Surveillance system, surveillance method, and room

Abstract

A monitoring system is disclosed for monitoring the performance of an enclosed system for processing pharmaceutical ingredients. The enclosed system comprises one or more inlets for receiving one or more pharmaceutical ingredients and one or more outlets, and the monitoring system comprises a first sensor and a processing unit operatively connectable to the first sensor. Also disclosed are methods for monitoring the performance of the enclosed system for processing pharmaceutical ingredients, and a room comprising the enclosed system and the monitoring system.

Description

[Technical Field]

[0001] The present disclosure relates to a monitoring system for monitoring the performance of a contained system for processing a pharmaceutical ingredient. The disclosure further relates to a method for monitoring the performance of a contained system for processing a pharmaceutical ingredient, and a room including the contained system for processing a pharmaceutical ingredient and a monitoring system for monitoring the performance of the contained system. [Background technology]

[0002] In pharmaceutical ingredient processing, one or more ingredients, such as ingredients also known as excipients or active pharmaceutical ingredients (APIs), are typically processed for the purpose of producing other pharmaceutical ingredients and / or pharmaceutical products. Such one or more ingredients are often introduced into a pharmaceutical ingredient processing system in the form of a powder or granules, and during processing, are typically subjected to processes such as blending and pressing to form a tablet.

[0003] However, the processing of such ingredients, e.g., in powder form, often requires that measures be taken to reduce risks to operators of the pharmaceutical system. For example, when a pharmaceutical system processes one or more ingredients, a portion of these one or more ingredients may be released into the air surrounding the pharmaceutical system. To prevent operator exposure to these pharmaceutical ingredients, pharmaceutical systems are often encapsulated to reduce the risk of ingredients leaking into the air surrounding the system.

[0004] Such containment capability should generally be evaluated to ensure that sufficient containment is established and that no leaks occur in the pharmaceutical system. Containment capability is typically determined based on checks before the manufacturing system is put into operation, for example, using a pressure decay test. In a typical pressure decay test, a negative pressure, often on the order of a few kPa, is applied inside the contained system, and the rise time for the pressure inside the contained system to rise from a first value to a second value is measured. If the pressure rise time is within a predetermined range, the pharmaceutical system is deemed to have sufficient containment capability and to be contained. If the rise time is outside the predetermined range, the pharmaceutical system is deemed not to be sufficiently contained, and a second test, such as a helium leak test, is usually then performed to detect any breaches.

[0005] However, performing a pressure decay test is complex and time-consuming. Furthermore, to perform a pressure decay test, the manufacturing system must be stopped from processing the pharmaceutical ingredient. This pressure decay test must typically be performed at intervals of several hours, resulting in periodic downtime of the manufacturing system.

[0006] Therefore, it remains desirable to provide improved methods and systems for monitoring the performance of enclosed systems. Summary of the Invention [Problem to be solved by the invention]

[0007] SUMMARY OF THE INVENTION It is an object of the present invention to address at least some of the above-mentioned drawbacks. [Means for solving the problem]

[0008] According to one aspect of the present disclosure, there is provided a monitoring system for monitoring the performance of an enclosed system for processing pharmaceutical ingredients, the enclosed system comprising one or more inlets for receiving one or more pharmaceutical ingredients and one or more outlets, the monitoring system comprising: a first sensor disposed at a first point outside the enclosed system and configured to repeatably provide a sensor signal to the processing unit indicative of a particle density in air outside the enclosed system, the processing unit configured to compare the sensor signal with an expected sensor signal, and the processing unit configured to output an output signal indicating that the particle density in the air differs from the expected air density if the processing unit determines that the sensor signal differs from the expected sensor signal.

[0009] The first sensor may be configured to repeatably provide a sensor signal to the processing unit indicative of a particle concentration of particles having a size greater than 0.1 micrometers in air outside the enclosed system.

[0010] This allows the monitoring system to determine particles in the air outside the enclosed system, and thereby the monitoring system can determine encapsulation capacity and / or encapsulation breakage, for example, by detecting pharmaceutical ingredient particles in the air outside the enclosed system. Furthermore, using the first sensor, the monitoring system can also determine particle density while the enclosed system is processing the pharmaceutical ingredient, thereby making it possible to monitor the encapsulation capacity of the enclosed system during processing of the pharmaceutical ingredient. For example, such monitoring can be performed continuously during processing, so that encapsulation breakage, or insufficient encapsulation capacity, can be determined shortly after it occurs. This again allows appropriate measures to be taken after encapsulation breakage occurs, thereby improving operator safety.

[0011] The processing unit compares the sensor signal to an expected sensor signal and outputs a signal if the sensor signal differs from the expected sensor signal, allowing the monitoring system to determine if a leak is occurring and to alert and / or take action if a leak is occurring, such that if a leak is detected in the contained system, the monitoring system can take appropriate action, such as sounding an alarm, shutting down the contained system, interlocking access to the contained system, and / or sending a message to one or more operators.

[0012] It is further recognized that by configuring the first sensor to be positioned outside the enclosed system, the first sensor and / or monitoring system may be easily installed onto an existing enclosed system and may be retrofittable onto the enclosed system without breaking the enclosure.

[0013] Furthermore, by configuring the first sensor to be located at a first point outside the enclosed system, the monitoring system can detect a breach in containment or leak from a particular area of ​​the enclosed system that is proximate the first point, thereby enabling the monitoring system to determine where in the enclosed system the leak is occurring.

[0014] By the term "enclosed system" herein, it is to be understood that the system meets certain requirements for containment, i.e., that the system is at least dust-tight when in operation. Correspondingly, an enclosed system may be a system configured such that, when in operation, a wide range of amounts of one or more components, for example detectable amounts and / or amounts of one or more components above a certain threshold, are prevented from being emitted from the enclosed system into the environment, for example into a room in which the system is located. By "enclosed system" herein, it is meant that the system is configured such that the dust content is less than 1 m3 3 It can be seen that the encapsulated system has an encapsulation capacity of up to 10 μg per ml when functioning. 3 The system may be configured to have a dust content of up to 10 μg per particle.

[0015] It should be understood that throughout this specification, the term particle density in the air refers to the particle density in the air outside the enclosed system, and therefore the term particle density in the air refers to the particle density in the air outside the system.

[0016] The particle density in the air outside the enclosed system and / or the particle density in the air may be the particle density in the air excluding gas particles. Additionally or alternatively, the first sensor may be configured to repeatedly provide a sensor signal to the processing unit indicative of the particle density of particles, free of gas particles, in the air.

[0017] The enclosed system may be configured to be placed in a room, for example, in a facility and / or room that complies with GMP (Good Manufacturing Process), and / or may be placed in a GMP facility or room.

[0018] One or more of the one or more ingredients may be in powder form. The one or more inlets for receiving the one or more pharmaceutical ingredients may be configured to receive the one or more pharmaceutical ingredients in powder and / or granular form.

[0019] As used herein, by a first sensor configured to be located outside an enclosed system, it is meant that the first sensor is configured to be located outside the enclosure. Thus, the term "outside" may refer to the room in which the enclosed system is located and / or may refer to the surroundings of the enclosed system, for example, an area accessible by an operator.

[0020] In some embodiments, one or more inlets and / or outlets may define an interface between the enclosed system and its exterior.

[0021] Thus, by the term "air outside the enclosed system" is understood air that is not enclosed by the enclosed system. Thus, the air outside the enclosed system may be the air around the enclosed system and / or the air in a room surrounding the enclosed system. Alternatively or additionally, the air outside the enclosed system may be in fluid communication with air that may be inhaled by an operator.

[0022] It will be understood throughout this specification that fluid communication between two elements may be a connection that allows a fluid, such as air, to flow, e.g., uninterrupted, from one element to the other, e.g., during normal operation of an enclosed system. As an example, two elements located within the same enclosed volume, such as a room, may be in fluid communication and / or two elements connected by a tube through which a fluid, such as air, can flow may be in fluid communication.

[0023] The monitoring system for monitoring the performance of an enclosed system for processing a pharmaceutical product may be a monitoring system configured to monitor the performance of an enclosed system for processing a pharmaceutical product.

[0024] In addition to at least one inlet and at least one outlet, the enclosed system for processing pharmaceutical products may comprise further elements such as one or more containers for one or more pharmaceutical ingredients, any one of which may be connected to any one of said one or more containers, and potentially pharmaceutical ingredients may be delivered into one or more containers via one or more of the one or more inlets.

