Registration Systems

Typical rules include converting nitro groups to the uncharged form (6.8), expanding shortcuts (6.9), replacing dative bonds in coordination compounds with separated charges (6.10), and neutralising zwitterions (6.11). 

For tautomers, the ideal situation is to store one preferred tautomeric form and register other forms as synonyms of this preferred one. However, there is no universally accepted algorithm for tautomer generation, and each registration system will have its own implementation. There will be cases where the system perceives two structures to be tautomers but the chemist knows better and wants to store them separately. Conversely, due to limitations in the tautomer perception algorithm, two tautomeric forms may not be recognised as such. A practical registration system must therefore allow chemists to override the system-provided default. 

In a pharmaceutical context, the biologically active part of a structure is of the most importance, and it is convenient to group biologically equivalent forms together. A technique which has worked for many years in GSK is the concept of a parent structure. The parent structure is derived from the version structure (as supplied by the chemist) by stripping off any salts and solvates and converting any unnatural isotopes to their normally abundant form. Isotopically labelled compounds are typically used for metabolism studies and are therefore normalised and grouped under the same parent as the nonisotope form. 

Other typical transformations to make the parent include breaking any covalent bonds to group I metals and neutralising charges as far as possible by adding or removing protons subject to maintenenance of the correct valency. 

It is important to realise that the parent structure may not actually exist it is simply used for the grouping of biologically equivalent structures. Parent structures are also beloved of modellers who don t want salts and isotopes complicating their SAR work. 

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Obviously a compound registration system is already a fundamental part of the informatics infrastructure for any pharmaceutical company. However, there is a powerful efficiency gain in not having scientists input information twice into different systems the reaction information into the ELN and then the product molecules into the registration system. One would rather have a mechanism of pushing the product molecule information from the ELN to the registration system. The obvious corollary to this is to have the ability to retrieve compound information from the registration system and have it automatically entered into the ELN—an example would be for the scientist to... 

As one of the indispensable software tools, the compound registration system provides a mechanism for the medicinal chemist to capture chemical structure information as well as analytical and other data in a database. We mention two of the systems below. 

All 10 countries have a registration system for allopathic/modem drugs, but only seven countries (Australia, Estonia, Malaysia, Netherlands, Tunisia, Uganda and Venezuela) make registration of herbal medicines compulsory. 

Venezuela developed its dmg regulation system relatively early. Its first dmg-related law was issued in 1883 as the Ordinance of the Council of Physicians on Secret Medicines and Patents. Dmg laws have been revised regularly a significant number of dmg laws were adopted over the course of the 20 century. The law which established the dmg registration system— the Law on the Exercise of the Pharmacy— was passed... 

The first Venezuelan dmg law, the Ordinance of the Council of Physicians and Secret Medicines and Patents (1883), stated its objective as the control and registry of medicines, in order to develop a pharmacopoeia of dmgs with established pharmacological properties, composition, indication and dosage, for the purposes of standardization. A product registration system was developed and the DRA was created some decades later. 

An official product assessment and registration system for pharmaceuticals exists in each of the 10 countries. Their functions are determined by legal provisions. Systems for registration of pharmaceutical products came into operation at quite different times in the 10 countries — as early as 1942 in Tunisia and as late as 1993 in Uganda. Some of the systems have evolved in response to dmg-related crises such as the thalidomide disaster, public pressure to expand the scope of dmg assessment and the pressure from industry and consumers to expedite the registration process. 

Fast-track registration systems now exist in Australia, Cypms, Estonia, Malaysia, the Netherlands, Tunisia and Zimbabwe (see Table 8.1), although probably not all of them were established as a result of political pressure. Different fast-track systems serve different purposes. In Australia, Cypms and Malaysia, fast-track registration is intended to facilitate the assessment and registration of new dmgs for treating serious, life-... 

The purpose of registration is to assess drugs for efficacy, safety and quality and to ensure that they are of an acceptable standard for use. When similar products are processed, the rates of registration approval and rejection reflect the ability of the registration system to prevent questionable products from gaining market access (3). 

In Estonia, however, as many as 17% of the applications are withdrawn Ifom the process. Rejection rates are highest in Venezuela and Malaysia (30% and 29%, respectively). In both countries, withdrawal rates are small (0% and 3%, respectively). In Australia in particular, the number of applications withdrawn before a final decision has increased significantly in the past four years. This increase in withdrawals is probably a result of the way in which the registration system now operates, with a proposed decision to reject being made by the Delegate, prior to obtaining formal advice from the Australian Dmg Evaluation Committee. 

Monitoring studies in the actual fields are not required because Japan has no provisional registration system. Most companies, however, have been voluntarily monitoring their chemicals in river water after distribution. 

Provisions and criteria should be established for the production and management of intermediates containing POPs. The Name List for Hazardous Chemicals Banned and Restricted Strictly should be adjusted to add Mirex and other emerging POPs related toxic chemicals into the controlled substances subject to the Environmental Management Registration System for Import/Export of Toxic Chemicals. 

A separate application has to be made to cover the goods in each class. Across the European Union, each mark must be separately registered for the appropriate class or classes of goods in each individual country, either according to the applicable procedure or through the recent Commrmity trade mark registration system. 

While different nomenclature conventions and historical discontinuities are at best confusing to the human searcher, they lead to serious problems in terms of multiple registration of entities in registration systems as well as information compartmentalization a mapping of polybutadiene onto poly(but-l-ene-l,4-diyl) is not straightforward for a human and even less so for a machine (polybutadiene does not indicate the position of the double bond in the polymer backbone) and therefore any data associated with either registration may or may not be equivalent. 

Elvin, John. The Thinning Ranks of America s Gun Dealers. Insight on the News, vol. 13, April 7, 1997, p. 23. Reports that there are 100,000 fewer gun dealers, and argues that ever more strict gun laws are the reason. Elvin describes a number of proposals that would go beyond the Brady Bill in increasing paperwork and expense for gun dealers and that could lead to a national registration system that would facilitate gun confiscation. 

A typical photoelectron image (PEI) of a UF-F2 needle tip is presented in Fig. 5. The laser intensity was varied in the range 4 x 103—8 x 103W/cm2, determined by the dynamic range of the registration system used. Since the photoemitted electrons possess some nonzero transverse motion kinetic energy E m, each photoelectron must be imaged as a spot with a diameter defined by the expression... 

A mass spectrometer consists of the following major parts (a) inlet system (b) ion source (c) analytical system, and (d) amplifier-registration system. 

A Case Study Develop a Chemical Registration System (CRS)... 

Chemical registration is a task that all pharmaceutical and chemical companies have to fulfill in their chemical informatics systems. A robust chemical registration system makes sure that the intellectual properties a research organization produces are preserved and can later be queried and retrieved along with other data. 

As such, any chemical registration system should be structure centric. It must assist the user to get the structure right—make sure the structure is compliant with all business conventions and salts are added correctly and charge balanced. The whole process of structure handling must be optimized to be as efficient, fast, and accurate as possible. 

Some systems support various structure formats and need to convert the structures from one format to another from time to time. Although this may not be required by a registration system, it could be very useful in other types of chemical information systems such as molecular modeling. The good news is that some tools from the major chemical informatics software vendors can do the conversions. In this situation, commercial solutions make sense because you do not want to reinvent the wheel. 

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