Temperature measurement assembly, attachment, and system for determining temperature inside a medical container, method of temperature monitoring, process verification, and / or device validation

Abstract

The invention relates to a temperature measuring assembly (100) for determining a temperature inside a medical container (20), the medical container (20) having a hollow body (21) with an outer body wall (22) and a body opening (23). The temperature measuring assembly (100) comprises a temperature sensor (40) comprising at least one detector element (42) having a temperature sensing portion (41), and a sensor holder (30) holding the temperature sensor (40). The sensor holder (30) is configured to be mounted on the medical container (20) such that the sensor holder extends through the body opening (23) into the interior of the hollow body (21) and such that the temperature sensing portion (41) of the at least one detector element (42) is positioned inside the hollow body (21) at or near the outer body wall (22) of the hollow body (21). The invention further relates to a temperature measuring attachment (110) and a temperature measuring system (12) for determining a temperature inside a medical container (20), and to a method of using such a temperature measuring assembly (100), attachment (110) or system (120) for temperature monitoring, process validation and / or equipment qualification in connection with handling temperature controlled medical products.

Description

Technical Field

[0001] This invention relates to a temperature measurement assembly, temperature measurement attachment, and temperature measurement system for determining the temperature inside a medical container used to store medical products. The invention also relates to a method for temperature monitoring, process validation, and / or equipment verification related to handling temperature-controlled medical products using such a temperature measurement assembly, attachment, or system.

[0002] Such temperature measurement components, attachments, and systems, as well as such methods, can be used to ensure the reliability of equipment and processes deployed in connection with the handling of temperature-controlled medical products (e.g., transport equipment and processes) and to produce consistent results in accordance with applicable regulations. Such temperature measurement components, attachments, and systems, as well as such methods, can also be used for continuous monitoring, thereby ensuring that temperature conditions are correct throughout the handling of temperature-controlled medical products (e.g., throughout the transport chain). Background Technology

[0003] Generally, medical products (such as pharmaceuticals) are subject to strict regulation to ensure they are suitable for their intended use and free from inappropriate side effects. Not only products, but also related processes need to adhere to quality assurance programs to prevent errors or defects in manufactured products and to avoid problems when providing solutions or services to customers. In particular, in the pharmaceutical or medical industry, it is often crucial that products, devices, and processes consistently and reliably produce the intended results. To ensure this, process validation is typically required, and product and device verification is necessary.

[0004] As used herein, the term “validation” refers to the demonstration through objective evidence that the requirements or conditions for a particular application or use are met. Validation typically involves generating documented evidence that a performed process (e.g., a process performed in testing) maintains a required level of conformity to pre-established specifications at all stages. The result of a stable, validated process should always be the production of a product capable of performing its intended and declared tasks in real-world scenarios. Validation is a requirement of food, drug, and pharmaceutical regulatory agencies, such as the U.S. Food and Drug Administration (FDA). Good Manufacturing Practice (GMP) guidelines issued by these agencies stipulate that a separate set of procedures must be conducted to verify that the final product meets the predetermined specifications and requirements for its intended use and functions consistently within a given scope. Therefore, validation is essential for obtaining regulatory approval. Similarly, as used herein, the term “qualification” refers to documented evidence that the object to be validated is suitable and safe for its intended use or application. The object to be validated can be a system or device used to develop, test, manufacture, and process a final medical product.

[0005] Processes and equipment requiring validation or verification can involve any type of handling of medical products, such as their packaging and transportation. In this context, the packaging and transportation of temperature-sensitive products presents a significant challenge, requiring specific, stable, and therefore well-controlled temperature conditions that must be maintained throughout the entire process. Special care is needed for medical products packaged and transported frozen, as their temperature must not exceed critical temperatures. Quality guidelines and handling regulations may stipulate that temperature conditions are monitored continuously throughout the handling process and that only appropriately validated handling equipment is used to ensure proper transportation conditions. Therefore, appropriate temperature monitoring systems and procedures, as well as methods for validating handling processes and verifying handling equipment, are crucial.

[0006] Suitable methods for process validation and equipment qualification related to handling temperature-controlled medical products stored in large-volume medical containers already exist. However, while some devices for positioning probes in flasks are known, such as those described in US 5,447374 A, suitable measurement systems and procedures are lacking for process validation and equipment qualification related to temperature-controlled medical products stored in small-volume containers, particularly those with small openings. In particular, suitable tools are lacking to verify that the temperature inside such small-volume containers does not exceed a certain level.

[0007] Therefore, there is a need to allow for the validation of processing procedures and the verification of processing equipment involving small-volume medical containers, and in particular, to allow for temperature measurement tools and methods to determine the internal temperature of small-volume medical containers, especially those with small-sized openings. Summary of the Invention

[0008] According to the present invention, this need is addressed by a temperature measuring component for determining the temperature inside a medical container as defined in independent claim 1, a temperature measuring attachment as defined in independent claim 23, a temperature measuring system as defined in independent claim 24, and a method for temperature monitoring, process validation, and / or equipment verification related to handling temperature-controlled medical products as defined in independent claim 27. Preferred embodiments are the subject of the dependent claims.

[0009] In one aspect, the present invention relates to a temperature measuring component for determining the temperature inside a medical container. In the context of this invention, the term medical container preferably refers to a container for storing medical products. The medical container has a hollow body with an outer body wall and a body opening.

[0010] Specifically, medical containers can be small-volume containers with a maximum storage capacity of 10 ml or less, less than 5 ml, particularly less than 3 ml, more particularly less than 2.5 ml, such as 2 ml. The size of the body opening can depend on the size of the hollow body. The body opening can have a cross-sectional area of ​​less than 25 mm², particularly less than 20 mm², more particularly less than 18 mm². Similarly, the body opening can have a diameter or equivalent diameter of less than 8 mm, particularly less than 6 mm, more particularly less than 5 mm. The term "equivalent diameter" for the body opening is used herein in connection with body openings of non-circular cross-sectional shapes and is defined as the diameter of a circular body opening having the same surface area as a non-circular body opening. Medical containers can be made of sterilizable materials such as glass or plastics such as, for example, polypropylene. They may include caps or lids, which include seals such as rubber stoppers or diaphragms, and for many applications, the seals are designed to be puncturable.

