Medical product comprising an ampoule made from a plastic material comprising a neuraxial drug

Abstract

A medical product comprising an ampoule, wherein the ampoule is made from a plastic material, wherein the ampoule comprises an ampoule body part and an ampoule head part, wherein the ampoule body part comprises an opening comprising a connection portion, wherein the opening is closed by the ampoule head part, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016, and wherein the ampoule body part is filled with a neuraxial drug.

Description

[0001] Medical Product Comprising an Ampoule Made from a Plastic Material comprising a Neuraxial Drug

[0002] Technical Field of the Invention

[0003] The present invention is concerned with medical products for the administration of neuraxial drugs and the production process thereof. In particular, the present invention is concerned with medical products for providing neuraxial drugs to devices or delivery systems, preferably to systems for neuraxially administering said neuraxial drug.

[0004] Background of the Invention

[0005] Pharmaceutical solutions are typically stored in glass or plastic vials, glass or plastic ampoules, or plastic pouches having various types of connectors. Historically, vials, glass bottles, and plastic pouches were accessed through elastomeric stoppers using needles. Accessing vials, ampoules or pouches and transferring the pharmaceutical solution using needles has the drawback of potential risks using sharp devices, such as piercing of the container walls, creation of fragments of elastomeric stopper or plastic membrane, needle-stick injuries, and general difficulty of pushing the needle through the elastomeric stopper.

[0006] To overcome the problem of handling the solution with a needle, other kinds of containers such as glass ampoules and later plastic ampoules were developed over the years, which provide access to their content through an open neck after breaking off an ampoule head. Such ampoules can be accessed using a needle, similar to those used to pierce elastomeric stoppers or blunt needles. In addition, also plastic needles of transfer devices, as well as semi-flexible straws could be used to transfer the pharmaceutical solution. Moreover, for withdrawing the content of glass ampoules, needles or straws are typically equipped or combined with inline filters to prevent glass particles from being directed into the withdrawing devices and later being administered to the patient.

[0007] Another approach to overcome said problems has been suggested by WO 9600556 A1 thereby creating the possibility of transferring pharmaceutical solutions from ampoules to other devices without the use of needles. Therefore, needle-less connectors have been developed to overcome the above-mentioned problems. The most common needle-less connector is the Luer connector, as currently defined in ISO 80369-7:2021. This connector allows liquid-tight connection of two devices and transfer of a pharmaceutical solution in between these devices. However, the Luer connector, although being safe and convenient, is used to transfer many kinds of drugs regardless of their intended application route. There is, however, a medical risk to administer drugs in a route which they are not supposed to be administered into.

[0008] Summary of the Invention

[0009] Neuraxial drugs are often provided in containers, such as ampoules, which are used to transfer the neuraxial drug from the container to a syringe prior to administration. If containers described in the prior art are used, drugs different from neuraxial drugs could be accidentally neuraxially administered leading to major harm or even death of the patient.

[0010] Thus, it is an object of the present invention to provide neuraxial drugs without the risk of accidental harm or death of a patient.

[0011] It has now been surprisingly found that this object can be achieved by a medical product comprising an ampoule, wherein the ampoule is made from a plastic material, wherein the ampoule comprises an ampoule body part and an ampoule head part, wherein the ampoule body part comprises an opening comprising a connection portion, wherein the opening is closed by the ampoule head part, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016, and wherein the ampoule body part is filled with a neuraxial drug.

[0012] It has been further surprisingly found that above-mentioned object can be achieved by a process for manufacturing a medical product, the process comprising the steps of in a body part preparing step preparing an ampoule body part from a plastic material, wherein the ampoule body part comprises an opening; in a connection portion provision step providing a connection portion comprised by the opening, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016, and in a filling step filling the ampoule body part with a neuraxial drug, preferably via the opening, or in a filling step filling the ampoule body part with a neuraxial drug, preferably via the opening, and in a connection portion provision step providing a connection portion comprised by the opening, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016; in a head part provision step providing an ampoule head part at the opening of the body part; in a sealing step sealing the ampoule body and the ampoule head part.

[0013] Moreover, it has been surprisingly found that above-mentioned object can be achieved by a method of using an ampoule according to the present invention, the method comprising the steps of breaking off the ampoule head part thereby exposing the connection portion, connecting a male connector according to ISO 80369-6:2016 of a medical device to the connection portion, and transferring the drug from the ampoule body part into the medical device.

[0014] The present invention has the advantage that the neuraxial drug from the medical product according to the present invention can only be transferred to a system for neuraxially administering a drug. Other containers having different connector systems will not be able to provide their content to said system for neuraxially administering a drug. Thus, risk of accidental injection of a drug not meant for neuraxial administration into a system for neuraxially administering a drug can be highly reduced.

[0015] Finally, it has been surprisingly found out that above-mentioned object can be achieved by an active pharmaceutical ingredient (API) for use in the treatment of a patient in need thereof, wherein the treatment comprises providing medical product comprising an ampoule, wherein the ampoule is made from a plastic material, wherein the ampoule comprises an ampoule body part and an ampoule head part, wherein the ampoule body part comprises an opening comprising a connection portion, wherein the opening is closed by the ampoule head part, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016, wherein the ampoule body part is filled with a neuraxial drug, and wherein the neuraxial drug comprises the API, filling the neuraxial drug from the ampoule of the medical product into a syringe yielding a filled syringe, wherein the syringe comprises an opening comprising a male connection portion compliant with ISO 80369-6:2016, and administering the neuraxial drug via the filled syringe to the patient.

[0016] Brief Description of the Drawings

[0017] Figure 1 shows a schematic drawing of a preferred embodiment of the medical product according to the present invention having a twist-off cap. Figure 2 shows a schematic drawing of a preferred embodiment of the medical product according to the present invention having a twist-off cap with integrated finger stoppers.

[0018] Figure 3 is a close-up of the opening part of the embodiment shown in Figure 1.

[0019] Figure 4 is a close-up of the opening part of the embodiment shown in Figure 2.

