一种新型吸入用药定量评估仪器的质量控制检测方法探讨

Discussion on the Quality Control Test Method for a New Inhalation Drug Quantitative Assessment Instrument

背景吸入给药是慢性呼吸道疾病患者常用的给药途径。患者使用吸入给药装置的能力是影响治疗效果的关键因素。最近国内研发了一种新型吸入用药定量评估仪器,可测量在附加多种不同吸入器内置阻力条件下的吸气峰流量(PIF)和吸气容积(VI),精准评估患者使用吸入器的能力。然而目前国内外尚无关于此类吸入评估仪器的质量检测方法和通过标准。目的对吸入用药定量评估仪器进行质量检测,评估其检测性能,探讨该方法的应用价值。方法通过新型吸入用药定量评估仪器PF810模拟不同干粉吸入器内置阻力,共分为5个不同档位(R1~R5),并采用标准流量/容积模拟器对PF810的流量、容积和阻抗性能进行测试。吸气流量测试取固定容积(3.000 L)、在不同流量(在0~2.000 L/s范围内,以0.250 L/s为间隔步进取值)状态下进行。V_(1)测试取低(0.500 L/s)、中(1.000 L/s)、高(1.500 L/s)3种流量,并在不同容积(在1.000~4.000 L范围内以1.000 L为间隔步进取值)状态下进行。采用GraphPad prism 9.0软件的Bland-Altman图法评价不同阻力档位下吸入用药定量评估仪器的PIF、VI测量值与模拟器输出的实际值之间的一致性。结果流量检测质量控制评估结果显示,流量检测重复度、准确度和线性度达到性能要求的百分率分别为100.00%(40/40)、95.00%(38/40)、94.29%(33/35)。R5档位1.500 L/s及以上流量下PF810准确度和线性度不符合性能检测要求,其余档位和流量下全部达标。Bland-Altman一致性检验可见,95%一致性界限(LOA)为(-0.271~0.107)L/s,96.00%(192/200)数据点在95%LOA范围内。容积检测质量控制评估结果显示,容积测试重复度、准确度和线性度的性能检测通过率均为100.00%(60/60、60/60、45/45)。Bland-Altman一致性检验可见,95%LOA为(-0.058~0.017)L,100.00%(180/180)数据点在95%LOA范围内。阻抗检测质量控制评估结果显示,吸入用药定量评估仪器PF810阻抗值与相应吸入器内置阻力之间的相对误差绝对值均<5%。结论本研究采用标准流量/容积模拟器对吸入用药定量评估仪器在附加不同档位吸入器内置阻力条件下的吸气流量与容积进行质量检测,方法简便可行,并可客观、科学地对该类型仪器进行性能评价与定期检测维护,值得应用与推广。

Background Administration of drugs by inhalation is a common route for the treatment of chronic airway diseases.The ability of patients to use an inhaler device is a key factor in the effectiveness of treatment.Recently,a new type of quantitative assessment instrument for inhalation drugs has been developed in China,which can measure peak inspiratory flow(PIF)and inspiratory volume(V_(1))under conditions with various internal resistance of inhalers,thereby accurately assessing the ability of patients to use inhaler.However,there are no quality testing methods and adoption standards for this type of instrument at home and abroad.Objective To perform quality testing of the inhalation drug quantitative assessment instrument and evaluate its technical performance,in order to explore the application value of the method.Methods Various internal resistance of dry powder inhalers(DPI)was simulated by the inhalation drug quantitative assessment instrument(PF810)in 5 different gears(R1-R5 from low to high).A standard flow/volume simulator was used to test the flow,volume and impedance performance of the PF810 for inhalation.The flow test was performed at a fixed volume(3.000 L)and different flow rates(in the range of 0-2.000 L/s,with 0.250 L/s as the interval stepwise).The volume was carried out at three flow rates of low(0.500 L/s),medium(1.000 L/s)and high(1.500 L/s),and at different volumes(1.000 L as the interval stepwise in the range of 1.000-4.000 L).The Bland-Altman analysis chart method of GraphPad prism 9.0 software was used to evaluate the consistency of PIF and VI measurements of the inhalation drug quantitative assessment instrument with the actual values output by the simulator at different resistance gears.Results The results of quality control evaluation of flow detection showed that the percentages of repeatability,accuracy and linearity of flow detection meeting the performance requirements were 100.00%(40/40),95.00%(38/40)and 94.29%(33/35).The accuracy and linearity of PF810 at R5 gear 1.500L/s and above did not meet the performance testing requirements,while those of other gears and flow rates met the requirements.The Bland-Altman consistency test showed 95%limit of agreement(LOA)of(-0.271-0.107)L/s,with 96.00%(192/200)data points within the 95%LOA range.The results of volume test quality control evaluation showed that the pass rates of volume test repeatability,accuracy and linearity were all 100.00%(60/60,60/60,45/45).The Bland-Altman consistency test showed that 95%LOA was(-0.058-0.017)L,and 100.00%(180/180)data points were within the 95%LOA range.The impedance measurement quality control evaluation results showed that the relative errors between the impedance value of PF810 and the internal resistance of the corresponding inhaler were all<5%.Conclusion In this study,a standard flow/volume simulator was used to measure the quality of inspiratory flow and volume of the inhalation drug quantitative assessment instrument at different levels of internal resistance.The method is simple and feasible,can evaluate the performance of this type of instrument and regularly detect and maintenance it objectively and scientifically,which was worthy of application and promotion.