Lawrence X. Yu, Ph.D., C.V.
January, 2007
CURRICULUM VITAE
Lawrence X. Yu, Ph.D.
11600 Ranch Lane, North Potomac, MD 20878
E-mail:
PROFESSIONAL EXPERIENCE
Food and Drug Administration, Office of Generic Drugs
Deputy Office Director for Science (Actg) 02/02 – 06/02
Office Director for Science 06/02 - Present
· Provide scientific leadership for the Office of Generic Drugs with over 200 staff in addressing/resolving complex scientific issues related to Abbreviated New Drug Applications (ANDAs), including citizen petitions and complex company correspondences that raises concerns over ANDA approvals.
· Led the Office and developed a new pharmaceutical quality assessment system: Question-based Review (QbR). QbR is a concrete and practical implementation of the underlying concepts and principles of the FDA’s CGMPs and Quality by Design initiatives. It enhances the quality of generic drugs, increases the efficiency of CMC assessment, reduces manufacturing supplements, and facilitates continuous improvements.
· Oversee regulatory policy development. Led the Office in developing ANDA pharmaceutical solid polymorphism, impurity, and stability guidances. Developed pharmaceutical equivalence and bioequivalence policies for low molecular weight heparin and peptide drugs such as octreotide, desmopressin, calcitonin, teriparatide, and aprotinin.
· Manage the development of bioequivalence database. Initiated regulatory research in developing bioequivalence standards for topical products, inhalation products, and highly variable drugs. Established the bio-inequivalence concept and regulatory criterion.
· Initiate world class Pharmaceutical Science training program and Office of Generic Drugs Reviewer Forum to maintain, enhance, and expand the scientific capability of reviewers. Contributed to FDA’s cGMP and CDER’s PAT initiatives.
Food and Drug Administration, Office of Testing and Research,
Division of Product Quality Research
Team Leader 8/99 – 6/00
Deputy Division Director (Actg) 7/00 – 11/01
Division Director (Actg) 12/01- 01/02
· Led the Division of Product Quality Research and supervised approximately 20 staff. Planned, directed, implemented, evaluated, and solved complex issues in regulatory research in the areas of chemistry, manufacturing and controls (CMC), biopharmaceutics, and pharmacokinetics.
· Chair of FDA BCS Committee and member of FDA CMC Drug Product Technical Committee: Established the FDA policy on utilization of the BCS guidance, including implementation of Caco-2 system suitability. Identified the scientific issues related to the BCS extension. Contributed to the new CMC drug product guidance.
Major FDA Activities
· Chair: 11th FDA Science Forum: Advancing Public Health through Innovative Science (2005)
· Chair: Science and Risk-based CMC Review for Generic Drugs (2005 – present)
· Chair: Pharmaceutical Quality Stability Working Group (2005 – present)
· Chair/Co-Chair: Biopharmaceutics Classification System Committee (2000 – present)
· Co-Chair: Drug Substance and Drug Product Impurity Working Group (2003 – present)
· Chair: Pharmaceutical Solid Polymorphism Working Group (2002 - 2003)
· Member: FDA Safety Board (2005 – present)
· Member: FDA CDER Recruiting and Retention Working Group (2004 – present)
· Member: OPS Coordinating Committee (2004 – present)
· Member: OPS Therapeutic Inequivalence Coordinating Committee (2002 - present)
· Member: OPS Rapid Response Team (2000 – present)
· Member: Drug Product Technical Committee (2001 – 2003)
· Member: cGMP Initiative Dispute Resolution WG (2003)
· Sponsor/Originator: Bioequivalence for Gastrointestinal Acting Drugs (2005 – present)
· Sponsor/Originator: OGD Peptide Product Working Group (2004 – present)
· Sponsor/Originator: OGD Bioequivalence Database Working Group (2004 – present)
· Sponsor/Originator: OGD Reviewer Forum (2003 – present)
· Sponsor/Originator: OGD Highly Variable Drug Working Group (2003 – present)
· Sponsor/Originator: OGD Transdermal Dosage Form Adhesion Working Group (2003 – present)
· Sponsor/Originator: OGD Pharmaceutical Science training program (2002- present)
· Sponsor: OGD Bioequivalence Method for Inhaled Corticosteroids (2004 – present)
· Sponsor: OGD Bioequivalence Method for Topical Products (2003 – present)
· Sponsor: OGD Bioequivalence Method for Dry Powder Inhalers (2005 – present)
Glaxo Wellcome, Inc., Sr. Scientist 1/97 – 3/98
Research Investigator 3/98 – 8/99
· Leader of Glaxo Wellcome – US ADME Modeling Team with 5 staff: Established a human bioavailability data-base containing over 600 compounds, developed a novel quantitative structure bioavailability, and proposed an IDEAS model for processing high throughput screening ADME data.
