AAPS 2001 Annual Meeting and Exposition Pharmaceutical Sciences: Climbing New Heights October 21-25 Colorado Convention Center Denver, CO Headquarters Hotel - Adams Mark

Wednesday

Pediatric Rule: Mandating Clinical Trials in Children — Is It Time to End Guesswork in Dose Selection for Children?

Open Session
Wednesday, October 24, 2001
7:00 am - 8:15 am

Many parents might be surprised to learn that most of the drugs prescribed for children, from allergy relievers to asthma inhalants and antidepressants, have never been formally tested on children. Starting this December, however, a new Food and Drug Administration rule mandates that any new adult drug that could be used by children with the same disease must undergo pediatric study, and its manufacturers must list doses for children on the label. In addition, if an adult drug already on the market has the potential to help children with the same disease, or if it is widely used in children and the absence of labeling seems dangerous, the FDA can require pediatric tests. Until now, for a host of ethical, scientific and economic reasons, the agency has not mandated drug research on children. The new requirement comes three years after Congress, in an effort to encourage such research, offered a lucrative financial incentive to drug manufacturers, giving them a six-month patent and marketing extension on drugs they agree to test in children at the FDA’s request. With such prodding, more than 275 clinical trials involving nearly 20,000 children are completed, in progress, or about to begin. Advertisements soliciting children’s participation in the trials are appearing in newspapers, on public transportation and on the Internet.

In this Open Session, we will explore how the industry and the regulatory authorities are working together to answer the questions: what are the dose selection criteria in pediatrics and where are we heading?

Moderators
Vijay Tammara, Ph.D.
Sanofi-Synthelabo, Inc.

C.T. Viswanathan, Ph.D.
Food and Drug Administration

Design, Analysis and Interpretation of Pediatric Pharmacokinetics/Pharmacodynamics Studies — Regulatory Perspective
Peter Lee, Ph.D.
Food and Drug Administration

Bridging the Dosage Gap Between Adults and Children: A Case Study with Lamotrigine
Chao Chen, Ph.D.
GlaxoSmithKline, Inc., United Kingdom

European Regulatory Environment in Pediatric Drug Development
Pascale Burtin, M.D., Ph.D.
Norvartis Pharmaceutical, Switzerland

From Biological Thinking to Applications of Polymers in Pharmaceutical Technology Development

Co-Sponsored by The Society of Biomaterials
Symposium
Wednesday, October 24, 2001
8:30 am - 12:00 pm
ACPE Program Number: 073-999-01-232-L04

Advanced drug delivery is playing increasingly critical roles in the pharmaceutical industry. One of the most significant developments of the pharmaceutical dosage forms has been the fundamental studies and novel applications of polymers in the modern pharmaceutical industry. Since the effects of polymers on the biological environments and drug absorption are frequently of crucial importance for the biological responses of the pharmaceutical end products, it is very important to address and identify the expertise for developing knowledge to the preparation of pharmaceutical polymeric formulations.

This symposium is directed toward researchers who are in pharmaceutical technologies and drug delivery fields, and would like to understand the effects of polymers on the pharmaceutical applications to drug absorption. This symposium will include speakers at the forefront of the newest technology and provide a forum for discussion of the latest in polymers and drug delivery. This symposium will provide updated information and research data that will accelerate their research efforts and benefit their research projects.

Moderator
Jian-Hwa Guo, Ph.D.
BF Goodrich Company

Polymeric Material Effect on the Intestinal Absorption of Drugs
Hans E. Junginger, Ph.D.
Leiden University, The Netherlands

Controlled Drug Delivery Using In Situ Gelled Biodegradable Polymer Solutions
Richard Dunn, Ph.D.
Atrix Laboratory, Inc.

Local Regional Cancer Therapy by Biodegradable Paclitaxel Microspheres
Wenbin Dang, Ph.D.
Guilford Pharmaceuticals, Inc.

