Data evaluation substances/products

Corporate management systems in the areas of environmental protection, employee protection and consumer protection should be integrated further to avoid a shift in risks and also to save costs. All areas require reliable and systematic data about substance properties and application-related exposure. Mechanisms are also required for effective dialogue along the supply chain as well as between companies and authorities. In addition, the comparative assessment of chemical products (for example, in purchasing or in product development) can only be done intelligently if all essential risk areas are included in the evaluation. 

The stability data evaluation for drug substance or drug product intended for storage at room temperature should include evaluation of any significant change at... 

To bolster the FDA s ability to evaluate the safety of dietary supplements, a 2004 report ( Framework for Evaluating the Safety of the Dietary Supplements ) from the Institute of Medicine and the National Research Council of the (US) National Academies outlines a science-based process for assessing supplement ingredients, even when data about a substance s safety in humans is scarce. This approach to safety evaluation works within the regulatory parameters set by the Dietary Supplement Health and Education Act (DSHEA), which does not require manufacturers to provide safety data on their products. The report stated that supplement makers, the public, and others need to increase their reporting... 

The basic concepts of stability data evaluation are the same for single- vs. multifactor studies and for full- vs. reduced-design studies. Data evaluation from the formal stability studies and, as appropriate, supporting data should be used to determine the critical quality attributes likely to influence the quality and performance of the drug substance or product. Each attribute should be assessed separately and an overall assessment made of the findings for the purpose of proposing a retest period or shelf life. The retest period or shelf life proposed should not exceed that predicted for any single attribute. 

D. Data Evaluation for Retest Period or Shelf-Life Estimation for Drug Substances or Products Intended for "Room Temperature" Storage... 

APPENDIX A DECISION TREE FOR DATA EVALUATION FOR RETEST PERIOD OR SHELF LIFE ESTIMATION FOR DRUG SUBSTANCES OR PRODUCTS (EXCLUDING FROZEN PRODUCTS)... 

A final point is that (at least as far as the current proposal is concerned) REACH will probably have little immediate effect on the current situation at the work places with regards to OELs, because test requirements on suppliers in REACH are based on the annual production or importation volume of a substance and for substances between 1 and 10 tonnes they will not - for the reasons outlined in Chapter 1 - allow the development of OELs for substances which don t already have one. This might change in the long term, after all substances have been registered and the data evaluated. 

Stability data evaluation must begin when raw data is generated in the laboratory. cGMPs require that drug products and drug substances must meet their... 

The first step is to identify the substances present at the workplace. As a starting point, knowledge of the process is needed in order to formulate a list of all chemical agents used in the establishment. The list should include not only primary products but also intermediate and final products, as well as reaction products and by-products. For the chemical agents in the list, it is necessary to know their chemical properties, especially hazardous ones their OEL values, including biological limit values and, where these are not available, other technical criteria that can be used to evaluate the risk. It is also helpful to include any information on the safety and health risks of those substances provided by the supplier or other readily available sources. This information on dangerous substances and preparations, in the form of safety data sheets, is intended primarily for industrial users, to enable them to take the measures necessary to ensure the safety and health of workers. 

Initial Situation An experimental granulation technique is to be evaluated a sample of tablets of the hrst trial run is sent to the analytical laboratory for the standard batch analysis prescribed for this kind of product, including content uniformity (homogeneity of the drug substance on a tablet-to-tablet basis, see USP Section (905)" ), tablet dissolution, friability (abrassion resistance), hardness, and weight. The last two tests require little time and were therefore done first. (Note Hardness data is either given in [kg-force] or [N], with 1 kg = 9.81 Newton). 

In order to find points of equal degrees of conversion (or equal Q-values) in Figure 2.18, van Geel [115] developed the method to evaluate kinetic data from the so-called isoconversion lines. A heat generating substance that follows Equation (2-11), when stored under isothermal conditions at different temperatures has generated an equal amount of heat (Q) when the product of t exp(-Ea/RT) has the same value. Thus, for two heat generation/time curves measured at Ti and T2, the same amount of heat (Q) has been generated, and thus the conversion is equal when ... 

Article 6(1) of the Sixth Amendment requires PMN s to contain information and data necessary for evaluating the potential risks of new substances to humans and the environment. This specifically includes certain exposure information listed in Annex VII, concerning proposed uses and estimated yearly production volumes (in ranges, and broken down by use categories). Further, Article 6(1) requires submission of "a declaration concerning the unfavourable effects of the substance in terms of the various uses envisaged," which appears to require statements of the risks that may be associated with the use categories provided under Annex VII.(26)... 

Because notices for many new substances do not contain sufficient information and data for evaluating their toxicities (especially re chronic effects) and probable exposure patterns, EPA s primary focus in reviewing PMN s has been to determine whether it will request further testing. In some cases, the exercise (or threat of exercise) of the Agency s authority has proven sufficient to persuade a company either to hold up production of the substance voluntarily (while further data are developed), or to cease altogether its plans for bringing the chemical to market. 

Under 5(e), following receipt and review of a PMN EPA may order a company to develop test data "sufficient to evaluate the health and environmental effects" of the new substance. However, if the PMN submitter objects to the order (and provides sufficient grounds for that objection), the order does not take effect and EPA must obtain an injunction from a U.S. district court to impose the data requirements (and any appropriate production or use restrictions). 

At the same time, several types of data necessary to ensure proper management of occupational risks associated with a drug substance are not generally useful in evaluating potential patient risks. So the necessary tests—eye and skin irritation, sensitization and inhalation toxicity, as well as assessment of the hazards of byproducts and impurities that do not get incorporated into the final therapeutic product—are not performed in the normal course of development. 

Under the BPD, the biocidal substances are evaluated centrally by the EU Commission. The evaluation is based upon a very extensive data package submitted by the biocide substance manufacturer including a risk assessment of the use of the biocide in AF products. The outcome of the evaluation by the Commission is to decide whether the biocide is prone to be included in a positive list, also termed Annex I, or not. 

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