Provision of expert information on the tolerability of predicted doses of impurities in specified generic pharmaceutical products


A large generics Pharmaceutical company


Generic pharmaceuticals are often manufactured using methods different from those of the patented brand, and this can lead to a different impurities profile. Regulatory submissions have to address any novel impurities, as well as any common impurities present in the generic at level higher than the Quality Thresholds (QTs) established for the market leader. The Pharmaceutical company asked bibra to assess whether the presence of one novel impurity and two non-novel impurities at slightly above existing QTs might pose any significant health risks to the patients, and whether new QTs could be justified.

Project goals

Reassurance over the tolerability of the predicted doses of the impurities could be provided by risk assessments from independent, expert toxicologists. Bibra employs a number of experienced, professionally-registered (RSB/BTS/ERT) toxicologists and was commissioned to provide hazard and risk assessment reports on the impurities in question.


The client provided the relevant impurities profiles, identifying the individual impurities and their percentages in the active. The client also described the proposed exposure, which includes information on the dose per treatment, the dosing route, the frequency of treatment, and its likely duration.

Bibra then assessed the hazards (Inherent characteristics) of the individual impurities, and carried out risk assessments by combining hazard data with information on the proposed dosage. Worst-case assumptions were made to address uncertainties. Where adequate toxicity data were lacking, it was often possible to make use of QSAR and SAR modeling as well as the Threshold of Toxicological Concern approach. EMEA guidance on low level genotoxic impurities in pharmaceuticals was used.

Project outcome

Bibra was able to provide an independent, expert report explaining why the anticipated exposures would not pose any significant health risks to patients. Additionally, bibra was able to justify new QTs where needed. This allowed the client to pursue their proposed manufacturing and registration proposals with confidence that the health benefits of their products were not being undermined by differences in the impurity profiles

Bibra project leader

Pete Watts

Pharmaceutical Product Toxicological Support

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