Scientific Data

A variety of chemical data are required under this heading, including information on the nomenclature of the drug substance, its description, its manufacture and quality control during manufacture, development chemistry, details of impurities and results of batch analyses. Some of this information may also be necessary for excipients which have not been previously used in a medicinal product. 

Quality control of the drug substance manufacturing process requires the application of specifications to starting materials, intermediates, solvents and reagents. Any of these may include NMR tests, usually to provide identification of the substance in question. NMR spectroscopy comes into its own in the section on development chemistry, which should include evidence of chemical structure, discussion of potential isomerism, physico- 

A wide range of proton and carbon NMR techniques, almost exclusively using Fourier Transform (FT) spectroscopy, are presented in applications to support proposed chemical structures, with multinuclear NMR being used where appropriate. Polarisation transfer experiments (e.g. DEPT) are used to indicate carbon multiplicity and the use of two-dimensional techniques, which facilitate signal assignment, is seen more frequently in applications. Typical techniques include H- H correlation (COSY and related phase-sensitive experiments) proton-carbon heteronuclear correlation (including inverse 

Conformational data may be required for macromolecules, e.g. proteins, particularly where the correct conformation is essentitd for activity. As reported in the literature, NMR has been of substantial value in diis area through the analysis of coupling constants, use of NOE and relaxation measurements amongst other techniques, though this type of data has not yet been seen in regulatory dossiers (in any case, demonstration of appropriate biological activity would be necessary). 

The setting of impurity limits in the specification should take into account both the quality of the drug substance, i.e. the actual levels of related substances found in batch analysis, and also the safety of an individual impurity or given impurity profile at the specified levels. The acquisition and evaluation of data which establishes this safety is referred to as qualification. An impurity or impurity profile is considered qualified if it has been adequately tested in pre-clinical or clinical studies and such studies are needed for impurities present above the dose-dependent qualification thresholds prescribed in the note for guidance. 

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According to an elegant remark by Davies [5], "Modem scientific data handling is multitechnique, multisystem, and manufacturer-independent, with results being processed remotely from the measuring apparatus. Indeed, data exchange and storage are steps of the utmost importance in the data acquisition pathway. The simplest way to store data is to define some special format (i.e., collection of rules) of a flat file. Naturally, one cannot overestimate the importance of databases, which are the subject of Chapter 5 in this book. Below we discuss three simple, yet efficient, data formats. 

One was a water-moderated and water-cooled pressurized reactor the other was a Hquid-metal-cooled iatermediate neutron energy reactor. A land-based prototype submafine power plant called Mark I was built and tested at the National Reactor Testing Station. Argonne National Laboratory provided scientific data and Bettis Laboratory of Westinghouse Electric Corp. suppHed engineering expertise. 

Morplant A Summary of Scientific Data, The Population Council, New York, 1990. 

The new proved scientific data confirming the important role of chemical elements in maintenance of biological processes in human organism have appeared during the last three decades. 

In this scheme, OELs should be a dose somewhere between compensatory effects, in which the organism is able to detoxify, metabolize, or excrete the substance, and early impairment. Although there may be profound differences of opinion as to what constitutes this dose, this approach leads to the conclusion that available scientific data permits identification of a clear threshold dose below which exposure to the substance in question is not expected to lead to adverse effects. 

An indicative limit value is a more common type of limit that reflects expert evaluation based on scientific data where it is possible to identify the highest level of exposure along with the corresponding reference time period for which one can have confidence that there will be no adverse effects on health. For any chemical agent for which an indicative occupational exposure limit value is established at the community level, member states shall establish a national occupational exposure limit value, taking into account the community limit value and determining its nature in accordance with national legislation and practice. 

Because of the complexities of the materials and the effects of the processing on the materials, this is an area where predictability based on scientific data is very limited and casting experience is desirable. Successful products will result from close cooperation between designer, tool designer, mold maker, and processor to arrive at design compromises that make the products acceptable and producible at an economical price. 

Both techniques have their advantages and their limitations with respect to process time, process temperatures, and process costs. However, the crucial question is How much does crosslinking contribute to the desired properties of the material The performance of the final product is, of course, the major issue. A lot of information on crosslinked polymers is available in the literature. There have been several attempts in the past [1-7], and also more recently [8-10], to sort out this accumulation of scientific data. Yet, it is neither simple nor particularly rewarding to undertake such a venture due to the multitude of variables which make direct comparisons difficult, and to the incidence of apparent contradictions. 

Sufficient scientific data is still lacking to really pinpoint the bioactive sites of the pectic type polymers described in this chapter, but on the basis of the work of the group headed by Yamada over the last ten years, a better un-... 

It may also be beneficial to the reader if we define the sources of the scientific data in preclinical development. The following are examples of the development activities that generate the majority of the data ... 

In preclinical development, the GMP/GLP regulations are enforced not only for scientific data but also for text documents. This section discusses several types of controlled text documents used in preclinical development. Most of these documents are managed by the fully validated TIMS. 

The technical help rendered by my husband Dr Reddy Sastry Cherukuri in preparing the tables and collecting the scientific data and by my daughter Dr Anu Cherukuri who helped me in procuring the references from the National Library is greatly acknowledged. 

Organize and sponsor chapters to provide a forum for the presentation of scientific data and for the interchange and study of information about local concerns. 

The electronic data capture systems that have become commonplace in the research and analytical laboratory allow rapid and efficient acquisition, manipulation, and reporting of vast amounts of scientific data. In addition, they have provided a means to generate a permanent audit trail which describes the conditions under which a... 

With respect to development pharmaceutics data, the requirements stated in Directive 75/318/EEC (as amended) are included in the Annex to that document at Part 2 A 4 (page 20 of the Rules Governing Medicinal Products in the European Union, Volume 1, Pharmaceutical Legislation Medicinal Products for Human Use). With respect to the general requirement for pharmaceutical products this states 4.1 An explanation should be provided with regard to the choice of composition, constituents and container and the intended function of the excipients in the finished product. This explanation shall be supported by scientific data on development pharmaceutics. The overage, with justification thereof, should be stated. This, then, is the legal requirement. Needless to say, there is a... 

For pharmacopeial materials scientific data are not normally required in the application provided that the method of production is such that uncontrolled impurities will not be present in the material. Otherwise the impurities concerned should be declared and appropriate specifications and test methods put forward. 

In order to understand the characteristics of state-of-the-art scientific software, a description of the facilities of the RS/1 system is presented in this section as an example of the kind of software now available to support scientific data management needs. All facilities are based in a single integrated system. No extra steps are needed, for example, to use tabular data as the basis for statistics or to graph the results of modeling. 

In the new field of genetic engineering, scientific data management software is used to manage the long alphabetic codes that represent genetic sequences, as well as more traditional numeric and text applications. At Genentech, scientists use the software for these tasks as well as for laboratory data analysis. 

Scientific data points usually require curves, several lines, or both to divide them into homogeneous groups. 

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