An on-line detection system for cleanliness of medical material production

Abstract

The present application relates to the technical field of online detection, and more particularly to an online detection system for cleanliness of medical material production, comprising a surface feature acquisition module, a cleanliness determination module, a thermodynamic feature acquisition module, a process stability determination module and a process correction module, the surface feature parameters of the target material are acquired to analyze the surface feature representation value; the cleanliness determination module determines whether the cleanliness of the target material after cleaning, siliconization and sterilization meets the standard; when the cleanliness of the target material does not meet the standard, the thermodynamic feature acquisition module acquires the thermodynamic feature parameters of the target material to analyze the thermodynamic feature representation value; the process stability determination module determines whether the temperature sensor of the pulsating vacuum sterilization cabinet meets the standard; and the process correction module is used to determine the adjustment range of the silicon oil atomization pressure and the sterilization temperature. The present application improves the precision of online detection of the cleanliness of medical material.

Description

Technical Field

[0001] This invention relates to the field of online detection technology, and in particular to an online detection system for the cleanliness of medical material production. Background Technology

[0002] The surface cleanliness of medical materials, such as medical elastomers, directly affects their safety and compliance during cleaning, siliconization, and sterilization processes. Current methods for detecting the cleanliness of medical materials often only test for single parameters such as surface foreign matter and particles, failing to comprehensively consider multiple key surface characteristics such as puncture debris, insoluble particles, and changes in yellowness index. This makes it difficult to comprehensively and accurately reflect the cleanliness compliance status of medical materials. When cleanliness fails to meet standards, existing technologies typically cannot combine thermodynamic parameters from the sterilization process for root cause analysis, failing to effectively distinguish whether the failure is due to uneven siliconization or process instability factors such as F0 value deviation or abnormal temperature uniformity during sterilization. This results in a lack of targeted and often arbitrary process adjustments. Furthermore, the absence of a comprehensive calculation, grading, and closed-loop correction mechanism based on historical data leads to insufficient accuracy in online cleanliness detection and delayed process correction responses, making it difficult to meet the needs for efficient, accurate, and traceable online cleanliness control in the medical material production process.

[0003] Chinese Patent Publication No. CN116934763A discloses a method for detecting defects in medical rubber stoppers based on visual features. The method includes: obtaining the grayscale range of the defect region from the stopper's grayscale histogram; obtaining the connected component of the defect; acquiring several iterative windows of different sizes; obtaining the objective function of the iterative windows; obtaining the size of the optimal Gaussian filter kernel based on the objective function of the iterative windows; obtaining the brightness contrast parameters of the connected component of the defect; obtaining the standard deviation of the optimal Gaussian filter kernel based on the brightness contrast parameters of the connected component of the defect; obtaining the optimal Gaussian filter kernel for the connected component of the defect; obtaining the burr defect rate of the stopper edge image based on the stopper edge image and the template edge image; and completing defect detection based on the burr defect rate of the stopper edge image. This invention improves the accuracy of stopper defect detection by filtering noise in medical rubber stopper images while ensuring minimal image distortion.

[0004] Chinese Patent Publication No. CN110694996A discloses a cleaning process for high-purity butyl rubber stoppers. Accurately weigh the butyl rubber stoppers. Use an electrostatic hair removal machine to remove hair, fibers, and other fine solid impurities adhering to the surface of the butyl rubber stoppers due to electrostatic action. Place the stoppers into the loading tank of a fully automatic butyl rubber stopper cleaning machine using an automatic feeding device. Add water to the mixing water level, add cleaning agent, and spray high-purity nitrogen gas from the bottom of the cleaning machine for mixing and washing, controlling the water temperature. After mixing and washing, turn off the jetting device, open the water inlet valve, and allow it to overflow. Turn on the jetting device to spray high-purity nitrogen gas for rinsing. Turn off the water inlet valve and jetting device, drain the water to the siliconization water level, then turn on the jetting device to spray high-purity oxygen-enriched air, add an appropriate amount of silicone oil for siliconization. Siliconization is then performed. The siliconized stoppers are conveyed to a microwave oven via a conveyor belt, where high-purity nitrogen gas is introduced for drying. The drying process of this invention results in stoppers with low insoluble particulate matter content and high cleanliness. Summary of the Invention

[0005] To address this issue, the present invention provides an online detection system for the cleanliness of medical material production, which overcomes the problem of low accuracy in online cleanliness detection of medical elastomer stoppers in the existing technology, where the temperature sensor's aging response deviation makes it impossible to distinguish between foreign matter residue on the stopper surface and abnormal material aging.

[0006] To achieve the aforementioned objective, the present invention provides an online detection system for the cleanliness of medical material production, comprising:

[0007] The surface feature acquisition module is used to acquire surface feature parameters of the target material that has undergone cleaning, siliconization and sterilization treatment within a historical period.

[0008] The cleanliness determination module, which is connected to the surface feature acquisition module, is used to analyze the surface feature characterization value based on the surface feature parameters; and to determine whether the cleanliness of the target material that has completed cleaning, siliconization and sterilization treatment meets the standard based on the comparison result of the surface feature characterization value and the predetermined surface feature characterization threshold.

