PHARMACEUTICAL FACTORY AUTOMATION
- Ultraviolet(UV) treatment
- Proximity Sensors
- Water Pre-Treatment – Removal of suspended solids & Bacteria
- Iontec – Water Softening & Demineralization
- Revotec – Reverse Osmosis
- DeStill – WFI Distillation
- PureSteam – Pure Steam Generation
- DGS – Membrane water deaeration
- DeGas-Cold – Column water Deaeration
- DeGas-Hot – Column water Deaeration
- ADos – Additive Dosing
- MultiMixer – Multi Component Mixing
- FlashPasto – Flash Pasteurization
- CIP – Cleaning-in-place
- SIP – Sterilization-in-place
- Product Preparation – Production of Liquid drugs
WATER PRE-TREATMENT IN PHARMA & BIOTECH INDUSTRIES
Water Pre-Treatment for the Pharmaceutical and Biotech Industries
Raw water quality depends greatly on its source. Based on the raw water quality and the specifications for the purified water, Centec select the most appropriate technologies for each client. Usually, multi-stage regimes are necessary for water purification. For water pre-treatment, sand and multi media filters are used to remove suspended material (e. g. silt, clay, organic matter). Such material in water can reduce the effectiveness of downstream components such as ion exchange resins and reverse osmosis membranes. Soluble iron and manganese are found in water that contains no dissolved oxygen. They cause a metallic taste and form deposits in piping systems. The Centec De-Ironizer is designed for iron and manganese removal. If harmful bacteria and microbes are suspected, the water is disinfected by UV, ozone or free chlorine. Activated carbon (AC) filtration removes odours, tastes and oxidizing agents like free chlorine that can lead to chemical attack of membranes elements in subsequent purification steps.
WATER PRE-TREATMENT
Sand & Multi Media Filter
A sand filter only uses sand as filter medium. Whereas a multi media filter typically have 3 to 5 layers of different media types. Both are back-flushable. In a sand filter the smallest particles are trapped at the top of the media bed, while larger ones sink deeper proportional to their mass. The result is a very limited use of the media depth, because virtually all filterable particles are trapped at the very top of the filter bed. Multi media filters use several layers of different materials, each having a significantly different density. Due to the layering, larger particles are removed first at the top of the media bed, while smaller particles are trapped further below. Trapping particles in this manner, results in more effective removal of contaminants, even of very small turbidity forming particles. Furthermore, longer run times between backwash cycles are achieved.
De-Ironizer
Dissolved iron and manganese are removed from water by oxidation and subsequent filtration. Fe2+ is oxidized to Fe3+, which with oxygen, forms the insoluble iron complex Fe(OH)3. Mn2+ is oxidized to Mn4+, which with oxygen, forms insoluble MnO2. An ideal and low-cost method of providing oxidation is to use the oxygen in air as the oxidizing agent. For removal of the insoluble iron and manganese gravel can serve as filtration media. By cyclical back-flushing the iron and manganese particles are washed out and removed.
Activated Carbon Filter
Activated carbon filtration is a method of filtering that uses a bed of activated carbon to remove contaminants by chemical absorption. Due to the highly porous structure of activated carbon, each carbon particle provides an extremely large surface area. Contaminant molecules are trapped inside this structure. Activated carbon adsorbs organic substances which cause odours and tastes. Furthermore, it acts as a catalyst in contact with free chlorine supporting the reaction of free chlorine to harmless chloride ions.
Disinfection
Chlorine is an inexpensive treatment method for deactivating microorganisms like bacteria and viruses. Stored in pressurized containers, it can be injected as a gas directly into the water. Alternatively, a sodium hypochlorite solution can be used. This solution is easier to handle than chlorine gas. Disinfection can also be achieved with calcium hypochlorite, a solid disinfectant. This form can be stored as powders, granules or tablets. Ozone (O3) is another powerful oxidizing agent. It is pumped into water systems to kill biological contaminants like bacteria and viruses. Since ozone gas is very unstable, O3 needs to be created on site. Ozone is pure active oxygen and produces no residual odours or tastes in water. Also ultraviolet (UV) light can be used to kill harmful microorganisms. The UV process is an attractive option in many cases because it is chemical-free and investment costs are low.
FLASH PASTEURIZATION FOR PHARMACEUTICALS
FlashPasto – Flash Pasteurization for the Pharma & Biotech Industry
The flash pasteurization system is designed to pasteurize the product gently without adversely affecting its colour, taste or digestibility. For optimum results, pasteurization time, temperature and pressure have to be individually adjusted. Optimum parameters depend on various factors, such as product, type of packaging and anticipated shelf life. Based on highly accurate process control, the unit guarantees constant pasteurization quality even at variable product flow directly in front of the filler. To increase the energy efficiency of the system, the product is warmed up to the pasteurization temperature in two steps. In the first step it is heated in a heat recovery section where it flows in counter current to the hot, already pasteurized product. In the second step it is gently brought to the pasteurization temperature by the heating medium, e. g. hot water, heated by steam. If the flash pasteurization system is installed directly in front of the filling machine, it can compensate for variations of product quantity picked up by the filler. CIP cleaning of the unit can take place as the same time as the main line or separately.
