studies including posters, letters to the editors, and associated communication from scientific meetings.

Regulatory Guidance of EMA and FDA

According to the European Medicines Agency (EMA), marketing authorization holders (MAHs) are obligated to monitor scientific and medical publications in countries where they have marketing authorization, regardless of the commercial status of their products.
In the United States, the Food and Drug Administration (FDA) requires the submission of reports on serious and unexpected adverse drug reactions (ADRs) described in scientific literature for products with the same active ingredient as those marketed in the US, even if there are variations in excipients, dosage forms, strengths, routes of administration, and indications.
The “literature” section of the periodic benefit-risk evaluation report (PBRER) necessitates a summary of significant safety findings from published peer-reviewed scientific literature or unpublished manuscripts during the reporting period.
EMA guidelines also mandate the inclusion of relevant safety information for other active substances within the same class as the marketed drug. Therefore, any potentially significant event identified in the literature may be considered an emerging safety issue, requiring immediate analysis and, if necessary, corrective and preventive action.
Marketing authorization holders are expected to stay informed about possible publications through systematic literature reviews of widely used reference databases, such as Medline, Excerpta Medica or Embase, and Eudravigilance, at least once a week.
Each MAH should regularly screen global scientific literature using widely used systematic reviews or reference databases, adhering to local requirements or at least every two weeks.
Cases of ADRs reported in scientific and medical literature, including relevant abstracts from meetings and draft manuscripts, may qualify for expedited reporting. A regulatory reporting form with relevant medical information should be completed for each identifiable patient, citing the publication reference(s) as the source of the report. Additionally, the local regulatory authority may request a copy of the article to accompany the report. All company offices are encouraged to stay vigilant regarding publications in local journals and inform the company’s safety department when necessary.
The regulatory reporting timeframe begins as soon as the MAH becomes aware that the case meets the minimum criteria for reportability.
If the specific product source, brand, or trade name is not specified, the MAH should assume that it pertains to their product, while indicating in the report that the specific brand was not identified.
If multiple products are mentioned in an article, a report should only be submitted by the applicant whose product is suspected, as determined by the article’s author.

Regulatory Guidance of China NMPA

Per the China GVP1, MAH’s responsibility relative to ICSR generated from the literature is depicted as below:
Chapter IV Monitoring and Reporting Section 1 Collection of Information
Article 36 The holder shall conduct periodic screening on academic literatures, develop rational screening strategy and determine the frequency of such screening according to the safety characteristics of the product, etc., and the time range of the searches shall be continuous.
Chapter IV Monitoring and Reporting Section 3 Submission of Report
Article 50 For adverse drug reactions reported in the literature, if the suspected drug is the holder’s product, the reaction shall be reported as an individual adverse drug reaction. If it is uncertain whether it is the holder’s product, the reaction shall be analyzed in the periodic safety update report and may not be reported as an individual adverse drug reaction.

Processing of Confirmed ICSRs

  1. For literature reports of confirmed cases which can generate ICSRs, a full text of the citation is obtained and, if not in English, translated into English though it is not specified how/who does this or how long this takes).
  2. The article is reviewed and the number of valid ICSRs is determined, and seriousness/non-seriousness is noted.
  3. An ICSR is then created along with a case narrative for serious cases. No narrative is prepared for non-serious ICSRs.
  4. Causality assessment and relatedness also performed.
A regulatory reporting form with relevant medical information should be provided for each identifiable patient. The regulatory reporting time clock starts as soon as the MAH has knowledge that the case meets minimum criteria for reportability.
Reference: 1. China Good Pharmacovigilance Practice Announcement of the NMPA on the Publication of China Good Pharmacovigilance Practice (No. 65 of 2021)
Should you have any queries or seeking for consultation, please contact us via online chat or email.