[0009] The thermodynamic characteristic acquisition module, which is connected to the cleanliness determination module, is used to collect thermodynamic characteristic parameters of the target material during the sterilization cycle when the cleanliness of the target material that has completed cleaning, siliconization and sterilization does not meet the standard.

[0010] The process stability determination module is connected to the thermodynamic feature acquisition module to analyze the thermodynamic feature characterization value based on the thermodynamic feature parameters; and to determine whether the temperature sensor of the pulsating vacuum sterilizer meets the standard based on the difference between the thermodynamic feature characterization value and the predetermined thermodynamic feature characterization threshold.

[0011] The process correction module, which is connected to the process stability determination module, is used to determine the uneven siliconization and the adjustment range of the silicone oil atomization pressure if the temperature sensor of the pulsed vacuum sterilizer meets the standard.

[0012] If the temperature sensor of the pulsating vacuum sterilizer does not meet the standard, it is determined that the sterilization temperature is insufficient. Based on the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold, the adjustment range of the sterilization temperature is determined.

[0013] The surface characteristic parameters include the amount of debris shed during puncture, the amount of insoluble microparticles on the surface, and the change in yellowness index.

[0014] The thermodynamic characteristic parameters include the cumulative deviation of the F0 value and the extreme poor temperature uniformity;

[0015] The F0 value is the equivalent sterilization time at a standard temperature of 121.1℃, calculated by converting the actual sterilization temperature.

[0016] Furthermore, the cleanliness determination module analyzes the surface feature characterization values ​​based on the sum of the first feature-defined characterization parameter, the second feature-defined characterization parameter, and the third feature-defined characterization parameter, wherein,

[0017] The first feature defines the characterization parameter as the ratio of the amount of debris removed during puncture to a predetermined threshold for the amount of debris removed during puncture.

[0018] The second feature defines the characterization parameter as the ratio of the amount of surface insoluble particles to a predetermined threshold for the amount of surface insoluble particles;

[0019] The third feature defines the characterization parameter as the ratio of the change value of the yellowness index to a predetermined threshold value for the change of the yellowness index.

[0020] Furthermore, the cleanliness determination module is used to determine whether the cleanliness of the target material that has undergone cleaning, siliconization and sterilization meets the standard, provided that the surface feature characterization value is less than a predetermined surface feature characterization threshold.

[0021] Furthermore, the cleanliness determination module is used to determine the condition that the cleanliness of the target material that has undergone cleaning, siliconization and sterilization does not meet the standard is that the surface feature characterization value is greater than or equal to a predetermined surface feature characterization threshold.

[0022] Furthermore, the process stability determination module is used to analyze the thermodynamic characteristic values ​​determined based on the sum of the first process-limited characterization parameter and the second process-limited characterization parameter, wherein,

[0023] The first process-defined characterization parameter is the ratio of a predetermined cumulative deviation threshold for the F0 value to the cumulative deviation value of the F0 value;

[0024] The second process-defined characterization parameter is the ratio of a predetermined temperature uniformity range threshold to the temperature uniformity range value.

[0025] Furthermore, the process stability determination module determines that the temperature sensor of the pulsating vacuum sterilizer meets the standard when the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold is greater than the predetermined difference threshold.

[0026] Furthermore, the process stability determination module determines that the condition under which the temperature sensor of the pulsating vacuum sterilizer does not meet the standard is that the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold is less than or equal to the predetermined difference threshold.

[0027] Furthermore, the process correction module determines the condition for adjusting the silicone oil atomization pressure as follows: the temperature sensor of the pulsed vacuum sterilizer meets the standard.

[0028] Furthermore, the process correction module determines that the condition for adjusting the sterilization temperature range is that the temperature sensor of the pulsed vacuum sterilizer does not meet the standard.

[0029] Furthermore, the process correction module is used to determine the sterilization temperature adjustment range based on the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold.

