Hello,
Can anybody give me some pointers on setting up a validation plan for an assignment I have to do to complete my education?
Our cleaning methods are validated but in addition I need to define Clean hold time and dirty hold time for the multi pupose equipment used in our biotech downstreamprocessing plant.
I’m having trouble finding rules and regulations, specifically for hold times.
In other words, I don’t know where to start.
Kind regards,
Jerome
Typically hold times are based on manufacturing needs. So first see what a reasonable hold time for manufacturing would be. Dirty hold times may also be influenced by the nature of residual component(s). It might only be possible to hold a certain residue for a given period time without impacting the effectiveness of the cleaning cycle. Therefore, coupon studies may be needed to challenge the exiting cleaning process against different hold times or even field studies. As far as post-clean-hold times, this is dependent on a number of factors, mainly storage conditions and room qualification.
Again these are just my thoughts
Hope this helps…
[quote=PVAL]Typically hold times are based on manufacturing needs. So first see what a reasonable hold time for manufacturing would be. Dirty hold times may also be influenced by the nature of residual component(s). It might only be possible to hold a certain residue for a given period time without impacting the effectiveness of the cleaning cycle. Therefore, coupon studies may be needed to challenge the exiting cleaning process against different hold times or even field studies. As far as post-clean-hold times, this is dependent on a number of factors, mainly storage conditions and room qualification.
Again these are just my thoughts
Hope this helps…[/quote]
I am new to this site. I want to quote my own opinion regarding the CEHT and DEHT.
you should establish Clean Equipment Holing time by every day studing the microbial limit after you cleaned your equipment until the limit will exceeds. The day or hour till the equipment passes the limit will be your Clean Equipment Holding Time.
Whereas, I believe that you should establish a system that will enhance cleaning of the equipment immediately after processing is completed. Because keeping equipment dirty is a bad practice and I believe that validating a bad practice is not a good practice.
Hi,
Dirty Equipment Hold Time study - is required to establish the time frame limit for cleaning of the equipment after completion of process. It proves that the cleaning procedure is effective to remove all traces (previous product, detergents (if used) & Microbial cotamination) after keeping a long time ideally. The aim of this study is the traces on the equipment are sticked and difficult to clean, when u keep the equipment for hold. So, it proves that ur cleaning procedure is effective than ur ideal conditions. Normally it will be established thru validation study, under considerations of shift changes, holidays and non availability of man power in some sifts.
Clean Equipment Hold Time study - is required to establish the time frame limit for using of equipment after completion of cleaning. It is based on Microbiological conditions. Facility / Room qualification and environmental monitoring are additional backup data for CEHT.
So, the both studies should be done along with cleaning validation
Cleaned equipement holdtime study (CEHT) is basically time based microbiological sampling & testing. Cleaned equipments are resticted from further use & kept under the predetermined storage evironment (cross contamination is avoided). Microbiological sampling is carried out starting from 0 to several days untill the test result reaches the preestablished acceptance limit (alert limit) or prity near to it. The day in which the result will be close to alert level, is the CEHT.
But in case of studying dirty equipment holtime (DEHT), the knowledge about API & its degredated components are also very importent. The analytical method shall be developed & validated on the assay of likelihood degredated component(s). The chemical & microbiological sampling shall be carried out in this regards. DEHT study also validate the robustness of the cleaning method for removal of dried materials from equipment surfaces.
Practically, in a multiproduct facility only one or two products can be identified to conduct holdtime study considering their chemical & microbiological characteristics. Similarly one or two representative equipments or utensils can be identified among long equipment list. This will reduce the burden of cleaning holdtime study in a scientific & logical way.
Hello;
How many cycles of cleaning is necessary to verify the dirty equipment holding time? It is necesary 3 cycles or with one cycle of cleaning is enough.
Kind regards
3 cycles should be considered.
Hello!
Before starting a shift cleaning is required and validate it through testing quality control for contaminated chemicals (as dirt) and microbial contamination (as microbial contamination). Simulteniously after completion that shift cleaning also is required and validate it through testing quality control for contaminated chemicals (as dirt) and microbial contamination (as microbial contamination).