Genetically Engineered Epitopes in the Design of Targeted Drugs
Jindrich Kopecek, Ph.D.
University of Utah

Pharmacologically Active Biomaterials
Jennifer West, Ph.D.
Rice University

Harmonization and Interpretation of Bioanalytical Method Validation Guidance and Workshop/Conference Reports

Wednesday, October 24
8:30 am - 12:00 pm

Non-Chromatographic Methods in the Pharmaceutical Quality Control Environment

Symposium
Wednesday, October 24, 2001
8:30 am - 12:00 pm
ACPE Program Number: 073-999-01-233-L04

Many non-chromatographic analytical methods that were once used for drug characterization and preformulation studies are becoming routine quality control methods (examples: SEM, DSC, surface area, TGA). This symposium will examine validation of non-chromatographic methods; stability-indicating and stability-specific test methods; method transfer of non-chromatographic methods into the quality control environment; determining acceptance criteria for non-chromatographic methods; treatment of Out of Specification (OOS) and Out of Trend (OOT) results; and non-chromatographic methods considered for pharmaceutical development and quality control (Industry/FDA perspectives).

Moderator
Allan Bokser, Ph.D.
Neurocrine Biosciences, Inc.

Validation of Non-Chromatographic, Non-Spectroscopic Methodology
Harry G. Brittain, Ph.D.
Center for Pharmaceutical Physics

Presentation Title To Be Announced
Raymond Frankewich, Ph.D.
Food and Drug Administration
(Invited)

Penetration of Drugs and Macromolecules in Solid Tumors

Symposium
Wednesday, October 24, 2001
8:30 am - 12:00 pm
ACPE Program Number: 073-999-01-234-L04

Physiological processes and anatomical structures increasingly are recognized as barriers to the delivery of both small-molecule drugs and biotechnology-derived macromolecules. At the level of the circulatory system, specific and nonspecific clearance mechanisms impact biodistribution. At the tissue level, both vascular and tissue structural barriers limit drug penetration and distribution. Basic physical processes such as diffusion and convection also affect drug transport. For solid tumors, the delivery of small molecules and macromolecules is further compromised by the poorly developed vasaculatures. A broad range of investigation has provided details on the structure and function of barriers at the cellular-, tissue-, and organ levels. This knowledge provides a basis by which to rationalize experimental results on drug penetration, as well as possible strategies to overcome barrier functions, either by direct modification or by exploitation of physiological alterations.

This symposium will provide an overview of current research on the barriers to drug and macromolecule penetration of tumors from the perspective of cellular, tissue, and organ levels, and examine aspects of basic transport processes which impact the delivery of these agents to their target sites. The symposium will also highlight approaches to the modification of these barriers to improve drug and macromolecule penetration to solid tumors.

Moderator
To Be Announced

Angiogenesis/Capillary Flow in Solid Tumors
Speaker To BeAnnounced

Dynamics of Drug Penetration on a Suborgan Level
M. Gullaume Wientjes, Ph.D.
Ohio State University

Determinants and Barriers for Drug Penetration in Solid Tumors
Jessie L.-S. Au, Ph.D.
Ohio State University

Models for Antibody-Based Detection and Treatment of Avascular Tumornodules
Peter M. Bungay, Ph.D.
National Institutes of Health

Current Status of Drug Efflux Protein and Drug Transport
William Beck, Ph.D.
University of Illinois, Chicago

PK/PD Modeling: Issues and Opportunities in Drug Development

Symposium
Wednesday, October 24, 2001
8:30 am - 12:00 pm
ACPE Program Number: 073-999-01-235-L04

The symposium will focus on novel methods of PK-PD analysis and how these methods can be used to make decisions in drug development. Quantitative evaluation of the exposure-response relationship through the use of PK-PD models is particularly important during drug development. Modeling and simulation based on PK-PD models can be used as a basis to make key decisions about Phase I-III trial designs, dosage recommendations for different patient populations, optimal drug input rate, labeling recommendations, etc. Over the past few years, PK-PD modeling has increasingly been applied to measures of drug response that are actual clinical outcomes (e.g. seizure counts, pain scores, adverse effects scores, survival data). Speakers will provide examples of how nonlinear mixed-effects modeling has been applied to a variety of these non-continuous data. Modeling desired and adverse effects in the target patient population allows us to estimate the “therapeutic index” at various levels of exposure. Dosage recommendations can be developed based on defined target in terms of desired effect/toxicity/exposure and an individual-based loss function for deviations from this target. Finally, Bayesian analysis will also be discussed as a powerful approach to optimally use information from earlier trials as we gain new information on a compound. The presentations will be based on typical examples and an open discussion with audience participation will follow.

