Larger quick release connections are rarer and can now extend to a max. diameter of 300 mm. Quick release connections too can now be implemented in line with DIN standards. However, deviations may occur depending on the manufacturer. Therefore, it is important not to define the quick release connection as an interface between suppliers but to always order these quick release connections from one supplier and adapt them to the connection pipe of the connector.
Composition of a Tri-Clamp connection:
The Tri-Clamp connection halves are usually not form fitting connections, but are provided with a groove for the moulded flat seal or O-ring seal. Due to the lack of a form fitting connection between the two connection halves, it is very difficult to assemble large quick release connections without additional assistance by one or two helpers (figure 22).
During assembly, one person holds the part to be assembled, while a second helper, if necessary, checks that the seal is sitting securely and then closes the clamp securely around the connection. When tightening, it must be ensured that the seal does not slip and is not damaged during assembly. Unfortunately, improper installation of the seal is only ascertained during production, when dust escapes through the connection or liquid leaks during cleaning.
Installation of the seal is made all the more difficult if the flat seal used is made of silicone. In this case, installation with a diameter of >200 mm is only possible if more than two people are involved, as the very flexible flat seal must repeatedly be pushed back into the position prescribed for the seal before the clamp can be secured.
A very soft and flexible seal is, however, a prerequisite for a closed and leak-tight connection. There are also PTFE (Polytetrafluorethylene - Teflon) seals with a soft core. These are easier to fit and are also not so easily damaged during installation. However, they have the disadvantage that the connection is not dust-tight or liquid-tight during cleaning. With PTFE seals, the choice of clamp must be given particular attention.
Here, two half clamps should be used, which can be tensioned on both sides with a tool in order to produce a more secure connection (figure 23).
The following must be noted for quick release connection halves:
Note: In part, the product-contact surfaces (product-contact surfaces come into direct contact with the product or the solvent to be cleaned) are Halar or PTFE coated, in order to save costs for expensive Hastelloy. Halar and PTFE are very resistant plastic surfaces (see also chapter 3 Material: stainless steel), which are applied to the stainless steel surfaces. In this case, it must be ensured that around 0.2-0.5 mm of material is applied. Sharp edges must be avoided on the connection parts and replaced with radii before application. In the end, making a coated quick release connection leak-tight is so time-consuming that there is no price advantage over Hastelloy.
When selecting the seal between the connection halves to be connected, please note the following:
The most flexible connection is a seal made of silicone, followed by EPDM (ethylene-propylene dien rubber) and Viton, which are still flexible and are also more resistant to solvents. A very high resistance to most solvents can also be achieved with a PTFE seal (polytetrafluorethylene) on flat or shaped connections. With PTFE seals, it should be ensured that the sheath is made of PTFE and the core of a flexible material (e.g. silicone), in order to achieve better tightness of the connection. For connections with an O-ring seal, O-rings coated in PEP (perfluorethylenepropylene) are often used. These also consist of a soft core and a thin FEP sheath, which is resistant to the most frequently used solvents. Another material with the best resistance to nearly all solvents is Kalretz. However, Kalretz is a very rigid sealant material and can therefore only be used in certain cases. It is also barely economical due to its high manufacturing costs.
4.2 Flexible connections
In addition to rigid connections, flexible connections are also used. Flexible connections are required for uncoupling a balance, for example, or for uncoupling moving, vibrating parts from their rigid connections. Flexible connections can be produced in a wide range of shapes and materials. However, it must be ensured that the connections to the rigid connection are either easy to undo for cleaning or are suitable for CIP in a hygienic design (chapter 4.I CIP (Cleaning in Place)). There are also different implementations for the materials. The most frequently used material is silicone. The reason for this is that it is so flexible compared with the other materials. It is therefore used for uncoupling balance. Other materials include EPDM, NBR, Viton, PTFE and Kalretz. While EPDM, NBR and Viton are still considered to be flexible and can be used for balance uncoupling in certain conditions, PTFE and Kalretz are more rigid. With PTFE, more flexible materials like silicone can be coated in a thin layer of PTFE or thin PTFE films can be used, which in turn creates a flexible connection. EPDM, NBR, Viton, PTFE and Kalretz are resistant to current solvents such as acetone and toluene.