[0011] Specifically, medical containers can be vials or cartridges commonly used in the pharmaceutical industry and research. As used herein, the term "via" can refer to a vial in its literal sense, i.e., a relatively small vessel or bottle typically used to store pharmaceutical products, drugs, or preparations in liquid, powder, or capsule form. Similarly, the term "cartridge" as used herein can refer to a more cylindrical container, typically used to store pharmaceutical products, drugs, or preparations in liquid, powder, or capsule form.

[0012] Medical containers, more specifically hollow bodies, may have a substantially cylindrical shape (possibly except for the portion including the opening of the body). The cylindrical shape may have a circular cross-section, an oval cross-section, an elliptical cross-section, a rectangular cross-section, a square cross-section, a triangular cross-section, or a polygonal cross-section.

[0013] As used herein, the term "medical product" preferably refers to a pharmaceutical product or drug, or a pharmaceutical preparation or drug product. As used herein, the term "drug" refers to a therapeutically active agent, often also called an active pharmaceutical ingredient (API), and combinations of multiple such therapeutically active substances. The term also covers diagnostic or imaging agents that need to be administered to a patient in liquid form, such as contrast agents (e.g., MRI contrast agents), tracers (e.g., PET tracers), and hormones. As used herein, the term "pharmaceutical product" refers to a drug formulated or reconstituted in a form suitable for administration to a patient, as defined above. Particularly preferred pharmaceutical products may be drug solutions, particularly solutions intended for main orifice administration, injection, or infusion.

[0014] The temperature measurement assembly according to the invention comprises: a temperature sensor including at least one detector element having a temperature sensing portion; and a sensor holder for holding the temperature sensor. Specifically, the sensor holder can be connected to the temperature sensor to hold it. The sensor holder is configured to be mounted on a medical container, particularly on the exterior of the medical container. As used herein, the term "mounted on a medical container, particularly on the exterior of the medical container" can include one of the following: placing the sensor holder on the medical container, particularly loosely on the medical container; or attaching the sensor holder to the medical container, particularly to the exterior of the medical container, preferably reversibly attached to the medical container. Similarly, mounting the sensor holder on the medical container can be such that the sensor holder rests in a body opening, or directly contacts the body opening, or indirectly in a channel opening of a cap or plug, which may be part of the medical container or part of a temperature measurement attachment as further described below.

[0015] Placing the sensor holder on the medical container allows at least a portion of the medical container to rest on, and in particular on, the exterior of, the medical container, in contact with, and especially with, its exterior, preferably only under the influence of gravity. For example, a portion of the sensor may be placed at the edge of the body opening, or directly on the hollow body, or on a cap or plug, which may be part of the medical container or part of a temperature measurement attachment as further described below. Therefore, placing the sensor holder allows for easy and uncomplicated installation of the temperature measurement assembly onto the medical container.

[0016] Conversely, attaching the sensor holder to the medical container, particularly to the exterior of the medical container, preferably securely couples the sensor holder to the medical container. As will be described in further detail below, the sensor holder may preferably include a clamping mechanism, particularly one or more clamping supports, configured to attach the sensor holder to the medical container, for example, to a flange and / or cap or plug of the medical container. This advantageously prevents the temperature measurement arrangement from shifting relative to the medical container or even being lost during handling.

[0017] During installation, the sensor holder of the temperature measurement arrangement according to the invention extends through the main body opening into the interior of the hollow body, and positions the temperature sensing portion of at least one detector element inside the hollow body at or near the outer body wall. Therefore, the temperature measurement arrangement advantageously enables the measurement of the temperature inside the medical container in critical areas that are first affected by external influencing factors. For example, if cooling fails or the cooling chain is interrupted during temperature-controlled transport, this may first affect the area at or near the outer body wall of the hollow body inside the container. Therefore, measuring the temperature in this area allows for the detection of temperature changes as quickly as possible, which in turn allows for reliable verification / validation of the effectiveness and robustness of the processes and equipment involved in handling medical products stored in the medical container.

[0018] Specifically, the sensor holder can be configured to position the temperature sensing portion of at least one detector element at or near a sidewall portion of the outer body wall of the hollow body, i.e., at or near the outer body sidewall of the hollow body, inside the hollow body. The sidewall portion of the outer body wall (or the outer body sidewall) can be located between the body opening and the bottom portion of the outer body wall, the bottom portion being the portion of the outer body wall opposite the body opening. This allows for particularly efficient temperature measurements for verification and similar processes, especially compared to placement near the bottom portion.

[0019] To mount the sensor holder onto a medical container, the sensor holder may include a support member configured to span a body opening, preferably positioned outside the medical container. Spanning the body opening may include placement directly across the body opening or placement across a channel opening of a cap or plug mounted on the body opening, wherein the cap or plug may be part of the medical container or part of a temperature measurement attachment as further described below. The support member may be used solely to place or attach the sensor holder to the medical container. As will be described in more detail below, the support member may, for example, have a plate shape.

[0020] Furthermore, the sensor holder may include one (single) or more legs to extend into the interior of the hollow body when inserted into it, wherein the temperature sensing portion of at least one detector element of the temperature sensor may be positioned inside the hollow body at or near the outer body wall of the hollow body when attached to one of the legs. For example, for use with a container having a maximum storage capacity of about 10 ml, the sensor holder may include four legs, or for use with a container having a maximum storage capacity of about 2 ml, the sensor holder may include three legs. Each leg may be equipped with a detector element.

[0021] Advantageously, the legs have an elongated design, thus allowing the temperature sensor to be easily inserted into the interior of the hollow body, even with a small opening. Furthermore, the elongated design has proven beneficial in reducing thermal mass and heat conduction through the sensor holder, both of which minimize the thermal impact of the sensor holder on the temperature sensor. In this regard, one or more legs may, for example, have a maximum lateral dimension, transverse to the corresponding length extension / longitudinal extension of the leg, in the range of 1 mm to 3 mm, particularly between 1.5 mm and 2 mm, or less than 1 mm. Similarly, one or more legs may have a cross-sectional area in the range of 0.5 mm² to 2 mm², particularly between 0.75 mm² and 1.5 mm² (as shown in the corresponding cross-section perpendicular to the corresponding length extension of the leg).

[0022] Further advantages can be achieved through the slender design of the legs and / or the reduction in thermal mass of the detector elements, as this enables the temperature sensor to achieve shorter response times and increased sensitivity.

