Annual Report—Simcyp Consortium Meeting

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 (PBPK) and mechanistic modeling in the prior year, revealing some impressive statistics as shown below:

  • Based on the PBPK review knowledgebase of FDA’s Office of Clinical Pharmacology, 180 records between 2008 and 2015 address various clinical pharmacology issues (Mehrotra et al., DMD, 2016). 66% of these records fall into the category of predicting drug-drug interaction (DDI) potential, with the remaining 34% equally distributed between pediatric PK prediction and other applications (e.g., drug absorption, pharmacogenetics, and organ impairment).

Pie chart showing FDA's OCP records on uses of PBPK

  • The EMA is also focused on industrializing PBPK modeling in drug development and regulatory approval, having recently released draft guidelines on the subject. In about 75% of procedures where a PBPK model is suggested/ submitted, at least one of the purposes relates to DDI (as victim or as perpetrator), specially to CYP3A4 mediated interactions. Other purposes include:
    • Better understanding of PK, role of enzymes and / or transporters …
    • Dose recommendations
    • Food effect
    • Effect of polymorphisms / ethnic differences
    • PK in special population (renal/hepatic impairment)
  • The increased regulatory acceptance of PBPK aligns with the cumulative publications on the topic from the Simcyp team, as shown below:

Cumulative Simcyp publications by year

 

  • With the topics evolving toward the newest opportunities to leverage PBPK

Topics of Simcyp publications

  • Independent publications using Simcyp PBPK are also increasing:

Independent publications using Simcyp PBPK by year

  • With a complementary diversity of topics

Topics of independent publications using Simcyp PBPK

Scientific education

The main day of the meeting highlighted both Simcyp science and Consortium member case studies. The Simcyp team delivered a dozen presentations on current work, with topics ranging from the expansion of pharmacodynamic (PD) models to animal simulators and in vitro in vivo extrapolation (IVIVE) translation to ‘Simcyp in the cloud’ to a review of several new grant awards including a ‘just announced’ absorption grant from the FDA. Another half dozen case studies delivered by Consortium members focused on DDI label approvals from the FDA and EMA, the use of the Simcyp ADAM module for absorption, PBPK transporter models, and in vitroin vivo correlation (IVIVC).

As is the tradition, Simcyp presented awards to academic partners/users. This year, the awards were given to Long Island University for its pharmacological education program and Geneva University Hospital for using PBPK to study cardiovascular risk in HIV patients. And finally, the winner of the Grant and Partnership Scheme for 2015/2016 was Radboud University Medical Center to study the mechanisms of antiretroviral agents’ pharmacokinetics in pregnancy.

We anticipate another progressive year in PBPK, mechanistic modeling and regulatory science. Our continued commitment to advancing science and education remains steadfast.

In closing, the best way to summarize the evolution of Simcyp and PBPK was expressed by one of the Consortium members, who said,

“Just a few years ago, PBPK was an academic exercise. Now, it is an integral part of regulatory submissions.”

For more information, check out the list of Simcyp-authored and independent-authored published papers.

Ellen Leinfuss

About the Author

Ellen Leinfuss

Senior Vice President & Chief Commercial Officer, Certara

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Ms Leinfuss brings more than 25 years of experience leading marketing, business development and sales management groups for technical and scientific-based organizations. She spent the last nine years at UL EduNeering, a global provider of regulatory compliance educational solutions, delivered via cloud-based technology. At UL, Ms. Leinfuss directed the strategic development of the company’s solutions to the life science market, including pharmaceutical, medical device, biologics, clinical, and managed care health plans. In addition, she managed the Company’s strategic alliances, including the Company’s 15 year Cooperative Research and Development Agreement (CRADA) with the US FDA and its exclusive partnerships with AdvaMed and the Personal Care Products Council, among others. Ms Leinfuss possesses a Master's in Business Administration in marketing from the City University of New York and Bachelor's in Chemistry from the State University of New York.