The first Rapid Transfer Port (RTP) system was developed in France in the 1960s under licence from the CEA (Commissariat à l’énergie atomique et aux énergies alternatives) as part of a range of transfer and manipulation tools designed for working in the contained environments of the nuclear industry. It was named Double Porte pour Transfert Étanche or DPTE, i.e. Double Door for Leaktight Transfer.
The DPTE system that links two volumes is based on the interaction of two distinct parts (see Figure 1). The Alpha part, which is fixed to the surface of a chamber (e.g. the wall of an isolator or RABS), consists of a door (the Alpha door), a flange and a lip seal. The Beta part, which is attached to a container, isolator, or other suitable chamber, is the mobile part, consisting of a door (the Beta door), a lip seal and a unit made up of a flange and container.
The system was initially utilised in the nuclear industry for secure transfer of extremely toxic radioactive substances such as plutonium. In the 1980s, the pharmaceutical industry took an interest in the potential of this safe and leak-tight bidirectional transfer system. The DPTE system then found applications in a number of other industries where leaktight secure transfer of sterile and/or toxic material is a crucial issue, such as food and cosmetics. The system continued to develop (DPTE-S, DPTE-XS models) to comply with changing regulations, technological progress and the demands of the market.
Since its creation, this double door system has been recognised as the most effective industry standard for transfer systems; its design has inspired numerous other transfer systems that claim to be reliable alternatives to the DPTE system. La Calhène, the manufacturer of the DPTE system, has looked at the limitations of the concept at the heart of RTP systems (including the DPTE) based on 40 years of experience in isolator technology and on the results of a test programme that compared the DPTE with five other RTP systems for leaktightness, security and ergonomics.1
The study examined the DPTE and five standard secured transfer systems supplied to the nuclear and pharma markets. The systems were subjected to a series of tests designed to check their performances regarding five crucial aspects of any transfer operation in the pharmaceutical area.
1. Locking torque – This test compared the friction resistance of the connection to check whether the port could be connected and disconnected easily by a typical operator. Measured resistance varied from 10 Nm to 100 Nm, with the DPTE port requiring 16 Nm force to connect. One of the ports tested had non-rotating connection.
2. Leaktightness – Maintaining containment is vital to a transfer from one volume to another similar volume. The four assemblies comprising each transfer port – Alpha part; Beta part; Interface between the flanges; and Interface between the doors – were tested using a 1% concentration of NH3 and a revealing cloth. The test procedure did not quantify a leak rate. Only the DPTE and one other port displayed no leaks at 1000 Pa, while one port could not be tested at the Beta part level or at the doors interface, since the Beta part could not be opened.
3. Security operation – Several safety devices must feature on transfer systems to prevent accidental rupture of containment.
a) The Alpha part must open only when the Beta part is present.
b) Disconnection of the Beta part must not be possible once both Alpha and Beta doors are open.
c) The Alpha part must open only when the entire Beta unit is present; if the Alpha part can open when only the Beta flange is connected, there is a danger of exposing a sterile volume (e.g. isolator) to a non-sterile environment.
All the systems complied with test a). The DPTE and one other port performed correctly on all the tests. In one case, the system failed on tests b) and c).
4. Multiple connections – This test aimed to evaluate how robust the systems were by checking if they could be connected and disconnected 10 times, after which tests 1–3 were repeated. Although five of the six units could be reconnected several times, in three cases there was evidence of leaks at the first connection. Only two ports demonstrated that multiple connections (up to 10) had no impact on the system.
5. Ergonomics – The ergonomics test consisted of an evaluation of the ease of positioning, connection, disconnection, rotation and procedure. No formal test was done in this area of study so the results are based on observations noted by users who manipulated these systems as required by the test programme.
No serious ergonomics issues were noted, all the operating procedures being relatively straightforward and quick to implement. But any operation, however simple, can quickly become critical if it is repetitive and monotonous. Hence two points for improvement were identified:
- Most of the systems require the Beta part to be rotated for connection. This can be hard in the case of Beta parts that are heavy and/or cumbersome, and when the rotation requires substantial torque.
