Safety imperative

Leape, L., Berwick, D., Clancy, C., Conway, J., Gluck, R, Guest, J., Lawrence, D., Morath, J., O Leary, D., O Neill, R, Pinkiewicz, D. and Isaac, T. 2009. Transforming healthcare A safety imperative. Quality and Safety in Health Care, 18, 424-28. 

These systems evolved to those encompassing quality management principles and focused mainly on plant, equipment, and management systems. The tendency was for management to focus on specifics, or adopt a tunnel vision type of approach to safety. Safety imperatives were assessed individualistically, rather than by viewing the overall interaction of people, processes and systems as a whole. 

The article compares recent sociological studies of environmental inspectors, and the current state of regulations related to industrial activities in France. It gives also some examples from other countries, which are similar to the French situation. It addresses the question of whether safety imperatives can be negotiated. 

Lockout or blocking feature. Such a feature is necessary for complete safety of the machine after every trip for any of the reasons discussed above. It is imperative... 

More recently, the bottleneck of drug research has shifted from hit-and-lead discovery to lead optimization, and more specifically to PK lead optimization. Some major reasons are (i) the imperative to reduce as much as feasible the extremely costly rate of attrition prevailing in preclinical and clinical phases, and (ii) more stringent concerns for safety. The testing of ADME properties is now done much earlier, i.e. before a decision is taken to evaluate a compound in the clinic. 

In the end, because of the importance of the data, it is imperative that the entire adverse event form data are cleaned. Reconciling the adverse event data with other clinical data in the clinical data management system can be very difficult if the data management system does not provide variable keys for linking such data. Adverse event data fall into the safety area of statistical analyses and are considered an event from a CDISC perspective. 

It is further stated that any individuals who have an apparent illness or open lesions that could in any way affect the safety and quality of drugs shall be excluded from direct contact with the pharmaceutical products being prepared. It may be necessary to assign these individuals temporarily to other duties until they are in satisfactory health. It is imperative that the employees be instructed to report any of the foregoing conditions to their supervisors. The supervisory personnel have additional responsibility to ensure that this requirement is met. 

US tubes are thus protecting their contents from the normal effects of heating and melting this would not be the case when Nal is located outside the tubes, either adsorbed or bound in between bundled tubes (Kissell et al., 2006). These results demonstrated the robustness of the encapsulation by US tubes, and that the interior contents are not in rapid exchange with the exterior. Importantly, this indicates that filled US tubes will not release their contents under normal, physiological conditions, imperative for safety reasons in biomedical applications of metal-filled US tubes. 

The procedure described here for the preparation of peroxy-trifluoroacetic acid in methylene chloride has been carried out by the submitters several hundred times without incident and is believed to be the best available. However, it has been pointed out that suspensions of 90% hydrogen peroxide in methylene chloride can be detonated by impact under certain conditions. Accordingly, the use of the recommended safety screen is imperative, and the preparation should not be scaled up without special precautions. The homogeneous solution of peroxytrifluroacetic acid, once obtained, is undoubtedly much safer to handle than the suspension of hydrogen peroxide in methylene chloride. The latter suspension is not transferred, however, and exists for only a brief time period during the preparation. 

As in any process that uses cheniicals and electronic and mechanical equipment, a concerted safety effort is required in plasma etching. Proper shielding of reactors and power supplies to minimize operator exposure to rf radiation is imperative. An exposure level below 1 mW/cm has been suggested as a safe operating point (150). 

As it is imperative that the plant-derived hiopharmaceutical product must be obtained repeatedly and on a consistent basis, a master cell culture bank, seed bank for transgenic plants, or virus seed stock for transient expression systems must be constantly maintained. Storage conditions must therefore he optimized to prevent contamination and ensure viability. Both transgene stability (e.g., reversion to wild type or sequence drift of plant virus expression vectors) and protein expression levels must be monitored in a representative plant of a given bank or stock to minimize any possible variation in expression levels that may affect safety and consistency of the hnal product. A program that monitors lot-to-lot consistency of the hiochemical and biological properties by comparing the product with appropriate in-house reference standards could he implemented as a fundamental component of product development. 

Relief valves are preferred for use on clean materials, because automatic closure prevents excessive discharge once excessive pressure is relieved. Rupture disks are less susceptible to plugging or other malfunctions but may allow complete emptying of the vessel, thus creating a safety or environmental hazard. Where fluctuating pressures or very corrosive conditions exist, or where polymerizable materials could prevent proper operation of a relief valve, some designers install two safety devices in series, ie, either two rupture disks or an upstream rupture disk followed by a relief valve. With either arrangement, it is imperative that the space between the two relief devices be monitored so that perforation or failure of the relief device closest to the vessel may be detected (86). 

In dmg discovery, preliminary PK studies are usually conducted in rodents to evaluate the extent of dmg exposure in vivo. This is commonly followed by PK studies in larger animals such as dog or monkey to better characterize the PK profile of the compound and to support safety studies. Pharmacokinetic scaling (also called allometry) is a discipline that is used to predict human PK profiles using preclinical data and is widely used in predicting the dmg human half-life, dose, and extent of absorption. Accurate prediction of a human PK profile is imperative to minimize dmg failure in development due to poor PK attributes. A detailed description of methods in predicting human PK is beyond the scope of this chapter but can be found in many excellent reviews (Obach et al., 1997 Miners et al., 2004 Poggesi, 2004 Raunio et al., 2004 Thomas et al., 2006 Hurst et al., 2007). A more in-depth discussion of various PK concepts and their applications can be found in various references (Gibaldi and Perrier, 1982 Rowland and Tozer, 1995 Hurst et al., 2007). 

An important issue that has been recognized recently concerns the potential adverse effect of absorption enhancers on the rectal mucosa, as shown in rats after a single application [61,62], Safety evaluation of the applicability of absorption enhancers is imperative. In clinical application, medium-chain fatty acids such as sodium caprate are used only for suppositories containing antibiotics [36],... 

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