Day 1 :
Keynote Forum
Carmen Tamayo
Heterogeneity LLC, USA
Keynote: Botanical drug development: Right and wrong on clinical studies
Time : 09:05-09:45
Biography:
Carmen Tamayo, MD directs the Canada Region of Heterogeneity, LLC. She is trained in Internal Medicine at the Central University of Venezuela. After moving to Canada with family, she completed Post-graduate studies in Public Health and Epidemiology at the University of Toronto. Since 1995, she has actively participated in policy and regulatory activities addressing traditional, complementary and alternative medicine (TCAM) research, with the Canadian National Cancer Institute. Her consulting has included government, industry, and nonprofit scientific organizations, including heterogeneity (since 2008), McMaster University Centre for Evidence Based Medicine, and the University of Western Ontario School of Medicine and Dentistry at the University of Western Ontario. For Health Canada’s Natural Health Products (NHP) Directorate, she served as Clinical Trial Project Coordinator for product review and assessment, collaborating in the agency’s development of a framework for NHP clinical trials. She has chaired and directed numerous programs and workshops as a member of the Drug Information Association (DIA), the International Pharmaceutical Federation (FIP), and the Latin American Phytomedicine Society (Sociedad Latinoamericana de Fitomedicina). She also serves as an expert reviewer for the World Health Organization and other international committees and several CAM and Phytotherapy journals, and is a past Co-editor of the Journal of Integrative and Complementary Medicine (JICM) – An international forum for evidence-based practices.
Abstract:
Medicinal plants are inexhaustible sources from which many of today’s most be useful drugs have been developed. While the majority of plant-based drugs are new (single) chemical entities (NCEs), a category of botanical drugs has recently reappeared in the US. Botanical drugs are defined as finished drugs for which the active ingredient is a complex, polymolecular drug substance. Although the criterion of adequate and well-controlled [clinical] studies remains a basis of new drug approval for the United States, botanical products pose unique challenges to clinical development due to their complex nature. This session will describe the clinical development of botanical drugs, with a focus on the US market. It will touch upon the differences between botanicals and NCEs and how these differences impact the types, designs, and even the timeline of clinical studies conducted for US drug development. Through examples, it will also relate some of the hurdles posed by complex botanical drugs which have been experienced in clinical studies of these products-both in research and in regulatory settings.
Keynote Forum
Freddie Ann Hoffman
Heterogeneity LLC, USA
Keynote: Regulatory considerations of botanicals as new drugs for the US market
Time : 09:45-10:25
Biography:
Freddie Ann Hoffman, MD founded HeteroGeneity in 2003; a Washington, DC-based consultancy focused on complex natural products, and is also its Managing Member. She has over 35 years of product development experience. She has a BS in chemistry from UCLA and received her MD and General Pediatric Residency training from the University of California at Davis. She completed a fellowship in Pediatric Hematology-Oncology at the National Cancer Institute (NCI), staying on to direct the Nutrition and Supportive Care Section of the Division of Cancer Treatment, and later, as Director of Extramural Clinical Trials of the Biological Response Modifiers Program. Leaving NCI in 1986, she served at FDA for nearly 14 years, as Chief of the Cytokines, Growth Factors and Oncologic Products Branch of the Center for Biologics Evaluation and Research, and later as Deputy Director of the Medicine Staff in the Office of the Commissioner. During her tenure, she formed and chaired an internal FDA Botanical Working Group which developed the botanical drug guidance, which the agency finalized in 2004. She also served in the Office of Dietary Supplements at the Center for Food Safety and Applied Nutrition, before moving to the private sector in 1999, joining Warner-Lambert Pfizer Consumer Healthcare, where she was Senior Medical Director for New Product Development. She continues to serve on numerous working groups, task forces, and boards of both government agencies and private companies. She has chaired and participated in numerous scientific, regulatory and policy forums addressing the development of polymolecular drugs and development of complex product. In 2014, she was an invited speaker at the 18th Presidential Commission on Bioethics (BRAIN initiative). She is a member of the American Society of Pharmacognosy and a past chair of the Drug Information Association’s Natural Health Products Track.
Abstract:
Medicinal use of plant-based products has its origins in antiquity estimated to date back at least 60,000 years. Toda approximately 80% of the world’s population continues to utilize plants and plant products to treat or prevent clinical conditions. In the United States, plant-based medicines were a major part of pharmaceutical armamentarium that is up until the passage of the US Drug amendments of 1962. The drug amendments further established requirements for new drug approval in the US, specifically requiring that the US Food and Drug Administration must affirm the safety and efficacy of a new drug prior to market approval. It was not until FDA’s dissemination of its Botanical Drug Development Guidance document, several decades later, that the US development of botanicals as drugs has experienced resurgence. At present there are two FDAapproved new botanical drugs that are sold exclusively by prescription in the US. This session will discuss how the FDA defines a botanical and the implications of the US regulatory approach on the development and approval of this renewed drug category, along with some of the lingering hurdles to this special category of new drugs.