Moderator
Richard Lalonde, Pharm.D.
Pfizer Global Research and Development

PK-PD Modeling of Clinical Outcomes
Raymond Miller, D.Sc.
Pfizer Global Research and Development

Modeling Therapeutic and Adverse Effects to Clinical Trials: Estimation of Therapeutic Index and Optimal Dosage Regimen
Jaap W. Mandema, Ph.D.
Pharsight Corporation

Approaches for Implementation of Bayesian Analysis
Diane R. Mould, Ph.D.
Georgetown University, Center for Drug Development Science

Optimizing Dosing Strategies for Defined Therapeutic Targets
Mats O. Karlsson, Ph.D.
Uppsala University, Sweden

Structural Biology of Transport Proteins: Advances in Crystallization, NMR and Modeling

Symposium
Wednesday, October 24, 2001
8:30 am - 12:00 pm
ACPE Program Number: 073-999-01-236-L04

Mammalian solute transport proteins are indispensable to the cellular uptake and homeostasis of many essential nutrients. During the past decade it has become clear that a vast number of drugs share transport pathways with nutrients and a critical role has been recognized for transport proteins in the absorption, excretion, and toxicity of drug molecules, as well as in their pharmacokinetic and pharmacodynamic profile. Yet, most transporters are poorly characterized at the molecular level; since solute transporters are integral membrane proteins, they are inherently difficult to crystallize. As a result, we are unable to predict the interaction of drugs with this important class of membrane proteins a priori , and detection of drug-transporter interactions remains unacceptably serendipitous. This symposium will address recent advances in the structural biology of integral membrane proteins and provide the audience with the latest techniques addressing this important challenge.

Moderators
Peter W. Swaan, Ph.D.
The Ohio State University

Deanna L. Kroetz, Ph.D.
University of California, San Francisco

Novel Experimental Techniques for Structural Biology of Membrane Proteins
Ronald Kaback, M.D.
University of California, Los Angeles

Structural Biology of the Glucose Transporter SGLT1
Ernest M. Wright, D.Sc.
University of California, Los Angeles School of Medicine

Structure/Function Relationships within the Mitochondrial Citrate Transport Protein
Ronald S. Kaplan, Ph.D.
FUHS/The Chicago Medical School

Approaches to the Structural Basis of the Function of P-glycoprotein Nucleotide Binding Domains
David R. Rose, Ph.D.
Ontario Cancer Institute/Princess Margaret Hospital

Computational Biology of Membrane Transporters
Peter W. Swaan, Ph.D.
The Ohio State University

Characterizing Complex Absorption Kinetics

Roundtable
Wednesday, October 24, 2001
9:00 am - 11:00 am

New drug delivery routes, and even traditional oral routes of administration, may not necessarily follow classic absorption kinetics, i.e., first order. Classic examples include kinetic profiles with double peaks or models with first and zero order absorption kinetics. The purpose of this session is to present case studies with solutions to problems where simple absorption models fail and to open a dialogue examining the source(s) of these problems and the impact they might have on a pharmacokinetic analysis.

Moderator
Peter L. Bonate, Ph.D.
Quintiles

Case Studies in Complex Absorption Kinetics
William J. Bachman, Ph.D.
GloboMax LLC

More Case Studies in Complex Absorption Kinetics
Jack A. Cook, Ph.D.
Pfizer Global Research and Development

Gene Therapies for Ocular Diseases

Roundtable
Wednesday, October 24, 2001
9:00 am - 11:00 am

Antisense oligonucleotides have shown promise in suppressing the expression of viral or bacterial proteins responsible for infection and/or replication. The majority of antisense therapies investigated to date involve systemic delivery. For treatment of intraocular infections, such as cytomegalovirus (CMV) induced retinitis, both systemic and topical ocular routes are generally ineffective. As a result, antisense approaches have typically employed intravitreal administration, usually involving repeated injections.

Another approach to antisense is the use of a gene inserted via an adeno-associated virus (AAV) or related vector. Expression of the gene can possibly be turned “on” or “off” by: 1) viral/bacterial load, 2) predisposition to infection, or 3) a small molecule administered via the topical ocular route. The latter would allow gene expression “on demand” with routine topical eye drop instillation.

