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

Tuesday

The Basics of Prodrugs

Sunrise Pharmacy School
Tuesday, October 23, 2001
7:00 am - 8:15 am

Prodrugs are pharmacologically inactive derivatives of an active drug designed to ameliorate some identified, undesirable physical or biological property. The physical properties are usually solubility (too much or not enough lipid or aqueous solubility) or stability related, while problematic biological properties include too rapid metabolism or poor bioavailability which itself may be related to a physicochemical property. For each undesirable property a functional group(s) can usually be identified as being a major source of the undesirable property. A promoiety comprised of functional groups designed to change that property is then transiently attached to the problematic functional group with an enabling group that release the active drug at the appropriate time.

This instructional program will provide insights into implementing these steps in the development of a prodrug approach. The respective advantages of alkyl and acyl promoieties in the design drugs and the importance of the inclusion of lipid and aqueous solubility considerations in the design of the prodrug will be discussed. Finally, examples of the use of prodrugs to improve topical and oral delivery and extrapolation of animal models to human applications will be provided.

Speaker
Kenneth B. Sloan, Ph.D.
University of Florida

PK/PD: Implications for Drug Approval

Sunrise Pharmacy School
Tuesday, October 23, 2001
7:00 am - 8:15 am

In this Sunrise Session, the basic understanding of the relationship between plasma concentration and pharmacodynamic endpoints and/or surrogate markers to clinical endpoints, and regulatory perspective of PK/PD as an alternative/support to the well-controlled efficacy study in registering a new drug product will be discussed.

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

Jürgen Venitz, MD, Ph.D.
Virginia Commonwealth University

General Concepts of PK/PD Modeling
Mohammad Hossain, Ph.D.
Novartis Pharmaceuticals Corporation

PK/PD Considerations in Drug Development: A Regulatory Perspective
Vijay Tammara, Ph.D.
Sanofi-Synthelabo, Inc.

Analytical Laboratory Management Systems

Open Session
Tuesday, October 23, 2001
7:00 am - 8:15 am

FDA is progressing to agree on the format and content of a common technical document for the registration of chemistry, manufacturing and controls documents. One estimate named 133 technical documents in the CMC section, many of which will have analytical input. The analyst will be required to provide data and documents to support registration.

Meanwhile, electronic batch record initiatives and electronic signatures are driving the need for electronic reports to be issued from the QC laboratories directly into the batch records and to Annual Reports.

This session will provide an update on the progress of these initiatives, explain the approach some companies are making to build an electronic architecture capable of entering data directly into the document, and finally assess the impact on the analytical laboratory, especially on LIMS.

Topics to be discussed include: LIMS in 200X, exporting data to the CTD and batch records; special modules for LIMS, stability, calibration, maintenance, sample handling; setting up an analytical LIMS to meet scientific and business needs.

Moderator
G.W. “Bill” Martin, Ph.D.
Analytical Resources, LLC

Emerging Technologies: Regulatory Aspects and Detecting Solid-State Changes During Drug Development

Symposium
Tuesday, October 23, 2001
8:30 am - 12:00 pm
ACPE Program Number: 073-999-01-218-L04

This symposium, organized by the AAPS Preformulation Focus Group, will examine: (a) the impact of the FDA Q6A specification guideline on the drug development process with a particular focus on characterizing the solid-state form of API in the final drug product and (b) methods to detect potential solid-state changes during formulation development and storage. It has been well established that changes in solid-state form may adversely impact product performance and shelf life of the commercial dosage form. Although much research is conducted to identify an acceptable solid-state form for development, few techniques are available to rapidly assess changes in the physical stability of that form during the development and storage of the final product, e.g., blending, wet granulation, tableting. The focus of this symposium will be to describe new techniques to characterize drug substance in drug products without disrupting the integrity of the solid-state form.

Initially, the Q6A guidelines will be reviewed by a representative from the FDA, with an emphasis on the practical ways in which pharmaceutical scientists can address the points that are raised. The use of well established spectroscopic techniques, such an NMR and Raman, for characterizing the API form in drug product will then be reviewed by experts in the field. The symposium will conclude with reports of how recent advances in the application of newer techniques and variants, such as low temperature X-ray powder diffractometry and micro-thermal analysis, that can be used to address the difficult problems in this field.

Moderators
Joseph F. Krzyzaniak, Ph.D.
Pfizer, Inc.

Bruno C. Hancock, Ph.D.
Pfizer, Inc.

