EMA发布非蒸馏制WFI问答文件

GMP News

10/08/2016

EMA
publishes Q&A Document on Production of WFI not obtained by Distillation

EMA发布非蒸馏制WFI问答文件

The revision of the European Pharmacopoeia (monograph
0169) will introduce in Europe as of April 2017 the possibility to produce WFI
using other techniques than distillation - like in the USA and Japan. For
example, it will be allowed to produce WFI by reverse osmosis or ultrafiltration.
However, many questions are still unanswered like for example how the
robustness of the new procedure compared to distillation should be
demonstrated; that is to say how the procedural lower microbiological safety of
the membrane process should be compensated via further parameters. The now
published Paper "Questions and answers on production of water for
injections by non-distillation methods - reverse osmosis and biofilms and
control strategies" has been therefore highly anticipated.

EP各论0169修订自2017年4月起将非蒸馏技术WFI引入欧洲----像美国和日本一样。例如，它会允许采用反渗透方法或超滤方法制备WFI。但是，还是有一些问题悬而未决的问答，例如，新制备方法相比于蒸馏法的耐用性要如何证明，这就是说要如何通过更多的参数来证明新的膜过滤制备方法在程序方法能保证更低的微生物水平。现在出版的文章“非蒸馏方法制备注射用水问答---反渗透和生物膜及控制策略”是大家极度期盼的。

The document is composed of two parts. The first one
provides explanations for the use of reverse osmosis for the production of WFI
and the second one, instructions to control and avoid biofilms.

文章包括2部分。第一部分提供了使用反渗透法制备WFI的解释，第二部分是控制和避免生物膜的指导。

For the EMA, it is problematic that reverse osmosis is
usually operated at ambient temperature which is favourable for the formation
of a biofilm. The water system should thus be designed in such a way as to
minimise the risk of microbiological contamination. Here, the EMA quotes:

EMA认为，反渗透法通常在室温下运行，有利于生物膜的形成，这是一个问题。水系统的设计应该尽可能减少微生物污染的风险。这里引用EMA的话来说：

• Suitability of the materials composing the water system (not
  reactive, additive or absorptive)
• 水系统的组成材料持续能力（不会发生反应、释放或吸收）
• Suitability of the system for the routine steam sanitisation/chemical
  sanitisation
• 常规蒸汽消毒/化学消毒系统的持续能力
• Appropriate pre-treatment of raw water encountering the large
  membrane surface of the reverse osmosis
• 对大面积反渗透膜表面会接触的原水进行适当的预处理
• Suitability of the membranes of the reverse osmosis for routine high
  temperature sanitisation
• 日常高温消毒下反渗透膜的持续能力
• Further developments of resistant membranes should be considered and
  implementable in the system
• 应考虑在进一步开发防腐膜并在系统中使用
• Additional use of other techniques like nanofiltration,
  electro-deionisation or ultrafiltration
• 其它技术的附加应用，如纳滤、电去离子或超滤
• Binding use of on-line TOC and on-line conductivity measuring points
  in the system
• 在系统中绑定应用在线TOC和在线电导测量点
• Trending of the measurement data
• 测量数据趋势分析
• Appropriate chemical disinfectants, named are: peracetic acid, sodium
  hypochlorite, hydrogen peroxide
• 适当的化学防腐剂，名称有：过氧乙酸、次氯酸钠、过氧化氢
• Ozone should additionally be used for sanitization
• 应附加使用臭氧来消毒
  

The paragraph describing the qualification of such a
water system contains - by contrast - few concrete instructions. In the
following paragraph, the document addresses sampling during qualification and
operation. A sentence of the next paragraph is particularly interesting: It
mentions the use of rapid microbiological methods as a prerequisite to the
control strategy. The methods should include: rapid endotoxin testing and
alternative methods in line with Ph.Eur 5.1.6. For the EMA, preventative
maintenance - including of course regular inspections and replacing the
membranes of the reverse osmosis module - is utmost important.

与之相反，描述此类水系统确认的段落则只有很少具体的指导。在后续段落中，文件讲了确认期间和运行期间的取样。下一段的一句尤其有意思：它提到了使用快速微生物检测方法作为控制策略的前提。方法应包括：快速内毒素检测和符合EP 5.1.6的可替代方法。EMA认为，预防性维护---包括定期检查和更换反渗透膜模块---都是非常重要的。

The second part of the paper which is more comparable
to an article than a guidance document provides basic information on biofilms,
e.g. what is a biofilm and which strategies can help avoid or minimise the
spreading of a biofilm. Here, the document lists general elements like design
of the water system, monitoring, qualification and CAPA system, without any
further explanation. Indications to remove a biofilm are provided: chemical and
physical. Furthermore, the document explains that it may be difficult to remove
an already existing biofilm from the system. That's why here again the use of
rapid microbiological methods is mentioned as it allows to react more rapidly
to first microbiological impurities before a biofilm can be formed.

文章的第二部分则更象一份指南，提供了关于生物膜方面的基本信息，例如，什么是生物膜，哪些策略有助于避免或最小化生物膜的蔓延。文章在这里列出了一些通用要素，如水系统设计、监测、确认和CAPA系统，没有任何深入解释。提供了清除生物膜的指导：化学法和物理法。文章还解释说要从系统中清除已经存在的生物膜可能会很困难。这就是为什么要使用快速生物检测法的原因，因为它让公司在生物膜形成之前可以更快速地对于第一个微生物杂质采取行动。

The paper can be commented on until 4 November. The Q&A document on
the production of WFI by membrane procedure can be found on the EMA website.

草稿征求意见截止时间为11月4日。在EMA官网上可以下载全文。

来源;http://zhuyujiao1972.blog.163.com/blog/static/986947272016711112058845/