We are specialized in providing paper-based safety justifications for drug substances and impurities, ensuring full compliance with ICH Q3A and Q3B guidelines. These justifications are critical for demonstrating that any impurities present in drug substances or drug products are within acceptable safety limits, reducing the need for extensive in vivo studies and accelerating regulatory approvals.

Our Paper-Based Safety Justification Services Include:

Comprehensive Impurity Evaluation:

We begin with a detailed analysis of the impurities present in your drug substance (ICH Q3A) or drug product (ICH Q3B). This includes identifying organic impurities, inorganic impurities, and residual solvents to assess their origin, potential formation pathways, and impact on the drug’s safety and efficacy.

Safety Threshold Determination:

For each impurity, we determine safety thresholds based on established toxicological data. We apply Qualification Thresholds (QT) and Identification Thresholds (IT) as defined by ICH guidelines, ensuring that any impurity at or above these levels is rigorously assessed and justified.

Use of Scientific Literature and Historical Data:

Our team conducts a thorough review of toxicological databases, published studies, and historical data to provide robust safety justifications for identified impurities. This paper-based approach eliminates the need for costly and time-consuming animal studies by relying on existing scientific evidence to support the safety of the impurity.

Qualification of Impurities:

We assess whether each impurity poses any significant risk based on its concentration, route of administration, and duration of exposure. Our paper-based reports evaluate the potential for mutagenicity, genotoxicity, carcinogenicity, reproductive toxicity, and organ toxicity, ensuring a comprehensive safety assessment.

Genotoxic and Non-Genotoxic Impurities:

For genotoxic impurities, we provide a more detailed analysis in line with ICH M7 guidelines to determine their threshold of toxicological concern (TTC). For non-genotoxic impurities, we evaluate NOAEL (No-Observed-Adverse-Effect-Level) or LOAEL (Lowest-Observed-Adverse-Effect-Level) data to justify their safety in the final drug product.

Toxicity Thresholds and Exposure Limits:

We establish Permissible Daily Exposure (PDE) limits for each impurity and provide justification for levels that are within acceptable safety margins. Our assessments consider factors such as dose-response relationships, metabolism, and accumulation to ensure that exposure to these impurities does not pose any risk to patients.

Alignment with ICH Q3A and Q3B Guidelines:

Our services strictly adhere to the ICH Q3A (for drug substances) and Q3B (for drug products) guidelines. We ensure that all impurities are identified, categorized, and justified according to regulatory standards, providing you with a seamless pathway to approval.

Documentation and Reporting:

We provide detailed, scientifically rigorous reports that offer clear justifications for the presence of impurities in your product. These reports include all relevant toxicological data, calculations of acceptable limits, and a narrative that outlines the rationale for each safety threshold. Our paper-based justifications are designed to meet regulatory submission requirements and facilitate the approval process.

Impurity Control Strategies:

Based on our findings, we also recommend impurity control strategies to help you minimize or manage impurities during the manufacturing process. These strategies can help ensure ongoing compliance with regulatory requirements and improve the overall safety profile of your drug product.

Why Paper-Based Safety Justifications Matter: Paper-based safety justifications are an efficient and scientifically sound way to demonstrate the safety of impurities without the need for new experimental studies. By leveraging existing toxicological data and aligning with ICH Q3A and Q3B guidelines, we help you achieve faster regulatory approval while ensuring that your drug products meet the highest standards of safety.

For more information about our services or to request a consultation, contact us at info@toxway.com