The bulk drug industries use and produce chemicals which include highly inflammable, corrosive, toxic and hazardous chemicals. In the recent past several industrial disasters have occurred which have taken a heavy toll of human life and property.
These incidents have also focused the attention to know and control the various hazards involved in the production of bulk drugs and pharmaceuticals.
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According to the Factories (Amendment) Act 1987, the hazardous process has been defined for the first time and an exhaustive list of 29 categories of industries has been declared as hazardous.
The definition of hazardous process embraces all types of chemical industries including the bulk drugs and pharmaceuticals.
The hazards in the drug and pharmaceutical industry may arise due to the hazardous properties of the chemicals such as explosivity, inflammability, corrosivity, toxicity, chemical degradation and release of free radicals etc.
Therefore, it is essential that managers in drug and pharmaceuticals industry must put in their best efforts to identify the hazards involved in their industrial units and take necessary steps to control them efficiently:
1. Identification of Hazards:
The first step is to prepare an exhaustive list of the materials used in each and every bulk drug industrial units including intermediate chemicals and final products. The purpose of preparation of hazardous substances list is to identify “All known hazardous substances” under use. This documentation is necessary to know which substance possesses the “potential of being hazardous”.
The hazardous properties of all these substances must be recorded in details keeping in view of the probable, possible hazards, which may arise. A chemical data sheet must be prepared for every hazardous chemical under use.
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This data sheet must cover the major hazards associated with a single substance or family of substances along with the methods of their elimination or control. The data sheet must outline safe and effective handling procedures. The data sheets are written for use of safety professionals and management personnel and employees.
The data sheet may have to cover the following topics:
(i) Properties (Physical and chemical).
(ii) Identification tests.
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(iii) Uses.
(iv) Packing instructions.
(v) Transportation regulations.
(vi) Storage.
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(vii) Personnel hazards.
(viii) Personal protective equipment.
(ix) Handling procedures.
(x) Ventilation.
(xi) Fire explosion hazards.
(xii) Electrical hazards,
(xiii) Symptoms of poison,
(xiv) First aid.
(xv) Treatment of burns.
(xvi) Toxicity data.
(xvii) Threshold limit values.
(xviii) Medical examinations.
(xix) Waste disposal.
(xx) Equipment operation and repairs.
2. Classification of Hazards:
After the chemicals are listed and chemical data sheets are prepared the next step is to classify the substances according to the hazards inherent in them.
These hazards are:
i. Fire Hazard – This is the most common and major hazard in drugs and chemicals industry. Flash fires and fire balls radiate intense heat which further spread fire speedily.
ii. Explosion Hazard – The incidence of explosion in drag industry are much less when compared to fire but whenever explosion has occurred the extent of damage has been much greater than fire.
iii. Toxic Hazards – The release of toxic chemicals is also a major hazard. The intensity of hazard ranges from a sudden brief exposure at high concentration to prolonged exposure at low concentration for longer periods.
iv. Corrosion Hazard – This hazard arises due to splash of corrosive chemicals causing burn, cause damage to the skin of trapped persons.
v. Respiratory Hazards – In drugs and pharmaceutical industry impurities in air arise due to concentration of various substances such as ammonia, chlorine, hydrogen chloride, sulphur dioxide, hydrogen sulphide etc. and various types of dusts during powder handling.
These may be easily detected by their irritating odours while some of the gases such as carbon monoxide are odourless.
The managers of drugs units must classify the above hazards further as first degree or second degree hazards.
vi. First Degree Hazards – These represent the elements in the system that are inherently hazards e.g. materials and reactions, heat, pressure, oxygen, energy sources, ignition sources, possibility of human errors, mechanical failures, hazards from other processes and the environment.
vii. Second Degree Hazards – These are the result of first degree hazards and include fire and fire spreads, explosion and secondary explosion, release of hazardous materials collision and other impact blows, stumbling, falling, poisoning and other exposure effects on personnel.
The following hazard classification may be used:
(i) NAS Hazard rating for bulk water transportation.
(ii) NFPA Health Hazards.
