IA’s 2020 Latin America Regulatory Conference included nine sessions that described and discussed multi-regional cooperation, global harmonization, and best practices related to the regulatory landscape in Latin America.

Key Takeaways

• National Regulatory Authorities (NRAs) in Latin America are continuously working to progress advancement in the regulatory arena in their respective regions. Updates on several local, regional, and global projects were discussed and included priorities that would affect regulators and manufacturers in Latin America.
• Real World Data (RWD) and Real World Evidence (RWE) are playing an increasing role in healthcare decisions. RWE regulatory programs were explored for their potential use in medicinal product decision-making.
• Participants examined Pan American Health Organization (PAHO) activities related to the Latin America region, and delved into guidance regarding the World Health Organization’s (WHO) guidelines on procedures and data requirements for changes to approved biotherapeutics.
• Important topics of discussion included current progress, challenges, requirements, and perspectives for the future in areas such as advanced therapies and gene editing.
• An introduction to Continuous Manufacturing (CM) showed the future of integrated processing with fewer steps, no manual handling, shorter processing times, and increased efficiency. A harmonized approach to CM under ICH (International Conference of Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) Q13 also showed the benefits of how industry and regulators could work together.

National Regulatory Authorities (NRA) Updates

ANMAT (Argentina)
One concern for ANMAT is the exchange of e-training specifically on pharmacovigilance (PV). Safety monitoring efforts in Latin America are a focus for regional regulators. Cooperation and collaboration help prevent the duplication of effort without losing sight of regulators’ responsibility to society. They also allow for transparency into what the regulators are doing, which in turn helps build trust in their respective jurisdictions. The need for industry and regulators to work together was emphasized throughout the discussions at the conference.

ANVISA (Brazil)
ANVISA is working on developing a guideline for Chemistry, Manufacturing, and Controls (CMC) requirements. In 2019, ANVISA published a guideline relating to submissions in the Common Technical Document (CTD) format. The backlog of dossiers was reduced by 50 percent, and the Agency is continuing to work on improving their review of drug registration applications. One important aspect discussed was the need to work on regulatory reliance, which was defined as the willingness to rely on the decisions of some regulatory agencies and to apply them to other countries and/or regions.

ARCSA (Ecuador)
The technological advances and efforts reflected in the new ARCSA mobile app allow regulators to be connected to both industry and patients. Users of the app can see warnings, updates, news, the status of licenses, suspensions, and they can file claims to the Agency for inspections on products and establishments not complying with health regulations. Latin America is continuing to improve their efforts in practical applications of technology in the healthcare arena.

Medicines Regulatory Authority of El Salvador
El Salvador’s current strategies and efforts include standardizing a national medicines and other technologies’ code to overcome the difficulty of having different languages spoken in the region, acting to reduce response times and quality in the assessment of procedures, and improve service to users through technology and innovation. Like Ecuador, El Salvador has a mobile app, DNM, that allows agile handling of information for timely decision-making and improves communication with the Medicines Regulatory Authority of El Salvador, the Salvadoran population, medical establishments, and the pharmaceutical industry.

The regional agenda for El Salvador includes developing regulatory frameworks and regional strategies to guarantee the quality, safety, and efficacy of products that are authorized for marketing in the Central American Integration System (SICA). SICA is the institutional framework of regional integration in Central America and was created by Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama. The system also includes a group of regional and extra-regional observers that consider past attempts of regional unification as well as lessons learned from history.

INVIMA (Colombia)
One of INVIMA’s goals is to transition from paper to digital. They also summarized the various personalized medical devices they review and emphasized the importance of good manufacturing practice (GMP) and the adoption of ISO 13.

FIFARMA
FIFARMA is the Latin American Federation of the Pharmaceutical Industry that discovers and develops innovative, quality and safe health products and services that improve the lives of patients in Latin America and the Caribbean.. A representative from the Caribbean spoke about efforts by the Caribbean Public Health Agency (CARPHA), the Caribbean Regulatory System (CRS), VigiCarib (an electronic regional reporting system), and the Medicines Quality Control and Surveillance Department (MQCSD), and how these agencies and institutions work to verify medicine quality through an accredited laboratory for the detection of substandard and falsified medicines on the market.

Real World Evidence and Data

The possibilities of using RWE and RWD in Latin America were explored. Understanding if your RWD is fit for use, knowing if the trial or study design used to generate RWE provides adequate scientific evidence to help answer the regulatory questions at hand, and whether the study and data meet regulatory requirements are all important considerations when using RWD and RWE in regulatory decision-making. Lessons learned from industry included early interaction with health authorities, the need for data to be fit for purpose, pre-specified analysis plans, addressing potential study design biases, and cross-functional collaboration efforts. The future of RWE in Latin America is very promising and can be complementary to what is already available in clinical trials.

WHO and PAHO

Key regulatory strengthening activities at WHO include the WHO Global Benchmarking Tool (GBT), a harmonized and consolidated tool for medicines, vaccines, medical devices, and blood. PAHO (the Pan American Health Organization) is currently piloting the tool in El Salvador and Peru. The GBT also incorporates the concept of a maturity level that was adapted from ISO 9004, allowing WHO and regulatory authorities to assess the overall maturity of a regulatory system on a scale of 1 (some elements of regulatory system exist), 2 (evolving national regulatory system that partially performs essential regulatory functions), 3 (stable and well-functioning and integrated regulatory system), or 4 (regulatory system operating at an advanced level of performance and continuous improvement). This is tied to PAHO’S strategy and institutional development plan that ranks countries and regions according to the scale.

The Pan American Network for Drug Regulatory Harmonization (PANDRH) under PAHO has issued a document titled The Regulation of Advanced Therapy Medicinal Products: Concept Note and Recommendations that highlights the progress made in advanced therapies, the risks associated with these products, and the regulatory challenges these products face. Efforts to create this document were driven by the need to develop standards and rules for regulating these products in order to control the use of unapproved therapies and prevent risks to the population. PAHO’s challenges include the need to regulate, the need for advanced therapies to be safe and effective, development in specified centers, and the need to have authorities provide guidance on therapies. Due to a lack of regulation and clear guidance, ANMAT established a lab for advanced therapies. Among the challenges are the lack of knowledge about advanced therapies and the resulting insecurity among patients, pharmacovigilance, a need for training and ethical practices, and regulatory considerations.

Continuous Manufacturing and ICH Q13

The promise of CM in Latin America is real. A product of advanced manufacturing, CM brings flexibility, availability, scalability, and cost-efficiency by creating an integrated process.

Challenges in the CM of cell and gene therapies include the lack of capacity for the manufacture of lentiviral and adeno-associated virus vectors (which limits clinical development), production process issues with current cell lines, and the inability to meet demand despite great strides and improvements in recent years.

ICH Q13 provides guidelines on the harmonization of technical and regulatory aspects unique to CM of drug substances and drug products for small and large molecules. Current challenges for ICH include maturity of the technology, harmonization of operating paradigms, terminology, regional considerations, and lifecycle management. The current draft of ICH Q13 is undergoing review and the final guideline is projected to be released in November 2021.

The strengthening of regulatory systems globally is a continuous effort for all. Improving the mechanisms for sharing and disseminating information is important, provides transparency, and reduces the risk of improper procedures. The efforts of the Latin America region are promising, and initiatives are underway to improve global collaboration and cooperation.