A. CIP stands for ‘Cleaning In Place’ and is widely used in all types of process industries. It has been developed from the requirement that process industry plant must be used efficiently to gain maximum cost benefits. CIP covers a variety of areas but its main purpose is to remove solids and bacteria from vessels and pipework in the food and drinks processing industries.
The task of dismantling process plant for cleaning is time consuming and where tank entry is required, it becomes dangerous if it were feasible at all. CIP allows process plant and pipework to be cleaned between process runs without the requirement to dismantle or enter the equipment. It can be carried out with automated or manual systems and is a reliable and repeatable process that meets the stringent hygiene regulations especially prevalent in the food, drink and pharmaceutical industries.
The majority of cleaning and sterilizing liquids used in CIP systems are alkali or acid based and the CIP system will allow accurate dosing of the concentrated cleaning agent, normally into water, to give a low strength solution suitable for cleaning process plant. This solution is then used within the plant to clean and if necessary sterilize the system prior to the next production run.
A. Cleaning In Place has many benefits to the end user, some of the main reasons for implementing Cleaning In Place are :
- Safety operators are not required to enter plant to clean it
- Difficult to access areas can be cleaned
- Production down time between product runs is minimised
- Cleaning costs can be reduced substantially by recycling cleaning solutions
- Water consumption is reduced as cleaning cycles are designed to use the optimum quantity of water
- The cleaning system can be fully automated therefore reducing labour requirements
- Automated CIP systems can give guaranteed and repeatable quality assurance
- Automated CIP systems can provide full data logging for quality assurance requirements
- Hazardous cleaning materials do not need to be handled by operators
- Use of cleaning materials is more effectively controlled using a CIP system
A. Single Pass Systems
In a single pass system new cleaning solution is introduced to the plant to be cleaned and then disposed to drain. In most cases a single pass system would start with a pre-rinse to remove as much soiling as possible. The detergent clean and a final rinse would follow this.
In a recirculation system the cleaning solution is made up in an external tank then introduced to the plant to be cleaned. It is recirculated and topped up as required until the cleaning cycle is complete. When the detergent clean is complete it is then normal to carry out a final rinse.
In general recirculation systems use less water & cleaning detergents but require greater capital outlay and in some circumstances may be unsuitable due to cross contamination from one process to another. We can if required calculate usage for these types compared to an existing system to demonstrate potential cost savings and pay back periods.
A. With this information cleaning heads can be selected to meet the requirements described above. This then allows pumps to be selected to match the flow rates required for the heads and the type of cleaning material being used. The module size and configuration can also be calculated from this information.
The first design consideration for a Cleaning In Place system is the cleaning requirement for each process vessel. Factors to be considered can include the size of the process vessels; standard of cleaning required, the available cleaning time, the type of cleaning medium, and whether recycled detergent can be used.
The process diagram below shows an example of a three-tank Cleaning In Place system. There are three holding tanks, which are mounted in a stainless steel band. The tanks are normally a bulk caustic tank, dilute detergent tank and fresh water tank. The capacity of each tank is calculated according to the initial system requirements described above. In the case of the bulk cleaning liquid tank the customer may also specify the tank size to suit optimum delivery quantities. Bulk cleaning liquid is normally delivered to a connection point outside the process plant and pumped to the storage tank by the delivery vehicle. Heating can be specified for the bulk cleaning liquid tank depending on the properties of the cleaning agent. Lagging and cladding can also be fitted for improved energy efficiency.
The bulk cleaning liquid is pumped to the detergent tank before each cleaning cycle along with water to make up a batch of detergent. The detergent is normally more effective at a higher temperature. If this is the case it would then be pumped through a plate heat exchanger to bring it to the required temperature.
The system shown allows the detergent to be recirculated through the heat exchanger until it reaches the optimum temperature. The heat exchanger would be designed to suit the temperature drop in a recirculation system.
The strength of the cleaning detergent is normally stated as a percentage of the cleaning agent being used (usually with water). In the majority of cases this is between 1 and 10% by volume. There are various methods of achieving the required strength but the two main methods are a) using a positive discharge pump shown in the diagram for a calculated time and b) using a conductivity probe to read the strength of the detergent (this is only effective with alkalis, not acids). The conductivity probe is located in the recirculation/scavenge line.
