Toxicology
at Annion
Regulatory Toxicology
Our experts ensure your products meet global safety standards by assessing potential risks and supporting compliance with agencies like the FDA and EMA. We help you navigate complex regulations, ensuring your drugs are safe for human use.
Occupational Toxicology
Additionally, our team focuses on protecting your workforce by assessing chemical exposures and implementing safety measures in your facilities. We ensure a safe working environment while complying with industry standards.
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Regulatory Toxicology
At Annion, we specialize in Regulatory Toxicology, a critical field dedicated to assessing the safety and regulatory compliance of chemicals, pharmaceuticals, and other substances to ensure they comply with stringent regulatory standards and do not pose undue risks to human health or the environment. Our services encompass the preparation of comprehensive, tailored reports that meet all regulatory requirements, providing our clients with confidence that their products uphold the highest safety standards.
We take a personalized, collaborative approach, working closely with our clients to understand their specific needs and address any questions. Our team remains accessible and committed to offering clear guidance and support, ensuring a customized service experience that aligns with each client’s unique goals and regulatory demands in industries such as pharmaceuticals and chemicals.
Regulatory Toxicology Reports and Deliverables
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At Annion, we provide expert preparation of PDE (Permitted Daily Exposure) reports, which play a critical role in regulatory toxicology, especially in the pharmaceutical industry.
A PDE report determines the maximum amount of an active pharmaceutical ingredient (API), residual solvents, impurities, or contaminants that a patient can be exposed to on a daily basis without adverse effects. This document is essential for ensuring patient safety and compliance with stringent regulatory standards, particularly in drug development and manufacturing.
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The ICH M7 Assessment Report focuses on the identification and evaluation of potential mutagenic impurities that may be present in drug substances or drug products. These impurities could pose a carcinogenic risk, and a thorough assessment is essential to ensure product safety and compliance with regulatory expectations.
At Annion, we follow the ICH M7 guidelines, which emphasize identifying DNA-reactive impurities, evaluating their mutagenic potential, and proposing appropriate control strategies to mitigate these risks. Our ICH M7 reports are comprehensive, addressing the genotoxicity of identified impurities, and are crucial for pharmaceutical companies seeking regulatory approval. Our approach includes genotoxicity and carcinogenicity data analysis, structural alert detection, (Q)SAR analysis, and toxicological support for implementing control measures.
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Our team at Annion specializes in the toxicological assessment of impurities that may be present in pharmaceutical products. This process involves evaluating the potential health risks associated with chemical impurities to demonstrate patient safety and ensure regulatory compliance.
Our toxicological impurities assessments include comprehensive literature reviews, structure-activity relationship (SAR) analysis, and (Q)SAR predictions to identify the best strategies for impurity qualification. Data gap identification is also included when required.
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Nitrosamines are a class of impurities with potential carcinogenic risks, and their identification and control have become a key priority from both the pharmaceutical industry and the regulatory perspective.
Our toxicological expert assessment evaluates the carcinogenic potency and establishes the associated Acceptable Intake (AI) limits for nitrosamine impurities. This includes the analysis of small molecule nitrosamines and NDSRIs*, along with the evaluation of experimental data and mechanistic and metabolic fate data. We also perform read-across analysis from surrogates to identify potential risks and CPCA-derived limits.
We offer an in-depth assessment of the root causes of nitrosamine formation and propose mitigation strategies within the control measures for nitrosamines. Additionally, we provide regulatory support to guide strategic decisions related to nitrosamines, ensuring alignment with the latest regulatory updates. Our expertise includes keeping you informed about recent scientific developments and regulatory changes that are shaping the evolving regulatory landscape for nitrosamine impurities.
*Nitrosamine Drug Substance-Related Impurities
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An Extractables and Leachables (E&L) report is a detailed evaluation of the potential migration of chemical compounds from packaging materials, medical devices, pharmaceutical containers, or other products into their contents. This analysis is crucial in industries such as pharmaceuticals, medical devices, and food packaging, where chemical interactions between materials and products need to be assessed to ensure safety and regulatory compliance.
At Annion, we conduct comprehensive E&L assessments to identify and control risks associated with these potential chemical interactions. Our services include exhaustive bibliographic research, toxicological data analysis, and the determination of acceptable daily exposure values (PDE, ADI, or TTC) for each compound. If data is insufficient, we utilize SAR/QSAR predictions to establish appropriate exposure limits and provide a detailed toxicological profile.
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At Annion, we offer comprehensive Environmental Risk Assessment (ERA) services to evaluate the potential risks that medicinal products may pose to the environment. The ERA process is designed to protect both aquatic and terrestrial ecosystems, assessing impacts on surface water, groundwater, soil, species at risk of secondary poisoning, and microbial processes in sewage treatment plants (STPs). This critical assessment helps ensure that any pharmacologically active substances in medicinal products are thoroughly evaluated for their environmental impact.
