Asia Core Dossier: Standardizing CMC Requirement to Facilitate Best Case Submissions in Asia.

When the regulatory requirements are converged or harmonized, the country-specific variance of countries is often reduced or omitted, and this facilitates the possibility of preparing a core dossier that caters to multiple countries. When such options of a core dossier are acceptable to multiple countries, the resource required to prepare the dossier and the time taken to prepare it is also reduced, thus eliminating resource constraints in supporting dossier planning and preparation and indirectly facilitating earlier submission in countries. In this paper, the authors have illustrated a process applied to standardize the dossier requirements amongst selected countries in Asia, producing an output of a core dossier that applies to four submission types amongst these countries. The core dossier adopts the International Council for Harmonization-Common Technical Dossier format as a reference. Main focus is the standardization of format and requirements within the Module 3 or Chemistry Manufacturing Controls sections of the dossier, which from the authors' organizational experience usually notes a higher variances and country-specific elements. Development of the dossier standardization process is due to an internal hurdle within the authors' organization, where global resource constraints and prioritizations of dossier preparation and compliance review process needed to be improved to facilitate earlier or near-simultaneously submissions in the majority of the Asia countries. The paper demonstrates an assessment of the dossier components and standardization to assemble a fit-for-purpose core dossier termed 'Asia Core Dossier' (ACD). ACD has been successfully implemented within the authors' organization to reduce country-specific requirements and facilitate earlier (fit for strategy) submissions in the selected Asia countries. The paper also discusses the tangible benefits of the authors' experiences from utilizing the ACD. Regulatory professionals in different organizations could reference the ACD as a template for preparing a simplified and efficient dossier and as a relevant component of Good Submission Practice (GSubP).

Over-expression of translationally controlled tumor protein in lens epithelial cells seems to be associated with cataract development.

Inhibition of Na,K-ATPase causes opacification of the lens through abnormal increases in sodium and calcium levels, disturbed osmotic equilibrium, activation of proteolytic enzymes and cell damage. We previously identified Translationally Controlled Tumor Protein (TCTP) as a cytoplasmic repressor of Na,K-ATPase and confirmed that systemic hypertension is induced in transgenic mice over-expressing TCTP through inhibition of vascular Na,K-ATPase and increased intracellular calcium mobilization. In the current study, we confirmed the role of TCTP in causing intracellular calcium mobilization by inhibiting Na,K-ATPase in a human lens epithelial cell line and further showed that some of the TCTP-transgenic mice develop cataracts with an incidence rate of 7.38% compared to 1.47% in controls. We demonstrated that TCTP acts as a cataractogenic factor through the repression of Na,K-ATPase activity and calcium mobilization in lens epithelial cells.