[0020] Figure 5 is a schematic drawing of the non-interconnectability of connectors according to ISO 80369-6:2016 (NRFit) and ISO 80369-7:2021 (Luer).

[0021] Figure 6 is a schematic drawing of the structural dimension of the connection portion according to the present invention.

[0022] Definitions

[0023] The term ‘plastic material’ as used herein denotes a material comprising one or more polymer as the major component, preferably comprising more than 50 wt.-% of one or more polymer, more preferably more than 60 wt.%, even more preferably more than 70 wt.-%, and most preferably more than 90 wt.-%. The plastic material is characterized by being able to be molded, extruded or pressed into shapes. Usually, the plastic material comprises other components comprising additives besides the one or more polymer.

[0024] The term ‘additive’ as used herein denotes further components, which can be present in polymer compositions to modify their physical properties. Examples of additives are antioxidant(s), stabilizer(s), such as process stabilizers and UV stabilizers, acid scavenger(s), metal deactivators, crosslinking agents, such as free radical generating agent(s), e.g., organic peroxide(s), scorch retarder(s), crosslinking booster(s), processing aid(s), flame retardant additive(s), water tree retardant additive(s), inorganic filler(s), and voltage stabilizer(s). These groups of additives and the individual additive compounds therein are usually well known in the polymer field.

[0025] The term ‘ampoule made of a plastic material’ as used herein denotes that while the material of the ampoule comprises the plastic material, it can also comprise other materials. Preferably, the ampoule is produced such that at any cross section of the wall of the ampoule at least at some point the plastic material is present. More preferably, the ampoule is produced such that the plastic material used surrounds the ampoule inner cavity in one piece. The ampoule made of a plastic material optionally comprises inner and / or outer layers, which are made of different materials, such as metal oxide coating. Furthermore, further inner layers may be present, i.e. comprising EVOH. The term ‘polymer" as used herein denotes an organic polymer, preferably a polymer selected from polyolefins, polyethylene terephthalate, polystyrene, polyvinyl chloride, or mixtures thereof, more preferably a polyolefin selected from the list consisting of polyethylene, polypropylene, or mixtures thereof.

[0026] The term ‘oxygen scavenger’ as used herein denotes a compound, which is suitable for binding molecular oxygen from the surrounding atmosphere. The binding may occur physically or chemically. Preferably, the binding occurs chemically. Most preferably, the oxygen scavenger is an antioxidant.

[0027] The term ‘neuraxially administering’ as used herein denotes the administration process usually used in neuraxial anesthesia, wherein a local or regional anesthesia is placed around the nerves of the central nervous system. Specific embodiments thereof are spinal anesthesia, caudal anesthesia, epidural anesthesia, or combined spinal and epidural anesthesia.

[0028] The term ‘system for neuraxially administering a drug’ is a system, which is designed for receiving a drug and for neuraxially administering a drug. The system comprises a drug administering part and a drug receiving part. The drug receiving part preferably comprises a poka-yoke (or rigid-rigid) connector, such as disclosed in ISO 80369, which prevents inadvertent connection (i.e. by a key-lock principle). The drug administering part could for example be a syringe, or even a syringe in a syringe pump.

[0029] The term ‘liquid-tight’ as used herein denotes a quality of an object to function as a barrier for a liquid, preferably for a water-based liquid.

[0030] The term ‘barrier layer" as used herein denotes a material, which can slow down the process of oxygen permeation. Preferably, it comprises, more preferably consists of, a plastic barrier material, most preferably ethylene-vinyl alcohol (EVOH), or a metal oxide material, most preferably a silicon oxide layer or an aluminum oxide layer. Such barrier layer can require a supporting or binding layer to adhere to the ampoule wall material , such as in particular the EVOH layer. Metal oxide-based layers can be deposited directly onto the polymer material (e.g., by chemical vapor deposition).

[0031] The term ‘nominal volume’ is the declared volume of the neuraxial drug that shall, as per pharmacopeial requirements, at least be possible to be extracted from the ampoule during the shelf life of the product.

[0032] The term ‘total volume’ is the maximum volume which can be contained in the ampoule at pressure equilibrium with the surrounding environment. The total volume of an ampoule is measured by filling said ampoule with water at 23±2 °C and at zero-gauge pressure, wherein the water is filled in the ampoule without any further pressure other than provided by the gravity until the ampoule is completely filled with water without any visible introduced gas, wherein the volume of the ampoule cavity is the volume of the water.

[0033] The term ‘break-off cap’ denotes a cap, which can be opened by breaking off at least one part thereof. Preferably, the break-off cap comprises a tube, which is closed at the end extending from the ampoule. This tube preferably has a recess, preferably a circular recess having the same symmetry axis as the tube. In this recess, the material thickness is lower than the material thickness of the wall of the tube, preferably lower than 0.2 times the thickness of the wall of the tube, more preferably lower than 0.1 times the thickness of the wall of the tube. Preferably, the term break-off cap as used herein denotes caps, which are broken off by twisting the at least one part thereof, thereby opening the cap, and the ampoule at the brim of its connection portion.

[0034] Detailed Description of the Invention

[0035] As indicated above, the present invention relates to a medical product, a process for producing said medical product, a method for using said medical product, and an active pharmaceutical ingredient (API) for use in a treatment for a patient in need thereof. Each of these embodiments will be described in more detail in the following.

[0036] Medical product according to the invention

[0037] In the most generic embodiment of the medical product according to the present invention, the medical product is a medical product comprising an ampoule, wherein the ampoule is made from a plastic material, wherein the ampoule comprises an ampoule body part and an ampoule head part, wherein the ampoule body part comprises an opening comprising a connection portion, wherein the opening is closed by the ampoule head part, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016, and wherein the ampoule body part is filled with a neuraxial drug.