The above-mentioned materials are available in food or FDA-compliant implementations in light quality. If the plastics come into contact with solids which have a risk of exploding dust, the plastics must have additives that make them conductive. The colour of this plastic ranges from grey to black and it is only available in a food or FDA-compliant quality with limitations. To guarantee the use of light plastics when handling critical products, the product-contact side should be made inert in a closed process with nitrogen.
Examples of different flexible connections
Collar for adaptation of the same or different containers to one connection piece.
This variant is an open pipe with a collar or tension band. Both systems shown fit flush with the connection container. With variant 1 (figure 26), a connection pipe penetrates the flexible collar. The connection is dust and water-tight.
With variant 2 (figure 27), a connection flange, which is secured to the container outlet, is pressed onto the flexible collar. This connection enables quick and easy connection of very large containers. However, it usually only has limited dust and water-tightness. Slight unevennesses on the connection flange result in small gaps through which product can escape.
Flexible collar with two connection ends (figure 28). This specially produced collar for connecting two pipes is set apart by its material offset on the connection pipe. This means the collar is nearly flush with the material in the product-contact area. The interior of the connection can therefore be cleaned more easily. The collar is secured with tension bands at the inlet and outlet. This guarantees a dust-free connection. Disadvantages: The bulge in the collar means product can become trapped in the trough.
Flexible collar with Tri-Clamp connections
This specially produced collar can be very easily integrated as an intermediate piece in a quick release connection (Tri-Clamp connection, see screw connection and quick release connection in chapter 4 Connections). The connection is CIP (Cleaning in Place) capable and is extremely hygienic due to its dead-volume-free implementation.
Flexible collar for balance uncoupling (figure 29)
When uncoupling a balance via a flexible collar, the design of the collar is crucial. The collar shown in figure 29 is distinguished on the one hand by its optimal balance uncoupling via a horizontal and vertical connection, and on the other hand by the fact that it is easy to clean.
4.3 Screw connections
In contrast to a welded connection, a screw connection is a fixed but detachable connection. This type of connection is required if it is necessary to be able to disassemble parts for maintenance and repair, or if the parts are very large and can only be brought into the room when dismantled. The parts are reassembled in the room and connected to each other via a fixed screw connection. A screw connection can also bear very high forces and torques.
Another reason for using a screw connection is the safety of the connection. In the pharmaceuticals and API area in particular, quick connections are often used for easy cleaning of the facility (see also Quick release connections in chapter 4 Connections). In many cases, a quick release connection can be opened without a tool. The operator can therefore access the inside of a container or other systems at any time. This is not always desirable and can also be hazardous if, for example, there is a moving part inside. To protect this area from undesired access, a quick connection is sometimes implemented as a screw connection at a certain position. This single screw connection is quicker to release with a tool than if the operator had to disassemble an entire flange with screw connections. The remaining connection is opened via the quick release connection.
A screw connection is therefore not a quick release connection. A tool is required to open a screw connection and close it again. A screw connection consists of two connection components that are connected with a screw, washer and nut. The classic screw connection consists of a screw specified in accordance with DIN (German industrial standard). Depending on the requirements, various strengths, lengths and designs of screw can be used. The connection is tightened by turning the screw in a thread. The thread is located either in the counterplate or in a nut. This is used if the connection is made through two fastening elements without a thread.
The following designs are suitable as sanitation connections (figure 30 to figure 33).
Figure 34 and figure 35, however, are unsuitable as they contain dead space and protruding threads, which cannot be cleaned, or can only be cleaned with difficulty.
If the screw connection is to be unscrewed rarely, it is recommended to seal the transitions from one connection part to the other with a flexible connection (figure 36), which can also be removed again.
In particular, it must be ensured that a screw connection to a pipe (square, round, rectangular pipe, etc.), does not enter the inside of the pipe. When undoing the screw connection, this would create an open system from a contaminated area within the pipe to the clean area outside the pipe. Therefore, a plate or reinforcement should be welded onto the pipe in order to be able to attach a blind hole with a thread, so that the contaminated area within the pipe remains unopened (figure 37).
It should also be ensured that the washers between the screw head and the connection plate have a flexible surface. This flexible surface seals the space inside the screw connection so that no contamination can occur here either.
5 Hoists and roller conveyors
Lifting columns have become established in the hygienic area, as alternative hoists, such as chain hoists, fork-lift trucks or caterpillars can only be encapsulated with limitation.
