Residual Solvents/Organic Volatile Impurities (OVIs)

Residual Solvents or OVIs?

In pharmaceutical manufacturing, Residual Solvents is the modern, more descriptive term for what was once called Organic Volatile Impurities (OVIs).  Both refer to organic solvents that may remain in a pharmaceutical article if not completely removed during production.  Because these solvents can pose significant 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 of Residual Solvents to ensure clients meet applicable regulatory standards, including the ICH Q3C guidelines.  Our experienced team uses pharmacopoeial-based methodologies to ensure product safety and compliance across pharmaceutical and related industries. 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.  This analysis 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 any client-specific Residual Solvents or specification 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 risk-based exposure limit is not usually needed.

USP <467>:  United States Pharmacopoeia general monograph on residual solvents.

Ph. Eur. 2.4.24:  The 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.

While residual solvent analysis—particularly headspace gas chromatography (GC)—is most prominently recognized within pharmaceutical quality control under regulatory frameworks like ICH Q3C and USP <467>, the technique is equally valuable across a broad range of non-pharmaceutical sectors:

• Cosmetics and Personal Care: Ensuring that trace levels of volatile organic compounds (VOCs), extraction solvents, and impurities from raw ingredients (such as botanical oils, synthetic fragrance compounds, or emulsifiers) fall within safe consumer exposure limits.

• Medical Devices and Packaging: Testing raw polymers, adhesives, coatings, and primary packaging materials to confirm that volatile residues from processing or ethylene oxide sterilisation do not leach into final consumer products.

• Electronics and Advanced Materials: Detecting trace cleaning solvents or process chemicals on circuit boards, high-purity chemicals, or semiconductor components, where volatile residues could compromise physical integrity or performance.

Additional Resources

• White Paper: Enhanced Residual Solvents Analysis

• Blog Post: The Background to Residual Solvent Analysis at Butterworth Laboratories

• Service Page: Quality Control Services and Method Development & Validation Services
  

Why Butterworth?

• We offer GMP-compliant testing with rapid turnaround times, which is always tailored to specific client requirements.

• Butterworth has decades of experience in method development, validation and routine analysis for Residual Solvents.

Frequently Asked Questions