[0038] The neuraxial drug can be any drug generally used in neuraxial anesthesia. Thus, the neuraxial drug preferably is present in liquid form or in solution, preferably in aqueous solution. Moreover, the neuraxial drug comprises at least one active pharmaceutical ingredient (API). Preferably, the at least one API in the neuraxial drug in the medical product according to the present invention is selected from the list consisting of lidocaine and salts thereof, ropivacaine and salts thereof, bupivacaine and salts thereof, mepivacaine and salts thereof, prilocaine and salts thereof, fentanyl and salts thereof, sufentanil and salts thereof, baclofen and salts thereof, ziconotide and salts thereof, hydromorphone and salts thereof, morphine and salts thereof, dexmedetomidine and salts thereof, clonidine and salts thereof, beractant and salts thereof, poractant and salts thereof, and mixtures thereof. More preferably the at least one API in the neuraxial drug in the medical product according to the present invention is selected from the list consisting of lidocaine and salts thereof, ropivacaine and salts thereof, bupivacaine and salts thereof, mepivacaine and salts thereof, prilocaine and salts thereof, baclofen and salts thereof, ziconotide and salts thereof, and mixtures thereof. The advantage of the preferred active pharmaceutical ingredients comprised in the neuraxial drug is that these compounds are less sensitive to oxygen exposure thereby increasing the shelf life of the medical product.

[0039] In an alternative embodiment of the present invention, in the medical product the neuraxial drug further comprises epinephrine. More preferably, the neuraxial drug comprises a combination of lidocaine and epinephrine and / or bupivacaine and epinephrine. The advantage of the presence of epinephrine is an increased duration of the analgesia. Usually, the presence of epinephrine requires the presence of a barrier layer in the plastic material of the ampoule. Hence, preferably, the ampoule body part further comprises epinephrine.

[0040] The female connection portion of the ampoule of the medical product according to the present invention is compatible with a male connector according to ISO 80369-6:2016. Preferably, the female connection portion of the ampoule of the medical product according to the present invention is compliant with the female connector of ISO 80369- 6:2016. Male and female connectors according to ISO 80369-6:2016 are in particular different from connectors according to ISO 80369-7:2021. An example for a connector according to ISO 80369-7:2021 is the so-called Luer connector. Likewise, an example for a connector according to ISO 80369-6:2016 is the NRFit® connector commercially introduced by GEDSA. In both cases the male connector comprises a conical tube concentrically surrounded by a cylindrical tube. The inner space of the conical tube is connected with the flow path of the respective device of the connector. Likewise, the female connector comprises in both cases just one conical tube with an outer cone attached thereto. The conical tube of the female connector is designed to fit the space between the conical tube and the cylindrical tuber of the male connector. However, the diameters of the connectors according to ISO 80369-6:2016 are 20% smaller than the respective diameters of the connectors according to ISO 80369-7:2021. Furthermore, the lengths of the tubes of the connectors according to ISO 80369-6:2016 are 3 mm longer than the lengths of the respective tubes of the connectors according to ISO 80369-7:2021 . As a result, neither a male connector according to ISO 80369-7:2021 fits a female connector according to ISO 80369-6:2016 nor a female connector according to ISO 80369-7:2021 fits a male connector according to ISO 80369-6:2016. Consequently, a connector according to ISO 80369-7:2021 could not be accidentally connected to a connector according to ISO 80369-6:2016 and vice versa (cf. Figure 5).

[0041] The connection portion of the ampoule according to the present invention can be either directly molded into the wall of the ampoule or could be inserted in the wall of the ampoule as a preformed insert. In one preferred embodiment of the invention, the connection portion of the ampoule according to the present invention is inserted in the wall of the ampoule as a preformed insert. The advantage of this design is that the dimensions of the insert can be prepared in increased precision in comparison to the connection portion being molded into the wall of the ampoule, preferably by injection molding. In another preferred embodiment of the present invention, the connection portion is directly molded into the wall of the ampoule. This embodiment has the advantage of less complexity, therefore being less error prone, and the possibility to be achieved with existing machinery, thereby significantly reducing costs.

[0042] The female connection portion of the ampoule of the medical product according to the present invention preferably has a cylindrical shape. More preferably, the cylindrical shape is formed as defined in Figure 6. Thereby, the connection portion preferably comprises a lead-in part and a tightening part, wherein the lead-in part is closer to the intended opening of the connection portion than the tightening part. Generally, both the lead-in part and the tightening part are both of cylindrical shape. Preferably, the average inner diameters of the lead-in part and the tightening part are different, more preferably, the average inner diameter (c) of the tightening part is smaller than the average inner diameter (b) of the lead-in part and / or the maximum inner diameter of the tightening part is lower than the maximum inner diameter of the lead-in part. The larger average and minimum inner diameter of the lead-in part allows for easier insertion of a male connector into the female connector.

[0043] The connection portion may further comprise a transition part between the lead-in part and the tightening part, which allows for a smooth transition from the different inner diameter sizes of these parts. Moreover, the lead-in part may have an opening, which has a reduced inner diameter (a) in comparison to the average inner diameter (b) of the lead-in part.

[0044] Preferably, the maximum inner diameter of the tightening part is 3.9 mm or smaller, preferably 3.8 mm or smaller, and most preferably 3.7 mm or smaller. This has the advantage that a Luer male connector cannot accidentally enter the tightening part. More preferably, however, the maximum inner diameter of the lead-in part is 3.9 mm or smaller, preferably 3.8 mm or smaller, and most preferably 3.7 mm or smaller. This has the advantage that a Luer male connector cannot accidentally enter the whole connection portion in combination with the effect of a better fitting.

[0045] Additionally, the reduced inner diameter (a) helps further to prevent insertion of wrong male connectors.

[0046] Preferably, the distance between the opening of the connection portion and the beginning of the tightening zone (d) is equal to or smaller than 3.2 mm, preferably equal to or smaller than 3.0 mm, and most preferably equal to or smaller than 2.8 mm. This ensures that the mal connector reaches the tightening zone and overlaps with it at least to a certain degree.

[0047] More preferably, the axial length of the tightening zone (e) is larger than 1 mm, preferably larger than 1.5 mm, and most preferably larger than 2 mm. This ensures tightening and in particular a liquid tight or even fluid-tight connection (no gas permeation).

