Your shopping cart


Total (VAT incl.)

VAT (21%)
You have not added any reports to the cart yet.
Request reports
If you prefer to place your order via e-mail
contact us at: digital@azierta.com

Events and news

Home > Blog > Toxicology

Identification and quantification of impurities: a crucial aspect in pharmaceutical development



Any component present in an active ingredient or in a finished product which is neither the active ingredient nor an excipient is considered an impurity. The presence of impurities, even in small amounts, may influence the efficacy and / or safety of the drug, hence the importance of their toxicological assessment and control.

Impurities classification

According to ICH regulations, impurities are classified as organic and inorganic impurities as well as residual solvents. Organic impurities may arise from the starting materials, by-products or reaction intermediates and from degradation products which may arise after synthetic accomplishment.  Inorganic impurities generally come from the synthetic process elements, such as some inorganic reagents, inorganic salts, metals, catalysts, ligands, etc…, while residual solvents are impurities derived from the use of solvents in the synthesis and purification steps.

While inorganic impurities or residual solvents are readily identified and their toxicity is known, in the case of organic impurities, their number and structural variability is unlimited and their toxicity generally unknown.

Analytical control and Qualification of organic impurities

Synthetic and degradation organic impurities analysis is controlled by a series of tests collected in the monographs of the European and / or American Pharmacopoeia1, whereas the ICH regulation establishes its limits according to the quantity of active principle or finished product that is administered to the day.

ICH regulation distinguishes three levels in the evaluation of impurities, the reporting threshold, the identification threshold and the qualification threshold. These thresholds are values from which the impurities must be reported, identified and qualified respectively. Qualification means the process of acquiring and evaluating the data that define the biological safety and toxicity of the impurity at the specified level.

Following the decision tree of the ICH Q3A2 and Q3B3 guidelines, when an impurity reaches or exceeds the level of qualification, the manufacturer must justify the toxicity of the product. In this sense and based on these guidelines, any impurity that has been adequately evaluated in clinical and / or safety studies will be considered qualified. Impurities that are described as metabolites in human or animal studies will also be qualified. Where levels of an impurity cannot be lowered below the qualification limit, an impurity safety study shall be carried out by means of a toxicological evaluation. In a worst-case scenario, the inclusion of additional experimental data on genotoxicity (Ames test or chromosomal aberration) and general toxicity (14 to 90 days toxicity assays) would be required, also accompanied by a toxicological assessment.

At Azierta, we are experts in toxicological evaluations of impurities. We have wide experience and our expert team certified by EUROTOX.

For further information visit: https://www.azierta.com/en/pharma/toxicology/extractables-lixiviables-impurities



  1. EDQM (European Directorate for the Quality of Medicines) EU. European Pharmacopoeia (Ph. Eur.) 9th Edition. (2017).



Related posts

What do you need for the cultivation of medicinal cannabis in...

What do you need for the cultivation of medicinal cannabis in Europe?

Read more

Azierta Webinar on the new requirements for Safety Data Sheets...

Azierta Webinar on the new requirements for Safety Data Sheets that will come into force on 1 January 2021

Read more

Leading innovation in pharma & health

100 professionals

Over 100 professionals

500 clients

Over 2,000 clients

9 year experience

10 years of experience


Leading innovation

Client oriented

100% client oriented


We help you in everything you need. Contact us by filling out the form or book an appointment for a video call with one of our experts.

We use "cookies" to improve your experience on our site. Cookies enable us to tailor messages and display ads to your interests. They also help us understand how our site is being used. By continuing to use our site you consent to use our cookies.

We are at your complete disposal for any inquiry

Thank you for getting in touch! We will contact you as soon as possible to help you out
There has been an error while submitting your form, please try again, or call us at 912 77 10 76