Decoding China's Good Pharmacovigilance Practices (GVP)

On May 13, 2021, China National Medical Products Administration (NMPA) released the Good Pharmacovigilance Practices (GVP), which has been effective since Dec. 1, 2021.

GVP requires drug marketing authorization holders (MAHs) and drug registration applicants to establish and improve pharmacovigilance (PV) systems as well as conduct pharmacovigilance activities compliantly.¹ Pharmacovigilance activities are subject to national and provincial medical products' inspections according to the Pharmacovigilance Inspection Guidelines.

To help pharmaceutical companies with PV compliance in China, this article introduces:

1. GVP Application Scope

2. China GVP Contents

3. Pharmacovigilance for MAHs

3.1 Pharmacovigilance System Quality Management

3.2 Pharmacovigilance System Master File

3.3 Individual Case Safety Report

3.4 Post-market Safety Study

3.5 Periodic Safety Update Report

3.6 Risk Management

4. Pharmacovigilance for Drug Applicants

1. GVP Application Scope

The Chinese GVP applies to pharmacovigilance activities of

1.   Drug marketing authorization holders (MAHs); and

2. drug registration applicants approved to carry out clinical trials.

Pharmacovigilance activities refer to activities to monitor, identify, evaluate, and control adverse drug reactions (ADRs) and/or other negative reactions related to medication.

2. China GVP Contents

China's GVP contains 9 chapters, with 134 articles under 21 sections. Following Chapter 1 General Principles, Chapter 2-7 are mainly for MAHs, while Chapter 8 focuses on PV for drug registration applicants during clinical trials.

3. Pharmacovigilance for MAHs

3.1 Pharmacovigilance System Quality Management

MAHs shall establish the pharmacovigilance system that includes organization, personnel, rules & procedures, resources, and other pharmacovigilance-related elements. The system should be adapted to MAH's type, size, the number of held drugs, safety characteristics, etc.

MAHs shall manage the quality of pharmacovigilance system and related activities, and incorporate the critical pharmacovigilance activities into the quality assurance system. The following points should be paid attention to:

1. Setting up a properly structured organization;

2. Arranging qualified personal, equipment, and resources for pharmacovigilance activities;

3. Establishing management system in compliance with laws and regulations;

4. Establishing procedures that are comprehensive, clear, and operable;

5. Establishing effective and open channels for collecting information on suspected adverse drug reactions;

6. Reporting and handling the aforementioned information in compliant with laws and regulations;

7. Effectively identifying and evaluating risk signals;

8. Effectively controlling the identified risks;

9. Ensuring pharmacovigilance documents and records are available, checkable, and traceable.

MAHs shall make and update pharmacovigilance quality control goals which include but are not limited to:

1. the compliance of adverse drug reaction (ADR) report;

2. the compliance of periodic safety update report (PSUR);

3. the timeliness of signal detection and evaluation;

4. the timeliness of updating the pharmacovigilance system master file (PSMF);

5. the formulation and implementation of the pharmacovigilance plan;

6. the formulation and implementation of the personnel training plan.

Furthermore, MAHs shall conduct internal audit of the pharmacovigilance system periodically and take corrective and preventive actions (CAPA) for the issues found in the audit.

Pharmacovigilance work are permitted to be entrusted to a third party. The entrusted party should be a legal corporate entity in China and capable of ensuring the effective pharmacovigilance operation. Despite entrustment, MAHs remain as the responsible subjects for pharmacovigilance and shall assume relevant legal obligations.

3.2 Pharmacovigilance System Master File (PSMF)

MAHs should create and update the pharmacovigilance system master file (PSMF), which includes at least the following items:

1. Organization related to pharmacovigilance activities;

2. Information of the responsible person for pharmacovigilance;

3. Manning of specialized pharmacovigilance personnel;

4. Suspected adverse reactions and their sources;

5. Information tool or system for pharmacovigilance activities;

6. Pharmacovigilance management system and its operation rules & procedures;

7. Operation situation of the pharmacovigilance system;

8. Entrustment (if any) of pharmacovigilance activities;

9. Quality management;

10. Appendices:

1. Documents on pharmacovigilance system, operation rules & procedures;

2. Drug lists;

3. Entrustment agreement (if any);

4. Internal review report;

5. Record of master file revisions, etc.

3.3 Individual Case Safety Report

MAHs shall collect the information of suspected ADRs from multiple sources, including reports from manufacturers / distributors / medical institutions / patients / other individuals, post-market studies, data-collecting projects, academic literature, and relevant websites.

