Brazilian Regulatory Authority Research Articles

Responsiveness of water-sector regulation in Brazil to the Covid-19 pandemic: A view through the human rights lens.

This paper provides an overview of the regulatory responses to Covid-19 from the regulatory authorities of Brazilian states. This paper aims to provide new insights into the operationalization of the human rights to water and sanitation in the Brazilian regulatory authorities' actions during a health emergency. We find that communities located in unserved areas were not mentioned in the regulatory responses, nor were people in vulnerable situations. Equity and non-discrimination principles were correlated more with economic measures. This study has also identified the absence of responses related to access to sanitation facilities, with normative contents related to the issue not appearing in the content analysis.

A Cost-Effectiveness Study of Stereotactic-Body Radiation Therapy Compared to Surgery in Patients with Early Non-Small Cell Lung Cancer, from the Perspective of the Brazilian Private Health-Care System

<h3>Purpose/Objective(s)</h3> The standard of care for operable stage I non-small cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection. Stereotactic body radiotherapy (SBRT) has shown promising results in non-operable patients. Previous randomized trials, comparing those technologies, were closed early due to poor accrual, but pooled results have indicated that they are, at least, equally effective. Further trials were opened, and results are waited for the following years to come. The objective of this study was to evaluate the cost-effectiveness of SBRT, compared to lobectomy, in operable stage I NSCLC. <h3>Materials/Methods</h3> A Markov model was built based on the pooled analysis of two previous prospective randomized trials. Costs, in reais (BRL), were extracted from the database of a Brazilian nationwide health care provider (Capesesp). Utility values, recurrence, and death probabilities were adapted from the literature. The analysis was conducted from the Brazilian healthcare private system perspective. A 10 years' time horizon was used in the study. A yearly discount rate of 5% was applied, according to Brazilian regulatory authorities' recommendations. Deterministic (DSA) and probabilistic sensitivity analysis (PSA) were performed to evaluate the influence on the results of the assumptions that were made. <h3>Results</h3> SBRT and lobectomy total costs were 93,207.00 and 115,776.00 BRL and utilities were 2.72 and 2.55 QALYs (quality-adjusted life-years), respectively, showing that SBRT was dominant over surgery, with an incremental cost-effectiveness ratio (ICER) of -134,445.27 BRL. The DSA, performed based on every made assumption, showed that results depended mainly on the probability of progression after lobectomy, on the cost of chemotherapy, prescribed for patients that presented progression after both curative treatments, and on the probability of recurrence after SBRT. PSA revealed that SBRT had a considerably higher probability of being cost-effective, compared to lobectomy. <h3>Conclusion</h3> our results indicate that for patients with stage I, operable, NSCLC, SBRT is probably dominant over lobectomy. Sensitivity analysis has shown that those results are robust and not modified by the assumptions that were made during the construction of the model. It raises the importance of the open trials comparing those technologies, once SBRT can be a viable cost-saving option, in our environment, if its effectiveness is proven to be, at least, comparable to surgery.

Lessons From Implementing a Clinical Research Network in Brazil.

In this article, we discuss the strategy designed by a private oncology group to offer patients access to new technologies and treatments via a recently created research program, and we describe how the patient journey was the motivation for developing standard assistance flows and processes to integrate areas of care. The increase in Brazilians' life expectancy has raised the incidence of cancer, and it is now the second leading cause of death. Because it is a multifactorial disease, cancer treatment has several challenges. We elected to approach cancer research using a strategic program to obtain national attention and visibility. Starting in 2007, the initial project included three phases: phase I, diagnosis of units in major metropolitan areas; phase II, project design, with a central-office operation model; and phase III, implementation, with launch and integration of research activities at selected units. The foundation of the program was the construction of departmental and interdepartmental flows, standard operating processes, and guidelines (regulatory, ethical, legal, and financial). Recruitment of qualified professionals was another critical, successful determinant. The benefits of an additional central office include improved research-project distribution. Another advantage of the program is attracting and retaining trained professionals with alternative direct or indirect sources of revenue. We increased our corporate and academic partnerships, adhered to deadlines and noted an improvement in turnaround times, and we increased clinical staff engagement and motivation. Some barriers continue to challenge the program's continued expansion, including Brazilian regulatory authority approval, tax inefficiency, and a growing demand for qualified professionals. Research sites offering high-quality care are a reality in Brazil; they offer multiple lines of treatment in the public and private sectors.

