Meeting Highlights: DIA Global Pharmacovigilance and Risk Management Strategies

doctor with gloves clicking medical icons
Pharmacovigilance: Artificial Intelligence and Global Regulatory Changes During the Pandemic
Shyreen Kamal
Maria Paula Bautista Acelas
Drug Information Association

OVID-19 transformed many aspects of pharmacovigilance (PV) practice and reshaped the future of drug and vaccine development. Collaborative efforts between many stakeholders, especially pharmaceutical companies and regulatory bodies, made it possible to develop and approve safe and effective COVID-19 vaccines in a short period. The adverse event (AE) collection process evolved due to the enormous number of safety reports received globally in 2021, resulting, for example, in a shift toward automation (artificial intelligence) in handling safety data to reduce the chance of human error in the process, and in a number of important regulatory changes around the world.

AI Emerges, Safety Data Handling Evolves

Pharmaceutical companies handled an exceptionally large AE case volume for COVID-19 vaccines in 2021, which led to rapid adaptation to overcome this challenge. When planning for COVID-19 AE reporting, FDA predicted a five-fold increase in AE cases in comparison to the H1N1 vaccine, which is approximately 200,000 cases. FDA received over one million COVID-19 vaccine AE cases in that first year. Similarly, the European Medicines Agency (EMA) reported receiving over a million cases.

AI integration and process automation were crucial to handling COVID-19 vaccine case volume. To decrease the burden on their call centers, some companies created an electronic reporting portal that allowed patients to report their own AEs. This resulted in an increase in case reporting and a higher quality of case reports. While call centers were still being used, many were automated to more easily receive AE calls from patients. Companies also used other aspects of automation and simplification to eliminate repetitive tasks and increase efficiency. Smaller pharmaceutical companies lacking the same resources as larger ones relied on external vendors while slowly building their own (in-house) AE reporting capabilities.

Automation will continue to help add consistency, compliance, and the value of human insight. It will also allow for greater signal detection, better data mining, and superior interaction between global databases, data pools, or data lakes. Companies will also use structured data reporting to standardize AE data and integrate AI into their nonstructured data. Incorporating data entry and data review into the same workflows reduces handoffs and increases efficiency.

New Challenges, New Models

Challenges may arise when using automation and AI in pharmacovigilance. Isolating data from human processing can sometime reduce the power to understand potential errors; therefore, quality control to detect unusual or extraordinary cases is important. Companies may need to hire additional staff for this review step to ensure accuracy and realize the other benefits of AI. AI approaches to PV data must include good accuracy and confidence scores; PV data with lower confidence scores can be channeled to human review. Balancing technological and human power ultimately decreases costs and increases efficiency.

Aligned with continuing innovation in biogenomics and biopharmaceuticals, new PV business models will promote digital insights that connect patients with healthcare ecosystems. However, larger companies often have resources to invest in these innovations and digital platforms that smaller companies do not. One new model could allow innovation on a platform that companies can access at proportionate cost.

Global Regulatory Changes Affecting PV

As COVID-19 emerged, the global regulatory landscape developed flexible administrative and scientific procedures that ensured accelerated assessment of near “real-time” information to support agency responses to this public health emergency. National Regulatory Authorities across the world adopted modifications to enhance harmonization and refine methodologies to meet their challenges. Collaboration across international regulatory channels ensures continuous practice improvement and reinforces the importance of robust communication and engagement of a broad range of stakeholders to facilitate information exchange, as well as the importance of centralized databases, tools, and methods to ensure proper prioritization of such large volumes of data. However, developing strategies to adapt and respond effectively requires significant investments and technological upgrades across the supply chain, a challenge for countries with limited budgets.

Latin America: In general, PV regulations have increased in number and scope since the pandemic began. But there are still opportunities for improvement, such as the need for regulatory tools to control the exceptional responses that emergencies require when unforeseen challenges arise. Successful recent initiatives in Latin America include:

  • Brazil: The updated regulatory framework and national system for PV requires Marketing Authorization Holders to “double report” PV events to both ANVISA and the Health Surveillance Center (CVS).
  • Mexico: COFEPRIS published revised guidelines that describe requirements for PV reports associated with the Marketing Authorization renewal procedure.
  • Paraguay: Technology initiatives, such as VigiBase and a vaccine eReporting tool that facilitates AE reporting, helped make AE reporting easier.
  • Peru: The Ministry of Health (MINSA) approved a new Manual of Good Pharmacovigilance Practices including specific procedures to ensure the safety of medicinal products.

Regulatory reforms in China emerged from proactive collaboration across the global PV industry and the proactive role of the Chinese health authorities. The main regulatory reforms involved the Drug Administration Law (DAL) and the Vaccine Administration Law (VAL), two fundamental laws that provide stronger legal protection for public health, and enhancement of the Chinese Good Pharmacovigilance Practice (GVP).

Recent regulatory changes in Japan can be summarized into two categories:

  • Introduction and use of electronic distribution of package inserts (eLabeling) to mitigate challenges presented by physical package labeling
  • Optimization of real-world data (RWD) utilization for drug safety in post-marketing database studies. More regulatory considerations are necessary for utilization of RWD in efficacy evaluations.

Key lessons that the European Medicines Agency learned from monitoring COVID-19 vaccines that may apply across all PV processes in the future include creating vaccine Targeted Medical Events (vTMEs) that map information from a predefined list of Adverse Events of Special Interest, developing standard case definitions for new clinical entities, and the positive impact of flexible regulatory procedures that facilitate their accelerated assessment. The Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom published an updated guidance summarizing their approach to PV procedures and launched a COVID-19 Yellow Card reporting site to monitor the safety of products used to test and treat COVID-19.