请为我解惑：清洁前保存时间DHT和清洁后保存时间CHT

wildpant

APIC上说DHT是设备清洁前保存时间，我不是很理解，请高手解惑。
如果隔N批或譬如说20天彻底清洁一次的情形下，间隔的时间是否就是DHT，不管我N批的批间是否有进行小清或者是否间歇还是连续生产。

维塔斯Vitas

生产完成后到你清场的时间，就像你吃完饭到你洗碗的时间，是吃完就洗还是隔天再洗，吃完洗肯定要容易些，放半个月再洗早长霉、变质了，方法就不一定适用。

罗伊鲱

http://www.askaboutgmp.com/forum ... CEHT-and-DEHT-study

CEHT and DEHT study
    How to carry out Clean equipment hold time study in a pharmaceutical manufacturing faclity( formulation)? Is is required to take swab for active along with micro for the study period?
    How to carry out dirty equipment hold time study in a pharmaceutical manufacturing faclity( formulation)? How to make a sampling plan for this ?
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In my opininon if the cleaning validation is already done, then there is no need to perform the swab for active again. We performed swab for MLT immediately after cleaning and after holding the equipment in the area for the proposed hold period. Also we performed check for visually clean acceptance criteria immediately after cleaning and after hold for the proposed period.
In case of DEHT ,We performed check for bioburden , check for impurties after storage of the dirty equipment for the proposed hold time. Also here we established that the dirty equipment can be cleaned as per the same procedure specified in the cleaning sop after storage for the proposed period.
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Please check following references to understand more about CEHT and DEHT studies.
    Richard J. Forsyth, “Equipment Hold-Time for Cleaning Validation,” April 1, 2008; Pharmaceutical Technology (http://pharmtech.findpharma.com/pharmtech/Peer-Reviewed+Research/Equipment-Hold-Time-for-Cleaning-Validation/ArticleStandard/Article/detail/505369)
    T. Fugate, "Hold Time Studies: A Lost Parameter for Cleaning Validation," Journal of Validation Technology, 13 (3), 206-209, 2007.
    GXPandJVT.com Forums, “Cleaning validation equipment hold time,” (http://www.gxpandjvt.com/forum/forum_posts.asp?TID=115&PN=2&get=last)
    Joseph Pickett, “Dirty equipment holding time high risk with water left on equipment,” Validation Times, June, 2007 (http://findarticles.com/p/articles/mi_hb5677/is_6_9/ai_n29411135/)
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not much to add to the above references. As a general rule, after DEHT look for actives and degradation product, focusing on sticky, hygroscopic products, and equipment for wet or humid processing where caking is to be expected. CEHT is of microbiological concern.
One issue, which came up during a recent inspection, is the storage of the equipment. Although we have validated a DEHT of seven days, the inspectors did not accept that time. Their concern was that equipment stored dirty (in the dirty equipment storage area), even covered with stretch film, poses a cross contamination risk between stored dirty equipment, potentially passing the cleaning validation looking for one active but potentially contaminated with another active from neighbouring equipment, not considered in the cleaning validation. Although the risk seems low and the whole issue an "inspectional overshoot", we are now forced to clean the equipment immediately after use, and a DEHT of more than 24 hours is to be treated as a deviation and includes extensive sampling after cleaning, and equipment quarantine until approval.



补充内容 (2015-12-19 14:14):
http://www.pharmtech.com/equipment-hold-time-cleaning-validation

罗伊鲱

5.16.  Dirty  Holding  Time  is  defined  as  the  interval  between  use  and  cleaning  and  must  be
specified  in  the  protocol  and  validated
using  at  least  one  cycle.  If  the  validated  Dirty
Holding  Time  is  exceeded  a  risk  assessment  must  be  performed  and  if  necessary  the
equipment must be assessed for product and microbial contamination following cleaning.
5.17. Clean Holding Time is defined
as the interval between cleaning and use and must be
specified  in  the  protocol  and  validated.  If  the  Clean  Holding  Time  is  exceeded  the
equipment shall be cleaned again prior to use and verified as clean
http://www.gmpsop.com/sample/VAL ... uideline_sample.pdf

制药搬砖人

使用完毕到你清洁（不管是大清还是小清）之间的时间

xmango

连续生产的话就是连续生产结束再开始计算了，连续生产的原料药的连续生产批次应该是经验证的，验证时也要考虑清洁时间的问题

ansion851014

我们正在做DHT和CHT，二楼说的很对

wildpant

某某某 发表于 2015-11-10 12:51
使用完毕到你清洁（不管是大清还是小清）之间的时间

“使用完毕到你清洁（不管是大清还是小清）之间的时间”，按你的意思，如果我做了小清（简单冲洗），那DHT就是生产结束到小清开始的时间；如果我进行大清的话，DHT就是生产结束到大清开始的时间？是这样理解吗？意思是小清之前有小清的DTH，大清之前有大清的DTH吗？

windy

DHT:设备使用出空到开始清洁的间隔时间；
CHT:设备经过Full Cleaning后，设备保存的时限。

ztzhang

DHT，Dirty Holding Time, 是针对设备脏的状态下保持的时间。考察的目的是证明使用既定的清洁方法（按你的这个case就是小清的方法）是否能清除残留物料在设备中放置N天后可能产生的化学生物杂质和污染。
需要明白的是，清洁验证，不管是哪种，目的都是考察清洁方法的有效性。那么前提是要搞清楚，各种清洁方法，小清，大清的目的是清除什么东西。残留在设备内的又是什么东西。不要一味的去套，人家做什么验证，你也做什么验证。有时候是不需要的，有时候是不够的，有时候是不适用的。需要按照实际情况来。

wildpant

ztzhang 发表于 2015-11-10 14:40
DHT，Dirty Holding Time, 是针对设备脏的状态下保持的时间。考察的目的是证明使用既定的清洁方法（按你的 ...

请问”脏“该如何定义？

吾尔二思

wildpant 发表于 2015-11-10 15:05
请问”脏“该如何定义？

“脏”相对于“干净”，表示需要清洁的状态

wildpant

吾尔二思 发表于 2015-11-10 16:52
“脏”相对于“干净”，表示需要清洁的状态

呵呵，谢谢，我有点咬文嚼字了。我的看法是反向去定义吧，目检无可见异物是清洁的标准，那“脏”的定义必然是有可见异物了，这个异物应该包括产品和物料吧。

但是清洁的标准不只是无可见异物，还有残留符合限度要求，微生物符合限度要求等等，可见只要以上一个项目不符合就是脏了。

ztzhang

wildpant 发表于 2015-11-10 15:05
请问”脏“该如何定义？

就是设备用完没清洗之前的状态

罗伊鲱

"隔N批或譬如说20天彻底清洁一次"是另一种最差情况，也需要验证。当然也需要在SOP中规定最多允许连续生产的批次数。

yizhihaoyu

先想一下你要验证什么？你要验证是你的批间清洁后DHT还是你周期清洁完的保留时间？

瓶瓶罐罐

roadman 发表于 2015-12-18 20:21
5.16.  Dirty  Holding  Time  is  defined  as  the  interval  between  use  and  cleaning  and  must  ...

这个网站是一个付费网站么？怎么收费？

ThomasQ1

歇息楼主分享

winchetan

感谢二楼的正解

李洁12

CHT：clean  hold time
DHT:  dirty  hold   time