But there are also different designs of lifting columns. In general, all lifting columns in the external area are covered in stainless steel sheets or have stainless steel profiles.
A hygienic lifting column is distinguished by its inner guide and the sealing of the centring slide as well as the cable duct for the components to be actuated. The centring guides for the centring slide should always be inside the lifting column. Particular attention should be paid to the sealing of the centring slide on the lifting column, as this seales the lifting movement of the centring slide. The reason for this is the different variants that also protect the inner workings of a lifting column against contamination from the environment. In most cases, a plastic or stainless steel band is used as the cover, which is pulled through the back of the centring slide during the lifting movement of the lifting slide.
The design is superficially very good, but is not tight through to the inside of the lifting column. The plastic band can be removed by hand and intervention in the inside of the lifting column is possible. Nor does the cover band rule out contamination of the inner parts. A much more elegant and better design involves stainless steel cover bands or rollers, which close off the centring slide from the inside of the lifting column. These stainless steel rollers can be sealed in integrated guides, so that the lifting column can also be installed on the clean room wall.
In the event of installation in a clean room (wall installation), the back wall can be opened at the rear of the lifting column (in the services area outside the clean room) for maintenance and repair work, via quick-flange connections as on electrical switch cabinets (safety locks with special tool). This reduces the interruption to the use of the facility during maintenance work compared with the disruption caused by work that would have to be carried out inside the clean room.
General requirements: A lifting column should always be designed so that the external parts are smooth and easy to clean. The electrical cables and pneumatic tubes should be routed inside the lifting column.
It is easier to lay the cables inside the lifting column and this also ensures that the outside of the lifting column has a better design. If the cables are to be installed externally, it must be ensured that they are routed in an enclosed tube, the outer surface of which must be cleaned.
If the lifting column is set up in an area that is classified as at high risk of explosion, the closed tube must also be permitted for this area. This is an absolute requirement in accordance with ATEX (Atmosphere Explosible Directive a4/9/EC - Use of facilities in explosive environment).
External and internal surfaces: In most installations, the external surfaces of lifting columns are made of stainless steel and the inner parts are partially or totally of carbon steel. As there are moving parts inside the lifting column or an aggressive atmosphere in the environment which can cause temporary or permanent use of solvents, rust may start to form inside the lifting column. A better design is a lifting column made completely of stainless steel, even if this means a higher investment.
Part of the lifting column must not only execute a lifting movement, but must also pivot the lifting column from one to several other positions. The cover of the wheel flange must also be closed. The wheel flange is located near the floor where wet cleaning is often carried out. The wheel flange cover should be sealed to avoid the entry of spray water.
5.2 Roller conveyors
Roller conveyors are usually used as a delivery transport system or removal transport system for drums, fibre drums and other containers. A prerequisite is that the containers can be transported on rollers. A roller conveyor may also be necessary to make the operator's work easier, as they would otherwise have to transport the full and empty containers by hand. With the supply transport system, the empty containers are stacked up and moved under the filling system. In the filling position, there is usually also a short roller conveyor section. The removal transport system for the full containers buffers them before the containers are palletised. Roller conveyors are available in various implementations.
Manual roller conveyor
The simplest variant is a roller conveyor without a drive. With this type of design, the containers must be moved by hand or are transported by gravity. (The roller conveyor has a slight slope of around 5°.) With a manual roller conveyor, the facility's performance does not play a significant role. The advantage of this system is the design of the roller conveyor. It can be simple, which also makes the conveyor easier to clean. The side walls can be made of vertical plates which are connected by round tubes. The feet are also a closed square tube construction, which are sloping at the top end and closed. The roller conveyor support is designed so that the rollers are easy to remove for cleaning purposes (figure 38).
Driven roller conveyor
The other variant of the roller conveyor is the driven roller conveyor. The driven roller conveyors have the advantage over manual roller conveyors that performance is increased through the automation. However, automatic roller conveyors lose the advantage of easy cleaning. On driven roller conveyors, the walls are fitted in a sandwich construction, in order to accommodate the roller to roller drive elements in the spaces. The drive elements can be chain wheels with chains or a V-belt connection.
