La industria aeroespacial en México: una evaluación de las políticas públicas y de las posibilidades de capacidades industriales y desarrollo tecnológico / / / \ \ \ The aerospace industry in Mexico: an evaluation of public policies and the possibilities of industrial capacities and technological development

Resumen: realizamos una evaluación de las políticas públicas adoptadas en los últimos lustros por el Estado mexicano en materia de estímulo de la industria aeroespacial y la posible formación de capacidades industriales y tecnológicas. Para ello, exponemos los resultados de una investigación de campo orientada a desentrañar las especificidades que adopta la industria aeroespacial en México y, particularmente, en la región socioeconómica que se forma en torno a la ciudad de Querétaro. En este esfuerzo interpretativo es importante estudiar el comportamiento de la industria aeroespacial en el mundo y la centralización y concentración de las innovaciones tecnológicas en aras de comprender el carácter estratégico y duopólico que asume esta rama productiva en los países de origen de las matrices que coordinan las redes empresariales globales. El ejercicio de comparabilidad internacional brindó los elementos básicos para comprender que la especificidad de las políticas públicas orientadas al estímulo de la industria aeroespacial en México radica en la creación de empresarialidad y no en la formación de capacidades tecnológicas y/o en la adopción de una política industrial orientada a la articulación del mercado interno; situación que ahonda –en el citado país– las contradicciones de la dialéctica desarrollo/subdesarrollo. Palabras clave: políticas públicas, capacidades industriales, capacidades tecnológicas, funciones del Estado, desarrollo tecnológico. Abstract: Through this article, an evaluation of the public policies adopted in the last five years by the Mexican State regarding the stimulation of the aerospace industry and the possible formation of industrial and technological capacities is carried out. To achieve this purpose, the results of a field research aimed at unraveling the specificities adopted by the aerospace industry in Mexico and, particularly, in the socioeconomic region that forms around the city of Querétaro, are presented. In this interpretive effort, it is important to study the behavior of the aerospace industry in the world and the centralization and concentration of technological innovations in order to understand the strategic and duopolic nature assumed by this productive branch in the countries of origin of the matrices that coordinate the global business networks. The international comparability exercise provided the basic elements to understand that the specificity of public policies aimed at stimulating the aerospace industry in Mexico lies in the creation of entrepreneurship and not in the formation of technological capabilities and / or the adoption of a policy industrial oriented to the articulation of the internal market; situation that deepens - in the aforementioned country - the contradictions of the development/underdevelopment dialectic. Key words: public policies, industrial capabilities, technological capabilities, state functions, technological development.

FRI0085 RETENTION RATE OF ADALIMUMAB AND ABP 501 IN THE TREATMENT OF A LARGE COHORT OF PATIENTS WITH INFLAMMATORY ARTHRITIS: A REAL LIFE RETROSPECTIVE ANALYSIS

Background:The recent introduction of ABP 501, an adalimumab biosimilar, in treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking.Objectives:To compare the clinical outcomes of the treatment with adalimumab, both originator and biosimilar, in a large cohort of patients affected by autoimmune arthritis in a real life setting.Methods:We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or biosimilar ABP 501) in eight Rheumatology Units from January 2003 to January 2020. We stratified the study population according to biosimilar use. Descriptive data are presented by medians (interquartile range [IQR]) for continuous data or as numbers (percentages) for categorical data. Drug survival distribution curves were computed by the Kaplan-Meier method and compared by a stratified log-rank test. P values ≤0.05 were considered statistically significant.Results:764 patients (53.4% female, median age 55 [44-65] years, median disease duration 60 [25-149] months) treated with adalimumab were included in the analysis. 308 (40.3%) were affect by rheumatoid arthritis, 244 (31.9%) by psoriatic arthritis, and 212 (27.7%) by axial spondylarthritis. 558 (73%) were treated with adalimumab originator and 206 (27%) with ABP 501. Among the biosimilars 60 (29.1%) patients were naïve to adalimumab treatment. The overall 6-month retentions rate was 93.1%. The 6-month retention rate for adalimumab and ABP 501 were 93.3% and 91.2% respectively, without significant differences between the groups (p=0.541). Patients switching from originator to biosimilar showed and overall higher treatment survival when compared to naive (6-month retention rate 95% vs 90-4%), although it was not significant (p=0.179).Conclusion:In our retrospective study adalimumab originator and its biosimilar ABP 501 showed the same effectiveness. Patients switching from originator to biosimilar showed an higher retention rate when compared to naive.Disclosure of Interests:Andrea Becciolini Speakers bureau: Sanofi-Genzyme, UCB and AbbVie, rosalba caccavale: None declared, Simone Parisi: None declared, Salvatore Giordano: None declared, Elena Bravi: None declared, eleonora Di Donato: None declared, Federica Lumetti: None declared, Romina Andracco: None declared, Maria Chiara Ditto: None declared, Daniele Santilli: None declared, Gianluca Lucchini: None declared, Alessandro Volpe: None declared, Antonio Marchetta: None declared, Flavio Mozzani: None declared, Gilda Sandri: None declared, Francesco Girelli: None declared, eugenio arrigoni: None declared, Enrico Fusaro: None declared, marino paroli: None declared, Alarico Ariani: None declared

