Search results for "Waiver"
showing 10 items of 11 documents
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Ribavirin
2015
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release solid oral dosage forms containing ribavirin are reviewed. Ribavirin is highly soluble, but its permeability characteristics are not well defined. Therefore according to the Biopharmaceutical Classification System, and taking a “worst case” approach, ribavirin should be assigned to class III. As ribavirin is transported across the brush border membrane of the human jejunum by hCNT2, it shows saturable uptake in the intestine. However, no common excipients have been shown to compete for ribavirin absorption, nor have problems with BE of immediate release rib…
The Influence of Chitosan on the Oral Bioavailability of Acyclovir-a Comparative Bioavailability Study in Humans
2015
Purpose The effects of chitosan hydrochloride on the oral absorption of acyclovir in humans were studied to confirm the absorption enhancing effects reported for in vitro and rat studies, respectively. Methods A controlled, open-label, randomized, 3-phase study was conducted in 12 healthy human volunteers. Zovirax 200 mg dispersible tablets co-administered with doses of 400 and 1000 mg chitosan HCl were compared with Zovirax only. Results The expected increased absorption of acyclovir was not observed. On the contrary, mean area under the plasma concentration-time curve (AUC0-12 h) and maximal plasma concentration (Cmax) decreased following concomitant chitosan intake (1402 versus 1017 and …
Global testing of a consensus solubility assessment to enhance robustness of the WHO biopharmaceutical classification system
2020
The WHO Biopharmaceutical Classification System (BCS) is a practical tool to identify active pharmaceutical ingredients (APIs) that scientifically qualify for a waiver of in vivo bioequivalence studies. The focus of this study was to engage a global network of laboratories to experimentally quantify the pH-dependent solubility of the highest therapeutic dose of 16 APIs using a harmonized protocol. Intra-laboratory variability was ≤5 %, and no apparent association of inter-laboratory variability with API solubility was discovered. Final classification “low solubility” vs “high solubility” was consistent among laboratories. In comparison to the literature-based provisional 2006 WHO BCS classi…
Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Moxifloxacin Hydrochloride.
2020
Abstract In this monograph, literature data is reviewed to evaluate the feasibility of waiving in vivo bioequivalence testing and instead applying the Biopharmaceutics Classification System (BCS) based methods to the approval of immediate-release solid oral dosage forms containing moxifloxacin hydrochloride as the sole active pharmaceutical ingredient. To facilitate the feasibility decision, solubility and permeability and dissolution characteristics in the context of the BCS, therapeutic index, therapeutic use, pharmacokinetic parameters, bioequivalence/bioavailability issues, drug-excipient interactions and other relevant data were taken into consideration. Moxifloxacin is a BCS class I d…
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Metformin Hydrochloride.
2021
Abstract Data are examined regarding possible waiver of in vivo bioequivalence testing (i.e. biowaiver) for approval of metformin hydrochloride (metformin) immediate-release solid oral dosage forms. Data include metformin's Biopharmaceutics Classification System (BCS) properties, including potential excipient interactions. Metformin is a prototypical transporter-mediated drug and is highly soluble, but only 50% of an orally administered dose is absorbed from the gut. Therefore, metformin is a BCS Class III substance. A BCS-based approval approach for major changes to marketed products and new generics is admissible if test and reference dosage forms have the identical active pharmaceutical …
Regional Mobility Spaces? Visa Waiver Policies and Regional Integration
2016
Visa policies today are a central instrument for filtering wanted and unwanted types of travellers, leading to a hierarchy of mobility rights. While there is evidence of a “global mobility divide”, we still know little about the role of regional integration when it comes to the distribution of mobility rights and the (re)structuring of mobility spaces. Against this background, the paper examines the structure of visa relations in different bodies of regional integration (EU, MERCOSUR, ASEAN, ECOWAS, EAC, NAFTA, SADC and SICA). In this article, we compare visa policies in the member states of these institutions in 1969 and 2010 from a social network perspective. While one would generally exp…
Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Ondansetron.
2019
Literature data pertaining to the physicochemical, pharmaceutical, and pharmacokinetic properties of ondansetron hydrochloride dihydrate are reviewed to arrive at a decision on whether a marketing authorization of an immediate release (IR) solid oral dosage form can be approved based on a Biopharmaceutics Classification System (BCS)-based biowaiver. Ondansetron, a 5HT3 receptor antagonist, is used at doses ranging from 4 mg to 24 mg in the management of nausea and vomiting associated with chemotherapy, radiotherapy, and postoperative treatment. It is a weak base and thus exhibits pH-dependent solubility. However, it is able to meet the criteria of "high solubility" as well as "high permeabi…
L'orario di lavoro nel diritto dell'Unione Europea
2015
L’articolo analizza la normativa europea in materia di orario di lavoro (dir. 2003/88/CE) per come interpretata dalla Corte di Giustizia. Più in particolare vengono discusse le nozioni di orario e tempi di lavoro e la regolamentazione di ferie, lavoro notturno, riposi giornalieri e settimanali, e le discipline speciali; specifica attenzione è dedicata alle deroghe che secondo la direttiva possono essere apportate dall’autonomia collettiva ed individuale alla disciplina legale, per sottolineare come il diritto dell’Unione abbia determinato una marcata liberalizzazione dei tempi di lavoro. The present work analyses the EU legislative framework on working time (dir. 2003/88/EC) and the related…
Le rinunce e transazioni sottratte alla disciplina dell’art. 2113 c.c.
2022
The essay deals with waivers and transactions on employees’ rights. According to the consistent judicial overview of art. 2113 of the civil code, waivers and trans actions on rights guaranteed by mandatory rules of law or collective bargaining, only concern renunciations of rights already acquired by the holder, and not still disputed. In particular, art. 2113 of the civil code does not apply if the right can be dismissed by the right holder, as in the case of job retention.
Global epidemiology of coronavirus disease 2019 and lessons for effective control of this and future pandemics
2021
Barely 1 year after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first reported in China, the virus has infected approximately 120 million people, caused around 3 million deaths, and adversely affected the global economy Despite stringent measures to flatten the epidemiologic curve of the pandemic, there have been spikes and waves of the infection in many countries, particularly in the American, European, and Asian continents This review critically evaluated the global epidemiology of the novel coronavirus disease 2019 (COVID-19) to provide advice on other possible ways of managing the disease as various COVID-19 vaccines are being rolled out To effectively control this …