| Traces of impurities in pharmaceutical products can have drastic consequences; Dr Christian Zeine at LGC Standards GmbH outlines the ways in which their presence can be controlled and prevented
Impurities are always present in drug products in trace quantities. Limit and threshold values are specified by official bodies and legislation such as pharmacopoeias and ICH guidelines. Dedicated reference standards for impurities can help in the development and validation of analytical methods for impurity control, and are also used in the routine analysis of drug products. The use of such standards can provide an accurate assessment of products against regulatory limits and thereby ensures appropriate onward actions, be these data submission, process improvement or preclinical evaluation.
TYPES OF IMPURITIES
According to the International Conference on Harmonization (ICH), impurities are defined as substances in the active pharmaceutical ingredient (API) that are not the API itself (1). For a pharmaceutical formulation (that is, a tablet or suppository), impurities are defined as substances in the product that are not the API itself, nor the excipient used to manufacture the relevant pharmaceutical (2). Investigations for their presence or absence are important due to their risk potential. Impurities can themselves be pharmacologically or toxicologically active and they can also reinforce or diminish the pharmacological efficacy of the API. Sometimes impurities may even be teratogenic, mutagenic or carcinogenic. Impurities can be divided into three categories: organic impurities, inorganic impurities and solvents.
Organic Impurities
These arise during production and/or storage of the API and can be starting materials, by-products or degradation products. Organic starting materials and by-products are removed as much as possible after the production through downstream processing of the API. Degradation products, however, cannot be removed from the finished product. Stability tests must be carried out to prove that such degradation products do not exceed certain limits during the product shelf-life. Those limits must have been previously defined and justified for each degradation product. |
