Study on the sensitivity of a volumetric modulated arc therapy plan verification equipment on multi-leaf collimator opening and closing errors and its gamma pass rate limit / 生物医学工程学杂志

To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.

Statistical process control methods for quality inspection of blood component samples: a case study / 中国输血杂志

【Objective】 To explore the analytical methods for detecting data in the process of quality inspection of blood component samples. 【Methods】 The quality inspection data of blood component samples from 2018 to 2022 in our center were collected. Based on the principles of statistical process control, control charts were created using Minitab software to analyze key test items. 【Results】 The P control chart was used to analyze the pass rate of platelet content and revealed one out-of-control point. The normality test was performed on plasma protein content to analyze the causes of data fluctuations for further improvement. The mean and range control chart was utilized for hematocrit measurement, with abnormal data trends detected. Further analysis of the normality test and process capability analysis was conducted, resulting in a Cpk value of 0.67. 【Conclusion】 By applying statistical process control methods, the study employed P control charts to analyze count data in the quality inspection of blood component samples, conducted normality tests for measurement data, and utilized mean and range control charts to identify abnormal data trends. For data conforming to a normal distribution, the process capability index (Cpk) was calculated to explore effective monitoring methods for ensuring stability in the blood supply process.

Research on monitoring method of dripping pills dripping process based on laser detection and multivariate data analysis technology / 药学学报

At present, the digitalization and intelligence level of dripping pills production process is low, and there is a lack of process monitoring methods, which makes it difficult to effectively control the quality of dripping pills. Therefore, this paper proposed an online monitoring method for the dripping process of dripping pills based on laser detection technology and multivariate data analysis (MVDA) technology. Firstly, the width data of the falling droplets during the dripping process of the dripping pills were collected by the laser detector at a high frequency. Secondly, based on the width data, the nodes were selected for each droplet and the features were extracted. Then, the principal component analysis (PCA) model was established based on the feature dataset under normal process conditions, and Hotelling's T2 or DModX statistic was selected to determine whether the droplets in the dripping process were abnormal, and the abnormalities were classified and diagnosed by the principal component score map combined with K-nearest neighbor (KNN) algorithm. In this study, the feasibility of this method was investigated by taking the dripping process of Ginkgo biloba leaf dripping pills as an example. The results showed that the obtained model has good detection and diagnosis ability for abnormal valve opening, abnormal liquid temperature, and abnormal liquid volume. This method can provide some reference for the industrial production of dripping pills.

Loss sampling methods for soybean mechanical harvest

Harvesting is one of the most important stages of the agricultural production process. However, the lack of monitoring during this operation and the absence of efficient methodologies to quantify losses have contributed to the decline in the quality of the operation. The objective of this study was to monitor mechanized soybean harvest by quantifying losses through two methodologies using statistical process control. The study was conducted in March 2016 in an agricultural area in the municipality of Ribeirão Preto, SP, using a John Deere harvester model 1470 with a tangential-type track system and separation by a straw-blower. The experimental design followed the standards established by statistical process control, and every 8 min of harvest, the total losses by the circular framework and rectangular framework methodologies were simultaneously quantified, totaling 40 points. Data were analyzed using descriptive statistics and statistical process control. The averages of the circular methodology framework were values above those found in the rectangular methodology framework, presenting greater representativeness of losses. The process was considered unable to maintain losses of soybeans at acceptable levels during mechanical harvest throughout the operation of the two frameworks. The circular framework for collecting samples at different locations resulted in higher reliability of data.

Theories and perspectives of patient-based real-time quality control system in the laboratory / 中华检验医学杂志

Taking advantage of current advancements of the laboratory information system, patient-based real-time quality control (PBRTQC) has become a hot research topic with the potential of significantly improving the quality of clinical laboratories. PBRTQC has several advantages over conventional internal quality control, including the merit of continuous error detection, low maintenance cost, and no fear of loss of quality control due to commutability issue. This review summarized the recent research progress in PBRTQC. The review described the fundamental theories of PBRTQC and explained how to implement PBRTQC in clinical laboratories in detail. The review also provided prospective view on how to solve the current problems and what are the future research directions of PBRTQC.

