Impurities

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.

We use high-resolution LC-MS measurements to elucidate the chemical structure of degradation and synthesis by-products as well as unknown components. This enables us to make initial statements about the structure of the elemental impurities.

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

Finished medicinal products may contain materials originating from the packaging or introduced during the production process. These impurities may be toxicologically relevant and pose a health risk to the patient. It is therefore essential to determine the compatibility of these materials.

Our team of experts designs and performs the necessary regulatory analyses of plastic packaging materials for extractables and leachables in medicinal products.

We evaluate this data and provide you with a report for new marketing authorisation applications or variation procedures.

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 preparation of specifications and submission of justifications, expert reports and consultations.
• Matrix-specific method development and validation to perform leachables studies.

Genotoxic impurities can occur as by-products during the synthesis of active substances or certain excipients. Formation in the finished medicinal product is also possible. There are strict limits for genotoxic impurities in active ingredients, excipients, and medicinal products with very low limits in the lower ppm or ppb range. We develop and validate customised LC-MS and GC-MS test methods with appropriate detection and quantification limits. The determination of alkyl mesylates in mesylate salts as an example of current issues is well established in our laboratories.

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 present only in trace amounts.

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 for performing risk-based analytical testing as part of the purity validation. This includes method development or optimisation, method validation and the analysis of purity validation samples, for which we can also assist with sampling (swaps/rinse).