[0048] Optionally, the cylindrical parts of the connection portion may comprise one thread on each side. This is advantageous as during production usually molds with two halfs are used. Preferably, the connection portion has two threads at each side.

[0049] In another preferred embodiment, the cylindrical parts of the connection portion may comprise one lock on each side. The difference between a thread and a lock is that the lock has a 90° angle to the axis of the cylinder.

[0050] In a preferred embodiment of the present invention, the ampoule of the medical product of the present invention is manufactured or manufacturable using the process of the present invention, preferably a blow-fill-seal process. Nevertheless, it should be mentioned that also other processes may be used for the manufacture thereof. The ampoule of the present invention is preferably liquid tightly closed and sealed to prevent leakage of the neuraxial dug or contamination thereof.

[0051] Preferably, the plastic material from which the ampoule of the medical product according to the present invention comprises a polymer material, more preferably an organic polymer material, even more preferably a polyolefin material, and most preferably a polyethylene or polypropylene material. These materials have an ideal balance of material properties, processability, inertia in view of the neuraxial drug, and low price.

[0052] Preferably, the plastic material of the ampoule of the medical product according to the present invention has a haze value measured according to ASTM D1003, Procedure B, of less than 60%, preferably less than 30%, more preferably less than 25%, and most preferably less than 15%. This ensures that the user can easily control the filling status of the ampoule. More preferably, a wall of the ampoule of the medical product according to the present invention has a haze value measured according to ASTM D1003, Procedure B, of less than 60%, preferably less than 30%, more preferably less than 25%, and most preferably less than 15%.

[0053] In a preferred embodiment, the plastic material of the ampoule of the medical product according to the present invention is a multilayer plastic material. The multilayer plastic material can be prepared by coextrusion, e.g., in a blow-fill-seal process or by laminating or coating either the inner surface of the ampoule prior to filling the ampoule or laminating or coating the outer surface of the ampoule subsequent to sealing the ampoule. Hence, the ampoule can have an innermost layer, wherein the innermost layer denotes the layer forming at least parts, preferably all of, the inner surface of the ampoule, and the ampoule can have an outermost layer, wherein the outermost layer denotes the layer forming at least parts, preferably all of, the outer surface of the ampoule.

[0054] The innermost layer usually has the function of providing inertia of the ampoule material in view of the neuraxial drug. Hence, preferably, the material of the innermost layer is a material, which prevents or at least reduces migration of compounds of the multilayer plastic material of the ampoule into the neuraxial drug or solution thereof. Furthermore, the material of the innermost layer is preferably a material, which prevents or at least reduces migration of compounds from the neuraxial drug or solution thereof into the multilayer plastic material of the ampoule of the medical product according to the invention. Particularly preferably, the material of the innermost layer is a material, which prevents or at least reduces migration of the neuraxial drug or solution thereof into the multilayer plastic material of the ampoule of the medical product according to the invention. Hence, most preferably, the material of the innermost layer of the ampoule of the medical product according to the present invention is selected from the list consisting of a linear polypropylene, a linear polyethylene, or a cyclic olefin, more preferably is a cyclic olefin.

[0055] The function of the outermost layer of the multilayer plastic material of the ampoule of the medical product according to the invention is to provide impact protection from the environment to protect the ampoule wall. Hence, preferably, the material of the outermost layer is preferably a polymer material having improved mechanical properties, such as tensile strength, impact strength, and / or toughness. Hence, preferably, the material of the outermost layer of the ampoule of the medical product according to the present invention is a polyolefin material, most preferably is selected from a polyethylene or a polypropylene.

[0056] The multilayer plastic material of the ampoule of the medical product according to the present invention preferably further comprises a barrier layer. The function of the barrier layer is to slow down the process of oxygen permeation through the ampoule wall into the neuraxial drug. Furthermore, a barrier layer can also reduce water migration from the neuraxial drug in the ampoule to the environment, thereby increasing shelf life as the concentration of the neuraxial drug is maintained for a longer time. Hence, shelf life of the medical product is increased by the barrier layer, as oxidative degradation of the neuraxial drug is delayed. Hence, preferably, the barrier layer of the ampoule of the medical product according to the present invention comprises, more preferably consists of, a material selected from ethylene vinyl alcohol (EVOH) or a metal oxide, preferably aluminum oxide or silicon oxide, most preferably the barrier layer of the ampoule of the medical product according to the present invention comprises, more preferably consists of, ethylene vinyl alcohol (EVOH). If the barrier layer is made from EVOH, the barrier layer is preferably included in the multilayer material of the ampoule of the medical product according to the present invention by being coextruded in between inner and outer layers. Additionally, typically intermediate tie layers are extruded at the same time. If the barrier layer is made from a metal oxide, it is preferably deposited on the surface of the ampoule of the medical product according to the present invention, preferably via chemical vapor deposition.

[0057] In an especially preferred embodiment of the present invention, the barrier layer of the multilayer plastic material of the ampoule of the medical product according to the present invention is implemented in that the ampoule of the medical product according to the present invention comprises a barrier label layer, preferably an outermost barrier label layer.