Keynote Forum
Gus R Rosania
University of Michigan, USA
Keynote: The fine balancing act of drug formulation R&D in academia
Time : 11:00-11:40
Biography:
Gus R Rosania as Principal Investigator of the Subcellular Drug Transport Lab, is transforming the development of new drug formulations, by elucidating the micro pharmacokinetic properties of drugs in their biological, tissue microenvironments. His research group has pioneered new cheminformatic (mathematical modeling and simulation-based) approaches to the design of small molecule drugs with optimal permeability and intracellular accumulation properties, as well as application of hyperspectral Raman imaging approaches to discover new transport and disposition mechanisms acting at cellular and subcellular levels. His major contributions to pharmaceutical sciences is that his research group has discovered the most potent small molecule drug targeting mechanisms that has ever been identified to date, by studying the mechanisms of intracellular drug crystal formation. This knowledge is now being applied to the invention of new pharmaceutical formulation approaches that are poised to transform the manner in which drugs and formulations are designed, developed and regulated.
Abstract:
Statement of the Problem: In universities, pharmaceutical scientists are encouraged to dream of building marvelous creations, such as self-propelled drug delivery systems, self-assembling nanoscale devices and stimulus-responsive drug targeting mechanisms. While immense efforts are spent on accomplishing these transformative feats in chemistry, engineering and biomedicine research labs, the resulting advances are often not practical to translate into the clinical arena.
Methodology & Theoretical Orientation: In order to realign academic, drug formulation research with the more practical considerations inherent to drug product development, many challenges that precede clinical translation must be taken into account and dealt with, at the earliest, inception phase of formulation design. In this regard, my research group has grounded itself in reality, by carefully studying the nanoscale transport and distribution properties of existing drugs, prior to launching itself into a new, formulation design project.
Conclusion & Significance: By pioneering the formulation and development of biomimetic drug complexes, we have been able to balance fundamental discovery-driven research and technological innovation, with the more mundane necessities and regulatory requirements underlying successful clinical translation (from scale-up to manufacturing; and, from sterilization to commercialization).
Keynote Forum
Hai-Feng Ji
Drexel University, USA
Keynote: Diphenyl α-Aminoalkylphosphonates as prostate-specific antigen antagonists
Time : 11:40-12:20
Biography:
Hai-Feng Ji is currently working as a Professor, in Department of Chemistry, and Drexel University. His research interests focused on drug discovery, MEMS devices, nanomaterials for energy and environmental applications, nanopillars and phosphene for energy applications, and surface chemistry. He is currently a Co-author of 160 peer-viewed journal articles and book chapters. He has an H-index of 30. He is an Editorial board Member of several chemistry journals.
Abstract:
Prostate cancer (PCa) is one of the most prevalent cancers diagnosed in adult males. Chemotherapy has been widely used for PCa treatments. Although therapies targeting the androgen receptor, an upstream regulator of PSA, have been effective in treating prostate cancer, the disease state sometimes progresses and results in castrate-resistant prostate cancer. Alternative therapies should be pursued for prostate cancer treatment, especially in the scenario where androgen deprivation fails. PSA is a serine protease that has been found to control the growth of cancer metastasis and proliferation. Regulated by androgen receptor-mediated transcription pathway, the primary role of PSA biologically is the liquefaction of semen via proteolysis of coagulating proteins Fibronectin and Semenogelin within the matrix. However, with elevated PSA levels, the protease has been shown to cleave insulin-like growth factor binding protein-3 (IGFBP-3), a modulator of Mitogenic proteins insulinlike growth factors (IGF) I and II. It has been demonstrated that the involvement of PSA with the IGF molecular system leads to the progression of prostate cancer, which can in turn metastasize into the patient’s lymph nodes and bone, causing osteoblastic lesions via PSA-activation of latent transforming growth factor beta (TGFβ) and proteolysis of IGFBP-5. In this work, AutoDock 4.2 molecular docking suite was utilized to model covalent and non-covalent binding of this class of inhibitors to predict crystallographic poses and compare experimental IC50 dose-response curves and in silico potencies for providing future more specific rational drug design. The modeling study introduces novel aminoalkylphosphonates as a potential drug candidate for targeting PSA by optimizing P1 binding affinities. Several lead compounds will be reported as potent inhibitors of PSA activity.