WATER SOFTENING & DEMINERALIZATION FOR PHARMACEUTICALS
Water Softening & Demineralization for the Pharma & Biotech Industry
For ion exchange there are ion exchange resins in the unit. These resins are insoluble granular polymers appropriate for the specific application. In their molecular structure they contain loosely held positive cations or negative anions. These ions exchange with the ions in the treated water as it passes through the unit.
For softening of water a cation resin containing Na+ is applied. The calcium and magnesium ions which form hardness in water, creating scale deposits, are exchanged for the sodium ions of the resin. The resin binds more strongly with Ca2+ and Mg2+ than with Na+. When most of the ions in the resin have been replaced the resin is exhausted and a regeneration cycle is initiated. Regeneration with brine strips out Ca2+ and Mg2+ from the exhausted resin.
For water demineralization basically all dissolved ions are removed from the water. Therefore, the water passes through a cation resin containing H+ to replace all cations and through an anion resin containing OH- to replace all anions. The H+ and OH- then combine and form purified water. For regeneration the cation resin is treated with an acid. The anion resin is regenerated with a strong base. Cation and anion resin can be in separate vessels or together in a single vessel (mixed bed design). Systems for ion exchange are often used as the initial steps in a more complex water purification regime.
REVERSE OSMOSIS FOR PHARMA & BIOTECH INDUSTRIES
Reverse Osmosis for the Pharma & Biotech Industry
Reverse osmosis (RO) is the reversal of natural osmosis. If a semipermeable membrane is placed between pure water and water with dissolved ions (salts) osmosis will come into play. The pores of the membrane only allow the passage of H2O, but not of salts, suspended solids, bacteria and larger molecules. Osmotic pressure due to a concentration difference on both sides of the membrane causes the pure water to pass through the membrane to dilute the solution on the impure side. This will continue until osmotic equilibrium (the same concentration on both sides) is reached. In the REVOTEC unit this process is reversed. In order to separate pure water from water containing dissolved salts and solids, pressure is applied to the contaminated water. When the applied pressure overcomes the natural osmotic pressure, pure water will pass through the membrane into the pure water side. The purified water (permeate) is practically free of all impurities. This cross-flow technology minimizes fouling of membrane elements by quickly removing the impure water (concentrate). However, depending on the contamination of the raw water, pre-treatment may be required to prevent scaling and chemical attack from oxidizing agents like chlorine. In order to exactly reach the desired water quality and to increase the capacity of the system, permeate can be blended with raw water.
WFI (WATER FOR INJECTION) DISTILLATION
WFI (water for injection) Distillation for the Pharma & Biotech Industry
The distillation system consists of a series of interconnected columns and works according to a multistage principle. Pre-treated feed water enters into the first column that contains a double tube heat exchanger. Using external energy the feed water evaporates in the heat exchanger. In order to separate any water droplets that might harbour contaminants like salts and endotoxins, the column has an expansion chamber with demistor. The tubes of the heat exchanger are connected with the expansion chamber. While the steam moves further upwards in the chamber, unevaporated water droplets fall back into the lower section of the column by gravity and due to the specific column design with demistor. In this way they are separated from the steam. The non-evaporated water enters the next column where it is heated again in a heat exchanger. For heating steam from the previous stage is used. While another portion of the water evaporates, some of the steam condenses into WFI. This process is repeated in each column. The more columns, the more energy-efficient the system. In the last stage the steam is condensed in a double tube heat exchanger and cooled to 85 to 95 °C. The concentrated contaminants are directed to drain by a time controlled blow-down valve. As an important quality characteristic, the conductivity of the WFI is continuously monitored. If required, the distillation system can be designed for combined generation of WFI and pure steam at the same time.
PURE STEAM GENERATION FOR THE PHARMACEUTICAL INDUSTRY
Pure Steam Generation for the Pharma & Biotech Industry
For pure steam generation the feed water enters a tubular heat exchanger with an expansion chamber above. In the tubular heat exchanger the pre-treated water is heated and steam is generated. The tubes of the heat exchanger are connected with the expansion chamber that serves as a separating column. For production of pyrogen-free steam the chamber contains a demistor. After entering the expansion chamber, the steam moves further upwards in the column. By gravity and due to the specific column design, unevaporated water droplets fall back into the lower section of the chamber, thus separating from the steam. Since the droplets may contain contaminants like endotoxins, it is vital that they are not carried forward with the steam. As an important quality characteristics, the conductivity of the pure steam condensate can optionally be monitored. If required, the pure steam generator can be enlarged by additional columns to build up a multi effect distillation system. This allows combined generation of pure water and pure steam at the same time.