· Contributed to the development of an HIV protease inhibitor product, AgeneraseÒ. Discovered vitamin E-TPGS as a P-glycoprotein inhibitor and developed an in vitro test method to predict in vivo performance of microemulsion delivery systems.
Pharmacia & Upjohn Co., Research Pharmacist 1/92 – 1/97
· Planned and conducted preformulation studies of small and large molecules and discovered a new physically stable form of a quinolone (U. S. Patent No. 5,985,893, November 19, 1999).
· Developed a sterile injectable solution of quinolone and a suspension of cephalosporin, manufactured clinical testing materials, and completed CMC sections for IND/NDAs.
· Characterized pharmaceutical properties of a growth hormone peptide and examined its formulation feasibility in vivo.
University of Michigan, Research Assistant 9/93 – 12/96
· Developed a compartmental absorption and transit (CAT) model for predicting oral drug absorption under Prof. Gordon Amidon. The CAT model laid foundations of the commercial software, GastroPlusTM.
· Participated in FDA biopharmaceutics drug classification project and contributed to in vitro-in vivo correlation and oral drug product regulations.
University of Cincinnati, Visiting Scholar and Res. Assistant 5/89 – 12/91
· Introduced neural network into pharmaceutics and used it for product optimization and quantitative structure permeability relationship.
· Designed, prepared, and evaluated sustained release solid dosage forms (tablet & capsule). Investigated the effect of excipients (polymers) on drug release. Developed new formulations for GeBauer Pharmaceutical Co. to replace their CFC based products.
OTHER PROFESSIONAL EXPERIENCE
Adjunct Professor of Pharmaceutical Engineering,
Department of Chemical Engineering, The University of Michigan, 2000 - present
· Initiated and lectured a regulatory course with emphasis on quality and bioequivalence for Engineering and Pharmacy graduate students.
Adjunct Associate Professor of Pharmaceutical Sciences,
College of Pharmacy, University of Maryland, 2002 - present
· Ph. D. Dissertation Committee Member of Dr. Kimberley A. Lentz
· Ph. D. Dissertation Committee Member of Dr. Sanna Tolle-Sander
· Ph. D. Dissertation Committee Member of Dr. Wendy Wilson
Adjunct Associate Professor of Pharmaceutical Sciences,
College of Pharmacy, University of Tennessee, 2001 - present
USP Biopharmaceutics Expert Committee 2002 – 2004
Member of Editorial Board, Journal of Generic Medicine 2004 - present
USP Biopharmaceutics Expert Committee 2002 - 2004
Journal Reviewer for
Pharmaceutical Research
Journal of Pharmaceutical Sciences
International Journal of Pharmaceutics
Journal of Controlled Release
European Journal of Pharmaceutics and Biopharmaceutics
European Journal of Pharmaceutical Sciences
Journal of Pharmacology and Experimental Therapeutics
PharmSci
EDUCATIONAL BACKGROUND
Ph.D. in Pharmaceutics, The University of Michigan, 1994-1996 (part time)
Ph.D. in Chemical Engineering, Zhejiang University (not officially conferred since I chose to stay USA), 1986-1989
M.S. in Pharmaceutics, University of Cincinnati, 1990-1991
M.S. in Chemical Engineering, Zhejiang University, 1985-1987
B. S. in Chemical Engineering, Zhejiang Institute of Technology, 1980-1984
ADDITIONAL TRAINING
2001 FDA/CDER Coaching and Effective Feedback
2000 FDA Leadership Skill I, April 2000 (One Week Residential Training)
FDA Leadership Skill II, July 2000 (One Week Residential Training)
1996 Stephen R. Covery’s 7 Habits of Highly Effective People (One Week Residential Training)
HONORS AND AWARDS
· FDA Center for Drug Evaluation and Research’s Team Excellence Award for outstanding efforts in identifying a potentially fatal alcohol-related adverse reaction with Palladone, 2005
