Brazilian Health Surveillance Agency (Anvisa), Division of Bioequivalence, Brazil.
J Pharm Sci. 2011 May;100(5):1628-36. doi: 10.1002/jps.22413. Epub 2011 Jan 21.
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing levofloxacin as the only active pharmaceutical ingredient (API) are reviewed. According to the current Biopharmaceutics Classification System, levofloxacin can be assigned to Class I. No problems with BE of IR levofloxacin formulations containing different excipients and produced by different manufacturing methods have been reported and hence the risk of bioinequivalence caused by these factors appears to be low. In addition, levofloxacin has a wide therapeutic index. On the basis of this evidence, a biowaiver is recommended for IR solid oral dosage forms containing levofloxacin as the single API provided that (a) the test product contains only excipients present in IR levofloxacin drug products that have been approved in International Conference on Harmonization (ICH) or associated countries and which have the same dosage form; (b) both the test and comparator dosage form are "very rapidly dissolving" or "rapidly dissolving" with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8; and (c) if the test product contains polysorbates, it should be both qualitatively and quantitatively identical to its comparator in terms of polysorbate content.
审查了与豁免左氧氟沙星即时释放（IR）固体制剂体内生物等效性（BE）测试批准相关的文献数据，这些制剂仅含有左氧氟沙星作为唯一的活性药物成分（API）。根据现行的生物药剂学分类系统，左氧氟沙星可归类为 I 类。尚未报道含有不同赋形剂和采用不同生产方法的 IR 左氧氟沙星制剂的 BE 问题，因此这些因素引起的生物不等效风险似乎较低。此外，左氧氟沙星的治疗指数较宽。基于这些证据，如果 IR 固体制剂仅含有左氧氟沙星 API，且（a）测试产品仅含有已在国际人用药品注册技术协调会（ICH）或相关国家批准的 IR 左氧氟沙星药物产品中存在的赋形剂，且具有相同的剂型；（b）测试和比较剂型在 pH 值为 1.2、4.5 和 6.8 时均具有“速溶”或“快速溶解”特征，且显示相似的溶解曲线；（c）如果测试产品含有聚山梨酯，则其聚山梨酯含量应在质量和数量上与比较制剂完全相同，则可豁免 BE 测试。