[0025] Alternatively or additionally, the enclosed system may comprise a first module and a second module connected at an interface. Potentially, each of the first and second modules may be or comprise a container, such as an intermediate bulk container (IBC), that may be docked therewith, a mixer for mixing one or more pharmaceutical ingredients, and / or a tablet press for forming tablets. The tablet press may be for forming tablets from some or all of the one or more pharmaceutical ingredients or a mixture thereof. The outlet of the enclosed system may be the outlet of the mixer or the outlet of the tablet press.

[0026] An enclosed system may include multiple interfaces between its elements and / or modules, for example, between its inlets and outlets. For example, if the enclosed system includes a mixer, the enclosed system may include at least one interface between the mixer and any of the one or more inlets. Similarly, if the enclosed system includes a tablet press, the enclosed system may include interfaces between one or more inlets and the tablet press, between the mixer and the tablet press, and / or between the tablet press and the outlet, by way of example. Alternatively or additionally, the enclosed system may include multiple valves.

[0027] Each of the one or more pharmaceutical compositions may include or be an ingredient, an active pharmaceutical ingredient (API) and / or an excipient.

[0028] The sensor signal indicative of particle density may be an analog signal, a time-discrete signal, or a digital signal. The sensor signal may include a sensor reading, such as an analog or digital signal of light scattered on one or more particles. Alternatively or additionally, the sensor signal may include a sensor reading, such as a digital number of particle counts and / or a digital number of particle density in a predetermined volume of air.

[0029] The first sensor may be an optical sensor, such as a light scattering sensor, configured to measure particle density in the air.

[0030] The first sensor may include a sensor processing unit configured to output a sensor signal indicative of particle density. The sensor processing unit may be configured to output the sensor signal indicative of particle density in analog or digital form. The sensor processing unit may be a central processing unit (CPU), a microcontroller unit (MCU), a field programmable gate array (FPGA), or the like.

[0031] The first sensor may comprise a data interface, such as a wired or wireless data interface, for outputting the sensor signal to the processing unit.

[0032] The processing unit of the monitoring system may be a CPU, MCU, FPGA, or the like. It will be understood that the processing unit is operatively connected to the first sensor such that the processing unit is configured to receive a first sensor signal from the first sensor. The processing unit may also be configured to receive respective sensor signals from any other potential sensors of the monitoring system. If the sensor includes a sensor processing unit, the processing unit may be configured to be operatively connected to the sensor processing unit.

[0033] The processing unit may be configured to be located outside the enclosed system, for example, in a room surrounding the enclosed system or outside a room surrounding the enclosed system, or alternatively, the processing unit may be configured to be located inside the enclosed system.

[0034] The sensor signal can directly specify particle density, e.g., the sensor signal can specify a particle count in a predetermined volume of air. Alternatively or additionally, the first sensor signal can specify a particle count from which particle density can be estimated, e.g., using knowledge of the volume of air analyzed by the first sensor.

[0035] The processing unit may be configured to determine a particle density in the air based at least in part on the first sensor signal.

[0036] In some embodiments, the first sensor is configured to be positioned proximate to a first potential leak zone of the enclosed system.

[0037] Thereby, leaks, and therefore breaches, can be identified at an early stage, so that action can be taken early to further reduce the risk to the operator.

[0038] A potential leak zone, such as a first potential leak zone, may comprise one or more potential leak points. A potential leak zone may be a zone, region, and / or point in an enclosed system where there is an increased risk of leakage and therefore of containment breach. In some embodiments, the potential leak zone is one of one or more inlets or one of one or more outlets. Alternatively or additionally, if the enclosed system includes a first module and a second module connected at an interface, the potential leak zone may be an inlet, an outlet, and / or an interface. For example, if the enclosed system includes a mixer and / or a tablet press, the potential leak zone may be any of one or more inlets, any of one or more outlets, or an interface between the mixer and another element. Alternatively or additionally, the potential leak zone may be a valve in the enclosed system. A potential leak zone may comprise multiple potential leak subzones, each potentially containing a potential leak point, and / or a potential leak zone may comprise multiple potential leak points.

[0039] Additionally or alternatively, the first potential leak zone may be selected from a list of potential leak zones, such as a list including the potential leak zones described above.

[0040] In some embodiments, the monitoring system further comprises a second sensor operably connected to the processing unit, the second sensor disposed at a second point outside the enclosed system and configured to repeatedly provide to the processing unit a second sensor signal indicative of the particle density in the air outside the enclosed system.

[0041] Thereby, the enclosed system can be monitored at multiple points, and the monitoring system can aid or enable estimation of where a leak is occurring within the enclosed system without the need for further testing.

[0042] The second sensor may have any of the features described above in relation to the first sensor and / or may be similar to or identical to the first sensor.

[0043] In some embodiments, the second sensor is configured to be positioned proximate to a second potential leak zone, which may be a potential leak zone described above in connection with the first potential leak zone. Alternatively or additionally, the second sensor may be configured to be positioned at a distance relative to the first sensor and proximate to the first potential leak zone.

[0044] The predicted sensor signal indicates a predicted particle density of the air outside the enclosed system, for example, the air around the first point where the first sensor is located. The predicted sensor signal may represent a sensor signal as predicted if the performance of the enclosed system is deemed sufficient, for example, when the enclosed system has sufficient containment capacity. The predicted sensor signal may be based on the containment of the enclosed system. Alternatively or additionally, the predicted sensor signal may represent or be a threshold value. The processing unit of the monitoring unit is configured to determine that a leak has occurred and / or to determine insufficient performance of the enclosed system when the first sensor signal exceeds the threshold value. The threshold value may be a particle density threshold value, potentially predetermined. Alternatively, the threshold value may be dynamically determined based on other inputs to the monitoring system, for example, from a background sensor or a reference sensor.

[0045] Alternatively or additionally, the expected sensor signal may indicate and / or be a range of values. The processing unit of the monitoring system can be configured to determine that a leak has occurred and / or to determine insufficient performance of the enclosed system when the first sensor signal is outside of the range of values. The range of values ​​may be a potentially predetermined value range of particle densities. The processing unit of the monitoring unit may be configured to determine that a leak has occurred and / or to determine insufficient performance of the enclosed system when the first sensor signal indicates a particle density outside the value range of particle densities.

[0046] In some embodiments, the processing unit may be configured to compare the second sensor signal with a predicted second sensor signal. The predicted second sensor signal may have some or all of the characteristics described in connection with the predicted sensor signal above and / or may be the same as or similar to them. As an example, the predicted sensor signal and the predicted second sensor signal may each represent a respective threshold or value range. Alternatively or additionally, the processing unit may be configured to compare the second sensor signal with the predicted sensor signal.

[0047] The output signal may be an analog output signal or a digital output signal, such as a digital binary signal or a Boolean signal. The output signal may be sent to a further device, such as an alarm, a locking device, a display, or the like.

[0048] In some embodiments, the processing unit is configured to shut down the enclosed system, provide an audio and / or visual indication that the airborne particle density is different from the expected airborne particle density, and / or provide an interlock of access to the enclosed system, such as a housing to the enclosed system, for example an access door to a tablet press of the enclosed system, and / or prevent the IBC from being undocked, when the processing unit determines that the sensor signal is different from the expected sensor signal.

[0049] In some embodiments, the first sensor comprises an air suction means having an inlet, and the monitoring system further comprises an inlet adapter having one or more inlets and an outlet configured to be connected to the inlet of the first sensor, and the one or more inlets of the adapter are configured to enable the air suction means of the first sensor to take in air along at least 40% of the circumference of a cross section of the first potential leakage zone.

[0050] This can improve the robustness of the monitoring system by allowing air to be drawn from a larger portion of the circumference, making it easier to detect leaks at points along the circumference, especially when the potential leak zone has a larger surface area over which the leak can occur.

[0051] The one or more inlets of the adapter may be configured to allow the air suction means to draw air from at least 40% of the circumference, for example from at least 50%, at least 60%, at least 70%, or at least 80% of the cross section of the first potential leakage zone. The one or more inlets of the adapter may be configured to allow air to flow from the one or more inlets of the adapter to an outlet of the adapter, potentially to an inlet of the air suction means. Alternatively or additionally, the inlet adapter may comprise a flow path through which air can flow from the one or more inlets of the adapter to an outlet of the adapter.

