Hi All, I need your opinions or the best practice for the following situation:
our process for consecutive batches of the same product on a tablet press involves, vacuuming and brushing off of gross residue between batches, then at the end of the consecutive runs of the same product the equipment is thoroughly cleaned and sanitized prior to processing batches of different product (Product runs can be as long as 3 weeks). Since this facility does not work over the weekend, the equipment is vacuumed and brushed off prior to the end of business on fridays, the press itself is enclosed and the ancillary equipment is covered with plastic sheeting and then production starts back up on Mondays. There are times that the equipment sits longer prior to production starting back up (long weekends, power failures, etc), 5 days maximum so far. The question is about Dirty Hold Time: It is my understanding that Dirty Hold Time relates to how many days that the equipment may remain dirty before receiving its full clean prior to going to a different product but does the dirty hold time relate in any way to in-process hold time? I would appreciate any opinions or best practices on this matter or point me to any references.
I’ve tried to convince operations to do a full clean when they know that no product is to be processed for a while even if they are planning to make the same product but so far this advice has gone unnoticed.
FYI: Our product is a dry powder and does not create a residue on the equipment and the equipment cleans easily.
The dirty hold time should include in-process hold time also. Ideally speaking dirty hold time of equipment should be considered from start of the batch itself (as equipment gets contaminated once you charge the product). That means dirty hold time shall be equal to process time + in-process hold time + uncleaned equipment hold time.
Dirty hold time is critical as residue with moisture (Wet Granulation stage )will proliferate the microbes in 24 hrs . preferably I hope it was be dirty equipment shall be cleaned with in 24 hrs however DHT can be accessed for 72 hrs for micro. DHT shall be decided based on findings.Exceptionally if it is more then shall be addressed through Risk assessment
Thanks for providing this information here.
Are we have to include process time in dirty hold time ,
I think dirty hold time is nothing but effect of environmental conditions on perticuler meterial or equipment when it is in idle & dirty condition , is it or not.
dirty equipment hold time not only include the effect of environmental conditions on peculiar material or equipment. it gives u an idea that after completion of batch how much time i can keep my equipment with out cleaning, samples you are taking after cleaning only means your cleaning procedure is well able to remove the product traces efficiently even after holding for certain (hold time).
but take care as regulatory is now looking at RS also.
We measure dirty hold time from the end of processing on a piece of equipment to start of cleaning (first charge of cleaning fluid). The FDA supports this definition in their 1993 cleaning validation guidance…“identifying and controlling the length of time between the end of processing and each cleaning step.” Although in practicality, the processing time measurement noted by satishsattu1, is an appropriate consideration especially if the processing far exceeds routine processing steps. I say this because during normal processing the dwell time is consistent and, by default, included in how we measure dirty hold times.
In terms of your issue with the weekend or maximum 5 day dirty hold time within the same product, I would do the practical suggestion of ensuring the equipment is visually clean prior to starting back up. If the vacuuming and brush off acheives the visually clean criteria, that should be sufficient and meets the 1993 FDA guidance of visually clean between the same product.
by the term ‘dirty hold time’ i understand the time upto which we can hold the dirty equipment and use it for next batch of same product without cleaning. Thus, if in my facility dirty hold time is 24 hours, it means i can use that equipment for the same product within 24 hours, after 24 hrs i have to reclean it.
now my question is if this is correct then for a facility having multiproducts (tablets and capsules), then how to perform the dirty hold time study? currently we are doing the study by processing the equipment with lactose and then holding it for a specified time say 72 hrs. is this method correct or we have to perform the study product wise?
secondly how to select the equipment or do we need to perform on all equipments?
The concepts of “clean-hold time” and “dirty-hold time” have been part of cleaning validation since its inception.
Clean hold time is generally considered to be the time between the completion of cleaning and the initiation of the subsequent manufacturing operation.
Dirty hold time can begin when the clean equipment is initially soiled, but more often is defined as the time between the end of manufacturing and the beginning of the cleaning process.
Both the hold times are to be evaluated during the cleaning validation. There is no fixed time periods given by any regulatory guideline. In general practice it is to clean immediately, but hold the clean equipment and have with 'Clean/ Rinse before use.It depends up on how many days you write in your SOP’s.
This “dirty” hold time has to be defined according to the property of products used during manufacturing and so no fixed time can be given. The cleanability may change based on the risk of microbiological contamination or degradation of the soiled products on the equipments.
For establishing dirty hold time for an equipment you have to coduct the validation study in respect to microbiological bio-burden. the microbiological sample shall be collected at different time i.e. at 76 and 96 hours.