Physiologically Based Kinetic (PBK) models are increasingly being recognized as powerful tools in various sectors, including academia, industry, and regulatory agencies. These models provide a detailed representation of the human body through interconnected compartments that simulate the absorption, distribution, metabolism, and elimination (ADME) of chemicals. The growing interest in PBK models is driven by their potential to offer insights into dosimetry related to adverse health effects without relying on animal testing.
The Rise of PBK Models
The use of PBK models has surged over the past two decades, thanks to advancements in good modelling practice (GMP) and the integration of new approach methods (NAMs) such as in vitro studies and in silico predictions. These methods offer a viable alternative to traditional animal testing by providing experimental data that can be used to parameterize models for chemicals lacking in vivo data.
Challenges in Regulatory Acceptance
Despite the advancements in PBK modelling practices, regulatory acceptance remains a challenge. Regulatory agencies often exhibit reluctance to incorporate these models into risk assessment processes due to concerns about their validity and applicability. A survey conducted among the modelling community highlighted this issue, indicating a need for further guidance and standardization in GMP.
Implementing Good Modelling Practice
The development of PBK models involves a systematic approach that includes defining a conceptual model, translating it into mathematical equations, parameterizing these equations with reliable data, evaluating model performance, and using simulations for predictions. Practitioners can enhance their skills by adhering to GMP guidelines that emphasize transparency, documentation, and reproducibility.
- Defining the Model: Start with a simplified representation of the biological system and develop a conceptual model.
- Mathematical Translation: Formulate differential equations for each compartment based on the conceptual model.
- Parameterization: Use literature data or experimental results to define equation parameters.
- Solve and Simulate: Calculate compound concentrations and simulate scenarios to make predictions.
The Importance of Peer Review
An independent peer review system is crucial for gaining regulatory acceptance of PBK models. By establishing a network of experts knowledgeable in GMP, practitioners can ensure that their models undergo rigorous evaluation before submission for regulatory purposes.
The Future of PBK Models
The next generation of PBK models could be developed using data exclusively from NAMs. This shift requires practitioners to stay informed about emerging methodologies and technologies that enhance model accuracy and reliability.
Encouraging Further Research
Pursuing further research in PBK modelling can significantly improve practitioners' skills and contribute to broader acceptance of these models in regulatory contexts. Engaging with workshops, conferences, and publications will provide valuable insights into cutting-edge practices and challenges within the field.