[0030] Compared with existing technologies, the beneficial effects of this invention are that it provides an online detection system for the cleanliness of medical material production, including: a surface feature acquisition module, a cleanliness determination module, a thermodynamic feature acquisition module, a process stability determination module, and a process correction module. The surface feature acquisition module collects data on the amount of puncture debris, the amount of insoluble particles on the surface, and the change in yellowness index of the target material after cleaning, siliconization, and sterilization treatments over a historical period, comprehensively capturing the surface cleanliness and material stability of medical rubber stoppers after multiple processes. The cleanliness determination module analyzes surface feature characterization values ​​based on surface feature parameters. The comparison between surface feature characterization values ​​and predetermined surface feature characterization thresholds determines whether the cleanliness of the target material that has undergone cleaning, siliconization, and sterilization meets the standards, achieving an objective quantitative judgment of the cleanliness of medical rubber stoppers. When the cleanliness of the target material that has undergone cleaning, siliconization, and sterilization does not meet the standards, the thermodynamic feature acquisition module collects the cumulative deviation of the F0 value and the extreme poor temperature uniformity during the sterilization cycle of the target material. This can accurately capture the fluctuations of key process parameters during the sterilization process, providing core data for tracing the root cause of cleanliness non-compliance. The process stability judgment module analyzes thermodynamic characteristics based on thermodynamic feature parameters. The system uses thermodynamic characteristic values, based on the difference between these values ​​and predetermined thermodynamic characteristic thresholds, to determine whether the temperature sensor in the pulsed vacuum sterilizer meets standards. This enables a quantitative assessment of the sterilization process stability and allows for rapid differentiation between cleanliness defects stemming from the siliconization process and sterilization process anomalies. When the temperature sensor meets standards, the process correction module identifies uneven siliconization and determines the adjustment range of the silicone oil atomization pressure, enabling targeted optimization of the siliconization process. This addresses the issue of substandard cleanliness on the rubber stopper surface caused by uneven siliconization, improving the stability of the siliconization process. Conversely, when the temperature sensor does not meet standards... If the sterilization temperature is insufficient when the standard is met, the adjustment range of the sterilization temperature is determined based on the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold. This allows for precise correction of the sterilization process, ensuring that the sterilization effect meets the standard and thereby improving the pass rate of medical rubber stoppers cleanliness. At the same time, relying on historical periodic data, a closed-loop management system of detection, judgment, traceability, and correction is achieved, continuously optimizing the detection accuracy and process parameters, improving the efficiency and automation level of online detection of medical rubber stopper cleanliness, meeting the GMP compliance requirements and high-quality management needs of medical rubber stopper production, and ensuring the safety of medical rubber stoppers as pharmaceutical packaging materials.

[0031] In particular, by summing the changes in puncture debris, surface insoluble microparticles, and yellowness index with their respective preset thresholds to obtain surface characteristic values, the physical cleanliness and chemical stability of the rubber stopper surface can be evaluated by combining these values. Comparing these surface characteristic values ​​with preset surface characteristic thresholds, with values ​​below the threshold used as the criterion for cleanliness compliance and values ​​above or equal to the threshold used as the criterion for non-compliance, provides a clear and repeatable quantitative criterion for the cleanliness testing of medical rubber stoppers. This avoids the uncertainty caused by relying on fluctuations in single indicators or operator experience, thus making the conclusion of whether the cleanliness is qualified objective and reliable, and providing a clear basis for determining whether further analysis of the sterilization process is needed.

[0032] In particular, by using the cumulative deviation of the F0 value as an indicator of sterilization adequacy and the temperature uniformity range as an indicator of the consistency of temperature distribution within the sterilization cabinet, the sterilization process is characterized from two dimensions: the degree of sterilization effectiveness and the uniformity of the sterilization process. This reflects the degree of deviation between the sterilization intensity and the set standard, as well as the level of temperature distribution uniformity. The difference between the thermodynamic characteristic values ​​and predetermined thermodynamic characteristic thresholds is compared, and a threshold is set as a judgment boundary: when the difference is greater than this boundary, the process stability is considered to meet the standard; when the difference is less than or equal to this boundary, it is considered to not meet the standard. This judgment method establishes a clear quantitative basis for the state assessment of the sterilization process, making the judgment of process stability repeatable and objective. When the process stability meets the standard, the cause of unqualified cleanliness can be attributed to the siliconization process; when the process stability does not meet the standard, insufficient sterilization temperature can be confirmed, and the adjustment range can be quantified based on the specific magnitude of the difference.

[0033] In particular, when the temperature sensor of the pulsating vacuum sterilizer meets the standard, it indicates that the temperature distribution and sterilization intensity of the sterilization process are within the normal range. At this time, the cause of the unqualified cleanliness is identified in the siliconization process to determine the adjustment range of the silicone oil atomization pressure, thereby improving the uniformity of silicone oil spraying and reducing the amount of puncture debris or excessive surface particles caused by uneven siliconization. When the temperature sensor of the pulsating vacuum sterilizer does not meet the standard, the cause is identified in the sterilization process, and a sterilization temperature correction command is triggered. The method of determining the sterilization temperature adjustment range is further defined, that is, the difference between the thermodynamic characteristic value and the preset threshold is directly used for quantitative calculation, so that the temperature adjustment amount corresponds to the actual deviation. For the production of medical rubber stoppers, the two-step correction mechanism can automatically distinguish the root cause of the fault when an abnormality in cleanliness is detected, avoiding repeated trial and error between the siliconization and sterilization processes, while ensuring that the correction range matches the actual deviation, thereby shortening the troubleshooting cycle of process abnormalities and reducing the scrap rate caused by ambiguous attribution or improper adjustment. This improves the fault location accuracy and quality control efficiency of online detection of cleanliness of medical rubber stoppers. Attached Figure Description

[0034] Figure 1 This is a structural block diagram of an online detection system for the cleanliness of medical material production according to an embodiment of the present invention;

[0035] Figure 2 This is a flowchart illustrating the steps of an online detection method for the cleanliness of medical material production according to an embodiment of the present invention.

[0036] Figure 3 This invention provides a logic diagram for determining whether the cleanliness of a target material that has undergone cleaning, siliconization, and sterilization meets the required standards.