Regulation &amp; registration of drugs and biologics in Brazil

Registration of medicinal products is a challenging task in various countries as the regulatory requirements differ from country to country around the world. Like in regulated countries medicinal products regulation is a difficult piece of work in Semi-regulated countries as they are not coordinated. Being the sixth most populous country, Brazil gives a great opportunity for the bio/pharmaceutical market. Superior health maintenance, high quality, and modern medicines are being demanded by Brazilians which gives a huge opportunity for overseas investment. Medicinal products registration is a lengthy process in Brazil. Obtaining access to the marketing of drugs and biologics from the Brazilian Regulatory Authority is not an easy business for bio/pharmaceutical companies. One of the most difficult tasks facing regulatory agencies is ensuring that medications are manufactured in accordance with the country's regulatory requirements. This Review article's primary objective is to explain how pharmaceuticals and biologics are regulated and registered in Brazil. Keywords: Brazil, ANVISA, Drugs, Biologics, Regulation.

The InsurTechs in Brazil: a legal and regulatory analysis

The insurance industry is facing an unprecedented wave of disruption. While all stakeholders welcome the new insurance products and the improved consumer experience resulting from technological advances, jurists face a number of challenges. In particular, it could be asked: is the current Brazilian legal system able to regulate InsurTechs adequately? The following paper will analyze the legal and regulatory aspects of the operation of companies characterized as “InsurTechs” and how they are functioning in Brazil. To this aim, the following will be addressed: (i) the concept of InsurTech; (ii) the Brazilian regulatory authority’s Regulatory Sandbox approach and; (iii) The functioning of InsurTechs in Brazil.

Dynamics of patents, orphan drug designation, licensing, and revenues from drugs for rare diseases: The market expansion of eculizumab.

BackgroundThis study examines the dynamics of the eculizumab patenting, orphan designation, and marketing authorization process in different countries and regulatory systems and analyzes drug revenues since its first marketing authorization.MethodsA retrospective case study was conducted. Multiple information sources were used to: determine the status of eculizumab patents; examine the designation of orphan drug status by US, European, Japanese, and Brazilian regulatory authorities to determine registration status and approved clinical indications; estimate the prevalence of associated clinical conditions; investigate the history of the drug manufacturer, Alexion Pharmaceuticals, Inc., and its financialized business model; and examine global eculizumab sales revenues since its first marketing authorization.ResultsOur search yielded 32 patent families divided into 98 applications. The first patent granted was filed in 1995 by Alexion Pharmaceuticals, Inc. in the US. Eculizumab has always been as an orphan drug, except in the Brazilian regulatory agency. All clinical indications approved thus far refer to rare diseases (e.g., paroxysmal nocturnal hemoglobinuria syndrome, atypical hemolytic-uremic syndrome, refractory and generalized myasthenia gravis, and neuromyelitis optica spectrum disorder). Alexion’s revenues amounted to more than US$25 billion between 2007 and 2019, showing a growing trend. Eculizumab led sales from the beginning, being the only product in the company’s portfolio until 2015. In 2019, the drug accounted for 79.1% of all revenues.DiscussionOur findings show that a strategy focused on obtaining orphan drug designation, expanding therapeutic indications and the geographic range of marketing approvals, extending monopoly periods, and prioritizing public procurement niches has enhanced revenues and helped the company achieve leadership in a highly specific and profitable market.

Brazilian regulatory authority contribution to the shielding dimensioning model of radiotherapy rooms proposed by the NCRP 151

The National Council on Radiation Protection and Measurements (NCRP) Report No. 151 is an essential document for bunker design commonly applied for radiotherapy treatment rooms. This document is used as a reference by several countries, including Brazil. The objective of this study is to evaluate the shielding dimensioning methodology recommended by NCRP 151, and compare it with the one adopted by the Brazilian regulatory authority. Radiotherapy rooms and respective doors were designed to use linear accelerators operating at 6, 10, 15, and 18 MeV under two different ways: (a) applying exclusively the methodology recommended by the NCRP 151, and (b) taking into consideration the complementary recommendations from the Brazilian authorities. The results suggest that designers in Brazil can count on at least 4 and 11% safety margin for dimensioning primary barriers in controlled and free areas respectively. Also 8% for secondary barriers in controlled areas, 9.7% for secondary barriers adjacent to the primary belt of free areas, and 6.6% for the lead of the doors.