[0052] The first potential leakage zone may be substantially tubular and / or may have a substantially elliptical cross-section, such as being substantially circular.

[0053] In some embodiments, the one or more inlets of the adapter may be configured to direct air and / or allow air to flow towards the suction means of the first sensor. Alternatively or additionally, the one or more inlets of the adapter may be configured such that the air suction means of the first sensor can induce an air flow through at least 40% of the circumference of a cross section of the first potential leakage zone, potentially such that the air flow through at least 40% of the circumference of a cross section of the first potential leakage zone is taken in by the suction means of the first sensor.

[0054] Each of the one or more inlets may be in fluid communication with the outlet, and potentially with each other. Each of the one or more inlets may be provided as an opening, a flow path having an opening, potentially facing a first potential leakage zone.

[0055] In some embodiments, the inlet adapter comprises a plurality of inlets arranged such that the air suction means can take in air at respective portions around the circumference of the cross-section of the first potential leakage zone, or the inlet adapter is configured to surround at least a portion, for example at least half, of the circumference of the cross-section of the first potential leakage zone.

[0056] The plurality of inlets may comprise or be at least two inlets, e.g., at least three inlets, at least four inlets, or at least five inlets. Each of the plurality of inlets may be positioned at a respective position around the circumference of the cross-section of the first potential leakage zone. Each of the plurality of inlets may be in fluid communication with an outlet of the inlet adapter. Alternatively or additionally, each of the inlets of the adapter is positioned to allow a respective portion of the total flow that passes through the outlet of the inlet adapter to the air suction means and that is comprised by a respective portion of the total flow to flow through each of the plurality of inlets.

[0057] An inlet adapter configured to surround at least a portion of the circumference of a cross section of the first potential leakage zone may be configured to be positioned such that an air path is formed between at least a portion of the inlet adapter and a portion of the circumference of the cross section. Alternatively or additionally, when the inlet adapter is configured to surround at least a portion of the circumference of the cross section, it may be configured to surround at least a portion of the potential leakage zone and / or may include only a single inlet. The inlet adapter may be configured to surround at least 40%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80% of the circumference of the cross section of the first potential leakage zone.

[0058] The inlet adapter may be configured to allow air to cross-flow across the first potential leakage zone. Alternatively or additionally, the inlet adapter may be configured to direct particles in the air surrounding the first potential leakage zone to the sensor.

[0059] In some embodiments, the first sensor comprises an air suction means, such as an air suction pump.

[0060] If further optional sensors, such as a second sensor and / or a background sensor, are provided, the further sensor(s) may comprise air suction means, such as an air suction pump.

[0061] The air suction means may be configured to draw in a predetermined volume of air from outside the enclosed system.

[0062] In some embodiments the air suction means is configured to provide an air flow of 0.5-12 l / m, preferably 1-10 l / m, preferably 2-8 l / m, preferably 2-5 l / m.

[0063] In some embodiments, the air suction means is configured to provide an air flow of about 2 l / min or about 5 l / m.

[0064] In some embodiments, the first sensor is configured to be positioned at a distance of 0.5-20 cm, preferably 1-15 cm, preferably 1-10 cm, preferably 2-8 cm, preferably 3-8 cm, preferably 4-6 cm from the enclosed system, for example from a potential leak zone of the enclosed system.

[0065] The distance may be to a particular point relative to the enclosed system, such as the desired point of measurement and / or a potential leak zone. In some embodiments, the first sensor may be configured to be fixed to a portion of the enclosed system, such as an outer wall of an element of the enclosed system, and may be configured to be positioned at a distance of 0.5-20 cm, preferably 1-15 cm, preferably 1-10 cm, preferably 2-8 cm, preferably 3-8 cm, preferably 4-6 cm, from the desired point of measurement.

[0066] The above distance may be determined as the distance from the measurement point of the first sensor and / or from the air inlet of the first sensor to the enclosed system, for example to the desired measurement point and / or potential leakage zone of the enclosed system, etc.

[0067] The distance may be determined as the shortest distance and / or the distance along a straight line between the first sensor, e.g., the measurement point or air inlet of the first sensor, and the enclosed system, e.g., the desired measurement point and / or the potential leak zone of the enclosed system. If the distance is between the first sensor and the potential leak zone of the enclosed system, the distance may be the distance to the closest point within the leak zone and / or the distance to the center point of the potential leak zone. Alternatively or additionally, the distance may be the horizontal distance only, the vertical distance only, or the total distance in both the horizontal and vertical directions.

[0068] The first sensor may be configured to be fixed to the outside of the enclosed system. The first sensor may be configured to be fixed to the enclosed system, for example, on an outer surface of the enclosed system and / or to an element thereof. The monitoring system, potentially the first sensor, may include a fixation element for fixing the first sensor relative to the enclosed system at a first point outside the enclosed system. The fixation element may be or include one or more of an adhesive, a screw, a bracket, a clip, or a magnet. Alternatively or additionally, the fixation element may be configured to be positioned at the first point using a holding element such as a stand or holder. The fixation element may be configured to ensure that the first sensor is positioned at a distance of 0.5-20 cm, preferably 1-15 cm, preferably 1-10 cm, preferably 2-8 cm, preferably 3-8 cm, preferably 4-6 cm, relative to the enclosed system, and / or may be configured to help maintain a distance to the enclosed system.

[0069] If the monitoring system comprises a second sensor, the second sensor may be configured to be positioned at a distance of 0.5-20 cm, preferably 1-15 cm, preferably 1-10 cm, preferably 2-8 cm, preferably 3-8 cm, preferably 4-6 cm from the enclosed system, for example from a potential leak zone of the enclosed system.

[0070] In some embodiments, the first sensor is configured to be positioned to have a distance relative to the enclosed system, the distance relative to the enclosed system being based at least in part on the air flow that the air suction means is configured to provide.

[0071] The distance to the enclosed system may be determined such that it increases if increased airflow is provided. Potentially, the distance may be increased proportionally to the increase in airflow. In some embodiments, the first sensor is configured to be positioned within a distance range to the enclosed system, such as the distance ranges described above, and this distance range is determined based on the airflow that the air suction means of the first sensor is configured to provide.

[0072] If the monitoring system includes a second sensor, the second sensor may be configured to be positioned at a distance relative to the enclosed system, the distance relative to the enclosed system being based at least in part on the air flow that the air suction means of the second sensor is configured to provide, which distance may be determined in a similar or identical manner as described in relation to the first sensor.

[0073] In some embodiments, the monitoring system is configured to determine particle density of particles having a size within a first range, the first range being a subrange of a range of 0.1-40 micrometers, preferably a range of 0.2-25 micrometers, preferably a range of 0.3-17 micrometers, preferably a range of 0.5-15 micrometers, preferably a range of 0.7-13 micrometers, preferably a range of 1-10 micrometers.

[0074] Alternatively, in some embodiments, the monitoring system is configured to determine particle density of particles having a size within a first range, the first range being a sub-range of a range of 0.1-300 micrometers, preferably a range of 0.1-100 micrometers, preferably a range of 0.1-40 micrometers, preferably a range of 0.2-25 micrometers, preferably a range of 0.3-18 micrometers.

[0075] Thereby, the robustness of the monitoring system may be improved as the monitoring system may be configured to detect only the particle density of particles released from the processing of the pharmaceutical ingredient.

[0076] In some embodiments, the processing unit is configured to determine a particle density of particles having a size within the first range. The processing unit may be configured to determine the particle density of particles having a size within the first range based on a sensor signal from the first sensor. The processing unit may be configured to determine the particle density of particles having a size within the first range by filtering the sensor signal. Alternatively or additionally, the first sensor may be configured to determine the particle density of particles having a size within the first range, potentially by a sensor processing unit of the first sensor. Alternatively or additionally, the first sensor signal may be indicative of the particle density of particles having a size within the first range.

[0077] If the monitoring system includes a second sensor, the monitoring system may be configured to determine a particle density of particles having a size within a second range based on a second signal from the second sensor, which may be the same as the first range.

[0078] In some embodiments, the first sensor is configured to determine a particle density of particles having a size within a first range, the first range being based at least in part on knowledge of the one or more pharmaceutical ingredients of the encapsulated system and / or based at least in part on a location of the first sensor.

