The costs of the COVID-19 (SARS-CoV-2) pandemic to public health have been significant worldwide. COVID-19 has affected the health of more than 770 million people, with more than 6.9 million deaths reported worldwide, in addition to devastating direct and indirect health outcomes (Msemburi et al., 2022). This pandemic was shortly followed by the introduction of innovative COVID-19 vaccine products. These novel vaccines have required expedited procedures to enable assessment of their quality, efficacy, and safety, and ultimately protect public health.

From the beginning, and in response to the pandemic, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, 1999), the Medical Dictionary for Regulatory Activities (MedDRA) Maintenance and Support Services Organization (MSSO) (MedDRA Mainte nance and Support Services Organization, 1999), and ICH expert working groups worked together to develop a rapid and unique response.

In this article, the authors outline the MSSO’s standard approaches to developing and maintaining MedDRA terminology and then explain its role in addressing global public health challenges posed by COVID-19. The authors describe the effective response of ICH and MSSO to the pandemic by accelerating the development and maintenance of new MedDRA terms and tools for COVID-19. These exceptional activities have played a pivotal global role in diagnosis, prognosis, indication, and prevention, as well as monitoring the safety of novel COVID-19 vaccines by enabling the timely reporting, coding, and analysis of adverse events following immunization (AEFIs).

MedDRA is the international medical terminology developed under the auspices of the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, 1999). A dedicated MedDRA Maintenance and Support Services Organization (MedDRA MSSO) was established to support its development and maintenance. MSSO’s first release of MedDRA (version 2.1) was in March 1999. When the European Medicines Agency (EMA), the Japanese Ministry of Health, Labour and Welfare (MHLW), and US Food and Drug Administration (US FDA) adopted MedDRA as a standard, MedDRA started on the path to its current role as an international standard. The ICH MedDRA Management Committee (MedDRA MC) is responsible for the direction of MedDRA and overseeing all the activities of MSSO which is charged with the maintenance, development, and distribution of MedDRA.

MedDRA is maintained in English and has been translated and maintained in several additional languages (MedDRA Maintenance and Support Services Organization, 2025b). MedDRA is available as a free subscription to all regulators worldwide, while paid subscriptions are on a sliding scale linked to the annual turnover of commercial organizations. Academics and healthcare providers can also access MedDRA at no cost.

To support the efficient use of MedDRA, the ICH M1 Points to Consider Working Group (M1 PtC WG) updates with each MedDRA release two PtC documents on MedDRA Term Selection and MedDRA Data Retrieval and Presentation (MedDRA Maintenance and Support Services Organization, 2025a). The fully translated version of the PtC documentation is available in six languages. While the condensed version is available in all other MedDRA translations (MedDRA Maintenance and Support Servi ces Organization, 2025b). In addition, since 2017, the scope of the M1 PtC WG has been expanded to include the maintenance of a companion document to the PtC documents which provides more detailed guidance, examples, and questions and answers on topics of regulatory importance (e.g., data quality, medication errors, and product quality issues) (ICH M1 PtC Working Group, 1999).

MedDRA is a rich and highly specific standardized medical terminology for regulators and regulated biopharmaceutical industry to facilitate sharing of regulatory information internationally for medicinal products used by humans. MedDRA is used for the registration, documentation and safety monitoring of medical products both before and after a product has been authorized for sale. Products covered by the scope of MedDRA include pharmaceuticals, biologics, vaccines and drug-device combination products (Harrison and Mozzicato, 2009).

The scope of MedDRA includes all phases of the development of medicinal products for human use, excluding animal toxicology. This encompasses medical, health-related, and regulatory concepts pertaining to such products. The terminology also addresses the health effects and malfunction of medical devices. Furthermore, the terminology may support other types of products that are regulated in at least one region (e.g., food or cosmetics).

MedDRA is structured as a five-level hierarchy (Figure 1), ranging from very specific to more general terms: Lowest Level Terms (LLTs), Preferred Terms (PTs), High Level Terms (HLTs), High Level Group Terms (HLGTs), and System Organ Classes (SOCs). It is grouped into 27 SOCs that represent parallel axes (Bousquet et al., 2014). This characteristic, known as “multiaxiality,” allows a term to be represented in more than one SOC and to be grouped by different classifications, enabling retrieval and presentation via multiple data sets. Multiaxial links of terms are pre-assigned, allowing automatic assignment of grouping terms higher in the hierarchy and ensuring comprehensive and consistent data retrieval, regardless of which SOC is selected at retrieval. Each MedDRA PT is assigned a primary hierarchy and, in some cases, secondary hierarchies (Brown et al., 1999). MedDRA also includes “Standardised MedDRA Queries (SMQs)”, which are groupings of MedDRA terms at the PT level that relate to a defined medical condition or area of interest (Brown et al., 1999). SMQs are intended to aid in the identification and retrieval of potentially relevant individual case safety reports (Chang et al., 2017; Hartford et al., 2006; Brown, 2004). The included terms may relate to signs, symptoms, diagnoses, syndromes, physical findings, laboratory and other physiologic test data, etc. The only LLTs represented in an SMQ are those that link to a PT used in the SMQ; all others are excluded.

