【讨论】FDA关于混粉取样的进展问答
发布于 2014-01-26 · 浏览 1.9 万 · IP 河北河北
这个帖子发布于 11 年零 102 天前，其中的信息可能已发生改变或有所发展。
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 FDA recently announced the withdrawal of its draft guidance for industry on Powder Blends and Finished Dosage Units — Stratified In-Process Dosage Unit Sampling and Assessment.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FDA’s major concern was that Sections V and VII of the withdrawn draft guidance no longer represented the Agency’s current thinking, as explained below.
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.
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 211.110 Sampling 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.1
References:
FDA’s major concern was that Sections V and VII of the withdrawn draft guidance no longer represented the Agency’s current thinking, as explained below.
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.
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 211.110 Sampling 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.1
References:
- FDA CGMP regulations: 21 CFR 211.110; 211.160; 211.165. Available at:http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRsearch.cfm?CFRPart=211
Contact for further information:
Karthik Iyer, Consumer Safety Officer
CDER/OC/OMPQ/RSIPT
Karthik.Iyer@fda.hhs.gov
CDER/OC Office of Manufacturing and Product Quality: CGMP Subject Matter Contacts
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm096102.htm
Date: 8/6/2013
最后编辑于 2022-10-09 · 浏览 1.9 万
40 97 5
