Artigos

1. INTRODUCTION
Timely access to innovative therapies is a critical aspect of modern healthcare systems. However, differences in the timing of regulatory approval—commonly referred to as relative time difference or launch delay—remain a persistent challenge in many countries, particularly in emerging economies. Such gaps can significantly impact patient access to innovative treatments and contribute to inequities in global health outcomes (1).
In recent years, several countries have prioritized efforts to assess and reduce the gap in regulatory approval. The U.S. Food and Drug Administration (FDA) is often used as a benchmark, as it is frequently the first to approve new molecular entities (NMEs) (2). In contrast, the approval process conducted by the Brazilian Health Regulatory Agency (Anvisa) in Brazil may experience longer intervals that postpone patient access to innovative treatments (3). Comparative studies involving the FDA and other regulatory agencies—such as the European Medicines Agency (EMA), the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan, and the National Medical Products Administration (NMPA) in China—have revealed substantial differences in launch times, some of which have been mitigated through policy and procedural reforms (5-7).
Regulatory processes can be lengthy, influenced by various factors, including differences in submission requirements, review procedures, and available resources within regulatory bodies. However, it is important to recognize that regulatory review is not the sole determinant of a drug's availability in the market. A variety of additional factors can contribute to time differences in drug availability. These include commercial strategies, such as prioritizing larger or more profitable markets, pricing and reimbursement negotiations, supply chain limitations, and the coordination of marketing campaigns (7). In some cases, companies may choose to postpone registration in countries where price controls or mandatory discounts could affect profit margins. Studies indicate that marketing authorization holders tend to prioritize launching in markets with free pricing or higher prices, as these countries often serve as external price references for other jurisdictions, impacting global revenues (25, 26). Furthermore, infrastructure readiness, local clinical guidelines, and national demand expectations also play a role in determining the timing of product introduction (8-11).
In Brazil, the marketing authorization granted by Anvisa is a prerequisite for initiating the mandatory pricing process conducted by the Drug Market Regulation Chamber (CMED). This two-step regulatory structure means that obtaining Anvisa approval is not sufficient for a drug to be launched; a price cap must also be approved by CMED before commercialization can occur. As a result, the Brazilian regulatory pathway involves additional complexity and can potentially extend the timeline for actual market access compared to other countries. Despite institutional advances in the last decade, concerns persist regarding the pace of access to new therapies when compared to reference markets. Although previous studies have highlighted this gap (12, 13), few have systematically quantified the time difference between the FDA and Anvisa using public drug-level approval data.
The term "relative time difference" describes the temporal gap between when a drug is approved or introduced in one country compared to another, while absolute time difference refers to disparities in the total number of new medicines accessible in each country (14, 15). The present study aims to evaluate the relative time difference specifically concerning the marketing authorization (registro sanitário) between the Brazilian market and the United States between 2014 and 2023. By analyzing and matching drug approval dates from both the FDA and Anvisa, this study seeks to quantify temporal gaps in regulatory availability and identify potential patterns across therapeutic areas. Importantly, this evaluation strictly compares the dates of marketing authorization decisions and does not measure overall market availability or commercial introduction, given that pricing approval steps are outside this study's scope. Understanding these temporal discrepancies can help identify potential barriers beyond the regulatory process, such as commercial strategies, market dynamics, and logistical challenges that may influence drug availability.
2. METHODS
Study Design and Data Sources
