Containment solutions for milling systems
George Tunnicliffe and Martin Thomson of Kemutec outline some of the containment options available for mills
The surge in demand for containment in the pharmaceutical industry, and indeed in other industries too, is a direct reflection of the increased potency of modern drugs and the demands of more stringent legislation. This has challenged pharmaceutical companies and, in turn, their equipment manufacturers to meet these more exacting criteria. Manufacturers of size reduction equipment have to contend with impact, air-flow, temperature, high speed rotating components, bearings and seals when designing equipment in addition to the hazards of the product actually processed.
The issues
As pharmaceutical compounds become more potent, acceptable Operator Exposure Levels (OELs) are reduced. This is at odds with the trend towards finer particle size distributions (PSDs) which tend to make effective containment more difficult. In addition, finer PSDs make products more of an explosion risk and subject equipment to more scrutiny under the requirements of ATEX. Added to these requirements are commercial pressures to ensure that equipment costs are kept under control whilst meeting these higher standards.
Factors influencing containment
The key factors that influence the containment of any process are the toxicity and associated OELs of the materials under consideration, their PSDs, both before and after processing, the pressure at which the process takes place, any change in product characteristics after processing and, finally the explosion risk characteristics of the product. Milling systems throw up all of these problems, particularly at the system endpoints ie the material in-feed and discharge points and also at the mill air/gas intake and exhaust vent.
Handling potentially explosive products
The four recognised ways of dealing with the explosion risk in a milling system are: venting, suppression, inerting and containment. Firstly, venting is clearly not an option when you are dealing with hazardous products. The last thing that anyone wants is to spread such materials far and wide aided and abetted by an explosive force! Although suppression does not compromise the containment requirements, it is not widely used in the pharmaceutical industry, because of the amount of cleanup required after a suppressant discharge. It also introduces materials that may be detrimental to the particular product. This leaves the two methods most favoured by the pharmaceutical industry as inerting and containment.
Inerting
An inerting system uses nitrogen or argon to reduce the oxygen level to below the limit that will support combustion. The main advantages are that it completely eliminates the possibility of an explosion, allows the system to be sited anywhere and makes it suitable for low Minimum Ignition Energy (MIE) materials. However, systems of this kind come at a cost and there is the need to protect operatives against hazards such as asphyxiation and ‘cryo burns’ if the gas is generated from its liquid state. Safe venting of the inert gas must also be catered for which can be a problem depending on site layout.
Containment
Containment systems contain the maximum pressure rise during an explosion and this means that systems can be sited anywhere. They do not compromise 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 appropriate for sensitive, low MIE materials.
Closed loop root
One solution is the Closed Loop Milling System which has the advantage of being compact and cheaper than traditional containment designs. Mill process gas is re-circulated around the system, eliminating the need for filters, valves, etc. Systems also offer easier cleaning with less chance of cross contamination. However, these systems may be unsuitable if the product has a low MIE and is prone to dust explosion.
  The Inert/Closed Loop Hybrid System is a development designed to cater for these low MIE materials. It has many of the advantages of the closed loop method (compactness, cleanability, etc), with the advantage that the inert processing atmosphere enables it to be used with highly sensitive materials. There is a requirement for filtration, but, because only top up volumes of gas are vented, these can be small ‘throw away’ units featuring a construction that does not have to withstand pressure shock containment.
Ultimate containment system
The ultimate in containment is the milling system enclosed in a glovebox. Closed loop and Inerted Closed Loop systems are ideal for this purpose. Compact design means 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.

