User safety assessment process

Toxicologists must rely on results obtained from an alternative method if it is to serve as a replacement for an in vivo toxicity test. Two measures of alternative method performance must be known in order to define reliability from a test user s point of view. First, a toxicologist must know it is possible to consistently reproduce the data obtained from the alternative method over long periods of time. A test that does not provide the same results on the same test substance repeatedly would not be useful in the safety assessment process. Second, it must be possible to consistently predict in vivo toxicity endpoints at a known level of accuracy and precision. These measures of reliability are objective endpoints that can be measured experimentally. The part of the validation process that provides the data needed to confirm the reliability of an alternative method as proposed by its developers is the validation study. 

Additionally, the test materials used in the validation process should be as closely related as possible to the characteristics of the unknowns to be tested. It is clear from the literature, for instance, that many cytotoxicity assays give good correlations with the in vivo ocular irritancy data for surfactants, but the correlations fail when compounds from other chemical classes are tested. Since any particular assay may be used differently by individual safety assessment programs, users must evaluate potential methods under conditions likely to be encountered in their own situations. 

Prior to development of the application software, the user provides a process risk and hazard assessment which is used to identify the software safety requirements in terms of the safety instrumented functions and their SIL. Once the decision to implement the safety instrumented functions in software is made, any conflicts, discrepancies and omissions in the safety requirements specification which come to the attention of the software designers should be addressed. One example might be the effect of the order of execution of the safety instrumented functions within the software. Another example would be the response of the application software as it relates to energy outages. 

From the preceding, it is clear that SIS and reliability go hand-in-hand. A functional safety assessor (FSA) assesses the safety assessment/analysis report (SAR) after SIS is developed to check the system reliability and SIL. In order to achieve a tolerable risk level, the end-user, who needs to install SISs in the plant, initiates SIS projects. Detailed process outline for the same has heen elaborated as follows ... 

Cenfral to regisfration is fhe Chemical Safety Assessment (CSA), in which the registrant identifies and describes the conditions under which the manufacturing and use of a subsfance are considered to be safe. A CSA must be performed by registianfs for substances manufactured and imported in quantities at or above 10 tonnes per year and by downstream users if their uses are not addressed by their supplier. The CSA entails three major steps, hazard assessment, exposure assessment, and risk characterization, which are documented in the Chemical Safety Report (CSR). Figure 3.4 summarizes the process [95]. 

Assessment. An analysis of the hazards present in this laboratory show the most significant hazard to be the release of vapor CSM from engineering controls and into the workplace. The significance of this hazard mandates further efforts in system safety in the form of a Preliminary Hazard List (PHL) and a Preliminary Hazard Analysis (PHA). The user must in this instance take an active role in the design review process. 

Gather the requirements for the systems including functional (e.g. operational checks) requirements, nonfunctional (e.g., coding standards) requirements, users, company-wide regulatory compliance (e.g., Part 11 technical control), safety, process, and other applicable requirements Characterize information, assess its value to the organization, and incorporate information quality as part of the project plan Conduct a system (hardware, software, and process) risk analysis. New requirements may be found as the result of the risk analysis. Any new requirements must be documented in the requirements specification deliverable... 

Safety Authority will take responsibility in this area. How this will work out has to be seen in the near future. Nevertheless, the straightforwardness of the approach does not hide the relatively complex methods that are used or have to be used. The models applied in the determination of the PEC are far from simple they contain the current state-of-the-art of the scientific description of chemical, physical and microbiological processes in the environment. The methods will be kept update and communications with the research institutes and the users of the models will continue. The main aim is to keep having available a system of methods to carry out risk assessments for plant protection products. 

If a SNUR cross-references a subsection of 40 C.F.R. 721.72 then it will be a significant new use to manufacture, import, or process the SNUR substance unless the manufacturers, importers, processors, and users have a hazard communication program to warn about the risks that the substance poses. This group of significant new uses builds on a system of hazard communication established by the Occupational Health and Safety Administration (OSHA). OSHA has promulgated Hazard Communication Standards that require employers to assess hazards posed by the chemicals they make or import and provide hazard information on labels and in MSDSs. Employers and processors of chemicals that pose hazards must make the labels and MSDSs available in the work place and train their employees in safe handling procedures. 

A complete lEC 61508 assessment includes a FMEDA, a study of Prior Use and adds an assessment of all fault avoidance and fault control measures during hardware and software development as well as detail study of the testing, modification, user documentation and manufacturing processes. The objective of all this effort is to provide a high level of assurance that an instrument has sufficient quality and integrity for a safety instrumented system application. This is clearly more important for products containing software as many end users have the strong opinion that software is "bad... 

As indicated in Chapter 1, pharmacovigilance is essentially a risk management process for medicines. The process starts with identification of a possible hazard, this is then evaluated and investigated and, if necessary, some action is then taken with a view to minimising risk. Implementation requires tools for communicating with users and the final step should be that an assessment of effectiveness is made. The process is iterative because new evidence may emerge or the measures taken may mm out to be insufficient. Rarely can a dmg safety issue be considered completely and permanently resolved. 

Cross-national studies require effective coordination within and between countries. We believe that the first step is a European netwoik of HSPSC users and, to a certain degree, the process of writing this chapter has contributed to such a network by identifying researchers and practitioners with an interest in safety climate assessment. Such a network would also help to connect groups within countries that have developed parallel versions (e.g. Spain and Italy). 

---