Day 1 :
Keynote Forum
Jim Jingjun Huang
Ascendia Pharmaceuticals, USA
Keynote: Parenteral drug delivery systems for insoluble drugs
Time : 10: 10- 11: 10
Biography:
Jim Jingjun Huang has Founded Ascendia Pharmaceuticals in the year 2012 after 15 years of Pharmaceutical R&D and Management experience at Pfizer, Baxter, AstraZeneca and Roche. He has led the formulation development efforts for the successful transition of several oral and parenteral dosage forms from discovery through formulation, manufacturing, technical transfer and ultimately commercialization. He holds a PhD in Pharmaceutics from the University of the Sciences in Philadelphia (formerly Philadelphia College of Pharmacy and Sciences) where he worked with Joseph B Schwartz. His research interests are centered on improvement of solubility and dissolution, and controlled delivery of poorly water soluble drugs through Nano-emulsion and Amorphous Solid Dispersion Technologies. He has been a Reviewer for the Journal of Pharmaceutical Sciences, International Journal of Pharmaceutics, Journal of Controlled Release, Drug Development and Industrial Pharmacy, PDA Journal of Pharmaceutical Science and Technology, Molecular Pharmaceutics and Pharmaceutical Research. Currently, he is a Member of American Association of Pharmaceutical Scientists (AAPS) and American Chemical Society (ACS).
Abstract:
Poor water solubility of more than 60-80% of new chemical entity present a major hurdles in the design of suitable drug delivery systems for the market dosage form. Administration of those compounds by parenteral route without causing injection site reaction and systemic toxicity effects constitutes another barrier. Current solubilization and parenteral delivery technologies for water insoluble drug are summarized. The key considerations in design of stable parenteral drug delivery system, such as drug physico-chemical and biopharmaceutical properties, selection and evaluation of solubilization and delivery technology, and excipients are presented. Case studies in development of nanoemulsions and nanosuspension are presented.
Keynote Forum
Mewa Singh
Meda Biotech LLC, USA
Keynote: Hybrid-Nanoengineeringâ„¢: A new platform for nanomedicine
Time : 11:25- 12:25
Biography:
Mewa Singh heads the Research and Product Development at Meda Biotech LLC., with over 24 years of experience in the field of biopharmaceuticals. He has successfully launched products for diagnostics, vaccines, nutraceuticals and nanomedicines. He has applied five patents and is the Founder of Meda Biotech LLC and Nano Biotech (P) Ltd. He has completed MS in Biochemistry, MPhil in Biochemistry, Microbiology and Immunology and PhD in Microbiology and Immunology. His discovery of Hybrid-Nanoengineering™ could have real significant therapeutic value for patients. Since 2002, his company Meda Biotech has been working to commercialize a technology that could make the treatment of cancer, pain and inflammation, more effective and less harmful to patients.
Abstract:
Nanomedicine, a fusion of nanotechnology and medicine, is an emerging technology ideally suited to the targeted therapies. Nanoparticles overcome the low selectivity of anti-cancer drugs toward the tumor as compared to normal tissue and hence result-in less severe side-effects. Our new technology, Hybrid-Nanoengineering™, uses a new molecule (MR007) in the creation of nanoparticles that not only helps in nanonizing the medicine but also provides synergy to the medicine. The simplified manufacturing process will result in reduced manufacturing costs. Treatment is made more convenient because hybrid nano-medicines can be produced in oral, injectable or transdermal formulations. The manufacturing process uses no protein, oil or detergents. The particle size is below 180 nm with a narrow distribution of size. Importantly, these properties confer great stability of the structure. The formulation does not aggregate in plasma and is stable over a wide range of pH. The final hybrid formulation is stable for at least 18 months as a powder. More than 117 drugs, including paclitaxel, docetaxel, tamoxifen, doxorubicin prednisone, and artemisinin, have been nanonized in water soluble formulations. Preclinical studies on cell cultures of tumors show promising results. Our Hybrid-Nanoengineering™ platform enables the design and development of hybrid nanopharmaceuticals that combine efficacy with tolerability, giving patients hope for both extended overall survival and improved quality of life. I would discuss this new discovery of Hybrid-Nanoengineering™ which targets drug delivery, synergistic and potentiating effects, and barriers of drug delivery and advanced drug delivery systems.
