The Certara Blog: PBPK Modeling & Simulation

Modeling & Simulation Take a Prominent Role in FDA’s Newly Published DDI Guidances

On October 25, 2017, the FDA published two new guidance documents on drug-drug interactions (DDI). These guidance documents replace the February 2012 guidance, “Drug Interaction Studies—Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations.” According to the FDA, these new guidances reflect the agency’s current thinking and greater learnings on DDI and provides a […]

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A Chat with Biopharmaceutics Expert, Professor Jennifer Dressman

Professor Jennifer Dressman is fearless—both in her science and her career. Born and raised in Australia, she holds degrees in pharmacy and a doctorate in pharmaceutics. Having held positions at Burroughs Wellcome and the University of Michigan, College of Pharmacy in the United States, she was offered her dream job as a professor at the […]

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FDA Reauthorization Act (FDARA) Affirms Commitment to Innovative MIDD Strategies

Quietly, without any political rancor, the FDA Reauthorization Act of 2017 (FDARA) was passed by the US Congress and was signed into law by President Trump in late August. The FDARA reauthorizes the Prescription Drug User Act Fee Amendments (PDUFA) for the fifth time, the Medical Device User Act Fee Amendments (MDUFA) for the third […]

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New FDA Commissioner Endorses Use of M&S to Advance Drug Development

With the swearing in of Dr. Scott Gottlieb as Commissioner of Food and Drugs in May, many have wondered as to the climate he will set for the US FDA. Certara’s mission and business thesis aligns with the FDA’s July 7 announcement regarding the steps it is taking to implement the 21st Century Cures Act. […]

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Mechanistic Modeling of Genome Scale Molecular Interaction Networks

Upon the completion of the Human Genome Project, the lead investigator, Dr. Francis Collins remarked: Science is a voyage of exploration into the unknown. We are here today to celebrate a milestone along a truly unprecedented voyage, this one into ourselves. Alexander Pope wrote, “Know then thyself. Presume not God to scan. The proper study […]

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Nurturing the Pharmacometricians of the Future

As a scientist, you always remember your first conference. The ability to share your research and learn from your peers is an invaluable part of any scientist’s training. That’s why I’m so proud that Certara helps support the travel and accommodation expenses for a selected number of students wishing to attend the Population Approach Group […]

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PBPK Modeling of Supersaturating Drug Product Behavior

The problem of supersaturating drug products might loosely be summed up as: “If you’re not part of the solution, you’re part of the precipitate!” Indeed, more than 60% of new drug candidates are poorly soluble1 which can severely limit their bioavailability. To ameliorate this issue, a common approach is formulating to create supersaturated solutions of […]

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Predicting Drug Exposure During Pregnancy Using PBPK Models

Moms want the best for their kids even before they’re born. When I was pregnant with my son and daughter, I watched my diet and tried to stay active. During both of my pregnancies, I had to take medications several times. And I was always concerned about whether the medications could impact my unborn children. […]

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New Tools Support Developing Better TB Drugs

Tuberculosis (TB)—caused by infection with the mycobacterium Mycobacterium tuberculosis—is one of the top 10 leading causes of death worldwide with a total of 1.8 million people dying from the disease in 2015. TB is also the leading cause of death in HIV-infected individuals. TB usually attacks the lungs but can infect any part of the […]

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The Ides of March—FDA’s Pharmaceutical and Clinical Pharmacology Advisory Committee Meeting

While ominously scheduled for March 15, no such drama (like the assassination of Julius Caesar, the origins of ‘beware the Ides of March’) occurred during the FDA’s Pharmaceutical Science and Clinical Pharmacology Advisory Committee meeting. It was quite productive, acknowledging the tremendous impact of modeling and simulation in drug development and regulatory review moving the technology further into the mainstream.

