Residual Solvents/Organic Volatile Impurities (OVIs)

Residual Solvents or OVIs?

In pharmaceutical manufacturing, Residual Solvents is the modern, more precise term for what was once called Organic Volatile Impurities (OVIs).  Both refer to organic solvents that may remain in a drug product if not completely removed during production.  Because these solvents can pose health risks when present above safe limits, pharmacopoeias such as the USP and Ph.Eur. set strict guidelines to ensure their control and monitoring.

At Butterworth Laboratories, we provide comprehensive testing for residual solvents to ensure clients meet stringent regulatory standards, including ICH Q3C guidelines.  Our experienced team uses pharmacopoeial-based methodologies to ensure product safety and compliance across pharmaceutical and related industries.

While not intentionally added, their presence must be strictly controlled as these substances can pose toxicity risks and must be identified and quantified to ensure patient safety.  Butterworth Laboratories utilises sensitive and accurate analytical techniques such as headspace gas chromatography (HS-GC) to detect and measure Residual Solvents in accordance with ICH Q3C guidelines, USP <467> and Ph.Eur 2.4.24.  They can be applied to raw materials, intermediates, and final dosage forms.  Our analysts are adept at handling complex matrices and developing customised methods to meet client-specific requirements.

Regulatory Compliance and Risk Assessment

Regulatory authorities such as the EMA, FDA, and ICH classify residual solvents into three categories based on toxicity and specify permitted daily exposures (PDEs).

• ICH Q3C: Guideline residual solvents in drug products. Classifying the solvents into three categories:
  • Class 1: Known to be genotoxic or carcinogens, or environmentally harmful.
  • Class 2: Suspected of causing reversible but severe toxic effects or other non-genotoxic toxicities. 
  • Class 3: Solvents with low toxic potential to humans, and a health-based exposure limit is not usually needed.
    
• USP <467>: United States Pharmacopoeia chapters on residual solvents.

• Ph. Eur. 2.4.24: European Pharmacopoeia’s general chapter on residual solvents.

The results we supply assist clients in conducting risk assessments to identify potential sources of solvent impurities, evaluating their impact, and implementing control strategies to ensure product safety and compliance.

Additional Resources

• White Paper: Enhanced Residual Solvents Analysis
• Blog Post: The Background to Residual Solvent Analysis at Butterworth Laboratories
• Service Page: Quality Control Services
  

Frequently Asked Questions