what are impurities and sources of impurities

1. PHARMACEUTICAL IMPURITIES
Prepared by:
Dr. Ram Babu Tripathi
Associate Prof.
Ram Eesh Institute of Voc. &
Tech Edu.Greater Noida, UP

2. IMPURITIES
According to International Conference on Harmonization
(ICH) guidelines
“Impurities are substances in the product that are not the Active
Pharmaceutical Ingredients (API) itself or the excipient used to
manufacture it
While, IP has defined impurity as any component of drug
substances for pharmaceutical use or of a drug product that is not
the chemical entity that defines the substance or in the case of a
drug product not an excipient in the product

3. Q3A ICH guidelines “Impurities in New Drug Substances”
Q3B ICH guidelines “Impurities in New Drug Products”
Q3C ICH guidelines “Impurities: Guidelines for residual solvents”

4. SOURCES OF IMPURITIES
Sources of
impurities
Raw materials used in
manufacturing
Method or process
employed in
manufacturing
Presence of trace metals which may catalyze
and accelerate the reaction
Due to impact of
heat, light, oxidants
on drug products,
Change in pH
Packing error, Microbial
growth, Cross
contamination

5. PHASE OF IMPURITIES

7. CLASSIFICATION OF IMPURITIES
According to ICH guidelines, impurities in drug substance produced by
chemical synthesis can be broadly classified into following three categories
1. Organic Impurities (Process and drug-related)
2. Inorganic Impurities (Reagent, ligands, catalysts)
3. Residual Solvents (Volatile solvents

8. Organic Impurities (Process and drug-related)
These types of impurities arise during the manufacturing process and/or
during storage of the drug substance. These include following sub-impurities.
I: Starting Materials or Intermediate Impurities
II. By-products
III. Degradation Products

9. INTERMEDIATE IMPURITIES
Production of paracetamol from intermediate, p-Amino-phenol

10. RESIDUAL SOLVENTS
Residual solvents are organic or inorganic liquids used during the
manufacturing process. It is very difficult to remove these solvents completely
by the work-up process. Some solvent that are known to cause toxicity
should be avoided in the production of bulk drugs.
As per the ICH guidelines, the solvents used in the manufacturing of drug
substances classified in to four types

11. Class I solvents
These solvents not employed in the manufacture of drug substances ,excipient
and formulations because of their unacceptable toxicity or their deleterious effects
likes: benzene and carbon tetrachloride etc
Class II solvents: Class II solvents usage should be limited in pharmaceutical
products because of their inherent toxicity. Likes Acetonitrile, Chloroform,
Cyclohexane, Methanol
Class III Solvents: These are less toxic and possess
lower risk to human health than class I or class II solvents likes Acetic acid,
anisole, butanol,
Class IV Solvents: Class IV solvents
Adequate toxicological data is not available. Likes petroleum ether