Bulk hold time study

bulk hold time study need to be done on unfiltered bulk or sterilized filtered bulk.

The question to be answered by the ‘bulk hold time study’ is whether the quality of the drug product is impaired by holding it. Typically, quality is implied by your specifications like assay, related substances, moisture, endotoxins…

Agreed with Boomer_Chemist.

There might also be a bulk hold prior to filtration (Boomer_Chemist addressed this) - this is likely longer in duration than a hold after filtration, and is done to wait for the filler to become available or to hold over a weekend/holiday, etc. Check is visocity has changed over time at this point.

Bulk hold AFTER the filtration will show that the product can be stored without getting contaminated with bioburden. I actually, wouldn’t recommend this at all. I would fill it and seal it as soon as it gets sterile filtered. The possibility for bioburden contamination goes up the longer you hold it. The best practice is to filter it in-line with the filling equipment if this can be obtained. But if there is a sterile hold time, this must be part of your media fill (sterile process simulation) qualification. I would actually start calling this hold a “bulk sterile hold time” (or bulk SHT), so as to avoid confusion when talking internally.

So to answer your questions - will you hold it after filtering? Then yes, qualify that in a media fill (but try to design around needing to do this). I suspect holding prior to filtering is what your process has been designed to do, but ask the process engineers what they are proposing (when will it be held).