Safety Relevant Data

The data required for the safety assessment belong to two categories  

kinetic data allowing the assessment of the dynamic stability issues, and 

thermochemical data, allowing the assessment of the thermal risks in general, according to the procedures depicted in Sections 3.3 and 3.3.4. 

Worked Example 6.2 Substitution Reaction Example in a Batch Reactor 

Since the process may be carried out under the same temperature conditions as those in industry, a complete set of data may be evaluated from the experiment. The overall heat of reaction (300 kj kg-1) is obtained through integration of the heat release rate over time. The maximum heat release rate of 18 Wkg 1 is reached after 3.6 hours at a temperature of 53 °C. The specific heat capacity (1.7 kj kg 1 l ) is calculated from the steps in heat released rate at the beginning and end of the temperature program. As an example, we consider a cooling failure at 3 hours. The reactor temperature is 47 °C and the thermal conversion is 0.35. Thus, the temperature after cooling failure can be calculated as 

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Transport incidents while the external verification report identifies that Bayer records safety-relevant data covering the whole transportation process , this data is not discussed in the CER and a no score has been given. 

In addition, information is available from several reputable sources, including the World Offshore Data bank (WOAD) of Det Norske Veritas (DNV), which contains data and analyses on more than 6,000 accidents from 1970, the SINTEF Offshore Blowout Data Base on major blowouts and spills since 1955, and periodic studies done for Oil and Gas UK on accidents dating back to 1990. Such a comparative analysis would be useful to the new DOI regime in which BOEM and BSEE are expected to develop regulatory reforms and to their counterparts in Norway and the United Kingdom as well. Performance indicators and the reporting and evaluation of safety-relevant data are discussed further by Blakstad in Ghapter 9. 

Figure 12.7 illustrates a notional representation of typical safety-relevant data and information flows as would be reviewed in the V-shape safety case process illustrated in Figure 12.4. Note that this is just showing some of the safety information exchanges that would occur within an SMS and is not how an SMS is audited. Of course, the SMS also includes all the management systems that manage these information flows.

FIGURE 12.7 Notional representation of safety-relevant data and information flows. 

Investigators have access to an enormous amount of safety-relevant data that are captured within the airline, along with a large amount of information that is circulated within the broader industry. Within their own airline, this includes each aircraft s electronic technical log, which records in detail the technical history of the aircraft. Investigators can request tapes of radio communication between pilots and air traffic... 

In addition to these selection criteria, the limitations of the author s contacts and the willingness of companies to participate, narrowed the search for a suitable case down to a small Dutch company (< 30 people). This company produces in batches, falls under the Dutch Seveso-II directive (BRZO, 1999) and authorized access to the relevant data. The selected company had experienced some serious accidents recently, in spite of using many technical safety systems. Thus the management was aware of the necessity to enhance both safety and the reliability of the operational process. 

The next step, given that no relevant data can be found from any literature sources or from any internal files (and that it has been determined what data are needed or most likely to allow selection of desirable candidate compounds), is to perform appropriate predictive tests. The bulk of this section addresses the specifics of performing such evaluations using in vitro models. Before considering how to design, develop the components of, and conduct such a testing program, we must first consider how the practice of safety assessment came to its current state of acceptance and utilization of such tests. 

Before a new substance is first marketed, the placer on the market , i.e. manufacturer and importer, has to notify it and to present proof that not risk arises from the use of this substance. In Germany the Notification Unit of the Federal Institute for Occupational Health and safety (FIOSH) receives the relevant data. 

The Value of Safety Pharmacology Data the Value and Relevance of Complete, Standardized Data Matrices for In Silica Prediction of Adverse Events... 

Any findings indicative of toxicity to reproduction should be explained thoroughly and supplemented with tables of relevant data if there is any concern for the safety of the product. If any findings are considered not to be indicative of a risk to patients, then a full justification of the scientific reasoning behind that judgement should be provided. 

Bradbury Baeyens (2002a, b) provided sorption data bases for Opalinus Clay and MX-80 bentonite, respectively, based on numerous experiments with varying aqueous solution compositions. Since sorption can be influenced by the complexa-tion of radionuclides with various ligands, corrections had to be made to account for the differences in speciation between the experimental solutions and the Opalinus Clay and bentonite porewaters. For this purpose, the Nagra/PSI TDB 01 /01 was used to model the speciation of all safety-relevant radionuclides in the experimental solutions and in the Opalinus Clay and bentonite porewaters. 

Selection in this chapter is strictly focused on safety related data in the field of explosion protection, neglecting all the other aspects like maintenance or financial considerations (this will be the objective of Chapter 9). Here, selection means the appropriate choice of electrical apparatus according to temperature class and MESG or MIC/MIC (CH4) grouping, taking into account the combustible raw materials and products in the relevant plant. 

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... 

Technical and other practical factors also merit consideration. Are there indeed technical difficulties in the manufacture of a bulk drug that would render marketing of the eutomer cost-prohibitive Accumulation of relevant data for each stereoisomer is a time-consuming process. Are these delays justifiable therapeutically When an IND is submitted for a race-mate, there may be limited or negligible safety and/or pharmacokinetic data on the individual enantiomers. Should this delay initiation of phase I clinical trials ... 

Section 14, Safety, describes briefly the types of formulations in which the excipient has been used and presents relevant data concerning possible hazards and adverse reactions that have been reported. Relevant animal toxicity data are also... 

Does the manufacturer monitor the adverse drug reactions, safety and efficacy of the product If yes, relevant data are to be enclosed. 

Reproductive toxicity testing has no place in this item. Relevant data must be included in Use during pregnancy and lactation. The reader is to be referred in the preclinical safety data to this paragraph for this type of data. 

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