Ping Zhao, Ph.D.
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CURRICULUM VITAE
Ping Zhao, Ph.D.
EDUCATIONAL BACKGROUND
· Ph.D. Pharmaceutics, 1998-2002. Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA
· B.S. Pharmacy, 1990-1994. School of Pharmacy, Peking University Medical Center, Beijing, China
PROFESSIONAL EXPERIENCE
v 04/2013-present: Scientific Lead, physiologically-based pharmacokinetic modeling (PBPK) program, Division of Pharmacometrics, Office of Clinical Pharmacology (OCP), Office of Translational Sciences (OTS), FDA
v 06/2008-04/2013: Senior Clinical Pharmacologist, Immediate Office, OCP/OTS, FDA
1. REGULATORY REVIEW IN OCP, FDA
· Delivered 100+ PBPK IND/NDA/BLA reviews in 7 years
o Evaluated sponsors’ models, conducted FDA analyses, and used PBPK results to support dose recommendations in reviews and drug labels (approved NDA/BLA summarized in Table 1)
o Strived to set evidentiary standards for PBPK review through establishment of OCP PBPK knowledgebase and scientific research (See #2 below)
o Responded and resolved far-reaching, complex review issues related to the effect of multiple intrinsic/extrinsic factors (e.g., co-medications, organ impairment, pediatrics, food, gastric pH) on drug exposure and response
o Provided recommendations to review teams and externally to sponsors on the design and analysis of clinical pharmacokinetic (PK) and pharmacodynamic (PD) studies using clinical pharmacology principles and standard (e.g., compartmental and population PK/PD) as well as contemporary (e.g., population-based PBPK) modeling tools
o Authored/co-authored PBPK reviews (Examples available online for drugs listed in Table 1)
· Led PBPK review as a subject expert in modeling and drug disposition
o Determined adequacy of PBPK results and provided labeling recommendations to review teams
o Oversaw the use of PBPK modeling tools for support of clinical pharmacology reviews
o Supervised direct report and provided scientific directions to colleagues on PBPK reviews
o Represented office and the FDA at sponsor meetings concerning clinical pharmacology issues
2. REGULATORY POLICY AND REGULATORY SCIENCE IN OCP, FDA
· Led PBPK research projects and policy development
o Led the development of the first FDA guidance on format of content of PBPK submissions (ongoing)
o Contributed development of clinical pharmacology guidance documents (drug interactions, organ impairment, pediatrics, pregnancy, pharmacogenomics) and office policy/procedures
o Provided scientific, managerial and technical supervision to fellows, visiting academic scientists, and visiting drug regulators from other countries to accomplish impactful regulatory research projects (See Table 2)
o Strived to establish evidentiary standards on the use of PBPK to support review and policy development through scientific research and publications (See Peer Reviewed Journal Publications)
o Disseminated PBPK regulatory science through teaching and meeting presentations (See Oral Presentations and Teaching)
o Oversaw the planning and execution of multiple scientific projects (Commissioner’s Fellowship, Critical Path Initiative, Medical Counter Measure Initiative, Office of Women’s Health)
o Established internal PBPK expertise and organized workshops and trainings
· Collaborated with others internally and externally
o Regularly participated in discussions with EMA and PMDA colleagues on the use of PBPK modeling and simulations in clinical pharmacology drug development and review
o Collaborated with international thought leaders in academia and other regulatory bodies (e.g., Wu, Pharm Res,, 2014, Jiang, CPT-PSP, 2013, Hsu, Clin Pharmacokinet, 2013, Ke, four publications, Vieira, Clin Pharmacol Ther 2012, Zhao, J Clin Pharmacol, 2012, Grillo, Biopharm Drug Dispo, 2012, Duan, J Clin Pharmacol 2011, Zhao, J Clin Pharmacol 2009 under Peer Reviewed Journal Publications)
o Led FDA-PharmaIQC-academic initiative on model-based prediction (e.g., Vieira, Kirby et al, Clin Pharmacol Ther, 2013, and Einolf et al, Clin Pharmacol Ther 2013 under Peer Reviewed Journal Publications)