[0023] The sensor holder, or (ultimately) at least one or more of its legs, can be manufactured by precisely cutting spring steel sheets using laser technology, particularly in an elongated design. After such cutting, it can be shaped using a bending machine.

[0024] As described above, the sensor holder may include one (single) or multiple legs. A single leg can be used to place a single detector element of the temperature sensor, more specifically, the temperature sensing portion of the single detector element of the temperature sensor, inside the hollow body. Conversely, the use of multiple legs advantageously allows multiple detector elements of the temperature sensor, more specifically, the temperature sensing portions of the multiple detector elements of the temperature sensor, to be positioned at different locations inside the hollow body. Thus, the temperature inside the medical container can be measured at different locations and in different spatial orientations, making the temperature measurement assembly sensitive along multiple spatial orientations and less critical to a particular installation configuration. The ability to place multiple detector elements inside the medical container further enables temperature difference measurements. For example, the sensor holder may include two, three, or four legs, preferably used to position a corresponding number of detector elements (i.e., two, three, or four detector elements) inside the hollow body.

[0025] Preferably, the legs, particularly, branch off from the support member substantially along the central length axis of the sensor holder: the central length axis of the sensor holder can be given by the main direction in which the set of legs extends. The central length axis of the sensor holder preferably defines the insertion axis of the sensor holder through the opening in the body.

[0026] In particular, the legs can be arranged symmetrically relative to the central length axis of the sensor holder, branching off from the support member. More specifically, the legs can be evenly distributed around the central length axis of the sensor holder. In particular, as shown by projection along the central length axis of the sensor holder, the legs can be arranged in a star shape. Due to the symmetrical, evenly distributed, or star-shaped arrangement, temperature measurement can advantageously be performed uniformly in all spatial directions, for example, relative to the central length axis of the sensor holder.

[0027] One or more legs may be bent or angled, the angle being particularly between 1 degree and 90 degrees, more particularly between 2 degrees and 45 degrees, preferably between 5 degrees and 20 degrees, for example 10 degrees. Specifically, each leg may comprise a first section extending substantially parallel to the central length axis of the sensor holder; and a second section extending away from the central length axis of the sensor holder in a direction transverse to it, such that the second sections of the legs branch off from each other. Such bending or angled configuration advantageously facilitates the proper positioning of the temperature sensing portion of at least one detector element of the temperature sensor within the hollow body, at or near the outer body wall.

[0028] Preferably, at least a portion of each leg, or the entire leg, is flexible, particularly elastically flexible, in at least one direction transverse to the corresponding length extension of the leg, particularly in a direction parallel to the plane spanned by the body opening, and even more particularly in a direction radially transverse to the central length axis of the sensor holder or the insertion axis of the sensor holder through the body opening. Depending on the size of the body opening, the use of flexible legs makes it easier to insert the legs into the housing opening, especially when the legs are bent or angled radially outward relative to the insertion axis of the sensor holder through the body opening. Furthermore, the use of elastically flexible legs has proven advantageous in pressing the temperature sensing portion of the detector element against the outer body wall of the hollow body to ensure proper contact with the outer body wall when necessary.

[0029] As mentioned above, one or more legs can be advantageously used to position one or more detector elements of the temperature sensor inside the medical container. Therefore, the temperature sensor may include one or more detector elements, each of which has a temperature sensing portion.

[0030] Each of the one or more detector elements is preferably mounted to one of the one or more legs. More preferably, each of the one or more detector elements is mounted to a corresponding free end portion of one of the one or more legs. Mounting the detector elements to the free end portions of the legs makes it particularly easy to position the corresponding temperature sensing portion of the detector element at or near the outer body wall of the hollow body. Advantageously, the number of detector elements corresponds to the number of legs. Thus, the temperature sensor may comprise one, two, three, or four detector elements.

[0031] At least one detector element may be one of the following: a thermocouple, a resistance temperature detector, and a thermistor.

[0032] A thermocouple, also known as a thermoelectric thermometer, is an electrical device consisting of two different electrical conductors forming an electrical connection. Due to the Seebeck effect, a thermocouple generates a temperature-dependent voltage, which can be interpreted as a measured temperature. Advantageously, thermocouples are self-powered and do not require external excitation. In particular, thermocouples can be of one of the following types: Type E, Type J, or Type K, all of which are nickel alloy thermocouples. Other types are also possible. Various combinations of conductor materials can be used. Different types are best suited for different applications. The type can be selected based on the required temperature range and sensitivity. In the present case, the thermocouple is preferably a Type K thermocouple. This type is a general-purpose thermocouple with a sensitivity of approximately 41 μV / °C, is inexpensive, and offers a wide application range from -200 °C to +1350 °C, making it particularly suitable for applications involving the cooling or deep freezing of medical products stored in medical containers.

[0033] Resistance temperature detectors (RTDs) typically consist of a thin wire wound around a heat-resistant ceramic or glass core. Other structures are also used. The RTD wire is made of a pure material, typically platinum (Pt), nickel (Ni), or copper (Cu). These materials have an accurate and repeatable resistance / temperature relationship (R vs. T) used to provide temperature indication. The R vs. T relationship is defined as the change in resistance of the sensor per degree of temperature change. The relative change in resistance (temperature coefficient of resistance) varies only slightly within the sensor's useful range.

[0034] A thermistor is a semiconductor resistor whose resistance is more strongly dependent on temperature than that of a standard resistor. Based on the materials used, thermistors are classified into two types: negative temperature coefficient (NTC) thermistors, whose resistance decreases with increasing temperature; and positive temperature coefficient (PTC) thermistors, whose resistance increases with increasing temperature. The thermistor differs from a resistance temperature detector (RTD) in that thermistors typically use ceramic or polymer materials, while RTDs use pure metals. Their temperature responses also differ; RTDs are useful over a wider temperature range, while thermistors typically achieve higher accuracy over a limited temperature range (typically -90 °C to +130 °C).

[0035] The detector element is preferably a wire-based detector element, that is, the detector element includes some wiring for connecting the detector element to a readout unit and / or control unit, which is configured to generate a temperature signal indicating the measured temperature.

[0036] To prevent damage to the detector element due to strain acting on the wiring of the detector element or undesirable separation of the detector element from the leg, the leg may advantageously include a strain relief arrangement for the wiring of the detector element mounted to the respective leg.

