Patent Description:
New forms of treatment of patients with individualised pharmaceuticals, such as biopharmaceuticals, involve pharmaceuticals which are produced for a single patient or small group of patients. These individual pharmaceuticals therefore have to be produced and delivered (i.e. transported) as well as administered in single dosages or small numbers of dosages, so that traditional ways of distributing or delivering such pharmaceuticals are in many cases not practical or even feasible because of the strict requirements for production and delivery of pharmaceuticals.

Among these requirements relevant for the delivery of such pharmaceuticals is the sterility (when filling receptacles with the pharmaceuticals) and consequently the necessity of ensuring the integrity of the receptacles during the delivery process. The present invention is in particular concerned with liquid pharmaceuticals filled in bags (as receptacles). Here, ensuring the integrity of the bag means protecting the bag from impacts, pricks and the like which can all cause small damage down to the nanometre scale, since already such tiny damage (i.e. holes) can lead to the loss of sterile integrity of the bags.

The nature of such pharmaceuticals often also means that they have to be transported in a frozen state in order to prevent degradation of the product under normal environmental temperatures. The pharmaceuticals are also expected to withstand certain environmental influences (such as impacts) better in frozen state.

Another factor is the large value such small amounts of individual pharmaceuticals can represent. The large value must be seen as both monetary value, because the production process for such pharmaceuticals is very expensive, and in a more general sense, since the loss of a particular pharmaceutical in an inopportune moment can potentially lead to loss of (human or animal) life.

<CIT> discloses an arrangement with a container for receiving a bag filled with a pharmaceutical liquid. Unfortunately, the handling of this arrangement is unnecessarily complex without having any advantages regarding the structural integrity of the bag. The disclosure of <CIT> has similar deficiencies.

An arrangement from the prior art is also known from <CIT>.

Similar requirements for ensuring the integrity of bags of (bio-) pharmaceutical fluids are known during the production and delivery process for more traditional pharmaceuticals where fluids of such nature have to be transported and handled in bulk, i.e. in larger amounts. In this context the bag is known as Single Use Bag. Methods and apparatus for protecting bags filled with large or small amounts are known for example from <CIT>.

While such solutions are in principle applicable to the special case of delivery of the drugs to a single patient or a small group of patients, they do not yet take into account the special circumstance that the drug is best administered directly from the bag. Bags filled with bulk amounts of biopharmaceutical are in almost all cases processed in specialised facilities for handling the same. Such facilities are of course not expected to be present when the drug is directly administered to a single patient or a small group of patients.

<CIT> and <CIT> disclose general containers which are not specifically adapted for delivering pharmaceuticals.

The object of the present invention is therefore to provide an apparatus where not only the risk of loss of integrity is minimised during the production and transportation phase, but right until the moment of administering the pharmaceutical contained in the bag.

This is achieved by the invention which is defined by an arrangement according to claim <NUM>, a method of delivering a fluid according to claim <NUM> and a usage according to claim <NUM>.

A basic aspect of the invention is to use a bag to which connector tubing (can be a single tube or a plurality of tubes) is attached. So, both the bag and the tubing is contained in the container, which can then selectively be opened to only give access to the tubing (compartment) while the bag itself remains protected in the container (namely in the main compartment) potentially all the way through the administering of the pharmaceutical.

Before, while or after the container is closed with the bag and the connector tubing inside the fluid can be frozen in order to prevent degradation of the fluid inside the bag and in order to improve the resistance to mechanical influences from the outside during transportation and handling. Before, during or after the tubing compartment is opened the fluid can be thawed for use.

The bag is filled with a fluid and connected (in a fluid communication sense) to connector tubing both (the bag and the connector tubing) disposed inside the container.

It should be mentioned that part of the connector tubing (or simply tubing) can also be in the main compartment and reach over to the tubing compartment in an arrangement according to the invention.

The connector tubing can be flexible in order to allow for a bending of the connector tubing in order to facilitate a relatively easy connecting process to outside apparatus for example for administering the pharmaceutical.

The dish portion and/or the lid portion can be manufactured in one piece, e.g. in an injection moulding process.

The fluid in the bag can preferably be a liquid, particularly preferably a (bio-) pharmaceutical liquid.

The dish portion is divided into the main compartment and the tubing compartment through a constriction of the dish portion, which constriction is adapted to hold the connector tubing through a squeezing action between the constriction and the lid portion. Such a constriction, i.e. a narrowing of the cross section of the inside of the container, can be an easy way of manufacturing the divide between the main compartment and the tubing compartment.

Holding the connector tubing in the vicinity of the divide between the main compartment and the tubing compartment (in particular, through the mentioned squeezing action in the constriction) can be beneficial as it helps prevent movement of the bag and/or the tubing inside the container which could lead to loss of integrity.

