Why humidity matters

With the continual development of new products and manufacturing techniques in the pharmaceutical industry that require increasingly tight environmental conditions for production, specialist environmental control systems have never been more important.

It has always been the case that certain processing methods require control of the environmental conditions in terms of both humidity and temperature and conventional heating and ventilation systems have in the past been suitable.

However, the development of new products, particularly biotech-based ones, has shown that many of the systems currently installed cannot provide the close control of relative humidity necessary to ensure consistent quality and optimum productivity.

Conventional heating, ventilation and air conditioning (Hvac) systems are generally designed to provide comfortable, controlled conditions for the staff.

Typically, this will be over a range of 18C to 23C with a humidity range of 40 to 60% relative humidity (RH).

The human body is very comfortable in this range, feeling neither too hot nor too cold.

However, sensitive research and development methods and certain manufacturing processes require control of temperature and humidity at much tighter limits, typically +/-2%RH and +/-1C.

This degree of control cannot be achieved with standard Hvac systems, but it is possible with specialist systems, such as the JS Micro-Environment Control System (Mecs).

Mecs is developed specifically for the process application it is intended for.

It is the first system to provide consistently tight conditions and can be tuned to provide air anywhere in the range of 30% to 98%RH at 15 to 45C, making it ideal for research into establishing optimum production parameters.

It is not uncommon for companies planning new facilities or redevelopment of an existing facility to go to a non-specialist consultant to design the environmental control systems.

These consultants often select the same equipment for a process environment that they would for an office development, without realising the implication to the client.

The design of a system to run 24 hours per day, seven days a week, with close control, is very different to that required for an office system designed to work 12 hours a day, five days a week.

The net result of the wrong selection will be poor environmental control, low productivity and, often, extremely high maintenance costs.

To ensure the most appropriate environmental control is employed from the outset, it is essential that specialists are consulted to work with the designers in developing the appropriate solution to every application.

Poor environmental control, particularly in respect of humidity, can directly affect the pharmaceutical production line in a number of ways.

Levels of humidity below 45%RH will allow static charges to build up which can have major implications where solvents are used in the process and can also cause the product to dry out, affecting its performance.

Other problems associated with static build-up include products sticking to each other, leading to packing problems.

Equally, high humidity can cause products to absorb moisture during production and final packaging.

Some antibiotic tablets, for example, would become degraded and their effectiveness reduced if moisture were absorbed.

Where the product is long-term moisture sensitive it will degrade over time if packed under the wrong conditions.

The requirement for environmental control is not just relevant to production areas, it can also be important within a production machine.

Tablet coatings with aqueous solutions require extremely tight control of air humidity to ensure that the coating does not dry too fast or too slowly.

There are also pharmaceutical printing processes that require control of humidity between 95 and 98%RH, with temperature control to better than 1C to prevent water based inks from drying during processing.

These too are conditions which cannot be achieved with conventional systems.

Cleanroom problems.

The design of cleanrooms is well documented, but the technology used to provide environmental control is again often achieved using standard Hvac equipment.

It is not until low productivity levels are experienced and the problem traced back to temperature and humidity control that the importance of using the right equipment is truly appreciated.

The problem for many companies is that finance directors set a budget for process developments which will only allow the purchase of low cost equipment, particularly in terms of the environmental control plant.

It is rare that the operating costs are taken into account.

If they were, it is likely that it would be a very different picture.

While it may initially cost more to purchase specific equipment to provide the optimum control required, the overall running and maintenance costs of correctly selected equipment will often deliver a payback inside 12 months.

A classic example of this, particularly in respect of steam humidifiers, is an installation of a typical electrode boiler steam humidifier.

Allowing for spares, electricity, labour, etc, this would cost, on average, £10,000 a year to run and maintain and have a capital cost of around £2000.

By comparison, if medium temperature hot water, or even process steam, were available, the use of an indirect hot water-to-steam, or steam-to-steam humidifier would have almost negligible running costs, probably less than £500 a year.

However, the capital cost would be about four times that of an electric humidifier and because of this it is frequently not considered.

This is despite the fact that capital cost and running costs of the hot water-to-steam or steam-to-steam unit would be around 30% cheaper in the first year and some 95% cheaper in subsequent years.

