GMP pharmaceutical impurity testing to meet ICH Q3A and Q3B Guideline requirements for process impurities, elemental impurities or extractables/leachables

Pharmaceutical impurity testing and quantification is vital to address the purity, safety and quality of drug substances or finished drug products. Pharmaceutical impurities can arise from many sources and include starting materials and their contaminants, reagents, catalysts, solvents, intermediates, excipients and their contaminants, leachables and degradation products. They can be organic impurities, both process and drug-related, inorganic or elemental impurities. These impurities are often present at very low levels highly complex sample matrices, and consequently, sensitive and specific assay methods are required to determine the levels of the impurity to collect the data required to complete relevant risk assessments or to support submission requirements. A recent example is NDMA-related impurities potentially found in ranitidine or some angiotensin II receptor blocker (ARB) medicines that have been highlighted by the US FDA as a concern and are thought to be a result of the manufacturing process.

Our GMP compliant laboratories provide pharmaceutical impurity testing for new drug substances (ICH Q3A(R2)) and new drug products (ICH Q3B(R2)) which can support your product development from an early stage and across the lifecycle of your drug product.

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. As part of our comprehensive stability study capability, we examine degradation products under stressed conditions to help establish degradation pathways. Additionally, we offer highly sensitive and specific method development and validation expertise which is required to address the issues of genotoxic impurities.

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

Pharmaceutical impurity testing is one aspect of our global GMP and CMC laboratory services solutions which include pharmaceutical 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.

Elemental Impurities and Trace Metal Impurities

Inorganic impurities can result from the manufacturing process and typically include reagents, ligands and catalysts, heavy metals or other residual metals and inorganic salts. Our elemental impurity testing scientists and toxicologists help you to develop a testing and compliance strategy to achieve successful implementation of ICH Q3D requirements through tailored analytical programs and toxicological risk assessments.  Our laboratories utilise inductively coupled–optical emission spectroscopy (ICP-OES) and ICP–mass spectrometry (ICP-MS) to perform testing in accordance with USP General Chapter <232> and Chapter <233>, or suitable alternative procedures.

Organic impurities

Our experts conduct laboratory studies to detect a wide range of organic impurities such as identified or unidentified, volatile or non-volatile, starting materials, by-products, intermediates, degradation products, reagents, ligands and catalysts. For new drug substances, we can help you to understand the actual and potential impurities which are most likely to arise during synthesis, purification, and storage. For new drug products we can help you to assess the degradation products observed during manufacture and/or stability studies and impurities arising from the interaction with excipients and/or the immediate container closure system.

Residual Solvents

We provide expert determination and identification of residual solvents in pharmaceutical products, helping customers ensure that residual solvents have been reduced to acceptable levels  to ensure that the finished product will meet the limits specified in ICH Q3C(R5) or USP <467>/ Ph. Eur. 5.4, or the limit established by the drug product manufacturer for unique solvent(s).

Extractables / Leachables

Our experts have over 25 years’ experience in specialised analytical and toxicology assessment for extractables and leachables, and this is reinforced by our knowledge of polymer, plastic and packaging materials, allowing us to identify components from the most complex polymer formulations.

Biopharmaceutical product impurities

Our Biopharmaceutical product characterisation team provide determination of both product-related and process-related impurities in accordance with the ICH Q6B Guideline. Our scientists perform detailed studies using a wide range of analytical methods (e.g., HPLC, capillary electrophoresis, mass spectroscopy, NMR, FTIR, circular dichroism technology,  size exclusion chromatography) to determine modified forms, altered conjugated forms, aggregates, cell substrate-derived process impurities, cell culture-derived impurities and downstream-derived impurities.