可互換多源藥品（仿制藥）等效性評(píng)價(jià)用參比制劑的選擇指導(dǎo)原則（續(xù)）
（續(xù)）
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、一般原則
參比制劑被定義為多源藥品試圖在臨床實(shí)踐中可互換的藥品。
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.
一般原則是，多源藥品應(yīng)符合與其參比制劑相同的質(zhì)量、安全性和有效性標(biāo)準(zhǔn)。此外，多源藥品的質(zhì)量屬性應(yīng)該針對(duì)其試圖可互換的參比制劑進(jìn)行測(cè)試。
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，在國(guó)家或區(qū)域級(jí)別，由國(guó)家或區(qū)域監(jiān)管機(jī)構(gòu)選擇參比制劑。
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，創(chuàng)新藥品是最合理的參比制劑，因?yàn)槠滟|(zhì)量、安全性和有效性已經(jīng)在上市前和上市后研究中進(jìn)行了充分評(píng)估，而且，其安全性和有效性數(shù)據(jù)通常來(lái)自具有明確的質(zhì)量和性能規(guī)范的藥品。但是，這些創(chuàng)新藥品在市場(chǎng)上可能不易獲得或可能已經(jīng)停售。因此，經(jīng)常是，選擇的參比制劑是在市場(chǎng)上最廣泛使用的藥品（市場(chǎng)領(lǐng)導(dǎo)者），或者是最先在市場(chǎng)上推出的藥品。因此，其中一些，不同國(guó)家的參比制劑可能存在顯著差異。
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.
原則上，國(guó)家監(jiān)管機(jī)構(gòu)選擇參比制劑的原則，按優(yōu)先順序排列如下：
1、創(chuàng)新藥品，且質(zhì)量、安全性和有效性已經(jīng)確立，且已獲得國(guó)家銷售授權(quán)（國(guó)家批準(zhǔn)的創(chuàng)新藥品）；
2、全國(guó)市場(chǎng)主流藥品，且已獲得國(guó)家銷售授權(quán)；
3、WHO推薦的參比制劑，包括在參比制劑國(guó)際目錄[1]中，若藥物活性成分不同或存在異議，按資格預(yù)審小組的建議；
4、創(chuàng)新藥品，且已獲得嚴(yán)格監(jiān)管機(jī)構(gòu)（例如ICH成員國(guó)）批準(zhǔn)（ICH：指人用藥物注冊(cè)技術(shù)要求國(guó)際協(xié)調(diào)會(huì)）；
5、已在ICH成員國(guó)獲得批準(zhǔn)的藥品；
6、若按上述條件仍不能確定創(chuàng)新藥品或參比制劑，申請(qǐng)者應(yīng)仔細(xì)、全面的證明參比制劑的選擇。在這種情況下，最重要的選擇標(biāo)準(zhǔn)，按優(yōu)先順序排列如下：
-WHO的資格預(yù)審；
-被記錄廣泛用于臨床試驗(yàn)，且是同行評(píng)議的科學(xué)期刊報(bào)道的；
-上市后監(jiān)測(cè)經(jīng)歷了很長(zhǎng)時(shí)間而未出現(xiàn)問(wèn)題。
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，這些參比制劑應(yīng)符合所有相應(yīng)的官方質(zhì)量標(biāo)準(zhǔn)。
重要的是，要注意：一個(gè)多源藥品若是基于與尚未在該國(guó)獲得銷售授權(quán)的參比制劑進(jìn)行對(duì)比（包括可互換性研究）獲得批準(zhǔn)的，該多源藥品與目前國(guó)內(nèi)銷售的藥品可能可互換，也可能不可互換。
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.
申請(qǐng)者應(yīng)該證明其參比制劑的選擇是合理的。應(yīng)報(bào)告參比制劑的原產(chǎn)國(guó)、產(chǎn)品批號(hào)、有效期。強(qiáng)烈建議，在購(gòu)買參比制劑前，咨詢相關(guān)監(jiān)管機(jī)構(gòu)。
有關(guān)研究中使用的參比制劑選擇的詳細(xì)信息，按指導(dǎo)提交給WHO資格預(yù)審小組，見WHO網(wǎng)站藥品信息（www.who.int/prequal）和WHO參比制劑文件[1]。
參考文獻(xiàn)
[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).