MEMBRANE WATER DEAERATION FOR PHARMACEUTICALS
Membrane water deaeration for the Pharma & Biotech Industry
Based on the use of highly effective membrane modules, extraordinarily low values of residual oxygen are achieved. Each module contains thousands of hydrophobic, gas permeable hollow fibre membranes resulting in a large surface. This large internal surface of the modules maximizes the transfer area and the contact time between water and gas. While the strip gas (CO2 or N2) is applied on the inside of the hollow fibres, the water flows in counter current between them on the outside. The high partial pressure difference of O2 forces the oxygen out of the water to permeate through the gas porous membranes. Inside the membranes the oxygen flows away together with the strip gas. This fundamental scientific principle is described by Henry’s Law. The DGS system needs a minimum of energy and strip gas. Due to its modular design, the skid can easily be adapted to the required capacity (by parallel installation of membranes) and to the required residual oxygen content (by serial installation of membranes). The O2 content of the deaerated water is permanently monitored. Therefore, the system is equipped with a high precision optical OXYTRANS sensor made by Centec. Centec have decades of experience in the development and manufacturing of own precision instruments for O2 control. For further processing, the virtually oxygen free water can optionally be cooled, disinfected with UV light or carbonated. Hollow fibre membranes are sensitive against particles in water. Therefore, Centec membrane deaeration systems contain specific pre-filters.
COLUMN WATER DEAERATION FOR PHARMACEUTICALS
DeGas-Cold - Column water deaeration for the Pharma & Biotech Industry
For treatment in the column deaeration system, water is dispersed at the top of the column. The column contains densely packed, thin stainless steel sheets arranged in such way that the water takes multiple paths as it flows down through the column. This maximizes the transfer surface and the contact time between the water and the strip gas (CO2 or N2). The strip gas is fed into the bottom of the column and flows upwards inside it in counter current to the water. The large partial pressure difference of O2 forces the oxygen out of the water into the gas phase. This fundamental scientific principle is described by Henry’s Law. At the top of the column the removed oxygen leaves the system as a gas, together with the undissolved CO2 or N2. To further enhance the performance and to avoid carbonation or nitrogenation of the water, the system can optionally be operated under vacuum and completely without strip gas. This reduces capital and operating costs. The O2 content of the deaerated water is permanently monitored. Therefore, the system is equipped with a high precision optical OXYTRANS sensor made by Centec. Centec have decades of experience in the development and manufacturing of own precision instruments for O2 control. The virtually oxygen free water is collected at the bottom of the column. For further processing, it can optionally be cooled, disinfected with UV light or additionally carbonated.
COLUMN WATER DEAERATION FOR PHARMACEUTICALS
DeGas-Hot - Column water deaeration for the Pharma & Biotech Industry
For treatment in the column deaeration system, the water is first heated to 72 °C or more in an integrated, regenerative heat exchanger. Heating reduces the oxygen solubility and simultaneously disinfects the water. The hot water is then dispersed at the top of the column. The column contains densely packed, thin stainless steel sheets arranged in such way that the water takes multiple paths as it flows down through the column. This maximizes the transfer surface and the contact time between the water and the strip gas (CO2 or N2). The strip gas is fed into the bottom of the column and flows upwards inside it in counter current to the water. The large partial pressure difference of O2 forces the oxygen out of the water into the gas phase. This fundamental scientific principle is described by Henry’s Law. At the top of the column the removed oxygen leaves the system as a gas, together with the undissolved CO2 or N2. Hot column deaeration requires very little strip gas. The O2 content of the deaerated water is permanently monitored. Therefore, the system is equipped with a high precision optical OXYTRANS sensor made by Centec. Centec have decades of experience in the development and manufacturing of own precision instruments for O2 control. The virtually oxygen free water is collected at the bottom of the column. For further processing, it can optionally be cooled or additionally carbonated.
MULTI COMPONENT MIXING FOR PHARMACEUTICALS
MultiMixer – Multi Component Mixing for the Pharma & Biotech Industry
In multi component mixing different liquid or powder products are blended. The components to be mixed can be supplied from large storage tanks via supply lines or from vessels located on the skid. Mass flows and concentrations are permanently measured in the process and adjusted by ratio controllers. Therefore, the system is equipped with high precision flow meters and in-line sensors made by Centec. Centec have decades of experience in the development and manufacturing of own precision instruments. Frequently, the MultiMixer is also used for carbonation. In this case the skid contains a specifically designed Vortex-Venturi injector that feeds carbon dioxide in a very large number of very fine bubbles directly into the product stream. With the Centec mixing technology low-oxygen dosing of concentrates is possible. Based on the in-line measurements, the product steams and the carbon dioxide flow are instantly and fully automatically monitored and adjusted. Thus, repeatable results and minimum product losses are guaranteed. The modular design of the process unit allows for easy expansion, e. g. for mixing with deaerated water or for pasteurization of the finished product.