[0037] Figure 4 This invention provides a logic diagram for determining whether the temperature sensor of a pulsed vacuum sterilizer meets the standard. Detailed Implementation

[0038] To make the objectives and advantages of the present invention clearer, the present invention will be further described below with reference to embodiments; it should be understood that the specific embodiments described herein are merely for explaining the present invention and are not intended to limit the present invention.

[0039] Preferred embodiments of the present invention will now be described with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are merely illustrative of the technical principles of the present invention and are not intended to limit the scope of protection of the present invention.

[0040] Please see Figure 1 The diagram shown is a structural block diagram of an online detection system for the cleanliness of medical material production according to an embodiment of the present invention. The present invention provides an online detection system for the cleanliness of medical material production, comprising:

[0041] The surface feature acquisition module is used to acquire surface feature parameters of the target material that has undergone cleaning, siliconization and sterilization treatment within a historical period.

[0042] The cleanliness determination module, which is connected to the surface feature acquisition module, is used to analyze the surface feature characterization value based on the surface feature parameters; and to determine whether the cleanliness of the target material that has completed cleaning, siliconization and sterilization treatment meets the standard based on the comparison result of the surface feature characterization value and the predetermined surface feature characterization threshold.

[0043] The thermodynamic characteristic acquisition module, which is connected to the cleanliness determination module, is used to collect thermodynamic characteristic parameters of the target material during the sterilization cycle in response to the target material's cleanliness failing to meet the standard after cleaning, siliconization and sterilization.

[0044] The process stability determination module is connected to the thermodynamic feature acquisition module to analyze the thermodynamic feature characterization value based on the thermodynamic feature parameters; and to determine whether the temperature sensor of the pulsating vacuum sterilizer meets the standard based on the difference between the thermodynamic feature characterization value and the predetermined thermodynamic feature characterization threshold.

[0045] The process correction module, which is connected to the process stability determination module, is used to determine the uneven siliconization and the adjustment range of the silicone oil atomization pressure if the temperature sensor of the pulsed vacuum sterilizer meets the standard.

[0046] If the temperature sensor of the pulsating vacuum sterilizer does not meet the standard, it is determined that the sterilization temperature is insufficient. Based on the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold, the adjustment range of the sterilization temperature is determined.

[0047] The surface characteristic parameters include the amount of debris shed during puncture, the amount of insoluble microparticles on the surface, and the change in yellowness index.

[0048] The thermodynamic characteristic parameters include the cumulative deviation of the F0 value and the extreme poor temperature uniformity;

[0049] The F0 value is the equivalent sterilization time at a standard temperature of 121.1℃, calculated by converting the actual sterilization temperature.

[0050] In this embodiment, the present invention provides an online detection system for the cleanliness of medical material production, including: a surface feature acquisition module, a cleanliness determination module, a thermodynamic feature acquisition module, a process stability determination module, and a process correction module. The surface feature acquisition module collects data on the amount of puncture debris, the amount of insoluble particles on the surface, and the change in yellowness index of the target material after cleaning, siliconization, and sterilization treatments over a historical period, comprehensively capturing the surface cleanliness and material stability of medical rubber stoppers after multiple processes. The cleanliness determination module analyzes surface feature characterization values ​​based on surface feature parameters, and compares these values ​​with predetermined parameters. The comparison results of surface feature characterization thresholds determine whether the cleanliness of the target material that has undergone cleaning, siliconization, and sterilization meets the standards, achieving an objective quantitative judgment of the cleanliness of medical rubber stoppers. When the cleanliness of the target material that has undergone cleaning, siliconization, and sterilization does not meet the standards, the thermodynamic feature acquisition module collects the cumulative deviation of the F0 value and the extreme poor temperature uniformity during the sterilization cycle of the target material. This can accurately capture the fluctuations of key process parameters during the sterilization process, providing core data for tracing the root cause of cleanliness non-compliance. The process stability judgment module analyzes the thermodynamic feature characterization values ​​based on thermodynamic feature parameters. The difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold determines whether the temperature sensor of the pulsed vacuum sterilizer meets the standard, enabling a quantitative assessment of the sterilization process stability. This allows for rapid differentiation between cleanliness defects stemming from the siliconization process or sterilization process anomalies. When the temperature sensor meets the standard, the process correction module identifies uneven siliconization and determines the adjustment range of the silicone oil atomization pressure, achieving targeted optimization of the siliconization process. This addresses the issue of substandard cleanliness on the rubber stopper surface caused by uneven siliconization, improving the stability of the siliconization process. Conversely, when the temperature sensor does not meet the standard... If the sterilization temperature is insufficient, the adjustment range of the sterilization temperature is determined based on the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold. This allows for precise correction of the sterilization process, ensuring that the sterilization effect meets the standards and improving the cleanliness qualification rate of medical rubber stoppers. Simultaneously, relying on historical periodic data, a closed-loop management system of detection, judgment, traceability, and correction is implemented to continuously optimize detection accuracy and process parameters, improve the efficiency and automation level of online detection of medical rubber stopper cleanliness, meet the GMP compliance requirements and high-quality management needs of medical rubber stopper production, and ensure the safety of medical rubber stoppers as pharmaceutical packaging materials.