Except of the above cycle, cleaning is required of any equipment after completion of process and through swab test by quality control will be opted that no-contamination should be there.
Environmental microbial study will be require per week to find out why and from where microbial contamination will be occure? It is require to find out the burden of cleaning holdtime study in a scientific & logical way.
Tuhin Saha
(iamtuhins)
DEHT- After processing the equipment considered as dirty shall not remaon as such uncleaned more than 24 hrs or as validated but any case NMT 48hrs. Specially to avoid micro proliferations
CEHT- Cleaned equipments can stored as per validation , equipment shall remain with acceptable limit ( Micro)
In both cases logs / lables are mandetary
What shall be the requirements in case of API manufacturing facility where cleaning involves use of solvents?
Hey Sims,
The query of yours is the same of mine too. I had searched all the websites. All do point out towards the formulation. If anyone is there then please guide to what requirements is there in API manufacturing facility…
[quote=ravi238873]Hey Sims,
The query of yours is the same of mine too. I had searched all the websites. All do point out towards the formulation. If anyone is there then please guide to what requirements is there in API manufacturing facility…[/quote]
If the equipment system is dedicated, you should consider solvent and microbial residues. It the system is non-dedicated, you should consider residual of API, solvent and micrbial. You could get more insights by referring to information in the webpage,
http://apic.cefic.org/pub/4cleaningval9909.pdf
.
On each cleaning validation study DEHT to be doone ?
How much batches/ on which batches/ when to execute CEHT ?
What is periodic verification requirement for both ?
Thank you
Sandip V. patel
Typically, the DEHT and CEHT is over a long weekend (4 days). There is no guideline.
Hello,
I am quite new in cleaning validation topics, so I would like to ask you about the holding times.
How we should define the DHT and CHT? When we perform testing after 15days, 30 days and 60days, could you tell me which of those periods should be our holding time? The longest or the shortest?
Could you please let me know how to perform CHT and DHT testing? We would like to use swabbing methods, but my question is - how should I plan swabs collection? If I would like to validate 30days pareiod as our holding time, should I checked one equipment after 1 day, 15days and 30 days or three equipments after 30 days?
Many thanks for your help.
Hello,
I am quite new in cleaning validation topics, so I would like to ask you about the holding times.
How we should define the DHT and CHT? When we perform testing after 15days, 30 days and 60days, could you tell me which of those periods should be our holding time? The longest or the shortest?
Could you please let me know how to perform CHT and DHT testing? We would like to use swabbing methods, but my question is - how should I plan swabs collection? If I would like to validate 30days pareiod as our holding time, should I checked one equipment after 1 day, 15days and 30 days or three equipments after 30 days?
Many thanks for your help.
In the past, I have set the CEHT and DEHT (Clean And Dirty Equipment Hold Times) as 4 days or a long weekend. Do you ‘seriously’ expect production to be down for 60 days?
I have selected a ‘stainless steel’ drum or fill tank that is representative of my manufacturing process train, so that the entire train is not put out of action. It really depends on your cleaning procedure and it effectiveness cleaning ‘dirt’ or formulation.
The established time is the shortest of the 3 run validations.
For DHT and CHT, you can go about this 2 ways. Record the times that soiling, cleaning, and then use were done during cleaning validation activities. Then calculate the CHT and DHT.
Option 2 is to predict what CHT and DHT is required from a review of your manufacturing practices. Then design your study to match these. Record times soiled, cleaned, and then used, and make sure that they meet/exceed the CHT and DHT.
Option 3 is to establish a CHT and DHT time, but also to realise that this CHT and DHT might increase with further data and support. In this case, validate a CHT/DHT initially, but then create a proceedure to review data, hold product temporarily until data can be reviewed, if ever the CHT or the DHT is exceeded. This would be “continual review”. As your process matures, and you collect and analyze more data, then your CHT and DHT change accordingly.
Many thanks for your help.
One more question – how often should I check microbiological residuals on equipment surface in one validation run? If I know that the surface is clean 30days after cleaning, can I perform only one check?
I think so as long as you can justify the limits based on your specifications. Also, remember microbes to not spontaneously appear which means there has to be a source of contamination.