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:
  1. Organizational structure: describe the organizational structure, responsibilities and mutual relationships related to pharmacovigilance activities;
  2. Basic information of the pharmacovigilance responsible person: including residential region, contact information, resume, responsibilities, etc.;
  3. Staffing of full-time personnel: including the number of full-time personnel, relevant professional backgrounds, responsibilities, etc.;
  4. Sources of information on suspected adverse drug reactions: describe the main channels and methods of information collection on suspected adverse drug reactions;
  5. IT tools or systems: describe IT tools or systems used to carry out pharmacovigilance activities;
  6. 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;
  7. The operation of the pharmacovigilance system: describe the monitoring and reporting of adverse drug reactions, and the identification, assessment and control of drug risks;
  8. Entrustment of pharmacovigilance activities: specify the content and time limit of entrustment, entrusted unit, etc., and provide a list of entrustment agreements;
  9. Quality management: describe the quality management of pharmacovigilance, including quality objectives, quality assurance systems, quality control indicators, internal audits, etc.;
  10. 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)
Should you have any queries or seeking for consultation, please contact us via online chat or email.

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:
  1. 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;
  2. 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;
  3. 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.
See also Management System – PSMF
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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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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Comparison Between China PV and Europe PV

Comparison of China GVP and EMA GVP

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.
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China PSMF vs EMA PSMF

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.
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Responsible Person for Pharmacovigilance – A Thorough Analysis of Current China “QPPV” System

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.

Analysis of QPPV Position Requirements in China – General Requirements for QPPV Qualifications

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.

Analysis of QPPV Position Requirements in China – Professional and Technical Responsibilities of QPPV

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.

Comparison of QPPV Positions between China and the European Union – Qualifications for Appointment

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.
QualificationChina RPPVEU-QPPV
Educational Backgraound Bachelor or Mid-level and above Technical Titles University/College
Major Medicine, Pharmacy, Epidemiology or related majors Medicine, Pharmacy, Epidemiology, Biostatistics and others
Knowledge/Skill Familiar with China’s pharmacovigilance-related laws and regulations and technical guidelines, with knowledge and skills in pharmacovigilance management Familiarity with EU pharmacovigilance requirements
Experience At least three years of experience in pharmacovigilance related work Experience in pharmacovigilance required
Roles Managerial positions May be an independent individual, not mentioned as requiring a managerial position
Residence not mentioned, generally within China Norway, Iceland, or Liechtenstein
Personnel Attibute Not mentioned if non-MAH employee is allowed MAH Employee or Entrusted
Table 1 Comparison of QPPV Qualification between China and EU.

Comparison of QPPV Positions between China and the European Union – Job Responsibilities

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.

Outsourcing Analysis of QPPV – Current Human Resources Situation of QPPV in China

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.

Outsourcing Analysis of QPPV – Relevant Regulations on Pharmacovigilance Agreements

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
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Individual Safety Case Report

NMPA

Reporting timelines:
  • Fatal ADRs: immediately (For cases received during the weekend, submit within next business day, no later than Day 3)
  • Other serious ADRs: within 15 calendar days
  • Non-serious ADRs: within 30 calendar days.

EMA

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.

FDA

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.

MAH Responsibility

MAH responsibilities elucidated in China GVP

China GVP1 predominantly emphasizes the responsibilities of the Marketing Authorization Holder (MAH), as a substantial portion of its articles are dedicated to the comprehensive obligations.
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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Local Representative of Overseas MAH