Application of Statistical Process Control in Evaluation of Performance for Beam-matched Medical Electron Linacs / 中国医疗器械杂志

Clinically, beam matching can greatly improve the flexibility and efficiency of treating patients between different medical electron linacs. However, in addition to the regular quality assurance (QA) test of the machine performance of linacs, there is still a lack of comprehensive evaluation of the clinical radiotherapy performance of beam-matched linacs. In this paper, the performance of volumetric modulated arc therapy (VMAT) between three closely matched linacs was evaluated by statistical process control (SPC) technology. It was found that the average and median γ passing rates of the VMAT QA processes of the three linacs had little difference, but the process capability levels were at three different levels. The results show that SPC technology can effectively evaluate the performance of beam matching for medical electron linacs, improve the patient-specific VMAT QA processes, and guide clinical decision-making.

A strategy for population pharmaceutical quality assessment based on quality by design / 药物分析学报

From a regulatory perspective,drug quality consistency evaluation must concern different processes used for the same drug.In this study,an assessment strategy based on quality by design(QbD)was developed for population pharmaceutical quality evaluation.A descriptive analysis method based on QbD concept was first established to characterize the process by critical evaluation attributes(CEAs).Then quantitative analysis method based on an improved statistical process control(SPC)method was established to investigate the process indicators(PIs)in the process population,such as mean distri-bution,batch-to-batch difference and abnormal quality probability.After that rules for risk assessment were established based on the SPC limitations and parameters.Both the SPC parameters of the CEAs and the risk of PIs were visualized according to the interaction test results to obtain a better understanding of the population pharmaceutical quality.Finally,an assessment strategy was built and applied to generic drug consistency assessment,process risk assessment and quality trend tracking.The strategy demon-strated in this study could help reveal quality consistency from the perspective of process control and process risk,and further show the recent development status of domestic pharmaceutical production processes.In addition,a process risk assessment and population quality trend tracking provide data-based information for approval.Not only can this information serve as a further basis for decision-making by the regulatory authority regarding early warnings,but it can also reduce some avoidable adverse reactions.With continuous addition of data,dynamic population pharmaceutical quality is meaningful for emergencies and decision-making regarding drug regulation.

Critical quality attribute assessment of big brand traditional Chinese medicine: quality control method of Huangjing Zanyu Capsules based on chemical properties of characteristic components / 中国中药杂志

The chemical properties of characteristic components are significant to the manufacturing quality control of big brand traditional Chinese medicine. In this study, the Huangjing Zanyu Capsules were used as the research carrier to determine the content of five characteristic components including icraiin, emodin, schisandrin A, 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside, and osthole simultaneously by high-performance liquid chromatography(HPLC). The results showed that the chemical properties of five cha-racteristic components had a good linear relationship(r>0.999 9) within the quantitative range; the relative standard deviations(RSD) was 0.11%-2.0% and 0.25%-2.8% respectively for intra-day and inter-day precision; the RSD of repeatability was 1.8%-2.6%; the RSD of stability within 48 hours was 0.19%-2.8%, and the average recovery rate was 95.52%-100.1%, all meeting the requirements of pharmaceutical quantitative analysis. Additionally, the interval estimation method was used to directly reflect the distribution of samples with abnormal chemical properties of characteristic components, and the results showed ten samples were detected beyound the 95% control line of confidence level. Multivariate statistical process control(MSPC) method was used to monitor the abnormal samples of Huangjing Zanyu Capsules collectively, and the results showed that two samples were beyond the 95% control line of Hotelling's T~2 and three samples beyond the 95% control line of squared prediction error(SPE), indicating consistent quality control of Huangjing Zanyu Capsules. In conclusion, the proposed method is not only accurate and efficient but also a compensation for the traditional single-component quality control method, providing a scientific basis for the quality control in manufacturing process of Huangjing Zanyu Capsules. Furthermore, it could also serve as a reference method for the quality control in manufacturing big brand traditional Chinese medicine.

