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Pharmaceutical Analysis - Determination of Residual Solvents
 
Residual Solvent analysis is required under ICH Topic Q3C when 'production or purification processes are known to result in the presence of such solvents'. The guidelines set limits on residual solvent levels and recommend methods for both qualitative and quantitative analysis.

USP Residual Solvents methods <467> are radically changing (July 2008) and the procedure now requires a different approach (similar to the current EP methods):

  • Preliminary GC Screening
  • Confirmatory analysis using dissimilar column chemistry
  • Identification of any solvent identified under both analyses above
  • Quantitative analysis


    • There are now 57 solvents listed as either Class 1 (unacceptable due to toxicity), Class 2 (solvents without adequate Toxicological Data) or Class 3 (least toxic, preferred solvents), all of which need to be screened and if identified subsequently quantified under proposed USP (and existing EP) guidelines.

    We offer an expert service for the analysis of residual solvents which includes:

  • GC-MS Screen using alternative selectivity columns (with Thermal Desorption as required)
  • GC (or GC-MS) quantitation of Class 1 Solvents
  • Identification and Quantification of Class 2/3 solvents (or solvent residues)
  • Expert spectral interpretation where required
  • Method development, validation (ICH Q2A, Q2B) and Technical Transfer of the method
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    Cleaning Validation
    21 CFR 211.67 requires that cleaning of manufacturing and storage equipment is undertaken to ensure no toxic or physiologically active substances remain.

    Many manufacturers now use Total Organic Carbon (TOC) Analysis for cleaning validation studies - assuming that all carbon detected is due to residual drug substance and/or drug product as appropriate.

    Limits for this analysis are typically 1/1000 of the lowest therapeutic dose of the previous drug substance (or 10ppm whichever is lower) or the LD50 limit of the cleaning detergent used.

    Whilst TOC analysis is useful for the broad estimation of residual detergents and other carboniferous material - it is unhelpful when issues develop regarding identification and quantification of specific contaminating materials.

    We have developed a range of target analysis services which allow the identification and quantitation of contaminating materials which allows efficient troubleshooting and remediation of issues relating to cleaning of process equipment.

    Our services include:
    • Rapid identification of contaminants in Cleaning In Place (CIP) or Out of Place (COP)
    • Small molecule and detergent identification and quantitation
    • Analysis of swabs, wipes, rinse and immersion solutions to sub ppm levels of detection
    • Identification and quantitation of contaminants identified via Total Organic Carbon (TOC) and Non Purgable Organic Carbon (NPOC) techniques
     
     

     


     
     
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