Dear Network,
Need guidance on performing Nitrosamine Risk Assessment for Purified Water which is used for manufacturing of Pilot Bio/Clinical Trial Batches only and No commercial batches are manufactured in this plant.
can you please clarify the reason for particularly focussing on purified water.
as an practical implementation approach, this is subject various scenarios., does the product you are dealing with is flagged for risk? ( not possible / probable / identified risk ); have you assessed the purified water system for any other product, and what is the outcome/status of it. etc.,
further, this discussion can be in two parts.
- is there separate/different approach for pilot bio/clinical batches; in my opinion,
- If this is for new molecules ( NCE ) then the assessment would be naturally part of one of the phases of development.
- I am not aware of any exception / separate for existing molecules.( already approved molecules) it could depend upon the phase of clinical trials; and for bio/pilot-bio studies, there would not be any exception.
we could possibly take benefit of the three phases of nitrosamine assessments. ( QRA - control strategy - manufacturing controls )
- QRA for purified water.
here’ are few very interesting references which will enable the QRA.
"The concentration of nitrite in Purified Water of WFI is expected to be far below 2×10-7 M (approximately 0.01 mg/L) as this level is typically seen in potable water. "
N-nitrosamine removal by reverse osmosis for indirect potable water reuse
– A critical review based on observations from laboratory, pilot and full-– A critical review based on observations from laboratory, pilot and full-
scale studies
. A comprehensive analysis of the existing data reveals significant variations in the rejection of NDMA by RO membranes reported in the literature, ranging from negligible up to 86%.
N-nitrosamine removal by reverse osmosis for indirect potable water reuse – A critical review based on observations from laboratory, pilot and full-scale studies (uow.edu.au)
Potential for the Formation of N -Nitrosamines during the Manufacture of Active Pharmaceutical Ingredients: An Assessment of the Risk Posed by Trace Nitrite in Water
https://pubs.acs.org/doi/10.1021/acs.oprd.0c00224
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Dear Experts
Can you please provide any recent updates on below topic
Nitrosamine Risk Assessment for Purified Water Used in Manufacturing for Pilot Bio/Clinical Trial Batches/Production batches.
What is the limit of Nitrite content we should consider as safe limit in context of Nitrosamine risk assessment.
As per WHO, for drinking water, Nitrite content limit is 3mg/L.
Regards
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