[0079] This allows the monitoring system to be configured to determine leakage of particles within a size range corresponding to one or more pharmaceutical ingredients, thereby providing a more robust and accurate monitoring system. For example, if a first sensor is positioned proximal to the inlet of a particular pharmaceutical ingredient, the first range may be a size range within which some, most, or substantially all of the particles of the pharmaceutical ingredient are located. This allows the first sensor to detect leakage of only this pharmaceutical ingredient because the sensor does not detect interference from, for example, larger or smaller particles, thereby improving the robustness of the monitoring system.

[0080] The knowledge regarding the one or more pharmaceutical ingredients may be knowledge regarding particle sizes of any of the one or more pharmaceutical ingredients, such as typical particle sizes and / or typical particle size ranges for a particular pharmaceutical ingredient.

[0081] Knowledge of the location of the first sensor may be based on a first point at which the sensor is configured to be placed, and may include knowledge of potential leak zones, for example, which pharmaceutical ingredients pass through potential leak zones inside the enclosed system when the enclosed system is in operation.

[0082] In some embodiments, the first sensor is further configured to provide a sensor signal to the processing unit indicative of a size distribution of particles in the air outside the enclosed system.

[0083] In some embodiments, the first sensor is configured to provide a sensor signal to the processing unit indicative of particle density in a plurality of subranges. As an example, the first sensor may be configured to provide a signal indicative of particle counts in a plurality of subranges, e.g., at least two subranges, at least four subranges, or at least eight subranges. Alternatively or additionally, the processing unit may be configured to determine a particle size distribution based on a sensor signal indicative of a particle size distribution in the air outside the enclosed system, such as a sensor signal indicative of particle density and / or particle counts. When the monitoring system is configured to determine a particle density of particles having sizes within a first range, the subrange may be a subrange of the first range.

[0084] If the monitoring system includes additional sensors, such as a second sensor and / or a background sensor, the additional sensors can be configured to provide the processing unit with additional sensor signals, such as a second sensor signal and / or a background sensor signal, respectively, indicative of the particle size distribution in the air outside the enclosed system. Alternatively or additionally, the additional sensors may be configured to provide the processing unit with additional sensor signals indicative of particle densities in multiple subranges, potentially identical to the multiple subranges of the first sensor. In some embodiments, the processing unit can be configured to compare the particle densities in the subranges determined by the first and second sensors, e.g., to compare the particle density and / or particle counts in each subrange from the first sensor with the particle density and / or particle counts in each subrange from the second sensor. The processing unit can be configured to apply any arithmetic operation to the particle densities, such as subtracting the particle density determined based on the sensor signal from the second sensor from the particle density determined based on the sensor signal from the first sensor, or vice versa. In some embodiments, the processing unit may be configured to compare particle size distributions and / or particle size densities in one or more subranges.

[0085] In some embodiments, the monitoring system further comprises a background sensor configured to be positioned outside the enclosed system and configured to repeatedly provide a background sensor signal to the processing unit indicative of particle density in the air outside the enclosed system, the background sensor configured to be positioned at a distance from the first sensor, and the predicted sensor signal being based at least in part on the background sensor signal.

[0086] This allows the monitoring system to ignore background particle densities, i.e., the density of particles not emitted by the enclosed system, such as dust particles inside the room in which the enclosed system is located, thereby allowing for more robust detection of leaks from the enclosed system.

[0087] The processing unit may be configured to determine a background particle density based on the background sensor signal, and may be configured to subtract and / or compare the background particle density from the particle density determined based on the sensor signal from the first sensor and / or based on the sensor signal from the second sensor.

[0088] In some embodiments, the predicted sensor signal is a background sensor signal. Alternatively or additionally, the predicted sensor signal may be a threshold, where the threshold is determined based on the background sensor signal, potentially as an adaptive threshold that is iteratively adapted based on the background sensor signal. For example, when the background sensor signal indicates an increase in particles, the threshold may be increased. When the background sensor signal indicates a decrease in particle density, the threshold may be decreased.

[0089] The background sensor may include any feature(s) described in connection with the first and / or second sensors and / or may be similar to or identical to the first and / or second sensors.

[0090] In some embodiments, if a second sensor is provided, the second sensor may be and / or function as a background sensor for determining particle density based on the sensor signal from the first sensor.

[0091] In some embodiments, the background sensor is configured to be placed in connection with the enclosed system.

[0092] In some embodiments, the background sensor is configured to be positioned to have a distance of 0.5-20 cm from the desired point of measurement.

[0093] The desired point of measurement may be a desired point of measurement within a room surrounding the enclosed system, or may be a potential leak zone, such as a second potential leak zone, if the background sensor is and / or functions as a second sensor.

[0094] In some embodiments, the background sensor is configured to be positioned at a distance of 0.5-20 cm, preferably 1-15 cm, preferably 1-10 cm, preferably 2-8 cm, preferably 3-8 cm, preferably 4-6 cm from the desired point of measurement.

[0095] The background sensor can then be used to monitor other potential leak zones.

[0096] In some embodiments, the background sensor is configured to provide a background sensor signal indicative of particle density in the intake air into a room surrounding the enclosed system. In some embodiments, the monitoring system is configured to measure particle density in the intake air into a room surrounding the enclosed system.

[0097] In some embodiments, the background sensor is configured to be positioned at a distance of 20 cm or greater from the enclosed system.

[0098] This allows the background sensor to more accurately estimate the background particle density.

[0099] In some embodiments, the background sensor is configured to be positioned at substantially the same vertical height as the first sensor.

[0100] This compensates for the effect of gravity on the particle distribution, i.e., larger and heavier particles will settle to lower heights, while smaller and lighter particles may be present at higher heights, thus improving the robustness of the monitoring system.

[0101] In some embodiments, the monitoring system is configured to determine a particle density of particles having a size within a first range, the first range being based at least in part on a sensor signal from a background sensor.

[0102] The monitoring system, potentially its processing unit, may determine particle density based on the sensor signal from the first sensor. The processing unit and / or the sensor processing unit of the first sensor may determine particle density based on the sensor signal and subsequently select, such as by applying a filter, the density of particles having a size within a first range. Alternatively or additionally, the processing unit and / or the sensor processing unit of the first sensor may select a portion of the sensor signal and determine the density of particles having a size within the first range based on the portion of the sensor signal.

[0103] In some embodiments, the background sensor is configured to provide a sensor signal indicative of the particle size distribution to the processing unit.

[0104] The processing unit may be configured to compare the particle size distribution determined based on the background sensor signal with the particle size distribution determined based on the respective sensor signals from the first sensor and / or the second sensor, and the processing unit may be configured to compare these and / or apply arithmetic operations as described in relation to the first sensor and the second sensor.

[0105] The predicted sensor signal may have multiple thresholds, i.e., a respective threshold for each respective particle size subrange. For example, if the background sensor signal indicates an increase in particles within a particular subrange of the distribution, the predicted sensor signal threshold for the particular subrange may be raised. If the background sensor signal indicates a decrease in particle density of particles having sizes within the particular subrange, the threshold for the particular subrange may be lowered.

[0106] According to a second aspect, a method is disclosed for monitoring the performance of an enclosed system for processing pharmaceutical ingredients, the enclosed system comprising one or more inlets for receiving one or more pharmaceutical ingredients and one or more outlets, the method comprising: identifying a first potential leakage zone; positioning a first sensor outside the enclosed system adjacent to the first potential leakage zone, the first sensor configured to repeatedly provide a sensor signal indicative of particle density in the air; determining a performance of the enclosed system based on the sensor signal, wherein determining the performance of the enclosed system includes comparing the sensor signal to a predicted sensor signal, and if the sensor signal is determined to be different from the predicted sensor signal, outputting an output signal indicating that the airborne particle density is different from the predicted airborne particle density.

[0107] The method according to the second aspect may provide the same or similar advantages to a monitoring system as described according to the first aspect of the present disclosure. In particular, by positioning the first sensor outside the enclosed system and proximate to the first potential leak zone, a leak can be identified within a short time of its occurrence, and appropriate action can be taken upon detection. In this way, operator safety is improved, as well as test complexity and test time are reduced.

[0108] It should be understood that by "determining performance" it is possible to determine whether an encapsulated system is sufficiently encapsulated, i.e., whether leakage or release of one or more pharmaceutical ingredients exceeds a particular level, e.g., a threshold value or the like.

[0109] The first sensor may be the first sensor of a monitoring system according to the first aspect of the present invention.