Therefore, all the pollutants along with their permissible limits of concentration must be listed. The facilities must be created for detection of each and every such material to be handled in the pharmaceutical industrial unit.
A manual for air samples and analysis must be prepared. In order to ensure the hazards exists or not in an environment, a survey must be made, samples to be taken and analysed and the result must be correlated with clinical observations of person exposed.
If a hazard exists appropriate measures such as process modifications, substitution of materials, revision of practices, changes in shifts schedule, better ventilation or other control alone or combination may be recommended.
3. Solvent Hazards:
The severity of hazards in the use of organic solvents depends on the following factors:
(i) How the solvent is used.
(ii) Type of job operations determined, how workers are exposed?
(iii) Work pattern.
(iv) Duration of exposure.
(v) Operating temperature.
(vi) Exposed liquid surface
(vii) Ventilation efficiency
(viii) Evaporation rate of solvent
(ix) Pattern of air flow
(x) Concentration of vapour in work room and house-keeping.
The solvent hazard therefore is determined not only by the toxicity of the solvent itself but by the conditions of its use who, what, how, when and how long.
For convenience, the operations employing solvents may be divided into three categories.
They are:
(i) Direct Contact – Is a consequence of hand operation; emergency repair of equipment, spraying or packaging volatile materials without ventilation, cleanliness of spills, normal cleaning using clothes or brushes wetted with solvent.
(ii) Intermittent or Infrequent Contact – Is encountered where solvent is contained in semi-closed system where exposure can be controlled e.g. paint spraying in exhausted spray booth. Changing reaction or kettles in a batch type operation, transferring liquids to secondary containers are examples where the worker is exposed at infrequent intervals.
(iii) Minimal Contact – Is characterised by remote operation of equipment totally isolated from work area. This type of operation includes directing chemical plant operation from a control room.
Mechanical handling of bulk packaged materials and other operation where the solvent is contained in a close system and is not discharged to the atmosphere in the work area.
4. Hazards in Operation and Processes Involving High Pressure and Temperature:
These operations warrant special attention and care and must be carried out by specially trained and qualified personnel. The safe working procedure for each and every operation must be prepared and the persons must be trained by demonstrating the safe operations to all employees.
The equipment are to be tested according to SMPV rules and all the safety instruments provided must be maintained in ready-to-use condition. The periodic checking and testing has to be maintained rigorously and the proper records of the checking, testing and maintenance must be kept of inspection by any statutory authorities. The compressed gases under use also be paid similar attention.
It is necessary to prepare Do’s and Don’ts for the safe storage, loading, unloading and safe handling of compressed gases, and proper care to be taken to identify the compressed gases. It is essential to prepare a comprehensive plan to control leakage of gases if any emergency develops.
A new pressure vessel is installed with its necessary piping and fittings such as relief valve, drains, gauge glass, and pressure temperature controller must be inspected prior to putting into service. It is important that the user must have full knowledge of the installation and operation of pressure vessels.
5. Powders:
In the drugs and pharmaceuticals industry, many a substances are handled in powder form. Almost all the operations required for the preparation of formulations in tablet forms such as mixing, granulation, drying, tableting etc. involve the handling of fine powders.
Special care has to be taken while handling the fine powders as some of them may be toxic and hazardous in short/long run exposures and on inhalation. Therefore, these powders have to be handled, taking proper precautions at the point of dust generation such as isolating and enclosing the dust generation areas and to provide with suitable exhausts.
In case if this is not adequate and if the powder substances to be handled possess respiratory and exposure hazards such as formulations of hormones for family planning drugs under schedule H, narcotics, sedatives etc. the appropriate approach is to enclose the area and provide full PVC uniform along with compressed air breathing line for each and every individual.
In order to reduce the time of exposure further, the duration of working in such hazardous areas may be reduced by increasing the number of persons or changing the persons frequently.
The following precautions must be taken to control the dust hazards:
(i) Area of handling above drugs must be isolated fully from other areas.
(ii) Proper inflow and outflows of ventilation must be provided taking care that the exhaust air is fully deoxified and made devoid of any drug before being let out into the atmosphere.
