Non-clinical overview

Safety - M4S(R2) Module 4 Non-clinical + Module 2 Non-Clinical Overview and Summary... 

Update or Addendum to quality summaries, non-clinical overviews and clinical overviews (the former expert reports ) as may be relevant. When nonclinical or clinical study reports are submitted, their relevant summaries should also be included in Module II. 

Module 2 - Summaries in addition to a table of contents and a one-page introduction, this module contains the Quality Overall Summary, the Non-clinical Overview, and the Clinical Overview these are followed by the Non-clinical Written Summaries, the Non-clinical Tabulated Summaries, and the Clinical Summary separate documents (M4Q, M4S, and M4E) give guidance on the format and content of the summaries)... 

Module 2, quality overall summary (general introduction, quality summary, non-clinical overview and summary, clinical overview and summary)... 

The CTD is organised into five modules. A schematic representation of the stmcture and hierarchy is shown in Figure 6.1. Module 1 is designed to contain region-specific information such as application forms and other administrative provisions that may apply. As such, it is not harmonised and is not considered part of the CTD. The other four modules present the technical data in a harmonised format. Module 2 should contain critical overview assessments of the quality, non-dinical and clinical data, together with summaries of the non-clinical and clinical data. The objective of this section is to provide reviewers with an introduction to the submission, and to orient... 

Overviews / Summaries of Quality Non-Clinical and Clinical Expert Reports I c... 

Overview of the non-clinical testing strategy Pharmacology Pharmacokinetics Toxicology... 

Figure 6.6 Structure of the Non-clinical and Clinical Overview and Summary sections.

CTD consists of four modules, preceded by a Module 1 that is region-specific and includes administrative and prescribing information. Module 2 comprises of CTD summaries and overviews of the quality, non-clinical and clinical data. Module 3 contains data on quality. Module 4 consists of the non-clinical study reports and Module 5 comprises the clinical study reports. There are guidelines on the details to be included in each module and these are summarised in Box 17.2. The non-clinical and clinical overviews and summaries are equivalent to the previous Expert Reports submitted under sections IC2 and IC3 respectively of part I, data. 

Module 2 Common technical document summaries Overall common technical document table of contents Introduction Quahty overall summary Non-chnical overview Clinical overview Non-chnical summary Pharmacology Written summary Tabulated summary Pharmacokinetics Written summary Tabulated summary Toxicology... 

M4 is another very important multidisciplinary guideline, which combines information for the 3 disciplines within the ICH Process for Quality, Safety and Efficacy. The following section focuses predominantly on the preclinical safety issues. The total document is divided into 5 modules Module 1 contains regional specific aspects, it provides for the European Union e.g. the European Community specific data. This module therefore is not harmonized but region-specific. Module 2 provides the Summaries for Quality, for Safety and Efficacy. The quality part uses as a headline Quality Overall Summary , for safety and efficacy the terms Non-Clinical or Clinical Overview . The different names signal that the quality part is a clear summary, while the non-clinical and clinical part should be critical evaluations. Module 3 provides chemical, pharmaceutical and biological information. Module 4 contains the non-clinical reports and Module 5 provides clinical study reports. 

As noted in the Overview, GLP is a series of guidelines that cover the conduct and data production for non-clinical safety studies. 

The Commission, in conjunction with the Notice to Applicants Working Party, completed its work on the incorporation of the ICH Common Technical Document (CTD) into a revision of Volume 2B of the Notice to Applicants. A schematic representation of the correspondence between the five modules of the CTD and the four parts of the European registration dossier has also been prepared in order to facilitate the transition from the old application format to the new one. The non-clinical and clinical overviews and summaries are equivalent to the present expert report described above. The clinical summary may replace the Integrated Summary of Efficacy and Integrated Summary of Safety Required by the FDA, and the Clinical Overview and Clinical Summary have been designed to replace the Japanese GAIYO. 

Kawashima, K., Fujii, T. (2008). Basic and clinical aspects of nonneuronal acetylcholine overview of non-neuronal cholinergic systems and their biological significance. J. Pharmacol. Sci. 106 167-73. 

Here we review current knowledge on the enzymes and related binding proteins that are involved in covalent modifications to histones. We begin with a brief overview of the field aimed at the non-expert, then focus on the covalent modifications themselves as catalysed by specific enzymes. We also focus on the consequences of these modifications for binding interactions with other proteins that modulate gene expression. The field is one that is rapidly evolving and we hope to convey some of the excitement that we feel about recent discoveries in histone science, particularly from a molecular perspective. Two inhibitors of histone modifying enzymes are in clinical use, with more likely to be introduced in the near future. Thus, the development of modifiers of histone biochemistry is of medicinal as well as basic interest. 

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