Pharmaceutical Solids: Regulatory Perspective
Charles P. Hoiberg, Ph.D.
Food and Drug Administration

Solid-State NMR Spectroscopy of Small Molecules: From NMR Crystallography to the Characterization of Solid Oral Dosage Forms
Susan M. Reutzel-Edens, Ph.D.
Eli Lilly and Company

Raman Spectroscopy as a Tool to Probe Solid-State Form in Tablets
Lynne S. Taylor, Ph.D.
AstraZeneca, Sweden

Use of X-Ray Powder Diffractometry to Monitor Phase Transitions During Processing
Raj Suryanarayanan, Ph.D.
University of Minnesota

MicroTA: An Innovative Tool for Microscale Topography and Thermal Analysis for Pharmaceutical Systems
Gerard P. Frunzi, Ph.D.
Bristol-Myers Squibb Company

Lipid-Based Prodrug Products and Technology: Regulatory and Development Issues

Symposium
Tuesday, October 23, 2001
8:30 am - 12:00 pm
ACPE Program Number: 073-999-01-219-L04

This symposium is organized by the AAPS Lipid-Based Drug Delivery Systems Focus Group. In the past, the pharmaceutical use of lipids was primarily limited to drug delivery formulations (liposomes, micelles). Over the past decade there has been a recognition that lipids covalently bound to pharmacological agents can direct drug action to specific tissues and organs. This has led to a major increase in the use of lipids conjugated to drugs so as to create a lipid-based prodrug. These New Chemical Entities are designed to improve tissue/organ targeting, penetration across membrane barriers (such as the blood brain barrier) and pharmacokinetic profiles, with the added potential benefits of reduced toxicity and/or improved efficacy.

Speakers will highlight recent developments in lipid-based prodrug technology and the resulting diagnostic and therapeutic products. Since lipid-based prodrugs represent New Chemical Entities and unique composition of matter, the session will deal not only with the development of these novel products but also address the regulatory issues involved. Traditional drug delivery development and regulatory strategies will probably not apply to these prodrugs, so companies pursuing new products will be breaking new ground. The speakers will discuss a range of products and applications spanning the delivery of small organic molecules to DNA vectors for this exciting new technological approach, as well as the formulation challenges for these lipophilic substances. Should the pioneering companies and researchers in this field continue to achieve developmental success, it will certainly convince more biotech and traditional pharmaceutical companies to consider lipid-based prodrug products for enhancing product pipelines.

Moderators
Leonid Lurya, M.D., Ph.D.
Kiryat Weizmann Science Park, Israel

Jonathan E. Friedman, Ph.D.
Kiryat Weizmann Science Park, Israel

Fatty Acid- and Glyceride-Drug Conjugates as Prodrugs
Didier M. Lambert, Ph.D.
Université Catholique de Louvain, Belgium

Fine Tuning of Drug Action with Modified Polar Lipids
Alex Kozak, Ph.D.
Kiryat Weizmann Science Park, Israel

Cytofectin Mediated Delivery of Plasmid DNA: An “Informational” Prodrug
Carl J. Wheeler, Ph.D.
Vical, Inc.

DHA-Paclitaxel: Preclinical and Clinical Development of a Fatty Acid-Cytotoxic Conjugate Targeted to Tumors
Matthew O. Bradley, Ph.D.
Protarga, Inc.

Lipid Formulations for Oral Administration of Hydrophobic Drugs Colin Pouton, Ph.D.
University of Bath, United Kingdom

New Analytical Technology Applications For In Situ Analysis of Dosage Forms

Symposium
Tuesday, October 23, 2001
8:30 am - 12:00 pm
ACPE Program Number: 073-999-01-220-L04

This session brings together industry and academic leaders in the field of spectroscopy: Raman, Near-Infrared, NMR, Mass Spectroscopy, and Photon Migration Spectroscopy. Speakers will demonstrate the utility of these varied techniques in the analysis of dosage forms, in situ, in the presence of their complex matrix structure.

Moderator
Emil W. Ciurczak, M.Sc.
Purdue Pharma L.P.

Application of X-Ray Powder Diffraction to Characterization of Solid Dosage Forms
Marek Zakrzewski, Ph.D.
Purdue Pharma L.P.

Drug Product Analysis Using Raman Spectroscopy
David E. Bugay, Ph.D.
SSCI, Inc.