- Challenges in Drug Development I Bioavailability Studies I Assessment of Bioequivalence I Clinical Pharmacology and Therapeutics
Chair
Akwete Lex Adjei
Rhodes Pharmaceuticals L.P, USA
Co-Chair
Muneesh Garg
Sitec Labs. Pvt. Ltd., India
Session Introduction
Julia Ding
PPD Labs, USA
Title: New analytical methodology in assessing comparability of Biosimilars
Time : 12:30-13:00
Biography:
Julia Ding has completed her PhD from Emory University and Post-doctoral studies from University of California at Berkeley. She is currently the Manager at PPD Labs®, a premier contract research organization.
Abstract:
The regulation of biosimilars is founded on the scientific principal of comparability. This talk will present a new analytical methodology in assessing product comparability between innovator and biosimilar rituximab products from United States, Europe and Indian markets. A novel methodology with SpeB based middle-down proteolysis coupled with imaged capillary isoelectric focusing (iCIEF) and capillary gel electrophoresis (CGE) will be presented to characterize difference in post translational modifications, process related modifications and impurity profiling among the three marketed products. Forced stress conditions were applied to these three products, and difference in their degradation profiles and degradation rates will be presented.
Khairia M. Youssef
Future University, Eygpt
Title: Design and synthesis of potential ribonucleotide reductase enzyme (RNR) inhibitors as antileukemic and/or antiviral 2'-Deoxymethylene Nucleosides
Time : 14:00-14:30
Biography:
Khairia M Youssef is a Professor of Organic Chemistry since 1999. She has completed her Bachelor of Pharmaceutical Sciences, Master degree and PhD in Organic Chemistry from Faculty of Pharmacy, Cairo University. In 1992, she was on a Peace Fellowship for Post Doctoral Research at the University of Southern California, USA under the supervision of Dr. Eric J. Lien. She is interested in drug design, synthesis and evaluation of certain pharmacologically active compounds. She has published 62 papers in national and international journals and supervised many researchers and teaching assistants.
Abstract:
In order to improve the antitumor and/or antiviral activities of existing nucleoside analogs, eight new compounds (9a, b, 14a, b, 15a, b and 16a, b) were designed and synthesized. Halogen atom were incorporated at the 2-position of the purine base to render the amino group at the 6-position less susceptible to metabolism by adenosine deaminase. A methylene group was introduced at the 2'-position following the lead of nucleoside antibiotics angustmycin A and neplanocin A. The two key intermediates 9a and 9b were prepared from guanosine after protection of the 3' and 5' hydroxyl groups and oxidation of the 2' hydroxyl group to the corresponding carbonyl group using Swern method. The conversion of the carbonyl group to the methylene function was carried out by applying Wittig reaction conditions. The final compounds 14 a, b, 15 a, b, 16a, b was prepared by means of non-aqueous diazotization of 9a and 9b. The prepared compounds were subjected to in vitro antileukemic and antiviral activity upon a new L1210 cell line that is doubly resistant to both hydroxyurea and deoxyadenosine which was grown and characterized. The new compounds showed potent antileukemic activity.
Kate Zupanets
National University of Pharmacy,Ukraine
Title: Risk assessment with the help of FMEA analysis in BE studies
Time : 14.30-15.00
Biography:
Kateryna Zupanets has completed her PhD from National University of Pharmacy, Kharkiv, Ukraine. Currently, she is pursuing her Post-doctoral studies at Clinical and Diagnostics Center of the National University of Pharmacy. She is the author of more than 25 papers in reputed journals (5 articles for SCOPUS journals). She has been working as a Co-Investigator in more than 40 trials of Bioequivalence studies and Phase I at Clinical and Diagnostics Center of the National University of Pharmacy.
Abstract:
Nowadays, bioequivalence (BE) study of drugs is considered to be a complex and multistage process where groups of professionals from different branches of pharmacy, medicine, and biostatistics are involved. It is a long way from the trial design and the enrollment of the first study object to the point the first results are entered into the corresponding documents. For that matter, even in case of planning the study accurately there may be issues that can emerge during the study and that require mobilizing all the parties/participants of clinical trial of a given drug to discuss, approve and solve possible problems. Such problems can include assessing abnormal ranges, registering and processing data entry, verifying source data, interpreting study data concerning adverse events/reactions (AE/AR). Consequently, we have decided to carry out the assessment of the above mentioned risks with the help of FMEA methodology that functions as a modern tool of risk assessment, helping to identify potential errors of any clinical trial. The experts of Clinical and Diagnostics Center of the National University of Pharmacy (Ukraine) which specializes in conducting BA/BE studies have been interviewed for them to assess the risk probability (P) and the level of its influence on the quality of clinical trial with the help of a five-rating scale. The risk value has been determined by means of priority risk parameter (PRP). As a result, it has been found out that the risk “AE/AR data missing due to incorrect conclusions about its significance ” has been found among the highest values (PRP=5.07). Thus, during the BA/BE study it is desirable that investigators should pay their special attention to the revealed risk and make the relevant attempts at its minimization.