Incorporação de medicamentos sem registro sanitário no SUS: um estudo das recomendações da Comissão Nacional de Incorporação de Tecnologias no período 2012–2016

Introduction: Drug registration is an essential tool in assessing quality, safety and efficacy.In Brazil, the current regulatory framework prohibits the incorporation of any technology into the Brazilian Public Health System (SUS) without prior registration by the Brazilian regulatory authority, the National Health Surveillance Agency (Anvisa). The National Committee for Technology Incorporation (Conitec) advises the Ministry of Health on which health technologies should be incorporated. Objective: Conitec’s recommendations to incorporate non-registered medicines and their federal procurement between January 2012 and June 2016 were studied. Method: The study was based on the information from Conitec’s website and on purchases registered in the Integrated General Services Management System database. Results: Six of the 93 drugs incorporated by SUS during the period were not registered in the Brazilian Health Regulatory Agency (Anvisa). The main reasons for incorporation of non-registered medicines were severity of disease, minor adverse events, and low budgetary impact. In 50% of the cases, medicines were already present in the SUS for the approved indications, but in presentations that made it difficult for them to be used in pediatric patients or situations of greater severity. R$ 3,159,085.96 were spent on the purchase of these drugs. Conclusions: The recommendation of incorporation of medicines not registered by Anvisa contravenes the legislation related to Conitec and the public acquisition of medicines. On the other hand, it is important to highlight the importance of drug incorporations that meet relevant therapeutic gaps.

INTERNATIONAL REACH OF SECURITIES REGULATION: A COMPARATIVE VIEW ON BRAZILIAN AND U.S. LAW

This paper examines the international reach of securities regulation, focusing on the Brazilian and U.S. experiences in this field. The aim is to provide the reader with a view on how the issue first developed in the U.S. (and how the U.S. Supreme Court has recently changed, in part, the U.S. solution) and on how Brazilian Law, on its part, addresses regulation of transnational securities markets – mentioning particularly a landmark Administrative Enforcement Proceeding judged by the Brazilian regulatory authority (CVM).

INTERNATIONAL REACH OF SECURITIES REGULATION: A COMPARATIVE VIEW ON BRAZILIAN AND U.S. LAW

This paper examines the international reach of securities regulation, focusing on the Brazilian and U.S. experiences in this field. The aim is to provide the reader with a view on how the issue first developed in the U.S. (and how the U.S. Supreme Court has recently changed, in part, the U.S. solution) and on how Brazilian Law, on its part, addresses regulation of transnational securities markets – mentioning particularly a landmark Administrative Enforcement Proceeding judged by the Brazilian regulatory authority (CVM).

INTERNATIONAL REACH OF SECURITIES REGULATION: A COMPARATIVE VIEW ON BRAZILIAN AND U.S. LAW

This paper examines the international reach of securities regulation, focusing on the Brazilian and U.S. experiences in this field. The aim is to provide the reader with a view on how the issue first developed in the U.S. (and how the U.S. Supreme Court has recently changed, in part, the U.S. solution) and on how Brazilian Law, on its part, addresses regulation of transnational securities markets – mentioning particularly a landmark Administrative Enforcement Proceeding judged by the Brazilian regulatory authority (CVM).

Produção de biológicos em plataformas vegetais e seus impactos na segurança alimentar – análise de lacunas na regulação vigente

The use of genetically modified plants to synthesize proteins that are subsequently processed, regulated, and sold as pharmaceuticals is already a global reality. However, the issue of technological development and industrial production of biological products being expressed in transgenic plants and their impact on the safety of the food chain needs to be discussed more deeply. In this paper, we present an extensive literature review on the standards and regulatory guidelines as well as on biosafety in Brazil with regard to the production of plant-made pharmaceuticals; compare them with the regulatory guidelines of other countries/regions such as USA, Canada, European Union, Cuba, and Argentina; and analyze gaps in the Brazilian regulation. We suggest that some regulations must be reviewed and conclude that the Brazilian regulatory authorities should establish an interrelated regulatory framework together, which would enable industrial production while protecting human and animal health as well as the environment.

INTERNATIONAL REACH OF SECURITIES REGULATION: A COMPARATIVE VIEW ON BRAZILIAN AND U.S. LAW

This paper examines the international reach of securities regulation, focusing on the Brazilian and U.S. experiences in this field. The aim is to provide the reader with a view on how the issue first developed in the U.S. (and how the U.S. Supreme Court has recently changed, in part, the U.S. solution) and on how Brazilian Law, on its part, addresses regulation of transnational securities markets – mentioning particularly a landmark Administrative Enforcement Proceeding judged by the Brazilian regulatory authority (CVM).

