Impurities are critical quality attributes of drug substances and drug products because they have the potential to affect the safety and efficacy of the product.
As per ICH Impurity is any component of the drug substance that is not the chemical entity that is defined as the drug substance; for a drug product, any component of a drug product that is not the drug substance or an excipient in the drug product.
Impurities can be classified into process impurities, degradation products, excipients, and packing-related impurities. Process impurities are produced during the manufacture of the drug substance and drug product, while degradants are formed by chemical degradation during the storage of the drug substance or drug product. Understanding the degradation pathways in order to achieve First to know the degradation paths to attain the stability of both drug substances and drug products.
Basically, there are 3 main types of drug degradation as per below:
The physical state such as solubility, dissolution, and disintegration of a drug will decide its physical characteristics in the final drug product. All these parameters will directly affect bioavailability and ultimately its efficacy. Additionally, it will also raise safety issues for that drug product. Drug substances may exist in different physical forms such as amorphous forms or various crystalline, hydrated, and solvated forms of the drug.
The following are the different forms of physical degradation.
- Particle size
Drugs is having several chemical natures along with different functional groups. Therefore, it will undergo different forms of degradation. Following are the different pathways of chemical degradation:
- Chemical incompatibilities,
- Decarboxylation and
A stability study is very useful during the formulation development and selection of packaging material.
Biological degradation states microbiological degradation. Liquids, Solutions, Suspensions, Parenteral, and sterile formulations are more susceptible to microbial degradation.
The following are the reasons for microbial degradation.
- The microbial load of drug substances and excipients will be responsible for the stability of the drug product throughout its shelf life. Also, manufacturing processes and the available facilities will have a substantial effect.
- Packing material plays important role in the stability of formulations against microorganisms throughout its shelf life.
- The organic chemistry of Drug Degradation, Min Li
- ICH Guidance for Industry, Q1 B: Photostability Testing of New Drug Substance and Product.
- FDA Guidance for Industry, Analytical Procedures, and Method Validation: Chemistry, Manufacturing, and Controls Documentation, Draft Guidance, Food, and Administration.
- CDER, Reviewer Guidance: Validation of Chromatographic Method, Centre for Drug Evolution and Research.
- ICH Guidance for Industry, Q2B: Validation Analytical Procedures: Methodology.
- ICH, Q6A: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances.
- ICH, Q3B (R2): Impurities in New Drug Products
- FDA Guidance for Industry, ANDAs: Impurities in Drug Substances
- ICH Guidance for Industry, Q6B: Specifications: Test Procedure and Acceptance Criteria for Biotechnological/ Biological Products