The NMPA published Interim Provisions for the Administration of Local Representatives of Overseas Marketing Authorisation Holder1 as the guidance provision for Local Representative of Overseas MAH
Basic requirements for becoming a MAH local representative
Based on the relevant requirements of the Drug Administration Law and the Interim Provisions,we have sorted out the two basic requirements for foreign holders to appoint domestic agents: corporate legal person and legal responsibility.
  • An enterprise legal person established in China. It can be a subsidiary, but not a branch, not a branch of a foreign company set up in China.
  • Legal liability: Article 136 of the Drug Administration Law If the holder of a drug marketing licence is an overseas enterprise, and its designated enterprise legal person in China fails to fulfil the relevant obligations in accordance with the provisions of this Law, the provisions of this Law concerning the legal liability of the holder of the drug marketing licence shall apply: i.e. civil liability, administrative liability, criminal liability, etc.
Liability as a MAH local representative
The new Drug Administration Law and the Interim Provisions further clarify the responsibility for quality and safety throughout the life cycle of a drug. The liability is borne by the MAH local representative
At present, large multinational pharmaceutical companies have set up their head offices outside of China, and one or more branch companies are usually responsible for registration, commercial representation, and pharmacovigilance representation in China, while small and medium-sized overseas pharmaceutical companies usually perform the above-mentioned duties through pharmaceutical business enterprises in China. According to the “Drug Administration Law” and the “Interim Provisions” requirements, the overseas MAH can only appoint a representative to perform its duties, which requires the domestic agent for registration, production, distribution, quality, customs, pharmacovigilance and a series of performance of the integration, and its responsibility for the entire process in the territory.
The relationship between the two is reflected in the obligations to be performed by the ” MAH local representative “
1. Responsible for establishing a drug quality assurance system to ensure that it has continuous quality assurance and risk control capabilities. Enterprises need to develop a quality assurance system document that meets their business needs and can be effectively implemented to cover the entire life cycle of the agent’s medicines.
2. Responsible for establishing and implementing a drug traceability system and providing traceability information in accordance with regulations to ensure that the whole process of the relevant listed drugs can be traced. The regulatory authority has made it clear in 2018 that it will take the lead in establishing a drug information traceability system for key varieties such as vaccines, narcotic drugs, psychotropic drugs, easily controlled chemical drugs and blood products, and has pointed out in 2020 that it will basically achieve traceability of key varieties by 31 December 2020. Domestic agents are required to establish a drug traceability system, and according to the general principle of “one item, one code, one code, one trace”, they can build their own traceability system or commission a third-party technical institution to build one, and assign a unique traceability mark to all levels of drug packaging units in accordance with the unified drug traceability code requirements.
For overseas MAHs, how and where to assign the code, the assignment of the code to the overseas production plant or the assignment of the code in the free trade zone, the printing requirements of the traceability code and the display of the traceability code consumer query results are topics that need to be discussed separately.
3. responsible for the establishment and can implement the drug annual report system, on behalf of the overseas holder will be confirmed by the overseas holder each year after the relevant drug production and sales in China, post-marketing research evaluation, risk management and other information in accordance with the provisions of the provincial drug supervision and management department where the agent is registered. The NMPA has recently issued the Regulations on the Administration of Annual Reports of Pharmaceutical Products, in which it is clarified that “if the holder is an overseas enterprise, the enterprise legal person (domestic agent) designated by it in accordance with the law to assume joint and several responsibilities in China shall perform the annual reporting obligations”. At present, the State does not specify the agency filing requirements for domestic agents, but the Regulations on the Administration of Annual Reports of Pharmaceutical Products show that the holder of an overseas listing permit can designate a domestic corporate legal person to fill in the information, and the corporate legal person has to bind the drugs held by the overseas listing permit holder, and a drug can only be bound by one domestic agent, and if there is a change in the agency, the original corporate legal person has to unbind the drug and unbind the new domestic agent. If there is a change in the agency practice, the original corporate entity will have to unbind the medicine and the new MAH Local representative will be re-bound. The basis for the binding is the submission of proof of agency status by the MAH Local representative, such as the enterprise information and power of attorney of the unit.
4. Responsible for the establishment of a post-marketing change management system for pharmaceutical products and for handling changes in strict accordance with the regulations. In January 2021, the S The NMPA issued the “Measures for the Administration of Post-marketing Changes to Medicines (for Trial Implementation)”. In the requirements for reporting information, it can be understood that if a drug is manufactured outside China and the overseas holder appoints an enterprise in China to act as MAH local representative for the relevant drug registration matters, it should provide a power of attorney and notarized and certified documents with Chinese translation, as well as a copy of the business license of the registered representative in China.
5. Undertake matters such as post-marketing recall, quality complaint handling and quality compensation of drugs, and report to the provincial drug supervision department where the representative is registered as required. According to the Measures for the Administration of Drug Recalls (Draft for Public Comments), which was again made available for public consultation in 2021, in relation to the recall of drugs manufactured outside China involving implementation within the country, the designated enterprise legal person within China shall organise the implementation in accordance with the provisions of the Measures. In the case of a drug recall implemented outside China only that does not involve a domestic drug variety or batch, the designated corporate entity in China will report the recall information to the drug regulatory authority. And the designated domestic corporate entity will carry out the website publication of the recall information and act as the recipient of the service of the recall order notice.
6. It is responsible for establishing a pharmacovigilance system, formulating a post-marketing risk management plan for drugs, and carrying out monitoring, identification, assessment and control of post-marketing adverse drug reactions and other harmful reactions related to drug use as required. MAH local representative is required to establish and carry out pharmacovigilance quality systems and activities within their enterprises in accordance with the Pharmacovigilance Quality Management Code and the Pharmacovigilance Inspection Guidelines. As a domestic agent, you can carry out pharmacovigilance work on your own or commission pharmacovigilance-related work according to the actual situation of your company. It is required to have the ability to collect information on drugs outside of China and to promptly report the suspension of sales, use or withdrawal of drugs from the market due to safety reasons.
7. Responsible for submitting standard substances to the China Academy of Food and Drug Administration in accordance with relevant regulations, and accepting sampling tests organised and carried out by the drug regulatory authorities. When the drug agent accepts the sampling and testing requirements of the drug regulatory authorities, the domestic agent is responsible for submitting the standard substances and cooperating with the relevant work.
8、Responsible for liaising with the overseas holder and cooperating with the drug regulatory authorities to carry out inspections, investigations and investigation of violations of the law at the production site of the overseas holder. In summary, as a domestic agent, there will be multiple identities in the act of representation, which may be both the customs service provider of the represented pharmaceutical product, the domestic sub-package manufacturer of the represented pharmaceutical product, or its domestic business distribution enterprise. Regardless of the identity, as a domestic agent itself, you need to have comprehensive quality assurance capabilities, as well as the ability to perform under different regulatory areas, and even if you outsource some of the functions, you need to have the ability to manage the third party entrusted to you in order to control the risks and achieve mutual benefits for both parties.
Reference: 1. Public consultation request for “Interim Provisions on the Administration of Local Representative for Overseas Marketing Authorisation Holder” by the General Department of the NMPA 2. https://www.ciopharma.com/article/explain/497
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PV Safety Databases