[0037] As an example, each leg, and more particularly, the corresponding free end portion of each leg, may include multiple lugs through which the wiring of the detector element passes alternately. For instance, each leg, or the corresponding free end portion of each leg, may include two lugs extending transversely to the length of the leg from one side to the opposite side, wherein the wiring of the detector element passes through the first lug from a first side of the leg to the opposite second side and through the second lug back to the first side of the leg. The same arrangement is possible for a greater number of lugs.

[0038] As another example, each leg, and more specifically the corresponding free end portion of each leg, may contain one or more clamps for securing the wiring of the detector element.

[0039] Advantageously, the detector element can be mounted to the leg, particularly solely through the connection provided between the detector element's wiring and the strain relief arrangement. Therefore, no additional mounting device is required to attach the detector element to the leg. This allows for the simple and cost-effective manufacture of the temperature measuring device. Furthermore, the mass of the temperature measuring assembly, especially its thermal mass, is reduced.

[0040] To securely attach the sensor holder to a medical container, the sensor holder may include a clamping mechanism. Specifically, the clamping mechanism may include one or more clamping supports configured to attach the sensor holder to the medical container, particularly to a flange of the medical container, or to both a flange and a cap (the cap being positioned on the flange). For example, the clamping supports may clamp around a flange or a flange and a cap, and extend from the top of the flange or cap around a circumferential side of the flange or around a circumferential side of the cap and flange to an undercut on an opposite side of the flange. The clamping supports may be configured as resilient, flexible clamping supports for clamping attachment to the medical container. Alternatively, the clamping supports may be configured as bending clamps to bend into a support shape for attaching the sensor holder to the medical container.

[0041] Preferably, the clamping mechanism can be part of the support member of the sensor holder. In particular, the clamping mechanism can be integrated with the support member of the sensor holder. The clamping mechanism and the support member can also be different components.

[0042] Not only can the clamping mechanism and support members be integrated with each other, but the entire sensor holder can also be a one-piece sensor holder. In particular, the support members, legs, and clamping mechanism, if present, can be integrated with each other, preferably made from a single piece of material. That is, the entire sensor holder can be made from a single piece of material. Advantageously, this allows the sensor holder to be manufactured in a simple and cost-effective manner.

[0043] More specifically, the entire sensor holder, or at least a portion thereof, may be made from sheet material, particularly spring steel sheet. Sheet material allows for the production of 3D sensor holders from flat, quasi-2D material by cutting (e.g., laser cutting) or stamping 2D folded patterns (potentially including fold lines and embossed cuts), the patterns of which can then be folded into the final 3D shape of the sensor holder, similar to the process of producing a folding box.

[0044] Furthermore, the temperature measurement component may further include a readout unit and / or a control unit configured to generate temperature signals that respectively indicate the temperature measured by the temperature sensor or one or more detector elements. For this purpose, the temperature sensor or one or more detector elements may be operatively coupled to the readout unit and / or control unit.

[0045] The present invention also relates to a temperature measuring attachment for attaching to a medical container and determining the temperature inside the medical container, wherein the medical container has a hollow body with an outer body wall and a body opening, as described above regarding the temperature measuring assembly. The temperature measuring attachment of the present invention comprises a temperature measuring assembly according to the invention and as described above, and a cap or plug for mounting at the body opening of the medical container. The cap or plug may have a channel opening through which a sensor holder extends into the interior of the hollow body when mounted on the medical container. The plug may be made of an elastic material (such as rubber), or glass or metal. The cap or plug may also be configured to form a channel opening therethrough, allowing the sensor holder to extend through it (such as into the interior of the hollow body) when mounted on the medical container. For example, the cap or plug may include a diaphragm through which the channel opening can be formed by piercing the sensor holder through the diaphragm or by pre-piercing it with a piercing element, to create a channel opening for subsequent insertion of the sensor holder.

[0046] This aspect of the invention relates to a temperature measuring attachment, preferably configured for use with medical containers that do not have plugs or caps; that is, it relates to a temperature measuring attachment capable of being installed into medical containers that do not have plugs or caps. Advantageously, combining the temperature measuring component according to the invention and as described above with a cap or plug allows for easy installation of the temperature component into the medical container.

[0047] Temperature measurement attachments can be supplied pre-assembled, with the temperature measurement components attached to a cap or plug. Thus, the temperature measurement attachment is ready for installation at the medical container. If present, the clamping mechanism of the sensor holder can be in a ready-to-use configuration, which can be converted to a clamping configuration when the temperature measurement arrangement is positioned at the medical container. For example, as described above, the clamping bracket can be configured as a bending clamp to bend into a bracket shape for attaching the sensor holder to the medical container when the temperature measurement arrangement is positioned at the medical container.

[0048] Alternatively, a configuration in which the temperature measurement attachment is detachable is provided, wherein the temperature measurement assembly is removed from the cap or plug.

[0049] The present invention also relates to a temperature measurement system comprising a medical container, wherein the medical container has a hollow body with an outer body wall and a body opening. According to the invention, the temperature measurement system further comprises a temperature measurement component according to the invention and as described above, or a temperature measurement attachment according to the invention and as described above.

[0050] A temperature measurement system can be understood as a ready-to-use temperature measurement system placed at a location in the process of handling temperature-controlled medical products to enable temperature monitoring, process validation, and / or equipment verification related to the process under study.

[0051] Preferably, the medical container may be filled with the same medical product as the medical product processed in the investigated process. Alternatively, the container may be filled with a test product. The test product may be a substitute that has similar or at least partially identical properties to the medical product in the investigated process.

[0052] As described above, the area inside the medical container, at or near the outer wall of the hollow body, is the first to be affected by external factors and is therefore particularly important for temperature monitoring. Thus, the sensor holder can advantageously be configured to position the corresponding temperature sensing portion of one or more detector elements at a distance from the outer wall of the hollow body that is less than 15%, less than 10%, or less than 5% of the inner diameter of the hollow body. Similarly, the sensor holder can advantageously be configured to position the corresponding temperature sensing portion of one or more detector elements at a distance from the outer wall of the hollow body that is less than 1 mm, or less than 0.5 mm, or less than 0.25 mm, preferably 0 mm (i.e., in contact with the outer wall of the hollow body).

