EP3429546B1 - Procede de fabrication d'une preparation medicamenteuse - Google Patents

Procede de fabrication d'une preparation medicamenteuse Download PDF

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Publication number
EP3429546B1
EP3429546B1 EP17710921.2A EP17710921A EP3429546B1 EP 3429546 B1 EP3429546 B1 EP 3429546B1 EP 17710921 A EP17710921 A EP 17710921A EP 3429546 B1 EP3429546 B1 EP 3429546B1
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EP
European Patent Office
Prior art keywords
peristaltic pump
target container
liquid
producing
pump
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP17710921.2A
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German (de)
English (en)
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EP3429546A1 (fr
Inventor
Martin Biehl
Michael Hock
Henrik SCHAAKE
Ulla Schöbel
Martin Bohm
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fresenius Kabi Deutschland GmbH
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Fresenius Kabi Deutschland GmbH
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Priority to EP23168051.3A priority Critical patent/EP4218709A1/fr
Publication of EP3429546A1 publication Critical patent/EP3429546A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/002—Compounding apparatus specially for enteral or parenteral nutritive solutions
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/12—Machines, pumps, or pumping installations having flexible working members having peristaltic action
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J2200/00—General characteristics or adaptations
    • A61J2200/70—Device provided with specific sensor or indicating means
    • A61J2200/74—Device provided with specific sensor or indicating means for weight