When the detergent is ready for use the process vessel to be cleaned is selected and the system will run through a cleaning cycle. A pre rinse will be carried out first using water from the rinse water tank. The detergent will then be cycled through the process system before being returned to the detergent tank. A final rinse will then be carried out again using water from the rinse water tank.
Depending on customer requirements this detergent can then be re-used, bulk cleaning liquid being added as necessary to maintain the required cleaning strength by use of the previously mentioned conductivity probe. It may be undesirable in some cases to re-use detergent in another part of the process system due to cross contamination. If this were the case the detergent would be dumped to drain after use. If it is not practical to discharge the detergent to drain as an alkali/acid then we can install a system to neutralise the solution.
If the CIP system is being used to clean a number of vessels as shown in the diagram below then to safeguard the vessels/plant not being cleaned it is necessary to have a safe valve or similar system. The double seat (block and bleed) valves shown have a chamber between two valve seats. When the valve is open liquid will flow through. When it is closed the chamber between the two valve seats has an open part so that any cleaning liquid passing through the inlet seat will drain out of the chamber and cannot cause contamination at the outlet side of the valve.
Another method of ensuring that there is no contamination of other process lines during cleaning is to use a swing bend flow plate system where a direct connection is made from the CIP feed to the pipeline feeding the process plant to be cleaned. Proximity switches may be used with the swing bend to ensure that the correct path is selected before valves can be opened and cleaning started.
A. The control of Cleaning In Place systems can vary from simple manual operation to fully integrated PLC controls with touch screen operator interfaces. The design of the control system will vary according to the process being cleaned and the customers’ requirements.
A. There are a variety of different spray devices available the selection of which is dependant on a variety of factors including capital and running costs, supply pressure, cleaning time, vessel size, spray type and soil type. Some of the most common are listed below.
Fixed spray balls are low cost, low maintenance. They operate at low pressure (2 bar) but use high volumes of water. Cleaning times are long and range tends to be about 2 – 3 metres. These items have a fixed spray pattern and are not really suitable when the vessel is badly soiled or has material baked on.
Rotary cleaning heads are higher cost than spray balls. They operate at higher pressure but use a lower volume of water. They are normally more effective over shorter periods so reducing down time of plant and lowering detergent costs. They can be supplied with a variety of different spray patterns, some of the common ones are shown in the diagram to the right.
Rotary Cleaning Heads For Larger Vessels
These heads are high-pressure units, with directional jets offering fast cleaning times. Higher capital costs are involved but fully indexed coverage at long range using low volumes of water and detergent will compensate for this.
This Diagram shows some of the common spray patterns available. There are many more patterns to suit individual requirements and in the case of Large Rotary Cleaning Heads specific areas of the vessel can be avoided if necessary.
The illustrations above cover cleaning heads, which may be used on most projects, but there are applications where specific cleaning requirements mean more specialist heads.
Sterilization In Place (SIP)
A. When process equipment reaches commercial-scale proportions, the sterilization of essential units by autoclaving becomes impractical and some means of sterilizing the equipment in situ is needed. Such installations, in order to comply with cGMP, must be design, installation, and operationally qualified
(DQ, IQ, and OQ) and the sterilization process must be validated. So, here is a short introduction to the Sterilization In Place (SIP) validation procedure.
A. A Sterilization In Place (SIP) installation will usually comprise one or more pieces of processing equipment, such as a fermentor and a centrifugal separator to handle harvests, connected by rigid stainless steel or flexible Teflon®-lined piping. The installation will be capable of withstanding steam pressure up to, say, 20 psi and corresponding sterilizing temperatures in the 121° to 125°C range. There will be a supply of steam suitable for the procedure, under pressure control, and a “trapped” drain at a low point on the system, which will pass condensed water, but not steam. The safe operation of the installation will be controlled by suitable safety valves or “burst disks”.