This was a retrospective descriptive study designed to compare the time difference in regulatory approval of new molecular entities (NMEs) approved in the United States and Brazil. The analysis included all NMEs that received marketing authorization from the U.S. Food and Drug Administration (FDA) between January 2014 and December 2023. For each of these drugs, we investigated whether a corresponding approval had been issued by the Brazilian Health Regulatory Agency (Anvisa) and, if so, on what date. The cut-off date for determining regulatory status in Brazil was May 31, 2025, meaning we assessed whether the selected NMEs had received marketing authorization from Anvisa by that date. Data were extracted from publicly available regulatory databases maintained by the FDA, Anvisa, and the Drug Market Regulation Chamber (CMED).
Selection of New Drugs
A list of NMEs approved by the FDA was obtained from the Center for Drug Evaluation and Research (CDER), which provides consolidated annual records of newly approved drugs. All NMEs approved between 2014 and 2023 were included. Diagnostic agents and products not intended for therapeutic use were excluded.
Data Integration and Matching Process
Since Anvisa does not provide a consolidated list of NMEs, matching with FDA-approved drugs was performed using a combination of non-hierarchical clustering algorithms and manual verification of active ingredients or trade names. To identify corresponding drugs in Brazil, a structured database was developed in Python by the research team, integrating data from CMED price records and Anvisa marketing authorization records, using the CNPJ (National Registry of Legal Entities) of Brazilian companies as a key variable. This integrated dataset included the Anvisa marketing authorization number, product name, company information, approval date, regulatory status, formulation, and pricing data from the Maximum Price List (managed by GGREM - General Management of Economic Regulation and Market Monitoring). The corresponding regulatory category for NMEs matched in Brazil was specified as "Medicamentos Novos" (New Drugs) within Anvisa's database. The identification of each drug and its approval date in Brazil was performed using this dataset. When necessary—for example, in cases of incomplete or ambiguous records—information was cross-validated manually using Anvisa's online consultation tool.
Outcome and Calculation of Time Difference
The primary outcome of this study was the regulatory approval time difference, defined as the interval (in months) between the marketing authorization date granted by the FDA and the corresponding approval date by Anvisa for each matched drug. This metric reflects the temporal gap between the regulatory decision for a new drug in the US and Brazil. Importantly, the time difference does not measure regulatory review time, as submission dates were not available for either agency. Instead, it captures the difference in approval dates, serving as a proxy for the time gap in regulatory entry into the Brazilian market. To explore potential factors associated with longer approval intervals, we performed analyses stratified by therapeutic class, as defined by the Anatomical Therapeutic Chemical (ATC) classification system. To explore patterns in regulatory timelines, drugs were categorized into three groups:
• Group A: drugs approved by Anvisa after FDA approval;
• Group B: drugs approved by Anvisa before FDA approval (either during 2014-2023 or previously);
• Group C: drugs not granted marketing authorization in Brazil by the end of the observation period.
Cases where a drug was approved in Brazil before the FDA were kept in the dataset and analyzed separately to assess the frequency and characteristics of these occurrences. These cases were carefully reviewed for data inconsistencies or exceptional regulatory pathways (e.g., locally developed drugs or those approved via international cooperation agreements). Sensitivity analyses were conducted to assess the impact of excluding such exceptional cases on the overall findings.
Statistical Analysis
Continuous variables, such as the approval time difference, were described using means, standard deviations (SD), medians, and interquartile ranges (IQR). Categorical variables were summarized as frequencies and percentages. The Kruskal-Wallis non-parametric statistical test was employed for comparisons between therapeutic classes. Statistical significance was defined as a p-value less than 0.05. All statistical analyses were conducted using Python.
3. RESULTS
Sample and overall time difference
Between 1985 and 2023, the FDA approved 1,289 drugs, including those for diagnostic use. For this analysis, 437 drugs approved between January 2014 and December 2023 were eligible. These drugs constituted the study sample and were subsequently matched with Anvisa data.
Of the 437 drugs approved by the FDA, 46.7% (n = 204) were also authorized in Brazil, while 53.3% (n = 233) had not received marketing authorization from Anvisa by the end of May 2025. The mean difference (± standard deviation, SD) in approval time between the FDA and Anvisa was 12.40 ± 53.58 months, with a median (interquartile range, IQR) of 16 (21.01) months and a range of -439 to +111 months (Figure 1).