Definitions

  • the invention relates to a method and a system for producing a medicinal preparation.
  • the invention relates to a method by means of which infusion bags and/or syringes for parenteral nutrition are filled, as well as an associated system.
  • Preparations for parenteral nutrition are manufactured specifically for the patient, for example in pharmacies or clinics. These are mixtures of different
  • TPN Total Parenteral Nutrition
  • the target container can be weighed to check the dosage.
  • a compounding system in which the target container is weighed is in the document U.S. 5,697,407 described.
  • the medicinal preparations to be produced include components with main constituents such as water, fat, sugar and amino acids, which are supplied in quite large amounts.
  • main constituents such as water, fat, sugar and amino acids
  • Such components are also referred to as microamounts.
  • the invention is based on the object of providing a method for producing a medicinal preparation in which precise dosing of the individual components of a medicinal preparation is made possible by means of a peristaltic pump and in which precise monitoring of the dosage is also possible.
  • the object of the invention is achieved by a method for producing a medicinal preparation according to one of the independent claims.
  • the invention relates to a method for producing a medicinal preparation, in particular the invention relates to a method for producing a preparation for parenteral nutrition.
  • Liquids are taken from a number of source containers and transferred to a target container using a peristaltic pump.
  • the peristaltic pump is a displacement pump in which the medium to be pumped is pushed through the hose by external mechanical deformation of a hose.
  • the hose pump preferably has a pump wheel with rollers, with which the hose is compressed.
  • the production of the medicinal preparation is automated, with the user of the system used for the method being able to enter the composition desired in the target container or to select it from a database with a plurality of recipes.
  • a defined quantity of liquid is removed from the individual source containers in a predetermined sequence, also referred to below as the "dosing step". After completion of all dosing steps provided for a target container, a "filling process" is finished by definition.
  • such a medicinal preparation typically consists of main components that are supplied in relatively large amounts, and so-called “micro-amounts” that can contain, in particular, vitamins, minerals or drug components.
  • a transfer set designed as a disposable component which includes the hose that is inserted into the hose pump.
  • the transfer set also includes connection hoses for the source container and a connection for the target container.
  • the transfer set preferably includes a valve unit, by means of which the connections to the individual source containers can be opened and closed.
  • the universal liquid also known as a "universal ingredient” (UI)
  • UI universal ingredient
  • This liquid is allowed to come in direct contact with any other ingredient without undesired side effect and is used in any preparation in a relatively large amount, especially to make up the preparation to the desired total amount.
  • the universal liquid is mostly isotonic water.
  • the target container is preferably weighed at each individual dosing step and the quantity of liquid transferred into the target container is thus checked at each individual dosing step.
  • All dosing steps are preferably checked by weighing the target container, ie also the dosing steps of micro-amounts of less than 10 ml, preferably less than 5 ml, particularly preferably less than or equal to 3 ml.
  • the preferred embodiments of the invention described below relate to measures for increasing the dosing accuracy and/or the accuracy when checking the individual dosing steps.
  • the peristaltic pump used for the method has a range with a linear characteristic and a range with a non-linear characteristic of the pump output.
  • the angular range of an impeller is understood in which the pump capacity, i.e. the volume compared to the Angle of rotation of an impeller of the peristaltic pump is constant.
  • the conveyed volume is proportional to the angle of rotation.
  • rollers of the impeller engage at certain phase angles and disengage at other phase angles. At least one roller is engaged at all times, the pump is never "open". Theoretically, a roller pump therefore has no slippage, i.e. no deviation between the angle of rotation and the quantity pumped.
  • a review of each dosing step is improved according to one embodiment of the invention, even with micro-amounts in that the amount of at a Dosing step in the target container transferred liquid is calculated taking into account the pressure-side characteristic of the pump capacity of the peristaltic pump.
  • the target container is weighed and the amount of liquid transferred is checked.
  • this check based on the weight of the target container is not based on the calculated amount of liquid removed from the source container, but rather the amount of liquid transferred into the target container is calculated, taking into account the pressure-side characteristic of the peristaltic pump.
  • the respective dosing step can be regarded as correct. If, on the other hand, the results do not match or if they are outside a specified tolerance range, an error can be shown on the system side, e.g. on a display.
  • the user of the system can be prompted, for example by being shown on a display, to discard the target container and to fill a new target container and/or to calibrate the system.
  • a precisely working load cell can be used at the end of the filling process, i.e. after all dosing steps have been completed, to check whether the increase in weight of the target container corresponds to the target quantity of the individual components to be dosed.
  • the individual dosing step can also be checked for micro quantities by weighing the target container.
  • the amount of liquid to be removed from the respective source container is used to calculate the required rotation of the impeller on the basis of the suction-side characteristic curve of the peristaltic pump.
  • the amount of liquid removed from the respective source container can be determined in a calculated manner in each dosing step via the rotation of the peristaltic pump, in particular via the angle and the number of revolutions of a pump wheel of the peristaltic pump. Based on the specified amount of liquid to be removed, the pump is controlled and the required angle of rotation for a dosing step is calculated.
  • a constant delivery rate is not assumed during dosing and thus when controlling the peristaltic pump in each dosing step;
