Spino M, Tsang Y C, Pop R
Apotex Inc., Weston, Ontario, Canada.
Eur J Drug Metab Pharmacokinet. 2000 Jan-Mar;25(1):18-24. doi: 10.1007/BF03190051.
The WHO List of International Comparator Pharmaceutical Products (CPP) For Equivalence Assessment of Interchangeable Multi-Source (Generic) Products will address an important issue in developing new generic drugs because it will identify the 'correct' reference product. This list will reduce unnecessary clinical studies in jurisdictions requiring new generics to be compared with brand products sold locally. Eventually, by employing the CPP, there will be a world-wide standard for brand and generic drugs, assuring the same level of quality internationally. The strategy of a single global reference is meritorious, but there are several hurdles to overcome. Most important is that the same brand may differ in dissolution and/or bioavailability in various jurisdictions, including some drugs with a narrow therapeutic index like phenytoin. Several examples are provided in this manuscript. This issue of regional differences has relevance, not only to the WHO list, but also to the matter of how safety and efficacy was established for that product in the first place. Normally, phase III clinical studies are conducted on a product manufactured in a single site, set to one standard. If the product differs in bioavailability in different jurisdictions, one is left with the question: 'which product has remained true to the original formulation?' Alternatively, if safety and efficacy is maintained with all formulations, then one is faced with the question: 'are the criteria currently employed for bioequivalence unnecessarily restrictive?'
世界卫生组织国际比较药品清单（CPP）用于可互换多源（仿制药）产品的等效性评估，这将解决开发新仿制药过程中的一个重要问题，因为它将确定“正确的”参比产品。该清单将减少在要求新仿制药与当地销售的品牌产品进行比较的司法管辖区内进行的不必要的临床研究。最终，通过采用CPP，将形成全球范围内品牌药和仿制药的标准，确保国际上药品质量处于同一水平。单一全球参比的策略是值得称赞的，但仍有几个障碍需要克服。最重要的是，同一品牌在不同司法管辖区的溶出度和/或生物利用度可能存在差异，包括一些治疗指数较窄的药物，如苯妥英钠。本手稿中提供了几个例子。区域差异这个问题不仅与世界卫生组织清单相关，也与该产品最初如何确定安全性和有效性的问题相关。通常，III期临床研究是在按照单一标准在一个地点生产的产品上进行的。如果该产品在不同司法管辖区的生物利用度不同，就会产生一个问题：“哪种产品与原始配方一致？”或者，如果所有配方都能维持安全性和有效性，那么就会面临另一个问题：“目前用于生物等效性的标准是否过于严格？”
