With the trend towards pharmaceutical products of higher toxicity requiring greater standards of containment, the protection of mill systems against the consequences of a powder explosion are of ever greater importance. George Tunnicliffe and Martin Thomson from Kemutec explain
The selection of explosion protection methods is often made at a late stage in the mill system design when many other parameters have already been fixed. However, the method of protecting the system from an explosion can be highly interactive with other process requirements. In order to achieve an optimum overall design for the system it is therefore necessary to have a good understanding of the relative merits of the various methods of explosion protection and to consider these at in early stage in the design process. The purpose of this paper is to examine practical, cost-effective, solutions to a variety of mill applications where the need is to provide total protection against the risk of a powder explosion while maintaining effective operational control over product emissions. The surge in demand for containment in the pharmaceutical industry, and indeed in other industries, is a direct reflection of the increased potency of modern drugs and the demands of ever more stringent legislation. This has challenged the pharmaceutical companies and, in turn, their equipment manufacturers to meet the criteria. Here we consider the implications for manufacturers of size reduction equipment where impact, air-flow, temperature, high speed rotating components, bearings and seals are all design considerations in addition to the hazards of the product being processed. As pharmaceutical compounds become more potent, acceptable Operator Exposure Levels (OEL) are reduced. The trend towards finer Particle Size Distributions (PSDs) makes effective containment more difficult. Finer PSDs also make products more of an explosion risk. In addition, legislation is getting tougher – the ATEX regulations came into effect on 1 July in the European Union. Despite all this, there are still the commercial pressures to ensure that equipment costs are kept under control while meeting these higher standards. The key factors influencing the containment solution for any process includes the toxicity and associated OEL levels of the materials to be handled, their PSDs both before and after processing, the pressure at which the process takes place, any change in product characteristics after processing, and the explosion risk characteristics of the product. Milling systems pose all of these problems and particularly at the system endpoints i.e. the material in-feed and discharge points and at the mill air/gas intake and exhaust vent. The provision of explosion protection for a milling operation can significantly add to the costs, size and complexity of the system. Poor selection of explosion protection method will waste money and compromise the system's operational efficiency. It is important to have a good understanding of the relative merits of explosion protection methods in relation to the process requirements. The four recognised ways of dealing with the explosion risk in a milling system are: 1. Venting 2. Suppression 3. Inerting 4. Containment. Although the principle of suppression does not compromise the containment requirements of a system, it is not widely used in the pharmaceutical industry. This is due mainly to the amount of clean-up required in the system after a suppressant discharge and because it involves the introduction of materials that may be detrimental to the product whose value may be considerable. The two methods preferred by the pharmaceutical industry are inerting and containment.
Inerting systems Inerting systems (Fig. 1) use an inert gas such as nitrogen or argon to reduce the oxygen level to below the limit that will support combustion. Their main advantages are that they do completely eliminate the possibility of an explosion, the system can be sited anywhere and they are ideal for low Minimum Ignition Energy (MIE) materials. Disadvantages include increased system cost, ongoing cost of the inerting gas, the need to protect operatives against hazards such as asphyxiation and 'cryo burns', if the gas is generated from liquid. Safe venting of the inert gas must also be catered for which may be problematic dependant upon site layout etc.
Containment systems Containment systems (Fig. 2) are constructed to contain the maximum pressure rise during an explosion. Such systems can be sited anywhere, they do not compromise the containment OELs in the event of an explosion and there are negligible maintenance requirements. On the other hand, there is the higher initial cost of manufacture and explosions can take place which may not be suited for use with sensitive low MIE materials.
Are there alternative designs? At Kemutec we have asked ourselves: "Can we utilise the 'best bits' from the standard traditional methods? Can we produce compact mill designs to aid containment issues – e.g. use gloveboxes? Does this need to incur additional expense?" One solution is the closed loop milling system. Closed loop systems can be based upon the containment principle. They are much more compact and cheaper than traditional containment designs. The mill process gas is recirculated around the system, which eliminates need for filters, slam shut valves, etc. These systems offer easier cleaning with less chance of cross contamination. Closed loop mill systems have many advantages but they may still not be suitable if the product has a low MIE and is prone to dust explosions. We need to consider a system to cater for this class of materials hence the development of the inert/closed loop hybrid system. This offers many of the advantages of the closed loop method, such as compactness and cleanability, with the additional advantages that the inert processing atmosphere enables its use with even the most sensitive materials. They do require the use of filtration, but because you are only venting 'top up' volumes of gas, these can be small throw-away units. Also they do not require construction to withstand pressure shock containment.
Gloveboxes For the ultimate in containment, milling systems can be enclosed in "gloveboxes". Closed loop and inerted closed loop systems are ideally suited for use within gloveboxes. Their compact design requires a smaller enclosure with fewer penetrations through the walls. Where required the gas flow through the enclosure can be chilled to limit the temperature rise of the mill. Our experience confirms that system mock-ups benefiting from operator input at an early stage of the design process allow confirmation of the ergonomics. This saves potential costly rework of equipment and manufacturing delays.
Key Factors 1. Milling Equipment: Impact Mills are suitable for average PSDs of 30 microns 2. OEL Levels: Gloveboxes to suit OEL's sub 10mg/m3 3. MIE Value: Nitrogen inerting to suit MIEs of 3mJ 4. CIP: Glovebox allows access to mill with wash lance 5. Product Value: One final (not insignificant) point – the value of the product (which can be $100,000 per gram and higher) can also impact upon the design criteria!
Summary 1. Choice of explosion protection method needs to be considered early on in the system design process 2. Explosion protection is an integral part of the overall containment philosophy 3. Material characteristics, site conditions and operational requirements will all influence choice of explosion protection method 4. Closed loop mill systems can show savings in overall cost and space requirements, particularly when used in conjunction with a glovebox etc 5. Low MIE products can be treated effectively with hybrid closed loop-inerted operation while retaining most of the benefits of closed loop containment operation.