The invention relates to a safety device for a single-use mixing or storage system, especially for use in a biopharmaceutical process.

Single-use (disposable) mixing and storage systems are of great importance in the biopharmaceutical industry. Key applications are the preparation of buffer solutions, media and chemical reactions. Further, the storage of the final product or the storage of process-relevant substances which have to be transferred are possible applications.

Mostly, single-use mixing and storage systems include flexible bags made of thin film material. These bags are usually accommodated in fixed containers made of stainless steel or hard plastic for support and mechanical stability. A disadvantage of flexible film materials is their sensitivity to pressure. If a bag is filled too quickly, overfilled or a filter used for venting is blocked, the pressure inside the bag can rise critically. Increased pressure can lead to leakage, resulting in contamination of the content, or bursting of the bag. This can entail a high financial loss, especially when a final product of a biopharmaceutical process, e.g. purified antibodies, is stored in the bag. Moreover, if a toxic medium is processed, operating personnel is at risk if the bag is damaged.

It is therefore an object of the invention to increase the safety of a single-use mixing or storage system, especially when it is used in a biopharmaceutical process.

The above problem is solved by a safety device according to claim 1. Advantageous and expedient embodiments of the invention are apparent from the dependent claims.

The invention provides a safety device for a single-use mixing or storage system, especially for use in a biopharmaceutical process. The safety device according to the invention comprises a flexible bag made from a film material and a support structure for receiving and supporting the bag in several directions. The support structure allows an expansion of the bag in a (main) expansion direction. The safety device further comprises a detection unit adapted to detect an expansion of the bag in the expansion direction, and a control unit connected to the detection unit and adapted to initiate a safety measure in case the expansion of the bag in the expansion direction exceeds a given threshold.

The invention is based on the finding that single-use bags used in biopharmaceutical applications are usually installed in rigid support structures that surround the bag at the bottom and at the sides, but not at the top, i.e. the support structures are not closed by a top cover. During normal operation the bag lies flat on the surrounding walls of the support structure. In case of an overpressure the bag can only expand upwards. This expansion in a defined direction can be detected and used to initiate a safety measure, like triggering an alarm and/or interrupting the filling of the bag. Thanks to the safety device the bag can be protected from damage caused by overpressure.

Compared to a conventional single-use pressure sensor which could be installed in the single-use bag for the same purpose, the safety device according to the invention provides several advantages. The safety device can be used several times and is therefore more cost efficient in the long term. Furthermore, the safety device has a lower probability of failure and can be designed with a very high sensitivity. For example, pressure increases of less than 10 millibar can be detected.

The safety device according to the invention can also be used for monitoring the freezing of a single-use bag filled with a liquid medium. When the medium freezes, its volume may expand by 10 to 15%. Since the bag is supported in several directions, expansion is mainly or only allowed in the above-mentioned expansion direction (usually upwards) and can be detected by the detection unit. Vice versa, the safety device can also be used to monitor the thawing of a frozen single-use bag filled with a medium. In this case, the expansion is negative and the expansion direction is opposite to the expansion direction of a corresponding freezing process. In a preferred embodiment of the invention, the detection unit includes a sensor element being in contact or coming into contact with the bag when the bag expands so that the sensor element is displaced or rotated by the expansion of the bag in the expansion direction. Thus, the expansion of the bag is transformed into a displacement or a pivoting movement of the sensor element, which can be a lever, for example.

According to a first aspect of detection, the movement of the sensor element is monitored in a contactless manner. In this case the detection unit further includes a trigger element emitting a trigger signal to the control unit in case the expansion of the bag in the expansion direction exceeds the threshold.

Preferably, the contactless trigger element includes a photoelectric sensor. The photoelectric sensor can be placed in relation to the movable sensor element such that the sensor element interrupts the light beam of the photoelectric sensor when a given threshold pressure is reached. There are photoelectric sensors available for determining the position of a sensor element that meet a certain performance level, especially a so-called safety integrity level (SIL). This ensures that the safety measure is really initiated independently of a process software controlling the filling of the bag by a filling means (e.g. a pump).

According to a second aspect of detection, the detection unit includes a trigger element physically performing a switching operation in case the expansion of the bag in the expansion direction exceeds the threshold. This corresponds to a mechanical detection of the bag expansion.

Preferably, the mechanical trigger element includes a contact switch, i.e. a switch performing a switching operation when it is contacted by another element (here: the sensor element). This solution is easy to install at low cost.

Irrespective of the type of detection (mechanical or contactless), especially a pivotable lever can be used as the sensor element. The pivotable lever is preferably mounted to the support structure by a mechanical bearing like a hinge.

A pivotable lever is also suitable for a further alternative which embodies an angle sensor as the trigger element. As already indicated, the safety device according to the invention is especially useful in connection with a filling means (e.g. a pump or means causing a pressure difference) which controls a fluid transfer into the bag. The control unit of the safety device is preferably connected to the filling means so that in case of a detected overpressure in the bag the operation of the filling means can be immediately ceased.

As an alternative or in addition, the control unit can be connected to an alarm system to trigger an audible and/or visual alarm.