  • the peristaltic pump for dosing from at least one source container is brought into a position such that the entire dosing from this source container takes place in a range with a linear characteristic.
  • This embodiment of the invention is based on the knowledge that the dosing of micro quantities is also possible with a hose pump with high accuracy if the hose pump is moved exclusively in the area with a linear characteristic curve during the entire dosing step.
  • the quantity of liquid to be metered in this metering step must be so small that the entire liquid to be metered can be conveyed in an angular range of the pump wheel of the peristaltic pump by not leaving the linear range.
  • the peristaltic pump preferably includes a rotary encoder.
  • the peristaltic pump is preferably brought into a position in which the suction-side characteristic curve of the peristaltic pump is linear.
  • the amount of liquid taken from the source container is particularly important and the linear range of the peristaltic pump available on the suction side is therefore used to dose the amount taken off as precisely as possible.
  • liquid can be taken from a different source container than the one from which dosing is to take place.
  • a source container with the universal liquid (UI) described above can be used as the source container for moving the impeller, for example to the beginning of the suction-side linear range. While the pump is working in the non-linear range, medium is taken from the source container with universal liquid.
  • one embodiment of the invention also provides for liquid to be removed from a source container in several dosing steps, with the peristaltic pump being moved to the beginning of a linear range between these individual dosing steps .
  • the peristaltic pump can be operated in a conventional manner, i.e. during the respective dosing step both the non-linear and the linear range of the suction and/or the pressure-side characteristic curve of the peristaltic pump.
  • the sequence of different liquids in the inlet of the target container is taken into account in order to include the density of the liquids in the check when weighing.
  • This embodiment of the invention is based on the finding that the accuracy of the check is increased for each dosing step by taking into account the density, ie the specific weight of the respective liquid transferred into the target container.
  • the liquid does not reach the target container immediately, but is initially in the transfer set, for example in the hose inserted in the peristaltic pump.
  • the liquid that is in front of this liquid in the transfer set and that is now pressed into the target container can have a different density. Therefore, the increase in weight of the target container alone cannot be used as a sufficiently accurate measure of the amount transferred.
  • this calculation divides the inlet of the target container into sections, each of which contains liquid with a different density.
  • This principle is based on the consideration that all liquids taken from the source containers ultimately arrive in the target container. Since the volume of the route from the source container or from the valve, from which the liquid from the respective source container flows into the valve unit, to the source container on the scale is known, it can be calculated which liquid or which liquids arrives in the target container during a dosing step or arrive.
  • the volume is determined by the valve unit from the position of the respective valve of the source container, as well as the tubing routed through the peristaltic pump that connects the valve unit to the target container.
  • the density of the liquid removed in the respective dosing step is not used as a basis, but rather the density of the liquid or liquids that are introduced into the target container.
  • the density of the liquid introduced can differ due to the volume of the feed and the peristaltic pump, at least at the beginning of the dosing step.
  • occlusions can also occur, which are difficult to detect on the plant side. If, for example, the tubing leading from a source container to the peristaltic pump is blocked, the peristaltic pump will still deliver liquid to the target container if the volume is small, especially if the volume is less than 3 ml, as the flexible tubes of the transfer set can contract. If the valve to another source container is then opened, the hose relaxes by sucking in liquid from the other source container. Under certain circumstances, this effect can mean that at the end of all dosing steps, the total quantity checked by weighing the target container is correct, but a single micro quantity is completely wrong or not available at all.
  • the flow rate of the peristaltic pump is therefore checked by means of a flow sensor.
  • the flow sensor is preferably arranged on the suction side.
  • a flow sensor can be provided, into which a tube of the transfer set is inserted.
  • the flow sensor can detect such a high deviation from a setpoint that it can be concluded that the flow rate is not plausible in relation to the current theoretical delivery rate of the pump.
  • the method can then be aborted and the user of the system can be informed of an error message.
  • a bubble sensor bubble detector
  • This bubble sensor which can be designed as an ultrasonic sensor, for example, is preferably located on the pressure side of the hose pump. In particular, it is a sensor into which the tubing of a transfer set can be inserted.
  • the process can also be stopped and the user informed of an error message.
  • the dosing factor of the peristaltic pump is determined in a preceding calibration step by weighing a target container.
  • the dosing factor is the volume that is pumped when pumping a specific liquid, in particular when pumping water, at a specific speed of the impeller and at one full pump revolution.
  • the dosing factor depends, among other things, on the tolerances of the hose inserted in the pump. This dosing factor can be calibrated when the system is started up when a target container is filled, in order to adapt the control of the peristaltic pump to a newly used transfer set.
  • a first target container is used, which is then discarded, a so-called "waste bag".
  • This waste bag is connected using the transfer set and the to all hoses leading to the source containers are vented by removing the amount of liquid required for this purpose.
  • liquid preferably water
  • the dosing factor is determined in the process. After discarding the waste bag, this dosing factor is now used as a basis for calculating the quantity delivered by the pump in further dosing steps.
  • the dosing factor is in turn to be set in relation to the above-described consideration of the non-linear range of the suction-side and pressure-side characteristic of the peristaltic pump.
