Containing solutions
Martyn Ryder of Extract Technology investigates solids charging into process vessels
Vessel charging in the process plant has long been identified as a major source of dust emission. Now, with increasing use of APIs (active pharmaceutical ingredients) in the processing and manufacturing stages, the need for assured operator protection is adding to the requirement for effective dust containment.
The maximum permissible operator exposure level (OEL) considered in this article is 10µg/m3. Containment during vessel charging falls into two key categories: • Airflow containment – local exhaust hoods • Isolation containment – vessel charge isolators Both of these containment solutions have merit, although for many processing operations the size of the containment solution and the high capital cost make these unenviable. Typical performance levels that may be attained with traditional solutions, as well as new developments in soft wall isolation will be discussed. The article concentrates on solids in the form of dust-generating powders, which will be transferred manually by operators scooping or tipping into the vessel. The safe disposal of empty drum liners, or bags of sub-division powders, is also a key area where containment is needed. Hence, the principal dust-generating sources to be contained during vessel charging are:
• Sub division of bulk solids • Solids scooping into vessel manually • Solids tipping into vessel manually • Disposal of empty liners, bags and containers
Simple airflow containment, using local exhaust hoods, often struggles with the varying positions of the dust-generating sources involved with vessel charging. To be effective in controlling dust in the process plants, local exhaust hoods or local exhaust ventilation (LEVs) must be located within close proximity to the source of dust clouds. During vessel charging, several drums may be located on a pallet that can be positioned wherever the operator chooses. The other major dust-generating source – the vessel manway – is fixed and is, therefore, easier to contain. Local exhaust hoods frequently give low levels of control, often due to poor positioning and poor work practices employed by the operator. During a recent trial, the open scooping and pouring of powders, utilising the existing LEV system, generated over 600µg/m3 operator exposure. This is clearly unacceptable when handling APIs. Although still reliant on airflow to achieve containment, booth-type solutions provide better operator protection. Operations are now confined within an airflow control zone. Large vessel charging booths form a localised compartment around the vessel head and can be equipped with access doors, gowning facilities and airlocks to segregate the vessel charge operation from the rest of the process plant.
Operator protection Smaller vessel loading booths, where the bulk solids' drums are outside the airflow control zone, are often worse in terms of operator protection performance, and may be assigned a similar performance band as local exhaust hoods. Ultimately, all types of airflow containment equipment suffer from the close interaction between the process operator and the powders being transferred. Dermal and clothing contamination is an ever-present risk and hence, with more active compounds, a single exposure may take the operator's ingestion above the permitted daily intake. In recognising that physical contact with the powders due to handling is the most common cause of unexpected peak exposures during powder transfer, a new development known as the FlexWall Barrier is marketed by some booth vendors. This device is essentially a section of clear glove bag material forming a physical floor-to-ceiling, wall-to-wall barrier between the operator and the powder or materials to be handled. The screen is flexible enough to permit a good degree of operator movement – but forms a total air and dermal barrier between the two. In recent tests, involving vacuum transfer loading, operator exposure was reduced from 416µg/m3 during conventional vacuum transfer, to below 8.0µg/m3 with the FlexWall Barrier screen in place. This low cost addition seems to be set for widespread use with vessel charging applications. Charging solids into the process via gloves and glove ports is a great leveller of physical abilities, and hence the lifting of loads above 10-15kg should be avoided in all glove-box isolator applications. As a result, many designs of vessel-loading isolators incorporate a drum lifter or drum tipping device. Before looking in detail at the various types of vessel-loading isolators, it is vital to accept a basic fact of life regarding highly active pharmaceutical ingredients – removing the drum lid may create unacceptable levels of exposure. Often APIs are transferred as in-house packages between one part of the plant and another. Hence, the security and cleanliness of polythene liner-bags within drums delivered for charging cannot be guaranteed. Different design variations exist in the containment industry: • Simple isolator designs that permit controlled drum-lid removal in an open environment • Contained lid removal within an inspection chamber Irrespective of the approach to drum-lid removal (protected or unprotected), the physical size of the equipment often necessitates location of the isolator on a "charge floor" above the reactor hall. Although large in "footprint" and costly in terms of capital expenditure, vessel-loading isolators should be considered the ultimate "safe solution" for containing APIs during vessel charging. The main advantages are: • Good ergonomics • Ease of use • Nitrogen purge options • Wash-in-place/clean-in-place systems for effective clean down (useful for decontaminating drums with split or damaged liners) In use, vessel charge isolators allow 100kg+ drums to be loaded into the vessel within a 5-10 minute cycle time, and assure operator exposure within the 5-1.0µg/m3 range.
