GEA Courtoy MODUL™ rotary tablet press
Today’s tablet production operations are faced with two increasingly important – but at first sight contradictory - demands: being able to handle more potent drugs, while the overall production costs must be reduced. At the same time, batch sizes become smaller and production planning must allow more flexibility.
There are technologies and procedures to tackle each of the above requirements individually, but no solution existed to answer all of these requirements simultaneously – until now. The concept of “Exchangeable Functional Module” – as integrated in Courtoy’s new MODUL™ tablet press – brings the solution.
This article describes how the EFM concept has been applied to a novel rotary tablet press, how it can be applied to its peripheral equipment and explores the consequences.
Increasing demands on pharmaceutical tableting operations
It is clear that increasing pressure from governments on health care costs, increasing
competition from generic manufacturers and increasing research & development expenses,
are forcing pharmaceutical companies to review their organisation and cut costs in all fields. In
consequence, we see the continuous mergers and take-overs, aiming to consolidate the
enormous R&D costs and increase efficiency in manufacture and distribution of their pharmaceutical products.
Tableting facilities are being closed and tablet production operations are concentrated in a few
plants, striving for the ultimate efficiency. These plants must be able to handle higher volumes of more variant – and more potent –products, in smaller batch sizes. At the same time, stocks
and lead-time must decrease, while reactivity to market demands must increase. All these demands can be grouped into 3 main areas of concern:
- Total Cost of Ownership (TCO) of the production plant, i.e. the total overall cost
per produced unit.
- Flexibility allowing to react quickly to external factors, such as sudden market
opportunities
- Containment of potent drugs for maximum operator safety and environmental protection.
The TCO approach is increasingly used by pharmaceutical manufacturers when selecting
new equipment, because it considers the real total cost of operating process equipment per
unit of production. This total unit cost is the only correct basis for comparison. It does not only
consider the capital investment for the equipment, but also:
- its overall productivity, based on the downtime of the machine for cleaning, product change over, maintenance and repair
- product losses
- the cost for spare parts and maintenance work
- the space required for installation and operation
- the manpower required to run the equipment
- energy and utilities consumption
It seems that very often the cost of space (clean room, air conditioning, cleaning, etc.) is underestimated, while it is sometimes higher than the cost of personnel. Therefore the use of
smaller or fewer clean rooms is important.
The answer to the increasing demands: the Exchangeable Functional Module
Considering these 3 main challenges – TCO, flexibility and containment – individually, one
would prioritise different aspects:
- for minimal TCO: a machine with a very high instantaneous output and with minimal downtime. Minimal downtime means here high reliability and very quick cleaning.
- for maximal flexibility: a machine that is extremely easy and fast to change over from product A to product B, with minimal risk for cross-contamination.
- for maximal containment: a machine which is completely isolated and sealed, with the necessary provisions for cleaning and replacement of format parts in a safe way for operator and environment.
Searching for a way to combine the solution to all three aspects in one, the concept of the
Exchangeable Functional Module was born. In fact, an EFM should:
- contain all product specific format parts;
- contain all product contacting parts;
- be isolated from the remainder of the machine;
- be extremely easy and fast to remove from/install in, the machine.
By using various – eventually product dedicated - EFMs on one machine, one will achieve very
quick product change over and product containment simultaneously when replacing a used & dirty EFM by a another prepared & clean EFM. The fact of removing all product contaminated parts from the machine in an isolated way, eliminates all cleaning operations from the machine. The cleaning problem is now completely off line – not influencing the machine’s downtime - and can be done in a dedicated area, with dedicated cleaning equipment. This dedicated area and the cleaning equipment, like an automatic washing station, can be shared among many machines using interchangeable EFMs. Once the definition for the EFM determined, it is easy to evaluate its applicability to various types of equipment.
The concept of EFM applied to a tablet press: the Modul™
The concept of EFM has been developed and integrated by Courtoy when designing the new
Modul™ rotary tablet press. This was particularly straightforward as on a rotary press, all product contact parts and product format parts are concentrated around the central part of the
machine: the turret or die table.
