We are looking for help in order to define the pressure cascade rationale between a primary packaging room a secondary packaging and the common adjacent corridor in an OSD facility (non highly potent). Please note that the primary and secondary packaging rooms are connected through the conveyor “mouse hole” and both rooms are accessed by a common clean corridor. For sure, we know that the common corridor should be in higher pressure than both packaging rooms, but what about the pressure difference between the two packaging rooms? There is a specific topic for this situation but for highly potent products in Annex 3 of WHO TRS 957, 2010, but i don’t believe this is applicable for non highly potent facilities. Can anyone please provide some guidance on the matter?
YOu are correct that the “highly potent facility” guide is not applicable here…if the product is truly non-highly-potent.
Pressure cascade protects 2 things. (1) The product and (2) The environment. When designing pressure cascade ask yourself both questions - do I need to protect the environment? and do I need to protect the product?
You stated that the product is OSD and non-potent. So that means you probably don’t need to protect the environment. Thus, Annex 3 of WHO TRS 957, 2010 is not perfectly applicable here.
Since this is a drug, you almost 100% need to project the product. So your air should flow away from the product, and you should isolate any activity which could cause a lot of particulate generation.
Because of this your cleanest area should be the primary packaging area. This is your product contact packaging, correct?
Also, you should isolate the secondary packaging area, where there might be cardboard, or other board, and paper inserts, etc.
Thus I would have the highest pressure in your primary packaging room, your lowest pressure in the secondary packaging room, and your medium pressure in the common corridor. In this way air will flow from the primary packaging room, to the clean room, and finally to the secondary packaging room.
Alternatively you could keep the common corridor and the secondary packaging room at the same pressure and use a “bubble” or a “sink” for an airlock. But this isn’t as good at having a cascade between the two areas.
Thank you very much for your response. However, please note that i am referring to a multiproduct OSD manufacturing site where different products are been packed at the same time, in different areas, with a common clean corridor. Correct me if i am wrong, but i believe that the pressure cascade should be such the direction of airflow is from the clean corridor into the primary packaging rooms, resulting in dust containment (prevent cross-contamination from one product to another).
I agree about the cross contamination consideration. That does change things. You did mention that it is non-potent and I took that a little too far. If cross contamination is a concern and you want somewhat segregated areas, then the principles mentioned in the highly-potent guidance will be more (but not fully 100%) applicable to your facility.
In this case many aspects of Annex 3 of WHO TRS 957, 2010 will be useful when designing your non-potent, but still segregated facility. But are you looking for a fully segregated facility, or just be somewhat cautious? It sounds like you are just being cautious. NOTE: Fully segregated facilities require a lot of precautions, while being somewhat cautious might require a different set of precautions.
If you are trying for being somewhat cautious, you might want to consider a single “sink” airlock into the manufacturing areas, and have the manufacturing area and the corridor at neutral pressure relative to each other. So basically the pressure would go 0 inH2O -> -5 inH2O -> 0 inH2O (corridor, airlock, processing room). The neutral pressure from corridor to processing room will keep air flow in neither into the area, nor out of the area. The “sink” airlock would keep both the contaminates and the product in the airlock. You might also want to change shoes covers, gloves, and an additional coverall when exiting the area. You might also consider wiping things down as they exit the area.
Also, you might need to look at sealing the room as much as possible, with correct ceiling tiles/clips, or a hard ceiling, and also good caulking of electrical outlets and wall penetrations. Be aware of air entering the plenum from the manufacturing area.
According to the old saying “A picture is worth a thousand words”.General Arrangement.pdf (87.8 KB)
This is our facility and what we are looking for. Thanks in advance.
Check out the following link pages 239-243
I noticed that your drawing does not have any airlocks. The examples given in the World Health Organization all have air locks.
Your secondary packaging I would make 15 Pa, this would keep any dust in the room.
For your primary packaging, check if you can squeeze in an airlock (similar to World Health Organization recommendation). If you cannot put in an airlock, then you have two options.
- Put the primary packaging at 15 Pa. This will keep the product in the room (help with cross contamination), but bring in other particles as well (hurt with product cleanliness)
- Put the primary packaging at 45 Pa. This will push product out of the room (hurt with cross-contamination), but will also push other particles out of the room (help with product cleanliness).
If you are more worried about cross contamination then go with 15 Pa, if you are more worried about product cleanliness then go with 45 Pa.
If you want something that can do both, then go with a “bubble” or “sink” but with an airlock for the primary packaging room. I don’t think you need an airlock with the secondary packaging room, just make that room 15 Pa (lower pressure compared to the clean corridor).
Thank you very much for your response.
Unfortunately the introduction of an airlock at this stage is not possible due to lack of space and budget. Regarding the two other options, please note below my concerns:
- Primary Packaging at 15 Pa. In this case the pressure of the primary and secondary packaging rooms will be equal, therefore, there is a risk that product from the primary packaging room may escape to the secondary packaging room. This is a personnel risk issue (non GMP) as the gowning rationale of the two rooms is not the same. Also, particles from the secondary packaging room may escape to the primary packaging room. This is a product risk (GMP).
- Secondary Packaging at 45 Pa. Pressure in secondary packaging room is higher than pressure of primary packaging room, therefore, there is a risk that particles from the secondary packaging room may escape to the primary packaging room. This is a product risk (GMP). Also, pressure in secondary packaging room is higher than the corridor, therefore, eliminating the clean corridor concept.
What about considering a third option? Please check the principle described in section 9.4 of page 203 of the below WHO guideline:
WHO TRS 957, Annex 3, WHO GMP for pharmaceutical products containing hazardous substances.pdf (148.3 KB)
Can we consider setting 20 Pa in the primary packaging room, 10 Pa in the secondary packaging room, keep the clean corridor at 30 Pa and install an extraction duct over the “mouse hole” in order to prevent airflow from the primary packaging room to the secondary packaging room?
I think at this point you are following 9.4 for containment (which is good). What can be done to follow the other recommendations (adding airlocks)?
As i have mentioned at my previous reply the introduction of airlocks at this stage is not possible due to lack of space and budget. Thank you very much for the interesting conversation.
I read that about not having money/space in your original post. I think it will be difficult to follow some regulations, but also not be able to follow some other regulations and still meet criteria. You might be able to avoid an airlock in the secondary packaging room, but I would suggest considering an airlock at least in the primary packaging room. Good luck with everything!