[0051] Please see Figure 2 The diagram shows a flowchart of the online detection method for the cleanliness of medical material production according to an embodiment of the present invention. The present invention provides an online detection method for the cleanliness of medical material production, comprising:

[0052] Step S1: Collect surface characteristic parameters of the target material that has undergone cleaning, siliconization and sterilization treatment within the historical period;

[0053] Step S2: Analyze the surface feature characterization value based on the surface feature parameters; determine whether the cleanliness of the target material that has undergone cleaning, siliconization and sterilization meets the standard based on the comparison result of the surface feature characterization value and the predetermined surface feature characterization threshold.

[0054] Step S3: In response to the target material's cleanliness failing to meet the standard after cleaning, siliconization, and sterilization, thermodynamic characteristic parameters of the target material during the sterilization cycle are collected.

[0055] Step S4: Analyze the thermodynamic characteristic values ​​based on the thermodynamic characteristic parameters; determine whether the temperature sensor of the pulsating vacuum sterilizer meets the standard based on the difference between the thermodynamic characteristic values ​​and the predetermined thermodynamic characteristic threshold.

[0056] Step S5: If the temperature sensor of the pulsed vacuum sterilizer meets the standard, it is determined that the siliconization is uneven and the adjustment range of the silicone oil atomization pressure is determined.

[0057] Step S6: In response to the temperature sensor of the pulsed vacuum sterilizer not meeting the standard, it is determined that the sterilization temperature is insufficient. Based on the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold, the adjustment range of the sterilization temperature is determined.

[0058] The surface characteristic parameters include the amount of debris shed during puncture, the amount of insoluble microparticles on the surface, and the change in yellowness index.

[0059] The thermodynamic characteristic parameters include the cumulative deviation of the F0 value and the extreme poor temperature uniformity;

[0060] The F0 value is the equivalent sterilization time at a standard temperature of 121.1℃, calculated by converting the actual sterilization temperature.

[0061] Understandably, the amount of puncture debris refers to the number of visible elastic microparticles that detach from the puncture site of a medical rubber stopper when punctured with a puncture instrument of a specified size under standard test conditions; this indicator directly reflects the rubber stopper's ability to resist the generation of microparticles during clinical use.

[0062] Understandably, the amount of surface insoluble microparticles refers to the number of insoluble microparticles remaining on the surface of medical rubber stoppers after cleaning and other treatments, which can be detached into the extract under specific extraction conditions. It is used to evaluate the cleanliness of the rubber stopper surface and the risk of microparticle contamination that it may cause to the drug solution.

[0063] Understandably, the change in yellowness index refers to the difference in the yellowness index of the surface of medical rubber stoppers before and after cleaning, siliconization and sterilization. It is used to characterize the degree of aging or discoloration of the rubber stopper material due to heat or other factors during processing.

[0064] It is understandable that the cumulative deviation of the F0 value refers to the difference between the actual cumulative F0 value at each monitoring point and the standard sterilization F0 value during the sterilization cycle. The F0 value is the equivalent sterilization time at a standard temperature of 121.1℃, which is used to comprehensively evaluate whether the sterilization effect of the sterilization process has met expectations.

[0065] It is understandable that poor temperature uniformity refers to the difference between the maximum and minimum temperatures measured at different monitoring points in the working area of ​​the sterilization equipment at the same time point during the sterilization cycle. It is used to evaluate the uniformity of temperature distribution in various parts during the sterilization process. The smaller the value, the better the temperature uniformity.

[0066] In the embodiments, the historical period refers to the sterilization period of the target material. The historical period in the embodiments is [3 days, 14 days], and the preferred historical period in the embodiments is 7 days.

[0067] In the embodiments, the total number of target material samples within the historical period is preferably 7 days, and the total number of samples in the embodiments is [100, 300], and the preferred embodiment is 200.

[0068] In this embodiment, the pulsating vacuum sterilizer removes cold air through pulsating circulation. During the heat preservation phase, it maintains a set temperature and uses saturated steam to kill microorganisms. Simultaneously, it monitors the F0 value and temperature uniformity range to assess whether the temperature sensor of the pulsating vacuum sterilizer meets the standard. The set temperature in this embodiment is [120℃, 125℃], preferably 121℃. Taking the preferred transitional sterilization method as an example, the F0 value for the temperature sensor of the pulsating vacuum sterilizer meeting the standard is [8 minutes, 15 minutes], preferably 12 minutes. Taking the preferred temperature monitoring during the heat preservation phase as an example, the threshold range for temperature uniformity range at each monitoring point in this embodiment is [1.0℃, 2.5℃], preferably 2.5℃.

[0069] Specifically, the cleanliness determination module analyzes the surface feature characterization values ​​based on the sum of a first feature-limited characterization parameter, a second feature-limited characterization parameter, and a third feature-limited characterization parameter, wherein,

[0070] The first feature defines the characterization parameter as the ratio of the amount of debris removed during puncture to a predetermined threshold for the amount of debris removed during puncture.

