🇰🇷 Case study on the Occurrence of Impurities in Pharmaceuticals (Focusing on NDMA Cases)

Guidance, Documents, Resources
1

Authored by Korean NIFDS

This case study collection focuses on NDMA cases to identify risk factors and evaluate the potential for impurity generation in each stage. It presents several cases related to this and suggests specific evaluation methods. It is expected that this case study collection will be helpful in product development design of pharmaceuticals which can produce nitrosamine impurities.

This document provides examples of identifying risk factors and evaluating the causes of nitrosamine impurity generation, such as NDMA, during the pharmaceutical manufacturing process. In the synthesis stage, the conditions such as synthesis process, solvent, reagent, reaction temperature, pH, etc., which are the main causes of nitrosamine impurities for valsartan drugs, were comprehensively summarized and described with a focus on cases where major amines were analyzed. In the formulation stage, a study was conducted to identify the causes of impurity generation using experimental design methods, focusing on metformin drugs and various causes such as heat, moisture, and excipients. A recently published literature review has shown that the wet granulation process, which introduces heat and moisture, is an important step in NDMA generation. Finally, for the storage stage, the study presents results on the tendency of NDMA generation during storage of nizatidine drugs and the prediction of the rate and reaction constant using temperature and humidity.

The contents are as follows:

I. Overview

II. Nitrosamine Generation Mechanism (General Conditions)

III. Considerations During the Manufacturing Process

  1. Synthesis Stage
  2. Formulation Stage
  3. Packaging Stage

IV. Synthesis Stage: Evaluation of NDMA Occurrence in Valsartan Synthesis

  1. Potential for NDMA Generation in Sartan Synthesis
  2. Examples of Nitrosamine Generation During Synthesis
  3. Analysis of NDMA Generation Potential

V. Formulation Stage: Evaluation of NDMA Occurrence in Metformin Formulation

  1. Potential for NDMA Generation in Metformin Formulation
  2. Analysis of NDMA Generation Potential

VI. Storage Stage: Evaluation of NDMA Occurrence in Nizatidine Storage

  1. Potential for NDMA Generation in Nizatidine Storage
  2. Analysis of NDMA Generation Potential

VII. Discussion

English Version (AI translated)
Machine Translated Document - IDRAC 384600 (1).pdf (9.4 MB)

Original Koren Version:
IDRAC_384600_31-May-2024_NIFDS Guide-11-1471057-000667-01_ Case study on the Occurrence of Impuritie.pdf (2.3 MB)

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