In fact, the turret with punches and dies, powder feeder, scraper and ejection finger, dust
extraction nozzles and tablet chute are all integrated in one isolated box, named the “Exchangeable Compression Module” or ECM. The ECM is removed from the machine as one
complete, isolated unit in less then 15 minutes. Installing an ECM takes also 15 minutes,
resulting in a complete machine change over of maximum 30 minutes. The complete ECM exchange procedure can be done by one operator, as most operations are handled by the machine’s control system. Minimising operator interventions reduces also human errors. Furthermore, the use of an isolated ECM eliminates the use of covers inside the machine to prevent dust from entering into the mechanics. This improves very much the visibility, accessibility and maintainability of the equipment.
The concept of EFM applied to the peripheral equipment
It is clear that the use of EFM technology on the tablet press brings advantages in productivity,
flexibility and containment. However the full advantage of the EFM concept can only be realised when the peripheral equipment of the tablet press also has extremely fast changeover,
flexibility and containment. In fact, as long as standard peripheral equipment is used in the
standard way, the time necessary to clean these peripherals as well as the clean room will still determine the total down time. There are three alternative solutions to this problem:
Alternative 1: duplicate the peripherals in two separate clean rooms
Peripheral equipment is standard but duplicated and set up in 2 separate clean rooms. At product changeover, the ECM of the tablet press is disconnected from:
- the tablet deduster, integrated with metal checker and eventually tablet distribution
system
- the sampling unit for on-line tablet analysis
- the dust extraction unit
and removed from the press. The clean ECM is installed and connected to the peripherals located in the adjacent room. The tableting process can restart, after which the equipment
in the first room is being cleaned. The tablet press can be located in a grey area. This allows
one big clean room to be replaced by two smaller ones.
Alternative 2: integrate the peripheral
Equipment in an isolated box - All peripherals are still duplicated, but are now
integrated in a dust tight transparent “box”. The level of isolation of this “box” depends on the
required level of containment. This can range from a “dust tight” box up to a high containment
isolator. Peripheral equipment becomes more complex, but tableting is now fully isolated, eliminating the need for a clean room. The complete tablet production operation can take place in a grey zone.
Alternative 3: apply the EFM concept to peripheral equipment
Only the EFM parts of the peripheral units need to be duplicated. This saves space and equipment compared to the previous solutions. Moreover, the EFM concept is easily applicable
to the metal checker and tablet diverter gate. With the metal checker, the product goes through a closed tube, which runs through a magnetic field. Removing and exchanging this tube in an isolated way is simple.
The application of the EFM concept to a tablet deduster is more complicated, but is simple
compared to the ECM on the tablet press. In fact the EFM of the tablet deduster has 5 identified
connections to the environment:
- tablet inlet
- tablet outlet
- air inlet for dedusting
- air/dust extraction outlet
- drive axis for vibratory action
Only the last interface is between the EFM and the machine base, making the interface and
disconnect/connect design straight forward.
Alternatives 2 and 3 achieve the ultimate goal of producing tablets in grey zones, eliminating
completely the need for clean rooms. This would result in a serious cost saving for both building design and construction.
Contained disconnects on the EFMs
When using various pieces of equipment in line, each using EFM technology, an important issue is to guarantee product containment. A high level of product containment is important for
processing high potency drugs and when working in a grey zone environment. Product containment needs to be maintained, not only during production but also during the disconnecting and removing of the different EFMs.
Today there are a number of solutions available on the market allowing a contained disconnection (i.e. a disconnection with minimal product loss).
- Split valve technology: a split butterfly valve, split ball valve or split piston valve. These
valves consist of two separate halves, each having a mating part. The two halves are
connected together so the surfaces of the mating parts that would otherwise be open to
the atmosphere are sealed to each other. This is to avoid these surfaces becoming contaminated by the product while the valve is open. The valve is opened by turning or sliding the connected mating parts, like a one-piece mechanism. When the valve is
closed again, the two mating parts can be disconnected, exposing the sealed noncontaminated surfaces to the environment.
- RTP technology or Rapid Transfer Port / Alpha-Beta ports. This system uses the same concept as the split valve, but is typically bigger. This type of valve is primarily used for transfer of parts rather than product feed.
