Percorrer por autor "Cardoso, Catarina"
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- Drilling down the bioequivalence assessment of topical antifungal products : microstructure and releasePublication . Miranda, Margarida; Cardoso, Catarina; Pais, Alberto A.C.C.; Brown, Marc; Vitorino, CarlaIn recent years, the regulatory mechanisms for topical generic product bioequivalence (BE) assessment have been subjected to noteworthy changes, with the FDA issuing product specific guidances, and the EMA adopting a more universal approach with the quality and equivalence of topical products draft guideline. The agencies advise on a modular strategy for BE documentation. Nevertheless, their scope, data analysis and criteria are rather distinct. This study aims to tackle bioequivalence assessment issues of complex topical formulations starting by statistical implications of the EMA/FDA approaches concerning the documentation of qualitative (Q1), quantitative (Q2), microstructure (Q3) and performance requirements (Q4). As a model drug product, a bifonazole 10 mg/g cream formulation was selected. For this specific formulation, the commercially available Reference Product (RP) was compared with two comparator products, also commercially available, referred to as comparator product A (CPA) and comparator product B (CPB). The former displays Q1 sameness and Q2 differences, whilst CPB is categorically considered as Q1/Q2 different. Furthermore, intending to establish a regulatory rationale for the submission of a generic product according to the updated regulatory requirements, the RP was likewise compared with a Test Product (TP). This formulation was designed to display equal Q1/Q2 profile to that of the RP. Validated rheology and in vitro release test (IVRT) methods were used to infer on Q3/Q4 characteristics. During rheology studies, statistically significant RP batch to batch differences were observed. Therefore, in an attempt to surpass this heterogeneity, the initial pool of RP batches was expanded to include RP product batches at different lifecycle stages. Despite this effort, it was not possible to classify the RP/TP, RP/CPA or RP/CPB as rheologically equivalent products. Nevertheless, product performance results, retrieved from IVRT, were able to sustain equivalence between the RP and the formulations exhibiting Q1 sameness (TP and CPA). It should however be mentioned, that for some RP batch combinations, the IVRT results failed to demonstrate equivalence according to the EMA requirements. Enlarging the RP batch pool was then a critical step in further understanding an optimum statistical approach for establishing equivalence in product performance. This study highlights the need to that a ‘one-fits-all approach’ may not be an optimum path way for establishing the regulatory strategy and requirements to support generic product bioequivalence.
- In vitro studies into establishing therapeutic bioequivalence of complex topical products : weight of evidencePublication . Miranda, Margarida; Volmer, Zoe; Cornick, Alicia; Goody, Aidan; Cardoso, Catarina; Pais, Alberto A.C.C.; Brown, Marc; Vitorino, CarlaOver the past decade, topically applied drug products have experienced extraordinary price increases, due to the shortage of multisource generic drug products. This occurrence is mainly related to the underlying challenges evolved in topical bioequivalence documentation. Although there has been continuing regulatory efforts to present surrogate in vitro methods to clinical endpoint studies, there is still a continued need for cost- and time-efficient alternatives that account for product specificities. Hence, this work intended to expose bioequivalence assessment issues for complex topical formulations, and more specifically those related with product efficacy guidance. As a model drug and product, a bifonazole 10 mg/g cream formulation was selected and two different batches of the commercially available Reference Product (RP) were used: RP1 that displayed lower viscosity and RP4 which presented high, but not the highest, viscosity. In vitro human skin permeation testing (IVPT) was carried out and the results were evaluated by means of the traditional bioequivalence assessment approach proposed by the EMA, as well as by the Scaled Average Bioequivalence assessment approach proposed by the FDA. Based on previous experience, there was an expectation of a high level of variability in the results, thus alternative methods to evaluate local drug skin availability were developed. More specifically, an infected skin disease model, where ex vivo human skin was infected and ATP levels were used as a biological marker for monitoring antifungal activity after product application. The results showed that permeation equivalence could not be supported between the different RP batches. In contrast, this statistical difference between the formulation batches was not indicated in the disease model. Nevertheless, in pivotal IVPT studies, the lowest permeant formulation (RP4) evidenced a higher antifungal in vitro activity as reported by the lower levels of ATP. A critical appraisal of the results is likewise presented, focusing on an outlook of the real applicability of the regulatory guidances on this subject.
