Residual solvents are volatile organic chemicals that remain in pharmaceutical products even after the completion of the manufacturing process. These solvents are often used in the production of active pharmaceutical ingredients (APIs), excipients, or the final drug product but may not be entirely removed during the process. Since residual solvents can pose health risks, particularly when they exceed established safety limits, it is crucial to monitor and control their presence.

Classification of Residual Solvents:

The ICH Q3C guidelines classify residual solvents into three categories based on their potential toxicity and health risks:

1. Class 1 Solvents (To be avoided):

These solvents are highly toxic and pose significant risks, including carcinogenicity and environmental damage. The use of Class 1 solvents should be avoided in the pharmaceutical manufacturing process.

• Risks: Carcinogenic to humans, environmentally hazardous.
• Examples: Benzene, Carbon tetrachloride, 1,2-Dichloroethane, 1,1-Dichloroethene.

2. Class 2 Solvents (To be limited):

Class 2 solvents should be limited in pharmaceutical production due to their potential to cause toxicity. These solvents may lead to neurotoxicity, teratogenicity (harm to fetal development), and are recognized as animal carcinogens.

• Permitted Daily Exposure (PDE): 0.1 mg/day.
• Examples: Acetonitrile, Methanol, Toluene, Chloroform, Hexane, Pyridine, Xylene.

3. Class 3 Solvents (Low toxic potential):

Class 3 solvents have low toxic potential and pose minimal risks to human health. These solvents have higher daily exposure limits, making them safer for use in pharmaceutical manufacturing.

• Permitted Daily Exposure (PDE): 50 mg/day or more.
• Examples: Acetone, Ethanol, Acetic acid, 1-Propanol, 2-Propanol, Formic acid.