Developing Process for Nitrite-free Excipients?

At the recent FDA Generic Drug Science and Research Initiative Public Workshop, Janet Vaughn shared interesting ideas. Thanks, @DAB for updating the community on it.

a) Are APIs which are themselves secondary amines may form the corresponding nitrosamines during
manufacturing and storage due to reaction with nitrites in excipients?

b) Impact Risks from Nitrites in Excipients and formulations challenges may impact the availability of generics on the American Public

c) Controlling the nitrite level in excipients, preferably at “ppb” level, to reduce the risk of nitrosamine impurities in drug products; however, Testing for nitrites in drug product formulations is complicated by the complexity of the matrix and solubility or lack of solubility of excipients which may interfere with the analysis

d) Identifying the root cause of nitrites in excipients and/or developing commercial processes for manufacturing nitrite-free excipients; however, 1) Excipient manufacturers may not have the necessary resources to develop processes; 2) There is an undue burden on drug product manufacturers to evaluate the presence of nitrites in every lot of excipient

To close How Can FDA help? FDA can support a collaborative effort to understand the source of nitrites in excipients and propose improvements in the manufacturing process of excipients leading to desirable nitrite levels

We know these are in many people’s minds. Wondering ‘What’s Next?’. It also a lot of regulatory bodies’ radar. What are your thoughts?

Deck posted here:
Nitrosamines at FDA’s FY2021 GDSR Workshop

1 Like

Controlling nitrite in excipients is a dream but every time there has been an effort to control excipient manufacture it has met the same problem—most excipients are manufactured primarily for other industries and therefore the manufacturers are not interested as the bulk of their product goes to, say, the food industry. However, would pharma companies be prepared to pay a premium price for certified “nitrosamine free” excipients and would manufacturers be prepared to offer that?

1 Like