Prediction of Machine Parameters to Achieve the Arrangement of the Target Plunger Depth of the Syringe

Abstract

A system and method for performing a characteristic evaluation of a recipe of a syringe filling system may include: (a) receiving a value of a plunger depth for a syringe; (b) receiving a value of a product parameter; (c) determining a value of a vacuum parameter of the syringe filling system used when filling the syringe with a product having the value of the product parameter by applying the value of the plunger depth and the value of the product parameter as inputs to a model; and (d) displaying or storing the value of the vacuum parameter. A further aspect may include performing a characteristic evaluation of a recipe of the syringe filling system for use with a second value of the plunger depth of a second syringe. Yet a further aspect may include operating one or more vacuum devices of the syringe filling system with the value of the vacuum parameter.

Description

【Technical Field】 【0001】 This application generally relates to the characterization of recipes for systems that achieve a target plunger depth when filling a syringe, for example, with a drug. 【Background Art】 【0002】 Syringe filling systems can be used for the production of pre-filled syringes (PFS) via unit production, batch production, mass production, or continuous production. Syringe filling systems can be used in commercial production (e.g., production of parts or supplies for a product), scientific supply production (e.g., production of resources or equipment for scientific research), or other types of production. Syringe filling systems can span academic and industrial fields, including, for example, life sciences / engineering, pure / applied chemical sciences / engineering, medical sciences / engineering, mechanical sciences / engineering, food sciences / engineering, beverage sciences / engineering, and manufacturing and assembly corresponding to the above fields and industries. In particular, syringe filling systems are often used in pharmaceutical development, pharmaceutical testing and clinical trials, and pharmaceutical manufacturing. Most commonly, liquid drugs are used for filling PFS, and syringe filling systems can accommodate a wide range of sizes and many different product characteristics, such as liquid viscosity. Syringe filling systems can be manual (e.g., operated by a hand lever used to extrude the product from the tip), semi-automatic (e.g., operated by a pump controlled by an operator), or automatic (e.g., operated by a pump controlled by a computing device). 【0003】 Strict quality control measures are required for the manufacture of PFS. In the case of the drug in the syringe, one such quality control measure involves inspecting each syringe to ensure that the plunger (e.g., rubber piston or stopper) is at the appropriate depth within the syringe barrel. The plunger depth is typically measured as the distance between the upper end of the syringe flange and the upper end of the plunger while the syringe is upright with the needle pointing downward. The plunger depth is a process-controlled attribute in pharmaceutical manufacturing for producing PFS. The plunger depth may have specific specification limits imposed by the manufacturer for each product or by regulatory agencies such as government agencies (e.g., the Food and Drug Administration) that the PFS must comply with. The plunger depth is typically inspected during the filling process and, in the case of combination / auto-injector devices, a second inspection is performed before assembly. The plunger depth is important in ensuring the proper functioning of the PFS. For example, if the plunger depth is set too high, there is a risk that the PFS will not dispense the full amount of the product or will inject the product prematurely. If the plunger depth is set too low, it leads to the risk that the product will penetrate the ribs of the plunger, resulting in dry residues and compromising sterility. Further, if the plunger depth is too far from the optimal height, the likelihood of the PFS glass breaking increases, for example, while injecting a large amount of air into the patient. 【0004】 The plunger depth during syringe filling is affected by the pressure difference between (1) the interior of the syringe between the bottom of the plunger and the uppermost part of the product, and (2) the space outside the syringe (e.g., approximately atmospheric pressure). Filling systems that may include Bausch + Stroebel VarioSys® , Optima® aseptic fillers, Nest Syringe Vial Line (NSVL) fillers, or VarioSys® syringe filling systems, etc., use a vacuum device to create a pressure difference to position the plunger at the desired location. Conventionally, prior to manufacturing each batch of filled units, calibration of the plunger depth is performed to achieve the desired plunger depth. During calibration, if the syringe is filled according to the vacuum settings input by the operator, the plunger depth can be compared to the specification limit values. If the plunger depth is outside the specification limit values, the vacuum parameters can be adjusted and the syringe filling process can be repeatedly iterated using a "guess and check" method until the plunger depth is within the specification limit values. Further, due to daily variations in the syringe filling system, additional adjustments to the degree of vacuum according to the prior art may be required. 【0005】 However, with these conventional methods of selecting vacuum settings by "guess and check", the operator of the syringe system cannot gain insight into the transferability of the vacuum settings selected when making changes. Changes include changes to the syringe filling system (e.g., expanding the production of PFS in a larger facility using a different syringe filling system), changes to the dose size of the product within the PFS (e.g., adjustment of the dose size due to new drug research), changes to the type of syringe or plunger within the PFS (e.g., change to a syringe with a different inner diameter and corresponding storage volume), changes to the target plunger depth (e.g., due to changes in regulations), changes to the concentration of the product (e.g., manufacturing the PFS using a new drug that was not previously used in PFS manufacturing), etc. With these conventional methods, the syringe filling system is always subject to large-scale recalibration measures each time a change is made to the syringe filling process or the PFS product, which may increase costs in terms of time, labor, and other resources. SUMMARY OF THE INVENTION MEANS FOR SOLVING THE PROBLEM 【0006】 Aspects of the present disclosure provide a method for evaluating characteristics of a recipe of a syringe filling system. The method includes: (a) receiving a first value of a plunger depth for a first syringe; (b) receiving a first value of one or more product parameters; (c) determining, by one or more processors that apply the first value of the plunger depth and the first value of the product parameters as inputs to a model, one or more first values of one or more vacuum parameters of the syringe filling system used when filling the first syringe with a product having the first value of the product parameters, wherein the model uses one or more experimentally determined correction factors to model the relationship between the plunger depth, the product parameters, and the vacuum parameters; and (d) displaying or storing, by one or more processors, the first value of the vacuum parameters. 