GOOD MANUFACTURING PRACTICE FOR BIOPROCESS ENGINEERING (ERT 425) School of Bioprocess Engineering UniMAP

4) Fault tree analysis - is a logically constructed diagram used to model the way that combinations of failures cause the event of interest (the top event) to occur. - provides valuable insights into the way that hazardous events interact even if no data is inserted for calculations (hazardous event frequencies or probabilities). - The logical arrangement of the 'And' and 'Or' gates of the fault tree is more critical to the overall calculation of the likelihood of the top event than the accuracy of the data inserted. - A rule of thumb is that if there are more than twenty elements in the tree then subdivision is worthwhile.

5) Human reliability estimation Problems: attempting to quantify risks accurately as human factors are hard to define precisely. when estimating the likelihood of a hazardous event, the probability of beneficial action by an operator should not be a critical factor to achieve the target criterion. There should always be adequate protection in place to ensure that the operator action is not critical to the safe operation of the system. Human tasks can be classified as 'Skill based', 'Rule based' or 'Knowledge based'. Skill based tasks that depend on physical skill and manual dexterity - can be estimated with some confidence.

Pharmaceutical Industry SHE Hazards Chemical reaction hazards 1)Chemical reaction hazards assessment - methodical assessment (described by Barton and Rogers: define the process chemistry and operating conditions and the process equipment to be used; evaluate the chemical reaction hazards of the process, including potential mal-operation; select and specify safety measures; implement and maintain the selected safety measures.

2) Control of runaway reactions Runaway reactions are thermally unstable reactions where the heat of reaction can raise the temperature of the reactants sufficiently to accelerate the reaction rate out of control. The temperature at which the runaway starts is often termed the onset temperature. Controlled by: cooling the reactor, or by controlling the addition of the reactants. Causes: Loss of reactor cooling or agitation during the course of an exothermic reaction can cause the reactor contents to boil, generate vapour or explode, and over-pressurize the reactor.

Example of runaway reaction: - Seveso, Italy, (1976) – In a manufacturing plant of 2,4,5 trichlorophenol sodium salt by alkaline hydrolysis of tetrachlorobenzene, a chemical mixture containing dioxin, in the form of aerosol cloud escaped into the air.  A large number of animals were killed and thousands of victims of diseases including cancer, chronic dermatitis, neuropathy and deformed babies.

3) Reactor venting Reactor over-pressurization can occur by: a- overcharging with compressed gases or liquids, b- excessive vapour generation due to overheating, or c- runaway reaction. - When control is lost, the most effective way to prevent damage to the reactor is to relieve the pressure through an emergency relief system. key questions to the design of reactor pressure relief systems: 1- what is the maximum pressure that the vessel can contain? 2- what pressure will activate the relief system? 3- will the relieved material be a liquid, a vapour or a two- phase mixture?

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Assignment 2 Summarize an issue (news) about GMP. Make a commentary and deduction based on what have been discussed in the class. Due date: 23 November 2016