(Q)SAR Computational Modeling & Simulation

In many regulatory and development scenarios, gaps in the scientific literature are inevitable, whether due to the novelty of a compound, ethical constraints on testing, or the absence of published studies. Computational Modeling & Simulation (CM&S), including (Q)SAR models, serve as a regulatory-backed and scientifically grounded solution where traditional experimental or literature-based data falls short.

How does a toxicologist use CM&S/(Q)SAR?

Quantitative structure activity relationship (Q)SAR modeling is a tool used to estimate the pharmacological and toxicological properties of a chemical based on its structure. As the investigator, Tox By Design provides the requisite computational power, tox literature, regulatory & toxicological expertise, and CM&S software proficiency required to assist the Marketing Authorization Applicant (MAA) as the sponsor with their experimental needs. By comparing the structure of a novel chemical to all other documented compounds in toxicological literature and interpreting the results, our team of expert toxicologists can perform the following in silico services:

• Predict toxicological endpoints (e.g., genotoxicity, hepatotoxicity, skin irritation) for compounds with little or no empirical data
• Estimate hazard or risk levels based on structural analogs or mechanistic knowledge
• Justify waiving certain in vivo or analytical tests for biotech drug candidate toxicity profile prediction, out of specification biotech impurity prediction, pharma batch release out of specifications, ICH M7
• Support read-across arguments when supplemental tox data is available pertaining to a novel compound

These predictions are not speculative—we ensure that every in silico (Q)SAR prediction has each of the following OECD principals:

• A defined endpoint
• An unambiguous algorithm
• A defined domain of applicability
• Appropriate measures of goodness of fit, robustness and predictivity
• A mechanistic interpretation, if possible

CM&S is especially valuable when testing is not feasible, not ethical, or not yet conducted, helping sponsors move forward with confidence while maintaining compliance and scientific integrity.

With which CM&S models are we proficient?

Our expert team is flexible and can use any regulatorily validated (Q)SAR model provided. We generally run several simulations with multiple different models for one procedure to fortify simulation results. In particular, we frequently use the following tools that are compliant with EMA, EU member states regulatory bodies and Swissmedics:

•  Instem (ex Leadscope) Model Applier
• ToxTree
• PreADMET
• Automated NDSRIs CPCA Digitalized Tool
• Advanced REACH Tool
• GenRA (EPA read across)
• PubChem Similarity Search
• Danish (Q)SAR Database
• ProtoQSAR
• QSAR Toolbox
• QsarDB
• VEGA

Is my confidential data safe with Tox by Design?

At Tox by Design, all confidential data related to your drug candidates and impurities is securely stored on our locally hosted IT infrastructure, which is inspected under Good Distribution Practice (GDP) standards and approved by the French regulatory authority (ANSM). We do not use cloud-based storage. Instead, all data is retained exclusively on a VPN-secured Network Attached Storage (NAS) system to ensure the highest level of confidentiality for your experimental data.

What are my responsibilities as the sponsor?

In anticipation of future Good Simulation Practices (GSP), current business practices tend towards the following division of responsibilities:

How is the quality of a simulation maintained?

We follow the standards of quality for (Q)SAR models and predictions that are laid out by the Organisation for Economic Co-operation and Development (OECD), ICH and EMA. Additionally, our experience with Socosur Chem as a Good Distribution Practices certified company demonstrates our ability to build a regulatory compliant quality system from the ground up, which will come back into play when GSPs are fully operational and enforced. If you are interested in a (Q)SAR quality assessment framework or in a (Q)SAR assessment for your compound, please request a quote below.