  • the pump performance of a peristaltic pump also depends, among other things, on the medium to be pumped, in particular on the viscosity of the liquid to be pumped. As provided in one embodiment of the invention, this dependency can also be taken into account when calculating the conveyed quantities.
  • a flow factor of 1.0 can be used for water; for other media, such as glucose, for example, this flow factor assumes higher values, for example values of up to 1.1. This can be taken into account when calculating the conveyed quantities, in particular the conveyed quantities of main components, by including the flow factor in the calculation of the conveyed volume.
  • a further aspect of the invention relates to a method for producing a medicinal preparation, in which a liquid is transferred from a plurality of source containers into a target container by means of a hose pump.
  • the dosing factor of the hose pump is calibrated during the manufacture of the medicinal preparation when a pump wheel of the hose pump rotates at least one full revolution.
  • the invention therefore provides that the dosing factor of the peristaltic pump is not only determined initially when the system is started up, but that, if this is possible, the dosing factor is also checked and, if necessary, re-determined during regular operation of the system, i.e. when producing medicinal preparations is calibrated.
  • this on-line calibration is performed when a sufficient quantity of universal liquid or water is transferred to the target container, since the flow factor of this universal liquid is always 1.0, so that no flow factor variation error is introduced into the calibration.
  • the calibration during operation is preferably carried out when the same liquid is pumped as was used to initially determine the dosing factor using the waste bag.
  • the calibration is particularly preferably only carried out during operation when the transfer set has been rinsed with a universal liquid, ie the inlet of the target container does not have any sections in which there is another liquid.
  • the method steps according to the invention described above can be implemented by devices that are appropriately designed or suitable for carrying out the method steps described. These devices can be part of a system.
  • the scope of the invention therefore also includes a system for producing a medicinal preparation, in particular a system for producing parenteral food, comprising a peristaltic pump and a system for carrying out a method according to the invention described above.
  • the method according to the invention can be carried out in particular by means of the system according to the invention.
  • the plant with the system according to the invention is designed in particular to carry out the method according to the invention.
  • FIG. 1 shows a system 1 for the production of a medicinal preparation.
  • the system 1 for producing a medicinal preparation comprises a large number of source containers 2, which are only partially shown in this view.
  • those source containers are not shown in this representation, which contain the main components of the medicinal preparation, as well as the container that is filled with universal liquid.
  • these containers can be hung remotely from the system, e.g. on a hook attached to a rail.
  • a target container 3 embodied as an infusion bag can be seen, which is arranged on scales 4 .
  • the amount of liquid transferred to the target container 3 can be checked via the scales 4 during operation of the system 1 .
  • a transfer set which includes a valve unit 5 and hoses 14, 15, with which the valve unit 5 is connected to the target container 3 on the one hand and to the source containers 2 on the other.
  • valve of the valve unit 5 is opened via the system 1 in each dosing step, so that liquid can be pumped from exactly one source container 2 into the target container 3 .
  • the system 1 has a single peristaltic pump 6 here, by means of which liquids can be pumped from all the source containers 2 into the target container 3 .
  • the system 1 also has a display 7, which is designed, for example, as a touch screen, by means of which the user can program the system 1 and, in particular, select a program by means of which a target container 3 is filled with a predetermined composition of components.
  • the system includes an electronic controller (not shown) via which the peristaltic pump 6 is controlled and which is connected to the scale 4 .
  • FIG. 12 is a detailed view of the peristaltic pump 6.
  • the pump 6 is preferably provided here as a roller pump.
  • the hose pump 6 has a pump wheel 8 with two rollers 9 .
  • the hose to be inserted is not shown in this view.
  • the method according to the invention can also be carried out using a hose pump with a different number of rollers, in particular using a hose pump which has three rollers (not shown).
  • the tube pump has an inlet 10 and an outlet 11 . In the position of the impeller 8 shown here, both rollers 9 are in engagement with the hose.
  • rollers 9 move from the outlet 11 to the inlet 10, they are partly disengaged from the hose. This results both on the suction side, ie on the side of the inlet 10, and on the pressure side, ie on the side of the outlet 11, a non-linear characteristic curve of the pump output, the peristaltic pump 6 pulsates.
  • the amount of liquid delivered is between 5 and 50 ml per full revolution.
  • the hose pump 6 is preferably brought into a position by rotating the pump wheel 8 in which the respective micro-amount is metered completely in the linear range of the hose pump 6, at least on the suction side can be.
  • the peristaltic pump includes a rotary encoder (not shown).
  • the pressure-side and suction-side characteristics are in 3 shown.
  • phase angle p is divided into 1600 units, which are plotted on the x-axis. These 1600 steps represent one full revolution of the pump.
  • the differential flow, ie the delivered volume per unit of angle of rotation, for the hose pump 6 is plotted on the y-axis.
  • the dashed curve represents the differential flow on the pressure side and the dotted curve represents the differential flow on the suction side.
  • the characteristic curves are constant over wide areas, i.e. there are areas with a linear characteristic curve.
  • the dips are in the areas where a roller comes out of engagement.
  • the tubing of the peristaltic pump returns to its original shape.
  • the hose increases in volume and the delivery rate of the pump is reduced on the pressure side.
  • the pumped volume on the suction side is relevant for the exact dosing, especially of a micro quantity. All liquid that is taken from the source container in the respective dosing step ultimately reaches the target container. It is therefore crucial that the correct volume is removed from the suction side in each dosing step.
  • liquid when dosing a so-called micro quantity, liquid is only pumped in one of the two linear areas of the suction side of the pump in a dosing step.
