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Usually, if percutaneous absorption tests are conducted in accordance with OECD Guideline 428, in vitro determination is accepted by mainly regulatory agencies. In this paper, we focus on the lack of comparability of the results regarding the permeation parameter/flow rate, although it is widely discussed in the literature. This work sought to evaluate the absorption of caffeine using Franz-type diffusion cell with porcine ear skin samples, varying the storage duration and the way to handle them. Metrological tools were used for caffeine quantification such as certified reference material candidate, calibrated instruments, and validated methodology. Our results corroborate with the recommendation that membranes should be freshly prepared or frozen for short periods. Samples frozen for approximately one year should not be used because they present high cutaneous absorption. The results obtained for the absorption rate (J) are comparable to the results obtained by previous studies using similar experimental conditions. The evidence of the barrier characteristic promoted by the stratum corneum and the effect promoted by the storage time is shown through J = 6.25 ± 0.48 µg/cm2/h. We demonstrated the importance of metrological tools to guarantee reproducibility and comparability of the results between different laboratories.

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The aim of the present study was to compare scores from the English and the Spanish versions of two well-known measures of psychological distress using a within-subject approach. This method involved bilingual participants completing both measures in four conditions. For two groups of people, measures were offered in the same language both times and for the other two groups, each language version was offered, the order differing between the groups. The measures were the Clinical Outcomes in Routine Evaluation-Outcome Measure and the Schwartz Outcome Scale-10, both originally created in English and then translated to Spanish. In total, 109 bilingual participants (69.7% women) completed the measures in two occasions and were randomly allocated to the four conditions (English-English, English-Spanish, Spanish-English and Spanish-Spanish). Linear mixed effects models were performed to provide a formal null hypothesis test of the effect of language, order of completion and their interaction for each measure. The results indicate that for the total score of the Clinical Outcomes in Routine Evaluation-Outcome Measure just language had a significant effect, but no significant effects were found for completion order or the language by order interaction. For the Schwartz Outcome Scale-10 scores, none of these effects were statistically significant. This method offers some clear advantages over the more prevalent psychometric methods of testing score comparability across measure translations.

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OBJECTIVE: To ensure consistency and reduce outcome measure reporting heterogeneity in clinical trials on pediatric functional abdominal pain disorders (FAPDs), a core outcome set (COS) was developed for pediatric FAPD trials. STUDY DESIGN: A mixed-method 2-round Delphi technique was used and key stakeholders, including healthcare professionals (HCPs), patients with FAPD, and their parents were invited to participate. In the first round, key stakeholders identified outcomes of importance through an open-ended questionnaire. Outcomes mentioned by ≥10% of the participants were included in a shortlist. In the second round, this shortlist was rated and prioritized. During a consensus meeting with an expert panel, the final COS was defined. RESULTS: The first round was completed by 152 of 210 (72%) HCPs, 103 (100%) parents, and 50 of 54 (93%) patients. A total of 104 from 167 (62%) HCPs, 102 (100%) parents, and 53 (100%) patients completed round 2. Pain intensity, pain frequency, quality of life, school attendance, anxiety/depression, adequate relief, defecation pattern (disease specific, irritable bowel syndrome), and adverse events were included in the final COS for FAPDs. CONCLUSION: A set of 8 core outcomes has been identified that should minimally be measured in pediatric FAPD trials. Implementation of the use of this COS will increase comparison between studies and, therefore, improve management of children with FAPDs.

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Resource specialization is a key concept in ecology, but it is unexpectedly difficult to parameterize. Differences in resource availability, sampling effort and abundances preclude comparisons of incompletely sampled biotic interaction webs. Here, we extend the distance-based specialization index (DSI) that measures trophic specialization by taking resource phylogenetic relatedness and availability into account into a rescaled version, DSI*. It is a versatile metric of specialization that expands considerably the scope and applicability, hence the usefulness, of DSI. The new metric also accounts for differences in abundance and sampling effort of consumers, which enables robust comparisons among distinct guilds of consumers. It also provides an abundance threshold for the reliability of the metric for rare species, a very desirable property given the difficulty of assessing any aspect of rare species accurately. We apply DSI* to an extensive dataset on interactions between insect herbivores from four folivorous guilds and their host plants in Papua New Guinean rainforests. We demonstrate that DSI*, contrary to the original DSI, is largely independent of sample size and weakly and non-linearly related with several host specificity measures that do not adjust for plant phylogeny. Thus, DSI* provides further insights into host specificity patterns; moreover, it is robust to the number and phylogenetic diversity of plant species selected to be sampled for herbivores. DSI* can be used for a broad range of comparisons of distinct feeding guilds, geographical locations and ecological conditions. This is a key advance in elucidating the interaction structure and evolution of highly diversified systems.

