dvanced Therapies have the potential to address major unmet health needs, changing the courses of diseases by alleviating the underlying causes and even potentially curing certain conditions. Health authorities around the globe are currently considering the development of standards and rules for regulating these products, in order to control the use of unapproved therapies and prevent risks to the population. To contribute to this rapidly evolving topic in Latin America, this article presents the industry perspective on considerations and recommendations for strengthening Advanced Therapies regulatory systems with a focus on establishing regulatory frameworks, adopting reliance procedures, and promoting regulatory capacity building.

Advanced Therapies: Importance of Regulatory Systems

Advanced Therapies (or advanced therapy medicinal products, ATMPs) are medicines for human use obtained from cells, genes, or tissues. These groundbreaking new therapies are pushing the boundaries of science and challenging expectations of what medicine can achieve. However, the benefits of these products also introduce novel regulatory challenges due to the breadth of therapeutic areas such products address and the innovative science and high level of complexity throughout development and manufacturing of these technologies. These challenges require changes in mindset and approach from all stakeholders and can be addressed by strengthening regulatory systems.

Increasingly robust regulatory systems enable governments and healthcare systems to address any ethical and reputational risks when currently licensed products or therapies may lack demonstrated benefits, efficacy, and safety, as well as any uncertainties for the healthcare centers administering such products. In addition, regulatory authorities and industry both benefit from effective, flexible, and innovative regulatory processes and oversight to manage these complex regulatory submissions and global supply constraints while ensuring science-based regulatory approval. Finally, strong regulatory systems allow patients and healthcare providers to access and understand the benefits of safe, effective, and quality Advanced Therapies.

However, even with their obvious benefits, regulatory systems face a number of issues when considering how to adapt frameworks, including new guidances and practices, to the unique specificities of Advanced Therapies. At present, regulatory agencies are hampered by the lack of harmonized international guidance documents, and the absence of globally aligned terminology, regulatory standards, and evidence requirements. These therapies’ high level of complexity and unique manufacturing considerations require training to develop expertise across diverse therapeutic areas and technologies. The need to undertake novel evidence generation strategies which routinely generate early and compelling data to address significant unmet needs, drive smaller and more diverse regulatory submissions compared to other medicinal products.

Strengthening Regulatory Systems for Advanced Therapies in Latin America

There is an absence of dedicated regulatory guidance for Advanced Therapies in the majority of countries within the Latin American region, though this situation is rapidly evolving. Different regulatory approaches are being taken as regulatory agencies consider how best to implement the suggestions in the 2019 PANDRH Concept Note, which may lead to future divergence in how these therapies are regulated across the region.

Building on the PANDRH recommendations, the innovative pharmaceutical industry and national trade associations in Latin America see three key areas of opportunity to strengthen regulatory systems for Advanced Therapies in the region:

• Establishing regulatory frameworks: The lack of consistent regulatory frameworks or the existence of divergent regulations across the region can delay access to safe, effective, and quality Advanced Therapies. Creating regulatory frameworks that enable adequate regulation of these therapies, recognizing the diversity of technologies while allowing for sufficient flexibilities to accommodate advances in science and growing experience in the field may be challenging. As a result, industry supports the adoption of international regulations and guidelines. If a national regulatory framework is developed, industry supports convergence towards international scientific standards to achieve harmonization of standards, guidelines, regulations, and implementation mechanisms within the region. A risk-based approach should be applied whenever feasible, while maintaining a robust set of key criteria to ensure patient safety and efficacy.
• Adopting reliance procedures: Ensuring the safety, quality, and effectiveness of these products can require a highly resourced enterprise and skilled human resources. Industry calls for Latin American regulatory agencies to adopt reliance procedures to increase efficiencies and improve regulatory capacities. The use of reliance procedures should span the entire product lifecycle (inspections, regulatory review, post-approval changes).
  
  The World Health Organization (WHO) defines regulatory reliance as “The act whereby the regulatory authority in one jurisdiction may take into account and give significant weight to – i.e. totally or partially rely upon – evaluations performed by another regulatory authority or trusted institution in reaching its own decision. The relying authority remains responsible and accountable for decisions taken, even when it relies on the decisions and information of others.” (WHO. Global Benchmarking Tool rev. VI ver. 1. Glossary and definitions, 2020.)
• Building regulatory capacity: Ensuring adequate capacity and capability within regulatory authorities for these complex products poses an immediate challenge to the development of both guidances and subsequent reviews. Industry supports a multi-stakeholder partnership approach to capacity training for regulators, officials, and healthcare professionals, and recommends training activities for national health authorities on Advanced Therapies developed by organizations such as the Asia Pacific Economic Cooperation (APEC) Centers of Excellence and the Pan American Health Organization (PAHO)/Pan American Network for Drug Regulatory Harmonization (PANDRH).

Conclusion

Advanced Therapies are a rapidly evolving field, with an inherently high level of complexity and recognized challenges. Industry sees three key areas of opportunity to strengthen regulatory systems for these medicines in the region, aligned with PANDRH’s Regulation of Advanced Therapy Medicinal Products: Concept Note and Recommendations, to ensure the use of approved Advanced Therapies and prevent risks to the population. Industry calls for Latin America regulatory agencies to ensure convergence when establishing regulatory frameworks, adopt reliance procedures, and embrace capacity training. All stakeholders should engage in an open dialogue and continue efforts to ensure the availability of Advanced Therapies for patients in Latin America.

Disclaimer: The opinions expressed in the paper are solely the authors’ and do not necessarily represent the views of their organizations.