Fig.1

The longest interval observed between approvals occurred with metreleptin, approved for the treatment of patients with lipodystrophy, which was authorized in Brazil nine years after its FDA approval.
A scatter plot (Figure 2) was constructed to visualize the relationship between approval dates by the two agencies. FDA and Anvisa approvals were limited to the 2014-2023 period. Points positioned near the central diagonal line represent drugs with similar approval dates in both agencies. However, a higher concentration of points above the diagonal suggests that most drugs were approved in the United States before approval in Brazil.
Most drugs approved by both agencies were authorized in Brazil within two years of FDA approval. As detailed below, 18 (8.8%) drugs were approved by Anvisa before the FDA, representing exceptional regulatory pathways, while the remaining matched drugs fell into Group A. Two exceptional cases were identified with minimal differences in approval dates: empagliflozin, with a difference of 11 days, and vosoritide, with a difference of 10 days.

Fig.2

Label: Each dot represents a new drug approved by the FDA between 2014 and 2023 and its corresponding Anvisa approval date. Anvisa approvals prior to 2010 were excluded. The central diagonal indicates simultaneous approval dates. Points above the line represent drugs approved first by the FDA; those below the line were approved first by Anvisa.
Source: Elaborated by the authors.
Group A - Drugs approved by Anvisa after FDA approval
Among Group A drugs (approved first by FDA, n = 186), the majority belonged to class L - Antineoplastic and immunomodulating agents (94 drugs; 50.5%), followed by class J - Anti-infectives for systemic use (24; 12.9%) and A - Alimentary tract and metabolism (18; 9.7%). Other classes, such as N - Nervous system (11; 5.9%), B - Blood and blood-forming organs (9; 4.8%), and C/R - Cardiovascular and Respiratory systems (7 each; 3.8%), were less frequent. The remaining categories represented less than 3.0% each. These findings highlight the predominance of oncology and infectious disease treatments among drugs approved by both agencies.
Figure 3. Distribution of Therapeutic Classes (ATC First Level) - Group A.

Fig.3

Source: Elaborated by the authors.
The approval interval for Group A varied among therapeutic categories defined by the first level of the ATC classification. The median interval ranged from approximately 8.8 months in the musculoskeletal system to over 37.4 months in systemic hormonal preparations. The Kruskal-Wallis test revealed a borderline statistically significant difference between ATC groups (H = 18.20; p = 0.0518), suggesting a potential variation in regulatory timelines by therapeutic class. Although this result does not reach conventional significance (p < 0.05), it indicates a possible trend warranting further exploration, particularly given the wide interquartile ranges observed in certain categories, such as the nervous system and anti-infectives.
Group B - Drugs approved by Anvisa before FDA approval
Among the 204 drugs approved by both the FDA and Anvisa between 2014 and 2023, 18 (8.8%) were approved first in Brazil. These drugs cover a broad spectrum of therapeutic classes, ranging from treatments for chronic diseases—such as dapagliflozin for type 2 diabetes and olodaterol for Chronic Obstructive Pulmonary Disease (COPD)—to medicines intended for rare or neglected conditions, such as benznidazole for Chagas disease and trabectedin for soft tissue sarcomas.
Approval intervals for these drugs ranged from -0.4 to -439 months, with a median of -32.5 months, meaning most were approved in Brazil several years before being authorized in the US. The distribution of therapeutic classes highlights Brazil's multifaceted regulatory priorities, balancing the need for broad access to treatments for chronic conditions with responsiveness to local epidemiological burdens (Supplementary Material). The most extreme case was benznidazole, approved by Anvisa in 1981 and by the FDA only in 2017—a difference of 439 months (36.6 years). Although the product was re-approved under the brand name Rochagan® in 2006, the original approval date was maintained for consistency.
Similarly, deflazacort (-256 months) and amisulpride (-287 months) also demonstrated long approval intervals. Manual verification confirmed that the earliest Anvisa marketing authorization for amisulpride was classified as a similar drug (branded generic), and subsequent entries did not specify the regulatory category—therefore, the earliest available date was used.
The antiviral product Viekira Pak® illustrates the complexity of cross-agency comparisons. The FDA approved a combination of ombitasvir, paritaprevir, and ritonavir, while the version approved by Anvisa included ombitasvir, veruprevir (equivalent to paritaprevir), ritonavir, and dasabuvir. Despite this discrepancy, the product was retained in the analysis due to its therapeutic relevance and clinical impact on hepatitis C treatment. Figure 4 summarizes the regulatory timelines and approval intervals for these 18 (8.8%) products.
Detailed ATC classification coding for all drugs included in the analyses is available in the Supplementary Material (Table S1).
Figure 4. Time difference for drugs approved first by Anvisa and subsequently by the FDA (n = 18).