(iii) The employees must be thoroughly examined for any abrasion of skin etc. before drafting them for handling the dangerous drugs.
(iv) The working area must be provided with air-conditioning, if so, required as is done in case of sterile working area.
(v) At regular intervals these employees must be examined medically.
(vi) The work in the above areas must be regulated by permit clearance system with written down detailed instructions.
(vii) Monitor the environmental condition to contain the hazards.
6. Controlling the Hazards:
After all the detailed informations are collected on hazardous substances, hazardous processes and operations, the safe-handling precautions for each item must be separately prepared. Detailed safety instructions must be prepared for storage, transportation and handling of each and every hazardous material, process or operations. Keeping in view the hazards which may arise ‘No compromise’ should be made at any time.
The safe practice procedures must be made known to all employees individually and practised without fail. If any situation develops, creating any emergency, the combat force must be mobilised immediately.
The safety skills must be developed by training and further improved by demonstration of safe handling practices at regular intervals in order to maintain and further update the safety skills.
7. Labelling:
The labelling of solvents, to indicate their properties and health and fire hazards, is an extremely important method for controlling the hazards.
The Manufacturing Chemist’s Association Guide to precautionary labelling of hazardous chemical Manual recommends the following steps:
(i) Name of product.
(ii) Single word designating degree of hazard, danger warning caution, poison, skull and cross bones should be used for chemicals defined as poisons or required by law to be labelled should be used in addition to the other signal words.
(iii) Statement of hazards (extremely hazardous, flammable).
(iv) Precautionary measures to be taken or action to be avoided (avoid breathing vapour, keep away from heat or open flame).
(v) Instructions in case of contact or exposure e.g. flush eyes or skin with plenty of water for at least 15 months.
(vi) If any poisoning takes place it is to be followed by first aid instructions or given antidote.
(vii) A complete list of solvents being used in the Plant should be maintained.
(viii) Extensive publicity is to be given for severe health hazards so that everybody knows not to use those chemicals as a general solvent.
8. Controlling Environment Hazards:
General methods of controlling environmental factors, stresses, which may cause sickness, impaired health, or significant discomfort among workers, include:
(i) Substitution of a more harmful material by one which is less dangerous to health.
(ii) Change or alteration of a process to minimise worker contact.
(iii) Isolation or enclosure of a process or operation to reduce the number of persons exposed.
(iv) Methods to reduce the generation of dust in operation and to provide local exhaust at the point of generation or dispersion of contaminants.
(v) General or dilution ventilation with clean air to provide a safe atmosphere.
(vi) Personal protective devices such as special clothing’s and/or respiratory protection.
(vii) Good house-keeping including cleanliness of workplace, disposal, adequate washing, toilet and eating facilities, drinking water and control of insects, rodents.
(viii) Special control methods for specific hazards such as reduction of exposure time, film badges, similar monitoring devices, continuous sampling with preset alarms and medical programme to detect intake of toxic materials.
(ix) Training and education to supplement engineering control.
9. Process Safety Considerations:
Early identification of process hazard and inherent risks is very much essential. The preliminary hazard risk analysis must be carried out as early as possible and the safety must be put into process at every stage.
If possible, attention may be paid to select a different process route or operation or other design option. The process sequence may be examined to improve the safety of process.
The scale, inventory, type and integration of process should be related to potential safety and health hazard. The size, frequencies of occurrence of dangerous leaks and their effect must be estimated.
The selection of a batch or continuous process is also important. Generally continuous process holds less material in process. The batch processes are easier to isolate. The chances of operating error or damage to equipment or number of failures must be reduced.
It is necessary to determine the maximum inventories of certain substances under normal and abnormal processing conditions. It should include inter-connected items of plant which are not capable of rapid isolation.
In the event of loss of containment or control quantities the loss should be ascertained compared and with quantities specified by statutory, legal notification, rules etc., the manufacturer of a raw material should be consulted about its properties and characterisation and its safety in storage handling and use.
Waste products must be classified and must be discharged according to the type, method of the composition and quantity of waste products. The disposal rate, temperature under all process conditions, hazard characterisation, control supervision and safe-guarding of discharge must also be studied.
