Regulatory Pathway for Licensing Biotherapeutics in Mexico.

Biotherapeutic products which are derived from living organisms using recombinant DNA technology significantly contribute to the progress in the treatment of life-threatening and chronic diseases. The worldwide sale of biological drugs in 2016 was near US $263,700 million. In Latin America, where monoclonal antibodies market was worth US $7000 million, being Mexico the second largest market. Approval is one of the key aspects which influences the market of medicinal products, thus it is responsibility of the regulatory authority to establish a regulatory framework that ensure safety and efficacy of the products, and it is responsibility of the applicants to provide a high quality dossier in accordance with the registration requirements of the country. The applicants submitting registration requests in Mexico need to be aware of the requirements. Similar to many other countries, Mexico has adopted the Common Technical Document (CTD) structure for organizing dossier of the medicinal product for submission into main modules (i.e., quality, non-clinical, and clinical). This facilitates the submission process of medicinal products following a logical sequence aligned to the International Council on Harmonisation (ICH) guidelines. Moreover, this structure improves the transparency and clarity of the dossier in process of evaluation of medicinal products. In Mexico, the Ministry of Health has published a regulation, NOM-257-SSA1-2014, which established the general requirements to be followed by applicants to complete the registration of biotherapeutics. This regulation stipulates that the evaluation process is supported by a regulatory framework involving Good Manufacturing Practices, labeling, stability, clinical trials, biocomparability studies, pharmacovigilance, and a technical evaluation performed by a multidisciplinary team of experts in biotherapeutics development. Additionally, the Mexican regulatory agency, COFEPRIS, has published specific guidelines to facilitate the application process. Despite the availability of this information, the scope is limited to regulatory and administrative purposes, rather than technical-scientific supporting knowledge. The aim of this article is to provide concise information to improve and promote communication between industry and regulatory agencies. Herein, we describe the current process of COFEPRIS in regulating biotherapeutics in Mexico. This process explains the basis for the organization and structure of the technical-scientific information of biotherapeutics required for registration application.

Regulatory pathways for vaccines for developing countries.

Vaccines that are designed for use only in developing countries face regulatory hurdles that may restrict their use. There are two primary reasons for this: most regulatory authorities are set up to address regulation of products for use only within their jurisdictions and regulatory authorities in developing countries traditionally have been considered weak. Some options for regulatory pathways for such products have been identified: licensing in the country of manufacture, file review by the European Medicines Evaluation Agency on behalf of WHO, export to a country with a competent national regulatory authority (NRA) that could handle all regulatory functions for the developing country market, shared manufacturing and licensing in a developing country with competent manufacturing and regulatory capacity, and use of a contracted independent entity for global regulatory approval. These options have been evaluated on the basis of five criteria: assurance of all regulatory functions for the life of the product, appropriateness of epidemiological assessment, applicability to products no longer used in the domestic market of the manufacturing country, reduction of regulatory risk for the manufacturer, and existing rules and regulations for implementation. No one option satisfies all criteria. For all options, national infrastructures (including the underlying regulatory legislative framework, particularly to formulate and implement local evidence-based vaccine policy) must be developed. WHO has led work to develop this capacity with some success. The paper outlines additional areas of action required by the international community to assure development and use of vaccines needed for the developing world.

Vaccine quality--can a single standard be defined?

To analyze the current global situation with respect to vaccine quality and to monitor progress in attaining it, it is first necessary to define what this means. While acknowledging that manufacturers are responsible for the quality of the vaccines they produce, World Health Organization (WHO) proposes a definition for "vaccines of assured quality" which depends on the existence of a competent and fully functional regulatory authority as assessed by an external expert team using widely agreed indicators to regulate the product. A vaccine of assured quality is defined as one that consistently meets appropriate levels of purity, potency, safety and efficacy as judged through an independent review system competent to take an evidence-based decision on the product for a specified population in a specific context. Such a review system would make use of all available information, such as licensing dossiers, surveillance of field performance, lot-by-lot scrutiny, appropriate laboratory testing, cGMP inspection of manufacturers, and evaluation of clinical trials, generally assumed by a fully functional regulatory authority. This definition implies that, faced with the same risk/benefit, any competent group would come to the same decision. The definition also indicates clear pathways to improve vaccine quality by strengthening national regulatory authorities and WHO is actively engaged in this task. By insisting on competent regulatory oversight, while recognizing the role of risk analysis in the selection of vaccines for use, WHO strongly reiterates the need for a single standard of quality. Only vaccine of assured quality should be considered for use in national immunization programs on the basis of the risk/benefit ratio for the particular population.