For drugs marketed on both Chinese and overseas markets, MAHs should collect ADRs in both markets.

The adverse reaction report for individual patients, known as individual case safety report (ICSR), shall be submitted to the National Drug ADR System. The ICSR should at least include identifiable patients, identifiable reporters, suspected drugs, and ADRs.

3.4 Post-market Safety Study

Post-market safety study refers to the study that identifies and quantitatively/quantitatively characterizes drug safety risks, investigating drug safety attributes, and/or evaluating risk control measures.

MAHs shall detect the signals of suspected ADRs in time to identify drug safety risks. After identification, MAHs shall evaluate the risks to see if it's necessary to take risk control measures. During the evaluation, MAHs shall take the drug's risk-benefit ratio into consideration.

If MAHs find any drug safety issues that may severely harm the patient's life or public health, they shall immediately suspend the drug's production and sales, recall the products, and report to the local medical products administration.

3.5 Periodic Safety Update Report

MAHs shall write periodic safety update reports (PSUR) based on collected safety information.

MAHs of Class 1 innovative new drug and Class 2 improved new drugs should submit a PSUR to the National Drug ADR System every year since they gain marketing authorization. The submission frequency will change to every five years after the drug product gets re-registered. For drugs under other classifications, MAHs should submit the report every five years since marketing authorization.

Unless otherwise specified by NMPA, PSUR is NOT required for active pharmaceutical ingredients (APIs), in vitro diagnostic products (IVDs), traditional Chinese medicine (TCM) ingredients, or decoction pieces of TCM.

3.6 Risk Management

For identified safety risks, MAHs shall take appropriate risk control measures, including general measures and special measures.

General measures include

• Revising medical package inserts, labels, and packages;

• Changing packaging specifications and management status;

Special measures include

• Communication and training for medical staff and patients;

• Limiting drug use;

• Registering the information of patients who use the drug.

When the evaluation result shows that risks outweigh the benefits, MAHs shall proactively apply for cancelling the drug registration certificate.

In addition, MAHs shall conduct risk communications by sending drug safety information to medical staff, giving patients medication reminders, and holding news conferences.

Also, MAHs shall formulate and implement the pharmacovigilance plan, which covers

• Drug safety summary;

• Pharmacovigilance activities;

• Planned measures for risk control;

• Implementation time and duration.

4. Pharmacovigilance for Drug Applicants

During the clinical trial related to drug registration, applicants should manage safety risks as the main responsible entity by cooperating with clinical trial institutes.

Applicants shall fulfil the following obligations:

• Establishing the pharmacovigilance system;

• Collecting comprehensive safety information;

• Monitoring, identifying, evaluating, and controlling risks;

• Taking necessary risk control measures for safety issues;

• Evaluating the measures' effectiveness;

• Minimizing the risks to protect the trial subjects.

For pharmacovigilance system and quality management, applicants can refer to the PV requirements for MAHs, and make appropriate adjustments during clinical trials.

5. BaiPharm's Pharmacovigilance Services

BaiPharm helps pharma companies comply with China's Good Pharmacovigilance Practice. Our services include but are not limited to:

ü  Development of safety and risk management plans

ü  Data collection, entry, and evaluation

ü  Follow-up of safety cases

ü  Preparation and submission of safety report

ü  Chinese and overseas literature retrieval

Contact BaiPharm for pharma regulatory compliance services.

Related Resources:

• China Releases MedDRA Coding Guidance for Adverse Drug Reaction (ADR) Reports

• Key Points for China Pharmacovigilance Inspections