ArisG Safety Database
ArisG1 uses artificial intelligence to automate case processing, facilitate decision-making and make safety workflows more efficient. It is a cloud-based solution that allows for easy updating to new regulatory standards and global PV teams to operate in one real-time system. You can visualize reporting measures and quickly generate compliance and local or regional regulatory reports. The safety database can be configured to individual client’s needs, the medicinal product(s), studies, reporting requirements etc.
features include:
  • Global cloud-based access with real-time review of cases
  • Automated coding
  • Automated duplicate checks
  • Automated validity and triage of cases
  • Configuration of client-based SOPs, workflows, review and reporting procedures
  • Integration with other PV systems, such as safety signal management
  • Automated case tracking and follow-up
  • Real-time benefit-risk analysis
  • Global automated submission options
Argus Safety Databases
Argus Safety is a comprehensive global safety database that leverages automation to streamline case processing and generate in-depth analytics and reporting. The platform is highly customizable and can be tailored to meet the unique needs of each client, including dynamic workflows and specific reporting rules. It can also integrate seamlessly with third-party or internal pharmacovigilance systems. By providing automated distribution and submission of reports, Argus Safety ensures regulatory compliance through the configuration of specific rules appropriate to the respective medicinal product(s) and offers reporting and compliance metrics to its users. Additionally, features such as automated reporting, document storage, and integration with safety signal detection and management make it an essential pharmacovigilance safety database. The ability to update the drug safety profile and integrate it into risk management decision-making further enhances its value. Other key features of Argus Safety include worldwide cloud-based access, automation-assisted case processing, duplicate control, case tracking, configuration for regional regulatory requirements, client-based rules for SOPs, workflows, review and reporting procedures, automated submission options, options for integration with other PV processes, and audit trails to ensure data accuracy and compliance.
Chinese Safety Databases
Regarding Chinese Local Safety Databases, sophisticated supplier like TAIMEI is the most popular on the market due to its strength in localization of electronic transmission with China local regulatory authories and facilitation of communication channels. However the local supplier may also experience challenges and encounter limitations on providing the Exhaustive resolution to meet the regulatory requirement.
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FAQs

