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摘要
The FDA withdrew the draft guidance document for industry "Powder Blends and Finished Dosage Units-Stratified In-Process Dosage Unit Sampling and Assessment." An FDA's primary concern was a lack of confidence that the results from USP < 905 > Uniformity of Dosage Units testing ensure the content uniformity of a batch. ISPE sponsored the Blend Uniformity and Content Uniformity Group (referred to as Group), which was formed in August 2013 to discuss approaches to assess blend and content uniformity. Modifications to the withdrawn draft stratified sampling guidance document are proposed by the Group for the assessment of adequacy of powder mix and content uniformity of the finished product in "Recommendations for the Assessment of Blend and Content Uniformity: Modifications to Withdrawn FDA Draft Stratified Sampling Guidance," accepted by J Pharm Innov, 2014. Specific statistical methodologies to construct acceptance criteria were not recommended in the paper. This paper provides an example and technical discussion of a statistical approach that can be inserted into the framework described in the Group's paper. There may be other approaches to sampling plans, statistical analysis, and acceptance criteria that are acceptable to demonstrate content uniformity. ASTM E2709, "Standard Practice for Demonstrating Capability to Comply with an Acceptance Procedure" and E2810, "Standard Practice for Demonstrating Capability to Comply with the Test for Uniformity of Dosage Units" for demonstrating dosage unit uniformity can be used to evaluate content uniformity. These standards are discussed and applied to the sampling plans given in the Group's paper. The method can provide with a high level of confidence that samples from a lot will have a high probability of passing the USP UDU test. The methodology can be used to evaluate content uniformity data based on a sampling plan that tests either one or more than one dosage unit from each of multiple locations throughout the lot. An acceptance limit table based on sample means and standard deviations can be generated that is easy for the user to apply to content uniformity results. Operating characteristic (OC) curves for process qualification and continued process verification/routine lot release sampling plans are presented and compared along with the USP UDU OC curve. The process qualification criteria/sampling plans are shown to be "conservative" compared to the USP UDU test. A two-stage tiered plan is shown that could be used during continued process monitoring/routine release. The ASTM E2709/E2810 methodology provides acceptance criteria for several sampling plans that could be used for the assessment of content uniformity during process qualification and continued process monitoring/routine release. Passing the acceptance criteria can assure with a high level of confidence that a lot can meet the USP UDU test.
- 出版日期2015-3
- 单位rutgers