Critical quality attribute assessment of big brand traditional Chinese medicine: quality control method of ginkgo leaves extract material based on powder physical properties / 中国中药杂志

The physical properties of ginkgo leaves extract(GLE) are the critical quality attributes for the control of the manufacturing process of ginkgo leaves preparations. In this study, 53 batches of GLE with different sources from the real world were used as the objects to carry out the research from 3 levels. First, based on micromeritics evaluation method, a total of 29 physical attribute quality parameters in five dimensions were comprehensively characterized, with a total of 1 537 data points. Further, with use of physical fingerprinting technology combined with similarity evaluation, the powder physical properties of 53 batches of GLE showed obvious differences from an overall perspective, and the similarity of the physical fingerprints was 0.876 to 1.000. Secondly, hierarchical clustering analysis(HCA) and principal component analysis(PCA) models were constructed to realize the reliable identification and differentiation of real-world materials produced by GLE from different sources. Multivariate statistical process control(MSPC) model was used to create GLE material Hotelling T~2 and squared prediction error(SPE) control charts. It was found that the SPE score of B_(21) powder exceeded the 99% confidence control limit by 22.495 9, and the SPE scores of A_1 and C_(10) powder exceeded the 95% confidence control limit by 16.099 2, realizing the determination of abnormal samples in the materials of GLE from the production in real world. Finally, the physical quality control method of GLE in the production process of ginkgo leaves preparations was established in this study, providing a reference for the quality control methods of ginkgo leaves preparations in their manufacturing process.

Critical quality attribute assessment of big brand traditional Chinese medicine: quality control of Tongren Niuhuang Qingxin Pills in texture and sensory attributes / 中国中药杂志

Texture sensory attributes are the key items in quality control of Chinese medicinal honeyed pills. The purpose of this study is to develop a quality control method for assessing the texture sensory attributes of Chinese medicinal honeyed pills based on real-world Tongren Niuhuang Qingxin pilular masses and finished products. First, parameters of texture profile analysis(TPA) were optimized through single factor and central composite design(CCD) experiments to establish a detection method for texture sensory attri-butes of Tongren Niuhuang Qingxin Pills. The results showed that the established detection method was stable and reliable, with the optimal parameters set up as follows: deformation percentage of 70%, detection speed at 30 mm·min~(-1), and interval time of 15 s. Furthermore, 540 data points yielded form six texture sensory attributes of pills from 30 batches were subjected to multivariate statistical process control(MSPC) with Hotelling T~2 and squared prediction error(SPE) control charts to establish the quality control method of Tongren Niuhuang Qingxin Pills. This study is expected to provide a reference for improving the quality control system of Chinese medicinal honeyed pills.

Daily quality control data analysis and process evaluation of linear accelerator / 中华放射肿瘤学杂志

Objective To analyze the quality control data of linear accelerator detected by Daily QA3 and to evaluate this quality control process using statistical process control.Methods After the calibrations of the accelerator and Daily QA3,Daily QA3 device was used to perform daily quality control by technicians and physicists and 100 groups and 30 groups of daily quality control data were collected.After the accelerator and Daily QA3 were re-calibrated,Daily QA3 device was utilized to perform daily quality control by technicians and 100 groups of the daily quality control data were repeatedly collected.The variations of normalized signal-to-noise ratio of quality control data collected after two calibrations were analyzed.The first 30 groups of daily quality control data measured by technicians and physicists were adopted to calculate the I-MR control chartsand compare the location of CL and the range of UCL and LCL.The process capability indices were calculated for three different quality control processes bytechnicians and physicists,respectively.Results For twice calibrations,normalized signal-to-noise ratio of quality control data significantly changed before 6 weeks,became stable between 6 and 8 weeks,and the changes became smaller after 8 weeks.For dose output measured by physicists,the rang of UCL and LCL was more narrow.In terms of flatness and symmetry,the location of CL was closer to zero.Regarding dose output and flatness,the process capability indices of three different quality control process were all satisfied ≥ 1,whereas unsatisfied for transverse symmetry.Conclusions The first 30-40 data points should be adopted to delineate I-MR control chart of the linear accelerator in daily quality control process.The quality control process should be completed by a fixed and small group of personnel and an optimal tolerance level should be customized.

