Information risk minimisation

The purpose of the safety specification is to explicitly consider the level of safety that has been demonstrated so far. It should identify what is and is not yet known about safety and the latter (i.e. what is not known) should be a major driver of the pharmacovigilance plan. The purpose of that plan is essentially to attempt to find out what is not yet known, largely because of the limitations of clinical trials. Risk minimisation plans are not invariably required - essentially they are needed when there are known or potential risks which cannot simply be managed through routine measures contained in the product information. 

Risks identified from risk analysis, measures to minimise and control risks and information on subject seiection... 

Part II provides detailed information on the main quality and safety issues related to the production of organic livestock foods. This includes three chapters (Chapters 7 to 9) which review the effect of livestock husbandry on nutritional and sensory quality of livestock foods including milk and dairy products (Chapter 7), poultry (Chapter 8) and pork (Chapter 9). It also includes four chapters (Chapters 10 to 13) which review the strategies used to minimise microbiological risks and antibiotic and veterinary medicine use in livestock production systems including safety of ruminants (Chapter 10), mastitis treatment in organic dairy production systems (Chapter 11), internal parasites (Chapter 12) and pigs and poultry (Chapter 13). 

The acquisition of substance data and the introduction of harmonised instra-ments for evaluation, conununication, documentation and limitation of application risks in the European market can only function at an extra-corporate level. In so doing, the following should be observed, if such solutions are in line with practice, their development catmot be left solely up to official bodies. If the costs are to be minimised, the companies have to develop standards jointly, which can however also entail the exchange of information that is relevant to a potential competitor. Thus, companies have to demonstrate courage, if efficient system solutions are to be developed at an extra-corporate level. 

The emphasis is essentially on safety rather than ethics, although, of course, a study that does not minimise risk is also unethical. As well as a summary of the preclinical information, some comment and interpretation about its significance should be provided. The choice of starting dose and increments for dose escalation should be justified. The number of subjects and amount of data that will form the basis for a decision to escalate should be clearly stated, as should the criteria for stopping the escalation. 

The outputs from risk assessment will normally include information about the relationship between dose and risk and estimates of levels of doses and thus risks in the population. For contaminants that have a toxicological threshold the Provisional Tolerable Weekly Intake (PTWI) might be defined and the number of consumers who have the potential to exceed this level of intake quantified. If a PTWI cannot be established (such as for genotoxic carcinogens) then it may be possible to quantify the proportion of a population exposed to a given level of risk by using QRA methods. If QRA methods cannot be applied then a qualitative assessment can be made such as to reduce intake levels to as low as is reasonably practicable. In either case it is the function of risk management to identify an optimal course of action to minimise the risk to consumers. 

Throughout the design of a chemical plant, issues relating to safety, economics and environmental impact must be considered. By doing so, the risks associated with the plant can be minimised before actual construction. The same principle applies whatever the scale of the process. The field of process control (Chapter 8) considers all these issues and is, indeed, informed by the type of hazard analyses described in Chapter 10. The objectives of an effective control system are the safe and economic operation of a process plant within the constraints of environmental regulations, stakeholder requirements and what is physically possible. Processes require control in the first place because they are dynamic systems, so the concepts covered in the earlier chapters of this book are central to process control (i.e. control models are based on mass, energy and momentum balances derived with respect to time). Chapter 8 focuses on the key aspects of control systems. 

Control of Inputs. The objective is to eliminate hazards and minimise risk associated with equipment, chemicals and materials, information and the people who... 

A fine balance must be maintained between the need to create and enhance the diversity and to minimise the damage caused by loss of information. In natural evolution, mutation rates which are very low lead to only gradual change in the characteristics of a population, and it may then be unable to adapt with sufficient speed to changes in the environment. At the other extreme, high mutation rates cause destruction of information and the risk that new individuals may not be viable because of the loss of vital genetic data. The optimum conditions for evolution in both natural and artificial systems seem to be those in which mutations occur at a rate which is just below that at which significant amounts of information are lost. 

Thus, a well-performed drug substance characterisation minimises the risk of a subopti-mal final formulation as a result of neglecting important biopharmaceutical prerequisites for a certain drug substance. Furthermore, such information also allows an efficient development process based on science, while trial and error approaches are avoided. 

The objectives of thorough documentation are to define the manufacturer s system of information and control, to minimise the risk of misinterpretation and error inherent in oral or casually written communication, to provide unambiguous procedures to be followed, to provide confirmation of performance, to allow calculations to be checked and to allow tracing of a batch history. 

A cohort study is a prospective analysis of a population with a particular disease. Participants who are exposed to the study drug and those who are not on treatment are followed for a period of time and observed for development of the disease or result. Information on exposure is known throughout the follow-up period for each patient. The classic example is the use of anthracycline in childhood cancer. A long-term, non-interventional, observational follow-up of 607 children has shown that 5% of patients develop clinical cardiac failure 15 years after treatment. The risk increases with the increase in cumulative doses (Kremer et al., 2001). Once a treatment is associated with certain toxicities, researchers can look at ways to minimise the effect. The relationship... 

None of these quinolones should be taken at the same time as any iron preparation that contains substantial amounts of iron (e.g. ferrous sulfate, ferrous gluconate, ferrous fumarate, iron-glycine sulfate). Since the quinolones are rapidly absorbed, taking them 2 hours before the iron should minimise the risk of admixture in the gut and largely avoid this interaction. Information about other quinolones seems to be lacking but the same precautions should be taken with all of them except fleroxacin, which appears not to interact, and lomefloxacin, which seems to interact only minirnally. 

Information from sensors can also help to correct an athlete s technique for optimum performance, to manage effort as well as to minimise risk of injury. Conclusions from data analysis can be used to set realistic development targets. Progress can be quantified and mrmitored versus goals during or after each training session. 

Many of these procedures already take place in primary schools, but often informally. It is important that a policy is not only in place but that it is implemented and monitored. The guidelines suggested will help schools not only meet their legal and professional duties but also to develop a safety culture that controls and minimises the chance that pupils will be exposed to unacceptable risks during science activities. 

Section 6 of HSWA places duties on designers, manufacturers, suppliers, erectors and installers to ensure that articles are, so far as is reasonably practicable, safe. They must also arrange any consequential tests and examinations, provide adequate information for safe use, and carry out necessary research to minimise risks to health and safety. 

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