Results from survey on Nitrosamines in Excipients -Any thoughts?

Today 16Sep21, USP India hosted “Workshop on Excipient composition and organic impurities”, a discussion track was dedicated to Nitrosamine in Excipients. As part of the presentations, my colleague @Mrunal (R&D, USP India) presented results from USP’s survey on Nitrosamines in Excipients.

I would like to share some fascinating and insightful observations:

  • Nitrosamines is the topmost impurities of concerns for DP, and DS manufacturers, BUT for excipients manufacturers Elemental Impurities and Residual Solvents top the list.

  • The survey pointed a large uncertainty about controlling nitrates and nitrites levels for each of the audiences groups (DP, DS, Excipients). Uncertainty is even higher for Excipients manufacturers

  • Risk assessment is not necessarily seen as effective and essential among the Excipients manufacturers responses

  • In terms of relevance, compliance to regulatory methods are more prominent than developing appropriate control strategies as per ICH M7

  • Loud and clear!.. A need for MORE information and guidance is sought on this topic to make informed decisions

What’s your take? Any thoughts?



Interresting outcome.

Was there also research done why for the DS/DP manufacturers they feel (or do i mis-interpret) that the nitrate/nitrate levels are not optimally monitored? and was within the excipients portfolio a separation in classes put in place to target the risks? eg natural, animal and/or chemical derived excipients?

And, were the responses (n=65) for the excipients done by excipient suppliers or a broader public? This as in line with IPEC guidelines etc a lot of work is done by excipient suppliers in general on this topic of nitrate/nitrite levels.

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@Bastiaan I will let my USP colleague @Mrunal provide more information.
Let me ask you, how has been your team’s approach to nitrate/nitrite testing? What is the target specification that has been used, if any?
I believe we will benefit from understanding the approach that excipient manufacturers are taking, and what they are offering to customers as part of the information for their respective risk assessments. Thx.
@Aaron what has been your experience on the excipient sector on capability building demand for nitrate/nitrite testing?

@DAB @Yosukemino @GENERAPHARM @David … Just tagging you on this information that I know it’s an area of your interest.

@Bastiaan @Naiffer_Host This is to let you know that only 4% Excipient manufacturers (out of 242 respondents) participated in the survey. Hence, the outcome is more from drug product manufacturers’ perspective.

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This mimics the responses we have had and just shows that we will not get help from excipient manufacturers. We will need to generate our own data and use that to influence these manufacturers to exercise more control over nitrate/nitrite

Like other reputable excipient suppliers, we have a clear risk assessment with some typical value for our products.
Its difficult to define maximum nitrate/nitrite values as DP manufacturers have different levels to target, based upon the potency of their active.
We as company have frequent pro-active discussions with our customers on our levels in our materials and advise which best to use of customers specific needs.


Have you participated in the survey? If not, would you like to take the survey?
@Naiffer_Host I am sure we have shared the survey link in the Nitrosamine Exchange. Could we share it again to get more participation of Excipient manufacturers?

@GENERAPHARM Do you think that’s something that as a community we could foster and lead in terms of influencing those manufacturers? I do recognize that there are many of them doing great work, and providing a full scientific value to their customers.
I’m really hoping @David and the Lhasa team working on the excipient database could shine some light on this with some insights.
I really would love to hear some perspectives on members closely familiarize with these manufacturers (BASF, Ashland, etc)

You can still provide your perspective and voice to USP’s survey on Nitrosamine in Excipients. Ignore the closing date!

Thanks Naiffer @Naiffer_Host .
This is something that we have been discussing in this community ever since I joined perhaps.
My views on this are as under:
As I said earlier, the onus of RA wrt Excipients is on MAHs. Excipients are not under the domain of GMPs to the extent of drug products & substances hence this activity will require a multi dimensional approach. There needs to be a hand holding wrt Trainings, Technical support & Testing support as required & as applicable to ensure a win win situation.
The MAHs need to sensitize the excipient mfrs wrt impact of Nitrosamines from excipients in the products for human consumption. Excipact can provide a good bridging support whenever a Excipient mfr applies for a Excipact Certification this aspect needs to be included as a clause so I guess there is plenty of work that needs to be done on this front by the MAHs, Excipient mfrs, Excipact & Regulators. As the Industry gets familiarised with Identification & Control strategies for Nitrosamines, am sure the same approach can further be extended to excipient & Packaging Material mfrs. It will call for a Multidisciplinary Team efforts.
Thanks for tagging me on this & apologies for the delayed response as I got caught up with sessions with US extending past midnight IST.
Nevertheless am glad we are discussing all aspects in the community which has experts across all disciplines, cheers to everybody who’s been a part of the discussions :smiley: :+1: It has been a great knowledge sharing platform on Nitrosamines.

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