This roundtable presents a review of gene therapies for ocular diseases, including the possibility of “on/off” gene expression employing small effector molecules delivered topical ocular.

Moderators
Shireesh Prakash Apte, Ph.D.
Alcon Research, Ltd.

James Chastain, Ph.D.
Alcon Research, Ltd.

Ocular Gene Therapy — Challenges and Opportunities
Peter M. Inhat, Ph.D.
Schering-Plough Research Institute

Ocular Gene Therapy — Control of Gene Expression
Speaker To Be Announced

PPDM Hot Topics
Drug Induced Liver Toxicity: Preclinical, Clinical and Post-Approval Issues

Wednesday, October 24, 2001
12:00 pm – 1:30 pm

Preclinical Issues
Francois Ballet, M.D., Ph.D.
Aventis Pharmaceutical Corporation

Clinical and Post-Approval Issues
John Senior, M.D.
Food and Drug Administration

Large Versus Small Companies

Education Committee Roundtable
Wednesday, October 24, 2001
12:00 pm - 1:30 pm

The purpose of the round table is to expose the young new scientists to the industrial world especially the differences between small, mid-sized, and large companies.

A large pharmaceutical company nowadays is defined as one which has employees in excess of 20,000 and has a large research organization within the company. On the other hand a small company is defined as a start up company with up to 1,000 employees. Anything in between 1,000 and 20,000 employees falls into the range of a mid-sized company. Each of the three types of companies has the research organization set-up differently. The large companies not only have large research groups, but would also have a large operating group, and a large marketing and sales group. On the other hand small companies focus on only one of those, either marketing, manufacturing, or research.

In the roundtable discussion examples will be given to show the advantages and disadvantages of each scenario. I will highlight points that will be beneficial to the young scientist in discovering their career paths.

All scientists between zero and five years of industrial experience should benefit from this discussion as this will help them confirm their career paths. Graduate students within one to two years of their completion should attend and will benefit from understanding what to pursue upon graduation.

The ABQ’s of Clinical Chemistry

Symposium
Wednesday, October 24, 2001
1:30 pm - 5:00pm
ACPE Program Number: 073-999-01-230-L04

The clinical analysis of biological matrices is critical to drug development and registration and essential in the daignosis and treatment of disease. Modern analytical techniques, with their imporved selectivity and sensitivity, allow the clinicians to analyze subtle changes in clinical chemistries and metabolites for safety, efficacy and PK/PD assessments. In addition, the effect of drugs or disease states on biological markers is being used as clinically significant surrogate endpoints in clinical studies and drug registrations. Quality systems that adhere to CLIA, ICH, FDA and ISO standards must be in place inthe clinical laboratory to assure the valididty, integrity and reliability of the traditional and innovative analytical and bio analytical techniques used in the clinical laboratory setting and their impact on health assessment and harmonized drug registration.

Moderators
Robert G. Bell, Ph.D.
Barr Laboaratories, Inc.

H. Thomas Karnes, Ph.D.
Virginia Commonwealth University

Molecularly Imprinted Polymers ("Plastic Antibodies") and Their Use in Clinical Chemical Analysis (LC/MS) of Biofluids
Karl-Siegfried Boos
Institut for Klinische Chemie
Klinikum der Universitat Munchen, Germany

Surrogate Endpoints in Drug Development
Jurgen Venitz, M.D., Ph.D.
Virginia Commonwealth University Medical College

Point of Care Testing Devices for Clinical Monitoring
H. Thomas Karnes, Ph.D.
Virginia Commonwealth University

Global Harmonization of Clinical Laboratory Data
Thomas P. Lohmann, M.D.
Quintiles Laboratories, Inc.

The Olympic Challenge: Clinical Drug Testing
Jean L. Fourcroym, M.D., Ph.D., MPH
Food and Drug Administration

Cellular Gene Delivery

Symposium
Wednesday, October 24, 2001
1:30 pm - 5:00 pm
ACPE Program Number: 073-999-01-241-L04

Gene delivery has been one of the most challenging areas of biopharmaceutical research for the last decade. Speakers will address current approaches on new vector systems for viral delivery and non-viral gene delivery with a particular focus on cellular aspects, and delivery in different cell types targeted to morphological/physiological features. This symposium will feature current experts who are pursuing intriguing and novel approaches to this complex area of biopharmaceutics.

