Residual solvents, formerly referred to as organic volatile impurities (OVIs), are trace level chemical residues that are used in the manufacture of drug substances and excipients or in the preparation of drug products. They can also be byproducts formed during packaging and storage of the drug product.
The US pharmacopeia has set guidelines as to what amount of a particular solvent a person can be exposed to on a daily basis without developing complications due to overexposure. The types of solvents are divided into three classes. Class 1 organics should never be used. Class 2 organics are not recommended for use outside of a Good Manufacturing Practice (cGMP) environment where these substances are tightly controlled and continuously monitored due to their dangerous effects. Class 3 are solvents that present no known human health hazard at levels normally accepted in pharmaceuticals.
More importantly, chemical residues can have a significant impact on the health of a patient, especially over time and with repeated exposure. Your laboratory must ensure that patients are receiving the highest of quality, solvent-free drug product possible.
The implementation of United States Pharmacopeia (USP)<467> requires expertise that can provide extensive experience in optimizing gas chromatographic methods and analyzing volatile organic compounds in a variety of matrices in a timely manner, and our consulting services that we provide it as complimentary service in this regard.
Synergy Bioscience provides expert, rapid analysis support of all three classes of residual solvents. Our experienced team of scientists allow you to manage the large number of methods that may be involved in identification and quantification of impurities, including residual solvents.
Our Expertise Encompasses
• Strict compliance of ICH guidelines
• Detection, profiling and control support of residual solvents in drug substances, excipients, and drug products
• Water-soluble/insoluble raw materials and drug substance
• Screening for potential interference
• Screening for identification of unknown peaks
• Feasibility studies
• Validation of analytical methods
• Comprehensive and accurate reports
Our Multiple Points of Interaction
• Joint review of DMF/physico-chemical properties of the API
• Meetings to ensure appropriate:
• Technology – GC-FID or GC/MS
• Limits, e.g., TDI
• Procedure for method transfer/validation
• Process – prescreening, routine testing, API qualification
To ensure that the highest quality of drug substance/drug product are being produced and made available to patients, Synergy Bioscience offers collectives Residual Solvent Test (RST). By testing for Residual Solvents, we are able to ensure that the producer’s process is sound, not only verifying that the producer has used a high-quality solvent, free of impurities and toxic solvents, but has also followed a proper manufacturing process (i.e. vacuum, desiccation, etc.) Utilizing a combination of Gas Chromatography/FID, Head-space analysis, and Mass Spectrometry, Synergy Bioscience Labs are able to identify all of the most commonly used solvents and trace residues of chemicals in the process, including:
• Isopropanol (iso-alcohol)
Synergy Bioscience offers a validated testing method to determine the amount of residual solvents introduced during processing of concentrates. By monitoring the ppm levels of solvents we will help identify raw materials and products that are free of harmful contamination.
• We are currently testing for residual solvents using GC-FID coupled with headspace sampling which is the technique recommended by USP 467 for residual solvents in pharmaceuticals.
• We have developed an in-house method that allows us to detect the light gases not included in USP 467.
• We are currently testing for propane, isobutane, n-butane, isopentane, n-pentane, isopropanol, ethanol, acetone, hexane and naphtha all in one assay.
As part of a standard residual solvent analysis, we report all Class 1 and Class 2 solvents that are amenable to GC headspace analysis as defined in USP <467> and shown to work in practice.
Reasons for Choosing Synergy Bioscience
• Expedited Turnaround Times Available
o Standard Turn Around Time: 10 days
• Accessible & Flexible
o You will have one point of contact for seamless project management and our Quality Unit and Chemists are available upon request
o Synergy Bioscience has tested residual solvents since 1986; specifically performing method feasibility, development and validation for USP <467>
o Our laboratory is cGMP complianct, FDA inspected/registered and DEA licensed.