ES10.05 Brazilian Health Regulatory Agency - Agência Nacional de Vigilância Sanitária

Abstract

Brazil, the largest country in South America, has become the second largest pharmaceutical market in the emerging world. The Brazilian Health Surveillance Agency (Agencia Nacional de Vigilancia Sanitaria – ANVISA) was created in 1999 with the primary goal to protect and promote public health surveillance over products and services in Brazil. Its hallmarks are administrative independence, financial autonomy, and the stability of its directors. Within the federal public regulatory structure, the agency is linked to the Ministry of Health [1]. Despite major advances in the regulatory process in Brazil, it is important to highlight that a major delay in cancer drugs approval over the last decade has had a negative impact on patient access to novel medications in Brazil. According to Barrios et al., [2] well-established and adequately functional drug approval legislation is indispensable to guarantee a country’s population health. Any malfunctions or delay in such a crucial process have serious consequences. As an example, the drug Crizotinib (Xalcori®Pfizer, NY, USA), which had its approval denied by ANVISA in June 2014 may be seen as a landmark. Assuming different premises, Barrios et al. [2] calculated 1.367 years of life lost over 34 months due to lack of access to Crizotinib between August 2011 (FDA approval) to June 2014 (refusal by ANVISA). Of note, Crizotinib was not approved in Brazil until Feb 2016, what may have added additional 804 years of life lost to final numbers due to this delay. Other example of unexplained delay in drug approval in lenalidomide. The gap between the drug approval in the US and Brazil was 12 years. Regarding drugs that do require a companion diagnostic, the situation may become more complicated since, unlike the US Food and Drug Administration, no clear mechanism is in place with ANVISA for the simultaneous linking of most companion diagnostic tests with their respective targeted therapeutic drug [3]. In trying to understand the reasons behind this delayed drug approval process, methodological, cultural, political and ideologic reasons may account. At odds with other regulatory agencies such the FDA that allow conditioned approval based on non randomized data for drugs addressing unmet medical needs. For many years ANVISA authorities mandated randomized phase 3 data for a definitive approval, since no conditioned approval was allowed. In this context, having a specific oncology area or committee, such as the FDA Oncology Drug Advisory Committee [4], may be crucial. Fast track approval, breakthrough designation, companion diagnostics, different surrogate endpoints, integration of real world evidence (RWE) into the regulatory process are very specific topics from the oncology field and do require to be analyzed under the perspective of cancer specialists. From a political, cultural and ideologic perspective, although it is notorious that Brazil has invested substantially in expanding access to health care for all of its citizens, the country has, essentially, two clear distinct and dissimilar health systems [3]. The public system allows drugs to become commercially available through processes that are different from those in place in the private health-care system. Although difficult to measure those disparities and difficulties to reimburse expensive drugs in the public system, may have influenced the delayed process during the last decade. Over the last decade, delays at ANVISA’s approval process have been considered the only reason for the inequitable access to oncology care between the USA and Brazil. Yet, this may be a biased conclusion and a more comprehensive analysis in needed. By analyzing a basket of twenty-three oncology products approved by ANVISA after 2002 Bustamante et al. [5] identified that on average there was a difference of 8.6 months (449 X 186 days). However, on average, a delay in the manufacturers’ submission for regulatory approval of 1.1 years (393 days between Brazil and the USA) was also identified. More recently, a trend toward improvements in the drug approval process has been identified (ex. Osimertinib and Durvalumab). Osimertinib was firstly approved by ANVISA in 2017 as a second line treatment in patients who did not respond well to the initial drug. With the new determination, in 2018 ANVISA approved its use as a first therapy to treat locally advanced non-small cell lung cancer. Durvalumab was approved by ANVISA in 2017. Nevertheless, there is clear room for a continuous improvement. Increase in the number of ANVISA technicians, continuous training and collaboration with academic institutions and other regulatory agencies elsewhere are mandatory. Close scientific collaboration and open and transparent dialogue between ANVISA and pharmaceutical companies are required. In sum, if we are to have a continuous improvement in the oncology drug approval process, all the stakeholders (ANVISA, drug manufactures, patient advocacy, players at the private and public health systems) must act together.