Preliminary study on monitoring patient-specific volumetric modulated arc therapy quality assurance process with statistical process control methodology on the basis of TG-218 report / 生物医学工程学杂志

Patient-specific volumetric modulated arc therapy (VMAT) quality assurance (QA) process is an important component of the implementation process of clinical radiotherapy. The tolerance limit and action limit of discrepancies between the calculated dose and the delivered radiation dose are the key parts of the VMAT QA processes as recognized by the AAPM TG-218 report, however, there is no unified standard for these two values among radiotherapy centers. In this study, based on the operational recommendations given in the AAPM TG-218 report, treatment site-specific tolerance limits and action limits of gamma pass rate in VMAT QA processes when using ArcCHECK for dose verification were established by statistical process control (SPC) methodology. The tolerance limit and action limit were calculated based on the first 25 in-control VMAT QA for each site. The individual control charts were drawn to continuously monitor the VMAT QA process with 287 VMAT plans and analyze the causes of VMAT QA out of control. The tolerance limits for brain, head and neck, abdomen and pelvic VMAT QA processes were 94.56%, 94.68%, 94.34%, and 92.97%, respectively, and the action limits were 93.82%, 92.54%, 93.23%, and 90.29%, respectively. Except for pelvic, the tolerance limits for the brain, head and neck, and abdomen were close to the universal tolerance limit of TG-218 (95%), and the action limits for all sites were higher than the universal action limit of TG-218 (90%). The out-of-control VMAT QAs were detected by the individual control chart, including one case of head and neck, two of the abdomen and two of the pelvic site. Four of them were affected by the setup error, and one was affected by the calibration of ArcCHECK. The results show that the SPC methodology can effectively monitor the IMRT/VMAT QA processes. Setting treatment site-specific tolerance limits is helpful to investigate the cause of out-of-control VMAT QA.

Application of Shewhart Control Charts in the Inspection of Pharmaceutical Manufacturing Process / 中国药师

Objective:Through the establishment of shewhart control chart,to grasp the variation of products and avoid the occur-rence of failures.Methods:According to the characteristics and control requirements of quality parameters,several types of typical pa-rameters were introduced to illustrate the detection results and create the control charts in order to confirm whether the production was under the control. Results:The analysis of control charts could expedite the operator discovering the process variation caused by spe-cial factors,and taking corrective/preventive actions so that the products consistently complied with the regulatory specifications and production instructions. Conclusion:Control charts can be used as a monitoring tool in pharmaceutical manufacturing process,which can reduce the reject ratio and promote the continuous improvement of products.

Application of statistical process control for spotting compliance to good pharmaceutical practice

ABSTRACT For the release of pharmaceutical products into the drug market; most of the pharmaceutical companies depend on acceptance criteria - that are set internally, regulatory and/or pharmacopeially. However, statistical process control monitoring is underestimated in most quality control in cases; although it is important not only for process stability and efficiency assessment but also for compliance with all appropriate pharmaceutical practices such as good manufacturing practice and good laboratory practice, known collectively as GXP. The current work aims to investigate two tablet inspection characteristics monitored during in-process control viz. tablet average weight and hardness. Both properties were assessed during the compression phase of the tablet and before the coating stage. Data gathering was performed by the Quality Assurance Team and processed by Commercial Statistical Software packages. Screening of collected results of 31 batches of an antibacterial tablet - based on Fluoroquinolone -showed that all the tested lots met the release specifications, although the process mean has been unstable which could be strongly evident in the variable control chart. Accordingly, the two inspected processes were not in the state of control and require strong actions to correct for the non-compliance to GXP. What is not controlled cannot be predicted in the future and thus the capability analysis would be of no value except to show the process capability retrospectively only. Setting the rules for the application of Statistical Process Control (SPC) should be mandated by Regulatory Agencies.