· US Department of Health and Human Service Outstanding Leadership Award (2005)
· American Association of Pharmaceutical Scientists Fellow (2004)
· FDA Group Recognition Award for promptly responding to concerns by assuring the quality of a drug product dispensed to members of the US Armed Forces, 2004
· FDA Center for Drug Evaluation and Research’s Regulatory Science Excellence Award for developing and communicating the appropriate regulatory approach to the controversial issue of Pharmaceutical Solid Polymorphism in ANDAs, 2004
· FDA Group Recognition Award for conceptualizing and establishing an innovative and ongoing scientific symposium program in the Office of Generic Drugs that is world class, 2003
· FDA Center for Drug Evaluation and Research’s Team Excellence Award for outstanding efforts in evaluating doxycycline stability and palatability towards developing a pediatric antibiotic treatment regiment in response to anthrax bioterrorism, 2002
· FDA Center for Drug Evaluation and Research’s Team Excellence Award for AAPS Presentations, 2001
· FDA Center for Drug Evaluation and Research’s Excellence in Communication Award, 2001
· FDA Center for Drug Evaluation and Research’s Team Excellence Award for Scientific Research in the Support of Drug Evaluation, 2001
· FDA Center for Drug Evaluation and Research’s Team Excellence Award for Laboratory Research in the Support of Decisions Related to Generic Cyclosporine, 2001
· FDA’s Outstanding Achievement Award for Superior Scientific and Management Leadership, 2000.
· American Association of Pharmaceutical Scientists Excellence in Graduate Research Award, 1995.
· Merck Fellowship, American Foundation for Pharmaceutical Education Fellowship, 1994 –1995.
· Pharmacia & Upjohn Inc. Special Recognition Award for Invention of a New Stable Form of a Quinolone, 1994.
· Dean’s list, University of Cincinnati, 1991.
MEMBERSHIP IN PROFESSIONAL SOCIETIES
Quality Assessment Session Chair, AAPS Annual Meeting, October 28-Novemebr 2, 2006.
Quality by Design Session Chair, DIA Annual Meeting, June 18-22, 2006.
Chair, 2005 FDA Science Forum: Advancing Public Health Through Innovative Science.
Co-Chair, AAPS/FIP/CPA Conference on Scientific and Regulatory Challenges in Pharmaceutical Science (2004)
Member of Planning Committee of International Pharmaceutical Federation (FIP) second Pharmaceutical Sciences World Congress (2004)
Co-Chair, AAPS Workshop on Scientific and Regulatory Challenges in Implementation and Potential Extension of Biopharmaceutics Classification System (2002)
Co-Chair, AAPS/FIP/CPA Conference on Scientific and Regulatory Challenges in Pharmaceutical Science (2002)
Member of Planning Committee of AAPS Conference and Workshop on Pharmaceutics and Drug Delivery (2002)
Member of Steering Committee of AAPS Drug Transporter and Uptake Focus Group, 2001 – Present
Member of Planning Committee of AAPS Workshop on Assuring Quality and Performance of Sustained Release Parenterals (2001)
Moderator of Symposium: “Functional Excipients and Novel Delivery Systems.” AAPS Annual Meeting 2001
Member of American Association of Pharmaceutical Scientists (AAPS), 1990 - present.
EDITORS/PATENT
1. Book (Co-Editor). Biopharmaceutics Applications in Drug Development. Kluwer Academic/Plenum Publishers, New York, 2007.
2. Theme (Co-Editor). Pharmaceutical Impurities: Analytical, Toxicological, and Regulatory Perspectives. Adv. Drug Del. Rev. (2007).
3. Theme (Co-Editor). Pharmaceutical solid polymorphism in drug development and regulations. Adv. Drug Del. Rev. 56 (2004).
4. Patent (Co-Inventor). A new physically stable form of a fluoroquinolone. U. S. Patent No. 5,985,893. November 19, 1999.
