Impurities

We determine the chemical structure of degradation and synthesis by-products as well as unknown components: Using high-resolution LC-MS measurements we make initial statements on the structure of impurities. To elucidate the complete structure, our LC-SPE trapping system provides the option of gaining minimum quantities for subsequent NMR measurements, which we coordinate in your projects in collaboration with cooperation partners.

Identified substances can then be synthesised in collaboration with cooperation partners or isolated using (semi-)preparative techniques, and then qualified by HWI as a reference standard.

Investigations, as required by regulations, of plastic packaging for extractables and subsequently of medicinal products for leachables are designed by our experienced team and conducted in our lab.

For new marketing-authorisation applications or amendment procedures, we assess this data and provide it to you as a report.

We offer:

• Extraction studies: exploratory investigations of primary packaging and/or devices to identify extraction profiles of potential extraction products, including the full identification and toxicological qualification of relevant extraction products
• Confirmatory migration studies of medicinal products as part of stability studies
• Regulatory support, including the creation of specifications and submission of justifications, expert reports and consultation
• Matrix-specific method development and validation to perform leachables studies

We have extensive experience in determining genotoxic compounds in active ingredients. For this method with the required limits of detection in the ppm or ppb range, we develop individual test methods, predominantly using GC-MS or LC-MS. The determination of alkyl mesylates in mesylate salts are established in our lab as examples of current issues.

We test for residual solvents according to European Pharmacopoeia and ICH Guideline Q3C (R7). Optionally, residual solvent determination is possible using our own in-house validated microprocess for substances and preparations only present in the lowest quantities.

We offer an express service for troubleshooting undesired impurities in your production. This service includes clarifying the structure of soluble organic impurities using LC-HRMS and GC-MS screening methods. We identify inorganic impurities at our cooperation partners using SEM-EDX or ICP-MS. We also have access to imaging methods such as X-ray microtomography/nanotomography, micro CT and Raman microscopy/imaging.

In accordance with the requirements of the current EMA guideline and literature data and as far as supported by qualified toxicologists in our network, we determine PDE values, which we use as a basis to perform risk-based analytical testing as part of the purity validation. This includes method development or optimisation, method validation and the analysis of samples from the purity validation, the sampling of which (swaps/rinse) we are also happy to help with.

In the course of risk analyses on the manufacturing route of your product including the complete supply chain and the used production equipment, we identify potential entry points of individual elemental impurities. Together with the results of screening for elemental impurities in product batches, this helps assess to what extent there needs to be a routine control strategy for a specific element in accordance with ICH Guideline Q3D.

If the risk analysis identifies it as necessary to have a testing concept for the routine control strategy of individual elements, we develop and validate an affordable method that is suitable for routine use for release analysis.