关于API生产中使用的树脂再生的问题

beiwei5du

各位蒲友：

针对于API或者一些中药中使用到的树脂的问题，大家针对于树脂的再生，一般是依照什么指标和标准进行判定？？？这个大家是否进行过相应的验证？？？同时关于树脂的使用次数的规定大家是否制定？？还是根据树脂使用前的相应测试进行判定？？

下文选自<FDA GFI dug substances CMC information>

hongwei2000

应该是一个PQ的标准而没有必要是OQ的标准
只有适用于你的标的物的柱效才是最合适的
我想标准应该是case by case的
最主要是能够分离开你的标的物（对于有的填料可能是多种）和杂质

给我往死里整

层析柱的最大使用次数是需要有控制的: 具体的次数可以在研发，小试等阶段就收集相关资料。实际生产中可以通过观察收率，柱效，流穿峰等 及时调整。

zysx01234

感觉这个还是比较痛苦的。
我之前的企业就是对工艺进行改进，避开了使用柱子，再来报注册。

中华骏捷

英文看不懂，呵呵。

beiwei5du

zysx01234 发表于 2016-9-5 09:34
感觉这个还是比较痛苦的。
我之前的企业就是对工艺进行改进，避开了使用柱子，再来报注册。

但是很对厂家肯定会使用到柱子（特别对于中药企业），不知道大家是怎样管控的呢？？？

ygkl12

本人也正有这个问题，过程的酸洗和碱洗如何判断是否清洗干净。

ygkl12

光以后面冲洗出纯水的PH值或电导率作为判断，是不准确的。

beiwei5du

hongwei2000 发表于 2016-9-5 08:19
应该是一个PQ的标准而没有必要是OQ的标准
只有适用于你的标的物的柱效才是最合适的
我想标准应该是case b ...

Van Kley (Cambrex): Initially, the process is carried out in its current state using the conditions provided by our clients. This approach allows us to observe the chemistry and get a feel for how it performs. From there, the next stages of development investigate ways to reduce solvent volumes, increase yields, reduce cycle times, lower raw material costs, and lower waste costs. These steps are crucial to improving product quality and the economics of the process, which allows us to pass efficiencies and qualityon to our clients. Most of this work is undertaken in the chemical development laboratory prior to going into production. Once in production, the chemist and engineer assigned to the program will further work on optimization of the process based on observations made during production. In addition, our continuous improvement/six sigma group will also contribute to the optimization process once the program is in validation or commercial launch. The group will help in managing the lifecycle of the program along with looking at ways to continually improve the efficiency of production by data mining.

Typically, we will see programs that have chromatography steps within the process, high volume issues, filtration issues, and/or long cycle times. Our development efforts are centered on removal of any chromatography processes if present for scaling purposes, volume reductions, faster filtrations, and cycle time reduction, either for efficiency or the possibility of telescoping steps to reduce unnecessary isolation steps if the process lends itself.

选自《Optimizing API Manufacturing》http://www.pharmtech.com/optimizing-api-manufacturing-0

为什么会尽量避免使用chromatography process???到底是基于什么的想法？？？？？@Jason@zysx01234

Jason

能够用结晶方法来纯化产品，就不要用层析柱子来纯化，因为层析柱子成本高，层析柱子的验证及再生都是挑战的工作。还有废液的处理，流出的溶液要浓缩，又耗费能量，有的产品有温度的因素，要用LUWA low temperature thin film evaporator来浓缩！

beiwei5du

Generally in the production of pharmaceutical drugs, a large part of the production costs stem from the downstream processing. One important, time consuming and expensive downstream process in pharmaceutical manufacture is Active Pharmaceutical Ingredient (API) purification.  To date the processes preferably used for API purification include distillation, adsorption–desorption, solvent extraction, fractional crystallisation and chromatography. For difficult separations where tiny amounts of impurities need to be removed, purification primarily relies on crystallisation or chromatography in their various forms. Crystallisation unit operations are complex processes while process chromatography is expensive and consumes large quantities of solvents, which require further downstream processing. In addition chromatography is poorly suited for large scale and continuous process operations. Thus developing new continuous downstream processing operations is an attractive area for research and development.