可互換多源藥品（仿制藥）等效性評價用參比制劑的選擇指導原則（WHO技術報告系列，992號）

發(fā)布于： 2016-03-18 22:14

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

可互換多源藥品（仿制藥）等效性評價用參比制劑的選擇指導原則

1、引言

2、背景

3、一般原則

參考文獻

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

近年來，對藥品質量監(jiān)管的要求不斷提高。大量多源藥品（仿制藥）由許多不同公司和不同國家生產，這可能市場上存在多種不同的產品。因此，在全球范圍內，不僅需要注意出口和進口多源藥品的質量、安全性、有效性，而且需要注意其可互換性。

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.

在過去，根據(jù)科學、監(jiān)管環(huán)境下的各種方法，考慮了發(fā)展國際參比制劑體系的可行性。最初，該建議發(fā)表于2002年，標題：可互換的多源藥品（仿制藥）等效性評價用參比制劑的選擇指導原則^[1]。該指導原則發(fā)表以來，世界衛(wèi)生組織（WHO）的基本藥物目錄（EML）已多次修改，目錄中的許多藥品不再銷售和/或不再收載，這意味著，WHO藥品制備規(guī)范專家委員會推薦的國際參比制劑目錄也需要更新。

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.

鑒于參比制劑目錄的復雜性，決定準備兩個新的、獨立的指導性文件：一個文件是參比制劑的選擇，包括如何選擇參比制劑的一般性指導原則；另一個文件是國際參比制劑目錄。這樣有利于更新和維護。

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

關于確立多源藥品（仿制藥）可互換性的注冊要求的指導原則^[2]，旨在向國家監(jiān)管機構和生產商提供關于多源藥品（仿制藥）在各自國家批準要求的建議。這些指導原則提供適當?shù)捏w內和體外要求，以保證多源藥品的可互換性。

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.

多源藥品應符合與創(chuàng)新藥品相同的質量、有效性和安全性標準。此外，應提供合理保證，以確保多源藥品和參比制劑是治療等效的、是可互換的。對于某些類別的藥品，例如，高水溶性化合物的非口服制劑，通過執(zhí)行藥品生產質量管理規(guī)范（GMP）并提供符合相關藥典規(guī)范的證據(jù)，就可以充分確保可互換性。

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.

該指導文件提供了此前公布的目錄^[1]的更新和關于參比制劑選擇的相應章節(jié)^[3,4]。

該信息還可以用于藥品采購。

表A8.1總結了參比制劑規(guī)范的發(fā)展歷程。

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A8.1參比制劑規(guī)范的發(fā)展歷程

年份	發(fā)展	簡介
1996之前	國際藥品監(jiān)管當局會議（ICDRA）（1991和1994）建議研究多源藥品可互換性的全球性標準和要求，WHO啟動該進程。	不存在任何選擇國際參比制劑目錄的規(guī)范，也不存在任何國際參比制劑目錄。選擇的參比制劑或者是在市場上最廣泛使用的（主要的）藥品，或者是h最先在市場上退出的藥品。因此，其中一些，可不同國家的參比制劑可能存在顯著差異。
1996	提出參比制劑選擇的問題。	多源藥品（仿制藥）：關于確立可互換性的注冊要求的指導原則（WHO技術報告系列，863號），附件9，包括附錄7關于“參比制劑選擇”。
2002	WHO發(fā)布可互換多源藥品（仿制藥）等效性評價用參比制劑第一個國際目錄。	可互換多源藥品（仿制藥）等效性評價用參比制劑的選擇指導原則（WHO技術報告系列，902號），附件11。
2006	澄清參比制劑選擇中的“優(yōu)先順序”原則	多源藥品（仿制藥）：關于確立可互換性的注冊要求的指導原則（WHO技術報告系列，937號），附件7。