  • the suction-side characteristic curve of the peristaltic pump is used to more precisely calculate the quantity of liquid removed from the source container.
  • the characteristic curve on the suction side of the hose pump can also be used for dosing steps that take place in the non-linear range of the hose pump in order to calculate the quantities of liquid removed.
  • the calculation takes into account that the suction-side flow rate of the peristaltic pump is not linear.
  • p1 is the position of the impeller at the beginning of the dosing step and p2 is the position after the dosing step.
  • Vs is the volume to be taken from the source container.
  • the pressure-side characteristic curve of the pump can in turn be used to check in an improved way by weighing the target container whether the quantity actually removed corresponds to the calculated quantity.
  • the volume of the liquid entering the target container is calculated.
  • the mass of incoming liquid calculated.
  • the characteristic curve Dd of the pressure side is used to determine the volume of the liquid arriving in the target container.
  • the characteristic curves which are preferably determined by empirical measurements, can be stored, for example, as approximate formulas or as a simple table of values, in order to calculate the suction-side and pressure-side pump power as a function of the phase angle.
  • the characteristics can be determined by measurement and then approximated by an empirical formula. The calculations in the system are then carried out using the empirical formula or a table of values.
  • FIG. 14 is a perspective view of the valve unit 5 used for the medicinal preparation manufacturing plant.
  • the valve unit 5 comprises a large number of inlets 12, which are connected to the source containers (2 in 1 ) get connected. Valves (not shown) integrated in the valve unit 5 can selectively connect a hose 15 , by means of which liquid is removed from a source container, to a hose 14 which is arranged on the outlet 13 of the valve unit 5 .
  • the hose 14 also has a section which is inserted into the hose pump.
  • FIG 4b the ends of the hoses 15 for connecting the source container are shown.
  • the connections 22 for the source container can be seen, which in this exemplary embodiment are in the form of a Luer lock connection with an attached spike.
  • Figure 4c shows the tube 14, which forms the outlet of the valve unit 5 and at the same time the inlet of the target container.
  • Connection 23 for the target container can be seen.
  • the valve unit 5 shown here forms, together with the hoses 14, 15 and their connections 22, 23, the transfer set, which is used to operate the system.
  • This transfer set is preferably designed as a disposable component and is regularly replaced. Because of this design come to Transferred liquids only come into contact with components of the transfer set on their way from the source container to the target container.
  • the transfer set described above is used to connect the source containers.
  • a so-called “waste bag” is also inserted as the target container, ie a container which is not intended to be used as intended for applying a medicinal preparation, but which is discarded after the system has been prepared.
  • the entire transfer set including hoses is filled with a universal liquid (UI), e.g. B. isotonic water, and each valve is opened long enough to allow the tubing (15 in Fig. 4a, b ) leading to the source tanks are filled and free of bubbles.
  • UI universal liquid
  • the dosing factor of the peristaltic pump can be determined by weighing the waste bag when pumping universal liquid.
  • the pump performance of the hose pump which changes due in particular to tolerances in the hose used, is now calibrated by determining this dosing factor.
  • the waste bag is then discarded and the first target container, which is to be filled with a medicinal preparation, can be connected.
  • a micro-amount is to be dosed in a first dosing step.
  • step 5 the impeller is brought into an area with a linear characteristic curve on the suction side, with universal fluid first being conveyed while the impeller is brought into this position.
  • a micro-quantity can now be removed from the source container completely in the linear range of the pump's characteristic curve on the suction side.
  • Each individual dosing step including the step of dosing a micro-quantity, is checked by weighing the target container.
  • the density of the liquid transferred into the target container is taken into account by calculating which liquid or which liquids are in the inlet of the target container when the microquantity is removed in step 5 and are transferred into it.
  • a main component of the medicinal preparation is then dosed, taking into account the suction-side characteristic curve of the peristaltic pump.
  • the peristaltic pump is also operated in the non-linear range when dosing the main components.
  • the suction-side characteristic curve of the peristaltic pump is taken into account in order to be able to precisely predict the volume removed on the suction side.
  • the mathematical verification of the quantity taken from the source container for a main component is also carried out taking into account the density of the liquid transferred to the target container and taking into account the pressure-side characteristic curve of the peristaltic pump.
  • a flow factor which is dependent on the type, in particular the viscosity, of the liquid being pumped, is preferably included as a further factor in the calculation of the volume of the pumped liquid.
  • a flow factor of 1.0 is assigned to water; the flow factor changes significantly in the case of viscous components such as glucose solutions.
  • the phases p1 and p2 can differ by several revolutions.
  • the flow factor F is therefore a correction for an additional slippage of the pump due to increased viscosity compared to water.
  • the volume to be dosed is set higher by a factor of F than with water.
  • This calculated weight is used to check the respective dosing step via the weighing.
  • Vd is the volume expected on the pressure side, i.e. the volume of liquid that is pumped into the target container on the scale during the dosing step.
  • Dd(p) is characteristic of the pressure side (constant).
  • the flow factor F is not included in the calculation of the volume pumped on the pressure side, since the "slip" of the pump is not pumped.
  • G Vd ⁇ ⁇ with the density P of the pumped medium.
  • P is therefore the specific gravity of the liquid transferred into the target container during a dosing step, ie initially the liquid that is already present in the inlet of the target container. If several different liquids are transferred to the target container during a dosing step, the specific gravity of the liquids is set in relation to their quantity.
  • Steps 5 to 9 can therefore be repeated until all the desired components are in the target container.