- In two of the six transfer systems examined, the manual control required to connect the Alpha and Beta parts was found difficult to operate, mainly due to its shape. This could be all the more problematic since in a real-life situation this operation has to be done via a manipulation system (glove or glove port).
To summarise, half the RTPs tested did not achieve adequate performance in the leaktightness tests, demonstrating a risk of leakage that could compromise the basic premise of sterile transfer. In a few cases the RTPs tested did not meet the requisite security levels since the Alpha port could be opened when the Beta door was not in fact connected (only the Beta flange was present). None demonstrated compatibility with the DPTE system. In view of these limitations, it is clear that the DPTE system – and RTP systems in general – need to evolve to find solutions for today’s trends in the pharmaceutical industry:
- Increasing productivity targets with consequent rises in production throughput and hence in transfer operations
- More stringent security requirements, both for the transfer port user and for the transfer itself
- Greater emphasis on ergonomics, driven by the evolution of labour legislation around the world to protect operators from musculoskeletal disorders.
Ergonomic interconnection principle
Many of the RTP systems on the market, including the DPTE, require that the Beta part rotates when it is connected or disconnected from the Alpha part. In some cases the Beta part also has to be presented to the Alpha part in a certain position, for the connection to take place.
These limitations, i.e. manual manipulation of the Beta part together with the rotating movement required for connection/disconnection, are problematic in terms of ergonomics2 since the DPTE alpha ports are in some cases positioned on the upper section of filling line isolators, which can make it dangerous for operators transferring components. Furthermore, various types of components cannot be transferred by this method, e.g. fragile components such as vials.
Adequate safety
Most RTP systems (the DPTE included) contain safety devices to reduce the risk of accidental manipulation breaking containment during connection and disconnection. These devices function as follows:
- By preventing the Alpha door from opening if the Beta part is not in position, is incorrectly equipped or incomplete;
- By preventing the two chambers from separating if the unit consisting of the two doors fastened together is open and transfer is not completely finalised.
These devices do help to lower the risk to an acceptable level for the majority of applications, without eliminating it completely. But for applications such as stopper transfer, aseptic liquid transfer, EM transfer, aseptic change parts transfer, and even waste transfer, sterile or potent powder transfer, any risk, however minimal, is unacceptable. Indeed, the consequences of a leak in such situations can be dire for the safety of the operators or simply for the economics of rejecting a production batch.
Manual manipulation for sterile transfer via DPTE system (view inside isolator)
The risk of human error occurring during transfer is proportional to the number of manual operations required, and the use of RTPs generally entails a series of manual interventions.
After positioning and connecting the Beta part to the Alpha part, the user actuates the opening and closure of the double door unit from the inside of the isolator (or other chamber) where the alpha part is fixed.
A manipulation system is installed for this purpose, but there is clearly an ergonomics issue here. This gives rise to an additional risk of leakage and hence potential contamination of the protected process and/or the environment and user. Additional security devices would be welcomed.
In conclusion, even though the DPTE transfer system is a proven solution for leaktight transfers with 33,000 Alpha doors currently in operation globally, a number of improvements are expected by the pharmaceutical industry. Attempts to provide answers by RTP manufacturers have failed to meet ever-evolving and increasingly demanding requirements. The remedies implemented are often only partially beneficial; they are frequently complex and inconvenient in terms of maintenance, cleanability and bulk. The industry is still waiting for answers.
DPTE and DPTE-BetaBag are registered trademarks of Getinge-La Calhène.
Authors
Chloé Guilmet, Innovation Manager; Anneke Evers, Sales Manager Europe – DPTE/SP; Thierry Girard, CEO; David Milligan, Director of Technical Sales; and Jean-Luc Schneider, Global Technical Director, are all with Getinge-La Calhène.
References
1. Mounier, C. and Guilmet, C., Rapid transfer port systems – a comparative study, Clean air and Containment Review, Issue 20, October 2014, pp 26–29
2. Dufour, C. and Guilmet, C., “Ensuring Ergonomic Design in Sterile Transfer Ports”. Pharmaceutical Technology e-Newsletter, www.pharmtech.com/enews. Last accessed 15.10.14