o Coordinated inter-office (Offices of Generic Drugs and New Drugs) and inter-center (CBER, CVM, CFSAN) training on PBPK
o Served as external adjunct faculty in academic institution and board member/ reviewer for numerous peer reviewed journals
v 02/2008-06/2008: Contract Scientist, Amgen Inc., Seattle, WA (40 hours/week)
· Supported clinical and preclinical pharmacokinetic studies
v 09/2005-12/2007. Pharmacokineticist, Sonus Pharmaceuticals, Inc. Bothell, WA (40 hours/week)
· Set up, led and supervised preclinical drug metabolism and pharmacokinetics (DMPK) and clinical pharmacology group to support both early discovery and late phase clinical/nonclinical oncology projects
v 10/2002-09/2005. Principal Scientist, Pfizer Inc. La Jolla, CA (40 hours/week)
· Represented DMPK line on multi-disciplinary project teams (Antiviral, oncology and ophthalmology)
· Conducted DMPK studies to support clinical pharmacology programs regarding dose section, drug interaction, and identification of potential liver and eye toxicities of compounds in development
EXTERNAL PROFESSIONAL APPOINTMENTS AND ACTIVITIES
· Adjunct faculty: School of Pharmacy, University of Florida (2012-present)
· Council member: Lake Nona Leadership Council, University of Florida Center for Pharmacometrics and Systems Pharmacology (2012-2013)
· Organizing committee member, Land of Lakes Drug Metabolism and Pharmacokinetics Annual Conference (2009-present)
· Organizing committee member, 2017 North American ISSX meeting (2015-2017)
· Committee member, ISSX Membership Committee (2011-present)
· Advisor to Editor: Journal of Pharmaceutical Sciences
· Member of editorial board: Journal of Clinical Pharmacology (2013-present)
· Frequent journal reviewer (Clinical Pharmacology Therapeutics (including CPT-Pharmacometrics and Systems Pharmacology), Bioinformatics, Drug Metabolism and Disposition, Molecular Pharmaceutics, Biopharmaceutics Drug Disposition, Journal of Clinical Pharmacology, Pharmaceutical Research, Expert Opinion of Drug Metabolism and Toxicology, Toxicology and Applied Pharmacology, European Journal of Pharmaceutical Sciences, Clinical Pharmacokinetics).
SELECTED HONORS, AWARDS AND RECOGNITIONS
· 2015 FDA CDER Excellence in Mentoring award
· 2015 FDA CDER Team Excellence Blincyto Review Team
· 2015 FDA CDER Team Award: Eliglustat Clinical Pharmacology and Clinical Review Team
· 2015 FDA Group Recognition Clinical Pharmacology Review Team for Ceritinib
· 2015 CDER Special Recognition Clinical Pharmacology Review Team for Panobinostat
· 2014 FDA CDER team award: CDER Special Recognition award – OCP Innovation Task Force I
· 2014 FDA CDER team award: CDER Frances O. Kelsey Drug Safety Excellence award: Clinical Pharmacology Team for OPSUMIT
· 2014 FDA CDER team award: CDER Regulatory Science Excellence award - Simeprevir Clinical Pharmacology Review Team
· 2013 FDA CDER team award: transporter scientific interest group
· 2012 FDA outstanding service award
· 2009 FDA CDER Center team awards: FDA-OCP Ambassadors and Staff
· 2009 FDA CDER Center team awards: CPRSC Faculty and Staff
· 2002 AAPS/Eli Lilly Award for Graduate Student Symposium in PPDM/CS, Toronto, Canada
· 2001-2002 Merck Fellowship for graduate research, University of Washington, Seattle, WA
MEMBERSHIPS IN PROFESSIONAL SOCIETIES
· 1999 – Present: International Society for the Study of Xenobiotics (ISSX), Member
· 2007, 2009-2013, 2015-present: American Society for Clinical Pharmacology and Therapeutics (ASCPT), Member
· 2013-present: American College of Clinical Pharmacology (ACCP), Member
Table1. PBPK reviews supporting regulatory decisions and dose recommendations in drug labels
Drug Name (Approval Year) / Summary of simulations /Sildenafil (2009) / Effect of ritonavir on sildenafil exposure /
Cabazitaxel (2010) / Lack of CYP inhibition by cabazitaxel /
Praziquantel (2010) / Effect of rifampicin co-administration /
