Unwanted moisture in pharma production

 Simon Mills explains the advantages of applying the latest desiccant rotor and dehumidification technologies:

While traditional humidity control methods are still very effective, continuing developments in the use of the desiccant rotor and dehumidification technologies provide unparalleled levels of RH control and system efficiency. Simon Mills discusses the methods and some of the benefits available.

Even the simplest form of pharmaceutical manufacturing processes can involve a range of process steps before the finished product gets to packaging and the consumer. Incorporating R&D, these processes may include:

· Lab scale development using glove boxes, small scale process driers and coaters, fluid bed driers

· Micronising

· Storage of powders or liquids

· Mixing

· Product drying

· Tablet Compression

· Film Coating

· Sugar Coating

· Aseptic Packaging

· Blister Packaging

· Storage of finished product

Throughout these processes, the effects of ambient humidity can have detrimental effects on product quality, yield, visual appearance and shelf life – issues that can often effectively be avoided by the careful control of humidity in the production spaces.

Furthermore, R&D may have determined that a certain product either cannot successfully be manufactured, or may have significantly reduced yield at differing humidities and there can then be a discussion concerning the balance of humidity control required to produce at lab level and the costs/benefits of those humidity controls once upscale production is commenced.

It may also be true that some products cannot physically be produced without careful control of ambient humidities, as there is significant degradation of the product above certain levels. Enzyme based diagnostics - for example - are very susceptible to changes in humidities and to levels of relative humidity much more than 10%.

These control requirements are also affected by changes in the seasons, with summer conditions generally being worse than those in the winter (as far as airborne moisture is concerned), and in a perfect world, the summer condition would be able to be controlled at the winter levels, so that production rates remain constant throughout the year – leading to more reliable production and satisfied customers whether internal or external.

Humidity Levels

Generally speaking, a production suite can be maintained at or near to 45%RH at a comfortable working temperature of 210C using refrigeration based air handling systems, with either chilled water or direct expansion systems at their heart, although the issue of latent moisture load (from personnel, product or machinery) requires careful selection of plant to ensure that dewpoints within the air handling plant do not approach 00C with the attendant risk of freezing of cooling coils.

Around 40%RH and 210C, there becomes a potential issue with the dewpoints necessary within the cooling plant, where conditions close to or at the freezing point of airborne moisture become necessary to achieve the humidity control in the production area. This can lead to frozen coil surfaces, reduced airflow through the plant and a spiralling and rapid build up of ice within the plant. This then requires defrost procedures, during which the conditions in the space may be lost.

For onward validation and reliable production, this is obviously unacceptable.

It is also very important to realise that the delivery condition of the air needed to MEET the requirements in the room, will always be less than the stated room requirements. Just as there has to be a difference in temperature between the air entering a room or process to allow for the heat gains within the room, where moisture has to be picked up, there has to be a similar difference in the delivered air’s moisture content.

Lower Humidities

It is perfectly possible to achieve conditions of relative humidity well below 5%RH within a production space or packaging hall – or within the enclosure of a tabletting machine, aseptic fill line, or coating pan, if that is what the particular product or process demands. These ‘micro-climates’ can represent a very cost effective solution to production issues.

These particular demands may have been introduced during the research phase, or due to other technical or product validation requirements.

A different type of technology is employed for these lower humidity conditions and it is generally true that for air conditions of less than 35 or 40%RH, the use of desiccant dehumidification technology needs to be seriously considered.

This technology is used extensively throughout the Pharmaceutical industry and is a reliable method of producing controlled relative humidities in all areas of the process.

It also provides for easily reproducible and constant production rates between winter and summer conditions and allows for the possibility of production to be moved to another more cost effective base without having to worry about the effects of ambient humidity at the new location.

When very low RH conditions are required, care needs to be exercised in the choice of a working temperature as well. As the RH is lowered, the vapour pressure between the room condition and the operator is abnormally high and leads to increased evaporation from the skin, leading to the impression of being cold due to the evaporative cooling effect. In these instances, it is usual to increase the dry bulb temperature in the room, typically to 23 or 240C.