Design qualification of a SIP installation will require confirmation that the process equipment, pipe work, and steam supply equipment meet preset specifications for materials and for pressure and temperature resistance. Attention must be paid to the quality of the steam, which will be used. This usually means that the steam is generated in a dedicated “clean-steam” generator. The steam may also pass a micro-filter before use. The cleanliness of the steam must be maintained by the use of pressure-grade stainless steel or Teflon®-lined tubing and suitably constructed pressure control and shut-off valves and pressure gauges.
Other design aspects of the equipment intended for SIP will include ensuring that the steam can reach all parts of the equipment in contact with product and that air is not trapped in the plant during sterilization. There must also be a means for the easy clearance of condensate during the heating process, through the steam trap. Finally, temperature sensors must be sited where they will represent reliably the state of the equipment during the sterilization cycle. Often, the most favored point for temperature measurement is at the condensate drain, since this will be the last area to reach operating temperature. However, there may be good reasons for siting thermo-sensors in difficult-to-reach areas of the plant.
Installation qualification of a well-designed SIP system will involve confirming the proper installation of the process equipment and correct siting and connections for all pipe work, including ensuring that proper condensate drainage can occur. All required services and monitoring devices should be in place. Operational qualification starts with the start-up of the steam generation set-up and confirmation that correct pressure and steam volume is achieved. The sterilizing cycle is then run. Steam under pressure is passed through the entire installation while allowing the escape of air through properly placed vents in the piping or on the equipment. These vents are usually protected by steam-resistant bacterial filters. After a suitable period of steaming, the air vents are closed and steam pressure is allowed to build to the required level. Pressure is maintained during a preset period, then the steam is released through a condenser. Temperature sensors in the system should indicate that the recorded pressure resulted in the required temperature being reached for sufficient time to ensure destruction of all contaminants. Cooling down of the equipment requires that air be allowed to pass back into the system through one or more of the sterilizing filters on the vents, to prevent the development of a vacuum.
Validation of the system operations will require the use of chemical and biological indicators, which should be placed in sections of the plant determined to be difficult to free of air, and near the condensate drain. The prescribed sterilization cycle should always yield sterile indicators. The process can be challenged by “worst-case” conditions, such as a reduction in sterilization period or steam pressure. Eventually, a set of operating conditions, which have been shown to produce sterile plant reproducibly, can be adopted as the validated process. Minimum and maximum limits on the steam pressure, indicated temperature, and exposure time will be set. If appropriate, the final evidence of the validity of the sterilization process may be achieved by running culture medium through the sterilized set up in imitation of the manufacturing processes and then incubating a large number of media samples, or the entire batch, to ensure no bacterial growth occurs. In any event, the regular manufacture of product batches, which pass sterility and endotoxin tests after processing in the SIP plant, will confirm PQ of the system. These records, however, will not substitute for proper SIP process validation.
Like all validation procedures, the DQ, IQ, and OQ of the system, as well as the validation run parameters and test results must be fully documented. Measurement devices must be properly calibrated in reference to an accepted standard. If sections of the plant are rebuilt or changed, the entire SIP set up must be revalidated. Given the critical nature of the SIP procedure, it is probably a good idea to schedule revalidation of the installation at regular intervals anyway.
A. Design Qualification (DQ)
This qualification verifies that the rigorous specifications and design review methods defined in the Quality Management System of the manufacturer have been followed.
Installation Qualification (IQ)
This qualification is performed at the site and time of installation. It documents that all key aspects of the installation comply with the manufacturer’s specifications, codes, safety and design parameters.
Operation Qualification (OQ)
This qualification is performed subsequent to installation and is repeated at certain intervals recommended by the manufacturer or defined by the customer. It documents that all modules of the equipment perform consistently throughout the specified operating ranges.
Performance Qualification (PQ)
This qualification is performed to ascertain that the instrument (system) is suitable to perform a specific analytical task. It can thus only be performed by the user himself who has to create the test procedure (PQ SOP) based on the analytical task, the CAMAG OQ procedure and the different instrument manuals. SOP – Standard Operating Procedure
CAMAG is a Swiss company, which is certified by SQS – The Swiss Association for Quality and Management Systems to meet the requirements of the international standard for quality management and quality assurance (ISO 9001) and has been awarded SQS Certificate ISO 9001: 1994.