The pharmaceutical industry requires specific grades of water for different applications. Kalpesh Shah, Veolia Water Technologies, takes a 360° look at water usage, supply options and overall cost efficiencies
A study of the pharmaceutical industry by the UK University of Hertfordshire in 2013 found that “because water use is viewed as a comparatively inexpensive resource, this undermines investment in water-efficient technologies.”
This is no surprise. Mention “water” in the same sentence as “pharmaceutical production” and most pharmaceutical engineers immediately think of compendial Purified Water and Water for Injection (WFI).
As both are critical and relatively expensive ingredients in the industry’s products, this is quite reasonable, but they should not be considered in isolation.
A typical pharmaceutical facility uses water for a variety of purposes and an overall water management approach can be beneficial both environmentally and financially.
Most UK pharmaceutical facilities, for example, take “raw” water from a mains drinking water supply at a cost of around £1.20/m3 and then purify it by reverse osmosis (RO) and electrodeionisation to produce Purified Water at an extra cost of about £1.00/m3. A typical example of the “packaged plants” available to produce Purified Water using this technology is the Continuous Deionisation (CEDI) IonPRO LX.
Orbis Consumer Products is a UK contract pharmaceutical manufacturer operating two production sites in Park Royal (London, UK) where it manufactures analgesic and anti-inflammatory suspensions, including products for children. These liquid products are produced using Purified Water that meets European Pharmacopoeia (Ph. Eur.) requirements, via an IonPRO system, which consists of a mains water tank, activated carbon filter, duplex softener, primary deionisation by RO and polishing deionisation by CEDI. The treated water is delivered to a storage tank from which it is recirculated via a UV disinfection unit and ring main supplying the various points of use.
For larger systems, a range of compendial packaged plants, such as Veolia’s Orion, uses the same basic process of softening, RO and final CEDI with the addition of a tank with a heater for automatic hot water sanitisation. This meets the water quality standards for USP and Ph. Eur. Purified Water and Ph. Eur. Highly Purified Water. The system is fully compliant with US Food and Drug Adiministration (FDA), cGMP and GAMP requirements.
Lofthouse (Fleetwood, UK) uses this compendial plant for its main production line for Fisherman’s Friend — a lozenge for cough and sore throat relief. Here, Purified Water is an ingredient, whereas the company’s new sugar-free lozenge line and a pharma suite have an IonPRO LX unit each to supply water for cleaning.
WFI demands the distillation of Purified Water, adding a further £1.00/m3, bringing the total to more than £3.00. Egyvac, an Egyptian vaccine manufacturer, recently upgraded its water system using an Orion to produce Purified Water and Polaris distillation to upgrade the purified water to WFI. The Polaris range includes a clean steam generator and both multiple effect and vapour compression stills, all designed in accordance with GAMP, cGMP, ISPE and FDA guidelines.
Although Purified Water and WFI are essential when manufacturing pharma products, there are many other equally essential uses of water in a pharma facility (Figure 1). Cleaning-in-place is an obvious one, but don’t forget the humble factory boiler. Without it, there would be no steam for heating, autoclaves or to run the WFI distillation plant or the clean steam generator.
Figure 1: Turnkey solutions for the pharmaceutical industry
The boiler needs a supply of make-up water, which has to be treated, as does the equally important factory cooling tower. Then, there’s water for “domestic” purposes — washrooms, showers and catering. And don’t forget the laboratory, which needs ultrapure water for analysis and media preparation.
Using water inevitably means producing wastewater. Aside from the Purified Water and WFI that is discharged to the drain, there are the waste streams from the water treatment systems themselves — spent regenerant from softeners and deionisers, reject water from RO plants and blowdown from the still. In addition, there is blowdown from the boiler and cooling tower, waste from laboratory sinks and domestic wastewater.
Most facilities dispose of this to the sewer, in accordance with a consent to discharge, and are charged for it according to the (trade effluent) Mogden formula. Sewer discharge averages about £2.00/m3, so buying mains water, treating it to WFI standard and discharging it to the sewer can cost more than £5.00/m3. But if the wastewater contains active pharmaceutical ingredients (APIs), it may have to be collected and taken off site for incineration or some other disposal route.
Delivering critical high performance in a sustainable manner, the Orion comes with a host of innovative and cutting-edge technologies
A typical 1000 L/h Purified Water RO plant will reject about 30 L/h, but a concentrate recovery unit can reduce this significantly. A biotechnology plant located at Ringaskiddy (Co. Cork, Ireland), a Phase IIb/III clinical trial-scale facility, manufactures, purifies, formulates and bulk fills mammalian cell culture derived proteins. The company already had an Orion on site to produce Purified Water, and Veolia was able to use the RecoBLUE online calculator to show the engineers how adding a recovery RO could take advantage of the plant’s “waste” water and turn it into a valuable resource. The plant is now recovering 75% of the Orion’s wastewater (up to 2700 m3 of reclaimed water per annum), which is recycled back to the plant inlet to begin the purification cycle once again, replacing mains water. The resulting reduction in both mains water and sewer discharge meant that the recovery RO paid back in only 7 months.
Onsite biological wastewater treatment using the latest generation of aerobic membrane bioreactors (MBRs), such as a Biosep, with ultrafiltration membranes, has a proven track record in removing some of the more recalcitrant chemical species that are often present in pharmaceutical wastewater. The resulting reduction in Mogden formula charges can often give a payback in a couple of years.
If the wastewater is particularly high in chemical oxygen demand (COD), it may be economic to invest in a Memthane anaerobic MBR to generate biogas fuel to reduce boiler energy costs. An MBR produces treated water that is very low in suspended solids and bacteria, and can often be discharged to surface water at a significantly lower cost than the sewer. But with this quality, it is clearly better to reuse the water for non-critical purposes such as flushing toilets or to feed an RO plant to produce boiler or cooling tower make-up water. Where biological treatment is not appropriate, evaporation can recover around 90% of the water, leaving a small volume of concentrated waste for disposal.
If wastewater contains APIs that are either non-biodegradable or toxic to biological treatment plant bacteria, there are options such as Actiflo Carb — combining adsorption and clarification — or wet air oxidation, which produces free hydroxyl radicals to break down even the most complex organic molecules into carbon dioxide and water.
Although very expensive, wet air oxidation is becoming increasingly attractive as alternative disposal routes become more expensive. But evaporation can provide an environmentally friendly disposal route as well as an opportunity to recover these valuable ingredients.
The latest generation of heat pump evaporators operate under vacuum, which means that water boils at about 35 °C, so that even heat-sensitive APIs can be recovered. And the option of scraped film technology can handle high viscosity or foaming wastes.
A manufacturer of nicotine products installed an Evaled PC R500 scraped film evaporator to process 550 L/day of waste alkaloid solution to produce 500 L/day of aqueous condensate, which can be discharged or recycled, and a concentrated stream containing the alkaloid that is then purified for recycling as a pharmaceutical-grade API.
Taking an holistic 360° look at the manufacturing facility’s water requirement from compendial water to final waste disposal can lead to better management. Combining the techniques discussed above to reuse and recycle water can reduce a facility’s water footprint by up to 50%, as well as offer substantial cost savings.