[0071] The second feature defines the characterization parameter as the ratio of the amount of surface insoluble particles to a predetermined threshold for the amount of surface insoluble particles;

[0072] The third feature defines the characterization parameter as the ratio of the change value of the yellowness index to a predetermined threshold value for the change of the yellowness index.

[0073] In this embodiment, the amount of rubber debris generated during puncture is based on a simulated puncture mechanism and high-resolution machine vision imaging. Through standardized puncture and sequential image differential processing, the number of rubber debris generated around the puncture point is automatically identified and counted to evaluate the physical integrity of the rubber stopper and the lubrication effect of the silicone oil. The amount of surface insoluble particles is based on dark-field imaging and polarization fusion technology. Low-angle dark-field light sources are used to enhance particle scattering signals, and orthogonal polarization is combined to suppress substrate reflection interference. Image segmentation and morphological analysis are used to identify and classify the number of particles larger than 10μm and larger than 25μm adhering to the rubber stopper surface to quantify the degree of surface foreign matter contamination. The change value of the yellowness index is based on multispectral reflectance analysis. By collecting the reflectance of the rubber stopper in the 450nm blue light band before and after sterilization, its change rate is calculated to quantify the degree of thermal aging or discoloration caused by high-temperature or irradiation sterilization. These three parameters comprehensively evaluate the cleanliness and material stability of the rubber stopper after sterilization from three dimensions: physical integrity, foreign matter contamination, and chemical aging, providing a quantitative basis for subsequent process attribution and correction.

[0074] In this embodiment, the threshold for the amount of debris shed during puncture is based on the industry-standard requirements for rubber seals used in injectable packaging. This value is based on the safety limits for the risk of particulate contamination of drugs under standard puncture conditions. The threshold for the amount of surface insoluble particles refers to the routine requirements for testing insoluble particles in injectables to control the risk of particulate contamination of injectables. There is no unified industry standard for the threshold for the change in yellowness index. It is usually set by the company itself based on the thermal stability or radiation tolerance of the material through process validation and compatibility studies to ensure the consistency of the appearance and chemical stability of the rubber stopper after sterilization.

[0075] Please see Figure 3 As shown, this is a logic diagram for determining whether the cleanliness of a target material that has undergone cleaning, siliconization, and sterilization meets the standards, according to an embodiment of the present invention. The process for determining whether the cleanliness of a target material that has undergone cleaning, siliconization, and sterilization meets the standards includes:

[0076] Extract the comparison results of surface feature characterization values ​​with predetermined surface feature characterization thresholds;

[0077] If the surface feature characterization value is less than the predetermined surface feature characterization threshold, then the cleanliness of the target material that has undergone cleaning, siliconization and sterilization is determined to meet the standard.

[0078] If the surface feature characterization value is greater than or equal to the predetermined surface feature characterization threshold, then the cleanliness of the target material that has undergone cleaning, siliconization, and sterilization is determined to be non-compliant with the standard.

[0079] In this embodiment, the predetermined surface feature characterization threshold is obtained in advance. All surface feature characterization values ​​of the target material that has completed cleaning, siliconization and sterilization treatment are collected in the historical period and its average value is calculated. The predetermined surface feature characterization threshold in this embodiment is selected in the range [3.05, 3.35]. Preferably, the predetermined surface feature characterization threshold in this embodiment is 3.15.

[0080] In this embodiment, the surface feature characterization value is obtained by dividing the amount of debris shed during puncture, the amount of surface insoluble particles, and the change value of yellowness index by their respective preset thresholds, and summing them up. This allows the physical cleanliness and chemical stability of the rubber stopper surface to be evaluated by combining the two values. The surface feature characterization value is compared with the preset surface feature characterization threshold. Values ​​less than the threshold are used as the basis for judging whether the cleanliness meets the standard, while values ​​greater than or equal to the threshold are used as the basis for judging whether the cleanliness does not meet the standard. This provides a clear and repeatable quantitative criterion for the cleanliness detection of medical rubber stoppers, avoiding the uncertainty caused by relying on fluctuations of single indicators or the experience judgment of operators. This makes the conclusion of whether the cleanliness is qualified objective and reliable, and also provides a clear basis for determining whether further analysis of the sterilization process is needed.

[0081] Specifically, the process stability determination module is used to analyze the thermodynamic characteristic values ​​determined based on the sum of the first process-limited characterization parameter and the second process-limited characterization parameter, wherein,

[0082] The first process-defined characterization parameter is the ratio of a predetermined cumulative deviation threshold for the F0 value to the cumulative deviation value of the F0 value;

[0083] The second process-defined characterization parameter is the ratio of a predetermined temperature uniformity range threshold to the temperature uniformity range value.