Regulatory outlook from concept to commercialization of Biosimilars in Brazil market

Biological products or biopharmaceuticals are medicinal products derived from living organism systems and manufactured by using modern biotechnology that differ widely from the conventional synthetic drugs. They are much larger and more complex molecules with inherent diversity; hence, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, biologics manufactured and marketed after patent expiration are usually referred to as biosimilars. Biosimilars endeavor to copy the original technology leading to the production of innovative biotechnological medicines to obtain a product which is similar to the reference product. These products reported to improve the treatment landscape for multiple diseases, particularly in the areas of oncology, blood disorders, rheumatology, endocrinology and are becoming choice of treatment regimen due to policy push by governments for it’s affordability without comprising on quality, safety and efficacy. Pharmaceutical exports from Brazil increased by around 41% between 2009 and 2013, touching a high of U.S. $1.516 billion. The valuation of Brazilian pharma markets has shown double digit growth in the past decade. Between 2012 and 2015, market valuations have increased from U.S. $25.2 billion to U.S. $35.3 billion. Biosimilarity is based on a comprehensive comparability exercise wherein unavoidable clinical differences are evaluated and must meet equivalence or non-inferiority criteria. Biosimilars need to comply with different regulatory requirements for market authorization in different sites. There are several other related issues that need to be defined by the national authorities, such as interchangeability, labeling and prescribing information. The Brazilian health surveillance agency shadows the key principles established by the World Health Organization for the assessment of biosimilarity. However, the regulations also widen the gap by having standalone application pathway that does not require the usual comparability exercise with the reference product, originating non-biosimilar copies. Interchangeability and the use of nonproprietary names are not regulated. The objective of this manuscript is to explore the Brazilian Regulatory outlook from concept to commercialization of Biosimilars.

Strengths and weaknesses of the Brazilian regulation on biosimilars: A critical view of the regulatory requirements for biosimilars in Brazil

Biological products or biopharmaceuticals are medicinal products derived from living systems and manufactured by modern biotechnological methods that differ widely from the traditional synthetic drugs. Monoclonal antibodies are the most rapidly growing type of biologic. They are much larger and more complex molecules with inherent diversity; therefore, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, legal follow-on biologics manufactured and marketed after patent expiration are usually referred to as biosimilars. Biosimilarity is based on a comparability exercise whereby unavoidable clinical differences are evaluated and must meet equivalence or non-inferiority criteria. Biosimilars need to comply with different regulatory requirements for market authorization in different sites. There are several other related issues that need to be defined by the national authorities, such as interchangeability, labeling and prescribing information. The Brazilian health surveillance agency follows the key principles established by the World Health Organization for the assessment of biosimilarity, although does not adopt the name ‘biosimilar’. However, the agency also made a compromise on a standalone application pathway that does not require the usual comparability exercise with the reference product, originating nonbiosimilar copies. Interchangeability and the use of nonproprietary names are not regulated, giving rise to pressures on physicians and conflicts of interest in the decision making on biosimilar use. The scope of this article is to present the Brazilian regulation on biosimilars, its strengths and weaknesses, and to discuss it in the face of regulations in the USA and Europe.

Concepts and Challenges of Biosimilars in Breast Cancer: The Emergence of Trastuzumab Biosimilars

With the development of anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibodies, trastuzumab-based therapy has become the standard of care among patients with early or advanced HER2-positive breast cancer. However, real-world data have shown that up to a half of patients do not receive trastuzumab or any other HER2-targeted agent, mainly due to high treatments costs. The prospect of a more enlarged access to trastuzumab treatment lies in the use of biosimilars, as the European and the US patent of the reference products has or will soon expire. Biosimilars are biologics highly similar in terms of quality characteristics, biological activity, safety and efficacy to already approved biologics. The biosimilarity of any European Union (EU)-approved biosimilar is guaranteed based on the comprehensive comparability exercise which includes comparative analytical, non-clinical and clinical studies. In the matter of biosimilars’ interchangeability and substitution, the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) have adopted different positions, triggering various discussions on the potential immunogenicity and efficacy in individual patients. As more biosimilars are gaining approval, the present review aims to offer concise information for oncologists and pharmacists about the production, approval, interchangeability, and substitution policies of biosimilars used in breast cancer therapy, with a special focus on trastuzumab.

