Recent trends in containment strategy

This article gives an insight into containment guidelines, what company policies should be and will be when it comes to risk assessment

R S Swaminathan, Adnan Khan

An activity that needs to be contained should always be based on a scientific risk assessment. While avoiding mix-ups and cross conta-mination is important, what makes high potent product manufacture different is that safety of operator exposure during manufacturing risk is dependent on the period of exposure. Selecting the activity with reference to the OEL a RA chart is prepared. The protection level indicated in the RA chart refers to protection required while carrying out these operations without any protection.

Containment

The overall manufacturing process involves three major components—ingredients, operators and surrounding area. In this, the purpose of containment may be protection of personnel from exposure to hazardous substances and solvents, protection of environment against the release of hazardous substances and solvents, and preventing the contamination of products.

The thought process for effective containment is multidisciplinary and aims to make containment as an in-built feature. It covers process equipment, equipment layout, general layout of facility and air-handling systems. More-over, it also covers functional areas like quality control and quality assurance, employee health and safety and outdoor environmental considerations. The right approach to flawless containment is to achieve the required level of containment as close to the source of emissions as possible. The best ways to achieve containment can be through process modification, modification in transfer operation, process equipment modific-ation, local containment provision and facility provision. Modification like use of double O-ring seal with gas purge instead of conventional mechanical seal and transfer by vacuum or pressure, use of magnetic coupled pumps instead of rotary pumps, can be very useful. Sampling is the critical step where the chance of system being closed becomes risky, use of special types of sampling valves and glove box eliminates the risk of material getting exposed at this stage. Selection of easily cleanable finishes for process equipments and actuated bottom valves operated from remote can play an important role in containment strategies.

Layout design

Layout planning should be based on the risk to operators arising from exposure of product and the level of protection required. While planning the layout, the operations to be carried out in the facility can be classified into three sections-non-potent processing area, intermediate potent processing area with potent substance in solution and slurry form with relatively lesser OEL, and final potent processing area with potent substance in slurry and powder form with relatively stringent OEL. The purpose of defining the areas for potent processing and making it separate is to have relatively easier control of movement inside the hazardous area, limit the number of persons working inside, reduce the volume of air to be controlled. With these three sections as the main parts of the facility, change rooms with toilets shall be planned adjacent to entrance. No dining facility shall be provided inside the building. Also no area of the building will be used for general administration activities. Electronic access control shall be provided at the main entrance and at each entry point to potent processing area. This will prevent entry of unauthorised persons in plant building and hazardous areas. Also it will help to keep track of time that people have spent inside the plant and the hazardous area.

Personnel protective equipments

The purpose of chemical protective clothing and equipment is to shield or isolate individuals from the chemical, physical, and biological hazards that may be encountered during hazardous materials operations. It is important that protective clothing users realise that no single combination of protective equipment and clothing is capable of protecting them against all hazards. For any given situation, equipment and clothing should be selected that provide an adequate level of protection. Overprotection as well as under-protection can be hazardous and should be avoided. Protective clothing must be worn whenever the wearer faces potential hazards arising from chemical exposure like entering hazardous area during emergency response for spillage mitigation, leakages, entering hazardous area for breakdown maintenance etc.

Checklist for maintenance

All the equipment shall have CIP arrangement. If any equipment is to be cleaned, it will be first cleaned thoroughly with an appropriate cleaning solution till it is visibly clean. The washings will be sent to a kill tank for deactivation. The second rinse will be for removal of clean-ing solution from the equipment. The complete removal of cleaning solution from the equipment will be ensured. After cleaning is over, the sample will be taken by an appropriate sampling method and sent to QC for testing of traces of previous product. Once QC gives the clearance for use, the equipment will be ready for the next use. If the equipment is to be cleaned for the maintenance, in addition to above procedure, it will be cleaned with deactivation agent and tested for complete deactivation by QC. The removal of deactivation agent will also be ensured. Before maintenance activity is started, the maintenance personnel need to be authorised by appropriate authority from safety production department. Before this, these authorities will have to ensure the clearance from QC for the particular cleaning of equipment.

Handling of samples in laboratory

The QC laboratory shall be planned such that the samples from both final product processing area and intermediate processing area will be sent to QC without coming out of the potent processing area. The minimum required quantity would be sampled. The label of sample will essentially highlight that it contains a potent product. The samples will be moved to the sample collection room through respective pass box.

A person will enter the sample collection room through a change room followed by an airlock. The person will wear over gown in the change room before entering the airlock. The samples from the pass boxes in sample collection room will be carried to the sample preparation room. The samples will be diluted with a suitable solvent in an isolator. The diluted solution in the closed container will be taken out of the isolator and moved to QC through a pass box. The balance quantity of sample solution will be sent to kill tank for deactivation.

Waste treatment and detoxification

It is preferable to have kill tanks and detoxification tank for deactivation. The recovered solvents which are to be recycled and supposed to have lesser concentration of potent substance will be treated with relatively mild agent and then stored in the tanks which are ancillary to detoxification tank. The washings/liquid waste from the process, which is supposed to have higher concentration of potent substance, will be treated with a strong agent in one of the two kill tanks. The deactivated solutions from the kill tanks will be sent to ETP if it contains lesser amount of solids. If the deactivated slurry is having very high solid content, as in the case of slurry of carbon cake from carbon filter, the slurry will be filtered on the filter press and the filtrate will be sent to ETP, while solid from the filter will be sent to incinerator.

Medical surveillance

Workers who are potentially exposed to chemical hazards should be monitored in a systematic programme of medical surveillance intended to prevent occupational injury and disease. The purpose of surveillance is to identify the earliest reversible biologic effects so that exposure can be reduced or eliminated before the employee sustains irreversible damage. The occurrence of exposure-related disease or other adverse health effects should prompt immediate re-evaluation of primary preventive measures (eg engineering controls, personal protective equipment). In this manner, medical surveillance acts as a check on the appropriateness of controls already in use.

(The authors are associated with Spectrum Pharmatech Consultants Email: swaminathan.rs@spectrumpharmatech.com)