Simcyp™ PBPK Tech-driven Services

PBPK is used throughout the drug life cycle to support decisions on whether, when, and how to conduct certain clinical pharmacology studies and to support dosing recommendations for product labeling. Used to support strategic decision-making, Simcyp PBPK provides valuable information for designing clinical trials and to obtain clinical trial waivers. Importantly, PBPK helps answer a myriad of “what if” questions about drug performance, dosing and alternate populations that could not be answered without lengthy, expensive and often challenging clinical studies.

Example projects include:

• Drug-drug interaction simulations – perpetrator and victim
• Absorption modelling – formulation effects/bioequivalence, food effect
• Dosing for special populations – pediatrics, elderly, organ impairment, disease conditions, ethnic differences
• Evaluation of drug performance from extrinsic factors – smoking, alcohol
• Novel routes of administration – dermal, inhalation, long-acting injectable, rectal, intravaginal
• Biologics – mAbs, ADCs, other proteins, cytokine mediated DDIs
• Virtual bioequivalence and formulations for complex generics
• Early PK prediction, FIH dosing

Children, older adults, pregnant women, patients with impaired renal or liver function.  These and other sub-populations are not typically included in clinical trials, resulting in a lack of prescribing instructions in the drug label.  Furthermore, dose recommendations typically reflect only a single factor and leave the prescriber guessing as to how to integrate any information for patients with multiple health conditions.

The Simcyp Simulator combines vitro-in vivo extrapolation (IVIVE) and PBPK approaches in virtual individuals to predict drug concentration and effect on these special populations.  It integrates intrinsic and extrinsic factors, data on the drug, the system and sub-population physiology into the PBPK model to account for the multiple covariates driving PK in specific populations. Simcyp has applied this approach and shared with regulators for the following populations:

• Pediatrics, including neonates
• Pregnant and lactating mothers
• Geriatric populations
• Organ impaired – kidney, liver
• Obese individuals
• Ethnic bridging
• Multiple disease states

Formulation development is an iterative process that maps across the drug development paradigm.  MIFD using the Simcyp Simulator supports each of these process steps—from early formulation development guidance and modeling the impact of salts, polymorph, excipients, prodrugs, or solid dispersions—to establishing virtual bioequivalence, bridging and biowaiver approaches. MIFD has demonstrated its value for optimizing drug formulation across different BCS Class drugs, reducing development cost and time.