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Background: Developing countries have an estimate of ten times more approved biosimilars than developed countries. This disparity demands the need of an objective regulation that incorporates health policies according to the technological and economical capabilities of each country. One of the challenges lies on the establishment of comparability principles based on a physicochemical and biological characterization that should determine the extent of additional non-clinical and clinical studies. This is particularly relevant for licensed biosimilars in developing countries, which have an extensive clinical experience since their approval as generics' in some cases more than a decade. To exemplify the current status of biosimilars in Mexico' a characterization exercise was conducted on licensed filgrastim biosimilars using pharmacopeial and extended characterization methodologies. Results: Most of the evaluated products complied with the pharmacopeial criteria and showed comparability in their Critical Quality Attributes (CQAs) towards the reference product. These results were expected in accordance with their equivalent performance during their licensing as generics. Accordingly' a rational approval and registration renewal scheme for biosimilars is proposed, that considers the proper identification of CQAs and its thoroughly evaluation using selected techniques. Conclusions: This approach provides support to diminish uncertainty of exhibiting different pharmacological profiles and narrows or even avoids the necessity of comparative clinical studies. Ultimately, this proposal is intended to improve the accessibility to high quality biosimilars in Latin America and other developing countries.

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The manufacture of biologics is a complex process involving numerous steps. Over time, differences may arise as a result of planned changes to the manufacturing processes of a biologic from the same manufacturer. Comparability is the regulatory process that outlines the scope of an assessment required of an already licensed biologic after a manufacturing process change made by the same manufacturer. The aim of a comparability assessment is to demonstrate that any pre-manufacturing and post-manufacturing changes have no adverse impact on quality, safety, and efficacy of the biologic. A comparability assessment is distinct from a biosimilarity assessment, which involves extensive assessment of a biologic that is highly similar to the originator (reference product) in terms of quality, safety, and efficacy. The US Food and Drug Administration, European Medicines Agency, and World Health Organization have applied the fundamental comparability concepts into their respective biosimilarity guidance documents. In this review, we examine the rationale behind the distinct, highly regulated approval processes governing changes that may occur over time to an originator biologic due to planned manufacturing changes (as described by a comparability exercise) and those that outline the approval of a proposed biosimilar drug, based on its relationship with the reference product (biosimilarity evaluations).

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Many patents for the first biologicals derived from recombinant technology and, more recently, monoclonal antibodies (mAbs) are expiring. Naturally, biosimilars are becoming an increasingly important area of interest for the pharmaceutical industry worldwide, not only for emergent countries that need to import biologic products. This review shows the evolution of biosimilar development regarding regulatory, manufacturing bioprocess, comparability, and marketing. The regulatory landscape is evolving globally, whereas analytical structure and functional analyses provide the foundation of a biosimilar development program. The challenges to develop and demonstrate biosimilarity should overcome the inherent differences in the bioprocess manufacturing and physicochemical and biological characterization of a biosimilar compared to several lots of the reference product. The implementation of approaches, such as Quality by Design (QbD), will provide products with defined specifications in relation to quality, purity, safety, and efficacy that were not possible when the reference product was developed. Actually, the need to prove comparability to the reference product by the biosimilar industry has increased the knowledge about the product and the production-process associated by the use of powerful analytical tools. The technological challenges to make copies of biologic products while attending regulatory and market demands are expected to help innovation in the direction of attaining more productive manufacturing processes.

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The global biopharmaceutical market is worth over $100 billion USD. Nearly 90% of these products will lose their patent in the next ten years, leading to the commercialization of their subsequent versions, known as 'biosimilars'. Biosimilars are much more complex molecules than chemically synthesized generics in terms of size, structure, stability, microheterogeneity, manufacture, etc. Therefore, a specific regulatory framework is needed in order to demonstrate their comparability with innovative products, as well as their quality, safety and efficacy. The EU published the first regulatory pathway in 2005 and has approved 14 biosimilars. Mexico has recently developed a clear regulatory pathway for these products. Their legal basis was established in Article 222 Bis of General Law of Health in 2009, clear specifications in the Regulation for Health Goods in 2011, and further requirements in the Mexican Official Norm NOM-EM-001-SSA1-2012. The aim of this review is to summarize the regulatory pathways for biosimilars in the world with a special focus on Mexican experience, so as contribute to the development of regulations in other countries.