[0058] It is preferred that the multilayer plastic material of the ampoule of the medical product according to the present invention comprises an oxygen scavenger. This further reduces the oxygen permeability of the material. In such a way, the amount of oxygen diffusing into the ampoule is reduced, which further reduces the likelihood of oxidative degradation of the packed pharmaceutical solution, hence increases its shelf life. The presence of the oxygen scavenger is preferably realized in that the multilayer plastic material of the ampoule of the medical product according to the present invention comprises an oxygen absorber layer, preferably an oxygen absorber layer comprising an oxygen scavenger substance, more preferably an oxygen absorber layer comprising an oxygen scavenger substance in a polypropylene or cyclic olefin polymer matrix. The ampoule of the medical product according to the present invention preferably has a nominal volume of equal to or more than 0.1 ml, preferably equal to or more than 0.5 ml, even more preferably equal to or more than 1.0 ml, still even preferably equal to or more 5 ml, and most preferably equal to or more than 10 ml. Likewise, the ampoule of the medical product according to the present invention preferably has a nominal volume of equal to or less than 100 ml, more preferably equal to or less than 75 ml, even more preferably equal to or less than 50 ml, and most preferably equal to or less than 20 ml. Moreover, the ampoule of the medical product according to the present invention preferably has a total volume of equal to or more than 0.1 ml, preferably equal to or more than 0.5 ml, even more preferably equal to or more than 1.0 ml, still even preferably equal to or more 5 ml, and most preferably equal to or more than 10 ml. Likewise, the ampoule of the medical product according to the present invention preferably has a total volume of equal to or less than 100 ml, more preferably equal to or less than 75 ml, even more preferably equal to or less than 50 ml, and most preferably equal to or less than 20 ml.

[0059] The shape of the ampoule can be spherical, cylindrical, cubic, or cuboid. Preferably, the shape of the ampoule is cylindrical or cuboid, most preferably, the shape of the ampoule is cuboid. If the shape of the ampoule is cylindrical or cuboid, the shape as a longitudinal dimension, which in case of the cylindrical shape equals the direction of the axis of the cylinder, and a at least one lateral dimension, which in case of the cylindrical shape equals the diameter of the cylinder. If the shape of the ampoule is cylindrical or cuboid, the opening of the ampoule is positioned at the area having lowest dimensions. Hence, for instance, if the shape of the ampoule is cylindrical and the diameter of the cylinder is smaller than the length of the cylinder, the opening is preferably positioned at one of the two parallel cyclic planes of the cylinder. Likewise, if the shape of the ampoule is cuboid, the opening is preferably positioned at one of the two areas having the smallest edge lengths.

[0060] Preferably, the ration of lengths of the longitudinal dimension to either the lateral dimensions of the ampoule of the medical product according to the present invention is in the range of from 1 :1 to 20: 1 , preferably form 2:1 to 15:1 , and most preferably from 4: 1 to 8:1.

[0061] The head part of the ampoule of the medical product according to the present invention is preferably a break-off cap. The break-off cap is preferably connected to the ampoule body part by a circular recess in the ampoule wall, which forms a predetermined breaking area. Hence, preferably, the head part of the ampoule of the medical product of the present invention can be broken- or twisted-off to open the opening and to expose the connection portion. Preferably, the head part comprises flaps or tabs. This has the advantage that the head part is easier to be broken- or twisted-off. Furthermore, the flaps or tabs preferably comprise finger stoppers to prevent touching areas, which should not be contaminated prior to connecting the ampoule to the system for neuraxially administering the neuraxial drug.

[0062] Process for producing the medical product according to the invention

[0063] In the most generic embodiment of the process for producing a medical product according to the present invention, the process comprises the steps of in a body part preparing step preparing an ampoule body part from a plastic material, wherein the ampoule body part comprises an opening; in a connection portion provision step providing a connection portion comprised by the opening, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016, and in a filling step filling the ampoule body part with a neuraxial drug, preferably via the opening, or in a filling step filling the ampoule body part with a neuraxial drug, preferably via the opening, and in a connection portion provision step providing a connection portion comprised by the opening, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016; in a head part provision step providing an ampoule head part at the opening of the body part; in a sealing step sealing the ampoule body and the ampoule head part.

[0064] It should be understood that at least some of these steps can be carried out in one step or at least in two joined steps. Nevertheless, the most generic embodiment of the present invention also covers embodiments, in which each of the described steps is carried out as a single step. The reason for joined steps is the production of the connection portion and the production of the head part. Depending on the method underlying the steps used, the steps could be linked in that the production either occurs in the same step as e.g. the production of the ampoule body part (i.e. the body part preparing step), or the steps are carried out using material left over from the production step of the ampoule body part.

[0065] The body part preparing step can be carried out using known methods for producing plastic containers, such as rotational molding, thermoforming, 3D printing, vacuum forming, or blow molding. Preferably, the body part preparing step is carried out using blow molding. The blow molding step can be an extrusion blow molding step, an injection blow molding step, or an injection stretch blow molding step.

[0066] In the extrusion blow molding step, plastic material is extruded in a parison, preferably a tube-shaped parison. The parison is inserted into a mold, preferably in that the mold comprises, preferably consists of two or more parts, which are disassembled (i.e. opened) before inserting the parison, and which are assembled (i.e. closed) after insertion of the parison. The mold preferably has a shape in that the assembled mold closes the tube-shaped parison at one end and allows for inserting pressurized gas, preferably air, into the tube-shaped parison via the other end allowing for inflating the parison onto an inner surface of the mold. The mold preferably cools the extruded material of the parison. The advantage of extrusion blow molding is that the process step is simple and cheap. Another advantage is, even if not often used yet, that by extrusion multilayered materials and thus containers can be obtained.

[0067] In the injection blow molding step, a preform is formed by injection molding on a hollow core pin in a first step. Subsequently the preform and the core pin are added into a mold, the preform is heated and inflated by pressurized air through the hollow core pin allowing for inflating the preform onto an inner surface of the mold. The mold preferably cools the extruded material of the preform and after disassembling. The injection blow molding step is advantageous, as the dimensional stability and thickness of the connection portion can be controlled as it is formed in the injection mold step before blowing. On the other hand, multilayered material is harder to achieve due to the injection molding step. Hence, barrier properties cannot be easily added into the process.

[0068] The injection stretch blow molding step adds a step of stretching and thus axially or even biaxially orienting the polymer before the blowing step.

[0069] Hence, most preferably, the body part preparing step comprises an extrusion blow molding step.

