Impurity Profiling Suite

ACD/Labs Impurity Profiling Suite is a toxicity and carcinogenicity prediction software designed to help pharmaceutical and biotech organizations assess the genotoxic and carcinogenic potential of impurities and degradants. Developed through a collaborative agreement with the US Food and Drug Administration (FDA), the software supports ICH M7(R2) compliance workflows and is accepted by the FDA, European Medicines Agency (EMA), and other regulatory bodies.

The software predicts 21 toxicological endpoints from chemical structure and provides ICH M7(R2) classifications for impurities and degradants. It is suited to small and medium-sized organizations as well as large pharmaceutical and biotech companies seeking to reduce experimental genotoxicity testing and streamline regulatory submissions.

Toxicological Endpoints and Classifications

• Predicts 21 toxicological endpoints from structure, covering mechanisms of hazardous activity including mutagenicity (AMES test and other prokaryote and eukaryote test systems), clastogenicity, other DNA damage, carcinogenicity, and endocrine disruption mechanisms
• Provides ICH M7(R2) classifications: Class 1 (known carcinogen), Class 2 (known mutagen), Class 3 (alerting/potentially hazardous structure), and Class 5 (no alerts or sufficient data for lack of mutagenicity)
• Reports ICH M7 Class as Inconclusive when a definitive classification cannot be made from experimental data alone
• Identifies potentially hazardous structural fragments responsible for carcinogenic and genotoxic activity, with structure highlighting to indicate alerting groups or substructures
• Provides insight into possible mechanisms of toxic effects

Prediction Models and Reliability

• Includes both a probabilistic model and a knowledge-based (expert system) model, following OECD validation principles
• The expert system identifies 67 alerting groups of toxicophores known from the literature: 53 account for point mutational and/or clastogenic mechanisms of DNA damage, and 14 substructures represent carcinogens acting by non-genotoxic mechanisms
• Predictions are based on curated public and regulatory data provided by the FDA
• A weight of evidence (WOE) approach is applied when a conclusive classification cannot be made from experimental data alone, incorporating probability of hazardous effects from statistical models, presence of alerting groups, evidence from similar compounds in the built-in database, and other mitigating factors
• Reliability is evaluated using a reliability index, display of similar structures, and literature references for experimental data
• Results from the probabilistic model are presented as a tree, with individual nodes grouped by species/test system and mechanism of action; each endpoint includes a p-value, coverage (applicability domain), and a positive/negative call
• Displays the five most similar structures in the training set, including name, CAS number, experimental results, quantitative TD50 values, and tumor target sites for carcinogenicity

Alerting Groups and Fragment Analysis

• View a full list of alerting groups and hazardous fragments identified in a structure
• For each alerting group, the software provides statistical data on positive and negative compounds, a Z score indicating statistical significance of the fragment's contribution to a positive test result, a description of the mechanism of action, and literature references
• Structure highlighting visually indicates the alerting group or substructure within the compound

Compound Input and Batch Processing

• Accepts structures drawn in-app, copied/pasted from third-party drawing packages, entered as SMILES strings or InChI codes, imported from MOL, SK2, SKC, or CDX files, or searched by name in the built-in dictionary
• Automatic detection of tautomeric forms, with the option to select the canonical or major form
• Calculates toxicological endpoints for single compounds or libraries of hundreds to thousands of compounds using a spreadsheet workspace
• Built-in tools support sorting, filtering, plotting, and ranking of results; user-defined label colors and numerical filters are available
• Activity history allows retrieval of previously calculated results

Workflow Steps

1. Draw or import the structure(s) of interest
2. Review results and make classification decisions, supported by weight of evidence information and alerting group data
3. Export the ICH M7(R2) assessment to PDF or copy/paste results to another application

ICH M7(R2) Compliance

• The software classifies structures according to ICH M7(R2) guidelines and provides supporting evidence for class assignments along with recommendations for appropriate control measures
• Both (Q)SAR and SAR methodologies are included, as permitted by regulatory agencies in lieu of in vitro testing
• Models adhere to OECD validation principles, requiring a defined endpoint, an unambiguous algorithm, a defined domain of applicability, appropriate measures of goodness-of-fit and predictivity, and mechanistic interpretation where possible
• Results are accepted by the FDA, EMA, and other regulators

What's New in Version 2025

• Automatic assessment of N-nitrosamines without experimental data using the Carcinogenic Potency Characterization Approach (CPCA)
• Batch reporting mode to analyze compounds within the context of an entire project
• Improved accuracy of the Bacterial Composite (Procaryote Mutagenicity) predictor

Impurity Profiling Suite is available as a Windows-based thick client application, installable on individual computers or deployed across a network from a central source. Custom models or algorithms can be added by connecting to an existing web service via XML protocol or as a DLL (available in thin client deployments). The software is part of ACD/Labs' broader Percepta platform and complements related tools such as ADME Suite and Tox Suite for broader physicochemical and toxicological property prediction.