  • steps 5 to 7, ie the dosing of a micro-amount, and steps 8 and 9, ie the dosing of a main component, are also interchangeable, ie can be carried out in a different order.
  • the transfer set is rinsed with universal liquid and, if necessary, the desired residual amount of universal liquid is fed to the target container.
  • this rinsing phase in which the impeller of the peristaltic pump rotates more than one full revolution, to re-determine the dosing factor of the peristaltic pump during operation by weighing the target container.
  • the dosing factor can thus be recalibrated during operation. This can change, for example, because the elasticity and shape of the hose inserted into the hose pump changes.
  • the target container After completing all dosing steps and rinsing the transfer set, the target container can be removed and a new target container connected.
  • FIG. 6 is another detail of the 1 .
  • the target container 3 can again be seen.
  • a valve unit 5 can also be seen.
  • the hose not shown here, which connects the valve unit 5 to the target container 3 and which is placed in particular in the hose pump, is first placed in a flow sensor 16 .
  • the flow rate in the hose on the suction side is measured via the flow sensor 16 and the delivery capacity of the hose pump can thus be checked for plausibility. If, for example, there is a blockage in the area of the valve unit or at the connection of a source container, the throughflow on the suction side will be reduced to such an extent that an error can be detected by means of the flow sensor 16 . In particular when dosing a micro-amount, the tube will initially also contract in the area of the flow sensor 16, with the result that the detected flow rate is reduced and a blockage can be concluded. An error message can then be generated via the electronic control and displayed to the user.
  • the flow sensor 16 is preferably designed as an ultrasonic sensor. In particular at low flow rates, such a sensor is generally not accurate enough to be able to determine the quantity of liquid conveyed on the suction side with sufficient accuracy using the flow sensor alone.
  • the flow sensor is therefore preferably used solely for monitoring such that an error is assumed if the difference between the calculated pump capacity of the peristaltic pump and the resulting calculated flow rate compared to the flow rate determined by the flow sensor exceeds a threshold value.
  • the hose is placed in a bubble sensor 17 on the pressure side.
  • This is an ultrasonic sensor that detects bubbles and switches off the system from a certain threshold value and displays an error to the user.
  • FIG. 12 is a schematic representation of the hose 14 connecting the valve unit 5 to the target container 3.
  • FIG. 12 In this exemplary embodiment, three valve units connected in series are shown, but this has no effect on the basic principle.
  • the three valve units 5 shown here can just as easily be combined into a single valve unit.
  • the inlet to a source container is opened by means of the valve unit 5 for each dosing step, so that liquid can flow from the source container via the respective valve of the valve unit first into the valve unit and then into the hose 14 .
  • the tube 14 and the collecting channels 22 of the valve units 5 form a volume into which the liquid taken from the respective source containers is initially transferred.
  • the calculation of the weight of the liquid which arrives in the target container 3 in a dosing step is therefore not based on the density of the liquid removed in the respective dosing step. Rather, the tube 14 and the collecting channels 24 of the valve units 5 are considered in such a way that different liquids, namely a first liquid 19, a second liquid 20 and a third liquid 21 are located in different sections of the tube 14 and/or the subsequent collecting channel 24.
  • the specific weight of the first liquid 19 is initially taken as a basis.
  • Fig. 12 is a flowchart used to explain verification of each dosing step by weighing the target container.
  • the weight transferred to the target container is calculated as a target weight. As described above, this is done on the basis of the pressure-side characteristic curve of the peristaltic pump and the specific gravity of the liquid transferred to the target container.
  • the filling process is aborted and an error message appears .
  • the user can then correct the error if necessary, insert a waste bag and recalibrate the systems.
  • the filling process is continued.
  • the user of the system receives a message that the system needs to be calibrated.
  • next target container can be inserted after the filling process is complete.
  • FIG. 12 is a flow chart used to explain the calculation of the target weight in a dosing step.
  • the volume of the liquid introduced is calculated using the pressure-side characteristic of the peristaltic pump.
  • the target weight can then be calculated from the specific weight of the transferred liquid or liquids.
  • This target weight is used to determine the in 8 mentioned limit values.
  • a first limit range could be defined as a deviation of more than 10% and a second limit range as a deviation of more than 5%.
  • limit ranges can also be varied as a function of the liquid removed during a dosing step, since there are components for which deviations in quantity are more or less critical for the quality of the medicinal preparation.
  • Fig. 12 is a flow chart for explaining the bubble sensor control.
  • the amount of bubbles in the transferred liquid is continuously monitored by the bubble sensor located after the peristaltic pump.
  • the filling process is interrupted and an error message is displayed.
  • next target container can be inserted after the filling process is complete
  • Fig. 12 is a flowchart for explaining flow sensor control.
  • the flow rate is continuously calculated, preferably on the basis of the suction-side characteristic curve of the peristaltic pump.
  • the flow rate is measured with a flow sensor arranged on the flow side in front of the peristaltic pump.
  • a deviation above a threshold value in this example 20%, an error (e.g. occlusion) is assumed and the filling process is aborted.
  • the user is informed of an error message.
  • the source container is preferably displayed to the user (e.g. via a number on a screen) in the event of any error message, from which liquid was taken when the error occurred.
  • the accuracy in the manufacture of a medicinal preparation using a peristaltic pump and at the same time the security against dosing errors can be improved.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nutrition Science (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • External Artificial Organs (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Loading And Unloading Of Fuel Tanks Or Ships (AREA)