[0070] The shape of the ampoule body part can be spherical, cylindrical, cubic, or cuboid. Preferably, the shape of the ampoule body part is cylindrical or cuboid, most preferably, the shape of the ampoule body part is cuboid. If the shape of the ampoule body part is cylindrical or cuboid, the shape as a longitudinal dimension, which in case of the cylindrical shape equals the direction of the axis of the cylinder, and a at least one lateral dimension, which in case of the cylindrical shape equals the diameter of the cylinder. If the shape of the ampoule body part is cylindrical or cuboid, the opening of the ampoule body part is positioned at the area having lowest dimensions. Hence, for instance, if the shape of the ampoule body part is cylindrical and the diameter of the cylinder is smaller than the length of the cylinder, the opening is preferably positioned at one of the two parallel cyclic planes of the cylinder. Likewise, if the shape of the ampoule body part is cuboid, the opening is preferably positioned at one of the two areas having the smallest edge lengths.

[0071] Preferably, the ration of lengths of the longitudinal dimension to either the lateral dimensions of the ampoule body part of the medical product according to the present invention is in the range of from 1 : 1 to 20:1 , preferably form 2:1 to 15:1 , and most preferably from 4: 1 to 8:1.

[0072] The plastic material used in the process according to the invention is as defined for ampoule of the medical product herein. Hence, the plastic material may also be a multilayer plastic material. If the plastic material is a multilayer plastic material, the body part preparing step preferably comprises an extrusion blow molding step. Hence, preferably, in the process according to the present invention the body part preparing step comprises the steps of extruding a parison and blowing the ampoule body from the parison.

[0073] The body part preparing step may comprise further steps in particular step for applying coatings or layers either on the innermost surface of the body part of the ampoule or on the outermost surface of the body part of the ampoule.

[0074] As already indicated above, the body part preparing step can include the connection portion provision step. However, this does not necessarily need to be the case. Also, in case that the body part preparing step is a blow molding step, the connection portion could be provided later. Thereby, the connection portion provision step can comprise a molding step, in which the connection portion is molded using rotational molding, thermoforming, 3D printing, vacuum forming, or blow molding. Thereby, the precision of the connection portion is defined by the method and in particular by the molds used. However, the connection portion provision step could also be a step of shaping the connection portion out of a preform.

[0075] Nevertheless, shaping the connection portion could also be used, if the connection portion provision step comprises a molding step, as the shaping step can improve the precision of the shape of the connection portion. Hence, preferably, in the process according to the present invention, the connection portion provision step comprises shaping an inner conduit of the connection portion.

[0076] Finally, the connection portion provision step could be either carried using completely separate material or could be carried out using material from the body part preparing step. For instance, if the body part preparing step is an extrusion blow molding step, the connection portion provision step could be using the part of the parison not being formed by the body part preparing step.

[0077] Likewise, for instance, if the body part preparing step is an injection blow molding step, the connection portion provision step could be using the part of the preform not being formed by the body part preparing step. Alternatively, the connection portion could be separately formed and simply placed in the opening of ampoule body portion and liquid tightly connected thereto, i.e. by sealing, welding or melting, in the connection portion provision step.

[0078] The connection portion is compatible with a male connector according to ISO 80369- 6:2016. Male and female connectors according to ISO 80369-6:2016 are in particular different from connectors according to ISO 80369-7:2021. An example for a connector according to ISO 80369-7:2021 is the so-called Luer connector. Likewise, an example for a connector according to ISO 80369-6:2016 is the NRFit connector. Hence, preferably, the male connector according to ISO 80369-6:2016 is a male NRFit connector. In both cases the male connector comprises a conical tube concentrically surrounded by a cylindrical tube, both having the same length. The inner space of the conical tube is connected with the flow path of the respective device of the connector. Likewise, the female connector comprises in both cases just one conical tube with an outer cone attached thereto. The conical tube of the female connector is designed to fit the space between the conical tube and the cylindrical tuber of the male connector. However, the diameters of the connectors according to ISO 80369-6:2016 are 20% smaller than the respective diameters of the connectors according to ISO 80369- 7:2021. Furthermore, the lengths of the tubes of the connectors according to ISO 80369-6:2016 are 3 mm longer than the lengths of the respective tubes of the connectors according to ISO 80369-7:2021. As a result, neither a male connector according to ISO 80369-7:2021 fits a female connector according to ISO 80369-6:2016 nor a female connector according to ISO 80369-7:2021 fits a male connector according to ISO 80369-6:2016. Consequently, a connector according to ISO 80369-7:2021 could not be accidentally connected to a connector according to ISO 80369-6:2016 and vice versa (cf. Figure 5).

[0079] Hence, preferably, in the process according to the present invention, the connection portion provision step comprises placing a male connector insert compatible according to ISO 80369-6:2016 into the opening of the ampoule body part. Moreover, also preferably, in the process according to the present invention, the connection portion provision step comprises shaping an external surface of the connection portion. In the filling step, the neuraxial drug is filled into the ampoule body part. The filling step can be carried out with any means of filling, such as funneling or injecting. Preferably, the filling step comprises an injecting step. Thereby, the neuraxial drug is injected, preferably using a hollow, more preferably tubular, filling device, more preferably a nonsharp tube made from a metal or a plastic material, even more preferably a cannula, such as an injection needle, preferably through the opening of the ampoule body, into the ampoule cavity defined by the ampoule body. Thus, preferably, the neuraxial drug is present in liquid form or in solution, preferably in aqueous solution. Moreover, the neuraxial drug comprises at least one active pharmaceutical ingredient (API). Preferably, the at least one API in the neuraxial drug in the medical product according to the present invention is selected from the list consisting of lidocaine and salts thereof, ropivacaine and salts thereof, bupivacaine and salts thereof, mepivacaine and salts thereof, prilocaine and salts thereof, fentanyl and salts thereof, sufentanil and salts thereof, baclofen and salts thereof, ziconotide and salts thereof, hydromorphone and salts thereof, morphine and salts thereof, dexmedetomidine and salts thereof, clonidine and salts thereof, beractant and salts thereof, poractant and salts thereof, and mixtures thereof. More preferably the at least one API in the neuraxial drug in the medical product according to the present invention is selected from the list consisting of lidocaine and salts thereof, ropivacaine and salts thereof, bupivacaine and salts thereof, mepivacaine and salts thereof, prilocaine and salts thereof, baclofen and salts thereof, ziconotide and salts thereof, and mixtures thereof. The advantage of the preferred active pharmaceutical ingredients comprised in the neuraxial drug is that these compounds are less sensitive to oxygen exposure thereby increasing the shelf life of the medical product.

