Ensuring reliable, consistent production in pharmaceutical water systems
Water system equipment design and quality play a role in optimizing pharmaceutical manufacturing.Pharmaceutical water systems ensure the safe, continuous and efficient operations of the pharmaceutical manufacturing facilities as well as the quality of the final end products. It is therefore critical to design pharmaceutical water systems to prevent conditions that compromise water quality by providing continuous recircula-tion at turbulent flows and no dead legs. It is also important that equipment support good manufacturing practice (GMP) and good documentation practice (GDP) in terms of materials, surface finishes, welding joints, cleanability and documentation.
Selecting the right equipment is paramount to securing delivery of the right quality water to the point-of-use at the required flow and temperature. Proper equipment design and quality can help address challenges involving potential contamination, rouge, energy use and environmental emissions as well as issues involving installa-tion, validation and maintenance.
Biofilm buildup
Populations of live microorganisms as well as dead microbial cells can form a layer, or biofilm, on the surfaces of pharmaceutical water system equipment. This film also contains noncellular materials, such as mineral crystals, corrosion particles or silt particles. More than 99% of all microbial activity occurs in biofilm. Biofilm buildup poses contamination risks to pharmaceutical water systems. However, proper equipment and system design can reduce these risks.
Concerns
Unfortunately, there will always be a small amount of bacteria that will grow and multiply – even in the best pharmaceutical water systems. The degree of harm caused by such contami-nants is difficult to predict due to variable factors, such as temperature, pH, velocity, stress and heat. Most water systems contain gram-negative bacteria with the outer membrane of the cell wall, which releases endotoxins when the bacteria are killed. If injected into the bloodstream, these en-dotoxins cause fever and, in the worst-case sce-nario, septic shock which can be fatal.
Methods to reduce risk
Minimizing the growth of gram-negative bacteria is the best way to reduce the risks associated with endotoxins. Pharmaceutical water systems must therefore operate at temperatures that pre-vent bacterial growth and undergo periodic sani-tization. The water’s pH value, concentration and content of organic nutrients also influence bacterial growth. A matrix of primarily polysaccharide material that constitutes the building blocks for the biofilm also provides nutrients to the bacteria. It is therefore critical not only to minimize the presence of nutrients by employing a fully closed system, but also to minimize biofilm buildup.
When setting forth the functional specifications (FS) and design specifications (DS) of pharma-ceutical water systems, it is important to:
• Secure continuous recirculation to prevent stagnant water conditions that promote bacte-rial growth by choosing an efficient and fully re-liable centrifugal pump
• Secure sufficient velocity and high shear force in the system to prevent biofilm buildup.
• Design systems and select hygienic equipment without dead legs, crevices, pockets or diffi-cult-to-clean areas where stagnation can oc-cur. For instance:
– Choose a circulation pump, which is de-signed for ease of cleaning, especially for cleaning the hard-to-reach back side of the
impeller.
– Choose a heat exchanger, which is designed to create turbulence and can be completely flushed of the existing water, and “new” wa-ter can replace the old.
– Select diaphragm valves and other equip-ment designed without any dead legs.
• Include a visual inspection of product contact surfaces as part of routine maintenance proce-dures to ensure that surfaces are smooth and without imperfections or visible signs of rouge or other deterioration, which can lead to micro-bial colonization.
Reducing energy use and carbon emissions
Because of the need for high temperatures and continuous circulation, hot water systems are en-ergy-intensive. This, of course, leads to high costs and adversely affects emissions. It is there-fore important to minimize energy consumption and emissions of pharmaceutical water systems.
Concern
There are several ways to reduce energy con-sumption and emissions. Reducing temperatures in a hot circulation loop from 90°C to between 65°C and 75°C saves energy, but can potentially increase the risk of bacterial growth in the sys-tem. It is therefore important to maintain a tem-perature that is sufficiently high to prevent bacte-rial growth, yet sufficiently low enough to provide cost savings. Hygienic systems are designed to have high velocity and turbulence. The more hy-gienic the system, the greater the possibility to re-duce system temperatures that, in turn, leads to energy savings while safeguarding the quality of water.
Methods to reduce risk
Attention to detail pays off when selecting equip-ment for a distribution loop. Reducing energy use by selecting the right pumps, valves and heat ex-changers can deliver energy savings.
Pumps: Because the circulation pump is in con-stant use, it is important to select a robust, relia-ble and energy-efficient pump. Be sure to size the pump correctly; oversizing the pump wastes energy . Click here to learn more about how selecting the right pump reduces energy use and costs.
Diaphragm valves: Choosing the right dia-phragm valves for the distribution loop can also save energy and reduce emissions. Some of the largest valve manufacturers now offer a new generation of diaphragm valves with low pressure drops that provide up to twice the flow rate compared to traditional diaphragm valves. Another benefit of selecting diaphragm valves with low pressure drops is that it may be possible to reduce pipe diameters as well as the required pump capacity, which can lead to significant cost savings. Click here to calculate your potential energy savings. Furthermore, some valve manufac-turers offer T and tank outlet valves made of forged material, with lower mass and weight, which require less energy to heat and less time to sterilize.
Heat exchangers: Both tubular and plate-type heat exchangers can be used in the distribution loop for heating and cooling. Compared to plate heat exchangers, shell-and-tube heat exchangers often have higher initial investment costs as well as higher energy usage and thereby higher operating costs due to high-pressure drops. Other maintenance costs for shell-and-tube heat exchangers, however, are generally lower than those of plate heat exchangers .
Summary
To ensure reliable, consistent production in pharmaceutical watersystems, it is critical to design the systems to minimize the risk of rouge and biofilm buildup, to reduce energy consumption and emissions, and to ease installation, validation and maintenance. This calls for employing the best practices to achieve systems that are both cost-effective and energy-efficient.
• Invest in hygienic design. No dead legs, crevices, pockets or other difficult to clean areas.
• Use high-grade stainless steel with good surace finish quality.
• Maximize the shear force of the surface. Keep
in mind that high flow rates generate a turbulent flow, which reduces the risk of biofilm.
• Try to maintain the temperatures of hot water
systems at approximately 65°C to 75°C. Water above 65°C is generally recognized as selfsanitizing because most bacteria are killed at
temperatures above 55°C. Lowering the temperature has two benefits: Decreased energy
consumption and prolonged equipment lifetime.