Case Reporting (ICSR Reporting)

What are the requirements for reporting overseas adverse drug reactions (ADRs) in pharmacovigilance?</strong > According to the Provision for Adverse Drug Reaction Reporting and Monitoring (Order No.81 of the Ministry of Health), for Serious adverse drug reactions (including those collected by the spontaneous reporting system, those found in post-marketing clinical studies and those reported in the literature) occurring overseas for both imported and domestic drugs shall be reported to the National Adverse Drug Reaction Monitoring Centre (NADRMC) within 30 days from the date of notification. If the National Adverse Drug Reaction Monitoring Centre requires the original report and related information, the MAH shall submit it within 5 days.
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Responsible Person for Pharmacovigilance (RPPV) in China

Who can serve as a RPPV in China?
According to China GVP, Article 24 The pharmacovigilance responsible person shall be in certain managerial positions, have a medical, pharmaceutical, epidemiology or relevant professional background with a bachelor degree and above or with a professional technical title of mid-at level and above, have an experience in pharmacovigilance-related work for more than 3 years, be familiar with China pharmacovigilance-related laws, regulations and technical guidelines, and have the knowledge and skills to manage pharmacovigilance work.
The pharmacovigilance responsible person shall be registered in the National Adverse Drug Reaction Monitoring System. If the relevant information is changed, the pharmacovigilance responsible person shall complete the update within 30 days from the date of the change.
What are the responsibilities of a RPPV in China? Per China GVP Article 25, The pharmacovigilance responsible person is responsible for the operation and continuous improvement of the pharmacovigilance system, ensuring that the pharmacovigilance system meets the requirements of relevant laws, regulations, and this practice. The main responsibilities of this person include:
  1. To ensure compliance of adverse drug reactions monitoring and reporting;
  2. To oversight the identification, assessment and control of drug safety risks and ensure the effective implementation of risk control measures;
  3. To be responsible for the management of drug safety information communication and ensure timely and effective communication;
  4. To ensure smooth communication channels within the holders and with the drug regulatory authorities and the drug adverse reaction monitoring authorities;
  5. To be responsible for the review or sign-off of important pharmacovigilance documents.
Normally the transnational corporations have global PV system, so can the QPPV from headquarter play the role of QPPV in China and does China NMPA require QPPV shall be reachable 24 hours?</strong > In China, it’s called Responsible Person for Pharmacovigilance, which equals to QPPV. There is no specific requirement that only persons based in China can take the role of RPPV. But practically speaking, it is recommended to assign a person based in China to be local RPPV and keep contact available always so that authorities can reach the RPPV when necessary.
Can the leader of PV or QA Department play the role of QPPV?</strong > According to NMPA experts, it is not suggested to assign department managers, like PV or QA department, to be RPPV/QPPV because it’s required that the lead of PV shall have enough power to control PV activities and make decision in the company, like vice president. However, every company may have different situation to appoint the RPPV, but the key is the continuous training on the appointed person and RPPV is not just a role with title.
Reference: 1. China Good Pharmacovigilance Practice (GVP) Announcement of the NMPA on the Publication of China Good Pharmacovigilance Practice (No. 65 of 2021)

Pharmacovigilance Inspection

How is the inspection performed? China National Medical Products Administration (NMPA) is the leader who designate or set up the inspection institutions and assign inspectors to support local MPAs. With practical assistance of provincial MPA, they build inspector information platform together and then assign inspection team to actually conduct the on-site inspection in pharma companies. The lower tiers of MPA can apply inspector supports from the higher authority. The inspection team is consisted of inspectors from centers for drug control/testing, evaluation for approval, reevaluation, and ADR monitoring of national or local authorities. If there are any unlawful cases, then the legislative affairs office may be involved in and assist with the case handling.