Kate Zupanets
National University of Pharmacy,Ukraine
Title: Some aspects of clinical trials on bioequivalence studies
Time : 15.00-15.30
Biography:
Kateryna Zupanets has completed her PhD from National University of Pharmacy, Kharkiv, Ukraine. Currently, she is pursuing her Post-doctoral studies at Clinical and Diagnostics Center of the National University of Pharmacy. She is the author of more than 25 papers in reputed journals (5 articles for SCOPUS journals). She has been working as a Co-Investigator in more than 40 trials of Bioequivalence studies and Phase I at Clinical and Diagnostics Center of the National University of Pharmacy.
Abstract:
Under the conditions of financial resource shortage in public and/or insurance financing of health care, the high price of original drugs make for a high demand of generic drugs. The issue of the generic and original medication action identity on the human body is the main one for doctors and patients. One of the requirements imposed to generic drugs is the proof of their bioequivalence (pharmacokinetic equivalence) to the original ones. Clinical and Diagnostics Center (CDC) of the National University of Pharmacy is the first Ukrainian University hospital which specializes in running clinical trials with the participation of healthy volunteers. By the beginning of 2016 CDC has already gained wide experience and conducted more than 40 trials on studying bioequivalence. Selecting healthy volunteers carefully is one of the most important factors affecting the result of the study. From our point of view, it is not enough to merely assess volunteers’ health status at their screening visit. It is also extremely important to assess the results of personal genotyping at least with respect to metabolic rate (fast or slow acetylators of isoniazid) at the pre-screening stage. This procedure will correspondingly increase the cost of the study but at same time it will provide more objective information and reduce the influence of genetic polymorphism on the results of the study.
Muneesh Garg
Sitec Labs. Pvt. Ltd., India
Title: Bioequivalence of Ipratropium bromide HFA pMDI 20 μg/ actuation in healthy volunteers with and without charcoal blockade; and with spacer device
Time : 15.30- 16.00
Biography:
Muneesh Garg has completed his MD (Physician) from Dagestan State Medical Academy, Russia in 1997 and MD in Pharmacology from Government Medical College, India in 2004. He has more than 17 years of experience in Clinical Practice and Clinical Research. He is the Principal Investigator of Sitec Labs Pvt. Ltd., India, for more than 10 years. He has published many research papers in reputed journals.
Abstract:
Ipratropium bromide is a short-acting anti-cholinergic bronchodilator used in the management of chronic obstructive pulmonary disease. The aim of these three studies was to determine the bioequivalence of test and reference formulations of ipratropium bromide HFA pMDI 20 μg/ actuation with and without charcoal blockade; and with spacer device. Study-1 was single dose, randomized, 4-period, 2 sequences, laboratory-blinded, crossover and replicate design conducted in 90 healthy volunteers under fasting conditions with concurrent oral charcoal blockade. Study-2 was single dose, randomized, 2-period, 2 sequences, laboratory-blinded and crossover design conducted in 24 healthy volunteers under fasting conditions without concurrent oral charcoal blockade. Study-3 was single dose, randomized, 2-period, 2 sequences, laboratory-blinded and crossover design conducted in 64 healthy volunteers under fasting conditions with AeroChamber Plus valved holding chamber. Blood samples were collected up to 24 hours post-dose for pharmacokinetic profiling. Safety evaluations included monitoring adverse events and vital signs as well as performing clinical laboratory tests. Plasma concentrations of ipratropium were determined with a validated LC-MS/MS method. The 90% CI of ipratropium were 91.30-99.91, and 90.42-97.77; 87.33- 121.30, and 88.94-120.34; 87.21-99.83, and 91.66-97.94 for Cmax, and AUC0-t for study-1, study-2, and study-3 respectively. Since the 90% CI for Cmax and AUC0-t were within the 80-125% interval, it was concluded that test and reference formulations of ipratropium bromide HFA pMDI 20 µg per actuation are bioequivalent in their rate and extent of absorption with and without charcoal blockade; and with spacer device.
