Pharmaceutical genotoxic impurities analysis to assist the control of DNA reactive (mutagenic) impurities in drug products. Our GMP labs support the identification, quantification and control of genotox impurity levels.

Genotoxic impurities (GI) analysis is critical to address the purity, safety and quality of drug substances or finished drug products related to potential genotoxic impurities. The ICH M7(R2), a genotoxic impurity guideline defines genotoxicity as “a broad term that refers to any deleterious change in the genetic material regardless of the mechanism by which the change is induced”. There are a range of sources of genotoxic impurities, contributed to reactive materials used in drug substances which have the capacity to interact with human DNA to cause mutations and cancer, even at extremely lowest levels. These substances include a group of potentially high potency mutagenic carcinogens which have “alerting structures” such as N-nitroso-, aflatoxin-like-, and alkyl-azoxy compounds. and are referred to as the
“cohort of concern.”

Identifying GIs early in the drug development process and/or limiting genotoxic impurities at acceptable levels in the API or drug product, can avoid risks associated with drug safety and quality later in development and/or marketing authorisation, that could potentially lead to expensive recalls. A key example of this are nitrosamine impurities such as N-nitrosodimethylamine (NDMA) which have been highlighted by the US FDA (2018) and other regulatory authorities as an area for concern.

Guidelines from drug regulatory authorities in both Europe and the United States of America (USA) require the control of GIs and potentially genotoxic impurities (PGIs) at parts per million levels in drug substances. Determination of genotoxic impurities at trace levels (lower than 0.01-0.03%) requires highly sensitive and specific analytical approaches that are suitable for the sample matrices of interest and ideally allow detection in the range of 1-to 5ppm.

Our GCP/GLP/GMP compliant laboratories provide genotoxic impurity testing services to detect and evaluate the potential of GIs for your API and/or drug substances which can support your product development from an early stage to market release. With scientists who are adept at method development and validation of suitable analytical procedures, we can overcome the challenges of low detection levels and difficult matrices. Using a range of technologies we can apply an orthogonal approach to ensure robust, specific and sensitive analysis.  Our comprehensive characterisation techniques include: 

  • High Performance Liquid Chromatography with (HPLC with UV/Vis detectors)
  • Gas Chromatography (GC) and GC-MS
  • Liquid Chromatography-Mass Spectrometry (LC-MS)
  • Inductively-Coupled Plasma Optical Emission Spectroscopy
  • (ICP-OES) and Inductively- Coupled Plasma Mass Spectrometry (ICP-MS)
  • Nuclear Magnetic Resonance Spectroscopy (NMR)

As part of our comprehensive stability study capability, we examine degradation products under stressed conditions to help establish degradation pathways. For a potential degradation product that has been characterized as mutagenic, it is important to understand if the degradation pathway and a well- designed accelerated stability study (e.g., 40°C/75% relative humidity, 6 months) in the proposed packaging, with appropriate analytical procedures is recommended to determine the relevance of the potential degradation product. Additionally, we offer highly sensitive and specific method development and validation expertise which is required to address the issues of genotoxic impurities including nitrosamines screening and quantification

Toxicological Risk Assessment
With many years of experience in toxicological risk assessments, our consultants conduct risk assessments to address the issues associated with exposure to genotoxic impurities and other substances of concern including residual solvents, process impurities, extractables & leachables, elemental impurities (ICH Q3D) and other substances that may find their way into a pharmaceutical product. 

Total Quality Assurance 
Genotoxic impurity testing is one aspect of our global GMP and CMC laboratory services solutions which include pharmaceutical impurity analysis, stability testing, quality control (QC) and batch release testing. Bringing quality and safety to life, we offer Total Quality Assurance expertise to help you to meet and exceed quality, safety and regulatory standards.


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