10. Controlling of Respiratory Hazards:
To prevent or reduce dangerous exposure to toxic materials.
(i) They should be confirmed as much as possible.
(ii) Gas releases should be vented outside buildings and away from work areas and other populated areas.
(iii) Exhausts, ventilations should be provided to remove emissions and or personal protective clothing and equipment must be worn.
(iv) In dealing with gases which are highly toxic, the detection and warning is difficult. In such cases the confinement of handling is important.
The following steps may be taken:
(a) The air in the building must be changed every two minutes with standby equipment to double this rate in case of emergency.
(b) The exhaust air must be completely de-harmed before it is let out in the atmosphere.
(c) In addition suitable respiratory equipment must be readily available so that it may be worn in a few seconds before starting work.
(d) It must be ensured that correct breathing apparatus is available.
(e) The users are properly trained in its use.
(f) The apparatus should be of size, type and simplicity, commensurate with practical and realistic needs.
11. Permit System:
This is the best means of controlling hazard. The permit system or a form of licensing and documentation in writing, is a convenient method for preparing a basic standard procedure for spelling out the task to personnel and equipment involved, method to be used, the location of task, precaution to be taken and the time required for the completion of operation.
The permit system offers one of the best method to make difficult operations safe to perform and have been developed as most satisfactory method for ensuring the proper control and safe performance of repeated operations that are proved hazardous.
(i) The permit system provides written information and instruction on hazards which are to be avoided in the operation.
(ii) Ensure that proper task and preparations made prior to starting the work.
(iii) Restrict the performance of work to adequately trained personnel.
(iv) Ensures the personal notification of all concerned parties prior to start of work, clarifies the responsibility for the operation.
(v) Provides a written record of operation and emphasis the responsibility for safety to all persons who sign the permit and supervise the operation.
(vi) Provides an unusual degree of control of operation to be performed.
Hazardous operation permit include – Jobs involving welding, cutting and open flame, vessel and closed spaces entry, disposal operations, testing permits, execution permit working on heights, line briefing, hazardous work area permits, acid area work permit, flammable area work permit, special hazard permit, toxic material permit, match or lighter permit, equipment operating permit, material handling permit, sprinkler valve closing permit etc.
12. Disaster Management Plan:
Every bulk drug and pharmaceutical unit must prepare its disaster management plan.
Disaster management plan is essential as it:
(i) Reduces the amount of thinking time required after the incident occurred.
(ii) Contains the incident and minimises the extent of the damage to the resources and business.
(iii) Reduces the conduct of disaster to a set of predetermined rules and a system of orderly procedure to make orderly and rational what is essentially chaotic and instinctive.
(iv) Helps to meet statutory obligation under various rules and regulations.
The success in disaster management depends on:
(i) Reliable early detection.
(ii) Careful planning.
(iii) Efficient personnel.
(iv) Adequate technical facilities.
(v) Problem free communication.
(vi) Proper training of all personnel concerned.
The disaster management must include the following:
i. Organisation – Of plan includes command structure disaster team, details of key persons, warning system, implementation procedure, emergency control centre.
ii. Communication – Identification of key personnel, list of addresses, telephone, telex, fax numbers, details of heavy lifting gear and specified fire equipment.
iii. Specialised Knowledge – Details of specialised bodies, firms, persons to be called immediately.
iv. Chemical Information – Details of hazardous substances stored and a summary of risk associated with them.
v. Other Arrangements – Emergency feeding, treatment of injured, first aid, ambulance, arrangement of getting weather information.
All the above measures, when put in practice, will create more awareness about the health and safety hazards in drugs and pharmaceutical industries. If every industrial unit formulates its plan of action to identify the inherent hazards and take suitable action systematically to contain, control and reduce the hazards, the loss of life and property will be drastically reduced.
The systematic identification and control of hazards will reduce the number of accidents resulting in mitigating the pains, sufferings anguish and will go a long way to build a healthy, safe work, environment in bulk drugs and pharmaceutical industry.