【0007】 In some aspects, the first value of the plunger depth is a distance value or a volume value. In some aspects, the first value of the product parameters includes one or more of a fill volume value, a fill mass value, or a fill weight value. In some aspects, the first value of the product parameters includes two or more of (i) a fill volume value, (ii) a fill mass value or a fill weight value, or (iii) a product density value. In some aspects, the first value of the vacuum parameters includes a vacuum pressure value. 【0008】 In some aspects, the model models the relationship between the plunger depth, the product parameters, the vacuum parameters, and one or more of (i) the internal size of the first syringe, (ii) the syringe-plunger contact distance of the first syringe, (iii) the height of the plunger stopper in the barrel of the first syringe, (iv) the reservoir volume of the first syringe, or (v) the plunger cone volume of the first syringe. 【0009】 In some aspects, the method further includes operating one or more vacuum devices of the syringe filling system with the first value of the vacuum parameters. 【0010】 In some embodiments, the method further includes: (a) receiving a second value of the plunger depth for a second syringe, the second syringe being a different size than the first syringe; (b) receiving a second value of one or more product parameters; (c) determining one or more second values of one or more vacuum parameters of a syringe filling system for filling the second syringe with a product having the second value of the product parameters by applying the second value of the plunger depth and the second value of the product parameters as inputs to a model; and (d) displaying or storing the one or more second values of the one or more vacuum parameters. 【0011】 In some embodiments, the method further includes determining one or more experimentally determined correction factors for the syringe filling system based on experimentally correlating the plunger depth, the vacuum pressure, and the product fill volume. 【0012】 Another aspect of the disclosure provides a computer-readable medium storing instructions that, when executed by one or more processors, cause the one or more processors to perform any one of the methods of the above-described aspects. 【0013】 Another aspect of the disclosure provides a system including: (a) one or more processors; and (b) one or more non-transitory computer-readable media storing instructions that, when executed by the one or more processors, cause the one or more processors to perform any one of the methods of the above-described aspects. 【0014】 Those skilled in the art will understand that the drawings included herein are for illustrative purposes and do not limit the disclosure. The drawings are not necessarily to scale and emphasis is placed on explaining the principles of the disclosure. In some examples, various aspects of the described embodiments may be exaggerated or enlarged to make the described implementation examples easier to understand. In these drawings, like reference numerals generally refer to functionally or structurally similar elements. BRIEF DESCRIPTION OF THE DRAWINGS 【0015】 【Figure 1】 A simplified block diagram of an exemplary system for performing characteristic evaluation of a recipe of a syringe filling system. 【Figure 2A】 An exemplary plunger insertion process is shown. 【Figure 2B】 An exemplary syringe with an exemplary plunger depth is shown. 【Figure 3】 An exemplary data example of the average plunger depth with respect to the required vacuum degree and the required vacuum filling volume is shown. 【Figure 4A】 An example of model prediction performance data is shown. 【Figure 4B】 An example of model prediction performance data is shown. 【Figure 5】 A 3D plot representing model prediction data for two different syringe filling systems. 【Figure 6】 A flowchart showing an example of a method for performing characteristic evaluation of a recipe of a syringe filling system. 【DETAILED DESCRIPTION OF THE INVENTION】 【0016】 The present disclosure aims to reduce problems of the prior art (e.g., described in the background section) by providing a technique for performing characteristic evaluation of a recipe of a syringe filling system. When used for filling a syringe with a product having specific values of product parameters, this technique can apply the values of the plunger depth and the product parameters as inputs to a model to determine the values of the vacuum parameters of the syringe filling system. By determining, displaying, and storing the values of the vacuum parameters, this technique performs characteristic evaluation of the recipe of the syringe filling system, enables the operator of the syringe filling system to gain insights, and makes it possible to transfer the recipe of the syringe filling system, thereby aiming to avoid many problems associated with the prior art. 【0017】 When an operator of a syringe filling system makes a decision regarding the setting of the vacuum level to achieve a specific plunger depth, it is advantageous for the operator to have specific insights regarding the impact of product parameters, vacuum parameters, the internal size of the syringe, the syringe-plunger contact distance of the syringe, the height of the plunger stopper within the barrel of the syringe, the storage volume of the syringe, the plunger cone volume of the syringe, etc. on the final plunger depth of the syringe. Thus, the operator can use these insights generated by the present technology, for example, to improve the performance or efficiency of the syringe filling system. 【0018】 As an advantageous feature, by providing improved insights, the present technology can significantly avoid the conventional approach of relying on guesswork for vacuum settings when attempting to achieve a specific plunger depth. Reducing guesswork through improved insights brings many advantages. One advantage is that fewer resources (e.g., drugs) are wasted during calibration of the syringe filling system, thus increasing resource efficiency and improving the sustainability of the syringe filling system. Making the syringe filling system more sustainable with respect to resource use also improves the energy efficiency of the syringe filling system and can reduce the financial or economic costs of manufacturing each syringe. Another advantage of improved insights is that production throughput may be increased because more syringes can be produced in a given time with a shorter calibration time. 【0019】 Further advantages of the present technology over conventional approaches for evaluating the characteristics of a recipe of a syringe filling system will be understood by those skilled in the art through the present disclosure. The various concepts and techniques introduced above and discussed in more detail below may be implemented in any of many ways, and the concepts described above are not limited to a particular implementation. Implementation examples are given below for illustrative purposes. 【0020】 Exemplary System FIG. 1 is a simplified block diagram of an exemplary system 100 for performing a recipe characterization of a syringe filling system 140 that achieves a target plunger depth, for example, when filling a syringe with a pharmaceutical. In some embodiments, system 100 may include a stand-alone device, while in other examples system 100 may be incorporated into other devices. At a high level, system 100 includes components of a computing device 110, one or more syringe filling systems 140, one or more plunger depth sensors 150, and one or more product parameter sources 160. One or more elements of system 100 may be communicatively coupled using, for example, wired (e.g., via wire / cable, address / data bus, or other suitable means) or wireless means. In FIG. 1, computing device 110, syringe filling system 140, and product parameter source 160 are communicatively coupled via network 170, which may be a dedicated network, a secure public internet, a virtual private network, or any other suitable type of network (e.g., dedicated access line, satellite link, cellular data network, combinations thereof, etc.), or may include these. In embodiments where network 170 constitutes the internet, data communication may occur via network 170 using internet communication protocols. In some embodiments, instances of the various elements of system 100 may include more or fewer numbers than shown in FIG. 1 (e.g., one instance of computing device 110, ten instances of syringe filling system 140, ten instances of plunger depth sensor 150, two instances of product parameter source 160, etc.) included in system 100. 