我国原料药生产企业执行WHO GMP的评估工具验证

Validation of an assessment tool for evaluating the implementation of WHO GMP standards by Chinese manufacturers of active pharmaceutical ingredients(APIs)

目的:为客观评估我国活性原料药(active pharmaceutical ingredients,APIs)生产企业执行WHO GMP中的能力和现状,对评估工具进行验证,考察工具的信度(可靠性)和效度(准确性)。方法:根据设定标准,筛选国内3家APIs生产企业和9名GMP专家参与验证。对于每家企业,先后应用评估工具进行自我评价和GMP专家独立评估,比较3种(严重、主要和次要)缺陷差异,考察信度。对参与评估的GMP专家进行问卷调查和访谈,评价工具对WHO GMP标准覆盖的全面性和代表性,考察效度。收集和整理企业和专家对于评估工具改进建议。结果:企业自评和专家独立评估结果均显示,3家企业均无"严重"缺陷项。在自评中,企业A,B,C的"主要"和"次要"缺陷项数量分别是(2;9),(22;36),(3;8);在独立评估中,企业A,B,C的"主要"和"次要"缺陷分别是(3;12),(26;41),(4;9)。经统计学分析,企业自评和专家独立评估结果之间没有显著差异。专家访谈显示,9名专家均认为评估工具覆盖性良好,除4名专家认为4个评估指标有重复外,其余5名专家均认为代表性良好。企业和专家提出建议,对于指标重复、规定过细、缺乏操作性的情况进行改进。结论:经适宜企业和专家参与验证,认为该评估工具具有良好的信度和效度,能够测评我国APIs企业执行WHO GMP标准的差距和进度,在进行适当调整和完善后,可以在国内推广使用。

Objective： To validate the reliability and validity of an assessment tool developed by World Health Organization （WHO） and implemented in China. The assessment tool is used to measure the gaps and pro- gress of domestic manufacturers of active pharmaceutical ingredients （APIs） in implementing WHO Good Manufacturing Practice （GMP）. Methods： According to pre-set criterion, 3 domestic APIs＇ manufacturers and 9 GMP ex- pelts were chosen to participate in the validation activities. For each manufacturer, the assessment tool was applied by the self-assessment of manufacturers and the independent evaluation by GMP experts. Three types of observa- tions in terms of serious, major and minor were statistically compared to evaluate reliability. The GMP experts who had completed the validation activities were surveyed by questionnaire and interviews on their opinions about the comprehensivity and representativity of the assessment tool for WHO GMP.standards to evaluate the validity. Suggestions given by manufacturers and experts for improving assessment tool were collected. Results： No ＂serious＂ observation was found among all 3 manufacturers. In the self-evaluation, the ＂major＂ and ＂minor＂ observations of manufacturers A, B, C were （2 ; 9）, （22 ; 36）, （3 ; 8） respectively. In the independent evaluation, the ＂ma- jor＂ and ＂minor＂ observations of manufacturers A, B, C were （3; 12）, （26;41）, and （4;9） respectively. Sta- tistical analysis indicated that there was no significant difference between the outcomes of self-evaluation and independent evaluation. In the expert interview, all the 9 experts considered that the assessment tool had good coverage. However, 4 experts thought that 4 indicators were repeated, and the remaining 5 experts thought that the tool had good representative. It was recommended that some aspects should be improved in terms of repetitive indicators of and micro-indictors, and lack of operability. Conclusion ： The assessment tool has satisfactory reliability and va- lidity, and can be used to evaluate the gaps and progress in implementing WHO GMP standard by the APIs＇ manufacturers in China. It can be promoted in China after appropriate adjustment and perfection.