• George Tunnicliffe and Martin Thomson can be contacted at Kemutec Group Ltd Tel: +44 (0)1625 412000

Towards total containment
A sharing of knowledge and expertise between Carlisle Life Sciences Europe (incorporating the brands of PBSC, Extract Technology and Barrier Systems) and CTT Ltd, manufacturers of the IChemE award-winning Drumvent system, has resulted in the PBSC Total Transfer Isolator.
  Drumvent, a ventilated high-containment liquid or powder transfer unit used to fill or empty standard industry drums, is contained within a sealed PBSC transfer hatch for secondary containment.
  Stuart Anderson, MD at CTT Ltd, said that development of Drumvent since 1995 allowed it to satisfy all pharmaceutical requirements, the latest model ensuring that emission levels of hazardous vapours are now controlled to less than 0.01ppm within the operator's breathing zone. However, to minimise risk when operators are handling highly corrosive, toxic, potent or dangerously odorous liquids, secondary containment becomes of paramount importance. CTT therefore turned to containment experts at Carlisle Life Sciences Europe.
  The result is a unit with flush viewing panels, vents and easy-open glass doors to ensure a user-friendly operation with almost total containment achieved through negative pressure. At the end of each filling or emptying operation there is a short air purge time which clears the isolator before the next operation. ‘Drumvent may already achieve the low emission figure of 0.01ppm’, says Martyn Ryder, product development director at Carlisle Life Sciences Europe, ‘but this new cost-effective isolator means that we can target zero emission, as this secondary containment will reduce this figure by a further factor of 1000.’ The isolator is designed to provide total containment during filling, emptying, sampling, sealing or weighing operations.
• Tel:+44 (0) 1484 317 000 or email: info@carlislelifesciences.com

High containment IBC system
When a process needs to be contained, the risk areas are at any breakable interface. For IBCs feeding a process, there is the potential for material leakage at three stages: as the container is delivered to the station – not usually possible, because all containers are sealed during transit; during container discharge – systems now available virtually eliminate leakage once the IBC is in position; and as the IBC is removed from the station – a possible source of contamination and the area that we are highlighting.
  Butterfly valves, commonly used to control discharge from an IBC, have a disadvantage, says ISL. During discharge, both sides of the valve are covered with powder and, once closed, the lower face can still be coated with powder which can escape to atmosphere. On a typical 250-mm valve the exposed area can be as much as 500cm².
  Development of the cone valve system brought improvements, providing an alpha/beta type connection, joining the two exposed surfaces of container and station, sealing any dirt and preventing powder from getting between the interfaces. The only surface on which powder is able to collect is around the ring at the edge. With a 500mm diameter and about 15mm high this equates to an area of 235cm² - in theory halving contamination. ISL says that, unfortunately, the soft sponge gasket that these type of systems use tends to trap more powder than the smooth surface of a butterfly valve.
  ISL’s solution to the problem is a high containment cone valve with an upper section that provides a positive elastomer seal, the lower level providing a metal to metal taper joint. This reduces the surface area on which residual material can remain to just 23cm². The parallel section at the upper seal ensures that no spillage occurs during transport.
  Levels of containment achieved with the valve do not differ greatly from those of a split butterfly valve and, by including an air sweep system, extraction and negative pressure receivers, an OEL of around 100 µg/m² is possible. The cone valve has the added advantage that it guarantees flow, preventing segregation and controlling feed.
   ISL are able to improve on these levels of containment by using systems that wash the interface between container and station prior to separation to eliminate residual material - a process that can be done with air, water, solvent or steam. Containers can be specified with full CIP facilities, allowing container cleaning to be done insitu.
www.conevalve.com

Split butterfly maximises containment
Glatt split butterfly valve isolation flap systems are for contained discharge of dry powders and are designed to offer maximum levels of containment when transferring from one unit operation to another.
  Benefits claimed for the system include: containment levels to 1m grm/m³ before, during and after product transfer; ability to be retrofitted in cases where conventional valves are in use; and easy disassembly without tools for cleaning, sterilisation and maintenance.
  Systems are available for use with IBCs, drums, bins, tanks and miscellaneous containers in 100, 200 and 250mm diameters. Construction can be in 304 or 316L stainless steel with FDA approved silicone elastomers and mirror polished for cGMP compliance.
www.glattair.com