Definition of "Related Substances"

[Sahav]

Hi,

my understanding of the expression "Related Substances" is, that it includes both, process related compounds as well as degradation compounds of APIs and drug products.

Is this a general understanding of the expression?

Thank you very much and have a nice day,

Sahav

[cjwitt]

With regards to API's, "related substances" includes all possible compounds it can break down to or built up from. This does include all process impurities and intermediates as well as degradants.

Usually the process impurities are taken care of on the API raw material side and the degradants are taken care of on the finished product side due to the interaction of the API with the various placebo components.

[krickos]

Hi

To my knowledge there is no real definition of the term "related substances", but as mentioned already it is used as a "sum up" phrase for the analytical test (or in pharmacopieas, discussions, research etc) and can include both synthetic impurities and degradation products.

Strictly from an ICH point of view the terms: "impurity or degradation product" is used regardless if you consult the ICH Q3A-C guidelines (impurities) or the ICH Q6A guideline (methods and specification).


Degradation product:
A molecule resulting from a chemical change in the drug molecule brought about over time and/or by the action of e.g., light, temperature, pH, water, or by reaction with an excipient and/or the immediate container/closure system. Also called decomposition product.

Impurity:
(1) Any component of the new drug substance which is not the chemical entity defined as the new drug substance. (2) Any component of the drug product which is not the chemical entity defined as the drug substance or an excipient in the drug product.



CLASSIFICATION OF IMPURITIES
Impurities can be classified into the following categories:
• Organic impurities (process- and drug-related)
• Inorganic impurities
• Residual solvents

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

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)