Agreeing to Submission Document Timelines & Sticking to Them: Fairy Tale or Reality?

Speaker(s): Steve Sibley
Date: September 14, 2017
Time: 11 am EDT
Duration: 1 hour

Setting and adhering to a timeline for planning, drafting, reviewing and editing regulatory documents needed for the submission dossier is a major challenge for drug development teams. The most common pitfalls in submission planning include:

  • Missing the opportunity to learn and discuss everything possible at the beginning
  • Scheduling summary document preparation in parallel with source document preparation
  • Not engaging all stakeholders in developing the submission

Keeping submission timelines on track can be further compounded when sponsors try to develop simultaneous global submissions. The consequences of a chaotic submission process include wasted time and money, employee burnout, and a suboptimal dossier.

How can teams facilitate the submission process?

In this webinar, Mr. Steve Sibley will define best practices for establishing submission timelines that won’t change, address regional differences to minimize document re-work when submitting to multiple countries, and identify leadership and project management skills helpful to regulatory writing.

About Our Speaker

With a career spanning more than 25 years in the pharmaceutical industry, Mr. Sibley has extensive experience across regulatory writing, consulting, and clinical project leadership roles. He has successfully supported projects from discovery through approval and life cycle management. These include significant roles in more than 50 submissions and, in several cases, leading the entire submission team overseeing all documentation from Modules 1 through 5. Mr. Sibley drives the expansion of the company’s submission leadership and consulting capabilities in guiding clients to successful clearance of regulatory milestones.


Using PBPK Models to Optimize Anti-HIV Drug Dosing for Pregnant Women

Speaker(s): Angela Colbers, Rick Greupink
Date: September 27, 2017
Time: 11am EDT
Duration: 1 hour

Pregnant women are generally excluded from clinical trials as the risks to the fetus posed by testing most new chemical entities or approved drugs cannot be sufficiently ruled out. As a result, the lack of data on maternal and fetal exposure to drugs complicates selecting treatment options and dosing during pregnancy.

An important example of this is treating pregnant HIV+ patients. HIV-1-positive pregnant women are commonly treated with combination antiretroviral therapy (cART) for their own health and to reduce the risk of perinatal transmission. Pregnancy-related physiological changes can alter the pharmacokinetics (PK) of antiretroviral agents, mostly resulting in reduced drug exposure during pregnancy. Decreased maternal antiretroviral exposure may lead to virologic breakthrough and/or development of antiretroviral resistance and increase the risk of perinatal HIV transmission. Also, excessive dosing may result in maternal and fetal toxicity.

Physiologically-based pharmacokinetic (PBPK) models can help predict maternal and fetal drug exposure based on in vitro pharmacokinetic data, guide dosing of antiretroviral drugs in this special patient population, and improve outcomes for both mother and child. Conversely, clinical pharmacokinetic data on antiviral agents administered to pregnant women provides an excellent opportunity to develop, optimize, and validate pregnancy PBPK models.

In this webinar, we will discuss how we combined clinical and pre-clinical approaches to develop a PBPK model to predict the exposure of darunavir, a protease inhibitor commonly used to treat pregnant HIV+ patients. We will discuss the integration of in vitro experimental data on drug metabolism and transport with data obtained from ex vivo human placenta perfusion experiments to quantitatively predict both maternal as well as fetal exposure of darunavir. Moreover, we will elaborate on the study design, data collection, and analyses that were used to investigate the clinical pharmacokinetics of antiretroviral agents during pregnancy.

About Our Speakers

Dr. Angela Colbers is a biomedical scientist trained at Radboud University Medical Center in Nijmegen, the Netherlands, where she also obtained her PhD in the field of Clinical Pharmacology. Since 1995, she has been involved in clinical trial management, analysis, and reporting. She worked for a pharmaceutical company and contract research organizations. Since 2008, she has worked as a researcher at the department of Pharmacy of the Radboud University Medical Center. The department of Pharmacy of the Radboud University Medical Center has taken the initiative to set up a network of hospitals investigating pharmacokinetics in pregnancy in Europe. Dr. Colbers is project coordinator of a protocol entitled “Study on Pharmacokinetics of newly developed ANtiretroviral agents in HIV-infected pregNAnt women (PANNA)”. In addition, she teaches and advises PhDs and other students on developing and executing clinical trials, and she supports senior scientists with their research.

