PowerPoint Presentation

[Virtual Presenter] Hi everyone. Today we will be discussing nitrosamine impurities, giving an overview of the general origin causes, potential threats and sources of amines that can result in the formation of nitrosamines. Let us start our journey and look into how these impurities can be averted and regulated..

This are the topic today which will be covered.

[Audio] N-nitrosamines may pose a potential risk in drug product risk assessment. These compounds are formed when a nitrosating agent, a secondary or tertiary amine, and suitable environmental conditions such as high temperatures and acidic conditions are present. Their presence persists as a global concern, making it necessary to focus on these factors and to continue researching N-nitrosamine formation and presence in medicinal products..

N-nitrosamines (nitrosamines) are a class of organic compounds that are associated with mutagenic carcinogens. Nitrosamines are formed by the reaction of secondary amines, amides, carbamates, derivatives of urea with nitrite or nitrosating agent.

Root cause analysis is a vital tool to find the original cause of a problem or issue. Let see.

Formation of nitrosamines is possible in the presence of secondary, tertiary, or quaternary amines and nitrite salts under acidic reaction conditions. Below is the Representative reaction to form Nitrosamines & Now Let us understand the stepwise formation in detail

[Audio] Nitrates can be reduced via enzymatic reduction to form Nitrite. Under mildly acidic conditions, Nitrite forms reactive species, Nitrous Anhydride, or N2O3. Caution should be taken when Nitrites and Nitrates are present in excipients and it is essential to be aware of the conditions in which they can be best regulated, such as high temperatures and acidic conditions..

Amines may be present in manufacturing process for various reasons & may also be added intentionally as reagents or catalysts. All of these types of amines can react with nitrous acid or other nitrosating agents to form Nitrosamines. Let see the Formation of NDMA from N,N-Dimethylformamide

Nitrosamine impurities can be present when sourced materials, including starting materials and raw materials, are contaminated. Below are few potential root cause. 1) Contamination can occur in water used during manufacturing. 2) Nitrate/Nitrite containing raw materials, such as Azo dyes may lead to nitrosamine impurities.

[Audio] Good afternoon. As you can see on this slide, inadequate optimization and control of the manufacturing process for APIs can lead to the formation of nitrosamine impurities. The FDA has observed instances where reaction conditions vary significantly between batches, and even between different processing equipment within the same facility. Not optimizing and controlling the manufacturing process correctly can create an environment in which nitrite, a precursor to nitrosamine formation, can exist, thus leading to the potential for nitrosamine impurities in the final product. It is essential to optimize and control the manufacturing process correctly in order to prevent the formation of nitrosamine impurities..

[Audio] In this presentation, we have been looking at Nitrosamine Impurities. This slide outlines the limits of these impurities which are deemed safe for consumer use, based on the data presented. It is therefore essential that we keep track of and manage the concentrations of these impurities to guarantee the protection of consumers..

[Audio] The FDA has conducted research into nitrosamine impurities and proposed acceptable intake limits for six compounds: NDMA, NDEA, NMBA, NMPA, NIPEA, and NDIPA. These limits are all below 96 nanograms per day, to protect public health..

[Audio] Slide presentation showcases what is involved in the manufacture of capsules, particularly on its absence of nitrosamine impurities. Two primary components which comprise capsules are gelatin, derived from animals, and HPMC, a polymer. Manufacturing process makes sure that no acidic conditions, solvents, or nitrosating agents are utilized, so compounds which might otherwise cause nitrosamine impurities do not form. Physical pin-moulding is the method used and no chemical reactions occur, making the capsules safe for consumption..

[Audio] Our Hard Gelatin Capsule Shells and Cellulose Capsule Shells are manufactured to the highest standards of quality and safety. We take special care to ensure that all our ingredients have been certified to have no risk of containing any Nitrosamine impurities. Our thorough process guarantees that our product is of the highest caliber, ensuring all users trust in its quality..

[Audio] Our company has developed a questionnaire based on IPEC Guidelines on Nitrosamine Impurities to ensure quality standards for the Hard Capsule Shells we produce. Through adherence of these guidelines, we strive to deliver the highest quality Hard Capsule Shells to our customers..

At the end of our presentation, I would like to bring to your attention a topic of great importance for Excipient and pharmaceutical industries. We are focusing on nitrosamine impurities, an incredibly small amount of chemical compounds that may be present in some drugs. To guarantee the safety of the products, we have created a regulatory department that can be contacted at the provided email address. I thank you all for being a part of this presentation.