【0021】 The syringe filling system 140 can include a single syringe filling system or a plurality of syringe filling systems that are co-located or remotely located and suitable for a wide variety of containers and applications and enable clinical sample and small batch commercial production on a sterile filling line. The syringe filling system 140 can generally include physical devices configured to be used for the production (e.g., manufacture) of filled syringes. In some embodiments, the syringe filling system 140 can be used to fill syringes with drugs, chemicals, biological substances, or other substances related to the development or production of pharmaceuticals. In other embodiments, the syringe filling system 140 includes equipment used in processes unrelated to the development or production of pharmaceuticals (e.g., food or beverage production systems, oil production systems, etc.). 【0022】 Examples of the syringe filling system 140 include the Bausch+Stroebel VarioSys® Optima® aseptic filler, the Nest Syringe Vial Line (NSVL) filler, or the VarioSys® syringe filling system. The syringe filling system 140 can include isolators (e.g., Vanrx® SA25, or other isolators), and mechanical modules that can be used for commercial manufacturing, clinical filling, filling of personalized pharmaceuticals, flexible contract manufacturing, product and process development, etc. The syringe filling system 140 can be a stand-alone device or incorporated into other equipment. The syringe filling system 140 can be a glove-free system and can use peristaltic or time / pressure filling. 【0023】 In some embodiments, the syringe filling system 140 can be connected to the computing device 110 via the network 170 or directly, so that at least a part of the functions of the syringe filling system 140 can be controlled by the computing device 110. In some embodiments, the syringe filling system 140 can be capable of receiving commands directly from the user (for example, the syringe filling system 140 can be manually configurable). For example, in some embodiments, the syringe filling system 140 can receive commands for controlling the operation directly from the user (for example, the vacuum device of the syringe filling system 140 can be set to operate according to the input from the user). 【0024】 The plunger depth sensor 150 may be included in (e.g., integrated with) the syringe filling system 140 or may be an external sensor connected to the syringe filling system 140. The plunger depth sensor 150 may be used to measure (e.g., directly or indirectly) the plunger depth of a syringe by collecting sensor data (such as distance values or volume values, etc.) regarding the plunger depth of the syringe produced by the syringe filling system 140. The plunger depth sensor 150 can provide the sensor data to, for example, the computing device 110 (e.g., via the network 170). The provided sensor data can be any suitable type of data, such as nominal data, ordinal data, discrete data, or continuous data, etc. The provided sensor data may be in the form of a suitable data structure and may be stored in a suitable format such as one or more of JSON, XML, CSV. The sensor data can be collected or provided automatically or in response to a request. For example, the user of the computing device 110 may wish to evaluate the characteristics of a recipe of the syringe filling system 140. In response, one or more plunger depth sensors 150 can collect the sensor data and provide it to the computing device 110. In some embodiments, one or more plunger depth sensors 150 may include a database of data / information related to vacuum parameters or may be configured to receive data / information related to vacuum parameters via user input or the like. 【0025】 The syringe filling system 140 may further include one or more vacuum devices (not shown) used when filling the syringe with a drug. The vacuum device may be, for example, a wet vacuum pump or a dry vacuum pump, and may also be a reservoir vacuum pump or a gas transfer vacuum pump (e.g., a kinetic vacuum pump or a positive displacement vacuum pump). The vacuum device can operate according to one or more vacuum parameters including pressure (measured in, for example, Pascals, standard atmospheres, Torr, pounds per square inch, technical atmospheres, barads, millimeters of mercury, feet of head / column millimeters, or any other suitable pressure measurement unit), flow rate (measured in, for example, cubic feet per minute, liters per minute, gallons per minute, or any other suitable flow rate unit), power (measured in, for example, watts, horsepower, or other suitable power units), electrical measurements (measured in voltage, current, or other suitable electrical measurement units), revolutions per minute (applicable to rotary vacuum pumps and measured in revolutions per minute, radians per second, or other suitable revolution rate units), or one or more other parameters related to the vacuum pump. 【0026】 The syringe filling system 140 may be configured to be controllable via manual input or automatic input. In some embodiments, the syringe filling system 140 may be configured to locally receive such control inputs, such as via a user input device local to the syringe filling system 140. In some embodiments, the syringe filling system 140 is configured to remotely receive control inputs from a computing device 110 (e.g., via a network 170). The control input may include an operation command that the operation of the vacuum device of the syringe filling system 140 should follow, such as a value of a vacuum parameter. 【0027】 Referring now to the product parameter source 160, the product parameter information 160 generally includes product parameter information corresponding to one or more products that can be filled into one or more syringes using the syringe filling system 140, for example, a liquid product that can be a pharmaceutical product. The product parameter information can include one or more values of one or more product parameters, such as a volume value, a filling mass value, a filling weight value, a filling height value, or a density value. Generally, the product parameter information can include information regarding one or more characteristics of the product or information regarding the quantity of the product. The values of the one or more product parameters can be historical values (e.g., the historical filling mass volume of a given drug) or new values (e.g., values currently or recently collected or measured). In some embodiments, the system 100 can omit the product parameter source 160 and instead locally receive the product parameter information through user input in the computing device 110 or the like. 【0028】 Referring now to the computing device 110, the computing device 110 can be included in the system 100. The computing device 110 can include a single computing device or a plurality of computing devices that are co-located with each other or at remote locations. The computing device 110 is generally configured to apply the plunger depth and the values of the product parameters as inputs to a model to determine the values of the vacuum parameters of the syringe filling system used when filling a syringe with a product having a specific value of the product parameters, and to display or store the values of the vacuum parameters. 