FDA-cGMP 问答系列
15. FDA recently announced the withdrawal of its draft guidance for industry on Powder Blends and Finished Dosage Units — Stratified In-Process Dosage Unit Sampling and Assessment. What were the Agency’s major concerns with this guidance?
FDA最近公布的指导草案的行业撤出的混合粉末和成品剂量单位-分层在进程剂量单位取样和评估。什么是该机构的这一指导重大关切？
FDA’s major concern was that Sections V and VII of the withdrawn draft guidance no longer represented the Agency’s current thinking, as explained below.
FDA的主要问题是，部分第五部分和第七部分撤回指南草案不再代表该机构当前的想法，解释如下。
Section V (Exhibit/Validation Batch Powder Mix Homogeneity) recommended that at least three replicate samples be taken from at least ten locations in the powder blender, but that only one of the three replicates be evaluated to assess powder blend uniformity. The Agency currently recommends that all replicate samples taken from various locations in the blender be evaluated to perform a statistically valid analysis. This analysis can demonstrate that variability attributable to sample location is not significant and that the powder blend is homogenous. Statistical tools are available to ascertain both the number of replicates and the number of sampling locations across the blender that should be analyzed to conduct a valid analysis.
第五节（图表/验证批次粉料混合均匀性）建议的至少在粉末混合器至少10个位置取三个重复样品，但只有对三个重复样品中的一个评估粉末混合物的均匀性。该机构目前正在建议，所有从搅拌机的不同地点采集的多个样品进行评估，以进行有效的统计分析。这种分析可以证明可归因于样品位置的变异是不显著并且该粉末混合物是均匀的。有可用的统计工具以确定整个搅拌机的重复样品数和采样位置数，及对其进行有效分析。
Section VII (Routine Manufacturing Batch Testing Methods) acceptance criteria designated to the Standard Criteria Method and the Marginal Criteria Method were based upon the limits published in the United States Pharmacopeia (USP) General Chapter <905> Uniformity of Dosage Units. However, the procedures and acceptance criteria in USP <905> are not a statistical sampling plan and so the results of the procedures should not be extrapolated to larger populations. Therefore, because the procedure and acceptance criteria prescribed in section VII provided only limited statistical assurance that batches of drug products met appropriate specifications and statistical quality control criteria, FDA no longer supports their use for batch release. Currently, there are several standard statistical practices (see references) that, if used correctly, can help to ensure compliance with the current good manufacturing practice (CGMP) regulations, including 21 CFR 211.110Sampling and testing of in-process materials and drug products, 21 CFR 211.160 General Requirements[Subpart I, Laboratory Controls],and 21 CFR 211.165 Testing and release [of the finished drug product] for distribution.
指定标准的判定方法和边际标准法第七条（日常生产批次测试方法）验收标准是根据发表在美国药典（USP）通则<905>的限制剂量单位的均匀性。然而，在USP <905>的程序和验收标准不是一个统计采样方案等的程序的结果不应该被推广到更广泛的人群。因此，由于在规定第七部分的程序和验收标准只提供了有限的统计保证药品的批次可满足适当质量标准和统计质量控制标准，FDA不再支持其用于批放行。目前，有几个标准统计方法（请参阅参考资料），如果正确使用，可帮助确保符合当前的良好生产规范（CGMP）的规定，其中包括21 CFR 211.110 取样和过程中的物料和药品的检验， 21 CFR 211.160 一般要求 [分部I，实验室控制]和21 CFR 211.65 测试和发运 [药品] 的放行。
粉末混合物均一性分析 [ASTM E2810-2011]
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发表于 2016-9-27 11:16:32
