LETTER TO EDITOR REGISTER OR PUBLISH? REFLECTION PAPER ABOUT TWO IMPORTANT ISSUES DURING THE DEVELOPMENT OF NEW DRUGS. CUBAN CONSIDERATIONS. (¿Registrar o Publicar? Manuscrito de reflexión acerca de dos importantes aspectos durante el desarrollo de nuevos fármacos) Diadelis Remírez Figueredo, Caridad Hernández y Deybis Orta. Centre of State Quality Control of Drugs and Medical Devices. ABSTRACT --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- The Regulatory Agencies are the responsible for controlling quality, safety and efficacy of drugs. One of the main objectives of the Drugs Regulatory Agency is to authorize the commercialization of pharmaceutical products (Register). It means to put into the market the drugs with the required quality, safety and efficacy. This work focuses the attention, about the importance of registering and publishing, the differences between both processes. It is described the main requirements for registration in Cuba and How to use the useful information of papers for registering. New Cuban products which have been registered with very high impact of papers will be included in this work. How deep should the papers be and how simple or complex should the registration be? Both of these aspects will be clarified in order to get better registration with papers included. Keywords: Register, Publishing, Cuba, Requirements. Rev. Farmacol. Chile (2015) 8(3) 7-9 Received 28-06-2015; Revised 20-11-2015; Accepted 24-11-2015 --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 1) BACKGROUND Drug approval is the goal of the long process of drug development. Once preclinical and clinical trial data have been collected, a New Drug Application must be submitted to the regulatory authority for approval. Registration of drugs is an essential element in drug regulation. All drugs that are marketed, distributed and used in Cuba should be registered by the national drug regulatory authority. Every drug, before receiving approval for marketing must undergo rigorous scientific testing and scrutiny to ensure that it is safe and effective for its intended use. Drug development starts with lab assays, in vivo animal studies in order to evaluate the pharmacodynamic, pharmacokinetic and potential toxicities of a product. Once theses studies are complete, the sponsor of a drug submits the authorization for starting the clinical trials. During the clinical trials, products typically undergo three phases of studies: Phase I, Phase II and Phase III, which represent the giving of the new drug to increasing numbers of patients in an effort to characterize safety and efficacy. Phase I consist of the initial administration of the product, the safety and tolerability is evaluated. During the phase 2 the therapeutic effect is explored and in the phase 3 the efficacy is confirmed. All these phases should be approved by Regulatory Agency, once the clinical trials are completed, the results are tabulated and analysed by the sponsor and then submitted as a New Drug Application (NDA) to the Regulatory Agency (RA). The NDA then presents to RA reviewers the entire history of the development of a drug product. It is the job of any regulatory agency to review the data and determine whether the product meets the criteria for marketing. How to assess?, Who should assess? --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Correspondence to: Dra. Diadelis Remírez Figueredo. Centre of State Quality Control of Drugs and Medical Devices. Address: Calle 5ta A #6020 e/ 60 y 62. Miramar, Playa. Código Postal 11300. La Habana, Cuba. Teléfono: +53-7 216 4100, Email: diade.remirez@infomed.sld.cu Rev. Farmacol. Chile (2015) 8(3) 7 Marketing authorization is a system for the pharmaceutical products for pre-trading for ensuring all the required standards for quality safety and efficacy settled by the Drug Regulatory Agency. A single marketing application should be sufficient to ensure product safety and effectiveness as well as to ensure consistent and appropriate post- marketing regulation. Cuba is a small country with limited resources but it has an almost 100 percent literacy rate. Cuba has generated scientific results with high technology, such as: the production of novel products (monoclonal antibodies, therapeutic vaccines, biological products etc), these advances have been the result of integrated researchproduction-trading organisations, the help of the state, social ownership, export orientation and the comprehensive integration of the Cuban biotechnology multi-institutional system. 2) INFORMATION REQUIRED FOR REGISTRATION OF NEW PRODUCTS IN CUBA. Administrative Information Chemical pharmaceutical and biological information. Preclinical Information Clinical Information Why publish the data? • In order to provide the information about the results the broader scientific community. • Evaluation of the results by international and/or national experts. • To avoid the duplicity of results. • To get prestigious or position in a specific field at national or international level. Types of papers. • Short communications • Scientific articles • Reviews Register or to publish? How many articles make up the register? Papers are written according to requirements of the journal, and it can be as in depth the author wish. Registration is according the requirement of regulatory agency and author should provide enough information required in order to convince the reviewers of the novelty of the product submitted. In this sense the registration can include papers published or not, the published papers in international journal denote that the results have been evaluated by international experts. These papers are considered as reliable evidence for the results presented in the register. Rev. Farmacol. Chile (2015) 8(3) 3) REQUIREMENTS IN CUBA. Chemical-Pharmaceutical Issues: Qualitative and quantitative composition stability, concentration of active principles, characterization of the components, risk excipients. In this issue is not necessary to publish all the content. Non clinical assessment It is included all the toxicology studies (mutagenesis, reproductive, carcinogenesis studies) and investigation of the mechanism of action of the new product. In these aspects new techniques related with alternative and molecular toxicology, and pharmacology as well could be carried out as well as these results could be published. Clinical assessment from phase I-III should be carried out before the registering, the results could be published. Main Cuban products registered with huge international papers. • Interferon • Vaccine hepatitis B • Ateromixol • Monoclonal antibodies • Vaccine Haemophylus influenzae • Heberprot Pharmacological mechanisms examined in non-clinical trials would be useful for selection of the appropriate endpoint in the clinical trials. For safety assessment, International Conference of Harmonization (ICH) Guideline on Safety Pharmacology Studies was officially notified. According to pharmacological data on safety, clinical investigators can better design clinical trials to prevent patients from suffering serious adverse events. To development new pharmaceuticals, continuous progress on pharmacological research will be indispensable. Further discussion among all interested parties such as pharmacological researchers, medical doctors, companies, and regulatory sites will be necessary and useful to develop more appropriate approaches in the pharmaceutical development process. With the current trends of globalization, where crossborder trade for pharmaceutical products increases in many parts of the world, the need for effective drug regulation at national and international levels becomes more important than ever. 4) CONCLUSION The most important is to know that papers can be as short or longer as the author decides, but the application for registering should fulfil the requirements settled for each country. 8 RESUMEN --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Las agencias reguladoras son los organismos responsables de controlar la calidad, seguridad y eficacia de los medicamentos. Uno de los objetivos principales de estas agencias es la autorización de comercialización de los productos farmacéuticos (Registro). Esto significa colocar en el mercado medicamentos con la calidad seguridad y eficacia requerida. Este trabajo enfoca la atención acerca de la importancia del registro y de las publicaciones científicas y las diferencias entre ambos procesos. Se describen los principales requisitos para el registro en Cuba y como usar la información de las publicaciones para el registro. Nuevos productos cubanos los cuales han sido registrados con publicaciones de alto factor de impacto serán descritos, además de la profundidad de las publicaciones y lo simple o complejo de los registros. Ambos aspectos serán aclarados con el objetivo de obtener mejores registros con publicaciones incluidas. Palabras Claves: Registro, publicación, Cuba, Requisitos Rev. Farmacol. Chile (2015) 8(3) 7-9 Recibido 28-06-2015; Revisado 20-11-2015; Aceptado 24-11-2015 ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------- Rev. Farmacol. Chile (2015) 8(3) 9