Regulatory Standards in Orphan Medicinal Product Designation in the EU

Twenty years of orphan regulation in Europe have now elapsed, with almost 2,400 orphan designated medicinal products and more than 190 orphan products authorised in the EU. Alongside the evolution in understanding of rare diseases, considerable regulatory knowledge has also been accumulated regarding the level of evidence that would support inclusion of products into the framework. This article reviews publications and regulatory documents pertaining to orphan medicinal product designation in the EU and discusses the general expectations in submitted applications as reflected in the current regulatory practise. Important elements to recommend granting a European orphan designation are the key considerations of orphan condition, medical plausibility, seriousness, and prevalence, while significant benefit is also assessed when there are authorised medicinal products for the sought indication. This review attempts to clarify the specific concepts currently used in that regard and discusses how the available data can be used to justify the criteria for designation. Moving away from theoretical expectations or assumptions, it stresses that the applications have to be complemented with nosological and epidemiological justifications pertaining to the proposed condition, as well as relevant data in specific non-clinical in vivo models or in affected patients to support inclusion into the orphan scheme.

Rotulagem de medicamentos industrializados: uma análise das diretrizes legais brasileiras e contribuições para a qualidade de produtos

RESUMOObjetivos: a rotulagem é um aspecto de qualidade fundamental no uso de medicamentos, seja pelo profissional de saúde, seja pelo paciente. Este trabalho propôs uma análise crítica do tema com base na legislação em vigor, bem como a triagem de documentos normativos úteis no processo de elaboração ou de avaliação da conformidade da rotulagem de medicamentos. Métodos: foi realizada uma pesquisa documental empregando-se como fonte de informações os sítios eletrônicos oficiais do Ministério da Saúde e da Agência Nacional de Vigilância Sanitária. Os documentos contendo itens pertinentes a rotulagem de medicamentos e classificados como vigentes ou vigentes com alteração foram selecionados para a realização do estudo. Resultados: os quesitos mais relevantes das disposições gerais e das disposições específicas da norma vigente para rotulagem de medicamentos foram sistematizados, verificando-se suas contribuições na qualidade e segurança de produtos. Embora a padronização da rotulagem de medicamentos seja necessária, a ocorrência de elevados graus de semelhança entre rótulos, embalagens ou mesmo nomenclaturas é discutida no âmbito da prática clínica e esta questão merece atenção especial. A busca de material complementar à legislação vigente resultou no levantamento de um total de 20 documentos, incluindo normas, guias, bancos de consulta e planilhas, que podem auxiliar no cumprimento dos requisitos de rotulagem de medicamentos. Conclusão: rótulos de medicamentos são recursos técnicos que contribuem na eficácia e na segurança do tratamento. Os esforços das Agências Reguladoras têm permitido a consolidação de diretrizes legais para que informações e formatos adequados de rotulagem sejam aplicados nas embalagens de medicamentos industrializados. A elaboração ou a análise da rotulagem de medicamentos requer amplo conhecimento regulatório, o qual é dinâmico e, portanto, um grande desafio.Palavras-chave: Rotulagem de Medicamentos. Legislação de Medicamentos. Vigilância de Produtos Comercializados. Segurança do Paciente. ABSTRACTObjectives: the labeling of drug products is an aspect of quality that is fundamental to the use of medicines, whether by the health professional or by the patient. This work proposed a critical analysis of the current legislation on the labeling of drug products, as well as the screening of normative documents useful for the process of preparing or assessing the conformity of labels. Methods: a documentary research was carried out using the official websites of the Ministry of Health and the National Health Surveillance Agency (Brazil) as sources of information. The documents containing relevant items on labeling of drug products and classified as current or current with changes were selected for the study. Results: the most important requirements of the general and specific provisions from the current legislation have been systematized, and their contributions to the quality and safety of products have been verified. Although the standardization of the labeling is necessary, the occurrence of high degrees of similarity between labels, packaging or even nomenclatures is discussed in the context of clinical practice and this issue deserves special attention. The search for material complementary to the current legislation resulted in the collection of a total of 20 documents, including normative documents, guides, databases and spreadsheets, which might help in complying with the requirements for the labeling of drug products. Conclusion: the labeling of drug products are technical resources that contribute to the effectiveness and safety of treatment. The efforts of the Regulatory Agencies have allowed the consolidation of legal provisions for the dissemination of appropriate information and labeling formats in the packaging of drug products. The drafting or analysis of the labels requires extensive regulatory knowledge, which is dynamic and, therefore, a great challenge.Keywords: Drug Labeling. Legislation, Drug. Product Surveillance, Postmarketing. Patient Safety.