Dr. Rick Greupink is an Assistant Professor of Pharmacology at Radboud University Medical Center in Nijmegen, the Netherlands. He holds a PharmD from the University of Groningen, the Netherlands, obtained a PhD in Pharmacokinetics and Drug Delivery from the same university and further specialized as a pharmacologist during postdoctoral fellowships in both clinical and pre-clinical settings in the pharmaceutical industry and academia. At the Radboud University Medical Center, Dr. Greupink is faculty in the department of Pharmacology & Toxicology, where his research focuses on investigating the pharmacological roles of drug-transporting membrane proteins in barrier and excretory tissues. The aim is to better understand and predict the impact of drug transporters on clinical pharmacokinetics, drug efficacy, and drug-induced toxicity. In this context, current projects include mechanistic studies on drug disposition in pregnancy, placental transfer, accumulation, and effects of small and large molecule pharmaceuticals.


How to Perform Level C IVIVC in Phoenix

Speaker(s): Jean-Michel Cardot
Date: October 31, 2017
Time: 11am EDT
Duration: 1 hour

In vitro in vivo correlation (IVIVC) is built on the premise that the in vitro dissolution characteristics of a drug can serve as a surrogate for a bioequivalance study. This type of analysis is attractive to sponsors because dissolution assays are cheaper and faster to perform than clinical testing. It also provides reassurance that a positive benefit/risk balance for patients is maintained throughout the life of a drug. IVIVC encompasses levels A, B, and C.

Level C correlation relates one dissolution time point (t50%, t90%, dissolution observed at 1h, etc.) to one mean pharmacokinetic parameter such as AUC (the area under the concentration-time curve), Tmax (the time after administration of a drug when the maximum plasma concentration is reached) or Cmax (peak concentration). Only a partial relationship between absorption and dissolution is established since it does not reflect the complete shape of plasma drug concentration time curve, which is the critical factor that defines the performance of a drug product.

Due to its limitations, the usefulness of a Level C correlation is restricted in predicting in vivo drug performance. In early formulation development, Level C correlations can help select pilot formulations. Waiver of an in vivo bioequivalence study (biowaiver) is generally not possible.

In contrast to level C, Multiple Level C correlations refer to the relationship between more than one pharmacokinetic parameter of interest (Cmax, AUC, or any other suitable parameters) and the amount of drug dissolved at several time points in the dissolution profile. Multiple Level C correlations are more powerful than a single level C as it could predict, for example, the two parameters of bioavailability rate (Cmax) and extent (AUC). In those conditions, it may be used to justify a biowaiver provided that the correlation has been established over the relevant dissolution point with all the bioavailability parameters of interest. A multiple Level C correlation should be based on at least three formulations and, if possible, on all the bioavailability parameters: AUC and Cmax.

The development of a level A correlation should also be possible when multiple Level C correlations are achieved for all relevant pharmacokinetic parameters describing rate and extent such that the effect on the in vivo performance of any change in dissolution can be assessed. However, this Level A correlation is not always possible even when a multiple level C exists, for example, when the drug of interest is a metabolite formed pre-systemically or during the elimination processes when administered as a prodrug. In this case, the multiple level C could be seen as the best possible achievable correlation.

Join this webinar with Professor Jean-Michel Cardot to learn how to perform Level C IVIVC using Phoenix. By attending this webinar, you will learn the following:

  • How to calculate pharmacokinetic parameters via the non-compartmental analysis (NCA) module
  • How to calculate dissolution parameters via the dissolution module
  • How to link the in vivo pharmacokinetic parameters and in vitro dissolution parameters via the linear relationship module
  • How to calculate dissolution limits

About Our Speaker

Jean-Michel Cardot is a professor and head of the Department of Biopharmaceutics and Pharmaceutical Technology at the Auvergne University in France. Prior to coming to Auvergne University, he worked in the pharmaceutical industry for 15 years. Prof. Cardot earned degrees in pharmacy (PharmD), a Masters in Bio-pharmaceutical, Statistical sciences and Pharmacokinetics, and a doctorate in pharmaceutical sciences from Auvergne University. His research interests include biopharmaceutical development of drugs, in vitro dissolution, and in vivo bioequivalence and in vitro-in vivo correlation.


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