Risk-based approaches

As explained above we must generally expect the following damaging phenomena 

A large number of event sequences and consequences are possible (vid. Fig. 10.1). For example, fires and explosions may occur within the containment of materials inside the equipment or result from a release of materials. Hazardous substances may be present in the process or be generated because of deviations of process parameters from their values (e.g. larger quantities of dioxin in Seveso) or be formed in the course of an accident (e.g. combustion gases). It is evident that even in a comprehensive and detailed risk analysis it is difiicult to treat all conceivable event sequences. This is even less the case in a risk-based analysis. 

For this reason the following phenomena are treated in [6], which is the basis of the following presentation. They are considered to be dominant for determining appropriate distances  

expected value 1,096.1 kg, 95th percentile 4,126.5 kg (calculated from released quantities in several accidents from [7]) 

Each phenomenon contributes to risk according to its expected frequency of occurrence. That frequency is determined as far as possible from observations of past events, i.e. empirically. 

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To encourage the implementation of risk-based approaches that focus both industry and Agency attention on critical areas. 

The computerized systems, both hardware and software, that form part of the GLP study should comply with the requirements of the principles of GLP. This relates to the development, validation, operation and maintenance of the system. Validation means that tests have been carried out to demonstrate that the system is fit for its intended purpose. Like any other validation, this will be the use of objective evidence to confirm that the pre-set requirements for the system have been met. There will be a number of different types of computer system, ranging from personal computers and programmable analytical instruments to a laboratory information management system (LIMS). The extent of validation depends on the impact the system has on product quality, safety and record integrity. A risk-based approach can be used to assess the extent of validation required, focusing effort on critical areas. A computerized analytical system in a QC laboratory requires full validation (equipment qualification) with clear boundaries set on its range of operation because this has a high... 

There has been a gradual move in environmental policy and regulation from hazard-based to risk-based approaches. This is partly due to the recognition that for many environmental issues a level of zero risk is unobtainable or simply not necessary for human and environmental protection and that a certain level of risk in a given scenario is deemed acceptable after considering the benefits. 

API RP 752, Management of Hazards Associated With Location of Process Plant Buildings, 2d ed. (American Petroleum Institute, Washington, 2003), which gives a risk-based approach to evaluating protection afforded by occupied structures... 

The American Chemistry Council s Responsible Care Security Code is designed to encourage continuous improvement in security performance by using a risk-based approach to identify, assess, and address vulnerabilities prevent or mitigate incidents enhance training and response capabilities and maintain and improve relationships with key stakeholders. As a condition of membership in the council, each member company must implement the Security Code for facilities, transportation and value chain, and cyber security. 

Cefic claims that polymeric materials, reaction intermediates and substances used for R D should not be subject to the REACH evaluation and authorisation process being proposed by the European Commission in its White Paper on future chemicals policy, it is briefly reported. On specific issues, Cefic wants a risk-based approach to chemicals assessment and regulation realistic deadlines for the REACH process and exemption from REACH of finished articles, so that it applies only to substances marketed as substances or as constituents of a preparation. 

Many of the steps involved in a risk-based approach are comparable to the standard transfer paradigm, but the risk-based approach requires significantly more upfront activities to better understand both process and methods. This increased investment increases both the likelihood of successful transfer, the risk of observing a step-change for ongoing stability testing, which could affect shelf-life of the product and the likelihood of future OOS investigations. 

Pharmaceutical cGMPs for the 21st century A risk based approach. US Food and Drug Administration, www.fda.gov/cder/gmp/index.htm... 

In August 2002, the FDA announced a new initiative to cGMP. The initiative is called Pharmaceutical cGMPs for the 21st Century A Risk-Based Approach. It is a 2 year program, and there are three goals to this initiative ... 

The risk-based approach merges science-based policies and standards with an integrated quality system. This is to ensure that the FDA s resources are directed to address those areas that are considered to have higher risks for example, companies with previous compliance problems, new companies with unknown history, and processes requiring aseptic procedures. 

There are three steps to implementing the risk-based approach ... 

The intention of the risk-based approach introduced by the FDA in 2002 was to modernize the FDA s regulation of the pharmaceutical quality of drugs. This was followed by the EMEAs regulation in recognition of such an important topic. This case study summarizes the progress to date for both the FDA and EMEA in the implementation of the risk-based approach. 

The risk-based approach introduced by the FDA focuses the pharmaceutical companies and regulatory authorities resources into addressing potential risk areas based on the scientific approach. The aim is to ensure pharmaceutical companies adopt new scientific developments and equipment for manufacturing safe, effective, pure, and consistent products. 

What are the benefits for the implementation of a risk-based approach in GMP manufacturing ... 

Refer to Section 9.8.The risk-based approach directs resources to address issues according to risk levels to assure the safety and quality of drug products being manufactured. 

The determination of hydrocarbon contaminants in soil is one of the most frequently performed analyses in the study of contaminated sites and is also one of the least standardized. Given the wide variety of hydrocarbon contaminants that can potentially enter and exist in the soil environment, a need exists for methods that quantify these chemicals satisfactorily. Formerly, the idea of total hydrocarbon determination in soil was seen as providing a satisfactory tool for assessing contaminated sites, but the nature of the method and the site specificity dictate a risk-based approach in data assessment. Quantitation of particular hydrocarbon species may be required. 

US Food and Drug Administration, Pharmaceutical current good manufacturing practices (cGMPs) for the 21st century - a risk-based approach final report, 2004. 

However the latest thinking provided by the United States Food and Drug Administration (FDA) in the Guidance for Industry for Quality Risk Management suggests that all qualification activities for analytical instruments should be performed using a risk-based approach. 

Over the last decade, much interest has been generated in monitoring environmental problems and associated risks of wastes, in particular, wastewaters generated by the pulp and paper industries. A major goal is to reassess the target pollutant levels and consider the use of risk-based discharge permit values rather than the absolute endpoint values. This risk-based approach requires analytical tools that can quantify the ecotoxic characteristics of discharges rather than the absolute concentration of specihc pollutants or the values of lumped pollution parameters such as BOD, COD, and so on. 

Pharmaceuticals for the list Century A Risk-Based Approach, FDA, 2004. 

GUIDING PRINCIPLES Encourage new technological advances State-of-the-art pharmaceutical science Risk-based approaches focus industry and agency attention on critical areas Eacilitate industry application of modern quality management Enhanced quality systems approaches into the agency s business processes... 

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