【0029】 The elements of the computing device 110 can be interconnected via an address / data bus or other means. The elements included in the computing device 110 can include a processing unit 120, a network interface 122, a display 124, a user input device 126, and a memory 128, which will be described in more detail below. 【0030】 The processing unit 120 includes one or more processors, and each processor can be a programmable microprocessor that executes software instructions stored in the memory 128 to perform some or all of the functions of the computing device 110 described herein. Alternatively, one or more processors within the processing unit 120 can be other types of processors (e.g., application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), etc.). 【0031】 The network interface 122 can include any suitable hardware (e.g., front-end transceiver hardware), firmware, or software configured to use one or more communication protocols to communicate with external devices or systems (e.g., the plunger depth sensor 150, the syringe filling system 140, the product parameter source 160, etc.). For example, the network interface 122 can be, or can include, an Ethernet interface. Using the network interface 122, the computing device 110 can communicate with any device(s) via a single communication network or via one or more types of multiple communication networks (e.g., one or more wired or wireless local area networks (LANs), or one or more wired or wireless wide area networks (WANs) such as the Internet or an intranet). 【0032】 The display 124 can present information to the user using any suitable display technology (e.g., LED, OLED, LCD, etc.), and the user input device 126 can be a keyboard or other suitable input device. In some embodiments, the display 124 and the user input device 126 are integrated within a single device (e.g., a touch screen display). Generally, the display 124 and the user input device 126 can be combined so that the computing device 110 can interact with the user through a graphical user interface (GUI) or other (e.g., text) user interface provided for purposes such as (for example) displaying data / information, recommending changes to one or more vacuum parameters, notifying the user of equipment failures or other malfunctions, etc. 【0033】 Memory 128 includes one or more physical memory devices or units including volatile or non-volatile memory, and may or may not include memory located in different computing devices of computing device 110. Any suitable one or more types of memory, such as read-only memory (ROM), solid-state drive (SSD), hard disk drive (HDD), etc. can be used. Memory 128 stores instructions of one or more software applications executable by processing unit 120, including recipe characteristic evaluation (RC) application 130. In exemplary system 100, RC application 130 includes data collection unit 132, modeling unit 134, user interface unit 136, and vacuum operation unit 138. Units 132 - 138 may be separate software elements or modules of RC application 130, or may simply represent the functions of RC application 130 that are not necessarily divided into different elements / modules. For example, in some embodiments, data collection unit 132 and user interface unit 136 are included in a single software module. Further, in some embodiments, units 132 - 138 are distributed among multiple copies of RC application 130 (e.g., executed by different elements within computing device 110), or among different types of applications stored and executed on one or more devices of computing device 110. 【0034】 The data collection unit 132 is generally configured to receive data. In some embodiments, the data collection unit 132 receives one or more values of one or more product parameters (e.g., volume value, filling mass value, filling weight value, or density value) of a product filled into one or more syringes. The data collection unit 132 can receive the value of the product parameter via, for example, a product parameter source 160, user input received via a user interface unit 136 by a user input device 126, or other suitable means. In some embodiments, the data collection unit 132 can receive one or more values of the plunger depth of the syringe (e.g., distance value or volume value). The data collection unit 132 can receive the value of the plunger depth via, for example, a plunger depth sensor 150, user input received via a user interface unit 136 with a user input device 126, or other suitable means. 【0035】 The modeling unit 134 is generally configured to generate or apply a model using one or more experimentally determined correction factors to model the relationship between the plunger depth, product parameters, and vacuum parameters. The modeling unit 134 can receive the plunger depth and product parameters via, for example, the data collection unit 132 or the user interface unit 136. The modeling unit 134 can determine one or more values of the vacuum parameters of the syringe filling system 140 used when filling a syringe with a product having product parameters by applying the value of the plunger depth and the value of the product parameter as inputs to the model. 【0036】 The user interface unit 136 is generally configured to receive user input. For example, the user interface unit 136 can receive user input for one or more values of product parameters or one or more values of the plunger depth. The user interface unit 136 can cooperate with the user input device 126. 【0037】 The vacuum operation unit 138 is generally configured to operate the vacuum device of the syringe filling system 140 using vacuum parameters. The vacuum parameters may be user selections received via the user interface unit 136, or the vacuum parameters may be determined by the modeling unit 134 using a model. In other embodiments, the vacuum operation unit 138 is omitted (e.g., the vacuum device of the syringe filling system 140 is alternatively configured manually using vacuum parameters). 【0038】 The operation of each unit 132 - 138 will be described more specifically below with reference to the operation of the system 100. 【0039】 Exemplary plunger insertion process FIG. 2A shows an exemplary plunger insertion process 200A of inserting a plunger 220 into a syringe 210. As shown, process 200A includes evacuating the syringe barrel at step 202A, aligning the plunger at step 204A, equalizing the plunger position at step 206A, and reaching the equalized plunger position at step 208A. Process 200A can be performed using equipment / devices that are the same as or similar to those described above in relation to system 100. For example, at least a part of process 200A can be performed using one or more filling systems 140. 【0040】 Step 202A of process 200A can include starting a vacuum device (e.g., the vacuum device described in relation to the syringe filling system 140) to create a vacuum within the syringe 210 filled with a product 230 (e.g., a pharmaceutical). The vacuum device can operate according to one or more vacuum parameters including one or more of pressure, flow rate, power, electrical measurements, rotational speed, or other parameters. The vacuum parameters can be provided to the vacuum device via user input by an operator or the like. 【0041】 Step 204A of process 200A may include aligning plunger 220 by covering the upper opening of syringe 210. The alignment of plunger 220 may be mechanically performed by a machine (e.g., an isolator of syringe filling system 140). By aligning plunger 220 with syringe 210, an airtight seal can be formed between the inside and the outside of syringe 210. 