眼科仿制药质量和疗效一致性评价的基本思路

Fundamental principles for assessment of the quality and efficacy of generic ophthalmic drugs

眼用制剂作为局部给药的外用制剂,仅在眼部起效,一般要求不得进入系统循环并发挥全身作用,故其难以通过传统的药动学方法,以测定血中的药物浓度并比对的方式来评价仿制药与参比制剂之间的生物等效性(BE);如果采用眼内房水中的药物浓度来进行眼用制剂的生物等效性评价,也因为房水取样量有限,难以多次取样,存在医学伦理问题而难以推广。目前国内外产、学、研各界均在积极探求对眼科药物这种给药途径特殊的无明确BE评价方法的复杂仿制药的可替代的体内/外生物等效性评价方法。本文根据眼用制剂的剂型原理、药物起效部位(眼表、眼内)差别以及药物本身作用机制的区别,汇总了ICH主要成员国当前对眼用制剂生物等效性评价方法的技术要求,并探索基于Q3的眼科药物的in vitro BE试验等评价手段,来扩展眼科药物的一致性评价的思路和方法。

As external drug products for topical administration,ophthalmic drug products only work in the eye,and generally do not enter the system circulation and exert a systemic effect. It is difficult to evaluate the bioequivalence between generic and brand drug products by traditional pharmacokinetic methods to determine the concentration of the drug in the blood and compare it. The method by using drug concentration in intraocular water to evaluate the bioequivalence of ophthalmic drug products,is also difficult to promote due to the limited volume of aqueous humor and the difficulty to sample for multiple times,and there are also ethical concerns. At present,the manufacture,academic,research and government at home and abroad are all actively exploring alternative in vivo/vitro bioequivalence evaluation methods for generic ophthalmic drugs. In this paper,based on the formulation principle of ophthalmic drug products,the difference between the active site of the drug( eye surface,intraocular)and the effect of the drug itself,the technical requirements for the current bioequivalence evaluation method of ophthalmic preparations in the main member states of ICH are summarized.