[0084] In this embodiment, the cumulative deviation of the F0 value is calculated by real-time acquisition of the temperature-time curve during the heat preservation stage by multiple temperature sensors in the sterilization chamber. The actual F0 value of each monitoring point is calculated according to the F0 value integral formula, and the lowest value is taken as the actual F0 value of this batch. The absolute value of the difference between the actual F0 value and the set target F0 value is the cumulative deviation of the F0 value, which is used to quantify the degree of deviation of the overall sterilization intensity. The temperature uniformity range is calculated based on the temperature data collected by multiple temperature sensors at the same time during the heat preservation stage. The difference between the highest temperature and the lowest temperature is calculated, and the maximum range of the entire heat preservation stage is taken as the characterization value, which is used to quantify the uniformity of steam distribution.

[0085] In this embodiment, the cumulative deviation threshold of F0 value is set based on the aseptic assurance requirements of the moist heat sterilization process. The target F0 value is usually required to be greater than or equal to 12, and the allowable deviation range is determined according to the process verification results. The temperature uniformity range threshold is based on the technical specifications of the moist heat sterilization equipment to ensure the uniformity of steam distribution and the consistency of sterilization effect at each location.

[0086] Please see Figure 4 As shown, this is a logic diagram for determining whether the temperature sensor of the pulsed vacuum sterilizer meets the standard according to an embodiment of the present invention. The process for determining whether the temperature sensor of the pulsed vacuum sterilizer meets the standard according to the present invention includes:

[0087] Calculate the difference between the thermodynamic characteristic characterization value and the predetermined thermodynamic characteristic characterization threshold;

[0088] If the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold is greater than the predetermined difference threshold, then the temperature sensor of the pulsed vacuum sterilizer is determined to meet the standard.

[0089] If the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold is less than or equal to the predetermined difference threshold, then the temperature sensor of the pulsating vacuum sterilizer is determined to be non-compliant with the standard.

[0090] In this embodiment, the predetermined thermodynamic characteristic characterization threshold is obtained in advance. All thermodynamic characteristic characterization values ​​of the target material are collected during the sterilization cycle and the average value is calculated. The predetermined thermodynamic characteristic characterization threshold is selected within the range [1.95, 2.35] in this embodiment. Preferably, the predetermined thermodynamic characteristic characterization threshold is 2.15.

[0091] In this embodiment, the predetermined difference threshold is obtained in advance. The difference between all thermodynamic characteristic values ​​of the target material during the sterilization cycle and the predetermined thermodynamic characteristic threshold is calculated, and the average value is calculated. In this embodiment, the predetermined difference threshold is selected in the range [0.05, 0.35]. Preferably, the predetermined difference threshold is 0.15.

[0092] In this embodiment, the cumulative deviation of the F0 value is used as an indicator of sterilization adequacy, and the temperature uniformity range is used as an indicator of the consistency of temperature distribution within the sterilization cabinet. These two dimensions—the degree of sterilization effectiveness and the uniformity of the sterilization process—combined to characterize the sterilization process's operational status. This reflects the degree of deviation between the sterilization intensity and the set standard, as well as the level of temperature distribution uniformity. The thermodynamic characteristic values ​​are compared with predetermined thermodynamic characteristic thresholds, and a threshold value is set as a judgment boundary: when the difference is greater than this boundary, the process stability is considered to meet the standard; when the difference is less than or equal to this boundary, it is considered to not meet the standard. This judgment method establishes a clear quantitative basis for the state assessment of the sterilization process, making the judgment of process stability repeatable and objective, thus providing reliable support for subsequent attribution decisions: when the process stability meets the standard, the cause of unqualified cleanliness can be attributed to the siliconization stage; when the process stability does not meet the standard, insufficient sterilization temperature can be confirmed, and the adjustment range can be quantified based on the specific magnitude of the difference.

[0093] Specifically, the process correction module determines the condition for adjusting the silicone oil atomization pressure range based on the temperature sensor of the pulsed vacuum sterilizer meeting the standard.

[0094] In this embodiment, when the temperature sensor of the pulsed vacuum sterilizer meets the standard, it indicates that the temperature distribution and sterilization intensity of the sterilization process are within the normal range. At this time, the cause of the unqualified cleanliness is identified in the siliconization process, so as to determine the adjustment range of the silicone oil atomization pressure, thereby improving the uniformity of silicone oil spraying and reducing the amount of puncture debris or excessive surface particles caused by uneven siliconization.

[0095] Specifically, the process correction module determines that the condition for adjusting the sterilization temperature range is that the temperature sensor of the pulsed vacuum sterilizer does not meet the standard.

[0096] In this embodiment, when it is determined that the temperature sensor of the pulsating vacuum sterilizer does not meet the standard, the cause is identified as the sterilization process, and a sterilization temperature correction command is triggered.

[0097] Specifically, the process correction module is used to determine the sterilization temperature adjustment range based on the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold.

[0098] In this embodiment, quantitative calculations are performed based on the difference between thermodynamic characteristic values ​​and preset thresholds to establish a correspondence between temperature adjustment and actual deviation. For medical rubber stopper production, the correction mechanism can automatically distinguish the root cause of the fault when an abnormality in cleanliness is detected, avoiding repeated trial and error between the siliconization and sterilization stages. At the same time, it ensures that the correction magnitude matches the actual deviation, thereby shortening the troubleshooting cycle for process abnormalities and reducing the scrap rate caused by ambiguous attribution or improper adjustment. This improves the fault location accuracy and quality control efficiency of online detection of medical rubber stopper cleanliness.