[0053] The present invention also relates to a method for temperature monitoring, process validation, and / or equipment verification in connection with handling temperature-controlled medical products, the method using at least one temperature measurement component, at least one temperature measurement arrangement structure, and / or at least one temperature measurement system of the present invention as described above, wherein the method includes: - In a processing procedure and / or processing equipment for handling temperature-controlled medical products, at least one temperature measuring component of the present invention and as described above, at least one temperature measuring arrangement structure of the present invention and as described above, and / or at least one temperature measuring system of the present invention and as described above are implemented at corresponding predefined locations, wherein, where present, at least one temperature measuring component and at least one temperature measuring arrangement structure are installed at the corresponding medical container. - During processing according to a predefined measurement scheme, the temperature inside the corresponding medical container where at least one temperature measuring component and at least one temperature measuring arrangement structure are installed is measured and preferably recorded, and / or the temperature inside the corresponding medical container where at least one temperature measuring system is measured and preferably recorded.

[0054] The method of the present invention can be particularly used for temperature monitoring during the transport of temperature-controlled medical products, and for process validation and / or equipment verification related to the transport of temperature-controlled medical products. To this end, the method may include: - Place one or more medical containers to be transported in a transport system under predefined temperature conditions, each medical container containing a corresponding medical product; - The present invention and one or more temperature measurement systems as described above are placed in a transport system, wherein the respective medical containers of the one or more temperature measurement systems are filled with a medical product contained in one of a plurality of medical containers to be transported or filled with a test product, wherein the one or more temperature measurement systems are placed at one or more predefined locations in the transport system. - The temperature inside one or more medical containers is measured and preferably recorded during transport according to a predefined measurement scheme by one or more temperature measurement systems.

[0055] One of the one or more temperature measurement systems may be located near the outer wall or corner of the transport system. Similar to the reason for locating the temperature sensing portion of the detector element inside the hollow body at or near the outer wall of the hollow body, the area near the outer wall or corner of the transport system is those areas that are first affected by external factors and are therefore particularly important for temperature monitoring.

[0056] One of the one or more temperature measurement systems may also be located in or near the center of the transport system. Attached Figure Description

[0057] The temperature measurement components, attachments, and systems according to the present invention, as well as the methods for temperature monitoring, process verification, and / or device validation according to the present invention, are described in more detail below with reference to exemplary embodiments and the accompanying drawings, wherein: Figure 1 shows a cross-section of an exemplary embodiment of the temperature measurement system according to the present invention; Figure 2 shows a perspective view of the sensor holder of the temperature measurement system in Figure 1; Figure 3 shows a side view of the sensor holder of the temperature measurement system in Figure 1; Figure 4 shows a top view of the sensor holder blank shown in Figures 2 and 4; Figure 5 shows a side view of the temperature measurement system shown in Figure 1; and Figure 6 shows a transport system involving multiple temperature measurement systems as shown in Figure 1. Detailed Implementation

[0058] In the following description, certain terms are used for convenience and are not intended to limit the invention. The terms “right,” “left,” “up,” “down,” “below,” and “above” refer to directions in the figures. Terms include explicitly mentioned terms and their derivatives, as well as terms with similar meanings. Additionally, spatial relative terms such as “below,” “below,” “below,” “above,” “above,” “near,” “far,” etc., may be used to describe the relationship between one element or feature and another element or feature as shown in the figures. These spatial relative terms are intended to cover different positions and orientations of the device in use or operation, in addition to those shown in the figures. For example, if the device in the figures is flipped, an element described as “below” or “below” other elements or features will be “above” or “above” other elements or features. Thus, the exemplary term “below” can cover both above and below positions and orientations. The device may be oriented in other ways (rotated 90 degrees or otherwise oriented), and the spatial relative descriptive terms used herein will be interpreted accordingly. Similarly, descriptions of movement along and around various axes include various specific device positions and orientations.

[0059] To avoid repetition in the description of the accompanying drawings and various aspects, as well as the illustrative embodiments, it should be understood that many features are common to many aspects and embodiments. The omission of an aspect in the description or drawings does not imply that that aspect is missing in the embodiment that includes it. Rather, the aspect may be omitted for clarity and to avoid lengthy descriptions. In this context, the following description applies to the remainder of this specification: if reference numerals in the drawings are not explained in the directly relevant parts of the specification for the purpose of clarifying the drawings, reference may be made to preceding or following sections of the specification. Furthermore, for clarity, if reference numerals in the drawings do not provide all features of a component, reference may be made to other drawings showing the same component. Similar reference numerals in two or more drawings denote the same or similar elements.

[0060] Referring first to Figures 1 and 5, an exemplary embodiment of a temperature measurement system 120 is shown, which is specifically envisioned for temperature monitoring during the handling of temperature-controlled medical products, as well as for validation processes and / or equipment verification related to the handling of temperature-controlled medical products. This handling may, for example, involve the transportation of temperature-controlled medical products, examples of which will be described in more detail below with reference to Figure 6.

[0061] The temperature measurement system 120 includes a medical container 20 for storing medical products and a temperature measurement attachment 110 according to the invention. The temperature measurement attachment 110 further includes a temperature measurement component 100 according to the invention and a plug 25 for mounting at the main body opening 23 of the medical container 20.

[0062] In this embodiment, the medical container 20 is a vial commonly used in the pharmaceutical industry and research. The medical container 20 includes a hollow body 21 with an outer body wall 22 and a body opening 23. The hollow body 21 has a bottle-shaped form, having a bottleneck 27 and a flange 24 including the body opening 23. The body opening 23 is configured to receive an insertion portion of a plug 25, with the collar portion of the plug abutting the top side of the flange 24 of the medical container 20.

[0063] The plug 25 includes a channel opening 26 through which the temperature measuring assembly 100 extends into the interior of the hollow body 21 when mounted on the medical container 20. The plug 25 may be made of a resilient material (such as rubber), or glass or metal. Here, the plug 25, together with the temperature measuring assembly 100, forms a temperature measuring attachment 110, which can be considered as a ready-to-use measuring unit for mounting to the medical container. Alternatively, the plug 25 may be part of the medical container 20.

[0064] The temperature measurement assembly 100 constitutes the core of this invention. Assembly 100 includes a temperature sensor 40 and a sensor holder 30 for holding the temperature sensor 40. The temperature sensor includes one or more detector elements 42, each detector element having a temperature sensing portion 41. The primary purpose of the temperature measurement assembly 100 is to determine the temperature inside the medical container 20, and more particularly, to determine the temperature in or near one or more areas of the outer body wall 22 of the hollow body 21. These areas are particularly important for temperature monitoring in relation to the handling of temperature-controlled medical products stored in the medical container 20, as they are primarily affected by the heat from external influencing factors.