Implementation of Frequency Domain Photon Migration Measurement for Monitoring and Validating Blend Uniformity
Eva Sevick-Muraca, Ph.D.
Texas A&M; University

Microscopic NMR Imaging Studies of Controlled Release Dosage Forms
Colin Fyfe, Ph.D.
University of British Columbia, Canada

High Resolution Spatial Chemical Analysis of Pharmaceutical Delivery Systems Using Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS)
Martyn C. Davies, Ph.D.
University of Nottingham, United Kingdom

Novel Tools to Study the Mechanisms, Expression and Regulation of Drug Transporters

Symposium
Tuesday, October 23, 2001
8:30 am - 12:00 pm
ACPE Program Number: 073-999-01-221-L04

The discovery of drug transporters is occurring at an accelerated pace. The latest and most advanced laboratory tools are needed to elucidate and understand the mechanisms, expression and regulation of these drug transporters. Such tools include model organisms (e.g., yeast, C. elegans), GFP-tagging of the transporters to elucidate their intracellular sorting, trafficking and targeting, and knockout models (e.g., yeast, C. elegans and mouse). In addition, many of these tools can be used for rapid and high throughput screening of transporters variants and for selection of lead compounds. In this symposium, the what, how and why of these novel laboratory tools will be discussed together with their optimum use, advantages and disadvantages.

Moderators
Jashvant Unadkat, Ph.D.
University of Washington

Kathleen A. Giacomini, Ph.D.
University of California, San Francisco

A High Throughput Method for Mapping the Binding Sites of the Equilibrative Nucleoside Transporter (hENT1) Using Yeast (Sacchromyces Cerevisiae) as an Expression System
Jashvant Unadkat, Ph.D.
University of Washington

Studies of Nucleoside Transporters In C. Elegans: What Can We Learn?
Kathleen A. Giacomini, Ph.D.
University of California, San Francisco

Intracellular Trafficking of Bile Canalicular Proteins: Models, Methods and Mechanisms
Irwin M. Arias, M.D.
Tufts University School of Medicine

In Vitro Cellular Models for Examining the Function and Regulation of Hepatobiliary Transport Systems
Kim L.R. Brouwer, Pharm.D., Ph.D.
University of North Carolina at Chapel Hill

Analysis of ABC Transporter Trafficking and Polarization Using Green Fluorescent Protein and Confocal Mircoscopy
Bruce A. Stanton, M.D.
Dartmouth Medical School

PK/PD: Can It Be An Alternative/Support to a Well-Controlled Efficacy Study for Registering a New Drug as Per FDAMA?

Symposium
Tuesday, October 23, 2001
8:30 am - 12:00 pm
ACPE Program Number: 073-999-01-222-L04

Compared to previous decades, the field of drug development has undergone major changes in recent years. With emerging technology in the next century, the current traditional clinical trial designs will be likely viewed as acceptable but not comprehensive. Drug development is a question-driven process as to: a) do we have the right drug?; If so, b) how do we appropriately administer it? The various phases of traditional drug development that could answer these questions include preclinical pharmacology and toxicology, Phase 1, Phase 2 (safety assessment and dose-response studies), and Phase 3 (efficacy studies) trials. Where does pharmacokinetic-pharmacodynamic (PK/PD) modeling fit in the above drug development plan? Traditionally PK/PD has been a parallel effort in drug development. However, the value of using PK/PD in each phase of drug development is becoming increasingly evident to optimize and individualize dose in general as well as in various compromised patient populations. In recent years the pharmaceutical industry and the regulatory authority in the U.S. (FDA) are interacting at regular intervals early to facilitate drug development to determine as to “what ought to be done” and “what would be acceptable” in contrast to past practices where FDA was informed of the drug development plans for individual drugs that were in development. Further, with the enactment of the Food and Drug Modernization Act (FDAMA), which provided for a provision that the sponsor could provide one pivotal study to demonstrate efficacy and safety of the drug with a supportive study which is either a well controlled study or a study which can adequately support the concept of efficacy.

This symposium will explore the relationship between plasma concentration and pharmacodynamic endpoints and/or surrogate markers to clinical endpoints and regulatory perspective of PK/PD as an alternative/support to the well controlled efficacy study in registering a new drug product.

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

Jürgen Venitz, MD, Ph.D.
Virginia Commonwealth University

PK/PD-Based Development of Modified-Release Dosage Forms of Established Drugs as an Alternative to Clinical Efficacy Testing
Hartmut Derendorf, Ph.D.
University of Florida

PK/PD as a Supportive Tool in Drug Development: An Industry Perspective
James Opperman, Ph.D.
Sanofi-Synthelabo, Inc.

Complexities and Frustrations in Using PK/PD for Regulatory Decisions: A Clinical Pharmacology Perspective
Lawrence J. Lesko, Ph.D.
Food And Drug Administration

Use of PK/PD in Regulatory Decisions: Clinicial Perspective
Robert Temple, M.D.
Food and Drug Administration

PK/PD: Where Can it be Most Effective and Why Does it Fail?
Steven Bramer, Ph.D.
Maryland Research Institute

Streamlining the CMC Regulatory Process

Symposium
Tuesday, October 23, 2001
8:30 am - 12:00 pm
Room C205 / Colorado Convention Center

FDA and AAPS co-sponsored a workshop earlier in the year on new approach to submitting and handling CMC information that, until now, required prior review and several months of delay to approve and implement CMC changes. The Agency has offered Industry the opportunity to discuss reducing the regulatory burden for many types of changes. FDAMA required CDER review the post-approval change process. The FDA has graciously opened the discussion on this process to Industry comment and the first session in June was a tremendous success.