【0042】 Step 206A of process 200A may include the movement of plunger 220 into syringe 210 due to the pressure difference between the inside and the outside of syringe 210 (e.g., the latter being atmospheric pressure P atm ). More specifically, the pressure inside syringe 210 is lower than the pressure outside syringe 220. During the execution of step 206A, it may not be necessary to apply an external force to plunger 220 because the pressure difference may be sufficient to "suck" plunger 220 deeper into syringe 210. 【0043】 In step 208A of process 200A, the pressure inside syringe 210 (i.e., above product 230 and below plunger 220 as shown in the figure) is equal to the pressure outside syringe 210 (e.g., P atm ). After stabilizing for a predetermined time (e.g., 20 minutes in step 206A), plunger 220 is considered to be "stable", and the pressure inside syringe 210 and the pressure outside syringe 210 are equal or substantially equal (e.g., the remaining pressure difference is insufficient to overcome the friction between plunger 220 and the wall of the barrel of syringe 210). At that point, the plunger depth of plunger 220 can be measured. The plunger depth may be measured using a measuring tool such as a sensor (e.g., plunger depth sensor 150) or manually. 【0044】 Exemplary syringe filled via a syringe filling system Figure 2B shows in more detail the syringe 210, plunger 220, and product 230 of step 200A of FIG. 2A according to one embodiment. FIG. 2B shows the plunger cone 222 and one or more lugs 224 of the plunger 220, along with the flange 212 and barrel 214 of the syringe 210. FIG. 2B further shows a needle shield 240 that protects and covers the needle of the syringe 210. The syringe 210 may be filled using the syringe filling system 140 or, for example, using step 200A. 【0045】 FIG. 2B shows one way in which the plunger depth can be defined. However, it should be understood that any suitable definition or technique (e.g., by the data collection unit 132 using the plunger depth sensor 150) can be used to define or measure the plunger depth. In FIG. 2B, the syringe 210 includes a plunger 220 disposed within a barrel 214. The proximal end of the barrel 214 (and of the syringe 210 as a whole) forms a flange 212, while the needle (shielded in FIG. 2B by the needle shield 240) is disposed at the distal end of the syringe 210. Typically, the barrel 214 and flange 212 are formed of glass and the plunger 220 is formed of rubber. However, other materials (e.g., suitable types of plastic) can be used for any of the elements. 【0046】 In the exemplary embodiments illustrated, the plunger depth of syringe 210 is defined as the distance between (1) the upper or proximal surface of flange 212 and (2) the upper or proximal surface of plunger 220. However, defining the plunger depth can be complicated by several factors. For example, the upper surface of flange 212 may be non-uniform (e.g., having undulations with distinct valleys or chamfered edges), in which case the average or peak value (minimum distance / depth) of the flange upper surface 212 may be used. As another example, as shown in FIG. 2B, plunger 220 may have small protruding "lags" or "indentations" 224, which may be ignored (e.g., discarding measurements / samples corresponding to lags 224 before averaging). The plunger depth may also be affected by other factors, such as the orientation of syringe 210 within a holder (e.g., star wheel, tab, round tray, etc.). For example, when syringe 210 is within a tray or tab, it is likely suspended from flange 212, which may not be perfectly orthogonal to the cylindrical body of syringe 210. As a result, it may be slightly tilted with angular displacement, i.e., be oblique. Plunger 220 may also be slightly tilted within barrel 214. In these examples, the plunger depth can be measured taking into account the angular displacement (e.g., by specifying the angle of the angular displacement). 【0047】 Figure 2B also shows one way to define the headspace. However, it should be understood that any suitable definition or technique can be used to define the headspace (e.g., by the data collection unit 132 using the plunger depth sensor 150). In the illustrated exemplary embodiment, the headspace of the syringe 210 is defined as the distance between (1) the bottom or distal surface of the plunger 220 and (2) the top or proximal surface of the product 230. However, defining the headspace can be complicated by several factors. For example, the bottom surface of the plunger 220 may be non-uniform. For example, as illustrated, the lower end of the plunger 220 may include a plunger cone 222. As another example, as illustrated, the top surface of the product 230 may be non-uniform, e.g., due to a meniscus. Similar to the plunger depth, the average or peak value (minimum distance / depth) of the bottom surface of the plunger 220 and the top surface of the product 230 may be used to define the headspace. 【0048】 Exemplary average data of plunger depth Figure 3 shows exemplary data 300 including the average values of the plunger depth for required vacuum degree (in PSI) versus required vacuum filling volume (in mL). As illustrated, the data 300 evaluates the characteristics of the plunger depth for five different filling volumes: 0.25 mL, 0.45 mL, 0.65 mL, 0.85 mL, and 1.05 mL, and five different vacuum pressures: 0.5 PSI, 1.0 PSI, 1.5 PSI, 2.0 PSI, 2.5 PSI, 3.0 PSI, and 3.5 PSI. These filling volumes are included in the exemplary data 300, but it should be understood that the techniques described herein can be applied to many different filling volumes (e.g., 1.00 mL syringe, 2.25 mL syringe, 3.00 mL syringe, etc.). The data 300 can be determined experimentally by measuring the plunger depth for five different filling volumes and five different vacuum pressures using, for example, the plunger depth sensor 150 and averaging the measured plunger depths. The data 300 shows that the plunger depth increases with an increase in vacuum pressure and a decrease in filling volume. 【0049】 Data 300 can be used to experimentally determine correction factors in a model that models the relationship of plunger depth, product parameters (e.g., fill volume), and vacuum parameters (e.g., vacuum pressure) using one or more experimentally determined correction factors. Based on the data 300, a model using one or more experimentally determined correction factors can be based on the following equation: 【Number】 where m fw is the mass of the fill weight of the product, P ATM is the absolute atmospheric pressure, d i is the inner diameter of the syringe, h s is the height of the syringe as shown in, for example, FIG. 2B (i.e., the length of the barrel of the syringe excluding the bevel and the plunger cone, which is the length of the conical tube portion in which the plunger slides within the syringe, and the length of the barrel is a good approximation), h pd is the plunger depth as shown in, for example, FIG. 2B (i.e., the length from the upper flat surface of the plunger to the start of the plunger cone excluding the tip cone portion), h p is the height of the plunger as shown in, for example, FIG. 2B (i.e., the length of the surface of the plunger that forms an airtight seal and contacts the inner barrel of the syringe excluding the plunger cone), V huv is the storage volume of the syringe, V PST is the volume of the plunger cone, ρ is the density of the product, A is the correction factor for the ideal gas law, and B is the correction factor for shape and static friction. The correction factors A and B are specific to each syringe and each syringe filling system. Based on the data 300, the data of plunger depth vs. vacuum pressure vs. fill amount can be fitted to Equation 1 by optimizing A and B to minimize the sum of the mean squared errors. It will be understood that alternative quantities can be substituted into Equation 1 while maintaining the functionality of the model. For example, instead of the quantity 【Number】 a quantity V fw representing the volume of the fill weight of the product can be used. 