Fig.4

Label: This horizontal bar chart displays the approval difference in months for 18 (8.8%) drugs that were approved first by the Brazilian Health Regulatory Agency (Anvisa) and only subsequently by the U.S. Food and Drug Administration (FDA). Negative values indicate the number of months by which approval in Brazil preceded approval in the United States. The drugs cover a wide range of therapeutic classes, and the longest observed interval was for benznidazole (-439 months), used to treat Chagas disease
Source: Elaborated by the authors.
Group C - Drugs not approved in Brazil by the end of the observation period
Group C drugs, which had not received marketing authorization from Anvisa by the end of May 2025, totaled 53.3% (n = 233). An analysis of the annual distribution of FDA-approved drugs and their marketing authorization status in Brazil reveals a clear temporal pattern. Between 2014 and 2017, the proportion of drugs authorized in Brazil was relatively high, with registration rates close to or exceeding 50.0%. For example, in 2014, 61.5% (n = 24) of 39 drugs were granted marketing authorization by Anvisa, compared to only 27.8% (n = 15) of 54 drugs in 2023. Figure 5 summarizes annual trends in the status of FDA-approved drugs in Brazil.

Fig.5

Label: This stacked bar chart displays the annual number of new drugs approved by the FDA between 2014 and 2023, categorized by their marketing authorization status in Brazil as of May 2025. The blue portion represents drugs authorized by Anvisa, and the orange portion represents drugs not yet authorized or with no identifiable records. A notable increase in the number of unauthorized drugs is observed in recent years (2022-2023), likely reflecting the typical time difference observed between regulatory approvals in the two countries.
Source: Elaborated by the authors.
4. DISCUSSION
This study compared the time difference in the regulatory approval of new drugs in Brazil and the United States. Instead of assessing the duration of the review process within each agency, the analysis focused on the difference between marketing authorization dates issued by the FDA and Anvisa. While this approach does not capture the exact timing of commercial launch or submission behavior, it provides valuable insights into the relative timing of regulatory access to new therapies in both countries.
International studies confirm that the approval interval is a global issue, although its extent and underlying causes vary. A recent study by Barreto et al. (2024) (12) on oncology drugs corroborates our findings, reporting a median time difference of 558 days between FDA and Anvisa approvals. Similarly, Alqahtani et al. (2015) found consistent differences even between the FDA and EMA, with the FDA approving 87.0% of shared drugs first (24). These patterns reinforce that regulatory gaps are not exclusive to low- and middle-income countries but reflect broader structural and procedural divergences between systems.
In China, Zhu et al. (2024) reported a median time gap of 3.5 years between FDA and local approvals, with only 41.3% of drugs approved in both markets by 2023 (16). Factors such as the inclusion of Chinese study centers in pivotal trials and the use of expedited regulatory pathways were associated with shorter intervals. In South Korea, Cho and Han (2022) found time gaps of 40 to 108 months prior to 2016, improving to 22-27 months thereafter (17). In contrast, our findings show a smaller median difference in Brazil—12.4 months on average, and 46.7% (n = 204) of FDA-approved drugs were also granted marketing authorization in Brazil by May 2025. These results suggest that, unlike in China and Korea, the interval in Brazil may be less influenced by local clinical data requirements and more by submission strategies and regulatory capacity.
While the FDA operates under structured pathways such as PDUFA (18), with standard and priority review timelines of 10 and 6 months respectively, Anvisa's processes are governed by Law No. 6.360/1976 (19). The amendments introduced by Law No. 13.411/2016 established explicit statutory limits for final regulatory decisions based on technical complexity and clinical, economic, and social benefits (Art. 17-A). Specifically, the legal frameworks define a maximum timeline of 120 days for priority categories and 365 days for ordinary registration procedures, counted from the respective protocol dates. To meet these deadlines and shorten overall evaluation times, recent work plans by Anvisa focused on workforce optimization and enhancing the number of health regulation experts to systematically reduce the administrative backlog ("filas") and clear pending processes. Despite these legislative and organizational improvements, resource constraints and procedural inefficiencies persist. Furthermore, the absence of publicly accessible submission date records in Brazil limits the ability to distinguish industry-driven submission timelines from agency review times.