[0080] In a preferred embodiment of the invention, the filling step, preferably the injecting step, is carried out in an oxygen reduced atmosphere, preferably in an oxygen depleted atmosphere. Most preferably, the filling step, preferably the injecting step, is carried out in an inert gas atmosphere, such as argon or nitrogen. This has the advantage of less oxygen being transferred into the ampoule body and less contact between the neuraxial drug and oxygen during the filling step, increasing the shelf life of the medical product produced and reducing the amount of neuraxial drug needed.

[0081] If the connection portion provision step has been carried out prior to the filling step, in the filling step, the neuraxial drug is filled through the connection portion into the ampoule body. Likewise, if the connection portion provision step has not been carried out prior to the filling step, in the filling step, the neuraxial drug is filled through the opening into the ampoule body. In parallel to the connection portion provision step, the head part provision step could also either be carried using completely separate material or could be carried out using material left over from the body part preparing step and / or the connection portion provision step.

[0082] For instance, if the body part preparing step is an extrusion blow molding step, the head part provision step could be using the part of the parison not being formed by the body part preparing step and / or the connection portion provision step. Likewise, for instance, if the body part preparing step is an injection blow molding step, the head part provision step could be using the part of the preform not being formed by the body part preparing step and / or the connection portion provision step. Alternatively, the head part could be separately formed and simply placed over the connection portion on the opening of the ampoule body portion. The head part and the opening could then be liquid tightly connected, i.e. by sealing, welding, melting, or overmoulding, in the sealing step.

[0083] In the most preferred embodiment of the present invention, the process according to the present invention is carried out using a blow-fill-seal process (BFS).

[0084] The BFS process is comparable to extrusion blow molding and is carried out in specific BFS machines. First, the plastic material resin is heated and compressed to a state to be extrudable. The conditions therefore depend on the material to be processed. Hence, for example, the plastic material can be heated to more than 140 °C, more preferably more than 160 °C, and compressed up to 35 MPa. In a second step, the heated and compressed plastic material is extruded in tubular parison. The tubular parison is inserted into an open multiple-part mold, preferably two-part mold. Subsequently, the bottom part of the multiple-part mold, preferably two-part mold, closes, thereby welding the bottom of the ampoule body part and shaping the opening in the upper part of the ampoule body part. It should be understood that the opening in the upper part needs to stay opened to be able to fill the ampoule subsequently. Simultaneously, the parison above the mold is cut, or filling needles are placed in the parison head without the parison being cut. Next, sterile compressed air is injected through the still intact parison or filing needles and the opening. Thereby, the parison in the mold is inflated and formed into the ampoule body part. For smaller ampoules no compressed air is used, but rather vacuum is drawn between the mould and the parison. The forming of the ampoule body part can already include forming the outer shape of the connection portion. After the ampoule body part has been formed, the neuraxial drug is filled into the ampoule body part, preferably under an oxygen-reduced or oxygen-depleted atmosphere, through the still intact parison or filling needles and the opening of the ampoule body part. After filling, an insert in the shape of the connection portion could be inserted in the parison. Alternatively, if the outer shape of the connection portion has not been formed during the forming of the ampoule body part, it will be formed by closing the connection portion part of the multiple-part mold, preferably two-part mold. Hence, after filling and optionally inserting an insert, the head part of the multiple-part mold, preferably two- part mold, is closed, thereby sealing the ampoule and forming the head part. In the last step, the multiple-part mold, preferably two-part mold, opens and the filled and sealed ampoule leaves the mold.

[0085] Method of using the medical product according to the invention

[0086] In the most generic embodiment of the method for using a medical product according to the present invention, the method comprises the steps of breaking off the ampoule head part thereby exposing the connection portion, connecting a male connector according to ISO 80369-6:2016 of a medical device to the connection portion, and transferring the drug from the ampoule body part into the medical device.

[0087] Furthermore, the method for using the medical product of the present invention , wherein the medical device is a syringe.

[0088] Active pharmaceutical ingredient (API) for use in a treatment

[0089] An active pharmaceutical ingredient (API) for use in the treatment of a patient in need thereof, wherein the treatment comprises providing medical product comprising an ampoule, wherein the ampoule is made from a plastic material, wherein the ampoule comprises an ampoule body part and an ampoule head part, wherein the ampoule body part comprises an opening comprising a connection portion, wherein the opening is closed by the ampoule head part, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016, wherein the ampoule body part is filled with a neuraxial drug, and wherein the neuraxial drug comprises the API, filling the neuraxial drug from the ampoule of the medical product into a syringe yielding a filled syringe, wherein the syringe comprises an opening comprising a male connection portion compatible with a male connector according to ISO 80369-6:2016, and administering the neuraxial drug via the filled syringe to the patient, preferably via a syringe pump comprising the filled syringe.

[0090] Neuraxial drugs can be administered as a bolus to induce the anesthesia (low volume, typically administered manually using small syringes) or as a continuous administration to maintain the effect (using a filled syringe and a syringe drive pump). Hence, preferably the administering the neuraxial drug via the filled syringe to the patient is directly achieved using the filled syringe, or via a syringe pump comprising the filled syringe. More preferably the administering the neuraxial drug via the filled syringe to the patient is achieved via a syringe pump comprising the filled syringe.

[0091] In a preferred embodiment of the active pharmaceutical ingredient (API) for use in a treatment, the medical product is the medical product according to the present invention.