Design solutions Several manufacturers offer designs that can handle multiple drum sizes and weights, including those that permit sub-division into small containers that dock to the vessel via split-butterfly valves or Alpha/Beta ports. For development scale plants, where vessel-loading additions in the 0-10kg range are commonplace, the focus of operator protection is split into multiple zones. Firstly, bulk sub-division is an area where operator safety must be considered. For this operation, downflow booths, dispensing glove-bags and rigid-shell isolators all provide feasible solutions. However, the selection must be driven by the OEL of the material to be dispensed. Common sub-division stations include the Downflow Booth Dispense Station (roughly 100µg/m3) and the Rigid Isolator Dispense Station (roughly 1.0µg/m3). The selection of the correct sub-division system should always be based on the level of operator protection needed. Compromising operator protection ultimately compromises GMPs, as cross-contamination between materials is a real possibility. Once the type of sub-division system has been decided, the vessel loading container type should be selected, again according to the OEL of the material to be handled. The key types available are : • Small glove bag (1-10µg/m3) • Polybottle with split-butterfly valve (1-5µg/m3) • Transit carrier canister with Alpha/Beta port (below 1.0µg/m3) Each solution has its own merits and limits. For example, the low cost glove bag system is intended to just provide containment during the life of a manufacturing campaign, hence it is difficult to decontaminate. The unit's limits are offset by its low cost "disposable" nature. However, the techniques required for charge-cube use, such as double-tie and cut-off, may not be adequately performed under shift operating conditions. More frequent small-additions vessel-loading applications require an engineered (reliable) dock/undock solution, and this is where the split-butterfly valve and low cost container have a role to play. The split-butterfly valve allows a direct container-vessel connection with a clean make/break connection. Some designs of split-butterfly valve can be equipped with vibratory devices to assist powder-flow from the container. The split-butterfly valve offers a reliable and cost-effective method for small additions loading into process vessels. The valve system can often be mechanised to permit "push button operation". This automation helps guard against one of the common weaknesses of the split-butterfly valve technology – the incorrect operation and closing of the valve before un-docking. It is not unusual to see containers being lifted away from docking stations while still discharging powder residues due to the split-butterfly valve not being fully closed. Most manufacturers of these valves now offer an automated version. Due to the trace contamination of split-butterfly valve disc faces, after powder transfer and undocking, OELs around the transfer point (vessel) are likely to be in the 1-5µg/m3 level. The Alpha/Beta ported-transit canister provides the highest level of containment for small additions to process vessels. The Alpha/Beta port mechanism will be protected from loose powder transfer by a simple procedural rule stating that the Alpha/Beta port must be closed during any powder transfer operation, and should ideally be wiped clean and dust-free before it is opened. By following this procedure, it is simple to reach containment levels below 1.0µg/m3 quite readily. One disadvantage of the Alpha/Beta ported-transit canister method is that a second isolator must be fitted to each receiving vessel. This makes the full system, incorporating isolator, controls package and pressure-rated ball valve, very costly for multiple reactor vessel applications. Where it is possible to do a solvent wash-down into the vessel, it is feasible to have a mobile version of the secondary isolator. In this instance, the isolator/vessel interface will be cleaned to a sufficiently safe level after powder transfer to permit undocking of the isolator vessel connection tube.
