Impurities in Pharmaceuticals

 

Impurities in Pharmaceuticals

Impurities

—  A drug product or any entity that is not a component of formulation ingredient.

—  In pharmaceuticals impurities are the unwanted chemical entities that remain with active ingredients, develop during formulation or with aging of active pharmaceutical ingredients or formulated product.

Classification

—  Organic Impurities

—  In organic impurities

—  Residual solvents

—  Organic Impurities

—  Identified or unidentified impurities that forms during manufacturing process or during storage of new drug substance.

—  They include the following

—  Starting materials

—  By-products

—  Intermediates

—  Degradation products

—  Reagents, ligands and catalysts

—  In organic impurities

—  Inorganic  impurities are mostly identified and arise during manufacturing process.

—  They include

—  Reagents

—  ligands and catalysts

—  Heavy metals or other residual metals

—  Inorganic salts

—  Other materials (e.g., filter aids, charcoal)

—  Residual solvents

—  Residual solvents are organic or inorganic liquids of known toxicity that are used as vehicle for solution or suspension preparations of new drug substance.

Important Terminologies Used During Impurities Studies as Per ICH Guideline

—  Chemical Development Studies:

—  Studies carried out during the development, optimization, up gradation and validation of a new chemical entity or drug.

—  Impurity:

—  A drug product, or any entity that is not a component of formulation ingredient.

—  Impurity profile:

—  Detailed presentation of identified and unidentified impurities associated with a new drug substance.

—  New drug substance:

—  A therapeutic substance developed for the 1^st time and that is not registered previously as a therapeutic entity. It may b a complex, ester form or salt form of already registered drugs. It is also called as new molecular entity or new chemical enetity.

—  Starting material:

—  A material used in the synthesis of new drug substance is called starting material. They are commercially available and of known physical and chemical properties.

—  Intermediate:

—  Any entity formed or produced during the step by step manufacturing of newly developed drug is termed as intermediate. Before it develops to new drug entity it has undergoes some chemical transformation.

—  Ligand:

—  Any substance that posses strong affinity towards a metal ion.

—  Identified impurities:

—  Any impurity that has known structural characterization is termed as identified impurity.

—  Unidentified impurities:

—  Any impurity the structural characterization of which is unknown and is defined by qualitative analytical techniques like HPLC retention time is termed as unidentified impurity.

—  Specified impurities:

—  Any identified or unidentified individual impurity which has proper limits of acceptance criteria and is listed in the specifications given to a newly developed drug is termed as specified impurity.

—  Unspecified impurities:

—  Any impurity that is included in the general acceptance criteria limitations but have no individual acceptance limits in the specifications allotted to a newly developed drug.

—  Identification threshold:

—  Identification threshold is a limit above which an impurity should be identified.

—  Qualification threshold:

—  Qualification threshold is a limit above which an impurity should be qualified.

—  Reporting threshold:

—  Reporting threshold is a limit above which an impurity should be reported.

—  Identification threshold:

—  Identification threshold is a limit above which an impurity should be identified.

—  Qualification threshold:

—  Qualification threshold is a limit above which an impurity should be qualified.

—  Reporting threshold:

—  Reporting threshold is a limit above which an impurity should be reported.

—  Identification threshold:

—  Identification threshold is a limit above which an impurity should be identified.

—  Qualification threshold:

—  Qualification threshold is a limit above which an impurity should be qualified.

—  Reporting threshold:

—  Reporting threshold is a limit above which an impurity should be reported.

Maximum Daily Dose	Reporting Threshold	Identification Threshold	Qualification threshold
≤ 2g/day	0.05%	0.10% or 1mg/day	0.15% or 1mg/day
˃ 2g/day	0.03%	0.05%	0.05%

 

Presented By

Muhammad Atif

PhD Scholar Pharmaceutical Sciences AWKUM Khyberpakhtunkhwa