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（WHO技术报告系列，992号）
Annex 8
Guidance on the selection of comparator pharmaceutical
products for equivalence assessment of interchangeable
multisource (generic) products
1. Introduction
2. Background
3. General principles
References
附件8
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
1、引言
2、背景
3、一般原则
参考文献
1. Introduction
In recent years the need for the regulation and assurance of quality of medicines has continued to increase. Large numbers of multisource (generic) medicines are being produced by many different companies and in different countries; this may result in different products. On a global level there is thus a need to address not only the quality, safety and efficacy of multisource products that are exported and imported, but also their possible interchangeability.
1、引言
近年来，对药品质量监管的要求不断提高。大量多源药品（仿制药）由许多不同公司和不同国家生产，这可能市场上存在多种不同的产品。因此，在全球范围内，不仅需要注意出口和进口多源药品的质量、安全性、有效性，而且需要注意其可互换性。
In light of the various approaches in scientific and regulatory environments, the feasibility of developing a system of international comparator products was considered in the past. This initiative led to the recommendations published in 2002 entitled, Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products (1). Since the guidance was published, the World Health Organization (WHO) Model List of Essential Medicines (EML) has been revised several times and many of the products originally listed are no longer marketed and/or available as indicated in the list, which means that the list of international comparators recommended by the WHO Expert Committee on Preparations for Pharmaceutical Specifications needs updating.
在过去，根据科学、监管环境下的各种方法，考虑了发展国际参比制剂体系的可行性。最初，该建议发表于2002年，标题：可互换的多源药品（仿制药）等效性评价用参比制剂的选择指导原则[1]。该指导原则发表以来，世界卫生组织（WHO）的基本药物目录（EML）已多次修改，目录中的许多药品不再销售和/或不再收载，这意味着，WHO药品制备规范专家委员会推荐的国际参比制剂目录也需要更新。
In view of the complexity of the list of comparators it was decided to prepare two new, separate, guidance documents: one on the selection of comparator products, including the general guidance on how to select comparator products, and the second one comprising the international list of comparator products. The aim was to facilitate the updating and maintenance process.
鉴于参比制剂目录的复杂性，决定准备两个新的、独立的指导性文件：一个文件是参比制剂的选择，包括如何选择参比制剂的一般性指导原则；另一个文件是国际参比制剂目录。这样有利于更新和维护。
2. Background
The Guidelines on registration requirements to establish interchangeability for multisource (generic) pharmaceutical products (2) are designed to provide recommendations to national regulatory authorities and manufacturers on the requirements for approval of multisource (generic) pharmaceutical products in their respective countries. The guidance provides appropriate in vivo and in vitro requirements to assure interchangeability of the multisource product.
2、背景
关于确立多源药品（仿制药）可互换性的注册要求的指导原则[2]，旨在向国家监管机构和生产商提供关于多源药品（仿制药）在各自国家批准要求的建议。这些指导原则提供适当的体内和体外要求，以保证多源药品的可互换性。
Multisource pharmaceutical products need to conform to the same appropriate standards of quality, efficacy and safety as those applicable to the innovator’s product. In addition, reasonable assurance should be provided that the multisource product is therapeutically equivalent and interchangeable with the comparator product. For some classes of products including, for example, parenteral formulations of highly water-soluble compounds, interchangeability is adequately assured by implementation of good manufacturing practices (GMP) and provision of evidence of conformity with relevant pharmacopoeial specifications.
多源药品应符合与创新药品相同的质量、有效性和安全性标准。此外，应提供合理保证，以确保多源药品和参比制剂是治疗等效的、是可互换的。对于某些类别的药品，例如，高水溶性化合物的非口服制剂，通过执行药品生产质量管理规范（GMP）并提供符合相关药典规范的证据，就可以充分确保可互换性。
This guidance document provides an update of the previously published list (1) and the respective chapter on selection of comparator products (3, 4).
The information could also be used for medicine procurement purposes. The historical development of comparator product criteria is summarized in Table A8.1.
该指导文件提供了此前公布的目录[1]的更新和关于参比制剂选择的相应章节[3,4]。
该信息还可以用于药品采购。
表A8.1总结了参比制剂规范的发展历程。
Table A8.1 Historical development of comparator product criteria
|
Year |
Development |
Description |
|
Pre-1996 |
International Conference of Drug Regulatory Authorities (ICDRA) (1991 and 1994) recommended development of global standards and requirements for interchangeability of multisource products; WHO initiated the process |
No agreement on the criteria for selecting a list of international comparator products or any list of such products exists. The comparator product chosen is either the most widely used (leading) product on the market or the product that was first introduced in that market. For this reason, among others, significant differences could exist between the comparator products used in different countries |
|
1996 |
The question of choice of reference product was raised |
Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability (WHO Technical Report Series, No. 863), Annex 9, including Appendix 7 on “Choice of reference product” |
|
2002 |
WHO issued the first list of International comparator products for equivalence assessment of interchangeable multisource (generic) products |
Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products (WHO Technical Report Series, No. 902), Annex 11 |
|
2006 |
“In order of preference” principle in comparator product selection was clarified |
Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability (WHO Technical Report Series, No. 937), Annex 7 |
表A8.1参比制剂规范的发展历程
|
年份 |
发展 |
简介 |
|
1996之前 |
国际药品监管当局会议（ICDRA）（1991和1994）建议研究多源药品可互换性的全球性标准和要求，WHO启动该进程。 |
不存在任何选择国际参比制剂目录的规范，也不存在任何国际参比制剂目录。选择的参比制剂或者是在市场上最广泛使用的（主要的）药品，或者是h最先在市场上退出的药品。因此，其中一些，可不同国家的参比制剂可能存在显著差异。 |
|
1996 |
提出参比制剂选择的问题。 |
多源药品（仿制药）：关于确立可互换性的注册要求的指导原则（WHO技术报告系列，863号），附件9，包括附录7关于“参比制剂选择”。 |
|
2002 |
WHO发布可互换多源药品（仿制药）等效性评价用参比制剂第一个国际目录。 |
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（WHO技术报告系列，902号），附件11。 |
|
2006 |
澄清参比制剂选择中的“优先顺序”原则 |
多源药品（仿制药）：关于确立可互换性的注册要求的指导原则（WHO技术报告系列，937号），附件7。 |
