The Latin American region of the globe—which includes large countries such as Brazil, Mexico, Argentina, Columbia, and Peru—is undergoing a transformation marked by the stepwise harmonization of pharmaceutical regulations with international norms and standards. While it is a slow process and each country’s regulatory agency faces its own unique journey, progress is being made.

At the FDA/Xavier PharmaLink conference held virtually in March 2020, Merck CMC Director and Senior Scientist Tatiana Gaban—who has led Merck’s CMC Latin America team based in Sao Paulo—provided an in-depth look at the changing CMC regulatory landscape in Latin America.

Part 1 of this three-part article explores Gaban’s insights into drug product approval processes within the region, including challenges and opportunities. The two subsequent articles will provide more details on specific country requirements for Brazil, Mexico, Argentina, Columbia, and Peru.

She characterized Latin America as a region with “a very evolving regulatory landscape with highly active health authorities.” Activity is measured by the volume of draft/final regulations a regulatory body promulgates and its frequency of interactions with trade associations and the drug companies it regulates, the Merck director explained.

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Harmonization and regulatory convergence in the region are primarily taking place in line with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). This occurs as national regulatory agencies become observers or members of ICH and adopt some of its guidelines.

Global versus Local Requirements

Although the agencies seek global harmonization, “they are struggling with the right balance of local versus global requirements,” Gaban said. While Brazil, Mexico, and Colombia are officially adopting the ICH guidelines, “there is a high demand for country-specific requirements.”

She characterized Latin America as a region with “a very evolving regulatory landscape

The governments rely on product approvals by reference regulators such as FDA and EMA to inform their decision-making but still carry strong sovereignty over regulatory processes. Even though Latin American health authorities are interested in knowing approval information that was submitted to the reference health authorities, on most occasions they require some level of CMC data for review by doctors within their country. 

The information that is required in addition to that submitted to reference health authorities Gaban terms “ancillary documents.”

“Country specific CMC requirements demand substantial coordination from pharmaceutical companies both pre- and post-approval,” Gaban emphasized. “When we work in regional companies and we must plan files that are going to be released and filed across the globe, there is a lot of coordination that has to be done. The more varieties that you have in the regulatory requirements worldwide, the more difficult it is going to be to manage the information. Working with global filings can be particularly challenging.”

There are many ancillary documents requested for filings in many countries—for example, declarations and raw data. The list of required documents is extensive. The Common Technical Document (CTD) Module 3 is used as a source of information, but customization is happening at the country level. And there is still some specific work that occurs at the country level, such as translations and templates for local forms. 

“Brazil is the only country in Latin America that has published a guideline on ICH and forms related to the structure of the CTD,” Gaban said.

Gaban provided a table that shows “the number of ancillary documents that could be required for small molecule registration for some markets in Latin America, sometimes with extremely specific demands. This is an example from the company I work for, Merck. There are specific documents that are needed in addition to the core content that is used worldwide” (Figure 1).

Latin America Overview

Figure 1 Overview of Ancillary Documents Needed for Small New Molecule Registration

Working with global filings can be particularly challenging

Approximately 48 ancillary documents are required in addition for Brazil, 23 for Mexico, 20 for Peru, 16 for Ecuador, and 13 for Argentina. 

“The number may vary, but it will be close to this,” Gaban explained.

Challenges and Opportunities

In summary, “when we think about the regulatory environment in Latin America, we think about regulatory convergence. We try to plan regulatory filings in advance using the principles of strategic and operational excellence,” Gaban said (Figure 2).

Challenges and Opportunities in Latin America

Figure 2 Challenges and Opportunities in Latin America

“Regarding regulatory convergence, we have some challenges. Convergence demands strong efforts with policy and advocacy. Health Authorities are open for dialog but implementation may be challenging. We also have opportunities to streamline regulatory processes and decrease approval timelines, allowing products to patients quicker.”

She noted that when planning regulatory filings in advance, challenges include a fast-evolving regulatory environment and that requirements and Health Authority expectations may change along the way. Opportunities include anticipating critical hurdles and pre-submission meetings in some large markets such as Mexico and Brazil.

When discussing balancing risks and benefits, challenges include the amount of work demanded by Latin America for filing may put the region in a lower prioritization wave inside the company. There are also opportunities, however, in that it is a region with a big population and various unmet medical needs.

The challenges in strategic and operational excellence include having qualified regulatory resources and considerable efforts to manage all operational demands. Opportunities include the use of bundling or shared packages—for example, in Central America and the Caribbean—taking advantage of the same language in Spanish-speaking countries.

Part II will look at specific requirements for Brazil while Part III will review CMC requirements for Mexico, Argentina, Columbia, and Peru.

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