All active substances in a medicinal product must undergo an ERA. If environmental risks are identified and cannot be excluded, we work with our clients to develop and implement specific strategies to mitigate these risks.
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In the field of regulatory toxicology, (Q)SAR (Quantitative Structure-Activity Relationship) and Read-Across methods are invaluable for predicting toxicological properties of substances when experimental data are unavailable. At Annion, we specialize in conducting risk assessments for potential mutagenic impurities, utilizing dual (Q)SAR models that integrate expert-rule and statistical estimations in accordance with ICH M7 guidelines. We employ high-quality, industry-leading (Q)SAR software for which Annion holds internal licenses.
Our (Q)SAR and Read-Across methods deliver reliable, scientifically rigorous predictions that strengthen regulatory submissions and help expedite approval processes. By reducing the need for further testing, these approaches save time and resources while ensuring products meet safety standards.
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We offer expert support for regulatory submissions, particularly when responding to deficiency letters issued by health authorities regarding impurities. Our team conducts thorough investigations and prepares scientifically grounded responses that address the concerns raised by regulatory agencies.
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Occupational Toxicology
At Annion, we specialize in Occupational Toxicology, a field focused on protecting workers health by assessing and managing exposure to hazardous substances in the workplace. Our services are designed to help employers implement effective safety measures, ensure compliance with occupational safety regulations, and maintain a safe working environment. We provide thorough toxicological assessments and essential support to manage chemical risks, safeguarding both employee health and organizational compliance.
We take a personalized, collaborative approach, working closely with clients to understand their specific needs and address any concerns. We remain reachable, offering clear, straightforward guidance and support to ensure a customized service that aligns with each client’s unique requirements in industries such as pharmaceuticals and chemicals.
Occupational Toxicology Reports and Deliverables
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We deliver expert Occupational Exposure Limit (OEL) Reports, which are critical for establishing the maximum permissible concentration of hazardous substances in workplace air. These reports are essential for safeguarding workers´ health by setting limits on their exposure to potentially harmful chemicals.
Our OEL Report service includes comprehensive literature research, a thorough evaluation of clinical, pharmacological, and toxicological data, and the identification of critical effects. We calculate the OEL by determining endpoint values, and present a detailed report that covers essential pharmacokinetic, pharmacodynamic, and toxicological findings, providing the necessary guidance for establishing workplace safety protocols.
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The Occupational Exposure Band (OEB) Report categorizes chemical substances based on their potential health risks when workers are exposed to them. This report is vital for determining safe handling practices and protective measures.
Our OEB reports provide detailed risk assessments that assist employers in establishing appropriate safety protocols, including personal protective equipment (PPE), engineering controls, and administrative controls. By following our recommendations, organizations can minimize health risks and comply with occupational safety regulations.
For investigational new drugs or pure substances, we conduct OEB investigations by considering key factors such as the mechanism of action and structure-activity relationship (SAR). Our process involves an extensive bibliographic search for relevant data on the active pharmaceutical ingredient (API), followed by a thorough review and analysis to identify critical effects and risks. Based on the pharmacological and toxicological potency of the API, we assign the appropriate occupational band/category according to the INSST*categorization system (NTP1104).
*National Institute for Safety and Health at Work
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Our CLP service focuses on the accurate classification of chemical substances and mixtures according to regulatory standards. We assess toxicological data to determine the appropriate hazard classes and categories, ensuring this information is clearly communicated on product labels. We also ensure that product packaging meets all safety standards to protect against harm during handling, transport, and use.
Our expert guidance includes label elements such as pictograms, signal words, and precautionary statements, aligning with the globally harmonized system (GHS) to effectively communicate potential risks to users. At Annion, we help clients navigate complex regulatory requirements, safeguard public health, and maintain market access for their products.
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Occupational health hazard assessment of intermediates used in the synthesis of active pharmaceutical ingredients (APIs) is essential for identifying potential intrinsic hazards that could lead to adverse effects.
Often, these intermediates are compounds with limited or no available toxicity data. To address this, we conduct a comprehensive toxicological assessment, covering the Occupational Exposure Limit (OEL) and Occupational Exposure Band (OEB) of the API. In addition, we evaluate the potential pharmacological activity of the intermediate by investigating the mechanism of action and analyzing the structure-activity relationships (SAR) relative to the API.
In our toxicological assessment of the intermediate, we identify compound-specific data and alerting features in the structure that could suggest potential toxicological concerns. We employ in-silico SAR models to assess relevant toxicological endpoints and use read-across analysis from surrogates where necessary.
Lastly, we provide an occupational band categorization of the intermediate and, if experimental data are available, propose a CLP classification to ensure proper safety and regulatory compliance.