The V-belt connection is always preferred to the connection chain, as the V-belt does not have to be lubricated and is also easier to clean. The arrangement of the roller conveyors and their accessories depends on the task. For example, to save space, the containers can be stacked one on top of the other as shown in figure 39.
The empty containers are buffered in the top area and transported to the bottom area as required, via a lifting device, where they are then automatically brought to the filling position. If the roller conveyors are in a controlled area (in a clean room), the empty and full containers must be brought through a material lock
In the locks, there may also be an air nozzle to clean the containers before they enter the clean room. Other additional equipment includes systems for palletising the containers, as well as vacuum lifters which lift the containers via suckers and allowing an operator to then set them on pallets. A pallet robot automatically sets the cover on the container, positions the container on the pallet and wraps the entire pallet in film. A fully automatic conveyor and palletising system is only worth while with high performance rates (more than 40 barrels per hour).
6 Pneumatic conveyor system
The use of pneumatic conveyor systems requires particular attention to the cleanability of the system. As a general rule, pneumatic conveyor systems are used wherever filling or emptying of a product is not possible via gravity. This can be the case if there is only limited space above the container or process system to be filled or below the container process system to be emptied. A pneumatic conveyor system may also be used for filling a reactor during API production. On the one hand for more gentle and controlled product feeding (quantity dosing) and on the other hand, as a lock from a depressurised container emptying system to a pressurised container, in which a chemical reaction takes place. The prerequisite is that the pneumatic conveyor system can be used as a lock.
Pneumatic conveyors are distinguished into pressurised conveyors and vacuum conveyors. Vacuum conveyor are usually used to transport products up to a distance of around 50 m from the feeding station to the separator. If the delivery distance of is greater than 50 m, pressurised conveyors are usually used. These conveyor sections are less likely in API production or in drug product manufacturing and are not to be advocated due to hygienic reasons.
There are two different kinds of vacuum conveyor system that can be used. First, a vacuum conveyor with a separator, and second, a powder transport system (PTS, see chapter 4.J.11 Containment on equipment).
6.1 Vacuum conveyor with separator
Dilute-phase conveyor system
Vacuum conveyors working with the dilute phase (little product with a high volume of air) usually have large separators which contain the filter medium for separating the product before the vacuum generator (figure 40).
Due to their size and filter surfaces, these systems are only suitable for use in sanitation if they are mono-production system or if the filters are easy to change and the system easy to clean. Another weakness of this system is the separation of the product during delivery. Due to the low product load during transport and the high delivery speed, the small, light particles are delivered more quickly than the larger, heavy particles. The abrasion and mechanical stress of the product during delivery are high. For products with a low ignition energy, this can even mean that they have to be transported with nitrogen.
Cleaning of these systems is usually very time-consuming and requires high manual effort. Preliminary cleaning by means of WIP (Washing in Place) is possible.
6.2 Powder transport system (PTS)
Dense-phase conveyor system
The powder transport system (PTS, see chapter 4.J.11 Containment on equipment) is also a system that works with a vacuum. The difference between this and a conventional system is that the PTS system works with a very high vacuum. This high vacuum means the product to be conveyed is delivered in a pipe or preferably a tube system with very high loads. Due to the high load and the lower air volume, the separator only has a small filter surface. The filter used is a membrane in the diameter of the separator. At around 6-8 m/sec, the delivery speed of the PTS systems is about a quarter the speed of a normal conveyor system. This also makes it easier to deliver very sensitive products with a minimum ignition energy of <1 mJ without having to add nitrogen during delivery. Separation of the product is prevented by the dense loads during delivery.
The product is added to the containers or reactor in a nitrogen atmosphere. To this end, the product delivered in air is placed under a very high vacuum in the separator and evacuated from the oxygen. Then the separator is filled with nitrogen and the outlet flap to the reactor is opened. The advantage is that the addition of nitrogen significantly reduces the oxygen concentration in the reactor.
The system can also be cleaned with validation by integrating a CIP system (Cleaning in Place) and a liquid separator. With a comparable delivery rate, the PTS system is about half the size of a conventional delivery system.
7 Dosing systems
Dosing systems are used to empty or fill a predefined quantity. This can be a blend of different raw materials or a single dose of the same product. A dosing system is also used to create portions in smaller containers or even to empty the product into a reaction vessel.
The dosing system is fitted between the pack, container or process equipment to be emptied and the pack, container or process equipment to be filled.