Moderator
Sarah Hamm-Alvarez, Ph.D.
University of California, Los Angeles

Targeting Viral Vectors for Tissue-Specific Gene Delivery
Nori Kashara, Ph.D.
Keck School of Medicine

Viral Vectors and Gene Delivery
Speaker To Be Announced

Receptor-Mediated Gene Delivery to Liver
George Wu, Ph.D.
University of Connecticut Health Center

Non-Viral Gene Delivery
Frank Szoka, Ph.D.
University of California, San Francisco

Novel Non-Viral Gene Delivery Strategies
Leaf Huang, Ph.D.
University of Pittsburgh

Heparan Sulfate: A Potential New Class of Receptors for Gene Delivery
Jian Liu, Ph.D.
University of North Carolina

Pediatric Exclusivity: Focus on Clinical Pharmacology and Biopharmaceutics Issues

Symposium
Wednesday, October 24, 2001
1:30 pm - 5:00 pm
ACPE Program Number: 073-999-01-237-L04

Proper use of drugs in pediatrics has brought significant awareness among the regulatory body and the pharmaceutical industry. Several initiatives were proposed by the regulatory body in collaboration with the pharmaceutical industry to ensure the safety and efficacy of drugs in pediatrics. However, there are several issues that remain to be well addressed. For example, when a transaction from adult to pediatric clinical use is made, the underneath assumption is that the PK/PD relationship is similar among adults and pediatrics. But, one is not sure as to how certain the PK/PD relationship is similar in adults and pediatrics. Under which theoretical assumption is it likely to be true?

When the difference in pharmacokinetic characteristics is suggestive or indicative of differences between adults and pediatrics, a dose adjustment will be made. However, with the unknown PK/PD relationship, what assumptions are we making to define such dose adjustment in pediatrics? Are we certain these assumptions are valid?

It’s essential to know the right dose for each age group’s metabolic state. Due to differences in enzyme maturation and total body water with age, kids actually need a higher dose. Infants, on the other hand, do not metabolize medicine as well because their liver and kidneys are immature in the first months of life. If you go simply by weight, they are going to end up with levels of the medicine in their bloodstream that are too high and can be toxic. Hence, there is a need to understand the metabolic state with age and also maturation of other organs of elimination.

To answer these questions, the best possible approach is to conduct a clinical pediatric PK/PD study in all age groups. Considering the limitation in obtaining adequate blood samples, ethics and others, what will be the most appropriate study design and methods for pediatric PK/PD studies? Can the same formulation be used in adult and pediatric population? Are there any dosage compliance issues that need to be considered? The above issues will be discussed by national experts from the academic, industry and regulatory agency.

Moderators
Vijay Tammara, Ph.D.
Sanofi-Synthelabo, Inc.

He Sun, Ph.D.
Food and Drug Administration

Application of a Clinical Pharmacology Approach to Optimizing the Dosage of Lamotrigine for Children
Chao Chen, Ph.D.
GlaxoSmithKline, Inc., United Kingdom

Performing Pediatric Clinical Trials — Adopting the Therapeutic Orphan
Edmond Capillary, Pharm.D.
Children’s Hospital San Diego

FDA Perspective
Diane Murphy, Ph.D.
Food and Drug Administration

Mixed-Effect Models in Pediatric Clinical Pharmacology and Biopharmaceutics
Thomas Ludden, Ph.D.
GloboMax, LLC

A Perspective on Pediatric Drug Development in the Pharmaceutical Industry
Pascale Burtin, M.D., Ph.D.
Novartis Pharmaceuticals Corporation

Pediatric Drug Development, Issues and Opportunities — The Industry Perspective
Speaker To Be Announced

Persistent Meta-Stable Forms of Pharmaceutical Solids — Theory, Prediction and Analysis

Symposium
Wednesday, October 24, 2001
1:30 pm - 5:00 pm
ACPE Program Number: 073-999-01-238-L04

This symposium addresses the issue of anticipating and quantifying the potential for meta-stable solid forms to relax to more stable forms of the same compound. Speakers will address the relevant theories of what controls the transformation at the molecular level, the affect of processing stress on the transformations, the "prediction" or estimation of potential for conversion, and finally techniques born of the theories that have proven suitable for monitoring transformations.