Pharmacovigilance Safety Update Report (PSUR)

What is the PSUR submission frequency in China? Per the Periodic Safety Update Reports Writing Guidelines1, the data for the Periodic Safety Update Report shall be summarised from the date of obtaining the drug approval document and shall be reported within 60 days of the data cut-off date. It is possible to submit a Periodic Safety Update Report starting from the international date of birth, but if the data cut-off date for the above-mentioned report is earlier than the cut-off date required in China, the data for this period should be supplemented and analysed.
Reference: 1. Guidance for Writing Periodic Safety Update Reports of Drugs Announcement of the National Food and Drug Administration (NFDA) on the Issuance of Guidance for Writing Periodic Safety Update Reports of Drugs (No.[2012]264)
Can MAH submit PBRER instead of PSUR and what’s the specific requirements?</strong > Yes, MAH can use PBRER to replace PSUR. According to the announcement (NMPA No. 2020/86) released in July 2020,PBRER can replace PSUR, and the format and submission deadline shall follow ICH E2C (R2) Periodic Benefits-Risks Evaluation Report, which means PBRER with reporting period no more than one year shall be submitted within 70 days since DLP and PBRER with reporting period more than one year shall be submitted within 90 days since DLP.
Which part of imported drug’s PSUR shall be translated into Chinese before submission?</strong > Except for Line Listings and Summary Tabulations, all the other parts of PSUR shall be translated into Chinese and submitted with CCDS (Company Core Data Sheet) and original English version of PSUR.
Which date shall be the starting date for PSUR submission? If the submission is overdue, will PSUR be rejected by the system?</strong > Usually globally speaking, it starts from IBD, but if no information about IBD then CBD (approval date in China).If you miss the deadline of PSUR submission, the National ADR Monitoring System will still accept the submission but it does not mean the report passes.

Pharmacovigilance System Master File (PSMF)

Is it feasible to convert EMA PSMF to China version of PSMF?</strong > Since the design of China PSMF is referencing EMA PSMF template, there is plenty of similarity in terms of structures of the Master File. it is feasible to convert the required elements into the Chinese version of PSMF suitable for China Regulatory Authorities. Contact us for our PV expert for PSMF conversion consultation.

Drug Safety Committee (DSC)

or transnational pharma corporations, can the drug safety committee from headquarter take the role for China?</strong > It depends. Generally the Drug Safety Committee concerns the drug safety globally from an overall point of view, but some markets may have different features and requirements. Furthermore, according to article 20 of GVP, the DSC is responsible for significant risk’s judgement & determination, significant or emergency events’solution, risk control decision-making and other important events related with pharmacovigilance. Significant events are normally very urgent and it is required to respond immediately accordingly. But HQ Safety Committee may not even have enough time to respond for emergencies. So, it would be better to have local Safety Committee. However, if the HQ can make sure that they can respond timely and the SOP is compliant with China requirement, it’s also feasible.

Risk Management Plan (RMP)

Shall all drugs create the RMP? Not all kinds of drugs are mandatory to create a RMP or PV Plan according to regulations. It is required for those marketed drugs found with significant risks according to risk assessment result and to keep the plan updated.
Shall we make RMP and PV Plan both or alternative? The PV Plan can be used as RMP and vise versa. For instance, if you already have a pre-marketing RMP, you can adjust it into a PV Plan or a post-marketing RMP accordingly.
Does the Regulatory Authority release the official Post-marketing Pharmacovigilance Plan Guideline document?</strong > Currently the regulatory requirement for PVP is included in the Clinical Risk Management Plan Writing Guideline document.

Safety Database in China

What is the regulatory requirement for safety databases in China?</strong > In China, it is mandatory for pharmaceutical companies to establish a safety database to collect and manage adverse drug reaction (ADR) reports as per the China GVP1 and ADR Reporting Guideline2 released by the National Medical Products Administration (NMPA).
Can the safety database in China be outsourced to a third-party service provider?</strong > Yes, outsourcing the safety database function to a third-party service provider is allowed in China, but the pharmaceutical company must ensure that the provider has adequate experience, expertise, and a robust quality management system.
Reference:
  1. China Good Pharmacovigilance Practice (GVP) Announcement of the NMPA on the Publication of China Good Pharmacovigilance Practice (No. 65 of 2021)
  2. Guidelines for the Collection and Reporting of Individual Adverse Drug Reactions Announcement by the NMPA on the Issuance of Guidelines for the Collection and Reporting of Individual Adverse Drug Reactions (No. [2018] 131)