[0065] For this purpose, the sensor holder 30 is configured to be mounted on the medical container 20, and when mounted, extends through the body opening 23 (via the opening channel 26 of the plug 25) into the interior of the hollow body 21, and positions the temperature sensing portion 41 of the detector element 42 at or near the outer body wall 22 of the hollow body 21 inside the hollow body 21.

[0066] As can be seen from Figure 1, the temperature sensor 40 according to this embodiment includes three detector elements 42, each detector element 42 being a K-type thermocouple having its own temperature sensing portion 41 and a corresponding wiring 43 passing through the body opening 23 (via the opening channel 26 of the plug 25) to the outside of the medical container 20.

[0067] The sensor holder 30 of this embodiment includes a support member 31 that extends across the opening channel 26 of the plug 25, thereby positioning itself across the body opening 23 of the medical container 20. To individually position each of the detector elements 42 within the hollow body 21, the sensor holder 30 further includes three legs 32, one leg for each detector element 42, configured and arranged to insert into the interior of the hollow body 21 through the body opening 23 (via the opening channel 26 of the plug 25). More precisely, each of the three detector elements 42 is mounted to a corresponding free end portion 35 of one of the three legs 32.

[0068] To prevent the detector element 42 from undesirably detaching from the support leg 32 due to strain acting on the wiring 43 of the detector element 42, the support leg includes a strain relief arrangement 36. In the present case, refer to Figure 2 and... Figure 3 The strain relief arrangement 36 is formed by two lugs 37 at the respective free end portions 35 of each leg 32. Each of the lugs 37 extends transversely to the length of the leg 32 from a first side through the leg 32 to the opposite second side. As shown in FIG1, the wiring 43 of the detector element 42 passes from the first side of the leg 32 through the first lug 37 to the second side of the leg, and returns through the second lug 37 to the first side of the leg 32, thereby ensuring that the wiring is not pulled out due to strain acting on the wiring 43.

[0069] In this embodiment, the detector element 42 is mounted to the leg 32 only through the connection provided between the wiring 43 of the detector element 42 and the strain relief arrangement 26. Therefore, advantageously, no additional means are required to mount the detector element 42 to the leg 32. Furthermore, the end portion of the wiring 43, which has a temperature sensing portion 41 at its extremely free end, is positioned substantially radially outward from the first lug 37, which proves advantageous in facilitating the positioning of the corresponding temperature sensing portion 41 at or near the outer body wall 22 of the hollow body 21.

[0070] The central length axis 38 of the sensor holder 30—given by the main direction of extension of the leg set 32—defines the general insertion direction of the sensor holder 30 into the interior of the medical container 20, which is substantially perpendicular to the planes spanned by the opening channel 26 of the plug 25 and the main body opening 23 of the medical container 20, respectively.

[0071] Further details of the sensor holder 30 are shown in Figures 2 and 3. To allow temperature measurements along different spatial directions around the central axis of the medical container 20, the legs 32 branch off from the support member 31 in a star-shaped arrangement symmetrical with respect to the central length axis 38 of the sensor holder 30. More specifically, as shown in the projection along the central length axis 38, the three legs 32 are evenly distributed around the central length axis 38 of the sensor holder 30, with each pair of legs spaced 120 degrees apart.

[0072] To position the temperature sensing portion 41 of the detector element 42 as close as possible to, or even at, the inner surface of the outer body wall 22, each leg 32 includes a first segment 33 substantially parallel to the central length axis 38 of the sensor holder 30, and a second portion 34 extending laterally (radially outward) away from the central length axis 38, such that the second portions 34 of the legs 32 are bifurcated from each other. In this example, the legs are at a 10-degree angle, meaning the second portions 34 of the legs 32 are at a 10-degree angle relative to either the first portion 33 or the central length axis 38.

[0073] In particular, as can be seen from Figure 1, the free end portion 35 of the legs 32 extends radially beyond the cross-sectional dimensions of the opening channel 26 of the plug 25 and the main body opening 23 of the medical container 20, respectively. To still allow the legs to be inserted into the interior of the medical container 20 through the opening channel 26 and the main body opening 25, the legs 32 are elastically flexible in the direction transverse to their respective length extensions (i.e., radially transverse to the central length axis 38), allowing them to be compressed to pass through the opening channel 26 and the main body opening 25. Furthermore, the elasticity of the flexible legs is advantageously used to maintain close contact between the temperature sensing portion 41 of the detector element 42 and the outer body wall 22 of the hollow body 21 when needed.

[0074] Preferably, the legs 32 of the sensor holder 30 are made of spring steel to give them elastic flexibility. Even more preferably, the entire sensor holder 30 is made of a single piece of material, i.e., it is realized as a one-piece sensor holder 30. Advantageously, this allows the sensor holder 30 to be manufactured in a simple and cost-effective manner.

[0075] The manufacturing details of the sensor holder 30 are shown in Figure 4. According to this embodiment, the entire sensor holder 30 is made from a flat, quasi-2D spring steel sheet material. A blank body (see Figure 4) is cut or stamped from the material sheet to achieve a 2D folding pattern, which may include fold lines and embossed cutouts. Similar to the process of producing a folding box, the blank body of Figure 4 can be folded to transform into the final 3D shape of the sensor holder 30 shown in Figures 1 to 3. In the present case, each of the legs 32, as a whole, forms an angle of approximately 90 degrees relative to the support member 31, and the second portion 34 of each leg 32 forms a desired angle relative to the corresponding first portion 33, here 10 degrees.

[0076] As can be further seen from Figure 4, the blank body of the sensor holder 30 further includes three shorter arms designed to form clamping supports 39 for attaching the sensor holder 30 to the medical container 20. Details of the clamping supports 39 are shown in Figures 2, 3, and 5. As can be seen from these figures, the clamping supports 39 according to this embodiment are configured as bending clamps, which are formed by bending the three short arms of the blank body shown in Figure 4 into a support shape, such that each clamping support 39 clamps around the flange 24 and the plug 25, i.e., from the top of the plug 25 around the circumferential side of the plug 25 and the flange 26 to the undercut on the rear side of the flange 26 formed by the neck 27 of the body. This prevents the temperature measuring assembly 100 from shifting or even being lost relative to the medical container 20 during processing.

