he DIA Global Annual Meeting 2023 hosted DIA’s first regulatory Town Hall fully dedicated to one regulator from Latin America, as leadership from Brazil’s Health Regulatory Agency, ANVISA, shared updates on the country’s regulatory priorities, the agency’s strategic priorities, and local trends, as well as ongoing regulatory convergence and collaboration initiatives. This article summarizes session highlights with a focus on ANVISA’s short- and midterm priorities, including its objective of being internationally recognized as a reference agency.

ANVISA’s International Presence

It is widely recognized that in a global environment no single regulator can perform all its tasks alone, or establish national regulations completely disconnected from the work of other regulators. Since its inception in 1999, ANVISA has prioritized engagement in international initiatives for regulatory convergence at the regional and global levels. This participation seeks to ensure that Brazil maintains a modern, up-to-date national regulatory framework and that the Brazilian perspective is considered in the development of international guidelines and reference documents which will guide product regulation around the world. Aligned with Brazil’s historical diplomatic trajectory of promoting multilateralism and dialogue, and representing a population of more than 200 million citizens, by far the largest in Latin America, ANVISA has a long tradition as a supporter and provider of formal and informal international cooperation initiatives and agreements aimed at promoting information sharing and capacity building among regulators of all levels of maturity.

A Reference for the Region

The diversity of the region translates into significant differences in economic development and consequently regulatory capabilities between countries in Latin America. The Brazilian agency is defined by the Pan American Health Organization (PAHO) as a National Regulatory Authority of Regional Reference (NRAr) for medicines and vaccines. Alongside its NRAr peers from Argentina, Canada, Chile, Colombia, Cuba, Mexico, and the US, and in close collaboration with PAHO, ANVISA has worked for more than a decade on activities prioritized by countries in the Americas for strengthening regulatory capacity and capabilities in the region, fostering better regulatory practices, and increasing cooperation. This cooperation entered a new phase after the COVID-19 health emergency, as one clear lesson learned from the pandemic is the value of regulators working together to find common solutions for shared challenges.

ANVISA’s current collaborations with their regional partners, especially with other NRArs from Latin America, promote and increase convergence of regulations in the region towards internationally recognized standards and guidelines such as technical documents from the International Council for Harmonisation (ICH), the Pharmaceutical Inspection Co-operation Scheme (PIC/S), the International Medical Device Regulators Forum (IMDRF), and the World Health Organization (WHO).

Advancing Reliance

ANVISA has also realized the benefits of increased engagement in international regulatory cooperation and convergence processes. By participating in forums like ICH and PIC/S, ANVISA has become experienced and familiar with the best practices of more mature regulators. This not only facilitated adoption of some of these practices in Brazil but also increased ANVISA’s trust in other regulatory organizations, enabling the agency to recognize the value of reliance as a tool to strengthen regulatory practices that can also be applied to different regulated products.

Last year, ANVISA published Resolution RDC 741/2022, which defines the general reliance principles for the Brazilian regulator. This resolution documents the overarching reliance policy of the agency, establishes criteria for the designation of organizations which ANVISA trusts (the concept of “Equivalent Foreign Regulatory Authorities”), and serves as an umbrella regulation that will be followed by specific guidelines with reliance procedures applicable to different categories of products regulated by the agency (medicines, medical devices, food, cosmetics, sanitizers, etc.).

ANVISA also began to revise and modernize its reliance pathways for drug registration and post-approval changes in 2022. At the same time that the agency started a public consultation with this objective (CP 1,108/2022), it launched a temporary pilot reliance regulation (Resolution RDC 750/2022) to enable verification of the effectiveness of some of the requirements included in the draft guidance under public consultation. The idea was to encourage sponsors to use the pilot, test the procedure, and provide concrete feedback to the agency.

The results of the pilot have been positive and promising. The main challenges evidenced so far have centered around the criteria to ensure product sameness (how to demonstrate equivalence of essential characteristics of the products approved for marketing in Brazil compared to those approved by the reference authority) as well as the challenges in ensuring that reviewers in Brazil can access complete assessment reports prepared by other regulators. Even with preliminary results, ANVISA has been able to identify, in most cases, an approximate 50 percent reduction in the total evaluation time when comparing standard pathways to reliance pathways. The complexity and number of clarifications and information requests sent by reviewers to the applicant have also been reduced. These elements prove that reliance achieves its objectives of promoting more efficient use of ANVISA’s limited resources, enabling faster evaluation both for products previously approved by reference authorities and drugs developed to be first approved in Brazil, to the benefit of Brazilian patients. Even so, ANVISA sees room for improving the future regulation and industry engagement in the use of reliance pathways in Brazil.

It is also worth noting that industry engagement and feedback have been essential components of this journey to a more robust and consolidated reliance regulation. Transparent communication from applicants has been significant and valuable in developing solutions to issues identified during this pilot and public consultation, including preparing a single dossier which highlights differences between the regulatory status of the product in different countries. The final reliance regulation for drugs is expected to be finalized by September 2023.

Short- and Long-Term Future

Alongside approval of an updated reliance framework, ANVISA is also enhancing its international engagement in collaborative programs like US FDA’s Project Orbis and EMA’s OPEN initiative. The agency is also prioritizing making registration procedures simpler, clearer, and better defined; finalizing work on regulations that allow the use of more than one reference drug in Brazil; adopting guidance for agency use of real-world evidence; organizing internal databases to more easily engage in collaborative international initiatives; implementing the electronic Common Technical Document (eCTD) and Identification of Medicinal Products (IDMP) standards; issuing a market authorization regulation on drug shortages; updating ANVISA’s biosimilar regulation; and preparing for an upcoming WHO audit with the Global Benchmarking Tool (GBT).

Another strategic priority for ANVISA is becoming a WHO-Listed Authority (WLA). The agency undertook its preliminary self-assessment with the GBT in 2021 and has since been working on adopting the adjustments needed to demonstrate full implementation of all mandatory subindicators evaluated by WHO. ANVISA acknowledges that the challenges in the path to become a WLA have been many, but they have also allowed for the growth of a more mature organization: a common quality management system for the entire agency was established and standard operating procedures (SOPs) for numerous routine activities, including international cooperation processes, were revised and adopted. Remaining hurdles include the shortage of staff available to deploy to these necessary adjustments, and other situations or circumstances whose governance is beyond the agency’s control. Furthermore, the federal system in Brazil mandates that some health regulation and surveillance activities are decentralized to local authorities in states and municipalities, and the incorporation of new practices requires agreement and joint, coordinated efforts among stakeholders at different government levels.

ANVISA views the GBT assessment and the WLA framework as important tools to foster better regulatory systems worldwide. The agency sees these processes as improvement opportunities for the Brazilian regulatory system and is committed to completing all necessary adjustments by the end of 2023, enabling ANVISA to undergo WHO’s formal WLA assessment in 2024.