Application of near infrared spectroscopy combined with multivariate statistical process control for in-line monitoring of extraction of Lonicerae Japonicae Flos / 中草药

Objective To develop a multivariate statistical process control (MSPC) model for in-line monitoring of the extraction process of Lonicerae Japonicae Flos (LJF). Methods The spectral data collected by near infrared spectrascopy coupled with MSPC technique were applied to establish the statistical model. Three kinds of multivariate control charts (PC scores, Hottelling T2 and DModX) were used to monitor the abnormal variations caused by the change of starting material quality attributes and abnormal operation conditions. Moreover, the extraction process trajectory was developed by applying principal component analysis on the process spectra, reflecting the changing trend with extraction time. Results The MSPC model with good repeatability and robustness could show the quality variation of extraction process of LJF and accurately predict the normal batches. The joint use of three control charts could effectively identify the abnormal conditions. Compared with the traditional monitoring methods, this approach was fast and nondestructive, and can implemente the in-line and real-time monitoring. Conclusion The near infrared spectroscopy combined with MSPC can be successfully applied to the extraction processes of LJF, which is of great significance for the improvement of the quality control of Chinese material medica (CMM).

Study on Extraction Process Trajectory for In-line Monitoring of Extraction Process of Lonicera Japonica of Re-Du-Ning Injection / 世界科学技术-中医药现代化

This study was aimed to develop in-line monitoring of extraction process of Lonicerajaponica in the extraction process trajectory of Re-Du-Ning (RDN) injection.Several batches of near-infrared (NIR) spectrum dates were collected and multivariate statistical process control (MSPC) method was in conjunction with.The results showed that using score,Hotelling T2 and DModX control chart,various normal and abnormal behaviors of the test batches were detected in time by comparison with the extraction process trajectory.It was concluded that the process trajectory for in-line quality control based on NIR spectrum dates and MSPC could indicate the changes of process.It was a feasible technology tool of the total process quality control during traditional Chinese medicine (TCM) manufacturing process.

Monitoring method of extraction process for Schisandrae Chinensis Fructus based on near infrared spectroscopy and multivariate statistical process control / 中国中药杂志

To establish an on-line monitoring method for extraction process of Schisandrae Chinensis Fructus, the formula medicinal material of Yiqi Fumai lyophilized injection by combining near infrared spectroscopy with multi-variable data analysis technology. The multivariate statistical process control (MSPC) model was established based on 5 normal batches in production and 2 test batches were monitored by PC scores, DModX and Hotelling T2 control charts. The results showed that MSPC model had a good monitoring ability for the extraction process. The application of the MSPC model to actual production process could effectively achieve on-line monitoring for extraction process of Schisandrae Chinensis Fructus, and can reflect the change of material properties in the production process in real time. This established process monitoring method could provide reference for the application of process analysis technology in the process quality control of traditional Chinese medicine injections.

Quality control of linac in daily volumetric-modulated arc therapy / 中华放射肿瘤学杂志

Objective To verify the daily delivery accuracy of volumetric-modulated arc therapy (VMAT) and achieve the process quality control (PQC) of linac using statistical process control (SPC)technology.Methods The log files of all treatments were taken out from the linac system.An in-house software which created by Matlab 7.14 was used to analyze the daily parameters accuracy and the mechanism and dose delivery accuracy of the linac for each VMAT,and an daily evaluation report was automatically created for the linac.The stability of the linac and the deviation of the delivery accuracy for various cancer sites were also analyzed.To achieve the process quality control of hnac using SPC technology,the control limit of each parameter was calculated by Johnson alternation and the single value control charts were drawn.Results 76 patients mainly with nasopharyngeal carcinoma,cervical carcinoma,rectal cancer and laryngeal cancer,got the treatment daily with VMAT technology,and a total of 2 446 arcs were delivered by the linac in continuous 16 days.The gantry angle error,y and x collimator position error,MLC leaf position error and dose delivery error were 0.49°,0.09 mm,0.38 mm,0.31 mm,0.05 MU,respectively.Compare to the nasopharynx,uteri,rectal and larynx cancer,it can be seen that the variation factors of dose delivery and gantry angle errors for various cancer sites were higher,which was 8.10％ and 4.54％,respectively.Through the process quality control of the linac,it was found that all the parameters were in control.While some abnormal points arose (the error was greater than UCL),and the ratio of the gantry angle which was out of control (0.45％) was the highest in all parameters.Conclusions linac delivery accuracy could be monitored and verified during the whole VMAT treatment for each patient,and the daily running condition of linac could be monitored.Through the introduction of SPC technology and the control charts,the process quality control of linac in VMAT could be achieved.It is a financial and valid method for the daily quality assurance of linac.