Additionally, this option would give more precise control of the desired set point because of its operating principle.

Cold-water humidification.

The development of cold-water humidification has also moved on in the past five years and gives even greater benefits in terms of power consumption as the water does not have to be heated.

The cold-water humidifier can be either a compressed air and water spray or an evaporative matrix system.

There has always been a reticence to use cold water systems because of fear about the safety in respect of legionella or other bacterial problems.

The recently published Health and Safety Acop L8 document states that, provided the systems meet all the requirements of L8, there is no more significant risk than using steam systems - in some cases less.

It is also often assumed that, because a system is steam based, there is no risk.

Unfortunately, this is not always the case.

The major advantage of cold-water humidifiers is that they use less than 10% of the energy used by electric steam humidifiers.

Moreover, because the principle of cold-water humidification is adiabatic, free cooling can be achieved throughout the year.

Winter is the main humidification season when the return air from the production area is warm and typically large quantities of fresh air are used to give free cooling.

But costs can also be cut when the outside ambient temperatures are high, as the air can be cooled by up to 6C by the humidifier.

Finally, it has always been thought that cold-water humidification cannot be controlled accurately, but again this is a misconception.

If fine control is required, high accuracy control valves can be fitted to allow control to +/-0.5C dew point.

In the field of research and development, the control of humidity and temperature can have major implications in bringing a product to market.

For example, from a production point of view, yields are often low until the humidity and temperature are accurately controlled - pharmaceutical coating applications and stability testing of pharmaceutical products are prime examples of this.

In both these areas, the control of the environment has been found to be critical.

Poor control can give variations in coating, making it necessary to reject entire production batches, often amounting to thousands of pounds worth of stock.

More importantly, falling outside of control parameters in long-term stability testing will lead to a restart.

This can put weeks, or even months, on to the research and development time of a new product, enabling competitors to launch similar items sooner and gain that all important competitive advantage.

It can even be financially beneficial to develop specific equipment for an application to ensure that the requirements of airflow, humidity and temperature are all met at an optimum level.

Although this does take higher levels of investment, the production yields have been known to increase by as much as ten times that achieved with standard equipment.

Maintenance considerations.

Maintenance also plays a major part in the overall stability of pharmaceutical manufacturing and cleanroom environments and humidifiers can require frequent attention, especially in areas with hard water where they will require maintenance periods every few hundred hours of operation.

Selection of the right type of humidifier allows the use of reverse osmosis (RO) treated water, which can reduce maintenance to a once a year overhaul.

This not only saves costs in terms of maintenance and down time in the production areas, but also reduces the overall operating costs, as the amount of water used to de-concentrate the mineral build up is reduced too.

Wrong choice can be expensive.

The costs of running humidifiers can be extremely high if the wrong selection is made and as outlined earlier, the choice of humidifier needs to be carefully considered at the start of a project.

A standard electrode boiler will, on normal mains water, require the cylinders to be changed or cleaned every few hundred hours of operation.

Cylinders can cost upwards of £150 a time, which means that on, for example, a three-cylinder unit, costs plus labour can mount up to £500 every two to three weeks.

If the initial selection had been for a resistive heater steam humidifier, there would be no replacement cylinders as the boiling vessels are normally made from 316 stainless steel.

The cost of a resistive humidifier is typically two and a half times the cost of an electrode boiler, but the savings on maintenance will very quickly lead to a payback.

Additionally, the resistive heater humidifier can be run on RO water, but the electrode boiler cannot as it relies on the conductivity in the water to cause the water to boil.

In areas that have naturally soft water, electrode boilers may not start or will take several hours to build up the mineral concentration to allow full output to be achieved and during this period poor control will be the net result.

The old adages "you get what you pay for" and "caveat emptor" often best describe humidification systems installed in many pharmaceutical applications.

Humidification has often been described as a black art, but in reality it is not.

It is an exact science that requires a full understanding of the application as well as the design and control of the process.

The selection of the right humidifier for the application and the support of the equipment once installed are critical to the overall cost, long-term reliability and operation of the system.

When considering these issues, it is therefore essential that a specialist environmental control expert is consulted.