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Hi everyone Regulatory Team is back with the REGULATORY FLASH with new content.

NITROSAMINE. IMPURITIES. A magnifying glass over a pill Description automatically generated.

NITROSAMINE. A black background with a black square Description automatically generated.

Global Concern & Potential Risk. Close up of pills in a pile Description automatically generated.

What is N-nitrosamine Impurities ?. A diagram of a molecule Description automatically generated.

General Root Causes of Nitrosamine Impurities. How to use 5 Whys Tree Diagram for Root Cause Analysis.

1. Formation of Nitrosamine in Drug product. Formation of nitrosamine is possible in the presence of secondary, tertiary, or quaternary amines and nitrite salts under acidic reaction conditions..

Nitrates react to form nitrite through enzymatic reduction..

2. Sources of Amines. Amines may be present in manufacturing process for various reasons & may also be added intentionally as reagents or catalysts..

3. Contamination in Sourced Raw Materials. Nitrosamine impurities can be present when sourced materials, including starting materials and raw materials, are contaminated. Below are few potential root cause..

4. Lack of Process Optimization and Control. Another potential source of formation of nitrosamine impurities is lack of optimization of the manufacturing process for APIs when reaction conditions such as temperature, pH, or the sequence of adding reagents, intermediates, or solvents are inappropriate or poorly controlled. FDA has observed instances of Deviations/Errors in which reaction conditions varied widely between batches and even between different processing equipment in the same facility for the same API. * Deviation/Error in process optimization & Control can lead to the formation of nitrosamines, due to present of nitrite..

Acceptable limits of Nitrosamine Impurities. Download Limits Push Man Royalty-Free Stock Illustration Image - Pixabay.

FDA recommends the following acceptable intake (AI) limits for the nitrosamine impurities NDMA, NDEA, NMBA, NMPA, NIPEA, and NDIPA..

CAPSULES. A close up of blue liquid. Capsule manufacturing is a physical pin moulding process which does not involve any chemical reaction..

The ingredients used in the manufacturing of our product “Hard Gelatin Capsule Shells & Cellulose Capsule Shells” does not contain the Nitrosamine impurities ..

Based on above information shared, we have readily prepared the questionnaire based on IPEC guidelines on Nitrosamine for our Hard Capsule Shells.

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