There are many kinds of dosing systems. This is due to the flow behaviour of the products, which varies from free flowing to sticky and splurging. Room heights, facility offset and metering accuracy also play a role in the selection of a dosing system.
7.1 Vibration dosing device
A vibration dosing device is usually suitable for easy flowing products and granulates.
Advantage of a vibration dosing channel: There are no attachments in the dosing system. A vibration dosing device consists of a dosing pipe or dosing feeder, usually with a round inlet and outlet. The drive is located beneath the dosing system and can be a magnetic drive or a pneumatic drive, which transfers vibrations to the dosing system and thus causes the product to flow. The product flow is reduced or increased by setting different frequencies on a magnetic drive or different pressures on a pneumatic drive, which enables dosing to a predefined value.
7.2 Dosing screw
A dosing screw can convey and dose a wider range of products than a vibration dosing device. These can range from very free flowing to sticky, heavy flowing products. The reason for this is that a dosing screw is a forced delivery system. Once the product has been added to the screw workings, it is usually then also conveyed. The dosing system consists of an external pipe, a screw, sealing flange at the ends with bearing and shaft feedthrough as well as a drive. By actuating the drive via frequency regulation, the speed of the screw can be increased or reduced. The dosing screw is always cleaned manually by dismantling the dosing screw. The dosing screw can be pre-cleaned when fully installed, but dismantling is unavoidable for complete cleaning. Easier dismantling can be guaranteed through the use of quick connections.
7.3 Slite dosing gate (knife-gate).
The slite dosing gate is used as a so-called in-line dosing system. In-line means that there is no offset between the area to be emptied and the area to be filled, as with the dosing screw, for example. The products are added to the dosing gate by means of gravity. The dosing gate consists of a housing and a sliding plate, which is actuated via a drive. For example, it might be a pneumatic cylinder which opens and closes the gate. To make the system into a dosing system, the pneumatic cylinder is fitted with a position sensor. This enables the dosing control to open or close the gate in different positions. The cross-section through which the product can flow is regulated in this way and the product is dosed. When selecting a slite dosing gate, it is important to note that it does not have any dead space and is quickly dismantled for cleaning purposes.
In the case of thicky, heavy flowing products, a product supply system must be added upstream of the dosing gate. The product supply system keeps the product moving and supplies it continuously to the gate. This means a high metering accuracy can be achieved even when dosing heavy flowing products.
7.4 Flexidos dosing system
The Flexidos dosing system, like the site dosing gate, is an in-line dosing system but with a dosing slit in the product-contact area. This dosing slit is opened externally by two synchronously controlled dosing pusher. A closing spring in the dosing system pulls the dosing slit together again after the dosing pusher have released the dosing system. The dosing pusher are moved by the dosing control and open the dosing slit according to the dosing output and accuracy. With the Flexidos dosing system, the slowest flowing products can be dosed with maximum accuracy <1g. The dosing system is easy to change and clean. As with the dosing gate, the Flexidos also needs a product supply system for heavy flowing products.
7.5 Transbatch feeder
The transbatch feeder is a combination of pneumatic convegor system and a vibration dosing device. The pneumatic conveyor sucks the product into the separator which is attached to the vibration dosing device. The vibration dosing device conveys the product, which has been loosened by the pneumatic conveyor, into the pack or container to be dosed.
8 Platforms and stands
Stands or platforms are required for the implementation, operation and maintenance a solids system. The stands hold adapters or components. The platforms make it easier for the operator or service staff to access the facilities. Here too, hygienic design is important.
The following points should be taken into account when designing a platform:
There should be spacer bolts between the square pipe or round pipe construction and the stud plate surface (figure 42) so that the space between can be more easily cleaned.
If the stud plate surface is welded directly onto the substructure, (figure 43), it must be guaranteed that the stud plate is welded right through. If this is not possible, due to excess warping of the platforms due to the long welds, the spaces between the individual welding seams must be filled with a flexible stainless steel jointing medium. The thread ends on screw connections on the substructure should also be sealed with a cover nut.
The question of which profile to choose for stands and the substructure of platforms cannot be answered in general. Round pipes certainly have an advantage in terms of cleaning. However, they are more costly to manufacture. When using square pipes, there is more available horizontal bearing surface on which the product or dust can be deposited, but this surface is too small to justify the higher costs of a round pipe construction. A cleanly processed stand or the substructure of a frame produced from square piping is in any case suitable for installation in a controlled area (figure 44).