REGULATORY GUIDANCE/PUBLICATIONS/BOOK CHAPTERS
1. Draft Guidance for industry, ANDAs: Impurity for Drug Product, 2005, CDER/FDA.
2. Draft Guidance for industry, ANDAs: Impurity for Drug Substance, 2005, CDER/FDA.
3. Draft Guidance for industry, ANDAs: Pharmaceutical Solid Polymorphism, 2004, CDER/FDA.
4. Draft Guidance for industry, Drug Products: Format and Content for Submission of New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs), 2004, CDER/FDA.
5. Draft Guidance for industry, Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP, August 2003, CDER/FDA.
6. Guidance for industry, Bioavailability and Bioequivalence Studies for Orally Administered Drug Products - General Considerations, February, 2003, CDER/FDA
7. Guidance for industry, Food-Effect Bioavailability and Fed Bioequivalence Studies. December 2002, CDER/FDA.
8. Guidance for industry, Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. August 2000, CDER/FDA.
9. L. X. Yu, G. J. Buehler, M. M. Nasr, H. N. Winkle, and J. Woodcock. Pharmaceutical Quality by Design: Principles and practice. Pharm. Res. To be submitted.
10. L. X. Yu et al. U.S. FDA Question-based review for generic drugs: A new pharmaceutical quality assessment system. J. of Generic Medicines, Submitted.
11. B. D. Rege, L. X. Yu et al. Passive transport of drugs across Caco-2 monolayers: Effects of solubilizing agents that modulate cell membrane fluidity and tight junction integrity. Eur. Pharm. Sci. Submitted.
12. D. A. Volpe, L. X. Yu, et al. Classification of drug permeability with a caco-2 cell monolayer assay. Clinical Research and Regulatory Affairs. Accepted.
13. P. Sathe, R. A. Lionberger, S. L. Lee, and L. X. Yu. Regulatory aspects of dissolution for low solubility drug products. In Ron Liu (Ed.). Water-Insoluble Drug Formulations, 2nd Ed., CRC Press, 2007.
14. S. L. Lee, A. S. Raw, and L. X. Yu. Significance of drug substance physicochemical properties in Quality by Design. In M. C. Adeyeye and H. G. Brittain (Eds.). Preformulation in Solid Dosage Form Development. 2007
15. A. K. Basak, Lawrence X. Yu et al. Pharmaceutical impurities: Regulatory perspective for Abbreviated New Drug Applications. Drug Del. Rev. 59:64-72(2007).
16. E. B. Asafu-Adjaye, Lawrence X. Yu et al. Validation and application of a stability-indicating HPLC method for the in vitro determination of gastric and intestinal stability of venlafaxine. J. Pharm. Biomed. Ana. Accepted (2007).
17. X. Cai, L. X. Yu et al. Why is it challenging to predict intestinal drug absorption and oral bioavailability in human using rat model? Pharm. Res. 23:1675-1686 (2006).
18. S. P. F. Miller, A. S. Raw, L. X. Yu. FDA Perspective on Pharmaceutical Solid Polymorphism. In: Rolf Hilfiker (Ed.). Polymorphism - In the Pharmaceutical and Fine Chemical Industry, Wiley-VCH, 2006.
19. N. Sadrieh, J. Brower, L. X. Yu , et al., Stability, Dose Uniformity and Palatability of Three Counterterrorism Drugs –Human Subject and Electronic Tongue Studies. Pharm. Res., 22:1747-1756 (2005).
20. X. Cai, L. X. Yu et al. Permeability dominates in vivo intestinal absorption of P-gp substrate with high solubility and high permeability. Mol. Pharm. 2:329-340 (2005)
21. Y. Yang, L. X. Yu et al. Determination of plasma and brain levels of isotretinoin in mice following single oral dose by high-performance liquid chromatography. J. Pharm. Biomed. Ana. 37:157-163 (2005).
22. L. X. Yu, A. B. Straughn, P. J. Faustino, Y. Yang, A. B. Ciavarella, E. A. Adjaye, L. J. Lesko, D. P. Conner, and A. S. Hussain. The Effect of Food on the Relative Bioavailability of Rapid Dissolving Immediate Release Solid Oral Products Containing Highly Soluble Drugs. Mol. Pharm. 1:356-362 (2004).
23. L. X. Yu, A. S. Carlin, G. L. Amidon, and A. S. Hussain. Feasibility studies of using disk intrinsic dissolution rate to classify drugs. Int. J. Pharm. 270:221-227 (2004).