Abstract Albendazole is an anthelmintic drug commonly used in parenchymal neurocysticercosis and cystic echinococcosis. The aim of this study was to explore whether disparities in the dissolution profiles of albendazole products lead to significant differences in pharmacokinetic parameters. Three generic products and the innovator were evaluated in vitro. Quality control tests were performed, and dissolution profiles were obtained according to the Mexican Pharmacopeia. Although all products passed the quality control tests, none of the generic products complied with the similarity factor (f 2). The product with the lowest f 2 value in respect to the reference was chosen for in vivo evaluation. The study was carried out in 12 healthy volunteers who received 400 mg of the generic or reference product according to a crossover design. No significant differences were found in Cmax and AUC for albendazole and its main metabolite, albendazole sulfoxide, between products. Two absorption peaks were observed in the pharmacokinetic profile, and a population (22%) with different absorption rates and delay time for the the second peak was found. Based on the results, due to the high variability in the absorption process the differences observed in vitro could not be observed in vivo.

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.

The aim of the present study was to assess the impact of the sampling times and the percentage dissolved on the similarity factor f2. Dissolution results of albendazole, ranitidine, ciprofloxacin and metronidazole previously performed were used. Data were evaluated using the criteria of regulatory agencies such as: a) Food and Drug Administration (FDA), which indicates that for the evaluation of similarity factor only one measurement should be considered after 85% dissolution of both the products and b) European Agency for the Evaluation of Medicinal Products (EMA) which specifies that for the evaluation of the similarity factor not more than one mean value greater than 85% dissolved for any of the formulations should be considered. The results showed that the f2 values were similar when both methods were used; however the test is more rigorous when the EMA criterion is used.

Se llevó a cabo un estudio para evaluar el impacto del número de tiempos de muestreo y el porcentaje disuelto, en el cálculo del factor de similitud ƒ2. Para el análisis se utilizaron los resultados de perfiles de disolución de productos comerciales conteniendo albendazol, ranitidina, ciprofloxacino y metronidazol previamente realizados. Los cálculos se llevaron a cabo empleando los criterios de las siguientes agencias regulatorias: a) Food and Drug Administration (FDA), que especifica que se debe tomar un valor después de que ambos productos alcanzan el 85% y b) European Agency for the Evaluation of Medicinal Products (EMA) que indica que se debe tomar un valor después de que el primero de los productos alcanza el 85% disuelto. Los resultados mostraron que, en general, los valores de ƒ2 son semejantes al emplear ambos criterios, sin embargo en aquellos casos en los que el promedio de las diferencias entre ambos productos es cercano al 10%, la prueba de ƒ2 es más estricta al emplear el criterio de EMA.