[0099] The technical solution of the present invention has been described in conjunction with the embodiments shown in the accompanying drawings. However, it will be readily understood by those skilled in the art that the scope of protection of the present invention is obviously not limited to the specific implementation methods of the embodiments. Without departing from the principles of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after such changes or substitutions will all fall within the scope of protection of the present invention.

Claims

1. An online detection system for the cleanliness of medical material production, characterized in that, include: The surface feature acquisition module is used to acquire surface feature parameters of the target material that has undergone cleaning, siliconization and sterilization treatment within a historical period. A cleanliness determination module is used to analyze surface characteristic values ​​based on the surface characteristic parameters; Based on the comparison results between the surface feature characterization values ​​and the predetermined surface feature characterization thresholds, it is determined whether the cleanliness of the target material that has undergone cleaning, siliconization, and sterilization meets the standards. The thermodynamic characteristic acquisition module is used to collect thermodynamic characteristic parameters of the target material during the sterilization cycle in response to the failure of the target material to meet the cleanliness standard after cleaning, siliconization and sterilization. A process stability determination module is used to analyze thermodynamic characteristic values ​​based on the thermodynamic characteristic parameters. The temperature sensor of the pulsating vacuum sterilizer is determined to meet the standard based on the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold. The process correction module is used to determine the uneven siliconization and adjust the silicone oil atomization pressure range in response to the temperature sensor of the pulsed vacuum sterilizer meeting the standard. If the temperature sensor of the pulsating vacuum sterilizer does not meet the standard, it is determined that the sterilization temperature is insufficient. Based on the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold, the adjustment range of the sterilization temperature is determined. The surface characteristic parameters include the amount of debris shed during puncture, the amount of insoluble microparticles on the surface, and the change in yellowness index. The thermodynamic characteristic parameters include the cumulative deviation of the F0 value and the extreme poor temperature uniformity; The F0 value is the equivalent sterilization time at a standard temperature of 121.1℃, calculated by converting the actual sterilization temperature.

2. The online detection system for the cleanliness of medical material production according to claim 1, characterized in that, The cleanliness determination module analyzes surface feature characterization values ​​based on the sum of a first feature-defined characterization parameter, a second feature-defined characterization parameter, and a third feature-defined characterization parameter, wherein... The first feature defines the characterization parameter as the ratio of the amount of debris removed during puncture to a predetermined threshold for the amount of debris removed during puncture. The second feature defines the characterization parameter as the ratio of the amount of surface insoluble particles to a predetermined threshold for the amount of surface insoluble particles; The third feature defines the characterization parameter as the ratio of the change value of the yellowness index to a predetermined threshold value for the change of the yellowness index.

3. The online detection system for the cleanliness of medical material production according to claim 2, characterized in that, The cleanliness determination module is used to determine whether the cleanliness of the target material that has completed cleaning, siliconization and sterilization meets the standard. The condition is that the surface feature characterization value is less than the predetermined surface feature characterization threshold.

4. The online detection system for the cleanliness of medical material production according to claim 3, characterized in that, The cleanliness determination module is used to determine whether the cleanliness of the target material that has undergone cleaning, siliconization and sterilization does not meet the standard. The condition is that the surface feature characterization value is greater than or equal to the predetermined surface feature characterization threshold.

5. The online detection system for the cleanliness of medical material production according to claim 4, characterized in that, The process stability determination module is used to analyze the thermodynamic characteristic values, which are determined based on the sum of the first process-limited characterization parameter and the second process-limited characterization parameter, wherein... The first process-defined characterization parameter is the ratio of a predetermined cumulative deviation threshold for the F0 value to the cumulative deviation value of the F0 value; The second process-defined characterization parameter is the ratio of a predetermined temperature uniformity range threshold to the temperature uniformity range value.

6. The online detection system for the cleanliness of medical material production according to claim 5, characterized in that, The process stability determination module determines that the temperature sensor of the pulsating vacuum sterilizer meets the standard if the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold is greater than the predetermined difference threshold.

7. The online detection system for the cleanliness of medical material production according to claim 6, characterized in that, The process stability determination module determines that the temperature sensor of the pulsating vacuum sterilizer does not meet the standard when the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold is less than or equal to the predetermined difference threshold.

8. The online detection system for the cleanliness of medical material production according to claim 7, characterized in that, The process correction module determines the condition for adjusting the silicone oil atomization pressure range based on the temperature sensor of the pulsed vacuum sterilizer meeting the standard.

9. The online detection system for the cleanliness of medical material production according to claim 8, characterized in that, The process correction module determines that the condition for adjusting the sterilization temperature range is that the temperature sensor of the pulsed vacuum sterilizer does not meet the standard.

10. The online detection system for the cleanliness of medical material production according to claim 9, characterized in that, The process correction module is used to determine the sterilization temperature adjustment range based on the difference between the thermodynamic characteristic value and the predetermined thermodynamic characteristic threshold.

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