Claims (14)

  1. Procédé de fabrication d'une préparation médicale, en particulier d'une alimentation parentérale, dans lequel des liquides sont transférés d'une pluralité de récipients sources (2) dans un récipient cible (3) à l'aide d'une pompe péristaltique (6), dans lequel le récipient cible (3) est pesé lors des étapes de dosage individuelles et la quantité de liquide transférée dans le récipient cible (3) est ainsi vérifiée lors des étapes de dosage individuelles, caractérisé,
    en ce que la succession de différents liquides dans une arrivée du récipient cible (3) est prise en compte afin de incorporer la masse spécifique du liquide lors de la vérification au moment du pesage.
  2. Procédé de fabrication d'une préparation médicale selon la revendication précédente, caractérisé en ce que la quantité de liquide transférée dans le récipient cible (3) est vérifiée à toutes les étapes de dosage.
  3. Procédé de fabrication d'une préparation médicale selon l'une quelconque des revendications précédentes, caractérisé en ce que la quantité de liquide transférée dans le récipient cible (3) lors d'une étape de dosage est calculée en tenant compte d'une courbe caractéristique côté pression de la capacité de pompage de la pompe péristaltique (6), dans lequel la quantité calculée est comparée à la quantité déterminée par le pesage du récipient cible (3).
  4. Procédé de fabrication d'une préparation médicale selon l'une quelconque des revendications précédentes, caractérisé en ce que la quantité de liquide prélevée dans un récipient source (2) est calculée en tenant compte d'une courbe caractéristique côté aspiration de la capacité de pompage de la pompe péristaltique (6), dans lequel la quantité calculée est comparée à la quantité déterminée par le pesage du récipient cible (3).
  5. Procédé de fabrication d'une préparation médicale selon l'une quelconque des revendications précédentes, caractérisé en ce que, lors d'au moins une étape de dosage, une quantité minimale inférieure à 10 ml, de préférence inférieure à 5 ml, de manière particulièrement préférée inférieure ou égale à 3 ml est transférée.
  6. Procédé de fabrication d'une préparation médicale selon l'une quelconque des revendications précédentes, caractérisé en ce que la pompe péristaltique (6) présente au moins une zone à courbe caractéristique linéaire et une zone à courbe caractéristique non linéaire de la capacité de pompage,
    dans lequel, pour le dosage à partir d'au moins un récipient source, la pompe péristaltique (6) est amenée dans une position telle que la totalité du dosage à partir du récipient source (2) s'effectue dans la zone à courbe caractéristique linéaire.
  7. Procédé de fabrication d'une préparation médicale selon l'une quelconque des revendications précédentes, caractérisé en ce que la pompe péristaltique (6) est amenée dans une position dans laquelle la courbe caractéristique côté aspiration de la pompe péristaltique (6) est linéaire.
  8. Procédé de fabrication d'une préparation médicale selon l'une quelconque des revendications précédentes, caractérisé en ce que, pour amener la pompe péristaltique (6) dans la position souhaitée à courbe caractéristique linéaire, du liquide est prélevé dans un récipient source différent de celui à partir duquel le dosage doit être effectué, en particulier dans un récipient source contenant un liquide universel ou de l'eau.
  9. Procédé de fabrication d'une préparation médicale selon l'une quelconque des revendications précédentes, caractérisé en ce que, dans la zone à courbe caractéristique linéaire, une quantité minimale est transportée avec un volume inférieur à 10 ml, de préférence inférieur à 3 ml.
  10. Procédé de fabrication d'une préparation médicale selon l'une quelconque des revendications précédentes, caractérisé en ce que le débit de la pompe péristaltique (6) est vérifié à l'aide d'un capteur de débit (16) et/ou en ce qu'il est vérifié à l'aide d'un capteur de bulles (17) qu'il n'y a pas de bulles dans une arrivée au récipient cible (3).
  11. Procédé de fabrication d'une préparation médicale selon l'une quelconque des revendications précédentes, caractérisé en ce que le facteur de dosage de la pompe péristaltique (6) est déterminé au cours d'une étape d'étalonnage préalable au moyen du pesage d'un récipient cible (3).
  12. Procédé de fabrication d'une préparation médicale selon l'une quelconque des revendications précédentes, caractérisé en ce que, pour transférer les liquides des récipients sources (2) dans le récipient cible (3), un kit de transfert est utilisé, qui comprend une unité de soupape (5), un tuyau (14) qui peut être inséré dans la pompe péristaltique et une pluralité de tuyaux (15) pour raccorder les récipients sources (2).
  13. Procédé de fabrication d'une préparation médicale selon l'une quelconque des revendications précédentes, dans lequel le facteur de dosage de la pompe est étalonné lors d'une étape de dosage à partir d'un récipient source, au cours de laquelle une roue de pompe (8) de la pompe péristaltique (6) tourne sur au moins un tour complet.
  14. Installation pour la fabrication d'une préparation médicale, en particulier installation pour la fabrication d'une alimentation parentérale, comprenant une pompe péristaltique, caractérisée par un système pour la mise en oeuvre d'un procédé selon l'une quelconque des revendications 1 à 13 précédentes.
EP17710921.2A 2016-03-15 2017-03-15 Procede de fabrication d'une preparation medicamenteuse Active EP3429546B1 (fr)

