可互换多源药品（仿制药）等效性评价用参比制剂的选择指导原则（续）
（续）
3. General principles
The comparator product is defined as a pharmaceutical product with which the multisource product is intended to be interchangeable in clinical practice.
3、一般原则
参比制剂被定义为多源药品试图在临床实践中可互换的药品。
As a general principle, multisource products should comply with the same standards of quality, safety and efficacy as are applicable to the corresponding comparator product. In addition, quality attributes of a multisource product should be tested against the comparator product with which it should be interchangeable.
一般原则是，多源药品应符合与其参比制剂相同的质量、安全性和有效性标准。此外，多源药品的质量属性应该针对其试图可互换的参比制剂进行测试。
The selection of the comparator pharmaceutical product is usually made at the national or regional level by the national or regional regulatory authority.
通常，在国家或区域级别，由国家或区域监管机构选择参比制剂。
The innovator product is usually the most logical comparator product because its quality, safety and efficacy should have been well assessed in preand post-marketing studies and, in addition, the data on its safety and efficacy are usually linked to a pharmaceutical product with defined specifications for quality and performance. However, these products may not always be easy to obtain or may no longer be available on the market. The comparator product chosen is therefore often the most widely used product (market leader) or the product that was first introduced in that market. For this reason, among others, significant differences may exist between the comparator products used in different countries.
通常，创新药品是最合理的参比制剂，因为其质量、安全性和有效性已经在上市前和上市后研究中进行了充分评估，而且，其安全性和有效性数据通常来自具有明确的质量和性能规范的药品。但是，这些创新药品在市场上可能不易获得或可能已经停售。因此，经常是，选择的参比制剂是在市场上最广泛使用的药品（市场领导者），或者是最先在市场上推出的药品。因此，其中一些，不同国家的参比制剂可能存在显著差异。
In principle, a national regulatory authority has several options for selection of a comparator product. These are listed below in order of preference:
1. the innovator product for which quality, safety and efficacy has been established if this product has been granted a national marketing authorization (nationally authorized innovator);
2. national market leader product for which a national marketing authorization has been granted;
3. the WHO-recommended comparator product included in the International list of comparator products (1) or, if different and if it exists for the active pharmaceutical ingredient in question, the one suggested within the context of the Prequalification Team;
4. an innovator product approved by a stringent regulatory authority, i.e. a country associated to The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH);
5. a product that has been granted approval in an ICH-associated country;
6. in the case that no innovator or comparator product can be identified according to the above, the choice of the comparator should be made carefully and should be comprehensively justified by the applicant. In this case, the most important selection criteria in order of preference are:
–– prequalification by WHO,
–– extensive documented use in clinical trials reported in peerreviewed scientific journals,
–– a long and unproblematic period of post-market surveillance.
原则上，国家监管机构选择参比制剂的原则，按优先顺序排列如下：
1、创新药品，且质量、安全性和有效性已经确立，且已获得国家销售授权（国家批准的创新药品）；
2、全国市场主流药品，且已获得国家销售授权；
3、WHO推荐的参比制剂，包括在参比制剂国际目录[1]中，若药物活性成分不同或存在异议，按资格预审小组的建议；
4、创新药品，且已获得严格监管机构（例如ICH成员国）批准（ICH：指人用药物注册技术要求国际协调会）；
5、已在ICH成员国获得批准的药品；
6、若按上述条件仍不能确定创新药品或参比制剂，申请者应仔细、全面的证明参比制剂的选择。在这种情况下，最重要的选择标准，按优先顺序排列如下：
-WHO的资格预审；
-被记录广泛用于临床试验，且是同行评议的科学期刊报道的；
-上市后监测经历了很长时间而未出现问题。
Additionally, these comparators should conform to all appropriate compendial quality standards.
It is important to note that a product that has been approved based on comparison with a comparator product that has no national marketing authorization in the country which approved the multisource product, including the study for interchangeability, may or may not be interchangeable with currently marketed domestic products.
此外，这些参比制剂应符合所有相应的官方质量标准。
重要的是，要注意：一个多源药品若是基于与尚未在该国获得销售授权的参比制剂进行对比（包括可互换性研究）获得批准的，该多源药品与目前国内销售的药品可能可互换，也可能不可互换。
The choice of comparator product should be justified by the applicant.The country of origin of the comparator product should be reported together with the product’s lot number and expiry date. Consultation with the relevant regulatory authority before purchase of the comparator product is strongly recommended.
申请者应该证明其参比制剂的选择是合理的。应报告参比制剂的原产国、产品批号、有效期。强烈建议，在购买参比制剂前，咨询相关监管机构。
有关研究中使用的参比制剂选择的详细信息，按指导提交给WHO资格预审小组，见WHO网站药品信息（www.who.int/prequal）和WHO参比制剂文件[1]。
参考文献
[1]. Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: thirty-sixth report. Geneva: World Health Organization; 2002:Annex 11 (WHO Technical Report Series, No. 902).
[2]. Guidelines on registration requirements to establish interchangeability for multisource (generic) pharmaceutical products. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: forty-ninth report. Geneva: World Health Organization; 2014: Annex 7 (WHO Technical Report Series, No. 992).
[3]. Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: fortieth report. Geneva: World Health Organization; 2006: Annex 7 (WHO Technical Report Series, No. 937).
[4]. Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability. Revision. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: forty-ninth report. Geneva: World Health Organization; 2014:Annex 7 (WHO Technical Report Series, No. 992).