Pengaruh Pengetahuan Peraturan, Komitmen Manajemen, Dan Lingkungan Birokrasi Terhadap Penyerapan Anggaran Terkait Pengadaan Barang/Jasa

This study aims to determine the effect of regulatory knowledge, management commitment, and the bureaucratic environment on budget absorption related to the procurement of goods / services in the government of Padang City. A sample of 82 respondents was determined by using a total sampling technique consisting of heads of fields or staff of the procurement department. Data were analyzed using multiple regression formulas with the help of the SPSS application. This study concludes that regulatory knowledge does not affect budget absorption related to goods / services procurement. Management commitment has a positive and significant effect on budget absorption related to the procurement of goods / services. Meanwhile, the bureaucratic environment has no effect on budget absorption related to the procurement of goods / services

Glyphosate Effect: Has the Glyphosate Controversy Affected the EU’s Regulatory Epistemology?

Glyphosate’s authorisation will expire in 2022 and its re-approval will take place in a changed legal and political landscape: the national phase of risk assessment is entrusted to a taskforce of four Member States, and, from 2021, the reform of the general food law will apply, imposing, inter alia, more ambitious transparency standards. Taking stock of these developments, this contribution analyses, from a legal perspective, whether and how the glyphosate dispute has contributed to the development of the EU’s regulatory epistemology, with specific regard to food governance. It identifies the “manifesto” of the EU’s regulatory epistemology in the 2002 guidelines on the collection and use of expertise and reads them in the light of the glyphosate dispute. In particular, it focuses on the legal arrangements reflecting the principles established in the 2002 guidelines (quality, openness, effectiveness) and analyses them against the tensions that emerged throughout the dispute with regard to the sources, levels and purposes of EU regulatory knowledge-making. It then considers whether and how such tensions have been addressed by legislative reform and whether this has resulted in a further refinement of the EU’s regulatory epistemology.

A pipeline to create predictive functional networks: application to the tumor progression of hepatocellular carcinoma

BackgroundIntegrating genome-wide gene expression patient profiles with regulatory knowledge is a challenging task because of the inherent heterogeneity, noise and incompleteness of biological data. From the computational side, several solvers for logic programs are able to perform extremely well in decision problems for combinatorial search domains. The challenge then is how to process the biological knowledge in order to feed these solvers to gain insights in a biological study. It requires formalizing the biological knowledge to give a precise interpretation of this information; currently, very few pathway databases offer this possibility.ResultsThe presented work proposes an automatic pipeline to extract automatically regulatory knowledge from pathway databases and generate novel computational predictions related to the state of expression or activity of biological molecules. We applied it in the context of hepatocellular carcinoma (HCC) progression, and evaluate the precision and the stability of these computational predictions. Our working base is a graph of 3,383 nodes and 13,771 edges extracted from the KEGG database, in which we integrate 209 differentially expressed genes between low and high aggressive HCC across 294 patients. Our computational model predicts the shifts of expression of 146 initially non-observed biological components. Our predictions were validated at 88% using a larger experimental dataset and cross-validation techniques. In particular, we focus on the protein complexes predictions and show for the first time that NFKB1/BCL-3 complexes are activated in aggressive HCC. In spite of the large dimension of the reconstructed models, our analyses over the computational predictions discover a well constrained region where KEGG regulatory knowledge constrains gene expression of several biomolecules. These regions can offer interesting windows to perturb experimentally such complex systems.ConclusionThis new pipeline allows biologists to develop their own predictive models based on a list of genes. It facilitates the identification of new regulatory biomolecules using knowledge graphs and predictive computational methods. Our workflow is implemented in an automatic python pipeline which is publicly available at https://github.com/LokmaneChebouba/key-pipe and contains as testing data all the data used in this paper.