Priority Applications (1)

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EP23168051.3A EP4218709A1 (fr) 2016-03-15 2017-03-15 Procede de fabrication d'une preparation medicamenteuse

Applications Claiming Priority (2)

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EP16160323 2016-03-15
PCT/EP2017/056137 WO2017158032A1 (fr) 2016-03-15 2017-03-15 Procédé pour élaborer une préparation médicinale

Related Child Applications (1)

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EP3429546B1 true EP3429546B1 (fr) 2023-04-19

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US (1) US10966906B2 (fr)
EP (2) EP3429546B1 (fr)
CN (1) CN108778228B (fr)
ES (1) ES2945413T3 (fr)
PL (1) PL3429546T3 (fr)
WO (1) WO2017158032A1 (fr)

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Publication number Priority date Publication date Assignee Title
WO2017158009A1 (fr) * 2016-03-15 2017-09-21 Fresenius Kabi Deutschland Gmbh Installation pour élaborer une préparation médicinale
US11846279B2 (en) 2021-01-29 2023-12-19 Masterflex, Llc Accurate volume dispensing using pump and flow sensor
US11920581B2 (en) 2021-01-29 2024-03-05 Masterflex Llc Flow rate control for pump with flow sensor
WO2023170680A1 (fr) 2022-03-08 2023-09-14 Equashield Medical Ltd Station de transfert de fluide dans un système de préparation pharmaceutique robotique

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US10966906B2 (en) 2021-04-06
ES2945413T3 (es) 2023-07-03
CN108778228A (zh) 2018-11-09
EP4218709A1 (fr) 2023-08-02
CN108778228B (zh) 2022-01-14
PL3429546T3 (pl) 2023-07-17
US20190070074A1 (en) 2019-03-07
WO2017158032A1 (fr) 2017-09-21
EP3429546A1 (fr) 2019-01-23

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