Further features and advantages of the invention will become apparent from the following description and from the accompanying drawings to which reference is made. In the drawings:

- Figure 1a shows a single-use mixing or storage system according to the prior art in normal operation;

- Figure 1 b shows the mixing or storage system of Figure 1 in case of an overpressure;

- Figure 2a shows a safety device for a single-use mixing or storage system according to the invention in normal operation; and

- Figure 2b shows the safety device of Figure 1a in case of an overpressure.

Figure 1a is a simplified illustration of a single-use mixing or storage system 10 as used in a biopharmaceutical process. A flexible bag 12 made of a film material is accommodated in a fixed, rigid holder made of stainless steel or hard plastic. The bag 12 may be empty or already partially filled with a fluid. In any case, no additional pressure acts on the bag 12.

The holder serves as a support structure 14 for receiving and supporting the bag 12 in several directions. In particular, the bag 12 is completely enclosed by the support structure 14 except for the top. This is a typical design allowing an operator to easily install the bag 12 inside the support structure 14 before operation and to easily remove the bag 12 from the support structure 14 after operation.

In the depicted example, a fluid is to be transferred from a reservoir 16 into the bag 12 by an electrically driven pump 18 or another filling means. The mixing or storage system 10 is not pressurized during normal operation. This means that the air contained in the bag 12 is displaced through a vent filter (not shown) when the fluid from the reservoir 16 is filled into the bag 12.

However, if the bag 12 is filled too quickly, overfilled or if the vent filter is blocked or in case of another fault, the pressure in the bag 12 can rise in an uncontrolled manner as shown in Figure 1b. Due to the overpressure, the bag 12 expands, especially in the upward direction where the support structure 14 does not confine the bag 12. The upward direction will thus be referred to as the main expansion direction A.

If further expansion of the bag 12 is no longer possible, especially owing to limited material strength, the bag 12 can rupture or burst. Such damage to the bag 12 must be avoided, not only for economic and process efficiency reasons (the process has to be stopped and valuable medium gets lost), but above all to protect the operator, especially in case of toxic content of the bag 12.

Figure 2a illustrates an embodiment of a safety device for a single-use mixing or storage system 10 which is similar to the single-use mixing or storage system 10 shown in Figure 1a. The safety device comprises a detection unit 20 adapted to detect an expansion of the bag 12 in the main expansion direction A.

In the depicted example embodiment, the detection unit 20 includes a sensor element 22 being in contact or coming into contact with the bag 12 when the bag 12 expands so that the sensor element 22 is displaced by the expansion of the bag 12 in the main expansion direction A. In particular, the sensor element 22 is a displaceable or pivotable element like a rod, a bar, or a lid, for example, and is hereinafter referred to as lever. The lever either rests on the bag 12 or takes a (predefined) initial position during normal operation of the mixing or storage system 10. The lever may be supported and/or guided to perform a defined displacement or pivoting movement. For example, the lever can be attached to the support structure 14 by a hinge 24 or another suitable mechanical bearing.

The detection unit 20 further includes a trigger element 26 which is connected to a control unit 28 of the safety device. The control unit 28 is adapted to initiate a safety measure when it is triggered by the detection unit 20. T o this end, the sensor element 22 interacts with the trigger element 26 when the expansion of the bag 12 in the mam expansion direction A exceeds a given threshold. This situation is shown in Figure 2b.

According to the example embodiment described here, the sensor element 22, i.e. the pivotable lever, is rotated by the expanding bag 12 until it physically acts on a contact switch constituting the trigger element 26. The contact switch is part of an electric circuit monitored by the control unit 28. As soon as the control unit 28 recognizes this switching operation, a safety measure is initiated to prevent the bag 12 from being damaged.

The control unit 28 may be connected to an alarm system and/or to the pump 18, so that an alarm can be triggered and/or the pump 18 can be shut down to prevent a further increase of pressure in the bag 12. Other safety measures can be initiated as well.

Instead of the contact switch, the detection unit 20 may include an angle sensor. According to this alternative, the safety measure is initiated as soon as the angle sensor detects that the pivotable lever has reached a given angular position due to a rotation of the lever caused by the expanding bag 12.

In an alternative embodiment, the trigger element 26 of the detection unit 20 does not require any physical contact with a sensor element 22 or directly with the bag 12 to emit a trigger signal to the control unit 28 in case the expansion of the bag 12 exceeds the threshold. For example, the trigger element 26 can include a photoelectric sensor. As soon as the photoelectric sensor detects an excessive expansion of the bag 12 in the main expansion direction A, the trigger signal is sent to the control unit 28, and the control unit 28 promptly initiates the safety measure.

It is to be noted that the bag 12 (possibly including pre-installed elements such as ports and directly connected hose lines etc.) is a dedicated single-use component, whereas the other components of the safety device, including the support structure 14 the sensor element 22 and the optional trigger element 26, are usually reusable, i.e. they are not configured as single-use components, although single-use configurations are not necessarily precluded. List of Reference Signs

10 single-use mixing or storage system

12 bag

14 support structure 16 reservoir

18 pump

20 detection unit

22 sensor element

24 hinge 26 trigger element

28 control unit