[0092] In another preferred embodiment of the active pharmaceutical ingredient (API) for use in a treatment, the neuraxial drug can be any drug generally used in neuraxial anesthesia. Thus, the neuraxial drug preferably is present in liquid form or in solution, preferably in aqueous solution. Moreover, the neuraxial drug comprises at least one active pharmaceutical ingredient (API). Preferably, the at least one API in the neuraxial drug in the medical product according to the present invention is selected from the list consisting of lidocaine and salts thereof, ropivacaine and salts thereof, bupivacaine and salts thereof, mepivacaine and salts thereof, prilocaine and salts thereof, fentanyl and salts thereof, sufentanil and salts thereof, baclofen and salts thereof, ziconotide and salts thereof, hydromorphone and salts thereof, morphine and salts thereof, dexmedetomidine and salts thereof, clonidine and salts thereof, beractant and salts thereof, poractant and salts thereof, and mixtures thereof. More preferably the at least one API in the neuraxial drug in the medical product according to the present invention is selected from the list consisting of lidocaine and salts thereof, ropivacaine and salts thereof, bupivacaine and salts thereof, mepivacaine and salts thereof, prilocaine and salts thereof, baclofen and salts thereof, ziconotide and salts thereof, and mixtures thereof.

[0093] Even more preferably, the treatment of the active pharmaceutical ingredient (API) for use in a treatment is neuraxial anesthesia, most preferably the treatment is selected from spinal anesthesia, caudal anesthesia, epidural anesthesia, or combined spinal and epidural anesthesia.

Claims

Claims1. A medical product comprising an ampoule, wherein the ampoule is made from a plastic material, wherein the ampoule comprises an ampoule body part and an ampoule head part, wherein the ampoule body part comprises an opening comprising a connection portion, wherein the opening is closed by the ampoule head part, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016, and wherein the ampoule body part is filled with a neuraxial drug.

2. The medical product according to claim 1 , wherein the neuraxial drug is selected from the list consisting of lidocaine and salts thereof, ropivacaine and salts thereof, bupivacaine and salts thereof, mepivacaine and salts thereof, prilocaine and salts thereof, fentanyl and salts thereof, sufentanil and salts thereof, baclofen and salts thereof, ziconotide and salts thereof, hydromorphone and salts thereof, morphine and salts thereof, dexmedetomidine and salts thereof, clonidine and salts thereof, beractant and salts thereof, poractant and salts thereof, and mixtures thereof, preferably selected from the list consisting of lidocaine and salts thereof, ropivacaine and salts thereof, bupivacaine and salts thereof, mepivacaine and salts thereof, prilocaine and salts thereof, baclofen and salts thereof, ziconotide and salts thereof, and mixtures thereof.

3. The medical product according to claim 2, wherein the ampoule body part further comprises epinephrine.

4. The medical product according to any of the preceding claims 1 to 3, wherein the ampoule is manufactured or manufacturable using a blow-fill-seal process.

5. The medical product according to any of the preceding claims 1 to 4, wherein the plastic material comprises a polymer material, more preferably a polyolefin material, and most preferably a polyethylene or polypropylene material.

6. The medical product according to any of the preceding claims 1 to 5, wherein the plastic material is a multilayer plastic material.

7. The medical product according to claim 6, wherein the ampoule comprises an inner layer of plastic material and / or an outer layer of plastic material, preferablyan outer layer of a polyolefin material, and / or an inner layer of a linear polypropylene, a linear polyethylene, or a cyclic olefin, preferably an inner layer of a cyclic olefin.

8. The medical product according to claims 6 or 7, wherein the ampoule comprises a barrier layer, preferably a barrier layer comprising, more preferably consisting of, ethylene vinyl alcohol (EVOH).

9. The medical product according to any of the preceding claims 6 to 8, wherein the ampoule comprises an oxygen absorber layer, preferably an oxygen absorber layer comprising an oxygen scavenger substance, more preferably an oxygen absorber layer comprising an oxygen scavenger substance in a polypropylene or cyclic olefin polymer matrix.

10. The medical product according to any of the preceding claims 6 to 9, wherein the ampoule comprises a coating layer comprising a metal oxide, wherein the coating layer preferably is the innermost layer of the ampoule.11 . The medical product according to any of the preceding claims 6 to 10, wherein the ampoule comprises a barrier label layer, preferably an outer barrier label layer.

12. The medical product according to any of the preceding claims 1 to 11 , wherein the ampoule head part can be broken or twisted off to open the opening and to expose the connection portion.

13. A process for manufacturing a medical product, the process comprising the steps of in a body part preparing step preparing an ampoule body part from a plastic material, wherein the ampoule body part comprises an opening; in a connection portion provision step providing a connection portion comprised by the opening, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016, and in a filling step filling the ampoule body part with a neuraxial drug, preferably via the opening, or in a filling step filling the ampoule body part with a neuraxial drug, preferably via the opening, and in a connection portion provision step providing a connection portion comprised by the opening, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016; in a head part provision step providing an ampoule head part at the opening of the body part; in a sealing step sealing the ampoule body and the ampoule head part.

14. A method of using a medical product according to any of the preceding claims 1 to 12, comprising the steps of breaking off the ampoule head part thereby exposing the connection portion, connecting a male connector according to ISO 80369-6:2016 of a medical device to the connection portion, and transferring the drug from the ampoule body part into the medical device.

15. An active pharmaceutical ingredient (API) for use in the treatment of a patient in need thereof, wherein the treatment comprises providing medical product comprising an ampoule, wherein the ampoule is made from a plastic material, wherein the ampoule comprises an ampoule body part and an ampoule head part, wherein the ampoule body part comprises an opening comprising a connection portion, wherein the opening is closed by the ampoule head part, wherein the connection portion is compatible with a male connector according to ISO 80369-6:2016, wherein the ampoule body part is filled with a neuraxial drug, and wherein the neuraxial drug comprises the API, filling the neuraxial drug from the ampoule of the medical product into a syringe yielding a filled syringe, wherein the syringe comprises an opening compliant with a male connector according to ISO 80369-6:2016, and administering the neuraxial drug via the filled syringe to the patient, preferably via a syringe pump comprising the filled syringe.

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