Ketoconazole (2010) / Lack of CYP inhibition by topically applied ketoconazole /
Rivaroxaban (2010) / Synergistic effect of drug-disease interaction /
Vilazadone (2011) / Similar drug interaction by ketoconazole under different dosing regimen /
Rilpivirine (2011) / Similar drug interaction by ketoconazole at a lower dose of rilpivirine /
Bosutinib (2012) / Support of post-marketing study on effect of moderate CYP inhibitor /
Perampanel (2012) / Similar drug interaction by ketoconazole under different dosing regimen /
Ponatinib (2012) / The effect of rifampin on ponatinib exposure /
Levonorgestrol (2013) / Similar drug exposure in adult and adolescent women receiving intrauterine device /
Canagliflozin (2013) / Lack of CYP inhibition by canagliflozin /
Simeprevir (2013) / Support of dose recommendations under different drug interaction scenarios and in subjects with East Asian ancestry /
Ibrutinib (2013) / Support of dose recommendations for situations when ibrutinib is co-administered with various CYP modulators /
Macitentan (2013) / Support of dose recommendation for the effect of ritonavir on macitentan exposure /
Naloxegol (2014) / Support of dose recommendation for the effect of efavirenz /
Eliglustat (2014) / Support of dose recommendations for situations when eliglustat is co-administered with various CYP modulators in subjects with different CYP2D6 genotypes /
Ruxolitinib (2014) / Support of dose recommendations for situations when ruxolitinib is co-administered with fluconazole /
Ceritinib (2014) / Support of dose recommendations for situations when ceritinib is co-administered with CYP modulators at steady state
Support of post marketing study of the effect of food at a different dose of ceritinib /
Rilpivirine (2014) / Support of dose recommendation for the effect of a moderate CYP inducer on rilpivirine /
Belinostat (2014) / Support of dose post-marketing study on the effect of UGT polymorphisms /
Blinatumomab (2014) / transient effect of “cytokine storm” on comedications that are CYP substrate and supported duration of hospitalization for patients initiated with biologic treatment /
Lenvatinib (2015) / The lack of drug effect on the PK of CYP3A and CYP2C8 substrates /
Panobinostat (2015) / Support of dose recommendations for co-medication that is strong CYP3A inducer and the lack of the effect of acid reducing agents on panobinostat oral absorption /
Aripiprazole Lauroxil (2015) / Support of dose recommendations for situations when the product is co-administered with various CYP modulators in subjects with different CYP2D6 genotypes /
Osimertinib (2015) / Support of multiple post-marketing requirement trials for drug-drug interaction potential /
Cobimetinib (2015) / Support of dose recommendations for comedications that are CYP3A inducers /
Dolutegravir (2015) / Support of dose recommendations for comedications that are UGT and/or CYP3A inducers /
Sonidegib (2015) / Support of dose recommendations for comedications that are CYP3A modulators /
Table2. Summary of impactful regulatory science projects completed by supervised fellows
Fellow’s name / Research title / Award and recognitionWagner C / Predicting the Effect of Intrinsic and Extrinsic Factors on the Exposure of Antiretroviral Medications / - 2015 ACCP Student Award Winner
Wagner C / Predictive Performance of Physiologically Based Pharmacokinetic (PBPK) Models for the Effect of CYP3A Inducers on Substrate Drugs: Analysis of Submissions to the FDA / - 2015 ASCPT Presidential Trainee Award and Jason Morrow Trainee Award, selected abstract for oral presentation
Duan VP / Physiologically-based Pharmacokinetic Modeling (PBPK) of Pitavastatin and Atorvastatin to Predict Drug-drug Interactions (DDIs) / - 2015 ASCPT Presidential Trainee Award
Jiang X / Applications of Physiologically Based Pharmacokinetic (PBPK) Model in Predicting acetaminophen Metabolism and Pharmacokinetics in Children / - 2014 ASCPT encore oral presentation
