Special Section: Pharmacovigilance

scientist pointing to graphics of scientific icons
Emerging Pharmacovigilance Framework Ensuring Safe COVID-19 Vaccines in China
Sophia Duan
PPC China

ince the breakout of COVID-19, many pharmaceutical companies in China have worked to develop preventative vaccines. In response, China’s regulatory authority (RA), the National Medical Products Administration (NMPA), worked closely with the World Health Organization (WHO) and COVID-19 vaccine evaluation experts to establish a standard review system, release relevant clinical development and review guidelines, and provide 24/7 support to facilitate COVID-19 vaccine development. The NMPA has released seven relevant guidelines, including Technical Guidelines for the Development of COVID-19 Vaccine (Trial version), to guide, monitor, and accelerate the development of COVID-19 vaccines in China.

Scientific guidance from regulators has helped speed up development. As of December 2021, six COVID-19 vaccines developed by Chinese pharmaceutical/biotech companies have been authorized for urgent use or conditionally licensed after scientific assessments of all safety and efficacy data by the NMPA; two of these six have also been approved for emergency use by the WHO. By the end of October 2021, more than 2.2 billion COVID-19 vaccine doses were administered domestically, and the Chinese government had provided 1.5 billion vaccine doses to more than 100 countries and international organizations.

Development of COVID-19 vaccines is being fast-tracked in China. To ensure that safety standards are not compromised by fast-track development, the NMPA has consistently worked to enhance safety monitoring to ensure that vaccine candidates have a solid quality and safety profile, and that the benefits of vaccination far outweigh the risks both during clinical trials and post-marketing (after authorization or approval). This rapid development may be attributed to the innovation and due diligence of safety monitoring and risk management applied to COVID-19 vaccine clinical trials by China’s RA in partnership with China’s pharmaceutical/biotech companies.

To maintain the safety and quality of these trials, the NMPA’s Center for Drug Evaluation (CDE) requests that COVID-19 vaccine clinical trial sponsors establish a comprehensive safety monitoring and risk management (pharmacovigilance) system, establish a data and safety monitoring board (DSMB) or data monitoring committee (DMC), develop plans for risk control and long-term safety follow-up, and enhance communication of safety information with RAs, healthcare professionals, and trial participants. Sponsors are also strongly advised to report trial progress, in particular daily enrollment status and results from early phase trials, to the CDE in a timely (expedited) manner.

CDE has designed and provided a specific form for COVID-19 vaccine trial sponsors to report antibody-dependent enhancement (ADE) and vaccine-enhanced disease (VED) monitoring and assessment, serious adverse events/suspected unexpected serious adverse reactions (SAEs/SUSARs), and related safety information. CDE has also strongly encouraged integrating electronic recruitment, remote informed consent, centralized monitoring, remote visits, electronic platforms, questionnaires and files, and other digital technologies to achieve real-time safety monitoring of trial participants during COVID-19 vaccine development.

The US FDA and European Medicines Agency (EMA) are well-known for their rigorous safety standards and proactive pharmacovigilance requirements for vaccine development. Under the pandemic, FDA issued the guideline Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency, which provides general considerations to assist sponsors in conducting safety monitoring in clinical trials of medical products including COVID-19 vaccines. Many alternative methods for safety assessments (e.g., phone contact, virtual visit, alternative location for assessment, including local labs or imaging centers, etc.) are encouraged to assure the safety of patients in these trials. The EMA offers informal consultation with its COVID-19 Task Force (ETF), rapid scientific advice, and prompt guidance and direction on the best methods and study designs to generate robust safety data. China’s RA is implementing similar proactive safety surveillance measures and offering scientific guidance but in a more detailed and specific way, since the safety monitoring paradigm of vaccine trials was less developed and there is not much existing experience to leverage.

From the clinical trial sponsor, regulatory, and patient perspectives, China is demonstrating that building an effective pharmacovigilance ecosystem and using agile and innovative ways of monitoring safety, and of collecting and exchanging safety information beyond the traditional safety monitoring paradigm, can effectively manage the risks while accelerating the development of COVID-19 vaccines so that these vaccines will ultimately protect and save more and more people.

References available upon request.