Process design contamination prevention

Freeder, B. G. et al., J. Loss Prev. Process Ind., 1988, 1, 164-168 Accidental contamination of a 90 kg cylinder of ethylene oxide with a little sodium hydroxide solution led to explosive failure of the cylinder over 8 hours later [1], Based on later studies of the kinetics and heat release of the poly condensation reaction, it was estimated that after 8 hours and 1 min, some 12.7% of the oxide had condensed with an increase in temperature from 20 to 100°C. At this point the heat release rate was calculated to be 2.1 MJ/min, and 100 s later the temperature and heat release rate would be 160° and 1.67 MJ/s respectively, with 28% condensation. Complete reaction would have been attained some 16 s later at a temperature of 700°C [2], Precautions designed to prevent explosive polymerisation of ethylene oxide are discussed, including rigid exclusion of acids covalent halides, such as aluminium chloride, iron(III) chloride, tin(IV) chloride basic materials like alkali hydroxides, ammonia, amines, metallic potassium and catalytically active solids such as aluminium oxide, iron oxide, or rust [1] A comparative study of the runaway exothermic polymerisation of ethylene oxide and of propylene oxide by 10 wt% of solutions of sodium hydroxide of various concentrations has been done using ARC. Results below show onset temperatures/corrected adiabatic exotherm/maximum pressure attained and heat of polymerisation for the least (0.125 M) and most (1 M) concentrated alkali solutions used as catalysts. 

Appropriate procedures, designed to prevent microbiological contamination of compounded drug products purporting to be sterile, shall be established and followed. Such procedures shall include validation of any sterilization process. 

According to 211.113 Control of microbiological contamination, pharmaceutical manufacturers need written procedures describing the systems designed to prevent objectionable microorganisms in both nonsterile and sterile drug products. All sterilization processes used to manufacture parenteral drugs need to be validated. 

Excipient plant air handling systems should be designed to prevent cross contamination. It is permissible to recycle a portion of the exhaust air back into the same area for dedicated areas processing the same excipient. The adequacy of such a system of operation for multi-use areas, especially if several products are processed simultaneously, should be carefully analyzed. In multi-use areas where several products are completely confined in closed vessels and piping systems, the extent of filtration of the supply air (combined fresh make-up air and recycled air) is acceptable if the conditions are consistent with other existent regulations (e.g., environmental, safety). 

Written procedures should be established and followed that describe the sampling methods for in-process materials, intermediates, and APIs. Sampling plans and procedures should be based on valid data and scientifically sound sampling practices. Sampling should be conducted in an area and using procedures designed to prevent contamination of the sampled material and other APIs or intermediates. Procedures should be established to ensure the integrity of samples after collection. Each sample should be labeled to establish its identity. 

Natural or precolored. If virgin resin is delivered in its natural (uncolored) form, it typically requires equipment to add colorant prior to processing. If virgin material is delivered precolored, care has to be taken in equipment selection and system design to prevent cross-contamination. 

The diaphragm cell (Figure 3.2) is so called because the anode and cathode compartments are separated by an asbestos diaphragm. This is designed to prevent contamination of the anode compartment by the products formed at the cathode. In addition to the fundamental reactions occurring at the anode and cathode the following may take place, reducing the current efficiency of the process. 

The gas processing options described in the previous section were designed primarily to meet on-site usage or evacuation specifications. Before delivery to the customer further processing would normally be carried out at dedicated gas processing plants, which may receive gas from many different gas and oil fields. Gas piped to such plants is normally treated to prevent liquid drop out under pipeline conditions (dew point control) but may still contain considerable volumes of natural gas liquids (NGL) and also contaminants. 

Shared equipment Design to avoid or minimize use of (e.g. auxiliary process- common equipment for incompatible ing scrubbers ). Pos- materials sihility of incompatible, Implement proper cleaning procedure materials coming between incompatible uses to prevent together. cross contamination Prescrub or treat process streams before transfer to common equipment API RP 750 CCPS G-11 CCPS G-22 Kletz 1991 Lees 1996 NFPA-91... 

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