[0077] As further described above, the temperature measurement system 120 shown in Figures 1 and 5 is specifically envisioned for monitoring the temperature of temperature-controlled medical products stored in medical containers similar to or identical to the medical containers of system 120 during the processing of medical products. Therefore, the system is specifically suited for validation processes and / or equipment verification related to the processing of temperature-controlled medical products. For this purpose, one or more temperature measurement systems 120 may be implemented at one or more predefined locations in the processing process and / or processing equipment to measure and record the temperature inside one or more medical containers 20 of one or more temperature measurement systems 120 during processing according to a predefined measurement protocol.

[0078] Preferably, the processing may involve transporting temperature-controlled medical products in medical containers similar to or identical to the medical containers of system 120. Temperature-sensitive medical products stored in such containers typically must be transported in a frozen state. For this purpose, they are packaged in suitable transport systems (transport equipment), such as cooling boxes. Since the temperature of the medical products must not exceed a critical temperature during transport, quality guidelines and handling rules may stipulate that temperature conditions are permanently monitored throughout the transport process and that only appropriately validated transport equipment is used to ensure proper transport conditions. For both purposes, one or more temperature measurement systems 120 according to the embodiments shown in Figures 1 and 5 may be implemented at one or more predefined locations in the transport system. Figure 6 schematically illustrates such a transport system 210 in the form of a cooling box, which provides a total of fifteen (3 x 5) container slots for storing medical containers 220 similar to or identical to the medical containers 20 of temperature measurement system 120.

[0079] To validate the transport system 210—that is, to verify through objective evidence that the transport system 210 meets the requirements or conditions for a specific application or purpose, such as ensuring that the temperature of the medical product stored in the medical container 220 does not exceed a critical temperature throughout the transport—this invention proposes placing one or more temperature measuring systems 120 in one or more predefined locations (container slots) within the transport system 210 under predefined temperature conditions, and measuring and recording the internal temperature of one or more medical containers 20 of the one or more temperature measuring systems 120 during transport according to a predefined measurement scheme. The remaining container slots may be filled with one or more medical containers 220 to be transported, each containing a corresponding medical product. One or more medical containers 220 are placed in the transport system 210 under the same predefined temperature conditions as the one or more temperature measuring systems 120.

[0080] For the verification procedure, the corresponding medical container 20 of one or more temperature measurement systems 120 may be filled with a medical product contained in one of the plurality of medical containers 220 to be transported, or alternatively filled with a test product, which preferably has similar or at least partially the same characteristics as one of the medical products to be transported.

[0081] The container tanks adjacent to the outer walls or corners of the transport system 210 are those areas that are first affected by external factors and are therefore particularly important for temperature monitoring. Therefore, as shown in Figure 6, the four temperature measurement systems are preferably located adjacent to the outer walls of the transport system 210, more specifically, one temperature measurement system at each corner of the transport system 210. Additionally, one or more temperature measurement systems 120 may be located at or near the center of the transport system 210, also as shown in Figure 6.

[0082] Instead of using a fully equipped temperature measurement system 120, one or more medical containers 220 to be transported may be equipped with a temperature measurement component according to the invention or a temperature measurement attachment according to the invention. In this case, one or more medical containers 220 may not be sealed to allow the temperature sensing portion of the detector element to be positioned inside the hollow body of the medical container 220.

[0083] The description and accompanying drawings illustrating aspects and embodiments of the invention should not be construed as limiting the scope of the claims. In other words, while the invention has been described and illustrated in detail in the accompanying drawings and the foregoing description, such description and illustration are to be considered illustrative or exemplary rather than restrictive. Various mechanical, compositional, structural, electrical, and operational changes may be made without departing from the spirit and scope of this specification and the claims. In some cases, well-known circuits, structures, and techniques have not been shown in detail so as not to obscure the invention. Therefore, it should be understood that changes and modifications can be made by those skilled in the art within the scope and spirit of the appended claims. In particular, the invention covers further embodiments having any combination of features from the different embodiments described above and below.

[0084] This disclosure also covers all other features shown in the figures. Although they may not be described in the preceding or following description, they are individual. Furthermore, a single alternative to the embodiments described in the figures and description, and a single alternative to the features thereof, may be excluded from the subject matter of the invention or from the disclosed subject matter. This disclosure includes the subject matter consisting of features defined in the claims or exemplary embodiments, as well as the subject matter including said features. Furthermore, this disclosure covers an intermediate generalization of features or groups of features of the embodiments described and illustrated in the figures. That is, specific features or groups of features disclosed in relevant portions of the figures and description may be combined with more general embodiments of the invention disclosed in conjunction with the description of the invention. In particular, such specific features or groups of features may be provided separately from other specific features shown in the figures in more general embodiments of the invention. For example,... It should be understood that those skilled in the art can incorporate specific features from the description of the figures into embodiments described in the invention.

[0085] Furthermore, in the claims, the term "comprising / including" does not exclude other elements or steps, and the indefinite article "a / an" does not exclude multiple. A single unit or step can perform the function of several features listed in the claims. The mere fact that certain measures are listed in mutually different dependent claims does not indicate that a combination of these measures cannot be advantageous. Terms related to attributes or values, such as "substantially," "about," "approximately," etc., also precisely define the attribute or exact value, respectively. In the context of a given numerical value or range, the term "about" refers to a value or range, for example, within 20%, 10%, 5%, or 2% of the given value or range. Components described as coupled or connected may be electrically or mechanically directly coupled, or they may be indirectly coupled via multiple intermediate components. Any reference numerals in the claims should not be construed as limiting the scope.

Claims

1. A temperature measuring assembly (100) for determining the temperature inside a medical container (20), the medical container (20) having a hollow body (21) with an outer body wall (22) and a body opening (23), the temperature measuring assembly (100) comprising: Temperature sensor (40), the temperature sensor including at least one detector element (42) having a temperature sensing portion (41); and A sensor holder (30) holds the temperature sensor (40). The sensor holder (30) is configured to be mounted on the medical container (20) such that the sensor holder extends through the body opening (23) into the interior of the hollow body (21), and the temperature sensing portion (41) of the at least one detector element (42) is positioned inside the hollow body (21) at or near the outer body wall (22) of the hollow body (21).

2. The temperature measurement assembly (100) according to claim 1, wherein the sensor holder (30) comprises: A support member (31) is configured to be placed across the main body opening (23), particularly outside the medical container (20); and multiple legs (32), particularly two, three or four legs (32), to extend into the interior of the hollow body (21).