What has to be avoided in all events is open profiles such as U-tubes or similar.
Sloping covers (figure 45) should be used. On the one hand, this makes the surfaces easier to inspect for impurities, if they are in an elevated position. On the other hand, the cleaning fluid can flow off more easily.
9 Clean room installations
For clean room installations, attention should be paid not only to the product-contact surfaces, but also to the overall design of the external parts. The surfaces in the clean room must be easy to clean not only on the product side, but also on the external surfaces. In order to enable cleaning of the exterior, the surfaces, cable ducts and attachments should be designed specifically.
9.1 Rail design
Example 1 (figure 46 and figure 47): Rails attached to a Pharma Terrazzo.
Example 2 (figure 48 and figure 49): Rails integrated in the hexagon tiled floor
Both systems initially appear to be hygienic implementations. The difference between the two systems is the implementation and attachment of the rails. In example 1, the rails are attached to the floor and screwed down. This is initially a very attractive, cost-effective and quick solution. In practice, however, the connection at the transition from the rail to the flooring will rip and contamination will build up in the chinks, thus increasing the gaps. After a foreseeable amount of time, there will be a GMP deficiency, which can only be improved with great difficulty. A further disadvantage is the greater risk of tripping.
The best solution is example 2. Here, a special rail design is integrated in the floor, before the hexagonal tiles are laid. The profile is integrated flush with the surface, making a semicircular sphere with the neighbouring flooring. This shape is optimal as a track for the carriage and is also easy to clean due to its geometric shape.
The disadvantage is that the installation costs are higher than with the first example. But the follow-up costs for maintenance and repair are much lower.
The choice of hexagonal tiles was also a good decision, as the tiles are more robust and durable and still look like new after ten years.
9.2 Control panels
If possible, installation flush with the surface of the clean room wall is always recommended (figure 50).
Installation of the control panel with the front flush with the wall means there are no surfaces as shown in figure 51 which require cleaning. In addition, the operating keypad has no surfaces on which anything can be deposited. The cables to the operating panel should in any case be routed and laid within the clean room wall (sandwich construction) so that no additional pipes for cable ducts are required in the clean room.
9.3 Cable ducts
Cables are required in a clean room to control valves, motors, sensor, etc. Flexible lines are also required for compressed air-operated facility components. Most errors are made when laying the connections or if, for cost reasons, clean room compliant installation is not used.
As shown in figure 52, cables or pneumatic tubes are bundled together here via cable ties and openly laid in the grating channels or half open in pipes. This has the disadvantage that the external parts cannot be cleaned. Product dust which collects between the tubes is difficult to remove through manual separation of the tubes or cables. The half open routing of cables and tubes (necessary to hold tubes or cables over a long distance) in open pipes increases the cleaning problem for facility components. If unavoidable, such cable ducts should be laid vertically and the ends should be sealed after the cables have been laid. As shown in figure 52 , the pipes are laid horizontally, which leads to a GMP deficiency. Product dust, which can rarely be avoided when handling solids, collects in the pipes. The external surfaces of the pipes can be cleaned, but the impurities remain in the pipe.
A closed cable system should always be used in clean room installations or in controlled rooms. This type of system contains the cable duct within closed square pipes used as mounting stands or in round pipes that are only used for holding cables. The design of the overall facility must be thought out in detail, as the openings at the cable inlets and outlets must be taken into account and provided for in the detailed design (figure 53 to figure 55).
The cables to the consumer should take the shortest route from the cable outlet to the consumer (around 300-400 mm). The cables should also exit the pipe via individual connections, so that each cable can be cleaned independently. The cable outlet is also the entrance from the black area to the white area in the clean room and, accordingly, must be leak-tight. Therefore, the cable feed into the pipe should be implemented with a closed system such as a PG screw fitting for cables or a quick screw fitting for hoses.
In any case, pneumatic boxes with the valves should be set up outside the clean room and the hoses then routed into the clean room bundled together and enclosed.
Compressed air should never be blown out in the clean rooms through quick ventilation valves on installed pneumatic cylinders. The air should be routed out of the clean room to the services area.