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En el presente artículo se analiza el concepto de inconmensurabilidad a la luz de lo que está ocurriendo en diferentes disciplinas relacionadas con la psicología. Se detecta que hay muchos conceptos que se aplican en diferentes estudios sin que exista una elaboración o re-elaboración conceptual a partir de nuevos atributos identificados en un determinado fenómeno; a veces es una mera sumatoria terminológica, y en otros casos se trasladan conceptos sin precisar la ontología o la taxonomía de la que forman parte. Se describen dos trabajos teóricos - el de Castorina y el de Bruner - para ejemplificar los argumentos que se exponen. Finalmente, se argumenta que existiría un cierto margen de espacio común entre las teorías psicológicas, el cual, se podría representar, por ejemplo, en la resolución de "problemas" (tanto teóricos como empíricos. Es decir, una teoría es válida mientras sea apelada por una parte importante de la comunidad científica (para investigación principalmente, y secundariamente para la práctica profesional).

In the present paper, the concept of incommensurability is analyzed in the light of what is happening in different disciplines related to psychology. It is detected that there are many concepts that are applied in different studies without a conceptual elaboration or re-elaboration from new attributes identified in a certain phenomenon. Sometimes it consists of merely adding together many terms; in other cases, concepts are transferred without specifying the ontology or taxonomy of which they are part. Two theoretical works are described - one by Castorina and the other one by Bruner - to exemplify the arguments expressed. Finally, it is argued that a certain margin of common space would exist between psychological theories, which could be represented, for example, in the resolution of "problems" (both theoretical and empirical). That is to say, a theory is valid while it is questionned by an important sector of the scientific community (mainly for research and secondarily for professional practice).

No presente artigo analisa-se o conceito de incomensurabilidade à luz do que está ocorrendo em diferentes disciplinas relacionadas com a psicologia. Detecta-se que há muitos conceitos que se aplicam em diferentes estudos sem que exista uma elaboração ou reelaboração conceitual a partir de novos atributos identificados em um determinado fenômeno; às vezes é uma mera somatória terminológica, e em outros casos se trasladam conceitos sem especificar a ontologia ou a taxonomia da que formam parte. Descrevem-se dois trabalhos teóricos - o de Castorina e o de Bruner - para exemplificar os argumentos que são expostos. Finalmente, argumenta-se que existiria certa margem de espaço comum entre as teorias psicológicas, que poderia ser representado, por exemplo, na solução de "problemas" (tanto teóricos como empíricos). Ou seja, uma teoría é válida enquanto for apelada por uma parte importante da comunidade científica (para pesquisa principalmente, e secundariamente para a prática profissional).

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El dato fundamental en el diagnóstico de la tripanosomiasis americana (enfermedad de Chagas), en su fase crónica, es el estudio serológico, ya que es difícil la demostración del parásito en circulación o en los tejidos. Una seria limitación en el diagnóstico serológico se relaciona con la estandarización de las diferentes técnicas accesibles, y esto depende considerablemente de la calidad de los antígenos usados para el inmunodiagnóstico. En México no se ha abordado este problema. Los laboratorios del Instituto Nacional de Cardiología y del Instituto Nacional de Diagnóstico y Referencia Epidemiológicos, compararon sus técnicas de inmunodiagnóstico: inmunofluorescencia indirecta, hemaglutinación y ensayo inmunoenzimático en fase sólida (ELISA), con cepas de T. cruzi aisladas en México. La concordancia interlaboratorios fue de 0.8 (Indice Kappa) y la sensibilidad, especificidad y valor predictivo positivo y negativo de las pruebas, aseguran resultados confiables en el inmunodiagnóstico de la enfermedad de Chagas

American trypanosomiasis (Chagas'disease) is becoming a relatively common condition in North America. Diagnosis at the chronic stage depends on demonstration of specific antibodies in body fluids, since parasitologic or pathologic diagnosis is uncertain at this stage. Therefore, standardization of immunodiagnostic techniques is mandatory, and it depends on antigen quality. Locally prepared antigens and crude extracts obtained from Mexican isolates, -both from infected vector and human cases- were compared using three different immunodiagnostic assays -indirect immunofluorescence, hemagglutination and enzyme linked immunosorbant assay (ELISA)- at two different laboratories from the Instituto Nacional de Cardiología and the Instituto Nacional de Diagnóstico y Referencia Epidemiológicos. Concordance between laboratories reached a significant Kappa value (0.8) and sensitivity, specificity and predictive values of individual diagnostic assays were adequate to use these tests in clinical diagnoses. This is the first attempt to standardize immunodiagnostic techniques in Mexico.

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