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The Model-informed Precision Dosing Revolution Is Coming

Modeling and simulation (M&S) has been widely accepted and adopted by biopharmaceutical companies and global regulatory agencies. However, its implementation in clinical care has been modest to date. Model-based approaches are essential to realize the goal of precision dosing—providing the right drug dose to maximize therapeutic benefit, while reducing risk for each individual patient. The […]

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Leveraging PBPK Modeling and Simulation for Neonatal and Infant Drug Development

Despite increased regulatory support for pediatric drug development, sponsors still face ethical, economic and practical constraints. Indeed, while children represent about 40% of the world’s population, only 10% of the drugs on the market have been approved for pediatrics. Children are not small adults, and all children are not the same. In particular, children under […]

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Prediction of Liver Volume; One Size Doesn’t Fit All!

When your physician writes you a prescription, they do so knowing that the dose prescribed will (on average) be safe and beneficial to you, but that it is likely certainly not optimal for you as an individual (as has been the topic of a previous blog post). The balance between absorption, distribution and elimination of […]

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Image of whole body PBPK model and USP-2 dissolution chamber

Transforming Drug Product Development the PBPK Way!—A Breakthrough Approach

Developing and optimizing drug formulations― a key component of a product development―is a very lengthy and capital intensive process. Today, most drug candidates are poorly water-soluble; this has led to greater emphasis on screening more complex formulation technologies. Formulation development is still largely an empirical process ― based on trial and error and formulation scientists’ […]

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drug drug interaction

Best Practices in PBPK: The Case of Efavirenz

According to the FDA’s Guidance for Industry on Drug-drug interactions (DDIs), assessment of a new drug’s DDI liability has three major objectives: determining whether any interactions necessitate dosing adjustment, informing the extent of therapeutic monitoring that may be required and identifying any potential contraindications to concomitant use when lesser measures cannot mitigate risk Physiologically-based pharmacokinetic […]

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A virtual Vitruvian man over a map of the United States

How PBTK Models Support Toxicological Triage

Did you know that only a small fraction of the tens of thousands of commercially-used chemicals have undergone toxicological assessment? Time and cost constraints, not to mention the ethical impossibility of studying these chemicals in human trials, hamper large-scale toxicological assessment. Physiologically-based toxicokinetic (PBTK) models can be leveraged to predict TK from in vitro measurements […]

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virtual man touching a strand of DNA

The Impact of Genetic Polymorphisms and DDIs on Exposure

Physiologically-based pharmacokinetic (PBPK) modeling and simulation is increasingly accepted due to the enormous cost and time saving benefits that can be realized through its ability to address regulatory concerns without always defaulting to clinical study — particularly relating to assessing complex drug-drug interactions (DDIs). Independent validation of simulations against clinical data provides confidence in the […]

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brain in a maze

Modeling and Simulation Guides Dosing for a New Anti-psychotic Drug

Drug development is becoming more complex than ever. Regulatory agencies expect sponsors to consider a wide variety of intrinsic and extrinsic factors that could impact drug safety and efficacy. These factors include intrinsic variability― CYP metabolizer status, age, sex, renal/hepatic impairment― as well as external variables― co-medications, food effects, smoker status, etc. Clinical trials alone […]

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A report on the Simcyp consortium

Annual Report—Simcyp Consortium Meeting

It may be 2016, but we just held the 17th annual Simcyp Consortium meeting in Sheffield, UK. This year’s gathering had >120 attendees with representatives from all but one of the 34 consortium member companies joining. The opening session reviewed the progress made by the Simcyp staff toward the field of regulatory science, physiologically-based pharmacokinetic […]

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Police crime scene tapes covers up the Vitruvian man.

How PBPK Can Help Solve Fatal Poisonings

My mom― a clinician scientist herself― would often say this about the power of pharmacology: Every medicine has its price. While most patients benefit from their medications, cases of fatal drug poisonings are tragedies wherein patients pay the ultimate price. Forensic toxicology probes cases of fatal poisonings where the cause of death is unknown. This […]

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