Basis of safety

The procedure to determine both the basis of safety for the reactor (see Annex 1) and the worst case scenario for that basis of safety is iterative. The same screening tests which help determine the worst case for pressure relief sizing may lead to the conclusion that pressure relief is not the best basis of safety. The results of screening tests may also indicate that it is worthwhile to seek a more inherently safe solution by designing out the possibility of certain maloperations or system failures (for example, if the screening indicates that a very large relief system would be required). 

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FDA contracts with the National Academy of Sciences/National Research Council to evaluate the effectiveness of 4000 drugs approved on the basis of safety alone between 1938 and 1962. 

The design assessments and basis of safety must be recorded and available for consultation, and the process must be operated as required. The operating phase involves two sets of process documentation—the detailed technical documentation, and safe operating instructions (HSE 2000) for every operational phase, including startup, shutdown, maintenance and emergency operations. 

The products already on the market on 1 September 1971, the date for implementation of the Medicines Act, were given the Product Licences of Right (PLR) that were subject to a review process at a later date. This proposal for review of PLRs is reminiscent of the FDA contract with the National Academy of Sciences/National Research Council (NAS/NRC) in 1966, to evaluate the effectiveness of some 4000 different drug formulations approved on the basis of safety alone between 1938 and 1962 - the year of the Kefauver-Harris Amendment. 

First, consider efficiency. Many people incorrectly assume that, in the absence of codes, consumers would be helpless against greedy firms. But without codes, builders would compete on the basis of safety and features, and consumers could hire inspectors to evaluate structural quality (which already happens during mortgage inspections). Builders could also hire firms to certify that their structures comply with best practice (the construction equivalent of Underwriters Laboratories). Uncertified builders would be at a quality disadvantage. 

Is there scope for obtaining a better design solution by changing the basis of safety for the reactor (see Annex 1)... 

It will then be necessary to check whether or not the credible maloperations can lead to exothermic runaway. Information on this is given in reference 1. Where it is shown that runaway can occur, and it is decided that emergency pressure relief may be used as part of the basis of safety, then it will be necessary to carry out further work to identify the worst case for relief system sizing. ... 

It may be possible to minimise the time spent on relief system assessment and design if the basis of safety for a multi-purpose reactor can be changed to prevention rather than emergency pressure relief. For example, if it can be arranged for all the reactions to operate in semi-batch mode with no significant reactant accumulation, then the use of a trip system of sufficient integrity may provide a suitable basis of safety. (This may not always be possible.)... 

The basis of safety for a chemical reaction process is the combination of measures which are relied upon to ensure safety. Defining the basis of safety for a reactor is essential as it highlights those aspects of the design and operation (hardware, protective systems and procedures) which are safety-critical. There are many factors to be considered and further advice is given in references 1 and 2. 

The basis of safety can only be selected once all the significant hazards have been identified and evaluated[3,41 (see Chapter 3). There are a number of options for the safe operation of chemical reactions and these are outlined below., ... 

Whatever the basis of safety selected it is important that ... 

The use of food additive petitions and GRAS procedures to evaluate the safety of a proposed new excipient would apply to the oral route of administration for the excipient and would not generally apply to other routes of administration. Some routes of administration (e.g., inhalation) result in unique toxicological requirements, and data would have to be developed for the specific route of administration. While toxicological data from systemic studies are important for excipients used for nonoral applications, separate data would be needed for the specific route of administration. Nevertheless, the amount of safety data, specifications, and intake information required for a food additive review is extensive, and therefore could provide a firm basis of safety for a new excipient. 

Two examples of alternative approaches to cancer risk assessment would be estimations based on threshold-response (EPA, 2005a) and benchmark dose modeling (EPA, 1995, 2000). As a practical matter, if the proposed basis of safety relies on a threshold or mode-of-action characterization to dismiss or mitigate animal tumor data, PDA would reconunend that the safety narrative clearly discuss the scientific rationale and present all relevant data for consideration. In the absence of adequate evidence to the contrary, PDA presumes that certain assumptions are appropriately protective of safety, namely that (i) the induction of tumors in animals is relevant to human... 

The FDA has classified the following topically applied products as OTC drugs on the basis of safety and efficacy review of the drug(s) constituents ... 

To assess the possibility of an explosion in a facility and to select the most appropriate basis of safety, explosion characteristics of the dust(s) that are being handled/processed in the facility should be determined. 

BASIS OF SAFETY FROM DUST CLOUD EXPLOSIONS... 

Finally, if the basis of safety from potential dust cloud explosions is the elimination of ignition sources, the answers to the following questions should be... 

The following guidelines should be applied when considering explosion containment as a basis of safety ... 

Optimisation finding the best biological candidate(s) on the basis of safety and effectiveness. 

The key factor in flare stack design is personnel escape time from the stack base at maximum discharge. Therefore, the selection of height and flare stack location should be made on the basis of safety for operating personnel as well as equipment. 

The incident probability itself is mainly determined by the implemented protective and preventive acting measures. These represent the basis of safety of the process. Therefore, using an analogous formulation, risk is determined by the combination of the basis of safety and the weighted hazard potential as shown in Figure 1-3. 

The basis of safety, as outlined above, results from partly organizational, partly technical measiues dedicated to preventing identified hazard potentials from taking effect. The systematic hazard identification procedures are discussed in Chapter 6 in more detail. Each element of this basis of safety is of a certain quality which is given by its type of action, the degree of efficiency and its availability. A first simplistic classification for some elements is given in Table 1-1 ... 

Table 1-1 Simplistic classification for some basis of safety elements...

Fig. 1-4. Interaction of process status and basis of safety concepts...

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