【0050】 Data 300 may be used to construct a model that models the relationship between plunger depth, product parameters, and vacuum parameters (e.g., using Equation 1) using one or more experimentally determined correction factors, but it is worth noting that additional or alternative other models or other training techniques may also be used. For example, using a machine learning model (e.g., by computing device 110 using RC application 130), the relationship between plunger depth, product parameters, and vacuum parameters can be modeled. The machine learning program or algorithm may employ a neural network that can be a convolutional neural network, a deep learning neural network, or a composite learning module or program that learns with two or more features or feature datasets in a particular field of interest. The machine learning program or algorithm may also include natural language processing, semantic analysis, automatic inference, regression analysis, support vector machine (SVM) analysis, K-nearest neighbor analysis, naive Bayes analysis, clustering, reinforcement learning, or other machine learning algorithms or techniques. Other machine learning models can identify and recognize patterns in the training data to facilitate prediction of new data. In some examples, due to the processing power requirements for training the machine learning model, additional computing resources (e.g., cloud computing resources) provided by a server (not shown) can be used to train the model. The training data may or may not be labeled (in the case of unsupervised training) or may be labeled, for example, by a human (in the case of supervised training). Training of the model can continue until at least the model meets the selection criteria for being verified and used as a predictive model. In some examples, the model can be verified (e.g., by computing device 110) using a second subset of the training dataset (commonly known as "test data") to determine the accuracy and robustness of the algorithm. Such verification includes applying the model to the test data to make predictions. The model can then be evaluated (e.g., by computing device 110) to determine whether the performance is satisfactory based on a comparison of the predicted values with the known labels of the test data.The sufficiency criteria for validating a model can vary depending on the size of the available training dataset, the performance of past iterations of the machine learning model, or user-specified performance requirements. 【0051】 Exemplary performance data FIG. 4A shows exemplary data 400A representing the performance when predicting vacuum parameters using a model implementing Equation 1. The model can model the relationship between plunger depth, product parameters (e.g., target fill weight of the product and density of the product), and vacuum parameters (e.g., predicted required vacuum level) using one or more experimentally determined correction factors. The model can be generated according to the techniques outlined above with respect to FIG. 3. The model can include one or more elements identical or similar to the system 100 of FIG. 1 and can be used with a syringe filling system that can be used to fill a syringe using a process identical or similar to process 200A. 【0052】 Data 400A includes measured plunger depths plotted for three different syringe sizes having different volumes (i.e., 0.2 mL, 0.4 mL, and 0.8 mL). For each syringe size, data 400A includes measured plunger depths for seven different tabs. Tab 1 and Tab 7 each correspond to the target plunger depths near the minimum and maximum volumes of the syringe, respectively, for each syringe size. Tabs 2-6 correspond to the target plunger depths near the intermediate volumes for each syringe size. Each measured plunger depth corresponds to the vacuum parameter determined by the model to achieve each target plunger depth. 【0053】 Figure 4B shows the data 400A of Figure 4A in tabular form as data 400B. The model input and the execution result are each included in the data 400B. As shown in the model input, each syringe size corresponds to a specific target fill weight (i.e., 0.244 g, 0.450 g, and 0.850 g) of a product having a specific density (i.e., 1.062 g / mL). As shown in the execution result, the data 400B further includes, for each target plunger depth of each syringe size, the measured plunger depth average value of the plunger depth determined experimentally when the vacuum of the syringe filling system (e.g., syringe filling system 140) is set to the predicted required vacuum degree corresponding to a number of tabs and containers. Finally, the data 400B includes in the execution result the standard deviation of the average of each of the measured plunger depths and the percentage difference between the average of each of the measured plunger depths and the corresponding target plunger depth. 【0054】 As shown in data 400A and data 400B, the technology of the present disclosure using a model that models the relationship between the plunger depth, product parameters, and vacuum parameters gave an accurate prediction of the vacuum setting required to achieve the target plunger depth with an error of less than 3% for all nine target plunger depths. Thus, data 400A and data 400B show the effectiveness of the present technology when developing a model that predicts the vacuum parameters in a specific scenario where there is a transition from a first syringe size and a first set of product parameters (e.g., first target fill weight) to a second syringe size and a second set of product parameters (e.g., second target fill weight). 【0055】 Exemplary Comparison FIG. 5 shows a three-dimensional plot 500 representing model prediction data for two different syringe filling systems. It is worth noting that the model according to the present technique, which can use one or more experimentally determined correction factors to model the relationship between plunger depth, product parameters, and vacuum parameters, is compatible with various different types of syringe filling systems. In fact, when applying the model to different syringe filling systems using Equation 1, the adjustment of the correction factors (e.g., A and B) may be the only adjustment required for the model. 【0056】 More specifically, FIG. 5 shows a plot 500 of the predicted vacuum parameters for each of an NSVL syringe filling system and a VarioSys® syringe filling system (either or both of which may be used as syringe filling system 140 and can fill a syringe according to process 200A). The vacuum parameters for each of the NSVL syringe filling system and the VarioSys® syringe filling system can be determined (e.g., by computing device 110 using RC application 130) using experimentally determined correction factors specific to each syringe filling system that can be applied to Equation 1 (e.g., by computing device 110 using RC application 130). 【0057】 A visual representation is shown in plot 500 to show to what extent the required vacuum settings for each syringe filling system are affected by differences in the correction factors. Each cell of plot 500 corresponds to a particular combination of input fill volume and input plunger depth. A particular cell of plot 500 contains a numerical value representing the difference between the predicted vacuum pressure of the NSVL syringe filling system and the predicted vacuum pressure of the VarioSys® syringe filling system for the corresponding fill volume and plunger depth. In fact, the numerical value of each cell of plot 500 can be described according to Equation 2, ΔP = P NSVL - P VS (Equation 2) where ΔP is the difference in predicted vacuum pressure (i.e., the numerical value of each cell), P NSVL is NSVL the predicted vacuum pressure of the syringe filling system, PVS is the predicted vacuum pressure of the VarioSys® syringe filling system. 