Intrinsic Process Safety

Considerations of intrinsic process safety often dictate the choice of /3 we often desire to minimize the hold-up of hazardous materials in the reactor. 

From the process safety point of view, the evaluation of the intrinsic safe character of HEX compared to batch or semibatch reactors has been investigated [33, 37]. Two points clearly show the interest in the HEX reactors ... 

Examples of strategies for safe designs are prevent large volumes, intensify contact, reduce the need for aids (like solvents), use little intermediate storage. One can immediately see the similarities between intrinsically safe design and process intensification. This also means that applying process intensification techniques is beneficial for process safety. 

In the same time, we have to supplement the above shown parameters by parameters that characterize safety. The system must not cause by its action any possible dangerous conditions in its surroundings. The safety properties of the instrumentation and control system of industry processes (mechanical, electrical, etc.) depend on its own (intrinsic) system safety and on external (extrinsic) aspects on the protection included into the system. 

Process safety is a prerequisite to worker safety and begins when the plant or manufacturing line is on the drawing board. From comprehensive design and hazard analysis through preventive maintenance and employee training, we assure our operations not only meet the Occupational Safety Health Administration s (OSHA) Process Safety Management standard, but also are intrinsically safe. 

Probes may be fixed or retractable, and access for removal or replacement of elements is an important consideration. Intrinsic electrical safety requirements must be followed. Probe materials of construction, including sealing compounds used for insulation, must be compatible with the concentrations, temperature, and pressure of species in the chemicail process. 

Safety cannot be treated as a separate discipline as it is already integrated from the early chemistry and process development (Chapter 11). Safety deals with a wide variety of technological aspects with respect to the environment (water, air, soU, and living species). However, economic aspects are usually taken into consideration also. Modem process development intrinsically includes safety and environmental aspects in all stages of the development. 

This method consists of characterizing the design features, especially in the safety system architecture, that are likely to pose problems in the operation, notably during the degraded situations in which the plant safety strongly depends on human reliability. The characterization of the intrinsic physical behaviour of the plant processes (safety functions), of the operating constraints of the safety systems and finally of the interrelations between these entities (most complexity theories consider these interrelations to be the main contributors to the complexity of a system), lead to the definition of an operational complexity index and to the identification of the sources of the operational constraints bearing on the operation crews. 

The first and most important point in the development of a medical device is the proper overall design. It is believed that the intrinsic quality, safety, and effectiveness of a device are established during the design phase. FDA statistics show that 30% of all medical device recalls are a result of inadequate design control [1], The design process is the foundation and skeleton that is the basis of a medical device from its inception to the end of its lifetime. The design process is a living and an iterative process it evolves and improves with time. 

Raghaven, K. V. (1992). Temperature Runaway in Fixed Bed Reactors Online and Offline Checks for Intrinsic Safety. Journal of Loss Prevention in the Process Industries 5, 3,153-59. 

In the elaboration of a safe process it is necessary to look for those synthetic routes which do not incorporate hazardous raw materials, solvents, and additives. This is unfortunately rarely achievable. Therefore, the best way to insure higher intrinsic safety is ... 

Processes can be divided into those that are intrinsically safe, and those for which the safety has to be engineered in. An intrinsically safe process is one in which safe operation is inherent in the nature of the process a process which causes no danger, or negligible danger, under all foreseeable circumstances (all possible deviations from the design operating conditions). The term inherently safe is often preferred to intrinsically safe, to avoid confusion with the narrower use of the term intrinsically safe as applied to electrical equipment (see Section 9.3.4). 

In the last 30 years, the use of in vitro tools for toxicological studies and evaluation has become relevant and the number of scientific works and techniques has increased day by day. One of the most important advantages of in vitro systems is their ability to serve as model for the central events in the in vivo toxicological process, and a depth evaluation of the intrinsic cellular toxicity can provide useful information for toxicological safety evaluation. 

Looking at the downstream processing of recombinant pharmaceutical proteins from different sources as a whole, there are more common steps than operations addressing expression system-specific problems or requirements. One of the most important common features is that a given end product must meet the same standards and specifications in terms of safety, quality, potency and efficacy, regardless of the production host. Furthermore, the physicochemical properties of such end products should be identical, so that the intrinsic features used for purification (affinity, hy-drophobicity etc.) are the same. Well-established procedures and protocols should therefore be utilized, and should be adapted to the special requirements of the source material only when absolutely necessary. This is particularly true in the case of pharmaceuticals, since the tendency in this field is to stick to established methods... 

The safety of a chemical process can be achieved through internal (inherent) and external means. The inherent safety (Kletz, 1984) is related to the intrinsic properties of the process e.g. the use of safer chemicals and operations. The essence of the inherent safety is to avoid and remove hazards rather than to control them by added-on protective systems, which is the principle of external safety. The largest payoffs are achieved by verifying that inherent safety has been considered early and often in the process and engineering design (Lutz, 1997). 

The intrinsic safety is however affected by both the process equipment and the properties of the chemical substances present in the process. Therefore also the index should reflect this fact. We have included parameters into the list (Table 5) to represent the process aspects of the inherent safety. These parameters are the type of equipment involved and the safety of process structure which describe the process configuration from a system point of view. Also a third parameter to describe the interaction (reactivity) of the chemicals present in the process has been included, since this is an obvious source of risk. 

Under the Medical Device Amendments of 1976, the FDA is responsible for premarket evaluation of all laboratory testing devices (in vitro diagnostics) intended to be commercially marketed in the United States. There are two major pathways for introducing a medical device into the marketplace the premarket notification [510(k) clearance] and the premarket approval (PMA). The purpose of the 510(k) is to establish that a device is substantially equivalent (SE) to a legally marketed (predicate) device. The purpose of the PMA evaluation process is to establish the intrinsic safety and effectiveness of a new device. Unless specifically exempt, a sponsor must have an approved PMA or cleared premarket notification [510(k)] by the FDA before a device may be legally marketed for IVD use (Fig. 1). 

The PMA evaluation process, unlike the 510(k) process, is intended to establish intrinsic safety and effectiveness of a device, rather than comparability with a legally marketed predicate device. For PMA, the performance characteristics of a device must be established as a stand-alone application. In order for an IVD PMA to be approved, the sponsor must demonstrate that the device has clinical utility and that it is safe and effective for its intended use. Generally, the agency bases its determination of clinical utility on whether the device is recognized widely by health practioners or supported by peer-reviewed scientific literature as having reasonable clinical utility or usefulness. The PMA is the more stringent of... 

Short residence time, minimal downstream separation, energy efficient, zero waste, low inventory, improved intrinsic safety, improved process flexibility, reduced area required, rapid product grade change, rapid response to market needs, improved control. 

A large hurdle to expanded use of hydrogen is public perception. Widespread hydrogen use represents an extraordinary educational challenge, as well as the absolute requirement that safety be intrinsic to all processes and systems. The development of reliable, low-cost hydrogen sensors is an important aspect of the Program, as is the development of codes and standards for the safe use of hydrogen. 

There are two aspects of this program that will effect the research and development investment decision. First, the costs of premanufacture notification (including testing costs) will increase the investment in R D necessary to develop and market new chemicals. The health and safety properties of a chemical must now be considered an intrinsic part of the new chemical development process, right alongside consideration of the substances commercial properties. Both are equal parts of the "total product". Tb the extent that this results in increased testing for health and environmental effects, the amount of investment required to achieve a given level of output from R D will also rise. 

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