Pan Y / Application of the FDA PBPK Knowledgebase in Evaluating Model Predictability for Drug-drug Interactions. / - 2014 ASCPT selected abstract for oral presentation
Hsu V / PBPK Models of Renally Eliminated Drugs and Their Application in Evaluating the Effect of Patient Factors / - 2014 ASCPT Presidential Trainee Award and Jason Morrow Trainee Award, selected abstract for oral presentation
Jiang X / Application of Physiologically-Based Pharmacokinetic (PBPK) Model in Predicting Drug Metabolism and Pharmacokinetics in Pediatric Populations – A Case Study of Acetaminophen / - 2013 ASCPT Presidential Trainee Award, selected abstract for oral presentation
- 2012 FDA OCP Science Day, 1st Place Poster Award
Ke A / Refinement and Validation of a PBPK Model to Predict Disposition of Drugs in Pregnant Women Cleared via CYP1A2 and CYP3A Metabolism. / - 2012 ASCPT selected abstract for oral presentation
- 2011 FDA OCP Science Day, 1st Place Poster Award
Vieira MLT / Evaluation of FDA and EMA Models’ Cut-off Values for CYP3A Inhibition Prediction: A Collaborative Effort among Academic, Regulatory Agencies, and Innovation and Quality Consortium (IQC) Pharmaceutical Scientists. / - 2012ASCPT Presidential Trainee Award, selected abstract for oral presentation
PEER-REVIEWED JOURNAL PUBLICATIONS (underlined as corresponding author)
· Pan Y, Hsu V, Grimstein M, Zhang L, Arya V, Sinha V, Grillo JA, Zhao P (2016) The Application of Physiologically-based Pharmacokinetic (PBPK) Modeling to Predict the Role of Drug Transporters: Scientific and Regulatory Perspectives. J Clin Pharmacol, Accepted
· Yoshida K, Sun B, Zhang L, Zhao P, Abernethy D, Nolin TD, Rostami-Hodjegan A, Zineh I, Huang SM (2016) Systematic and quantitative assessment of the effect of chronic kidney disease on CYP2D6 and CYP3A4/5. Clin Pharmacol Ther. [Epub ahead of print]
· Jadhav PR, Cook J, Sinha V, Zhao P, Rostami-Hodjegan A, Sahasrabudhe V, Stockbridge N, Powell JR (2015) A proposal for scientific framework enabling specific population drug dosing recommendations. J Clin Pharmacol. 55:1073-8
· Przepiorka D, Ko C, Deisseroth A, Yancey CL, Candau-Chacon R, Chui H-J, Gehrke BJ, Gomez-Broughton C, Kane RC, Kirshner S, Ricks TK, Schmiel D, Sinha B, Song P, Zhao P, Zhou Q, Farrell AT and Pazdur R (2015) U.S. Food and Drug Administration Approval: Blinatumomab. Clin Cancer Res. 21:4035-9
· Yeung CK, Yoshida K, Kusama M, Zhang H, Ragueneau-Majlessi I, Argon S, Li L, Chang P, Le C, Zhao P, Zhang L, Sugiyama Y, Huang S-M (2015) Organ impairment - drug-drug interaction database: A tool for evaluating the impact of renal or hepatic impairment and pharmacologic inhibition on the systemic exposure of drugs. CPT: Pharmacometrics & Systems Pharmacology, 4:489-94
· Wagner C, Pan Y, Hsu V, Sinha V, Zhao P. (2016) Predicting the Effect of CYP3A Inducers on the Pharmacokinetics of Substrate Drugs Using Physiologically Based Pharmacokinetic (PBPK) Modeling: An Analysis of PBPK Submissions to the US FDA. Clin Pharmacokinet. 55: 475-83
· Wagner C , Zhao P, Pan Y, Hsu V, Grillo J, Huang SM, Sinha V (2015) Application of physiologically based pharmacokinetic (PBPK) modeling to support dose selection: report of an FDA public workshop on PBPK. CPT: Pharmacometrics & Systems Pharmacology, 4; 226-230
· Varma MV, Pang KS, Isoherranen N, Zhao P (2015) Dealing with the complex drug-drug interactions: Towards mechanistic models. Biopharm Drug Dispos. 36:71-92.
· Khozin S, Blumenthal GM, Zhang L, Tang S, Brower M, Fox E, Helms W, Leong R, Song P, Pan Y, Liu Q, Zhao P, Zhao H, Lu D, Tang Z, Al Hakim A, Boyd K, Keegan P, Justice R, Pazdur R. (2015) FDA Approval: Ceritinib for the Treatment of Metastatic Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer. Clin Cancer Res. 21:2436-9
· Wagner C, Pan Y, Hsu V, Grillo JA, Zhang L, Reynolds KS, Sinha V, Zhao P. (2015) Predicting the effect of cytochrome P450 inhibitors on substrate drugs: analysis of physiologically based pharmacokinetic modeling submissions to the US Food and Drug Administration. Clin Pharmacokinet. 54:117-27