Impact Assessment of Divergence on Post-approval Changes Classifications of Latin America Region With Europe and the United States, and Propositions to Harmonize Classification Based on Risk as a Path to Build the Trust Between National Regulatory Agencies.

The lack of harmonization in the post-approval changes (PACs) classifications for pharmaceutical products may have an impact on the efficient implementation of PACs and in the supply of medicine, jeopardizing the continuity of therapies, especially in the case of chronic diseases. The percentage of similarity between the PACs classifications existing between countries of Latin America (Mexico, Brazil, Colombia, Venezuela, Argentina, Chile, Ecuador, Peru, and Central America) versus Europe and the United States (US) has been calculated, focused on the PACs for chemical products and on the minor and moderate variations as defined in the European Union (EU)1,2 and US3 regulations. Even though Mexico, Colombia, Brazil, and Argentina implemented a risk-based PACs classification, a wide diversity is observed, with a high percentage of variations classified as major or high risk for these countries and the rest of the Latin American countries, except for Venezuela (which previously adopted and recognized the EU classification). In addition, we identified a group/subset of PACs that are not categorized in the regulations of Mexico, Brazil, Chile, and Central America countries. Considering that Mexico, Brazil, and Argentina are members or observers of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use4 and the Pharmaceutical Inspection Co-operation Scheme,5 these countries could further align their PACs classification with the EU and US regulations. This could also be an opportunity for other countries of the Latin America region to recognize and adopt PACs classifications aligned to the EU or United States, which would also support the inclusion of reliance processes in their regulation for already considered/recognized reference countries. This would guarantee more health authority efficiency and optimization as well as more uniform implementation of PACs globally.

Worldwide Regulatory Reliance: Launching A Pilot on A Chemistry, Manufacturing and Control Post Approval Change for A Vaccine.

When an initial marketing authorization of a pharmaceutical product is granted, a substantial number of chemistry, manufacturing and control (CMC) post approval changes (PACs) have to be managed by the manufacturers. Despite efforts undertaken over the years by multiple regulatory jurisdictions, there is still heterogeneity in terms of regulatory requirements and timelines across national regulatory authorities (NRAs). This creates complexity in managing global CMC PACs, putting the supply of medical products at risk. Regulators have developed regulatory mechanisms which aim at accelerating the reviews and approvals of PACs by NRAs. The World Health Organization (WHO) is supporting the concept of 'reliance' amongst NRAs which are encouraged to rely on the assessment completed by a ″high-performing authority″. The objective is to accelerate the overall process for PACs, ultimately fostering more equitable and timely access of medical products to populations who need them. With the support of Health Canada, WHO, Pan American Health Organization, and the Paul-Ehrlich-Institut, Sanofi has launched a pilot using the principles of reliance for a CMC PAC for a vaccine, with 21 NRAs who accepted to participate in the pilot. The objective of this pilot was to apply these principles to reduce the approval timeline to a maximum of 6 months, in all countries after an initial approval is granted by a reference authority. We discussed the opportunities and challenges of implementing reliance principles for CMC PACs. We also described the pilot experience, by sharing initial lessons learned from the Step 1 of this pilot, which consist of engaging the reference authority and the NRAs.

Cooperation Agreements, Memorandums of Understanding, and Letters of Intent as Instruments to Facilitate the Implementation of Reliance in Latin America.

For more than a decade, the World Health Organization, Pan American Health Organization, Pan-American Network or Drug Regulatory Harmonization, and the International Conference of Drug Regulatory Authorities, have encouraged regulators to adopt reliance and recognition pathways to reduce duplication, improve efficiency and efficacy, and strengthen regulatory capabilities, in order to facilitate marketing authorization approval, thereby maintaining supply chain integrity. Several factors have limited the more widespread implementation of reliance pathways in Latin America, among which is having the appropriate legal tools in place between and among agencies. Key among these tools are the Memorandum of Understanding (MOU) and cooperation agreements. Herein we have reviewed the content and the characteristics of MOUs and cooperation agreements available on the official websites of the regulatory agencies of the region (we found 11 multilateral MOUs and 8 cooperation agreements published), signed by Latin American agencies and interregional organizations. In this commentary, common characteristics are identified and recommendations for further implementation are made to promote communication, information sharing, and trust, thereby supporting the broader use of reliance pathways in the region.

A Proposal of a Combined Convergence Regulatory Strategy Applied to Post-approval Changes by Latin American Countries, Reducing Workload and Allowing Continuous Improvement to Guarantee the Quality, Safety, and Efficacy of Medicines.

In recent years, post-approval changes (PACs) for medicinal products have increased faster than the national regulatory agencies can attend to without causing any negative impact. This study presents a proposal for regulatory management based on our analysis of the data available from the national regulatory agencies of Latin America on the total post-approval changes evaluated, and the time spent in the process. A retrospective search on the official websites of competent national regulatory authorities (NRAs) of 14 Latin American countries (México, Guatemala, Nicaragua, Honduras, El Salvador, Panamá, Costa Rica, Venezuela, Colombia, Ecuador, Peru, Argentina, Chile and Brazil) was conducted to collect data on post-approval changes in the last 4-6 years, up to January 2021. The NRAs considered were Brazil, México, Colombia, and Costa Rica. Our analysis was focused on the post-approval changes that required approval before implementation, those that were submitted, and those that were submitted and approved for small molecules, biologics, and biotechnological products. The results indicated differences in the regulatory processes and procedures applied by the different agencies. We also found that the implementation of the PACs was directly impacted by limited resources, which puts the medication supply for chronic treatments at risk resulting in serious consequences for patients. For local decision-making, Latin American NRAs should implement regulatory pathways already made by regulatory agencies included in the World Health Organization Listed Authorities on PAC approval to optimize their resources and to ensure the continuity of medicine supply for their patients.

Regulatory Agilities in the Time of COVID-19: Overview, Trends, and Opportunities.

PURPOSE: Crucial steps have been adopted by health and regulatory authorities around the world to respond to the COVID-19 pandemic. This review aims to highlight these steps by providing an overview of the regulatory approaches adopted during the onset of the pandemic, provide an assessment of observed trends, and offer some reflections and proposals to leverage learnings and opportunities from this current pandemic. METHODS: Documents and informational materials on regulating the development and management of medical products during the COVID-19 pandemic were collected and classified. These materials were sourced from official websites and press releases from health authorities and international bodies from selected markets across the globe, and covered the period between January and July 2020. Additional information to support this study was gathered through a literature review and analysis of related data available from the public domain, and was complemented with the authors' personal experience. FINDINGS: Communication has been vital in addressing the impact of COVID-19. A total of 1705 documents and informational materials related to health or regulatory response to the COVID-19 pandemic were gathered. Of these, 343 (around 20%) were identified as regulatory agilities. These agile approaches were classified into 3 categories, namely, where health and regulatory authorities had: (1) facilitated product management across the entire lifecycle, notably in expediting medical product use for COVID-19, ensuring the continuity of clinical trials, and addressing supply chain issues; (2) strengthened international cooperation; and (3) addressed regulatory burden with the adoption of electronic and digital tools. IMPLICATIONS: While many regulatory measures have been introduced temporarily as a response to the COVID-19 crisis, there are opportunities for leveraging an understanding from these approaches in order to collectively achieve more efficient regulatory systems and to mitigate and address the impact of COVID-19 and further future-proof the regulatory environment.