3. The temperature measuring assembly (100) according to claim 2, wherein the leg (32) branches off from the support member (31) substantially along the central length axis (38) of the sensor holder (30), particularly in a symmetrical arrangement relative to the central length axis (38) of the sensor holder (30).

4. The temperature measuring assembly (100) according to claim 3, wherein the legs (32) are uniformly distributed around the central length axis (38) of the sensor holder (30).

5. The temperature measuring assembly (100) according to claim 3 or 4, wherein the legs (32) are arranged in a star shape as shown by projection along the central length axis (38) of the sensor holder (30).

6. The temperature measuring assembly (100) according to any one of claims 2 to 5, wherein the leg (32) is bent and / or angled.

7. The temperature measuring assembly (100) according to claim 6, wherein the leg (32) bends and / or is angled at an angle, for example, at an angle of 10 degrees, within the range of 1 degree to 90 degrees, more particularly between 2 degrees to 45 degrees, preferably between 5 degrees to 20 degrees.

8. The temperature measuring assembly (100) according to any one of claims 3 to 7, wherein each leg (32) comprises: A first section (33) extends substantially parallel to the central length axis (38) of the sensor holder (30); and a second portion (34) extends away from the central length axis in a direction transverse to the central length axis (38) of the sensor holder (30), such that the second portions (34) of the legs (32) are spread apart from each other.

9. The temperature measuring assembly (100) according to any one of claims 3 to 8, wherein at least a portion of each leg (32) is flexible.

10. The temperature measuring assembly (100) according to claim 9, wherein at least a portion of the flexibility of each leg (32) is elastically flexible in at least one direction transverse to the respective length extension of the leg (32).

11. The temperature measuring assembly (100) according to claim 10, wherein the at least one direction transverse to the corresponding length extension of the leg (32) is a direction radially transverse to the central length axis (38) of the sensor holder (30).

12. The temperature measurement assembly (100) according to any one of claims 2 to 11, wherein the temperature sensor (40) comprises a plurality of detector elements (42).

13. The temperature measurement assembly (100) according to claim 12, wherein the plurality of detector elements (42) are three or four detector elements (42), wherein each of the plurality of detector elements (42) has a temperature sensing portion (41) and is mounted to one of the plurality of legs (32).

14. The temperature measurement assembly (100) according to claim 13, wherein each of the plurality of detector elements (42) is mounted to a corresponding free end portion (35) of one of the plurality of legs (32).

15. The temperature measuring assembly (100) according to any one of the preceding claims, wherein the at least one detector element (42) is one of: a thermocouple, a thermistor, and a resistance temperature detector.

16. The temperature measurement assembly (100) according to any one of claims 12 to 15, wherein the leg (32) includes a strain relief arrangement (36) for wiring (43) to the detector element (42) of the respective leg (32).

17. The temperature measuring assembly (100) according to claim 16, wherein preferably, the detector element (42) is mounted to the leg (32) by, in particular only by, a connection provided between the wiring (43) of the detector element (42) and the strain relief arrangement (36).

18. The temperature measuring assembly (100) according to any one of the preceding claims, wherein the sensor holder (30) includes a clamping mechanism.

19. The temperature measurement assembly (100) of claim 18, wherein the clamping mechanism of the sensor holder (30) includes one or more clamping supports (39) configured to attach the sensor holder (30) to the medical container (20).

20. The temperature measuring assembly (100) according to any one of the preceding claims, wherein the sensor holder (30) is a one-piece sensor holder (30).

21. The temperature measuring assembly (100) according to any one of the preceding claims, wherein the sensor holder (30) is made of sheet material.

22. The temperature measuring assembly (100) according to claim 21, wherein the sheet is a metal sheet or a spring steel sheet.

23. A temperature measuring attachment (110) for attachment to a medical container (20) and for determining the temperature inside the medical container (20), the medical container (20) having a hollow body (21) with an outer body wall (22) and a body opening (23), the temperature measuring attachment (110) comprising a temperature measuring component (100) according to any one of the preceding claims and a cap or plug (25) for mounting at the body opening (23) of the medical container (20), the cap or plug (25) having a channel opening (26) or being prepared to form a channel opening for a sensor holder (30) to extend through the channel opening into the interior of the hollow body (21) when mounted on the medical container (20).

24. A temperature measurement system, the temperature measurement system comprising: A medical container (20) having a hollow body (21) with an outer body wall (22) and a body opening (23); and a temperature measuring assembly (100) according to any one of claims 1 to 22 or a temperature measuring attachment (110) according to claim 23.

25. The temperature measurement system according to claim 24, wherein the sensor holder (30) is configured to position the temperature sensing portion (41) of the at least one detector element (42) at a distance from the outer body wall (22) of the hollow body (21), the distance being less than 15% of the inner diameter of the hollow body (21), less than 10% of the inner diameter of the hollow body (21), or less than 5% of the inner diameter of the hollow body (21).

26. The temperature measurement system according to claim 24 or 25, wherein the sensor holder (30) is configured to position the temperature sensing portion (41) of the at least one detector element (42) at a distance of less than 1 mm, or less than 0.5 mm, or less than 0.25 mm from the outer body wall of the hollow body, preferably at a distance of 0 mm.

27. A method for temperature monitoring, process validation, and / or device validation in connection with handling temperature-controlled medical products, said method using at least one temperature measurement component (100) according to any one of claims 1 to 22, at least one temperature measurement arrangement structure (110) according to claim 23, and / or implemented in the following manner: - In a processing procedure and / or processing equipment for handling temperature-controlled medical products, at least one temperature measuring component (100) according to any one of claims 1 to 22, at least one temperature measuring arrangement structure (110) according to claim 23, and / or at least one temperature measuring system (120) according to any one of claims 24 to 26 are provided at corresponding predetermined locations, wherein, if present, the at least one temperature measuring component (100) and the at least one temperature measuring arrangement structure (110) are mounted at the corresponding medical container (20); - During processing according to a predetermined measurement scheme, the temperature inside the corresponding medical container (20) on which the at least one temperature measuring component (100) and the at least one temperature measuring arrangement structure (110) are installed is measured and preferably recorded, and / or the temperature inside the corresponding medical container (20) on which the at least one temperature measuring system (120) is installed is measured and preferably recorded.

Images