Stability data information sources

Responses to the CSB industry survey50 indicate that most companies consult a variety of information sources as a first step in compiling data on reactive hazards. However, respondents prefer literature sources and expert opinion over computerized tools such as CHETAH, The Chemical Reactivity Worksheet, or Bretherick s Database of Reactive Chemical Hazards. Such programs can be used to predict the thermal stability of compounds, reaction mixtures, or potential chemical incompatibilities. In some cases, they provide an efficient means of identifying reactive hazards without having to conduct chemical testing. Survey responses showed that five of nine companies consider computer-based tools not valuable. Only two of the surveyed companies use The Chemical Reactivity Worksheet.51... 

The book is not intended to be a formulary but many preparations formulas are included in order to exemplify principles described in the texts. Some readers may wish to use the formulas in practice, however for that purpose more information is necessary, such as the detailed method of preparation, stability data, appropriate containers, background information and justification, etcetera. The original source formulary, e.g. FNA (see Sect. 39.4.5) or NRF (see Sect. 39.4.2) should be consulted to meet that demand. 

Stability studies on medicines are often published in pharmaceutical journals. Other sources for stability data could be useful as well, such as the Pharmaceutical Codex [29], Kommentar zur Europaisches Arzneibuch [72] (see Sect. 39.4.8), Martindale [85] (see Sect. 39.2.4), Ophthalmika [86], Coimors [15] and Trissel s Stability of Compounded Formulations [70] (see Sect. 39.4.14). Additional information can be found in Analytical and International Pharmaceutical Abstracts. These can be retrieved by the search engine OvidSP [87]. The German collection DAC-NRF [88] (see Sect. 39.4.2) also provides much information on stability. 

Information on hazards is available from various sources. Chemical manufacturers produce hazard data sheets for their products and some of the major companies produce comprehensive databases. Each data sheet contains information on the physical description of the compound, stability, hazards, first aid measures, storage, transport and disposal requirements. 

CMC information [ 312.23(a)(7)] and informational amendments related specifically to CMC [ 312.31] including product characterization, device information, formulation, labeling, lot release, manufacturing information, shipment of product, source information, specifications, lot release data, stability, sterility, and environmental assessment or claim for exclusion... 

As for the non-uniqueness of the solution, there is no method that can bypass this inherent problem. In inverse problems, one of the common practices to overcome the stability and non-uniqueness criteria is to make assumptions about the nature of the unknown function so that the finite amount of data in observations is sufficient to determine that function. This can be achieved by converting the ill-posed problem to a properly posed one by stabilization or regularization methods. In the case of groundwater pollution source identification, most of the time we have additional information such as potential release sites and chemical fingerprints of the plume that can help us in the task at hand. 

However, the most common sources of different results are both based on the approach used for the calculation of the activity coefficient (chapter 1.1.2.6) and the thermodynamic data sets themselves (chapter 2.1.4), which provide the respective program with the fundamental geochemical information of each single species. The thermodynamic databases available partly use severely differing data with different solubility products, different species, minerals and reaction equations. Nordstrom et al (1979, 1990), Nordstrom Munoz (1994), Nordstrom (1996, 2004) discuss this inconsistency of thermodynamic datasets in detail. For some species, for which stability constants have been published, not even the existence of the respective species has been proved doubtless, as can been shown in the following example. 

Sillen and Martell s Stability constants of metal-ion complexes [1]. This compilation is sufficiently comprehensive to show data for a variety of ligands and generally includes either the proposed ligand or a very similar compound. There is also sufficient information to investigate selectivity for a diverse collection of metals, providing clues to selectivity. Other compendia of data are available, such as the CRC handbook and Yatsimirskii and Vasiliev s, Instability constants of complex compounds [2]. An especially useful source of data on complex compounds is Gmelin and Meyer [3]. 

The properties of He that make it potentially useful in exploration, particularly for blind mineralisation (i.e., stability, inertness and radiogenic origin) are, it appears, the very properties that nullify its potential in exploration practice. The distribution and concentration of He cannot be interpreted unambiguously in terms of occurrence and location of mineralisation, and such data do not add usefully to information available from other sources. 

Data on private companies are difficult to assemble, and financial checking on the CROs is not straightforward. When published at all, these companies accounts are often in abbreviated format, and can be out of date. Organizations such as Dun Bradstreet may be able to provide useful information. However, it is likely that the best source of reassurance of financial stability of a CRO is via bankers references, obtained through the sponsor s own finance department. 

Thus, it is no longer acceptable for the formulator to delay this compatibility testing until later in the development programme. The key message is for the formulator to test early and ensure equivalence of the whole product throughout the development cycle. Leachables are specifically mentioned data on their identity and concentration in the product and placebo are required through the shelf life and also under accelerated stability test conditions. Information should be submitted on source, chemical composition and physical dimensions of the container closure system, together with control and routine extraction tests. Acceptance criteria are also required. 

A much more ambitious database that builds on the IUBMB classification is BRENDA, maintained by the Institute of Biochemistry at the University of Cologne. In addition to the data provided by the ENZYME database, the BRENDA curators have extracted a large body of information from the enzyme literature and incorporated it into the database. The database format strives to be readable by both humans and machines. The categories of data stored in BRENDA comprise the EC-number, systematic and recommended names, synonyms, CAS-registry numbers, the reaction catalyzed, a list of known substrates and products, the natural substrates, specific activities, KM values, pH and temperature optima, cofactor and ion requirements, inhibitors, sources, localization, purification schemes, molecular weight, subunit structure, posttranslational modifications, enzyme stability, database links, and last but not least an extensive bibliography. Currently, BRENDA holds entries for approximately 3500 different enzymes. 

V) c u S u C BIND BindingDB BRENDA DIP IntAct project InterDom MINT Biomolecular interaction network database Collection on experimental data on the noncovalent association of molecules in solution Enzyme Information System Sequence, structure, specificity, stability, reaction parameters, isolation data, and molecular functions ontology Database of interacting proteins Public repository for annotated protein-protein interaction data Putative interacting protein domain database derived from multiple sources A molecular interaction database http //www. bind.ca http //www. bindingdb.oig http //www. brenda. uni-koeln.de http //dip.doe-mbi.ucla.edu http //www.ebi.ac.uk/intact http //interdom.lit.org.sg http //mint.bio.uniroma2.it/ mint/... 

More extensive COM research was undertaken in the 1940s due to the wartime constraints on oil supply, and the data collected during this period still serve as a basic source of information. A resumption of readily available oil supplies at prices competitive with coal inhibited the widespread commercialization of the technology at that time. A subsequent constraint on oil supplies, initiated by the 1973 oil embargo, prompted the current era of increased COM research and development. A significant early development was the discovery of low-cost, effective chani-cal additives for stabilizing the mixture and enhancing other physical and chemical properties. An additional application of COM was as a fuel for blast furnaces. 

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