ince China joined ICH in 2017, much effort has been expended in developing national pharmacovigilance standards harmonized with ICH guidelines. The National Medical Products Administration (NMPA), China’s regulatory authority, has announced a series of pharmacovigilance regulations and guidelines including both the pre-market (clinical) and post-marketing phases. After several years of planning and alignment, NMPA announced its guidance for China Good Pharmacovigilance Practice (China GVP) in May 2021, and it became effective on December 1, 2021.

Many marketing authorization holders (MAHs) have studied its requirements, defined quality objectives, and worked to establish or acquire compliant PV organizations, systems, documents, databases, and dictionaries. For example, China GVP mentions the Pharmacovigilance System Master File and Pharmacovigilance Plan, as part of the marketing authorization holder (MAH) or sponsor obligation to establish a pharmacovigilance system, for the first time in China.

The China GVP and, for example, the European Medicines Agency GVP are generally similar. Specific operational-level characteristics include:

• China GVP devotes one full chapter to specifically describing quality requirements and goals to ensure and maintain the compliance and effectiveness of the pharmacovigilance system. This includes determining PV quality indicators and implementing regular internal audits of key routine PV activities. The document also describes how to plan, manage, and audit PV outsourcing.
• Requirements for establishing related work groups and resources, such as the Drug Safety Committee, and definition of PV personnel training, PV facilities and equipment, and other organizational responsibilities of the PV department.
• Requirements for signal detection, how to assess and process safety information, post-marketing safety studies, and requirements for transmitting individual case safety reports to the regulatory authority.
• Direction for preparation and management of the periodic safety update report (PSUR), pharmacovigilance system master file (PSMF), PV plan, and other procedural documents. Direction is also provided for preparation and management of other administrative documents as well as for data and records retention.
• One chapter specifically describes clinical trial PV requirements.

Overall, the change in China GVP can be described as moving from a modular focus on individual case safety reporting and compliance with specific regulatory requirements toward a more scientific and systematic approach to product safety under the mission to ensure patient safety. In response, the clinical research and pharmaceutical industries in China are turning their focus to building effective, end-to-end PV systems and to enhancing risk identification and management.

But as the saying goes: “Rome wasn’t built in a day.”

Encouraging innovation in therapeutic product development was an important driver behind the China regulatory reform that began in 2015. This innovation-friendly environment has led to the growth of many biotechnology start ups in China.

These relatively small and new organizations face the challenge and opportunity of building their PV capabilities from the ground up. Multinational companies often have the advantages of a longer history and more experience with PV, including pre-existing PV systems, facilities, frameworks, and personnel, than their local counterparts in China. The challenge for multinational companies will be integrating China GVP into existing resources.

Most local companies with drugs already on the market experience PV only through passive safety reporting and lack the resources to scientifically and systematically assess risk and safety. Building a comprehensive system that effectively manages risk and monitors safety of products and patients presents a large challenge.

For many manufacturers and MAHs in China, changing the concept of establishing and managing PV systems from “adverse drug reaction (ADR) monitoring work” to more scientific and systematic “pharmacovigilance” remains the primary challenge. As a result, China faces a huge gap in local PV resources; it is difficult to find experienced PV professionals to employ. Many local companies have sought external resources through clinical research organizations (CROs) and similar groups. But this changing concept and scope of China GVP has made it difficult to outsource this work and means that it will take some time to deepen the local talent pool.

Training programs related to establishing PV systems and conducting PV activities in compliance with GVP and other regulatory requirements are growing, however. For example, the National ADR (adverse drug reaction) Center organized two GVP training sessions in May 2021. In September 2021, the DIA China PV Community presented Quality from Daily: PV Inspection Is Always Ready, and the Shanghai Pharmaceutical Industry Association presented GVP implementation training courses.

Even with these training and education opportunities, a general lack of awareness about PV and PV systems and tools remains a considerable challenge to both industry and regulators and is a difficult place from which China must start.

How difficult? One survey of pharmaceutical manufacturers based on 2018 data showed that 75% of these manufacturers/MAHs had no computerized PV database, and that 70% of the persons responsible for the PV function served part-time and not full-time, raising concerns that not enough time or attention was spent on PV work.

Industry’s Digital Response to China GVP

Industry in China has responded to China GVP by exploring the concept of building entirely digital PV systems, from system construction to automated compliance testing, to help alleviate some of this confusion.

GVP can realize many of the same benefits of digitalization as other industries in China. Digital frameworks allow for quick and transparent management, updates, and optimization.

Machine learning and similar digital tools can provide intelligent recommendations for applicable system and regulatory documents, generate compliance risk identification rules, and assist PV professionals with timely interpretation and action on regulatory requirements.

Digitally interconnected databases create an accessible repository and allow for synchronous data collection and submission, “drilling down” into more details, and generation of the PSMF, compliance risk monitoring reports, and similar required documents.

Many in China still consider GVP and PV systems as if they were theoretical exams and requirements for preparing information and frameworks, but their specific content remains unknown in such areas as:

• Mapping the PV organization structure
• Defining PV personnel job descriptions
• Defining drug safety committee members and responsibilities
• Mapping reporting and communication channels for safety information
• Establishing SOPs compliant with GVP and company requirements
• Establishing software system accounts and account verification.

Moving forward, many questions must also be answered for activities related to PV but conducted outside of these digital systems, such as meeting frequency for the Drug Safety Committee and similar groups, and how to review the package insert and labeling.

Full implementation of China GVP may even impact physician education and patient-physician communication. For example, patients most often report an adverse event to their physician first; consequently, physicians often have the most first-hand patient safety information. But the rate of adverse reports submitted by physicians has historically been low. One way for MAHs and regulators to emphasize the importance of reporting adverse events is by collaborating on education and training for hospital physicians and other clinicians on pharmacovigilance systems and processes.