[0110] A potential leak zone may comprise one or more potential leak points. The potential leak zone and / or potential leak point(s) may be as described in relation to the first aspect of the present disclosure.

[0111] In some embodiments, determining the performance of the enclosed system includes comparing the sensor signal with an expected sensor signal by a processing unit operatively connectable to the first sensor, where the first sensor is configured to repeatedly provide the sensor signal to the processing unit, and if the sensor signal is determined to differ from the expected sensor signal, outputting, by the processing unit, an output signal indicating that the particle density in the air differs from the expected particle density in the air.

[0112] In some embodiments, the enclosed system is disposed in a room, and the step of disposing the first sensor includes disposing the first sensor inside the room and outside the enclosed system.

[0113] In some embodiments of the method, the step of positioning the first sensor includes positioning the first sensor less than 20 cm from the first potential leak zone.

[0114] In some embodiments, the first sensor comprises an air suction means, such as an air suction pump. In some embodiments, the step of positioning the first sensor includes positioning the first sensor at a distance greater than 0.5 cm from the first potential leak zone.

[0115] Potentially, the step of positioning the first sensor comprises positioning the first sensor a distance of more than 1 cm, for example more than 2 cm, for example more than 3 cm, for example more than 4 cm, from the first potential leak zone. Alternatively or additionally, the step of positioning the first sensor may comprise positioning the first sensor a distance of 0.5-20 cm, for example 1-15 cm, for example 1-10 cm, for example 2-8 cm, for example 3-8 cm, for example 4-6 cm, from the first potential leak zone.

[0116] In some embodiments, the enclosed system optionally comprises a first module and a second module connected at an interface, and the first potential leakage zone is selected from the inlet, the outlet, and optionally the interface.

[0117] The first module and the second module are each one or more of a container such as an intermediate bulk container (IBC) for pharmaceutical ingredients or mixtures thereof, a feeder, a mixer, or a tablet press.

[0118] In some embodiments, the method further comprises positioning the second sensor at a distance of at least 10 cm, preferably at least 20 cm, preferably at least 50 cm, relative to the first sensor.

[0119] In some embodiments, the method includes: Determining a second potential leak zone; Further comprising disposing a second sensor proximate to a second potential leak zone.

[0120] The second sensor may be operatively connectable to the processing unit and configured to repeatedly provide the processing unit with a second sensor signal indicative of the particle density in the air. In some embodiments, the method may further include determining performance of the enclosed system based on the second sensor signal.

[0121] Alternatively or additionally, determining the performance of the encapsulated system based on the sensor signal may include determining the performance of the encapsulated system based on the sensor signal and the second sensor signal. Potentially, determining the performance of the encapsulated system may be performed subsequent to placing the second sensor.

[0122] The second potential leak zone may be selected from an inlet, an outlet, and potentially an interface. Potentially, the step of positioning the second sensor includes positioning the second sensor at a distance of more than 1 cm, for example more than 2 cm, for example more than 3 cm, for example more than 4 cm, from the second potential leak zone. Alternatively or additionally, the step of positioning the second sensor may include positioning the second sensor at a distance of 0.5-20 cm, for example 1-15 cm, for example 1-10 cm, for example 2-8 cm, for example 3-8 cm, for example 4-6 cm, from the second potential leak zone.

[0123] In some embodiments, the method further comprises: The method further comprises the step of positioning a background sensor at a distance relative to the enclosed system, at least 20 cm, preferably at least 50 cm, preferably at least 1 m from any potential leakage zone.

[0124] In some embodiments, the method includes: The method further includes placing the background sensor proximate to an air intake of a room surrounding the enclosed system.

[0125] Alternatively or additionally, the above steps include positioning the background sensor relative to the enclosed system at a distance of at least 20 cm, preferably at least 50 cm, preferably at least 1 m from any potential leakage zones, and positioning the background sensor in proximity to an air intake of a room surrounding the enclosed system.

[0126] According to a third aspect, there is disclosed a room, the room comprising: an enclosed system for processing pharmaceutical ingredients, the enclosed system comprising one or more inlets for receiving one or more pharmaceutical ingredients and one or more outlets, the chamber further comprising: A room comprising a monitoring system according to a first aspect of the invention for monitoring performance of the enclosed system, the first sensor being positioned at a first point outside the enclosed system and within the room.

[0127] The room according to the second aspect may provide the same or similar advantages as the surveillance system as described according to the first aspect of the present disclosure.

[0128] The room enclosed system may be an enclosed system as described above in relation to the surveillance system according to the first aspect of the invention.

[0129] In some embodiments, the monitoring system may be configured to monitor the performance of the enclosed system.

[0130] According to a fourth aspect, the following pharmaceutical system is disclosed: an enclosed system for processing pharmaceutical ingredients, the enclosed system comprising one or more inlets for receiving one or more pharmaceutical ingredients and one or more outlets, the pharmaceutical system further comprising: A pharmaceutical system according to a first aspect of the present invention, comprising a monitoring system for monitoring performance of the enclosed system, wherein a first sensor is positioned at a first point outside the enclosed system and within a room.

[0131] The pharmaceutical system according to the fourth aspect may provide the same or similar advantages to the monitoring system as the encapsulated system as described by the first aspect of the present disclosure.

[0132] The encapsulated system of the pharmaceutical system may be an encapsulated system as described above in relation to the monitoring system according to the first aspect of the present invention.

[0133] In some embodiments, the monitoring system may be configured to monitor the performance of the enclosed system.

[0134] Different aspects of the present invention can be implemented in different ways, including a monitoring system for monitoring the performance of an enclosed system, a monitoring method for monitoring the performance of an enclosed system, a room comprising the enclosed system and the monitoring system, and a system comprising the enclosed system and the monitoring system, as described above and below, each of which provides one or more of the benefits and advantages described in connection with at least one or more of the above-described aspects, and each of which has one or more preferred embodiments corresponding to the preferred embodiments described in connection with at least one or more of the above-described aspects and / or disclosed in the dependent claims. Furthermore, it should be understood that embodiments described in connection with at least one or more of the aspects described herein may be applied to other aspects as well.

[0135] The above and / or additional objects, features, and advantages of the present invention will become more apparent from the following illustrative and non-limiting detailed description of embodiments of the present invention, taken in conjunction with the accompanying drawings. [Brief explanation of the drawings]

[0136] [Figure 1] FIG. 1 shows a schematic block diagram of an embodiment of a surveillance system according to the present disclosure. [Figure 2] FIG. 2 shows a schematic block diagram of an embodiment of a room with an enclosed system and a monitoring system according to the present disclosure. [Figure 3] FIG. 3 shows a flow chart of an embodiment of a method for monitoring the performance of an enclosed system according to the present disclosure. [Figure 4] FIG. 4 shows a flow chart of an embodiment of a method for monitoring the performance of an enclosed system according to the present disclosure. [Figure 5a] FIG. 5a shows a perspective view of the elements of the enclosed system. [Figure 5b] FIG. 5b shows a horizontal cross-sectional view of the elements of the enclosed system shown in FIG. 5a. [Figure 6a] FIG. 6a shows a perspective view of the elements of the encapsulated system. [Figure 6b] FIG. 6b shows a cross-sectional view of the elements of the enclosed system shown in FIG. 6a. [Figure 7] FIG. 7 shows a schematic diagram of elements of an inlet adapter of an embodiment of a monitoring system according to the present disclosure. [Figure 8] FIG. 8 shows a schematic diagram of elements of an inlet adapter of an embodiment of a monitoring system according to the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0137] Like reference numerals are used for like elements throughout the various embodiments and figures described herein.

[0138] In the following description, reference is made to the accompanying drawings, which show, by way of example, how the invention may be put into practice.

[0139] FIG. 1 shows a schematic block diagram of an embodiment of a monitoring system 1 according to the present disclosure. The monitoring system 1 is for monitoring the performance of an enclosed system (not shown in FIG. 1) for processing pharmaceutical ingredients, the enclosed system having one or more inlets for receiving one or more pharmaceutical ingredients and one or more outlets. The monitoring system 1 comprises a first sensor 10 and a processing unit 20 operatively connectable to the first sensor 10. The first sensor 10 is configured to be positioned at a first point outside the enclosed system. The first sensor 10 is configured to repeatedly provide the processing unit 20 with a sensor signal indicative of particle density in the air outside the enclosed system.