The particular benefits of the control of humidity levels as described may include:

· Reproducibility of results

· Reduced friability during tablet compression

· Reduced drying time in fluid bed driers

· Improved appearance of coated tablets

· Reduced moisture retention in powders or liquid pharmaceuticals

· Reduced waste due to clogged machinery

· Reduced downtime due to cleaning requirements

· Improved packaging processes

· Improved shelf life

· Reduction of micro-biological growth

· Reduction (or control) of static build-up

How Does The Technology Work

Desiccant dehumidification technologies work hand in hand with traditional refrigeration methods to create the required working conditions. Refrigeration is a very effective method of removing large quantities of moisture as a ‘first stage’ process, which is then further reduced using the desiccant dehumidifier.

These machines incorporate a rotor or wheel, impregnated with a desiccant salt (usually silica gel) bonded to the surface of a corrugated structure. This typically offers a transfer surface to the air stream of 2,500m2 per m3 of media (on a macro scale), offering a highly efficient moisture transfer medium.

The construction of these rotors is such that this massive surface area can be in contact with the air within a relatively small overall volume, and quite often, the machines required to achieve given duties can be very compact.

Within the machine the moisture is absorbed by the desiccant and the air leaves at a much-reduced moisture content. This is delivered to the room, further conditioned or mixed back into another air stream to provide a lower ‘average’ condition for the space. Such is the efficiency of the desiccant dehumidifier, that usually not all of the process air needs to be conditioned and a mixing of air streams is the usual solution.

To remove the collected moisture from the dehumidifier, a second air stream is heated using available energy (typically steam, electricity, gas or hot water), which provides an environment for the moisture to be removed from the desiccant, leaving the building in a hot and (relatively) wet air stream. At all times during this process, the moisture is adsorbed and desorbed in the vapour phase, meaning that no actual liquid is present at any time.

The absolute performance of this technology is determined by the method of application and for processes where it is required (e.g. Lithium Battery production) dewpoints as low as –600 can be achieved. This equates to a relative humidity of less than 1%RH at a sensible working temperature of 240C.

Other Design Considerations

Generally speaking, RH levels as low as 20% do not need specialist room construction, as long as sensible housekeeping measures are employed. These measures might include airlocks, the sealing of any wall and roof structures and the minimising of door openings and product transfer slots.

Below this RH condition, the influence of the ambient conditions surrounding the room will become increasingly relevant. In addition, the ambient air condition used in the design, and the quantity of that air included for either personnel comfort or production requirements becomes a major influence.

In the UK, it is not unusual for the dehumidification requirements on a Pharmaceutical production process to be designed to cope with an external ambient condition of 350C and up to 16g/kg.

The risk of NOT applying the correct ambient design during the initial calculations is that the required RH in the space or process may not be met in the medium term due to general annual increases in the peak levels of ambient moisture as a result of overall climate change.

The implications of this on the ability to produce are the potential loss of product if plant is installed which cannot cope with the changes in the ambient conditions. Any additional front-end capital costs to allow for the higher ambients is generally far less than the risk of loss of product.

Applications

As briefly discussed, the applications for this technology are manifold. They include:

· Air onto fluid bed driers for product drying

· Air into micronising processes for powder stability and reduced static

· Air into tabletting machine enclosures for increased throughput and reduced tablet friability

· Air into coating machines for film and sugar coating

· Air for production suites for ‘whole process’ conditioning

· Air to packaging machinery for extended shelf life

· Air at the same condition all year round to provide constant production rates

· Creation of ‘micro-climate’ within the confines of a machine enclosure

Plant Requirements

Depending on the system requirements and the physical space available within any plant room, it may be preferable to incorporate the general air handling components into a single machine, along with the dehumidification requirement. This will have a dramatic effect on the amount of space required to achieve the duties.

Within such equipment, we can incorporate cooling and heating requirements, high levels of filtration to HEPA, high system air pressures, control face and bypass arrangements, temperature and humidity control systems, special finishes, supply plant in breakdown form for ease of installation and with electrical components to meet any existing site requirements or client preference.

Conclusions

The technology available for the creation of these conditions has a proven reliability and performance track record and once installed can provide the required conditions with minimum maintenance for upwards of 10 years.

Once installed, production rates can be set up either to meet previously established validation requirements or customer needs, and these rates maintained at all times of the year, or if the production process is removed to another location.

In addition to the stable and reliable conditions achievable, there are added benefits in terms of reduced cleaning, improved product quality and lower drying times to be considered.

Working in conjunction with established cooling and heating techniques, the use of desiccant dehumidification systems can supply reliable and constant conditions all year round, allowing better quality and reduced production costs.

Simon Mills is Sales Director of HB Group Company, Sorption Wheel Services Ltd.