Moderators
Kenneth R. Morris, Ph.D.
Purdue University

Joseph G. Stowell, Ph.D.
Purdue University

Persistence of Metastable Forms: An Overview of Concepts
Joseph G. Stowell, Ph.D.
Purdue University

Control and Monitoring of Polymorphs Using Additives
Xiaorong He, Ph.D.
Pharmacia

Analytical Aspects of Metastable Forms of Pharmaceutical Solids
Ulrich J. Griesser, Ph.D.
University of Innbruck, Austria

Deformation: Conformational Liability and Polymorphism
Craig J. Eckhardt, Ph.D.
University of Nebraska

Strategies for Developing Global Specifications for New Drugs and Their Impact on Release of Products for Global Clinical Trials

Symposium
Wednesday, October 24, 2001
1:30 pm - 5:00 pm
ACPE Program Number: 073-999-01-239-L04

Development of specification for new drug substances and drug products is a critical step in the drug development process. Accelerating development of new drugs, global registration and worldwide launch of new drugs are major goals of all pharmaceutical companies. To achieve these goals, clinical trials are often conducted in multiple countries preferably using the same drug product released against a single specification acceptable globally. A critical prerequisite for release of clinical trial materials for global applications and successful worldwide registration is to start the development of globally acceptable specification at a very early stage in the drug development process. This presents a significant challenge to the analytical, safety, regulatory, formulation and manufacturing professionals in the pharmaceutical industry. ICH guidelines on development of specification and related ICH guidelines have streamlined the process for development of global specification and helped to develop a good understanding of worldwide requirements, but significant challenges remain in accomplishing a single global specification.

This symposium will address the key scientific issues in development of global specification, perceived differences among regions, and will provide the current understanding of the common and region specific requirements for a single global specification for new drugs.

Moderators
Dilip R. Choudhury, Ph.D.
Pharmaceutical Development Center

Ganapathy Mohan, Ph.D.
Sanofi-Synthelabo, Inc.

Nirdosh Jagota, Ph.D.
Wyeth-Ayerst Research

Strategies for Developing Specifications for New Drugs in Development Phases with the Target of Developing Global Registration Specification
Edward F. McNiff, Ph.D.
Bristol-Myers Squibb Company

Critical Region-Specific Regulatory Needs for Clinical Trial Materials for Global Use — Approaches for Successful Compliance
Gregory P. Martin
Merck Research Laboratories

Developing Scientifically Based Global Specification for New Drug Substances — Considerations for Developing Physical and Chemical Parameters
Michel Bauer, Ph.D.
Sanofi-Synthelabo, Inc.

Developing Rationale Based Specifications for New Drug Products for Successful Worldwide Registration
Christopher M. Riley, Ph.D.
DuPont Pharmaceuticals Company

Development of Specifications for Global Registration of New Drugs — A Scientific Approach and Role of ICH Guidelines
Eric B. Sheinin, Ph.D.
United States Pharmacopeia

Panel Discussion

State of the Art in Population Analyses

Poster Podium
Wednesday, October 24, 2001
1:30 pm - 5:00 pm

Authors whose research in the area of population analysis has been competitively judged to be outstanding and novel will present their work at this podium. All authors will address a specific topic. The papers will also be displayed on a poster board inside the room.

Moderator
Michael Brier, Ph.D.
University of Louisville

Current Issues in Drug Efflux Transporters: Industrial Perspectives

Roundtable
Wednesday, October 24, 2001
2:00 pm - 4:00 pm

The roundtable will focus on drug transport issues and problems as they relate to the drug discovery and development processes. As a part of the natural cellular defense mechanism against xenobiotics, drug efflux proteins serve to protect the cell from foreign influences. Therefore, it is not surprising that many compounds are being identified as substrates for these drug transport proteins during the drug discovery process. Many pharmaceutical companies are directing efforts to screen for substrate activity early in the discovery phase. However, several key questions remain and will be addressed during this session. For example, is this information "nice-to-know" or "need-to-know"? What factors does one need to take into account when determining the relevance of substrate efflux? How does one take dose and therapeutic concentrations into account when this information is not available sometimes until later in development? How does one set up models to reliably determine/predict substrate activity in the presence of interspecies differences in expression and localization of efflux transporters? What are the issues from a development perspective? How does one maximize the screening process to filter out false negatives and positives when bringing new compounds with a high probability of success into development? The roundtable will attempt to address these questions.

