Classification of Impurities
Impurities can be classified into the following categories:
- Organic Impurities (Process And Drug-Related)
- Inorganic Impurities
- Residual Solvents
- Organic Impurities :
Organic impurities can arise during the manufacturing process and/or storage of the new drug substance.
They can be identified or unidentified, volatile or non-volatile, and include:
- Starting materials
- By-products
- Intermediates
- Degradation products
- Reagents, ligands and catalysts
2. Inorganic Impurities:
- Inorganic impurities can result from the manufacturing process.
- They
are normally known and identified and include:
- Reagents,
ligands and catalysts
- Heavy metals or other residual metals
- Inorganic salts
- Other materials (e.g., filter aids, charcoal)
- Reagents,
ligands and catalysts
3. Residual Solvents:
- Residual are inorganic or organic liquids used as vehicles for the preparation of solutions or suspensions in the synthesis of a new drug substance.
3.1 Classification of Residual Solvents by Risk Assessment
a. Class 1 Solvents : Solvents to be avoided
- Solvents in Class 1 should not be employed in the manufacture of drug substances, excipients, and drug products because of their unacceptable toxicity or their deleterious environmental effect.
- However, if their use is unavoidable in order to produce a drug product with a significant therapeutic advance, then their levels should be restricted as shown in Table.
-Known human carcinogens
-Strongly suspected human carcinogens,
-Environmental hazards.

b. Class 2 solvents: Solvents To Be Limited
- Solvents in Table should be limited in pharmaceutical products because of their inherent toxicity.
- PDE*s are given to the nearest 0.1 mg/day, and concentrations are given to the nearest 10 ppm.
-Non-genotoxic animal carcinogens
-Possible causative agents of other irreversible toxicity such as neurotoxicity or teratogenicity.
-Solvents suspected of other significant but reversible toxicities.

c. Class 3 Solvents: Solvents With Low Toxic Potential
- Solvents in Class 3 may be regarded as less toxic and of lower risk to human health.
- Class 3 includes no solvent known as a human health hazard at levels normally accepted in pharmaceuticals.
-Solvents with low toxic potential to man; no health-based exposure limit is needed.
-Class 3 solvents have PDEs of 50 mg or more per day

3.2 Solvents for which No Adequate Toxicological Data was Found

* PDE: Permitted Daily Exposure is the maximum acceptable intake per day of residual solvent in pharmaceutical products.
Reference : ICH Q3
For any feedback or suggestions write to us at info@pharmastate.com