Intervenções Regulatórias, Volatilidade e Contágio: Uma Análise VIRF

Este artigo examina como intervenções regulatórias podem afetar o risco de mercado de empresas de eletricidade e de telecomunicações negociadas na BM&amp;FBOVESPA. O artigo utiliza um modelo GARCH (Generalized AutoRegressive Conditional Heteroskedasticity) bivariado para analisar o impacto de duas intervenções regulatórias em 2012: a primeira tomada pela Agência Nacional de Telecomunicações (ANATEL); a segunda, pela Agência Nacional de Energia Elétrica (ANEEL), na volatilidade e covariância do índice de ações pertencentes a esses setores. Neste artigo, adota-se também a função de resposta impulso desenvolvida por Hafner &amp; Herwartz (2006) para estimar a persistência desses efeitos. Os resultados revelam que o impacto da intervenção regulatória na volatilidade do setor de energia elétrica foi significativo, duradouro e contaminou o setor de telecomunicações. Além disso, mostram que o efeito da intervenção regulatória no risco do setor de telecomunicações foi pequeno.

Understanding and retention of trial-related information among participants in a clinical trial after completing the informed consent process

for assessing the level of understanding of trial-related information during the informed consent (IC) process in developing countries are lacking. To assess the understanding and retention of trial-related information presented in the IC process by administering an informed consent assessment instrument (ICAI) to participants in a clinical trial for a new tuberculosis (TB) regimen being conducted in Rio de Janeiro (Brazil). Methods The format of the ICAI was based on the language and structure of the United States National Cancer Institute's IC comprehension checklist. The ICAI was designed to assess points of the RioMAR study IC process that addressed the principles of research ethics requested by Brazilian Regulatory Authority: autonomy, beneficence, non-maleficence, and justice. Briefly, (1) Is the respondent participating in a clinical trial? (2) Are two different treatments being evaluated? (3) Is the treatment arm chosen by chance? (4) Is an HIV test required? (5) Are liver function tests required? (6) Can participants leave the study at any time? (7) Are the risks and benefits of taking part in the study clear? (8) May pregnant women participate in the study? (9) Can one of the study drugs reduce the effectiveness of contraceptives? (10) Are patients paid to participate in the study? The ICAI was applied at two time points: immediately after enrollment in the clinical trial and 2 months later. A total of 61 patients who enrolled in the RioMAR study participated in this study. The percentage of correct answers to all questions was 82% at the time of the first ICAI; 31 participants (51%) did not recall that an HIV test was required (question 4) and 43 (70%) did not know that they could leave the study (question 6). Other individual questions were answered correctly by at least 76% of participants. There was no association between incorrect answers and age, gender, monthly family income, neighborhood, or level of education (p > 0.07). When the responses to the first and the second ICAI questions were compared, 15% or more of participants had conflicting answers to 5 of the 10 questions. The ICAI uses dichotomous responses, leading to a 50% chance of guessing the correct answers. Two questions were asked only of women. Finally, only 6 of the 10 questions on the current version of the ICAI apply to most trials; others are trial-specific. The ICAI may be adapted to an individual trial and may prove to be a useful tool following a consent discussion to identify issues not fully understood by the research participants, thus prompting study staff to re-explain topics, possibly in a more elementary manner.

Bioequivalence evaluation of single doses of two tramadol formulations: A randomized, open-label, two-period: Crossover study in healthy brazilian volunteers

Background: Tramadol is a well tolerated and effective analgesic used to treat moderate to severe pain. Several generic formulations of tramadol are available in Brazil; however, published information regarding their bioequivalence in the Brazilian population is not available. A study was designed for Brazilian regulatory authorities to allow marketing of a generic formulation. Objective: The purpose of this study was to compare the bioequivalence of 2 commercial tablet preparations containing tramadol 100 mg marketed for use in Brazil. Methods: A randomized, open-label, 2 × 2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a washout period of 12 days. Two tablet formulations of tramadol 100 mg (test and reference formulations) were administered as a single oral dose, and blood samples were collected over 24 hours. Tramadol plasma concentrations were quantified using a validated HPLC method. A plasma concentration-time profile was generated for each volunteer and then mean values were determined, from which C max, T max, AUC 0−∞ k e, and t 1/2 were calculated using a noncompartmental model. Bioequivalence between the products was determined by calculating 90% CIs for the ratios of C max AUC 0−t and AUC0 −∞, values for the test and reference products using log-transformed data. Tolerability was assessed by monitoring vital signs (temperature, blood pressure, heart rate), laboratory tests (hematology, blood biochemistry, hepatic function, urinalysis), and interviews with the volunteers before medication administration and every 2 hours during the study. Results: Twenty-six healthy volunteers (13 men, 13 women) were enrolled in and completed the study. Mean (SD) age was 30 (6.8) years (range, 21–44 years), mean weight was 64 (8.3) kg (range, 53–79 kg), and mean height was 166 (6.4) cm (range, 155–178 cm). The 90% CIs for the ratios of Cmax (1.01–1.17), AUC 0−t (1.00–1.13), and AUC 0−∞. (1.00–1.14) values for the test and reference products fell within the interval of 0.80 to 1.25 proposed by most regulatory agencies, including the Brazilian regulatory body. No clinically important adverse effects were reported; only mild somnolence was reported by 4 volunteers and mild headaches by 5 volunteers, and there was no need to use medication to treat these symptoms. Conclusion: Pharmacokinetic analysis in these healthy Brazilian volunteers suggested that the test and reference formulations of tramadol 100-mg tablets met the regulatory requirements to assume bioequivalence based on the Brazilian regulatory definition.

