Mirabilis

Mirabilis is an in silico software solution developed by Lhasa Limited, designed to support pharmaceutical scientists in accurately assessing and managing the risk of potentially mutagenic impurities (PMIs) during drug substance synthesis. It provides an industry-standardised approach for calculating purge factors, helping organisations evaluate carry-over risk for PMIs and determine appropriate control strategies in line with regulatory requirements such as ICH M7.

Identification and control of impurities and degradants in active pharmaceutical ingredients (APIs) and pharmaceutical drug products is a critical aspect of chemical safety assessment during drug development. Mutagenic impurities can complicate formulation, lengthen development timelines, and impact shelf life, while several regulations now require greater reporting and control of impurities and degradants at lower levels based on the threshold of toxicological concern and daily dose.

Impurity Risk Management

• Mirabilis functions as a risk assessment tool to assist with the management of potentially mutagenic impurities throughout drug substance synthesis.
• The software generates a reactivity purge factor for impurities based on empirical data.
• Predictions are provided for reactivity, solubility, and volatility purges.
• Mirabilis can calculate the purge required to eliminate an impurity and determine the purge ratio, enabling users to identify whether Option 4 is the best control strategy as per ICH M7.

Purge Factor Prediction Capabilities

• Reactivity predictions are based on the actual reagents and conditions confirmed by the user, ensuring scientifically grounded outputs.
• A solubility purge calculator is included, applied for extractions, providing additional supporting information for such purges.
• A volatility calculator allows volatility purges to be applied based on the impurity's boiling point, as well as the operational temperature and pressure or solvent being removed.

Regulatory Alignment and Reporting

• Mirabilis provides an industry-standardised approach for calculating purge factors, directly supporting regulatory submission requirements.
• Users can create reports that include the predicted purge calculation, scientific rationale, and supporting evidence, suitable for inclusion in regulatory submissions.
• Mirabilis can be used to help satisfy ICH M7 Control Option 4 by producing estimated reactivity, solubility, and volatility purge factors for removal of impurities by a synthetic process.
• By demonstrating that impurities are unlikely to be present in the final drug product, Mirabilis can reduce the need for costly and time-consuming analytical methods.
• Mirabilis members have the opportunity to interact and exchange knowledge and experiences at regular conferences promoted by Lhasa Limited.

ICH M7 Regulatory Support

• Under ICH M7, potential degradation products likely to be present in the final drug product must be evaluated for mutagenic potential.
• Mirabilis supports Control Option 4 by providing purge factor calculations that demonstrate impurity removal through the synthetic process.
• The tool helps reduce reliance on analytical testing for impurities that are unlikely to reach the final drug product, saving time and resources during development.

Mirabilis is part of Lhasa Limited's broader suite of in silico tools for impurity and degradant control, which also includes Zeneth for degradation pathway prediction and Vitic Q3D for elemental impurity assessments. Together, these solutions are designed to support compliance with key regulatory frameworks including ICH M7, ICH Q3B, and RDC 964, helping pharmaceutical organisations streamline their drug development workflows and regulatory submissions.