Charge cube systems As the frequency of API handling in process plants increases, the industry is seeing a demand for effective, yet low-cost, containment technologies – the "80/20" requirement. Clients are demanding 80% of the performance ability of the mainstream containment solutions, but see low price as the key driver due to budget constraints, the large number of applications and infrequent usage. Hence, the design objective is to attain 80% of performance at 20% of the cost of traditional technologies. The "Charge Cube" range of vessel loading containment solutions was designed around this brief (see Fig.1). It has been assumed, in both research laboratory operations and chemical development facilities, that solids will be pre-dispensed into a suitable containment system elsewhere, to permit a compact and low-cost containment solution at the vessel head.
Charge cube 1 The Charge Cube 1 device permits contained solids additions into glass reaction rigs, and is intended to be loaded with pre-weighed solids in a fume cupboard or similar sub-division area. The bagged-up solids are placed into the charge cube, which is closed via the zip-open lid. The product transfer tube is fitted with a polythene over-bag, which is tied off to prevent any contamination escape during transport to the reactor vessel. Once the charge cube is mounted in place above the vessel, the stainless steel powder feed chute is inserted into the vessel mouth. The over-bag tube is carefully sealed around the vessel neck, before the cable tie below the main chamber is removed. At this stage, the charge cube may be nitrogen purged. The pre-weighed solids bag can now be opened via the glove ports and the powder transferred into the vessel under contained conditions. The removal of the charge cube from the vessel after charging is contained in a low-cost polythene over-bag tube. Withdrawal of the powder-feed tube is completed, leaving the over-bag tube in tension between the vessel neck and charge cube. This allows a "double tie-off-and-cut" operation to be performed on the uncontaminated bag, resulting in minimal exposure to APIs. Charge Cube 1 is heavily reliant upon correct operating procedures. However, its very low cost and disposable nature make it the ideal containment device for laboratory applications. The rigid base-plate and hopper of this glove-bag allows engineered easy wash-through for decontamination between campaigns. In the latest version, which allows for the inclusion of an isolation ball-valve, "wash-down-in-place" (at the vessel head) can be carried out without the risk of wash liquids entering the process.
Charge cube 50 The Charge Cube 50 is intended for applications where small drums or multiple bag packs need to be added to a process vessel. Charge Cube 50 has a rigid stainless steel base to support solids additions up to 50kg in weight. Under normal operating conditions it is assumed that clean packs of solids or clean drums will be added to the clean Charge Cube. At the end of each loading sequence a clean-down hose permits de-contamination of the entire envelope in readiness for re-loading. The connection chute to the vessel is over-bagged to allow a clean disconnect after solids additions have been transferred. Recent proving trials in Switzerland have shown operator exposure levels of around 4µg during a 50kg charge of fine micronised lactose.
Charge cube 100 The need for rapid and fuss-free drum transfer has been identified for production scale solids additions. Due to drum dimensions and weights, a drum-tipping system is seen as an essential ingredient, while in the interest of economy it has been decided to forego the drum-tipping chamber (which is useful to isolate drums with damaged liners) for a simple drum-holding canister. The operator is responsible for re-lidding any drums found to have torn or damaged liners. The drum-holding canister provides great flexibility in accommodating variations in drum height or diameter. One of the main aims in designing the Charge Cube 100 was to develop an ultra low-cost method of isolating the powder-transfer chamber from the process plant environment. The solution has been to use the outer liner-bag as a no-cost lid that can be replaced as each new drum is offered up for powder charge. Due to the large container weights and the physical effort needed to manipulate liners removed from the inclined drum, Charge Cube 100 has a rigid yet economical isolator shell with acrylic vision panels and ergonomically-friendly oval-shaped glove ports. It can be equipped with nitrogen purge systems and wash-in-place systems. Each of the containment devices mentioned here has different benefits. What works well for small-scale, high-containment needs is not necessarily ideal for production-scale applications. The new low-cost Charge Cube range is easy to use and the barrier isolation is the ideal way to safely handle APIs in the process environment.