- Heat sealing and cutting of plastic lay flat tubing. When plastic tubing like PE or PVC is
used, heat sealing, with electrical resistance threads or RF welding, can be used to close the tube. By cutting across the seal, or between two seals close to each other, a
contained disconnection is possible.
- Strapping and cutting of flexible tubing. When flexible tubing is used, a variety of systems such as plastic cable ties, steel bands, twisted wires or adhesive tape can be used to close the tube. By cutting across the strap or between two straps close to each other, a contained disconnection is possible.
Various solutions do exist. The optimal technology depends on the required level of containment. It should be clear that the effective OEL will also depend on the product
characteristics and the standard operating procedures.
Cleaning of the ECM
The EFM concept removes the cleaning process from the equipment, reducing its downtime and increasing its flexibility considerably. A WIP or CIP process on the equipment not
recommended as the time necessary for prerinse, washing, drying and cooling take takes
several hours. There are various alternatives for off-line cleaning depending on the level of containment required.
Manual cleaning in a washing booth or in a down flow booth
Once the ECM is removed from the press and installed on its dedicated trolley it can be moved
to a washing area, where it is opened and cleaned manually. Such washing areas exist in
all plants. The well-known ‘Courtoy Fast Change Over’ design of the ECM minimises the time and resources needed for such manual cleaning. This cleaning procedure can be performed
under a down flow booth for limited operator protection.
Manual cleaning after a WIP cycle
To accelerate the cleaning process and reduce the operator exposure to the product, a WIP
system is available on the ECM. In this case, the ECM is equipped with various spray nozzles
inside and a water drain via the tablet chute. Final cleaning and change over is still done
manually after opening the ECM.
Manual cleaning in an isolator
When processing high potency drugs, the ECM trolley can be equipped with an isolator, which is closed after putting the ECM on the trolley. The isolated unit is then transferred to a dedicated area. A washing booth is connected to the ECM isolator and the ECM opened manually through glove ports. Removable parts such as punches & dies, feeder, scrapers and dust extraction
nozzles are transferred to the washing booth for cleaning.
A cleaning liquid hose and drying air can be supplied from the washing booth into the ECM
isolator. The complete cleaning procedure is now performed in a contained and isolated
environment.
Manual cleaning after opening the ECM submerged in a liquid
An alternative to the above WIP and isolator is to submerge the ECM in a cleaning liquid
allowing the liquid to enter the ECM. The ECM is then completely filled with the cleaning liquid,
requiring all parts to be stainless. After this, the ECM can either be removed from the bath again, allowing the ECM to drain before opening and cleaning. Or the ECM is opened and cleaned while it remains submerged in the liquid bath.
Automatic CIP in a washing station or on a special internal washing machine
Finally, the most automated solution is to transfer the ECM into a closed washing machine
or onto a CIP skit. The first system encloses the ECM completely, will open it automatically and clean both the inside and the outside of the ECM. The second system requires spray nozzles and a drain to be integrated in the ECM, which are then connected to a CIP service skit.
Both solutions will need to overcome the problem of retracting the lower punches from the
dies for fully automatic washing: as there is only a few hundredths of a millimetre gap between
punch tip and die wall, powder trapped and compacted there can never be cleaned away
unless the punch tip is retracted from the die and intense cleaning is performed inside the die.
This particular problem is the reason why there is no real – meaning fully automated and fully
contained – CIP system available on any existing tablet press. The press will always need to be opened to remove the punches (or punch tips) and dies prior to final cleaning, breaking the
containment and requiring a manual operator action.
Conclusion
The “Exchangeable Functional Module” concept opens many perspectives for various types of
equipment. EFM technology will, undoubtedly, show up more and more in future process
equipment design as it offers an answer to the increasingly important requirements put on
production facilities: reduce cost, increase flexibility and product containment.
The EFM concept has been applied successfully to a novel rotary tablet press and can easily be applied to the peripheral equipment. The preferred method for off-line cleaning depends on the specific product portfolio to be manufactured.
MODUL™ – A new philosophy in tablet production.