[0140] The processing unit 20 is configured to compare the sensor signal with an expected sensor signal.

[0141] 2 shows a schematic block diagram of an embodiment of a room R comprising an enclosed system 50 for processing pharmaceutical ingredients and a monitoring system 2 according to the present disclosure. The monitoring system 2 comprises a first sensor 10′ and a processing unit 20 operatively connectable to the first sensor 10′. The first sensor 10′ is configured to be positioned at a first point outside the enclosed system 50. The first sensor 10′ is configured to repeatedly provide the processing unit 20 with a sensor signal indicative of the particle density in the air outside the enclosed system 50.

[0142] First sensor 10' differs from first sensor 10 of monitoring system 1 only in that first sensor 10' includes a sensor processing unit 110 and an air suction pump 112. It should be understood that in other embodiments of monitoring system 2, first sensor 10 may be used in place of first sensor 10'.

[0143] The encapsulated system 50 comprises a first inlet 51 for receiving one or more pharmaceutical ingredients and an outlet 56. The encapsulated system further comprises a second inlet 52 for receiving one or more pharmaceutical ingredients. The encapsulated system 50 comprises a first module 53 in the form of a mixer and a second module 55 in the form of a tablet press, connected by an interface 54. The first and second inlets 51 and 52 are each connected to the first module 53 via an interface (not shown). Additionally, the second module 55 is connected to the outlet 56 by another interface (not shown).

[0144] The first sensor 10' is positioned adjacent to a first potential leakage zone of the enclosed system 50, for example at a distance of about 5 cm, which is the inlet 51. The first sensor 10' includes a sensor processing unit 100 configured to output a sensor signal indicative of particle density. The sensor processing unit 100 is a CPU.

[0145] The monitoring system 2 further comprises a second sensor 11 operatively connectable to the processing unit 20. The second sensor 11 is positioned at a second point outside the enclosed system 50. The second point is a second potential leakage zone in the form of a boundary 54. The second sensor 11 is positioned at a distance of 5 cm from the boundary 54 and at a distance of more than 50 cm from the first sensor 10′. The second sensor 11 is configured to repeatedly provide the processing unit with a second sensor signal indicative of the particle density in the air outside the enclosed system.

[0146] The monitoring system 2 further comprises a background sensor 12 configured to be positioned outside the enclosed system 50 and configured to repeatedly provide a background sensor signal to the processing unit 20 indicative of the particle density in the air outside the enclosed system 50. The background sensor 12 is positioned at a distance from the first sensor 10 and at a distance from the second sensor 11.

[0147] The processing unit 20 is configured to output an output signal indicating that the particle density in the air differs from the expected particle density in the air when the processing unit determines that the sensor signal from at least the first sensor 10' differs from the expected sensor signal.

[0148] The first sensor 10 ′, the second sensor 11 and the background sensor 12 are all located within the room R and outside the enclosed system 50 .

[0149] The second sensor 11 and the background sensor 12 each comprise a sensor processing unit 110, 120, respectively.

[0150] The processing unit 20 is located outside the enclosed system 50 in a room R that surrounds the enclosed system 50 .

[0151] The processing unit 20 is configured to compare the sensor signal to an expected sensor signal. The expected sensor signal represents and / or can be a threshold value. The processing unit 20 of the monitoring system determines that a leak is occurring when the sensor signal of the first sensor 10′ and / or the sensor signal of the second sensor 11 exceeds the threshold value. The threshold value is dynamically determined by the processing unit 20 based on input from the background sensor 12.

[0152] Each of the first sensor 10', second sensor 11 and background sensor 12 is provided with a respective air suction pump 102, 112, 122. The air suction pumps 102, 112, 122 are each configured to provide an air flow of 2 l / min.

[0153] The first sensor 10' and the second sensor 11 are fixed relative to the enclosed system using respective holding devices (not shown).

[0154] The monitoring system is configured to determine a particle density of particles having a size within a first range, the first range being a subrange of the range of 0.3-17 micrometers.

[0155] The processing unit 20 is configured to determine the particle density of particles having a size within the first range. The processing unit 20 determines the particle density of particles having a size within the first range based on the sensor signal from the first sensor 10'. configured to determine The processing unit 20 calculates the particle density of particles having sizes within the first range based on the sensor signal from the second sensor 11. configured to determine .

[0156] The first sensor 10' is further configured to provide to the processing unit 20 a sensor signal indicative of the particle size distribution in the air outside the enclosed system 50, in the form of a signal indicative of the particle counts in the four sub-ranges. Similarly, the second sensor 11 and the background sensor 12 are each configured to provide to the processing unit 20 a sensor signal indicative of the particle size distribution in the air outside the enclosed system 50, in the form of a signal indicative of the particle counts in the four sub-ranges.

[0157] The processing unit 20 is configured to compare the sensor signal to an expected sensor signal, the expected sensor signal being based, at least in part, on a background sensor signal.

[0158] The processing unit 20 is configured to determine a background particle density based on the background sensor signal. The processing unit 20 is configured to compare the background particle density from the particle density determined based on the sensor signal from the first sensor 10′ with the background particle density from the particle density determined based on the signal of the second sensor 11.

[0159] The background sensor 12 is configured to provide a background sensor signal indicative of particle density in the intake air into the room R surrounding the enclosed system 50. The background sensor is positioned to have a distance of 20 cm or more from the enclosed system 50.

[0160] 3 shows a flow chart of an embodiment of Method 3 for monitoring the performance of an encapsulated system according to the present disclosure. Method 3 is a method for monitoring the performance of an encapsulated system for processing pharmaceutical ingredients, the encapsulated system comprising one or more inlets and one or more outlets for receiving one or more pharmaceutical ingredients. Method 3 comprises: a step 30 of identifying a first potential leakage zone; positioning 31 a first sensor outside the enclosed system adjacent to a first potential leak zone, the first sensor configured to repeatedly provide a sensor signal indicative of particle density in the air; and determining 32 the performance of the enclosed system based on the sensor signals.

[0161] 4 shows a flow chart of a fourth embodiment of a method for monitoring the performance of an encapsulated system according to the present disclosure. a step 40 of identifying a first potential leakage zone; and positioning 41 a first sensor outside the enclosed system adjacent to a first potential leak zone, the first sensor configured to repeatedly provide a sensor signal indicative of particle concentration in the air. The identifying step 40 and the locating step 41 are similar to steps 30 and 31 of Method 3.

[0162] In Method 4, the enclosed system is placed in a room. Step 41 of placing a first sensor includes placing the first sensor in the room and outside the enclosed system. Step 41 of placing the first sensor includes placing the first sensor less than 20 cm from a first potential leak zone, for example, about 5 cm.

[0163] The first sensor includes an air suction means, such as an air suction pump, and step 41 of positioning the first sensor further includes positioning the first sensor at a distance greater than 0.5 cm from the first potential leak zone.

[0164] Optionally, the enclosed system comprises a first module and a second module connected at an interface, and the first potential leakage zone is selected from one or more inlets, one or more outlets, and optionally the interface. Step 40 of identifying a first potential leakage zone includes selecting the first potential leakage zone from one or more inlets, one or more outlets, and optionally the interface.

[0165] Method 4 is determining 42 a second potential leakage zone; and positioning 43 a second sensor adjacent to a second potential leak zone.

[0166] The step 43 of positioning the second sensor further comprises positioning the second sensor to have a distance of at least 10 cm, such as at least 20 cm, such as at least 50 cm, relative to the first sensor.

[0167] The second sensor is operatively connectable to the processing unit and configured to repeatedly provide to the processing unit a second sensor signal indicative of the particle density in the air.

[0168] Method 4 is The method further includes step 44 of positioning the background sensor relative to the enclosed system at a distance of at least 20 cm, preferably at least 50 cm, preferably at least 1 meter from any potential leak zone. In method 4, step 44 of positioning the background sensor includes positioning the background sensor proximate to an air intake of a room surrounding the enclosed system.

[0169] Method 4 further includes determining 45 the performance of the enclosed system based on the sensor signal from the first sensor and the second sensor signal.

[0170] Figure 5a shows a perspective view of elements of an encapsulated system 50', while Figure 5b shows a horizontal cross-sectional view of elements of the encapsulated system 50'. The encapsulated system 50' comprises a first IBC 51', which is a first container for a pharmaceutical ingredient, and a second IBC 52', which is a second container for another pharmaceutical ingredient. The first IBC 51' and the second IBC 52' are both connected to a mixer 53' by respectable substantially tubular first and second interfaces 57a, 57b. The first and second interfaces 57a, 57b include potential leakage zones.

