Union volume

The Rules Governing Medicinal Products in the European Union, Volume 10, Clinical Trials. 

The CTD format has been incorporated into the E U regulations and is set out in the revised version of Annex I to directive 2001/82/EC, which was published as Commission Directive 2003/63/EC. It is also supported by detailed guidance in the Rules Governing Medicinal Products in the European Union, Volume 2B - Presentation and content of the dossier - CTD2001 edition. The relationship between the CTD format and the previous four-section format that was used in the E U is shown in Table 6.1. 

The Rules Governing Medicinal Products in the European Union, Volume 2, Notice to Applicants, Medicinal Products for Human Use. http //ec.europa.eu/enterprise/pharmaceuticals/index en.htm. 

The Community procedure for establishing MRLs of veterinary medicines in foodstuffs of animal origin is set down in Council Regulation (EEC) No. 2377/90 as amended by Council Regulation (EC) No. 1308/1999. The regulations are supported by detailed guidance contained in The Rules Governing Medicinal Products in the European Union, Volume 8 - Maximum Residue Limits. 

The procedures and timelines for obtaining marketing authorisations for veterinary products are essentially the same as those for human medicines. Extensive guidance can be found in The Rules Governing Medicinal Products in the European Union, Volume 6 - Notice to Applicants, Veterinary Medicinal Products. The products that may follow centralised procedures and receive Community authorisations are shown in Eigure 7.5. All other products must obtain authorisations from national... 

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... 

Voronoi vertices completely encloses the associated cavity. This union volume provides an upper bound of the cavity s volume. 

The suggested headings and arrangement of the document may be found in The Rules Governing Medicinal Products in the European Union Volume 2, Notice to Applicants Volume 2B Presentation and Content of the Dossier, Common Technical Document which can be accessed at the Commission website www.pharmacos.eudra.org. Information is also available at the European Medicines Agency website www.emea.eu.int. 

European Commission. The Rules Governing the Medical Products in the European Union, Volume 4, Good Manufacturing Practices. Brussels Directorate General BI—Industry, Pharmaceuticals and Cosmetics (1998). 

Figures from James M. McPherson, Battle Cry of Lreedom The Civil War Era (New York Oxford University Press, 1988) pp. 313, 336 and Allan Nevins, The War for the Union, volume 4, The Organized War to Victory, 1864-1865 reprinted. New York Konecky and Konecky, 2000), p. 254. Naval figures are from Ivan Musicant, Divided Waters The Naval History of the Civil War (New York HarperCollins, 1995), p. 57. 

A basic comprehension of the requirements for companies using the system will be useful, as will an understanding of the processes and targets which were built into the system in order to ensure that products reach the market in a timely fashion. We therefore recommend to the reader a review of The Rules Governing Medicinal Products in the European Union, Volume 2, commonly referred to as the Notice to Appli-... 

Council of Europe (2005) European pharmacopeia, 5th edn. Maisonneuve, Paris European Economic Community (1997) Pharmaceutical legislation for medicinal products for human and veterinary use in the European Union. Good manufacturing practices. (Directive 91/ 356/EEC). Eudralex, vol. IV. European Economic Community, Luxemboiug European Economic Community (1998) Notice to applicants for marketing authorization for medicinal products for human use in the Eiuopean Union, Volume IIA (III/3567/92)... 

In the second step, one or more primary site pockets are identified as seeds for generating larger site cavities consisting of a primary pocket and one or more neighboring secondary pockets. To identify the primary site pockets, the union volume of the superimposed molecules is now divided, usually manually, into distinct binding site cavities (see Figure 3). All ligand atoms that fall into a particular site cavity experience the same environment that is, a specific set of coefficients (c,y of Eq. [7]) will be attributed to each cavity. 

In the first step, the aligned molecules are surrounded by a 3D lattice of regularly spaced points. The distance between neighboring points, the resolution level of the parameterization, is generally 1-2 A. The walls of the lattice extend at least 4 A beyond the union volume of the superimposed structures. For molecules the size of drugs, these settings lead to at least hundreds of grid points. 

To speed the PLS calculations, one can drastically reduce the number of columns of fields included by rejecting all probe-ligand energies with a low standard deviation (generally 0.05-2.0 kcal/mol) among the molecules in the data set. This variable selection assumes that a property that does not vary significantly will not be statistically useful. For example, the lattice points inside the union volume of the superimposed molecules sample constant steric energies, hence cannot explain the differences in potency between different compounds. 

A difficult issue with CoMFA entails electrostatic fields calculated inside a particular molecule, because very small changes in location of a lattice point can make a dramatic difference in the potential. Keep in mind that the receptor could not occupy this position. In the default setting in SYBYL CoMFA, any electrostatic energy inside a molecule is assigned to the mean of the noncutoff values of molecules for which this point is outside the molecule. In other implementations, the electrostatic energies are calculated only outside the union volume of the superimposed molecules.[n some CoMFA studies, however, better results were achieved without any steric-based deletion of electrostatic descriptors.20.21... 

McNeal, R. H. (Ed.). (1974). On the results and coming tasks of kolkhoz construction. In Resolutions and decisions of the Communist Party of the Soviet Union, Volume 3 The Stalin years 1929-1953 (pp. 28-38). Toronto University of Toronto Press. 

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