ADos – Additive Dosing FOR PHARMACEUTICALS
Additive Dosing for the Pharma & Biotech Industry
In additive dosing smaller or larger amounts of ingredients are dosed directly into the main product stream according to a preselected recipe. The number of components can be adapted to meet individual needs. There are various possibilities to supply the additives, e. g. out of separate tanks via supply lines or out of smaller vessels located on the skid. Optionally, the vessels can be heated, purged with CO2 or N2 or equipped with agitators. Reliable flow meters, dosing pumps and pneumatic control valves permanently measure and adjust the quantities. Thus, highly accurate repeatable dosage of even smallest amounts is guaranteed. The modular system design allows for easy expansion, e. g. for mixing with deaerated water, carbonation or pasteurization of the finished product.
STERILIZATION-IN-PLACE FOR PHARMACEUTICALS
SIP – Sterilization-in-place for the Pharma & Biotech Industry
Centec provide a large variety of SIP systems. SIP systems are designed by Centec in such a way that optimal sterilization results are ensured, with the lowest consumption of water, chemicals and energy. While one part of the plant is sterilized other areas can continue to produce product. For the production of pure steam, Centec offer pure steam generators. The steam temperature is above 121 °C. If required the pure steam generator can be enlarged by additional columns to build up a multi effect distillation system. This allows combined generation of pure water and pure steam at the same time.
PRODUCT PREPARATION FOR PHARMACEUTICALS
Product Preparation for the Pharma & Biotech Industry
Highest manufacturing standards, outstanding material quality and extremely precise process control guarantee the most efficient handling of valuable pharmaceutical products. For product preparation, the vessel is first filled with Water for Injection (WFI). Previously weighted raw materials (e. g. concentrates, powders) are then added and dissolved in the water by a circulation pump. For accurate level control, differential pressure meters and load cells are used. To achieve optimum and repeatable product formation, temperature and pressure inside the vessel are controlled within narrow limits. At the outlet of the vessel, the finished product runs through a sterile filter. For Centec preparation vessels a large range of optional equipment is available such as agitators, homogenizers, valves, measurement instruments, and sampling devices. The design of the vessels provides excellent cleaning and sterilization characteristics.
CLEANING-IN-PLACE FOR PHARMACEUTICALS
CIP – Cleaning-in-place for the Pharma & Biotech Industry
Cleaning and sanitization must be performed periodically at appropriate intervals. A typical CIP cycle consists of various steps, e. g. pre-rinse with purified water, flushes with caustics and acid solutions, intermediate and final rinse with purified water. Chemicals and detergents are sometimes used to enhance cleaning performance. Depending on the system, after each cleaning step the cleaning media is either routed to drain (lost CIP) or back to the storage tank for later re-use (batch CIP). Temperatures, flow rates and times are adapted to the system dimensions and the cleaning tasks. Hot cleaning regimes use hot caustic and/or hot water. In cold cleaning regimes all media have ambient temperature. Centec provide a large variety of CIP systems. They can be small and mobile single channel units, or large stationary multi-channel systems, including storage vessels of any size for cleaning media and rinse water recovery. CIP systems are designed by Centec in such a way that optimal cleaning results are ensured, with the lowest consumption of water, chemicals and energy. While one part of the plant is cleaned other areas can continue to produce product. Double seat valve technology prevents intermixing of product and cleaning media at any time.
ULTRAVIOLET (UV) LIGHT IN PHARMACEUTICALS
Ultraviolet (UV) light for the Pharmaceutical Industry
Ultraviolet (UV) light in pharmaceutical and cosmetic industries is used at several points in the water treatment process to protect materials, pipelines and products from microorganisms, residual disinfectants and organics in the water.
bestUV delivers systems designed for these special requirements, including material certificates (3.1B), FDA-approved components, special construction of the UV measurement device, and any kind of hygienic tri-clamp connection (DIN, ISO, SMS) used at the site.
These requirements pertain to:
construction of the UV reactor and quality of welds
construction of the UV measurement device
material and roughness of the UV reactor and internals
type of inlet and outlet connections
type and material of O-rings
The selected UV reactor and internals are also resistant to high CIP-temperature, resistant to CIP-chemicals and resistant to present residuals.
Examples of different UV light applications are:
disinfection (inactivate present microorganisms)
deozonation (breakdown of ozone)
dechlorination (breakdown of free chlorine)
dechloramination (breakdown of bounded chlorine)
TOC-reduction (breakdown of small organic matter)
Each application requires a specific UV dose ranging from 40 up to 1500 mJ/cm2.
PROXIMITY SWITCHES