[0171] As shown in Figures 5a and 5b, the first sphere 58a represents a distance R of 20 cm from the center point of the substantially tubular first boundary 57a, i.e., a distance of 20 cm from the potential leak point of the first potential leak zone formed by the substantially tubular first boundary 57a. 2 The distance R is 20 cm from the center point of the boundary portion 57b, i.e., the substantially tubular 2The second potential leak zone formed by boundary 57b shows a distance of 20 cm from the potential leak point. First sphere 58a and encapsulated system 50' define a volume in which a first sensor of the encapsulated system (not shown in FIGS. 5a and 5b) may be advantageously located. The volume has a substantially spherical periphery. Second sphere 58a and encapsulated system 50' define a volume in which a second sensor of the monitoring system (not shown in FIGS. 5a and 5b) may be advantageously located. The volume has a substantially spherical periphery. In other embodiments, the volume in which a potential second sensor of the monitoring unit may be advantageously located may have a distance of 20 cm from any point on the periphery of the volume to the respective nearest point of the potential leak zone. For example, if the potential leak zone is annular, the volume may have a substantially cylindrical periphery and two hemispheres at each end of the substantially cylindrical periphery.

[0172] FIG. 6a shows a perspective view of the elements of the encapsulated system 50'', while FIG. 6b shows a cross-sectional view of the elements of the encapsulated system 50'' shown in FIG. 6a.

[0173] 6a and 6b show two openable tubes connected by a two-section split butterfly valve 57', which constitutes a potential leakage zone.

[0174] In Figures 6a and 6b, sphere 58' indicates a potential leak zone, i.e., a distance R of 20 cm from the center point of valve 57'. Similar to the sphere shown in relation to the elements of the enclosed system in Figures 5a and 5b, sphere 58' and enclosed system 50'' now define a volume of air outside the monitoring system in which the monitoring system may advantageously be located. In Figures 6a and 6b, the volume defined by sphere 58' is spherical, i.e., has a spherical outer shape, while in other embodiments the volume has an outer shape with a substantially tubular section. Alternatively or additionally, each point on the periphery of said volume may be a point on the periphery of a potential leak zone. That is, the valve 57' may have a distance of 20 cm to each of the nearest points.

[0175] The potential leak zone of valve 57' comprises a first potential leak subzone 570 and a second potential leak subzone 572, each comprising a plurality of potential leak points. First potential leak subzone 570 and second potential leak subzone 572 extend around the circumference of valve 57'. In some embodiments, the volume is defined such that each point on its circumference has a distance of 20 cm to the nearest potential leak point of first potential leak point 570 and second potential leak point 572.

[0176] FIG. 7 shows a schematic diagram of an inlet adapter element 60 of an embodiment of a monitoring system according to the present disclosure.

[0177] The inlet adapter 60 includes three inlets 61 a, 61 b, and 61 c, and an outlet 62. The outlet 62 is configured to be connected to the inlet of a first sensor (not shown in FIG. 7). The adapter's inlets 61 a, 61 b, and 61 c are configured so that the air suction means of the first sensor can draw air along at least 40% of the circumference of the cross section of the first potential leakage zone 54'. Air flow is indicated by arrows in FIG. 7.

[0178] The first potential leakage zone 54' is the boundary between the first and second modules of the enclosed system (not shown in FIG. 7).

[0179] Each of the three inlets 61 a, 61 b, and 61 c is in fluid communication with the outlet 62 and with each other. Each of the adapter inlets 61 a, 61 b, and 61 c is provided as a passage having an opening, each of which faces the first potential leakage zone 54′.

[0180] The adapter inlets 61 a, 61 b, and 61 c are configured so that the air suction means can draw air along at least 50% of the circumference of the cross section of the first potential leakage zone 54'. The adapter inlets 61 a, 61 b, and 61 c are configured so that air flow can flow from one or more of the adapter inlets to the adapter outlet 62.

[0181] The first potential leakage zone 54' is substantially tubular and has a substantially circular cross section.

[0182] The adapter inlets 61a, 61b, and 61c are configured so that the air suction means of the first sensor can induce air flow through at least 50% of the circumference of the cross section of the first potential leakage zone 54'.

[0183] The inlets 61a, 61b and 61c of the inlet adapter are positioned so that the air suction means can take in air at three respective locations around the circumference of the cross section of the first potential leakage zone 54'.

[0184] FIG. 8 shows a schematic diagram of elements of an inlet adapter of an embodiment of a monitoring system according to the present disclosure.

[0185] FIG. 8 shows a schematic diagram of an inlet adapter element 60' of an embodiment of a monitoring system according to the present disclosure.

[0186] The inlet adapter 60' includes an inlet 61' and an outlet 62. The outlet 62 is configured to connect to the inlet of a first sensor (not shown in FIG. 8). The adapter inlet 61' is configured so that the air suction means of the first sensor can draw air along at least 40% of the circumference of the cross section of the first potential leakage zone 54'. Air flow is indicated by arrows in FIG. 8.

[0187] The first potential leakage zone 54' is the interface between the first and second modules of the enclosed system (not shown in FIG. 8).

[0188] The inlet 61' is in fluid communication with the outlet 62. The inlet 61' is provided as an opening in the inlet adapter element 61' towards the surroundings.

[0189] The inlet adapter 60' is configured to surround at least 60% of the circumference of the cross section of the first potential leakage zone 54'.

[0190] An inlet adapter 60' configured to surround at least a portion of the circumference of the cross section of the first potential leakage zone 54' is positioned such that an air path 63 is formed between a portion of the inlet adapter 60' and a portion of the circumference of the cross section of the potential leakage zone 54'. The inlet adapter 60' includes a single inlet 61'.

[0191] The adapter inlet 61' is configured to allow air flow from one or more of the adapter's inlets to the adapter's outlet 62. The adapter inlet 61' is configured such that the air suction means of the first sensor can induce air flow through at least 60% of the circumference of the cross section of the first potential leakage zone 54', such that air flow exits at the outlet 62 having passed through at least 60% of the circumference of the cross section of the first potential leakage zone 54'.

[0192] While several embodiments have been described and shown in detail, the present invention is not limited thereto and may be embodied in other ways within the scope of the subject matter defined in the following claims. In particular, it is to be understood that other embodiments may be utilized and structural and functional changes may be made without departing from the scope of the present invention.

[0193] In a device claim enumerating several means, several of these means may be embodied by one and the same item of hardware. The mere fact that certain measures are recited in mutually different dependent claims or in different embodiments does not indicate that a combination of these measures cannot be used to advantage.