Ahmet Inal
Erciyes University, Turkey
Title: Prasugrel effect on In Vitro bleeding time tests in a single dose bioequivalence study
Time : 16:15-16:45
Biography:
Ahmet Inal has completed his PhD in Pharmacology from Erciyes University and Post-doctoral studies from Erciyes University, School of Medicine. He is the Principle Investigator of Hakan Çetinsaya Good Clinical Practice and Research Center. He is an Assistant Professor at Erciyes University, School of Medicine. He has worked on more than 800 bioequivalence studies
Abstract:
Prasugrel co-administered with acetylsalicylic acid is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndrome undergoing primary or delayed percutaneous coronary intervention. Prasugrel is a prodrug. It is rapidly absorbed after oral doses and undergoes hydrolysis in the intestine before being metabolized by several cytochrome P450 isoenzymes to the active metabolite. Binding of the active metabolite to human serum albumin is about 98%. The active metabolite is further metabolized to two inactive compounds which are excreted in the urine and feces; about 68% of a dose is excreted in urine and about 27% in faeces. The elimination half-life of the active metabolite is about 7.4 hours. Our study is comparative bioavailability study of prasugrel after single dose administration (fasting and fed conditions) of prasugrel 10 mg film-coated tablets (Test product) and Effient® 10 mg Filmtabletten (Reference product) in healthy male subjects. In this study, in vitro bleeding time tests (Collagen ADP and Epinephrine) were performed during first and final laboratory examinations. PFA 100 P2Y kit was used for the measurement of this test. When used in the treatment of prasugrel it was expected to extend in vitro bleeding time test. But, in our study, in vitro bleeding time or remained unchanged or decreased in the first and final laboratory examinations. Consequently, there is no need for bleeding time tests in a single dose bioequivalence study
Bipin Patel
RSServe, India
Title: Audits and Inspections - bioavailability and bioequivalence studies
Time : 16:45-17:15
Biography:
Bipin Patel has completed his Master in Pharmacy (specialization in Quality Assurance) in the year 2000 from Gujarat University (India). Since the year 2000, he has a worked as a Clinical Quality Assurance professional in various pharmaceutical companies and clinical research organization. He is currently the Director of Quality at RS Serve, a specialized clinical quality consultancy firm providing GxP services to pharma, bio tech and medical devices organizations. He has conducted more than 300+ GCP audits in Asia Pacific and EU regions. He has successfully faced regulatory inspections from DCGI – India, UK MHRA, US FDA, EMEA, Taiwanese FDA, Vietnamese MoH, South Korean FDA, ANVISA – Brazil, WHO, MCC – South Africa and Israel – MoH.
Abstract:
‘Quality-the degree of excellence’ is one of the most important aspect that human strive for, especially when it is related to human life and well being. Quality assurance audits and regulatory inspections are an important and essential part of clinical research with aim to evaluate the quality of the research conducted by sponsors, CROs and other institutions. Quality of clinical research revolves around two main parameters: Rights, safety and well being of subjects; and integrity of the data generated and submitted to regulatory authorities. Because of the steep increase in Bioavailability and Bioequivalence (BABE) centers and studies conducted in India, there is an increase scrutiny by the regulatory authorities across the globe to visit India based BABE centers to confirm quality of study conducted and to verify the integrity of data submitted. The outcomes of these inspections are mixed but sometimes negative with huge implications for sponsors. Although regulatory inspections for BABE studies generally occur after submission of data to regulatory authorities. These can something be unannounced and hence companies routinely runs ‘inspection readiness and ‘mock inspection programs’. The presentation aims to cover following topics: Brief introduction on quality in clinical research; quality control, quality assurance and regulatory inspections; process followed during audits and inspections; audit and inspections finding classifications; findings noted from recent regulatory inspections; and impact of regulatory inspections on BABE studies/centers and sponsors.
Roberto Molina de Souza
University of Parana, Brazil
Title: The use of asymmetric distributions in average bioequivalence
Time : 17:15-17:45
Biography:
Roberto Molina de Souza has completed his PhD from University of Sao Paulo, Brazil. He is an Adjunct Professor and Head of the Mathematics Department in the Technological University of Parana in the city of Cornelio Procopio, Parana, Brazil. He has published applications of statistical models in medicine and engineering.
Abstract:
The use of asymmetric distributions in average bioequivalence could be a good alternative for standard model to assess bioequivalence. In summary, we proposed an evaluation of bioequivalence using univariate and bivariate models based on an extended generalized gamma distribution and a skew-t distribution, under a Bayesian perspective. We introduced a study of the empirical power of hypothesis tests for univariate models, showing advantages in the use of an extended generalized gamma distribution. Three sets of bioequivalence data were analyzed under these new procedures and compared with the standard model proposed by the majority of regulatory agencies. In order to verify that the asymmetrical distributions are usually better fitted for the data, when compared with the standard model, model discrimination methods were used, such as the deviance information criterion (DIC) and quantile-quantile plots. The research concluded that, in general, the use of the extended generalized gamma distribution may be more appropriate to model bioequivalence data in the original scale.