Regulatory agencies require the control of residual solvents in pharmaceuticals, ensuring finished products are free from toxicologically significant levels of volatile organic compounds, as they provide no therapeutic effect and present a risk to patient health. Element provides residual solvents testing services per USP <467> and ICH Q3C residual solvents guidelines.
Solvents are often necessary for the production, manufacturing, or purification of drug products, excipients, and drug substances, as they can improve yield and solubility, in addition to enhancing crystallization. However, many of these solvents are harmful, and may be present in materials and finished products as process residuals. A determination of the risk to patient health can be made based upon on the toxicity and concentration of residual solvents present.
Permitted daily exposure (PDE) limits for commonly used solvents have been defined by the United States Pharmacopeia (USP) and the International Council for Harmonization (ICH) in USP <467> and ICH Q3C guidance. Analytical methodology for testing of common residual solvents is detailed within the USP guidelines for residual solvents as well as Ph. Eur./EP 5.4. The USP and ICH guidelines for residual solvents limits have divided solvents into three classes:
Class 1 solvents – Class 1 solvents are to be avoided. This class of solvents includes known human carcinogens, strongly suspected human carcinogens, and environmental hazards.
Class 2 solvents – Class 2 solvents are to be limited. This includes non-genotoxic animal carcinogens as well as other agents that could possibly cause other irreversible toxicity, such as teratogenicity or neurotoxicity. Additionally, this category extends to solvents that are suspected of other significant, but reversible, toxicities.
Class 3 solvents – Class 3 solvents have low toxic potential. Solvents included in this classification have a PDE of 50mg or more per day, as there is no need for a health-based exposure limit.
Residual solvent testing methods for unique solvents
However, if solvents other than those included in ICH Q3C or USP <467> residual solvents guidance are used, the manufacturer of the drug product is required to establish a suitable residual solvent testing method, as well as determine the acceptable PDE for that particular solvent. As some unique solvents are not addressed in the regulatory guidance, Element’s consultative regulatory and scientific experts offer product-specific analytical method development for residual solvents, as well as method validation according to ICH Q2 guidelines for the validation of analytical procedures. Our experienced scientists also conduct residual solvents testing using our internal internal gas chromatography mass spectrometry (GC/MS) methods. Additionally, existing methods can be transferred to Element’s laboratories. Talk to an expert today to explore Element’s residual solvent testing services.
Control residual solvents with USP <467> and ICH Q3C residual solvents testing
The identification and determination of residual solvents is critical to ensuring that finished products are safe. To that end, the control of residual solvents in pharmaceutical raw materials and excipients is often part of a robust quality control strategy. Element has deep expertise and experience conducting residual solvent testing in compliance with USP <467> and ICH Q3C in pharmaceuticals and other finished products. Our experience extends to the quantitation of residual solvents in medical tubing, as well as the modification of USP <467> for use with a water insoluble medical device.
The Element advantage
With decades of experience developing and validating product-specific residual solvent testing methods, in addition to utilizing existing methods, including USP <467> and ICH Q3C to identify and quantitate residual solvents to the lowest possible levels of detection, Element is the preferred partner of leading organizations for residual solvent testing. Working closely and collaboratively with our customers, our regulatory and scientific experts look for potential sources of solvent contamination and assist in working to eliminate and control residual solvents. We also help to resolve difficult out of specification (OOS) issues related to solvents. Furthermore, testing to USP <467> and ICH Q3C guidance for residual solvents can be performed on a rush basis to meet the needs of your business.
For more information about our USP <467> residual solvent testing and ICH residual solvents testing services, or to speak with one of our experts, contact us today.
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