Moderators
Rajesh Krishna, Ph.D.
Bristol-Myers Squibb Company

Martin Dowty M.E., Ph.D.
Procter & Gamble Pharmaceuticals, Inc.

P-Glycoprotein and Other Drug Transporters: BMS Experience
Saeho Chong, Ph.D.
Bristol-Myers Squibb Company

Clinical Implications of P-Glycoprotein-Mediated Transport
Jiunn H. Lin, Ph.D.
Merck and Company, Inc.

Injectable Nanosuspension Formulations of Water-Insoluble Drugs

Roundtable
Wednesday, October 24, 2001
2:00 pm - 4:00 pm

Nanosuspensions provide a new strategy for injectable formulations of water-insoluble compounds. The advantages of nanosuspensions over conventional formulations include (a) high drug loading (up to 10-15%), (b) an aqueous system without undesirable cosolvents or excipients, and (c) no precipitation and minimal irritation at injection sites. However, an injectable nanosuspension is still a relatively new concept with many potential development obstacles, such as long-term stability, sterilization processes, and regulatory issues. This roundtable will provide up-to-date information on the technology and share experiences in product development from the leaders in the field.

Moderator
Fang Zhao, Ph.D.
Bristol-Myers Squibb Company

NanoCrystals as Injectables: Opportunities in Discovery and Development
Elaine Merisko-Liversidge, Ph.D.
Elan Pharmaceutical Technologies

Formulating Microparticulate Suspensions for Parenteral Delivery: Problems and Prospects
Awadhesh K. Mishra, Ph.D.
RTP Pharma, Inc.

Small Scale Formulation and Process Development of NCEs

Funded by a grant from Elan

Roundtable
Wednesday, October 24, 2001
2:00 pm - 4:00 pm

In the early stages of New Chemical Entity (NCE) development, the quantity of available drug substance is often limited. At the same time it is usually necessary to formulate the NCE as quickly as possible for clinical trials. For a tablet dosage form this characterization typically includes excipient compatibility, flow characterization, compaction behavior, and chemical stability. An early assessment of the processing attributes of the NCE formulation is also often desired. This roundtable discussion will focus on the challenges the formulator faces of finding creative ways to gain as much information on the formulation and processing of NCEs while using minimal amounts of drug substance. Presentations will include studies related to this topic. Audience participation is strongly encouraged to share experiences and best practices in this area.

Moderator
Mickey L. Wells, Ph.D.
GlaxoSmithKline, Inc.

Maximizing Formulation Development with Minimal Drug Substance
Samir Mehta, Ph.D.
GlaxoSmithKline, Inc.

Early Clinical Tablet Development Using Predictive Tools and Risk Assessment
Cynthia A. Oksanen, Ph.D.
Pfizer, Inc.

Tools for Robust Process Development

Roundtable
Wednesday, October 24, 2001
2:00 pm - 4:00 pm

This discussion will focus on the use of statistical and quality engineering tools in the development of robust manufacturing processes. The benefits of utilizing these tools early in the development process include reduced manufacturing costs, accelerated time to market, enhanced process development efficiency, and better alignment with customers. Successful implementation of these tools requires active sponsorship by senior management, and support within the organization for training and facilitation of team sessions. To maximize their impact, it is also important to integrate the individual tools into an underlying business process and capture process information into a centralized data repository.

A case study will be presented where several of these tools (including Ishikawa, Gage R&R;, QFD, FMEA, Process Capability and SPC) are integrated into a disciplined approach to product development and control, and utilized in the development of a new tablet product.

Moderator
Dwayne Campbell, Ph.D.
GlaxoSmithKline, Inc.

Application of Robust Process Development Tools: A Case Study
Joe Kristof, Ph.D.
GlaxoSmithKline, Inc.

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