The hinge can be provided as flexural hinge which allows for bending of the tubing portion relative to the main portion, which can facilitate easy manufacturing of the container according to the invention. Other forms of hinges (e.g. with moving parts) are of course conceivable in the context of the invention.

The lid portion can be attached to the dish portion, preferably by way of a further hinge. Like the hinge, the further hinge can for example be a flexural hinge.

The lid portion, in particular the main portion, the tubing portion and/or the hinge can be transparent. This gives operating personnel the opportunity to visually check the bag and/or the connector tubing.

For an easy manufacturing process, the lid portion can be of the same material as the lid portion. Consequently, also the lid portion can be of a transparent material.

At least one layer of foam can be present inside the container. Firstly, such a foam can improve the protection of the bag and/or the connector tubing inside the container.

Furthermore, the foam can compensate a volume increase of the fluid in the bag which occurs during freezing of the same (due to the negative thermal expansion of water). This volume increase during freezing can result in damage or destruction of the container if there are no measures taken to accommodate for the volume increase.

After freezing the at least one layer of foam has preferably adapted to the new shape of the bag. Since the foam also becomes harder due to the lower temperatures the foam can at least partly, preferably fully, immobilise the bag and/or the tubing. Immobilising the bag and/or the connector tubing can be beneficial for protecting the bag and/or the connector tubing by preventing mechanical stress thereon.

<CIT> A contains tehnical details and effects regarding at least one layer of foam.

The dish portion and/or the lid portion can be made of a plastic - preferably a thermoplastic.

The bag can be made of two layers of thermoplastic welded together on the edge(s). In some applications the bag is the called Single Use Bag.

The material for the connector tubing can for example be silicone or other materials which stay flexible for a prolonged period of time.

The lid portion can be secured in a closed position relative to the dish portion by way of frictional locking connections. For this, protrusions can be present on the lid portion and/or the dish portion which fit tightly into recesses on the counterpart (i.e. the dish portion or the lid portion). Such frictional locking connections can be used to secure both the main portion of the lid portion and/or the tubing portion of the lid portion independently of each other.

Other locking connections for these purposes are in principle conceivable, such as positive locks (i.e. locks using the shape of objects).

Further details and advantages of the invention are apparent from the figures and the accompanying figure description. The figures show:.

<FIG> shows an embodiment of a container <NUM>. It comprises a dish portion <NUM> and a lid portion <NUM>. The dish portion <NUM> is divided into a main compartment <NUM> and a tubing compartment <NUM> by way of a constriction <NUM> in the shape of the container <NUM>.

The main compartment <NUM> is closed off by the main portion <NUM> of the lid portion <NUM>.

The tubing compartment <NUM> is closed off by the tubing portion <NUM> of the lid portion <NUM>.

The main portion <NUM> of the lid portion <NUM> is connected to the tubing portion <NUM> of the lid portion <NUM> by way of a flexural hinge <NUM> so as to allow for a swivel action of the tubing portion <NUM> relative to the main portion <NUM>.

The flexural hinge can for example be embodied as material thinning so as to allow bending of the material in the area of the hinge <NUM>.

In this embodiment the dish portion <NUM> and the lid portion <NUM> are also connected to each other by way of a further hinge. In this way the dish portion <NUM> and the lid portion <NUM> can be manufactured in one process, e.g. by an injection moulding process using plastic. Embodiments where the lid portion <NUM> is separate from the dish portion <NUM> are of course conceivable.

Both the main portion <NUM> of the lid portion <NUM> and the tubing portion <NUM> of the lid portion <NUM> are locked in the closed configuration by way of frictional locking connections <NUM>.

These each include a protrusion and a matching recess of different shapes, such that friction between the protrusions and the recesses lock the main portion <NUM> of the lid portion <NUM> and the tubing portion <NUM> of the lid portion <NUM> to the dish portion <NUM> due to the sizing of the protrusions and the recesses.

Arranged in the dish portion <NUM> is a layer of foam <NUM> the function of which will be described in connection with <FIG>.

<FIG> shows the embodiment of <FIG> in a configuration where the tubing compartment <NUM> is opened, i.e. the tubing portion <NUM> of the lid portion <NUM> is opened, independently of the closed configuration of the main compartment <NUM> / main portion <NUM> of the lid portion <NUM>.

<FIG> shows an arrangement <NUM> according to the invention where the bag <NUM> together with the connector tubing <NUM> is arranged in the container <NUM> of <FIG>, however without the layer of foam <NUM> (described in connection with <FIG> and <FIG>). it is possible to use the container <NUM> according to the invention in an arrangement <NUM> according to the invention with or without the layer of foam <NUM>.