【0058】 When using Plot 500, it may be transferred between syringe filling systems with different vacuum parameters in the filling recipe. Based on the data shown in Plot 500, the target plunger depth can be achieved in the first trial, thus reducing the execution of long characterization evaluations and line time. As a result, the techniques described herein not only reduce guesswork but also eliminate the need for testing on the clinical line, enable the use of pilot-scale fillers, and offset the time required for calibration. Therefore, Plot 500 demonstrates the effectiveness of this technology in developing a model that predicts the vacuum parameters that can be transferred between a first syringe filling system using a first set of correction factors and a second syringe filling system using a second set of correction factors. 【0059】 Exemplary Flow Chart FIG. 6 is a flow chart showing an exemplary method for performing a characterization evaluation of a recipe for a syringe filling system. The exemplary method 600 may include the following elements: (1) receiving a first value of the plunger depth of the syringe (block 602), (2) receiving one or more first values of one or more product parameters (block 604), (3) determining one or more first values of one or more vacuum parameters via a model (block 606), and (4) displaying or storing one or more first values of the vacuum parameters (block 608). 【0060】 Block 602 may include receiving, as an input from an operator, a first value of the plunger depth via the user input device 126 and the user interface unit 136. The first value of the plunger depth may correspond to a target plunger depth, a desired plunger depth, or other plunger depth. The first value of the plunger depth may include a distance value or a volume value that describes or represents the position of the plunger within the syringe. In some embodiments, a plunger depth sensor (e.g., plunger depth sensor 150) measures a particular plunger depth, which may then be received as the first value of the plunger depth at block 602. 【0061】 Block 604 may include receiving one or more first values of one or more product parameters via one or more of one or more product parameter sources, such as product parameter source 160, data collection unit 132, user input device 126, or the user interface unit, etc. The first value of the product parameter may include one or more of a volume value, a fill mass value, a fill weight value, a fill height value, or a density. In some embodiments, the first value of the product parameter includes two or more of (i) a fill volume value, (ii) a fill mass value or a fill weight value, or (iii) a product density value. In some embodiments, other data / information specific to the product itself, such as the product name or chemical / physical properties / information of the product, etc., may be included in the first value of the product parameter. 【0062】 Block 606 may include determining, via a computing device such as computing device 110, one or more first values of one or more vacuum parameters of a syringe filling system for filling a first syringe with a product having a first value of product parameters, using the first value of plunger depth and the first value of product parameters as inputs to a model, where the model models the relationship between plunger depth, product parameters, and vacuum parameters using one or more experimentally determined correction factors. The model used may be the same as or similar to (or may be expressible in the same or similar manner as) the model discussed with respect to FIGS. 3 or 4 and may be derived based on Equation 1. The one or more first values of the one or more vacuum parameters may be used with a vacuum device that is the same as or similar to the vacuum device described with respect to syringe filling system 140 that may be used to fill a syringe with product in the same or similar manner as in step 200A. The one or more first values of the vacuum parameters may include one or more of pressure (e.g., measured in Pascals, standard atmospheres, Torr, pounds per square inch, technical atmospheres, barads, millimeters of mercury, feet of head / column millimeters, or any other suitable pressure measurement unit), flow rate (e.g., measured in cubic feet per minute, liters per minute, gallons per minute, or any other suitable flow rate unit), power (e.g., measured in Watts, horsepower, or other suitable power unit), electrical measurement (voltage, current, or other suitable electrical measurement unit), revolutions per minute (applied to rotary vacuum devices and measured in revolutions per minute, radians per second, or other suitable revolutions per minute unit), or any other parameter related to the vacuum device. 【0063】 Block 608 can display or store a first value of a vacuum parameter via a computing device such as computing device 110. In some embodiments, the first value of the vacuum parameter itself can be displayed, while in other embodiments, an expression of the first value of the vacuum parameter can be displayed. The display of the first value of the vacuum parameter can specifically use, for example, the display 124 or the user interface unit 136 of computing device 110. In some embodiments, the first value of the vacuum parameter itself can be stored, while in other embodiments, an expression of the first value of the vacuum parameter can be stored. Storing the first value of the vacuum parameter can specifically use, for example, the memory 128 of computing device 110. 【0064】 In some embodiments, method 600 can be executed completely automatically, for example, by one or more processors (such as a CPU or GPU) that execute instructions stored in one or more non-transitory computer-readable storage media (such as volatile memory or non-volatile memory, read-only memory, random access memory, flash memory, electronically erasable programmable read-only memory, or one or more other types of memory). Method 600 can use any of the elements, processes, or techniques shown in one or more of FIGS. 1-5. 【0065】 Additional Considerations Some of the drawings referred to herein show exemplary block diagrams having one or more functional elements. It will be understood that such block diagrams are for illustrative purposes and that the devices described and illustrated may have more, fewer, or alternative elements than those shown. Also, in various embodiments, elements (and the functions provided by each element) can be associated with any suitable element or separately integrated as part of it. 【0066】 Some aspects of the present disclosure relate to non-transitory computer-readable storage media storing instructions / computer-readable storage media for performing various computer-implemented operations. As used herein, the term "instructions / computer-readable storage media" is used to include any medium that can store or encode a series of instructions or computer code for performing the operations, methods, and techniques described herein. The media and computer code may be specially designed and constructed for the purposes of the aspects of the present disclosure, or may be of the kind well-known and available to those of ordinary skill in the computer software arts. Examples of computer-readable storage media include magnetic media such as hard disks, floppy disks, and magnetic tape; optical media such as CD-ROMs and holographic devices; magneto-optical media such as optical disks; and hardware devices specially configured to store and execute program code, such as ASICs, programmable logic devices ("PLDs"), and ROM and RAM devices, among others, but are not limited thereto. 