Impurity Profiling Suite™

Impurity Profiling Suite is designed for various types of organic impurities that can arise during the manufacturing, synthesis, or storage of an Active Pharmaceutical Ingredient (API), including unreacted starting materials and intermediates, unwanted by-products, and degradation products resulting from the breakdown of the drug substance over time.

Under the ICH M7 guideline, computational safety assessment alone can be used for impurities present at an intake level of 1 mg/day or less. Therefore, whether computational assessment is sufficient depends not only on the identity of the impurity but also on the amount present. The same impurity may require only computational assessment in one formulation, while experimental safety assessment may be required in another if the impurity is present at a higher intake level.

ICH M7(R2) provides a framework for the identification, assessment, qualification, and control of DNA-reactive (mutagenic) impurities to limit potential carcinogenic risk in pharmaceuticals. The guideline permits the use of two complementary (Q)SAR methodologies, following Organization for Economic Co-operation and Development (OECD) validation principles, as an alternative to expensive in vitro testing.

Developed through a collaborative agreement with the US FDA, Impurity Profiling Suite supports ICH M7(R2) workflows by helping scientists assess the genotoxic and carcinogenic potential of impurities and degradants. The software predicts relevant toxicological endpoints and helps determine ICH M7(R2) classifications to support impurity risk assessment and regulatory submissions. 

Impurity Profiling Suite predicts 21 toxicological endpoints, including mutagenicity, clastogenicity, DNA damage, carcinogenicity, and endocrine disruption.

Yes. Impurity Profiling Suite can evaluate multiple compounds within a single project, including the parent API and a set of its impurities and degradants. Compounds can be analyzed individually or together as a project, with the software tracking which alerts are shared between the impurities and the parent compound.

The OECD recommends that (Q)SAR models have a defined endpoint, an unambiguous algorithm, a defined domain of applicability, appropriate measures of goodness-of-fit, robustness and predictivity, and, where possible, a mechanistic interpretation. These principles help ensure that predictions are scientifically robust and suitable for regulatory use. 

Yes. Impurity Profiling Suite supports the Carcinogenic Potency Categorization Approach (CPCA) for N-nitrosamines, enabling automatic assessment of compounds containing N-nitroso (N–N=O) functional groups when experimental data is unavailable. The software assigns a CPCA category, estimates CPCA scores and contributing factors, and provides acceptable intake limits directly within the interface and ICH M7 reports.

Impurity Profiling Suite is designed for organizations of all sizes, from small and medium-sized companies to large pharmaceutical and biotechnology organizations.

Impurity Profiling Suite uses a weight of evidence (WoE) approach to resolve ambiguous predictions. The WoE algorithm takes into account a variety of factors: 

• Raw values reported by statistical models 
• Presence of alerting groups known from literature 
• Evidence from experimental data for the most similar compounds 
• Other mitigating factors 

The algorithm summarizes these data to determine whether the compound can be treated as potentially safe (Class 5), or as requiring further attention (Class 3).

Reliability of predictions is assessed using a Reliability Index (RI), ranging from 0 to 1, which supplements the statistical model predictions in Impurity Profiling Suite. The RI helps determine whether predictions can be confidently classified as positive or negative and indicates whether a compound falls within the model’s applicability domain.

Impurity Profiling Suite is available as a windows-based thick client application. The software can be installed on individual computers or made available on a network from a central source. The graphical user interface of Impurity Profiling Suite offers all the tools you need to assess the safety of compounds.