definition of impurity, sources of impurities

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

2. LEARNING OUTCOMES
After the completion of this class students will know the
following things:
• Definition of pharmaceutical impurity on the basis of ICH and IP
guidelines
• Know about various sources of pharmaceutical impurities
• Students will also know about types and effect of impurities in
pharmaceutical products

3. 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

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

5. 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

6. PHASE OF IMPURITIES

8. 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

9. 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

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

11. 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

12. 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

13. EFFECTS OF IMPURITIES IN
PHARMACEUTICALS
Impurities which are present in the substances may have the following effects.
• Impurities may lower the shelf life of the substances.
• Sometimes Impurities changes the physical and chemical properties of the
substances.
•Therapeutic effect can be decreased.
•Shows toxic effect after a certain period.