- O papel da cultura na escrita de reviews da enconomia da partilha: Um estudo sobre o aribnbPublication . Cardoso, Catarina; Casais, BeatrizA presente dissertação investiga qual o papel da cultura na escrita das reviews de economia da partilha, no caso do Airbnb. Considerando as dimensões culturais de Hofstede, procedeu-se à análise das dimensões Individualismo e Masculinidade. Sabe-se que os fatores que influenciam a produção de opinião nos sistemas peer-to-peer podem ser características pessoais, background cultural ou atributos demográficos que alteram a forma como os consumidores percecionam o conteúdo, por isso as reviews online são escritas com base nas experiências pessoais. Este mecanismo de feedback é um complemento descritivo à classificação de rating, através da utilização de eWom. Por meio da produção do conteúdo gerado pelos utilizadores (ugc), são estabelecidas estratégias que contribuem para que exista co-criação de valor durante a experiência de consumo. Não sendo percetível qual o papel que as características culturais dos reviewers assume, constata-se que existe um gap na literatura ao qual esta investigação pretende responder através da análise da presença de fatores culturais Individualistas vs coletivistas, nas reviews do Airbnb, assim como a presença de características de Masculinidade e por fim, as diferenças culturais no processo de co-criação de valor. De modo a conduzir a investigação, foi coletada uma amostra de 774 reviews existentes na plataforma de dois alojamentos localizados em Portugal, Alfama-Amazing River view, localizado em Lisboa e Vitória 392 Central & Rustic Studio, no Porto. Os reviewers presentes para análise são provenientes de 32 países. Os resultados da análise conduzem à conclusão de que relativamente às dimensões culturais em foco, na amostra recolhida, não se verifica que existam diferenças significativas na produção do conteúdo mediante a proveniência cultural, ainda que estejam presentes várias características das mesmas, prevalece o modo como a plataforma recolhe o feedback, o que transforma o texto em conteúdo semelhante. Face à co-criação de valor, conclui-se que o contributo é feito de modo standardizado por parte dos hóspedes. O contributo que esta dissertação contém diz respeito à perceção da presença das dimensões culturais no Airbnb, sendo que se conclui que a classificação do host deveria ser tida como categoria de análise, dada a presença e importância para a experiência que é demonstrada em todas as reviews, como refletem os exemplos apresentados. A principal limitação refere-se à amostra que foi recolhida, embora a presença de uma vasta diversidade cultural. Por isso sugere-se a continuidade da análise da presença das dimensões culturais nas reviews online da plataforma Airbnb, com o objetivo de coletar também a presença de outras culturas distintas.
- Rheology of complex topical formulations : an analytical quality by design approach to method optimization and validationPublication . Chiarentin, Lucas; Cardoso, Catarina; Miranda, Margarida; Vitorina, CarlaAnalytical method validation ensures that a method provides trustworthy information about a particular sample when applied in accordance with the predefined protocol. According to regulatory standards, the rheological characteristics of topically applied semisolid formulations are one of the key elements involved in microstructure equivalence documentation. Therefore, for generic drug product manufacturers, it is a dire need to take a step forward in rheology method development and validation procedures. This paper aims to apply Analytical Quality by Design (AQbD) principles towards the development and validation of rheology methods for topical creams, as complex semisolid formulations. Risk assessment was carried out through an Ishikawa diagram and an estimate failure mode, effects, and criticality analysis (FMECA). Sample application, peltier temperature control, and sample rest time were identified as critical method variables (CMVs), and a 23 full factorial design was applied to understand their impact on rotational, creep recovery and, oscillatory measurements. The development of the method was carried out as per the ICH Q8-Q10, and Q14 guidelines and validated according to ICH Q2 (R2) guideline. The method demonstrated adequate precision (RSD < 15%), as well as selectivity. AQbD provided a comprehensive framework for developing a reliable and effective rheology method for this type of formulation.