REGULATORY GUIDELINES FOR APPROVAL OF BIOSIMILARS IN INDIA, EUROPE, BRAZIL AND CHINA: A COMPREHENSIVE OVERVIEW

<p>A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product (reference medicinal product). A biosimilar demonstrates similarity to the reference biological product in terms of quality characteristics, biological activity, safety and efficacy based on a comprehensive comparability exercise. EMA (European Medicines Agency) was the first to introduce the guidelines for biosimilar approval, effective from June 2006. Biosimilar guideline was released in 2010 in Brazil and 2012 in India. Recently China published its guideline for biosimilar approval in 2015.</p><p>This article summarizes the regulatory requirements for approval of biosimilars in India, Europe, Brazil, and China. These countries require comparability exercise of a biosimilar with reference biological product for generating comparative analytical, non-clinical and clinical data (usually one or two phase 1 and phase 3 comparative studies). A case study of infliximab biosimilar approval in India, Brazil and Europe has also been included.</p>

Anti-TNFs: Originators and Biosimilars

In the last 20 years, the advent of anti-tumor necrosis factor alpha (TNFα) biologics has revolutionized the treatment of patients with inflammatory bowel disease (IBD) but the cost of biologic therapy now constitutes a large proportion of all healthcare expenditures. Patent expiration has sparked the healthcare industry's interest in the production of biosimilar (BS) versions of first generation biologics (originators [ORGs]) for market sharing. Having no access to the production line of the ORG, the sponsor of a BS needs to develop his own manufacturing process to produce a highly similar version of the reference product. Similarity in structure, physicochemical properties, biologic activity, efficacy and safety must be demonstrated by a comprehensive comparability exercise that includes the most sensitive in vitro tests, models and clinical condition with pre-defined equivalence margins. Extrapolation of indications, inter-changeability and automatic substitution between BS and ORG depend on a legal framework that varies between different agencies. It is not, therefore, unexpected that marketing authorization by the European Medicines Agency and other regulatory agencies (but not Health Canada) of CT-P13 (Remsima™/Inflectra™) as infliximab (Remicade®) BSs for IBD by indication extrapolation has led to stormy discussions in the IBD community and beyond regarding the scientific adequacy of this decision. However, as we now have to live with BSs, we hope that the impeding automatic substitution in association with post-marketing pharmacovigilance, full traceability, registries and new studies will settle the controversy and will increase the confidence of physicians and patients. A universally adopted legal framework should be implemented because, as expected, the non-anti-TNFα BSs will be soon on the stage.

New Alternatives for Autoimmune Disease Treatments: Physicochemical and Clinical Comparability of Biosimilar Etanercept

Etanercept is a recombinant fusion protein approved for the treatment of TNF-αmediated diseases such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, and ankylosing spondylitis. Herein, we present an evaluation of the physicochemical and biological properties of a biosimilar etanercept and its reference product followed by a clinical study in patients diagnosed with RA intended to demonstrate comparability of their immunomodulatory activity. Identity analyses showed a total correspondence of the primary and higher-order structure between the two products. In regard to intrinsic heterogeneity, both products showed to be highly heterogenous; however the biosimilar etanercept exhibited similar charge and glycan heterogeneity intervals compared to the reference product. Apoptosis inhibition assay also showed that, despite the high degree of heterogeneity exhibited by both products, no significant differences exist in theirin vitroactivity. Finally, the clinical assessment conducted in RA-diagnosed patients did not show significant differences in the evaluated pharmacodynamic markers of both products. Collectively, the results from the comparability exercise provide convincing evidence that the evaluated biosimilar etanercept can be considered an effective alternative for the treatment of RA.

Physicochemical and Biological Characterization of a Biosimilar Trastuzumab

According to the World Health Organization, the incidence of malignant neoplasms and endocrine, blood, and immune disorders will increase in the upcoming decades along with the demand of affordable treatments. In response to this need, the development of biosimilar drugs is increasing worldwide. The approval of biosimilars relies on the compliance with international guidelines, starting with the demonstration of similarity in their physicochemical and functional properties against the reference product. Subsequent clinical studies are performed to demonstrate similar pharmacological behavior and to diminish the uncertainty related to their safety and efficacy. Herein we present a comparability exercise between a biosimilar trastuzumab and its reference product, by using a hierarchical strategy with an orthogonal approach, to assess the physicochemical and biological attributes with potential impact on its pharmacokinetics, pharmacodynamics, and immunogenicity. Our results showed that the high degree of similarity in the physicochemical attributes of the biosimilar trastuzumab with respect to the reference product resulted in comparable biological activity, demonstrating that a controlled process is able to provide consistently the expected product. These results also constitute the basis for the design of subsequent delimited pharmacological studies, as they diminish the uncertainty of exhibiting different profiles.