MedDRA integration is an indispensable component of pharmacovigilance systems. It ensures data standardization, regulatory compliance, and the ability to effectively detect and assess safety signals (Harrison and Mozzicato, 2009; Chang et al., 2017; Hartford et al., 2006; Brown, 2004; Mozzicato, 2007). By supporting the entire pharmacovigilance process, from data collection and coding to analysis and reporting, MedDRA plays a fundamental role in drug safety monitoring and risk assessment, ultimately contributing to safer pharmaceutical products for patients worldwide. Some key aspects of the MedDRA role in pharmacovigilance can be summarized as follows:

− Standardization: MedDRA ensures consistency in reporting adverse events, facilitating uniform communication among researchers, healthcare professionals, and regulatory authorities worldwide.

Through these capabilities, MedDRA substantively supports the robustness of pharmacovigilance systems, ensuring timely signal detection, effective regulatory communication, and high-quality safety data management while minimizing redundancy.

As outlined in Sections 2, 4, the MSSO, under the oversight of the ICH MedDRA MC, is responsible for the continued development and biannual releases of MedDRA to ensure alignment with evolving medical knowledge and pharmacovigilance needs (Harrison and Mozzicato, 2009). Releases occur on 1 March and 1 September in English, with translated versions in 23 supported languages following on 15 March and 15 September. MedDRA users can submit change requests (CRs) – such as adding new terms, modifying existing ones, or updating SMQs and translations–through an online MedDRA tool, called “WebCR” (MedDRA Maintenance and Support Services Organization, 2008). Each CR undergoes a structured review by the MSSO medical officers, including an international panel, to ensure compliance with MedDRA’s rules and conventions, medical accuracy, completeness, and internationally accepted medical standards. Approved changes are incorporated into the MedDRA data files following quality checks, and the updated user documentation made available for download via the MedDRA website (Harrison and Mozzicato, 2009).

The updated release of MedDRA Version 23.0 was well received by the global MedDRA user community. In response to the urgent need for rapid, standardized terminology during the COVID-19 pandemic, the ICH MedDRA MC, in collaboration with the MSSO, acted swiftly to support vaccine manufacturers and regulators. New MedDRA terms were introduced to capture key concepts related to COVID-19 vaccine safety and efficacy, enabling consistent data submission and independent analysis across regulatory authorities. The ability to deliver an out-of-cycle release - while maintaining the integrity of MedDRA’s quality standards - was a significant accomplishment.

A key lesson learned from this effort was the critical importance of organizational preparedness. In response, MSSO has expanded its internal standard operating procedures and work instructions to accommodate similar public health urgent scenarios in the future. The COVID-19 pandemic reinforced affirmed MedDRA’s role as a reliable and adaptable pharmacovigilance tool, of supporting timely responses to global health emergencies.

These MedDRA adaptations, though driven by the COVID-19 pandemic, demonstrate broader utility for future public health challenges, such as emerging infectious diseases, pandemic preparedness, and vaccine safety monitoring. The expanded and continuously maintained terminology can support timely and standardized data capture across diverse clinical and regulatory contexts.

Nonetheless, the key challenge in this process was determining how and which elements of the standard 6-month MedDRA maintenance cycle could be effectively condensed into just a few days without compromising the stringent quality controls applied to all MedDRA releases. While the flexibility of existing tools and the expertise of the technical team were critical in enabling this accelerated response, some aspects of the rapid implementation did not proceed as smoothly. Specifically, coordination across regions presented difficulties due to differences in regulatory timelines, local approval processes, and varying levels of readiness to integrate new terminology. These discrepancies occasionally led to delays in the uptake of updated terms by national authorities and users, reflecting broader challenges noted in cross-regional regulatory collaboration and real-world evidence integration (Beck et al., 2025).

Additionally, effective communication between the ICH MedDRA MC, MSSO, and MedDRA users supported agile and timely decision-making. However, the rapid onset of the pandemic underscored the importance of strengthening outreach efforts, particularly in regions with varying access to regular communication channels. From the MSSO’s perspective, a key takeaway from this experience was the importance of expanding the use of digital platforms (e.g., WhatsApp, Facebook, LinkedIn, WeChat) to support timely and inclusive information sharing during other potential disruptions.