Differences between Pharmacovigilance Regulatory requirements in Latin America

Pharmacovigilance is defined, according to the World Health Organization (WHO), as “science and activities related to the identification, evaluation, understanding and prevention of adverse effects or any problems related to the use of medicines”.


WHO has a forum for member countries to join the Program for International Drug Monitoring, so that these countries can collaborate in monitoring safety and, mainly, in identifying and analyzing new safety signs. Bearing in mind the sensitivity inherent in the collection of safety signs, there are certain requirements that all countries have to fulfill in order to be integrated in this program and, also, have an administrative structure for their Pharmacovigilance activities. One of the requirements is the creation of a National Drug Monitoring Center, designated and recognized by the Ministry of Health.


That said, each country has to develop its own Pharmacovigilance system based on the difference in manufacturing, local practices and genetics, all of which can lead to variability in terms of the use of medicines and the profile of adverse effects. In Latin America it is worth noting the existence of a medium to high level of Pharmacovigilance standards, in relation to the international standards recognized as high surveillance.


These differences in the organization and levels of development in the countries necessarily imply that a single approach is not suitable for all countries but sharing best practices across regions is an asset. In this sense, in 1990, the International Conference on Harmonization (ICH) was created. ICH’s mission is to achieve the greatest harmonization, worldwide, in order to guarantee the existence of safe, effective and high-quality medicines, and that these developments are done in the most resource efficient way. To apply this mission, ICH guidelines were developed, through a scientific consensus process formed by experts in regulation and industry, from all over the world.


A study was carried out in a comparative format in order to analyze the government laws that regulate the activities of the companies that have products registered in Latin American (LATAM), and compare with the guidelines proposed by the ICH. The countries included in this study were Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Jamaica, Mexico, Nicaragua, Panama, Paraguay, Peru, Uruguay and Venezuela.


  1. Periodic Pharmacovigilance Report:

It is mandatory to carry out this report, according to ICH, for all registered or commercialized products, however, 7 of the 18 countries analyzed, only require the existence of this report for commercialized products, another 5 require that it also be carried out for all registered products. , and the remaining 6 countries do not specify.

The safety report is one of the tools that facilitates communication between companies and regulatory agencies, in addition to the fact that these studies suggest a tool that contributes to 38% of post-MAH regulatory actions and 64% of new adverse drug reactions (RAM).

Although the importance of the continuous monitoring of the safety of medicines, big differences were identified in the reports submitted to the regulatory agencies, in these 18 LATAM countries, in topics such as definition of products that these reports must contain, language, periodicity and start date of the monitoring, report format, submission deadline. These differences lead to an increase in the difficulty of working together between the different agencies.


  1. Individual Report
  • ICHs suggest adopting the CIOMS-I format, but only 16% of the LATAM countries are using this format, and the rest are using local forms.
  • Of the 18 countries, only 5 have an online notification service, most of the others request via e-mail or telephone and 2 countries have the E2B system. ICHs do not specify the most correct method of submission.
  • 67% of these countries require minimum criteria for the report to be considered valid. The criteria that are in ICH are: patient, suspect product, adverse event and notifier.
  • 22% of countries mention people who may be notifiers, but ICHs do not specify this point.
  • 7 of the 18 countries specify in their legislation the type of cases that can be reported as adverse reactions.
  • 5 out of 18 countries specify that notification must be made within 24 hours after the adverse reaction, 4 within 72 hours and only 1 in 28 hours, for serious adverse reactions. The ICH suggest that adverse and unexpected reactions should be reported within a maximum of 15 days.
  • None of the countries specify in their legislation the need to notify foreign cases.


  1. Responsible for Pharmacovigilance

The person responsible for Pharmacovigilance is the professional officially designated by the holder of the MAH, who is responsible for the safety of pharmaceutical products for human use, marketed by the company in its country. It is necessary that this person is qualified for the position and that he / she still undergoes training for this position specifically.

83% of the countries under study refer the mandatory existence of a person responsible for Pharmacovigilance in the pharmaceutical companies, however only 33% specify that this must be a health professional.


  1. Search in Scientific Literature

The scientific medical literature is recognized as a valuable source of information for monitoring the safety and the benefit-risk balance of medicines, mainly in relation to the detection of safety signs or in the identification of emerging safety issues. For this reason, it is necessary, at least once a week, for those people responsible for Pharmacovigilance to review the literature of widely used databases. For the execution of this process, MAH holders must have established a standard operational procedure for monitor these scientific and medical publications in the local magazines and in the countries where your medicines are marketed. Of the identified cases, it is necessary to establish a causal relationship with the drugs, and the valid individual cases must be submitted according to the country-specific deadlines and methodologies, in accordance to its legislation.

40% of the countries under study require this search in the scientific literature, but none of the legislation mentions parameters, periodicity, strategy, selection and restriction of terms in this search in the scientific literature, necessary documentation for this procedure, description of standards, such as the date knowledge of information, analysis of duplicity and process of submitting the literature report to the Regulatory Agency.


  1. Self-inspection

Self-inspection aims to assess the manufacturer’s compliance with Good Manufacturing Practices (GMP) in all aspects of production and quality control. This procedure, in addition to detecting any deficiencies in the implementation of GMP, also aims to recommend corrective actions for them, and therefore, these should be carried out periodically or in special situations.

Of the countries under analysis, only 33% mention in their legislation the mandatory performance of these self-inspections.


  1. Signal detection

A signal is defined as a hypothesis of a risk with a drug with data and arguments that support it, derived from data or from other possible sources. The evidence of a sign is not considered conclusive, as it may vary over time as more evidences are accumulated, however, the signs may offer additional or new information about the adverse or beneficial effects of an intervention, or information about the causality between a drug and an identified adverse reaction.

Although 72% of the countries studied require the implementation of the signal detection process, many of these LATAM countries do not have this process effectively implemented.


  1. Risk Management Plan (RMP)

In 2005, the European Medicines Agency (EMA) introduced the RMP as a tool for planning Pharmacovigilance activities and minimizing risks for new drugs, which allowed the adoption of a more proactive approach regarding knowledge on health issues including the safety of medicines. The RMP is defined as the plan that identifies the risks associated with a drug and the methods to clarify the safety profile, as well as the tools designed to minimize the risk to individual patients during clinical practice.

78% of the countries in this study require the presentation of a RMP and only 6 of the 18 countries require a specific local format in Spanish, not being in harmony with the format of the other LATAM and European Agencies, and this lack of harmonization makes it difficult to assess the data presented and analyzed jointly by the Regulatory Agencies.


In conclusion, the evolution of Pharmacovigilance systems is extremely important to ensure the protection and safety of patients, and to obtain more effective systems. For the reason, it is important to share information about the safety of medicines between the different regulatory authorities and also the need for them to adopt the international standards accepted.

Regarding the regulatory authorities of LATAM countries, it is worth noting the adoption of this mentality more and more, with increased knowledge about the need to have a strong Pharmacovigilance system to ensure patient safety.