【0067】 Examples of computer code include files containing machine code such as generated by a compiler, and high-level code that is executed by a computer using an interpreter or compiler. For example, one aspect of the present disclosure may be implemented using Java, C++, or other object-oriented programming languages and development tools. Additional examples of computer code include encryption code and compression code. Further, aspects of the present disclosure may be downloaded as a computer program product and transferred from a remote computer (e.g., a server computer) to a requesting computer (e.g., a computer or a different server computer) via a transmission channel. Another aspect of the present disclosure may be implemented in a hard-wired circuit instead of, or in combination with, machine-executable software instructions. 【0068】 As used herein, the singular terms "a", "an", and "the" may include references to plural items unless the context clearly dictates otherwise. This specification and the following claims are to be read as including one or at least one, and the singular also includes the plural unless explicitly stating a negative meaning or it is not obvious. As used herein, the terms "comprising", "comprises", "including", "includes", "having", "has" or any other variation thereof are intended to cover non-exclusive inclusion. For example, a process, method, article, or apparatus that includes a list of elements is not necessarily limited to those elements and may include other elements not explicitly listed or inherent to such process, method, article, or apparatus. Further, unless explicitly negated, "or" refers to an inclusive "or" and not an exclusive "or". For example, condition A or B is satisfied by any of the following. That is, A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist). 【0069】 As used herein, the terms "substantially", "essentially", "substantial", "generally", and "about" are used to describe and account for minor variations. When used in conjunction with an event or situation, these terms may refer not only to instances where the event or situation occurs exactly, but also to instances where the event or situation occurs approximately. For example, when used in conjunction with a numerical value, the term may refer to a variation range of ±10% or less of the numerical value, such as ±5% or less, ±4% or less, ±3% or less, ±2% or less, ±1% or less, ±0.5% or less, ±0.1% or less, or ±0.05% or less. For example, two numerical values may be considered "substantially" the same if the difference between the numerical values is ±10% or less of the average value, such as ±5% or less, ±4% or less, ±3% or less, ±2% or less, ±1% or less, ±0.5% or less, ±0.1% or less, or ±0.05% or less, etc. 【0070】 Also, in this specification, amounts, ratios, and other numerical values are sometimes presented in a range format. Such a range format is used for convenience and brevity, and should be understood flexibly to include not only the numerical values explicitly specified as the limits of the range, but also all individual numerical values or sub-ranges subsumed within the range as if each numerical value and sub-range were explicitly specified. 【0071】 The techniques disclosed in this specification have mainly described specific operations performed in a specific order, but it should be understood that these operations may be combined, further divided, or rearranged to form equivalent techniques without departing from the teachings of this disclosure. Therefore, unless otherwise specifically suggested in this specification, the order and grouping of operations do not limit this disclosure.

Claims

[Claim 1] A method for characterizing the recipe of a syringe filling system, One or more processors receive a first value of the plunger depth for the first syringe, The one or more processors receive a first value for one or more product parameters, The one or more processors that apply the first value of the plunger depth and the first value of the product parameter as input to a model determine one or more first values ​​of one or more vacuum parameters of the syringe filling system used when filling the first syringe with a product having the first value of the product parameter, wherein the model uses one or more experimentally determined correction coefficients to model the relationship between the plunger depth, the product parameter and the vacuum parameter. The one or more processors display or store the first value of the vacuum parameter. A method that includes this. [Claim 2] The method according to claim 1, wherein the first value of the plunger depth is a distance value or a volume value. [Claim 3] The method according to claim 1, wherein the first value of the product parameter includes one or more of the following: a filling volume value, a filling mass value, or a filling weight value. [Claim 4] The method according to claim 3, wherein the first value of the product parameter includes two or more of the following: (i) the filling volume value, (ii) the filling mass value or the filling weight value, or (iii) the product density value. [Claim 5] The method according to claim 1, wherein the model models the relationship between the plunger depth, the product parameter, the vacuum parameter, and one or more of the following: (i) the internal size of the first syringe, (ii) the syringe-plunger contact distance of the first syringe, (iii) the height of the plunger stopper in the barrel of the first syringe, (iv) the storage volume of the first syringe, or (v) the plunger cone volume of the first syringe. [Claim 6] The method according to claim 1, wherein the first value of the vacuum parameter includes a vacuum pressure value. [Claim 7] The one or more processors cause one or more vacuum devices in the syringe filling system to operate at the first value of the vacuum parameter. The method according to claim 1, further comprising: [Claim 8] Receiving a second value of the plunger depth for a second syringe, wherein the second syringe is of a different size than the first syringe, by one or more processors, The one or more processors receive a second value of the one or more product parameters, The one or more processors that apply the second value of the plunger depth and the second value of the product parameter as inputs to the model determine one or more second values ​​of the one or more vacuum parameters of the syringe filling system used when filling the second syringe with a product having the second value of the product parameter, The one or more processors display or store the second value of the one or more vacuum parameters. The method according to claim 1, further comprising: [Claim 9] The method according to claim 1, comprising determining one or more experimentally determined correction coefficients for the syringe filling system based on experimentally relating the plunger depth, the vacuum pressure, and the product filling amount using one or more processors. [Claim 10] One or more non-temporary computer-readable media that store instructions causing one or more processors to perform the method according to any one of claims 1 to 8 when executed by one or more processors. [Claim 11] One or more processors, One or more non-temporary computer-readable media that store instructions causing one or more processors to perform the method described in any one of claims 1 to 8 when executed by the one or more processors, A system equipped with these features.

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