In the complex world of R&D, acronyms like PBPK and PBBM often seem interchangeable—but they’re not. These two powerful modeling approaches play distinct roles in drug development, and understanding their differences can make a difference in your research or regulatory strategy.
What is the difference between PBPK and PBBM?
Physiologically based pharmacokinetic (PBPK) models describe the pharmacokinetic and physiological mechanisms that control how drugs are disposed of in the body. Physiologically based biopharmaceutics modeling (PBBM) is an extension of PBPK modeling, focusing on drug product quality applications.
How would I use PBBM?
The first step in successfully implementing PBBM is to create and validate a strong PBPK model. Once this foundation is in place, PBBM expands on it by adding formulation-specific information to evaluate the ways in which product characteristics affect in vivo drug performance.
Through the integration of physiological aspects and drug formulation features, PBBM offers a mechanistic knowledge of absorption and how it affects pharmacokinetics (PK). From formulation design and bioavailability evaluation to regulatory approval and lifecycle management, this method is crucial at several phases of drug development. PBBM is becoming more and more acknowledged by regulators as a useful instrument for creating clinically relevant requirements and guaranteeing product consistency over the course of its lifecycle.
Finally, by connecting formulation properties with physiological responses, PBBM improves the predictive ability of PBPK modeling, facilitating better risk assessment and decision-making in drug development.
When should I use PBPK vs. PBBM?
When to apply PBPK modeling or PBBM depends on the specific question you are addressing in your drug development project.
Here’s a guide to help you choose:
Use PBPK When:
Understanding Systemic Drug Behavior
PBPK modeling is ideal when you need to describe how a drug is absorbed, distributed, metabolized, and excreted (ADME) within the body.
Example: Predicting drug concentrations in plasma and tissues over time.
Exploring Population Variability
PBPK excels at simulating drug behavior in special populations, such as:
- Pediatrics, geriatrics, pregnant individuals
- Patients with renal or hepatic impairments
Assessing Drug-Drug Interactions (DDIs)
Use PBPK to predict how co-administered drugs may affect each other’s metabolism or clearance, especially involving CYP enzymes or transporters.
Supporting First-in-Human (FIH) Dosing
PBPK helps in extrapolating preclinical data to humans, guiding safe and effective starting doses in clinical trials.
Use PBBM When:
Formulation Development is the Focus
PBBM is the go-to approach for understanding how formulation properties impact drug release and absorption.
Example: Comparing immediate vs. extended-release formulations.
Evaluating Bioavailability and Bioequivalence
Use PBBM to predict and compare the in vivo performance of different formulations or to justify biowaivers for in vitro-in vivo correlations (IVIVC).
Simulating Food Effects
PBBM is particularly useful for predicting how food impacts drug solubility, dissolution, and absorption in the gastrointestinal (GI) tract.
Assessing Drug Product Changes
When making changes to a formulation (e.g., excipient variations or manufacturing processes), PBBM can predict their impact on performance without additional clinical studies.
Optimizing Oral Delivery
PBBM focuses on the interactions between drug properties, formulation design, and the GI environment, making it indispensable for oral drug delivery systems.
How can PBPK and PBBM optimize my drug development pipeline?
Enhancing Early-Stage Drug Discovery
PBPK: Enables the prediction of systemic drug exposure using in vitro and preclinical data, guiding early decisions on compound selection and first-in-human (FiH) dose predictions.
PBBM: Helps assess the solubility and dissolution profiles of drug candidates, ensuring compatibility with desired formulation strategies.
Benefit: Minimize the risk of advancing unsuitable candidates into costly clinical trials.
Streamlining Formulation Development
PBBM: Predicts how formulation changes (e.g., excipient variations or particle size adjustments) will affect in vivo performance.
Benefit: Avoid unnecessary trial-and-error in formulation optimization.
Predicting Clinical Outcomes
PBPK: Models drug behavior in diverse populations, including pediatrics, geriatrics, or patients with hepatic/renal impairments, eliminating the need for some costly clinical studies.
PBBM: Demonstrates bioequivalence or predicts the impact of food on drug absorption, potentially supporting regulatory biowaivers.
Benefit: Reduce reliance on expensive and time-intensive clinical trials.
Managing Late-Stage Development and Post-Approval Changes
PBPK: Assists in adjusting dosing regimens or evaluating the safety of drugs in new populations or with concomitant medications.
PBBM: Predicts the impact of formulation or manufacturing changes on drug performance, reducing the need for clinical bridging studies.
Benefit: Support lifecycle management with data-driven decision-making.
Accelerating Time-to-Market
By integrating PBPK and PBBM early in the pipeline, you can identify risks, optimize formulations, and predict outcomes, all before significant resources are spent on clinical trials. This not only shortens development timelines but also reduces costs.
Supporting Regulatory Submissions
PBPK: Widely accepted by regulatory agencies to address drug-drug interactions (DDIs), population-specific dosing, and extrapolation from animal to human data.
PBBM: Gaining traction for biowaiver justifications and risk assessment for formulation changes.
Benefit: Streamline the approval process and increase confidence in regulatory interactions.
At Simulations Plus, we specialize in applying advanced modeling and simulation to drive results for our partners.
If you need support for your PBPK or PBBM efforts, we can help. Discuss your project needs with our experts.
By Frederico Martins