Around the Globe

Importance of Reliance to Support Strengthening Latin American and Caribbean Regulatory Systems
Maria Cristina Mota Pina
Abbvie on behalf of FIFARMA Regulatory & Biologics Working Group
R

egulatory reliance is increasingly used around the world by National Regulatory Authorities (NRAs) with different levels of maturity. This concept is actively promoted by organizations such as World Health Organization (WHO), the Pan American Health Organization (PAHO) as a mechanism for NRAs to better manage resource capacity issues while simultaneously strengthening regulatory systems. This article presents some practical considerations and opportunities for a successful implementation of regulatory reliance with a focus on the specificities of NRAs in Latin America and the Caribbean.

Regulatory reliance is defined as the act whereby the National Regulatory Authority (NRA) in one jurisdiction may take into account and give significant weight to assessments performed by another NRA or trusted institution, or to any other authoritative information source, for purposes of reaching its own decisions. The relying authority remains independent, responsible and accountable regarding the decisions taken, even when it relies on the decisions and information of others.

Regulatory reliance is anchored in the overarching Good Regulatory Practices (GRP) and provides a process for sound and effective regulation of medical products (i.e., medicines, vaccines, blood and blood products and medical devices including in vitro diagnostics and other health products), as an important part of strengthening health systems. Countries with efficient regulatory systems will serve their patients by ensuring that safe, quality, and effective medical products are approved and are accessible to patients in a timely manner. Clear public health priorities based on medical needs, availability of medical innovation and regulatory capacity assessments should guide NRAs approaches to regulatory reliance.

In recent years, regulators in Latin America and the Caribbean have been increasingly implementing (or at least considering the implementation of) different reliance pathways. This process was somewhat accelerated by the global health emergency which emerged in early 2020 and simultaneously highlighted the need for agile decision-making by health authorities around the world. COVID-19 proved that, in public heath emergencies, reliance can help in regulatory preparedness and response. Nevertheless, the use of regulatory reliance in the region is still inconsistent and could be better aligned to recommended international best practices.

We recommend the following considerations for enabling reliance to reach its full potential in Latin America and the Caribbean.

  • Regulatory reliance should be considered by NRAs across the region in the pursuit of regulatory efficiencies, regardless of their resource or capacity level and independent of their level of maturity. Reliance is relevant for all resource settings because reliance can be used for different reasons.
  • NRAs should be transparent in publishing a list of accepted reference authorities, and the rationale for relying on a specific entity should be disclosed and understood by all stakeholders. It is ultimately up to each individual NRA and its government to make the determination of who constitutes a reference authority. However, the decision should be informed by robust science-based data rather than reputation, historical international alignments or other considerations. One suggested approach is relying on NRAs that have been identified by WHO as regulatory systems performing at an advanced level and committed to continuous improvement, based on an established benchmarking exercise and additional performance evaluation processes.
  • Authorities being relied upon should possess and maintain competencies and operate within a robust and transparent regulatory system underpinned by globally accepted international standards and a well-functioning quality system.
  • An NRA can choose to rely on many accepted reference authorities. However, each individual regulatory procedure that uses reliance should require information from a single reference NRA, and not from two or more reference NRAs.

    • Practical example: Regulator X offers a regulatory pathway for market authorizations using reliance. This regulator publishes a list of “reference authorities” saying that it relies on regulator A, B, C and D. Ideally, this does not mean that applicants using this pathway must present documentation showing that a particular product has a market authorization issued by all the listed regulators (A, B, C and D). It should be sufficient that the company has the product authorized by only one of these reference regulators. If it is authorized by more than one reference regulator, the company would decide which approval to use for the reliance of regulator X.

    This recommendation derives from the fact that a reliance pathway is intended to simplify (and not complicate) the work of the regulator and the company submission process. If you compare authorizations granted by different regulators for the same product, there are some but relevant differences in indication, labelling and other elements, some motivated by local regulations, others by the company marketing strategy, among other reasons. These differences impact the product lifecycle because they determine the post-approval changes required for regulatory approval. If a regulator demands that a reliance pathway uses two or more reference countries for a single submission even though the product might be the same, they are in practice dealing with two or more different sets of documentation, which makes it complicated for companies to maintain the product in the market. In addition, waiting for several regulators to approve a product before using a reliance pathway might delay a particular submission.

    Those who study the use of reliance pathways have observed that when a regulator uses more than one reference regulator for an individual submission, the reliance pathway is not the best choice for applicants, who should instead opt for other submission pathways. In practice, this means that this reliance pathway exists but its potential is not fully realized.

Additional Reading

  • Regulatory reliance can be implemented at many stages in the product lifecycle and should result in a reduction of regulatory burden and offer an opportunity for faster and more predictable decision-making. When regulatory reliance is implemented effectively, reducing the effort for both NRA and industry, applicants will be more likely to use reliance-based regulatory procedures ahead of standard pathways.
  • Regulatory reliance should be transparent regarding standards and processes. NRAs should provide guidance on (i) what documents are required beyond a standard regulatory submission; (ii) how these documents will be used for the specific reliance process; and (iii) who should provide these documents.
  • The production and public availability of assessment reports by the reference agency and the reliant agency is a good practice.
  • Where possible, NRAs should use publicly available information to support reliance processes. However, different reliance mechanisms may require different approaches to supplying this information. In situations where non-public information is requested, the process should make clear the confidentiality basis under which the restricted information will be supplied and always use secure channels or information-sharing platforms.
  • When products are approved through reliance-based regulatory procedures, post-approval changes should also be managed through reliance-based procedures.
  • The timeline from reference authority approval to submission of dossiers in a reliance-based regulatory procedure should be flexible. Reliance-based regulatory procedures that require submissions within a defined time following reference authority approval may limit the usefulness of the procedure.
  • Agencies of equivalent level of maturity should consider work-sharing, an alternative mechanism to implement reliance. Work-sharing mechanisms can offer an additional opportunity to share best practices, strengthen regulatory science and develop capacity in reviewing novel technologies across the region.
  • Pilot programs for reliance-based regulatory procedures will provide initial practical experience for NRAs and applicants. Robust evaluation of results from these programs, including feedback and dialogue between NRAs and industry, could swiftly capture opportunities to improve processes and procedures leading to increased trust and acceptability by all stakeholders.
Regulatory reliance represents a functional and practical way for regulating medical products in a modern world of globalization, growing public health needs, limited resources, and demand for more, faster, and better treatments. If implemented effectively, regulatory reliance can benefit multiple stakeholders including patients, consumers, industry, and international development partners by facilitating and accelerating access to safe, effective, and quality-assured medical products. Reliance strategies and approaches strengthen regulatory systems and build capacity by incorporating new approaches and trends, while maintaining sovereignty over decision-making. Regulatory reliance enables sustainable learning and experience-sharing in the longer term. Collaboration and dialogue between all stakeholders participating in regulatory reliance activities will promote regulatory convergence, and create and build trust and acceptable reliance standards for Latin America and the Caribbean.

Disclaimer: The opinions expressed in the paper are solely the author’s and do not necessarily represent the views of her affiliated organizations.

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