The median time difference of 16 months reflects the interval until regulatory availability in the Brazilian market, encompassing both the industry's strategic decision time for submission and the agency's review time. However, the wide variation evidenced by the high standard deviation shows that a substantial number of approvals in Brazil occur more than two years after FDA authorization. Notably, some extended intervals may stem from strategic decisions by pharmaceutical companies regarding market entry in Brazil. As demonstrated in reference 13, structural differences in global launch orders indicate that marketing authorization holders often choose to postpone dossier submissions in secondary reference markets based on intellectual property and international reference pricing controls.
Furthermore, the lower authorization rates observed for FDA-authorized drugs in recent years likely reflect the natural regulatory approval interval rather than a decline in submissions to Anvisa. Given the median time gap of 16 months, many products approved after 2021 may still be under review or awaiting submission in Brazil. This highlights the importance of considering typical time lags when comparing regulatory data between agencies to avoid misinterpreting recent trends as performance declines.
Recent efforts to reduce the regulatory gap include the Confidentiality Commitment between Anvisa and the FDA (20), which allows shared access to clinical and post-marketing data. In parallel, Anvisa's RDC No. 204/2017 (21) established a national priority review mechanism, aligning with expedited pathways such as the FDA's Breakthrough Therapy and EMA's fast-track procedures (22). Furthermore, recent developments regarding expanded pathways for rare diseases or public health emergencies have accelerated international data integration. However, expedited reviews may involve trade-offs. Crizanlizumab (Adakveo®), approved in Brazil under RDC No. 205/2017 for rare diseases, was subsequently withdrawn due to an unfavorable benefit-risk balance, echoing similar action by the EMA (23). These cases illustrate the importance of post-marketing reassessment in accelerated pathways.
Interestingly, we identified 8.8% (n = 18) drugs approved first in Brazil. In two cases, the difference in approval dates was minimal, suggesting similar submission timelines. One such drug, benznidazole, targets Chagas disease, which is endemic in Brazil but rare in the US, possibly explaining its earlier approval. These examples highlight how national public health priorities can influence regulatory timelines.
A major limitation of this study is the absence of data on submission dates for marketing authorization applications to Anvisa and the FDA. Without this information, and despite the electronic search availability in portals like "Consultas Anvisa", it is not possible to accurately distinguish whether the observed temporal differences result from regulatory analysis times or from commercial strategies of companies, which may choose to postpone submission in certain markets. Furthermore, this study compared approvals based on the active ingredient, without controlling for differences in approved clinical indications, which may vary between agencies and impact evidence requirements and review times.
Collectively, these findings reinforce the need for continuous comparative analyses to identify barriers and promote timely access to innovation in Brazil.
5. CONCLUSION
Time differences in drug approval between regulatory agencies can have substantial consequences for public health and the pharmaceutical sector. The estimated mean approval time difference between the FDA and Anvisa was 12.4 months. While many drugs are incorporated into the Brazilian market within one to two years after FDA approval, a significant proportion still faces gaps exceeding 24 months, potentially compromising patients' timely access to innovation. The analysis revealed distinct patterns among groups: most drugs were approved in Brazil after the FDA, a small subset was approved first by Anvisa, and more than half had not yet received Brazilian approval by the cut-off date. These findings underscore the importance of strategies to reduce regulatory time differences and promote earlier submission and review of innovative therapies in Brazil.
The trend towards shorter approval times in recent years suggests that regulatory initiatives—such as the introduction of priority review pathways—may be having an effect. However, variability in regulatory approval times remains considerable, underscoring the need for continuous process optimization and improved transparency. Nevertheless, some limitations were noted, particularly inconsistencies in records available on the Anvisa platform, where the earliest approval date sometimes referred to a different pharmaceutical form or therapeutic context than that evaluated by the FDA.
As a preliminary and descriptive analysis, this study provides a foundation for future research aimed at exploring regulatory timelines more comprehensively. Incorporating additional variables—such as submission dates, marketing authorization type (standard vs. priority), and therapeutic class—could yield deeper insights into the determinants of regulatory approval times in Brazil. Such analyses may contribute to a more nuanced understanding of regulatory dynamics and help identify targeted strategies to increase efficiency and equitable access to new therapies.
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