The bag <NUM> has been filled with a biopharmaceutical liquid (i.e. a biopharmaceutical medicine) and placed inside the container <NUM>.

In <FIG> the container <NUM> is completely open, i.e. both the main compartment <NUM> and the tubing compartment <NUM> are opened by way of the further hinge.

<FIG> shows an arrangement <NUM> according to the invention where the bag <NUM> together with the connector tubing <NUM> is arranged inside the container <NUM> of <FIG>.

The bag <NUM> has been filled with a biopharmaceutical liquid (i.e. a biopharmaceutical medicine) and placed inside the container <NUM>. The container <NUM> then has been closed into the configuration of <FIG>.

It is noted that the connector tubing <NUM> is slightly squeezed in the constriction <NUM> of the container <NUM> so as to hold the connector tubing <NUM> in place.

As a next step the arrangement <NUM> can be placed inside a freezer in order to freeze the liquid inside the bag <NUM>. During the freezing the liquid experiences an increase in volume which causes also an increase of the size of the bag <NUM>. This can exert a force on the container which - as mentioned before - can lead to damage and even destruction of the container <NUM>. The container <NUM> can then not serve the purpose of protecting the bag <NUM> and the connector tubing <NUM> from outside influence in order to reduce the risk of loss of sterile integrity of the bag <NUM> together with the connector tubing <NUM>.

In order to prevent this, the layer of foam <NUM> (see <FIG> and <FIG>) compensates the volume / size increase of the liquid / the bag <NUM>. Because the foam also becomes harder because of the low temperatures the foam forms a conformal bedding for the bag <NUM> and the connector tubing <NUM>, such that the bag <NUM> and the connector tubing <NUM> is immobilised inside the container <NUM>. Impacts of the bag <NUM> and/or the connector tubing <NUM> onto the inside of the container <NUM> because of movement of the container <NUM> are therefore prevented to a large extent, which serves to improve the protection of the bag <NUM> and the connector tubing <NUM>.

Now the arrangement <NUM> according to the invention can be transported and delivered with the liquid in a frozen state. It is of course also possible to transport the arrangement without freezing the liquid.

At or near the point of use (e.g. where the pharmaceutical is to be administered) the liquid can be thawed, such that the volume increase and the hardening of the foam is reversed.

Before, during, but preferably after, the thawing process the tubing portion <NUM> of the lid portion <NUM> can be opened so as to allow for access to the tubing compartment <NUM>. This configuration of the arrangement is depicted in <FIG> and <FIG>.

The connector tubing <NUM> can now be connected to some outside apparatus for example for administering the pharmaceutical on a patient.

It should be noted that the liquid in the bag <NUM> has been protected in the closed main compartment <NUM> during the whole time from putting the bag <NUM> into the container <NUM> until the administering of the pharmaceutical, potentially until the administering of the pharmaceutical is finished, upon which the container together with its contents can be disposed.

In <FIG> and <FIG> the layer of foam <NUM> described before is visible.

<FIG> shows the configuration of <FIG>, where the container is in an upright position. This is a preferred position for emptying the bag <NUM> inside the container if the tubing <NUM> is connected (not shown) e.g. to further tubing for administering the pharmaceutical.

Claim 1:
Arrangement comprising a container, the container (<NUM>) comprising
- a dish portion (<NUM>) and a lid portion (<NUM>),
- wherein the dish portion (<NUM>) is divided into a main compartment (<NUM>) of the container (<NUM>) and a tubing compartment (<NUM>) of the container (<NUM>),
- and wherein the lid portion (<NUM>) includes a main portion (<NUM>), a tubing portion (<NUM>),
- and wherein the dish portion (<NUM>) is divided into the main compartment (<NUM>) and the tubing compartment (<NUM>) through a constriction (<NUM>) of the dish portion (<NUM>),
wherein the arrangement further comprises a bag (<NUM>) filled with a fluid, in particular a biopharmaceutical fluid, and connected to connector tubing (<NUM>) both disposed inside the container (<NUM>), said connector tubing (<NUM>) being attached to said bag (<NUM>), wherein the constriction (<NUM>) is adapted to hold the connector tubing (<NUM>) through a squeezing action between the constriction (<NUM>) and the lid portion (<NUM>);
said arrangement being characterised in that:
the lid portion includes a hinge (<NUM>) between the main portion (<NUM>) and the tubing portion (<NUM>), the hinge being adapted to allow for an opening of the tubing portion (<NUM>) while the main portion (<NUM>) remains closed, such that the bag (<NUM>) remains protected in the main compartment (<NUM>) while the connector tubing (<NUM>) in the tubing compartment is accessible from the outside.