[0194] It should be emphasized that as used in this specification, the word "comprise / comprising" is taken to specify the presence of stated features, integers, steps or components, but does not, however, exclude the presence of one or more other features, integers, steps, components or groups thereof. The present disclosure also includes the following aspects. [Aspect 1] 1. A monitoring system for monitoring the performance of an enclosed system for processing pharmaceutical ingredients, the enclosed system comprising one or more inlets for receiving one or more pharmaceutical ingredients and one or more outlets, comprising: the monitoring system comprises a first sensor and a processing unit operatively connectable to the first sensor, the first sensor being disposed at a first point outside the enclosed system, and configured to repeatedly provide a sensor signal to the processing unit indicative of a particle concentration of particles having a size greater than 0.1 micrometers in air outside the enclosed system; the processing unit is configured to compare the sensor signal to an expected sensor signal; and the processing unit is configured to output an output signal indicating that the particle density in the air differs from the predicted particle density in the air if the processing unit determines that the sensor signal differs from the predicted sensor signal. [Aspect 2] 2. The monitoring system of claim 1, wherein the first sensor is configured to be positioned proximate to a first potential leak zone of the enclosed system. Aspect 3 A monitoring system as described in aspect 2, wherein the first sensor comprises an air suction means having an inlet, and the monitoring system further comprises an inlet adapter having one or more inlets and an outlet configured to be connected to the inlet of the first sensor, and the one or more inlets of the adapter are configured such that the air suction means of the first sensor can take in air from a portion along at least 40% of the circumference of a cross section of the first potential leakage zone. Aspect 4 A monitoring system as described in aspect 3, wherein the inlet adapter comprises multiple inlets arranged so that the air suction means can take in air at multiple portions along the circumference of the cross-section of the first potential leakage zone, or the inlet adapter is configured to surround at least a portion, for example at least half, of the circumference of the cross-section of the first potential leakage zone. Aspect 5 A monitoring system according to any one of aspects 1 to 4, wherein the first sensor is configured to be positioned at a distance of 0.5-20 cm, preferably 1-15 cm, preferably 1-10 cm, preferably 2-8 cm, preferably 3-8 cm, preferably 4-6 cm from the enclosed system, such as from a potential leakage zone of the enclosed system. Aspect 6 6. The monitoring system of any one of aspects 1 to 5, wherein the monitoring system is configured to determine the particle density of particles having a size within a first range, the first range being a sub-range of a range of 0.1-300 micrometers, preferably a range of 0.1-100 micrometers, preferably a range of 0.1-40 micrometers, preferably a range of 0.2-25 micrometers, preferably a range of 0.3-18 micrometers. Aspect 7 A monitoring system as described in any one of aspects 1 to 6, wherein the monitoring system is configured to determine a particle density of particles having a size within a first range, the first range being based at least in part on knowledge of the one or more pharmaceutical ingredients of the encapsulated system and / or based at least in part on the location of the first sensor. Aspect 8 A monitoring system described in any one of aspects 1 to 7, wherein the first sensor is further configured to provide a sensor signal to the processing unit indicative of a particle size distribution in the air outside the enclosed system. Aspect 9 9. The monitoring system of any one of aspects 1 to 8, further comprising a background sensor configured to be positioned outside the enclosed system and configured to repeatedly provide a background sensor signal to the processing unit indicative of particle density in the air outside the enclosed system, the background sensor configured to be positioned at a distance from the first sensor, and the predicted sensor signal being based at least in part on the background sensor signal. Aspect 10 1. A method for monitoring the performance of an enclosed system for processing pharmaceutical ingredients, the enclosed system comprising one or more inlets for receiving one or more pharmaceutical ingredients and one or more outlets, the method comprising: identifying a first potential leakage zone; positioning a first sensor outside the enclosed system adjacent to the first potential leakage zone, the first sensor configured to repeatedly provide a sensor signal indicative of particle density in the air; determining performance of the enclosed system based on the sensor signal; the step of determining performance of the enclosed system includes comparing the sensor signal to an expected sensor signal, and if the sensor signal is determined to differ from the expected sensor signal, outputting an output signal indicating that the airborne particle density differs from the expected airborne particle density. Aspect 11 The method of aspect 10, wherein the enclosed system is placed in a room, and the step of placing the first sensor includes placing the first sensor inside the room and outside the enclosed system. Aspect 12 12. The method of any one of aspects 10 to 11, wherein the step of positioning the first sensor includes positioning the first sensor to be less than 20 cm away from the first potential leak zone. Aspect 13 A method according to any one of aspects 10 to 12, wherein the enclosed system optionally comprises a first module and a second module connected at an interface, and the first potential leakage zone is selected from the one or more inlets, the one or more outlets, and optionally the interface. Aspect 14 The method comprises: 27. The method of any one of aspects 21 to 26, further comprising positioning a background sensor at a distance relative to the enclosed system, at a distance of at least 20 cm, preferably at least 50 cm, preferably at least 1 meter, from any potential leakage zone. Aspect 15 A room, the room comprising: an enclosed system for processing pharmaceutical ingredients, said enclosed system comprising one or more inlets for receiving one or more pharmaceutical ingredients and one or more outlets, said chamber further comprising: A room comprising the monitoring system of any one of aspects 1 to 9 for monitoring performance of the enclosed system, wherein the first sensor is positioned at a first point outside the enclosed system and within the room.

Claims

1. A pharmaceutical system comprising an enclosed system having dust containment capability, said enclosed system for processing pharmaceutical ingredients, said enclosed system comprising one or more inlets for receiving one or more pharmaceutical ingredients and one or more outlets, said pharmaceutical system further comprising a monitoring system for monitoring the performance of said enclosed system for processing pharmaceutical ingredients; the monitoring system comprises a first sensor and a processing unit operatively connectable to the first sensor, the first sensor being disposed at a first point outside the enclosed system, and configured to repeatedly provide a sensor signal to the processing unit indicative of a particle concentration of particles having a size greater than 0.1 micrometers in air outside the enclosed system; the processing unit is configured to compare the sensor signal to an expected sensor signal; and and wherein the processing unit is configured to output an output signal indicating that the airborne particle density differs from the predicted airborne particle density if the processing unit determines that the sensor signal differs from the predicted airborne particle density.

2. 10. The pharmaceutical system of claim 1, wherein the first sensor is positioned proximate to a first potential leak zone of the enclosed system.

3. 3. The pharmaceutical system of claim 2, wherein the first sensor comprises an air suction means having an inlet, and the monitoring system further comprises an inlet adapter having one or more inlets and an outlet configured to be connected to the inlet of the first sensor, and wherein the one or more inlets of the inlet adapter are configured such that the air suction means of the first sensor can take in air from a portion along at least 40% of the circumference of a cross section of the first potential leakage zone.

4. 4. The pharmaceutical system of claim 3, wherein the inlet adapter comprises a plurality of inlets arranged such that the air suction means can take in air at a plurality of locations along the circumference of the cross-section of the first potential leakage zone, or the inlet adapter is configured to surround at least a portion of the circumference of the cross-section of the first potential leakage zone.

5. 10. The pharmaceutical system of claim 1, wherein the first sensor is positioned at a distance of 0.5-20 cm from a potential leak zone of the enclosed system.

6. 10. The pharmaceutical system of claim 1, wherein the monitoring system is configured to determine a particle density of particles having a size within a first range, the first range being a subrange of a range of 0.1-300 micrometers.

7. 10. The pharmaceutical system of claim 1, wherein the monitoring system is configured to determine the particle density of particles having a size within a first range, the first range being based at least in part on knowledge of the particle sizes of the one or more pharmaceutical ingredients in the encapsulated system and / or on knowledge of which pharmaceutical ingredients pass through potential leakage zones within the encapsulated system when the encapsulated system is operating.

8. 10. The pharmaceutical system of claim 1, wherein the first sensor is further configured to provide a sensor signal to the processing unit indicative of a particle size distribution in the air outside the enclosed system.

9. 2. The pharmaceutical system of claim 1, wherein the monitoring system further comprises a background sensor, the background sensor being positioned outside the enclosed system and configured to repeatedly provide a background sensor signal to the processing unit indicative of particle density in the air outside the enclosed system, the background sensor being positioned at a distance from the first sensor, and the predicted sensor signal being based at least in part on the background sensor signal.

10. A method for monitoring the performance of an enclosed system having dust containment capabilities, said enclosed system for processing pharmaceutical ingredients, said enclosed system comprising one or more inlets for receiving one or more pharmaceutical ingredients and one or more outlets, said method comprising: identifying a first potential leakage zone; positioning a first sensor outside the enclosed system adjacent to the first potential leakage zone, the first sensor configured to repeatedly provide a sensor signal indicative of particle density in the air; determining performance of the enclosed system based on the sensor signal; the step of determining performance of the enclosed system includes comparing the sensor signal to an expected sensor signal, and if the sensor signal is determined to differ from the expected sensor signal, outputting an output signal indicating that the airborne particle density differs from the expected airborne particle density.

11. 11. The method of claim 10, wherein the enclosed system is disposed in a room, and wherein the step of disposing the first sensor includes disposing the first sensor inside the room and outside the enclosed system.

12. 11. The method of claim 10, wherein the step of positioning the first sensor includes positioning the first sensor less than 20 cm from the first potential leak zone.

13. 11. The method of claim 10, wherein the enclosed system comprises a first module and a second module connected at an interface, and the first potential leakage zone is selected from the one or more inlets, the one or more outlets, and the interface.

14. The method comprises:

14. The method of claim 10, further comprising positioning a background sensor at a distance relative to the enclosed system and at a distance of at least 20 cm from any potential leakage zone, the background sensor configured to be positioned outside the enclosed system and configured to repeatedly provide a background sensor signal indicative of particle density in the air outside the enclosed system to a processing unit operatively connected to the first sensor.

15. A room, said room comprising a pharmaceutical system according to any one of claims 1 to 9.

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