Monica Juping Xu
Taimei Medical Technology

n May 2021, the National Medical Products Administration (NMPA) in China issued an announcement about Good Pharmacovigilance Practice (NMPA/Decree No.65/2021), hereafter referred to as GVP, the first pharmacovigilance guideline issued in accordance with China’s new Drug Administration Law of the People’s Republic of China. The expected official version of GVP has been released in final form and will be effective on 1 December 2021.

This is the first time the term “pharmacovigilance” is officially reflected in the Drug Administration Law of China, which provides its context in Article 12: “The State establishes a pharmacovigilance system to monitor, identify, evaluate and control adverse reactions or other problems related to drug use.” Article 1 of the China GVP clearly mentions that, “The Practice is formulated in accordance with Drug Administration Law of the People’s Republic of China, Vaccine Administration Law of the People’s Republic of China and other relevant provisions for the purpose of regulating the pharmacovigilance activities throughout the lifecycle of drugs.”

The above Articles emphasize that pharmacovigilance should be performed during the lifecycle of drugs – in a phrase, “lifecycle pharmacovigilance.” The China GVP requires the marketing authorization holder (MAH) and sponsor to establish the pharmacovigilance system in an early stage and implement pharmacovigilance activities and a pharmacovigilance quality management system (PV QMS) into their corporate quality management systems (QMS) (China GVP Article 2).

Following the official release of China GVP, lifecycle pharmacovigilance is definitely the focus of industry in China. But how well is lifecycle pharmacovigilance understood?

First, what is the “lifecycle” of a drug? Broadly speaking, it refers to the entire process undertaken from the beginning of research and development, market application evaluation, marketed product re-evaluation, and even eventually market withdrawal due to declining market size or other reasons. The process includes five stages: development, introduction, growth, maturity, and decline. It refers to all measures taken to maintain and increase the sales and profits of a drug and to protect them from being impacted by competing products following development and marketing.

The main process tasks in new drug development include project launch, compound structure screening, basic research, pharmaceutical research, pharmacodynamic and pharmacological research, toxicological and pharmacokinetic research, Investigational New Drug (IND) application and approval, Clinical Trial Application (CTA) and approval, clinical studies (phases 1, 2, and 3), New Drug Application (NDA) and approval, manufacturing and commercial activities, phase 4 (post-marketing study), and continuous safety monitoring. Giving birth to a new drug takes a long time, often estimated at 10 to 14 years.

Industry seems to hold different views on when pharmacovigilance should begin. Some suggest that it should start during the laboratory research, while others propose it should start when the drug is used in the first human. Consensus seems to favor the second position, because the focus of pharmacovigilance is patient safety, while laboratory research is more likely to comply with GLP (Good Laboratory Practice) and to focus on pharmacological and toxicological data far upstream in the lifecycle from human use.

The definition and logic of pharmacovigilance from WHO explains pharmacovigilance as the science and activities relating to the detection, assessment, understanding, and prevention of adverse reactions or any other medicine/vaccine related problem. The basic logic of pharmacovigilance is to detect these problems from data collection and then to manage, prevent, or control any drug risks from the first human use of the drug until withdrawal from the market.

For many if not most multinational pharmaceutical companies, when to establish the pharmacovigilance system is not a new topic because the global pharmacovigilance system is relatively mature. Even though this topic may sound unfamiliar to many Chinese enterprises, and there are fewer guidelines on establishing a pharmacovigilance system during development than during post-marketing, global PV systems will greatly improve with rollout of the China GVP.

Deepening understanding of “lifecycle pharmacovigilance” follows the CIOMS VI Working Group recommendation to use the term “pharmacovigilance” in the pre-market process where the safety data from the development period is being collected, managed, and assessed. While this recommended definition may differ from the traditional definition of the term pharmacovigilance, which is usually associated with post-marketing, the terms “risk assessment” and “risk minimization” apply to both the pre- and post-marketing setting.

Most innovative drug enterprises should establish their system in the clinical study stage because lifecycle pharmacovigilance ensures patient safety as early as possible.