Survey of compliance with labeling legislation in food containing GMOs in Brazil

Analysis of food products consisting of, or produced from, genetically modified organisms (GMOs) is required to verify compliance with labeling legislation and to detect any possible unauthorized transgenic crops. With these goals, 240 samples of soy-derived foodstuffs and 25 samples of maize-derived foodstuffs were analyzed from 2004 to 2007. All samples positive for Roundup Ready ® soybean were quantitatively examined using the TaqMan ® GMO 35S Soy kit. In food containing soy, 68 (28.3%) were shown to contain GM soy, whereas in food containing maize, neither Bt 176 nor MON 810 maize were found. Quantitative analysis revealed GMO contents ranging from 0.05 to 1% in 43 (63.2%) samples, and more than 1% in 25 (36.8%) samples. The absolute and relative limits of detection (LODs) were approximately 10 copies and 0.0125%, respectively, and the absolute and relative limits of quantification (LOQs) were approximately 40 copies and 0.05%, respectively, suggesting sufficient sensitivity to quantify genetically modified (GM) materials below and above the legal threshold of 1%. The presence of GM material in these samples was not indicated on their labels, indicating that none of these food products had been appropriately labeled. These results clearly demonstrate the need for a monitoring program of food products by the Brazilian regulatory authorities.

Proficiency test for radioactivity measurements in nuclear medicine

Proficiency tests established by ISO/IEC-43 were applied to assess the performance of 69 Brazilian nuclear medicine services in the radiopharmaceuticals activity measurements of 131I, 99Tcm, 67Ga and 201Tl. The 214 datasets originated from comparison programs promoted by the Laboratorio Nacional de Metrologia das Radiacoes Ionizantes (LNMRI) in 2006/2007 were also evaluated against acceptance criteria of ±10% limits for accuracy required by Brazilian regulatory authority. The results of performance evaluation were assigned as “Acceptable” or “Not-acceptable” accordingly and have shown a large dispersion when the statistical criteria assays were applied and also compared with regulatory requirements.

Proposal for a Brazilian centre on alternative test methods

Several initiatives have recently taken place in Brazil in order to foster the creation of centers dedicated to alternatives to animal testing. In 2008, Vanessa Sá-Rocha organized a meeting with Brazilian regulatory authorities and the major stakeholders in the field of testing to foster discussions on the process of funding, development, and validation of alternative methods in Brazil. Octavio Presgrave published a scientific article on "The Need for the Establishment of a Brazilian Centre for the Validation of Alternative Methods." Also in 2008, Jadir Nunes, together with Dermeval de Carvalho, prepared and presented a proposal to the Brazilian National Agency of Health Surveillance (ANVISA) for the creation of a Centre for the Validation of Alternative Methods. ECVAM and other European stakeholders have been involved in the initiatives. Furthermore, also in 2008, a new legislation has been adopted in Brazil regarding the use of animals for scientific purposes ("lei Arouca"). The legislation establishes, among other provisions, the task of monitoring and evaluating the introduction of alternative methods. However, the legislation does not provide for promotion of or information about, existing alternative methods to the larger Brazilian scientific community. In order to streamline the different activities, Chantra Eskes acted as a facilitator by establishing a new joint proposal with the current Brazilian stakeholders, aimed at setting up a Brazilian Center on Alternative Test Methods.

National intercomparison program for radiopharmaceutical activity measurements

Since 1998, the National Laboratory for Ionizing Radiation Metrology has lead an intercomparison program for activity measurements of radiopharmaceuticals administered to patients in the Nuclear Medicine Services (NMS) with the purpose of promoting the quality control. In this work, intercomparison results with the radionuclides 67Ga, 123I, 99mTc and 201Tl from the beginning of the program to the present will be presented establishing as a consequence, the radionuclide calibrators’ traceability used by the participants. The analysis of the results showed that 68% were within the limits of ±10% required by the Brazilian Regulatory Authority that demands this accuracy band for the radiopharmaceutical measurements in the NMS. The results also demonstrate an improvement in the measurement quality that this program has provided since its beginning.