欧盟解释：标准和非标准工艺

EMA工艺验证指南2014版指出，根据申报工艺是不是标准工艺，来确定上市申报资料中是否需要生产规模的验证数据（工艺验证批），指南中还列出了哪些是非标准工艺，如下：
Annex II: Standard/non-standard processes

附录2：标准/非标工艺

For the purposes of this guideline the designation of a process as non-standard is determined by a combination of the nature of the active substance, the nature of the finished product, the actual process itself and the production experience of the manufacturer. All biological products are considered to be non-standard.

本指南中说明了一个工艺是否作为非标工艺取决于活性物质的特性、制剂的特性、实际工艺本身、生产商的生产经验综合因素。所有生物制品均应作为非标工艺。

The following categories are examples of products or processes which could be considered as nonstandard, and for which production scale validation data should be provided in the marketing authorisation application dossier unless otherwise justified:

以下是一些可能会被认为是非标工艺的类型例子，这些情形下，除非另有论述，否则在上市申报资料中，需要提供生产规模的验证数据：

1. the manufacture of specialised pharmaceutical dose forms;

特殊药品剂型的生产

2. the incorporation of some new technology into a conventional process;

一些新技术与传统工艺的结合

3. (highly) specialised processes involving new technologies or an established process known, or likely, to be complex and therefore to require particular care;

涉及新技术的特殊工艺，或已知工艺，或很可能比较复杂因而需要特别注意的工艺

4. non-standard methods of sterilisation.

非标灭菌方法

In addition a manufacturing process type not previously approved for pharmaceutical products within the EU is usually considered a non-standard process.

如果一种药品的生产工艺类型之前在欧盟没有被批准过，一般会被认为是一个非标工艺。

1. Specialised pharmaceutical dose forms 特殊的药品剂型

A non exhaustive list of types of products which might be considered as “specialised” is provided below for illustrative purposes:

以下是可能被作为“特殊”工艺对待的产品类型的不完全清洁，仅供帮助理解

—       preparations for metered dose inhalation in the lungs e.g., pressurised metered dose inhaler (MDI’s) and dry powder inhalers (DPI’s);

—       定量吸入喷雾剂，例如，压力喷雾剂MDI和干粉喷雾剂DPI

—       suspensions, emulsions or other liquid dispersed sterile products;

—       混悬剂、乳膏剂或其它液体分散无菌产品

—       modified release preparations;

—       改释制剂

—       unit dose products containing drugs in low content (≤2% of composition);

—       低含量单元剂量药物（≤组分的2%）

—       other specialised dose forms e.g., parenteral depot preparations based on biodegradable polymers, liposomal preparations, micellar preparations, nanoparticulate preparations.

—       其它特殊剂型，例如，采用可生物降解的聚合物制剂的非肠道给药、脂质体凝胶剂、胶束制剂、纳米制剂

2. Conventional pharmaceutical processes incorporating new technologies 传统药品工艺与新技术相结合

A conventional process is well established and approved, and could, for example, include such activities as tabletting using wet granulation. However, the introduction of a new technology into such a conventional process e.g., a new drying technology not commonly used by the pharmaceutical industry, might result in the need for full-scale validation data based on a case-by-case consideration of the product and process development studies.

建立的很好并经过批准的传统工艺包括，例如，湿粒压片。但是，引入新技术到传统工艺中，例如，不常用于制药行业的新的干燥技术，可能会需要根据各案实际产品和工艺研发情况进行全批量验证。

3. Specialised processes or established processes known to be complex 特殊工艺或已知复杂的工艺

—       processes with critical steps such as lyophilisation, microencapsulation;

—       具有例如冻干、微囊等的关键步骤的工艺

—       processes where the physicochemical properties of the active substance or a key excipient (e.g., lubricant, coating agent) may give rise to processing or scale-up difficulties, or stability problems during manufacture at larger scale;

—       活性物质或关键辅料（例如，润滑剂、包衣剂）理化特性可能会增加工艺难度，或使批量放大产生困难，或在更大批量生产时有稳定性问题

—       aseptic processing.

—       无菌工艺

4. Non-standard methods of sterilization 非标灭菌方法

—       terminal sterilisation by moist heat using conditions other than pharmacopoeial reference conditions;

—       采用非药典对照条件下湿热终端灭菌

—       terminal sterilisation by irradiation using less than 25 KGy.

—       采用不超过25千戈瑞终端辐射灭菌

可以好好讨论一下的。