AAPS has allowed a session at the annual meeting to provide an update from that workshop. The views discussed at the workshop are only proposals of what might be changed. Some at the agency seem willing to think outside the current “box”. The driving force for the new initiative is FDAMA's requirement for a risk based reporting system for post approval submissions. FDA encouraged discussion on a wide array of topics designed to reduce the regulatory burden and promote CBE and Annual Report status for post-approval CMC change requirements. The June workshop was just the beginning and this session offers attendees the opportunity to participate in this change process. The speakers will attempt to provide an general understanding of the history of 314.70, FDAMA, SUPAC and other FDA guidances; update the current initiative and its impact on existing guidances; and future direction. Although, these proposals are designed to reduce the regulatory burden, they do not address the review process. Are there potential actions related to this process to help relieve the review burden, also.

Moderators
Jerry Skelly
Food and Drug Administration

Validation of Computerized Systems in Drug Development

Symposium
Tuesday, October 23, 2001
8:30 am - 12:00 pm
ACPE Program Number: 073-999-01-223-L04

This symposium will address issues related to computerized systems used to create, maintain, retrieve or transmit pharmaceutical development data intended for submission to the Food and Drug Administration as well as government regulations and requirements. The essential elements of systems validation requirements, electronic records and electronic signatures will also be addressed. Case studies of prospective and retrospective validations will be presented.

Moderators
Chris Bapatla, Ph.D.
Alcon Research, Ltd.

Joseph F. Mastronardy, Ph.D.
Quality Regulatory Consultants

FDA Regulations and Requirements for Its Validation of Computerized Systems
Paul Motise, Ph.D.
Food and Drug Administration
(Invited)

Computer Validation in Laboratories — Pharmaceutical Development
David Judd
Agilent Technologies

Auditing Computer Systems and Records
Martin Browning
EduQuest, Inc.

Integrity of Data Transfer from Original Measurements to Computerized Databases and Data Verification
William Buote
VelQuest Corporation

The Value of Requirements Traceability Matrix (RTM) from User Requirements Through Design Specifications and Testing
John Vadnais
RCM Solutions, Inc.

AAPS Graduate Symposium in Pharmacokinetics, Pharmacodynamics and Clinical Sciences

Sponsored by Eli Lilly and Company
Tuesday, October 23, 2001
8:30 am - 12:00 pm

Graduate students whose research has been competitively judged to be outstanding will present the findings of their research efforts. Special awards will be given to the presenters at the conclusion of the session.

AAPS Graduate Symposium in Drug Delivery and Pharmaceutical Technology

Sponsored by Procter & Gamble Pharmaceuticals, Inc.
Tuesday, October 23, 2001
8:30 am - 12:00 pm

Graduate students whose research has been competitively judged to be outstanding will present the findings of their research efforts. Special awards will be given to the presenters at the conclusion of the session.

Current Issues and Experiences with Electronic Signatures

Roundtable
Tuesday, October 23, 2001
9:00 am - 11:00 am

In March 1997, the FDA issued 21 CFR Part 11, Electronic Records; Electronic Signatures; Final Rule. This regulation paved the way for acceptance by the FDA of electronic records and electronic signatures. Four years later, many questions continue to arise as to its interpretation and implementation. How does one interpret this ruling? Has a norm arisen within the pharmaceutical industry as to how and when electronic signatures are used? How are electronic signatures being generated, verified? What is the current status of this regulation within the FDA? Has the experience of the past four years revealed major issues in either interpretation or the availability of acceptable technology? These topics will be explored in this roundtable discussion.

Moderator
Joseph F. Mastronardy, Ph.D.
Quality Regulatory Consultants

FDA Perspective
Speaker To Be Announced

Industry Perspective
Donna M. Radzik, Ph.D.
Medeva Americas, Inc.

Emerging Drug Distribution Channels and Their Impact on Pharmacy and Patient Care

Roundtable
Tuesday, October 23, 2001
9:00 am - 11:00 am

New technologies such as genomics, internet, and bioinformatics will likely change the dynamics of the drug distribution channels in the new millennium. Patients and healthcare professionals will be significantly impacted in the ways they use information to make therapy decisions. The emerging innovative technologies will also demand that drug therapy be designed and distributed via newer channels to optimize patient therapy monitoring. The profession of pharmacy will therefore have to address the impact of such events on the practice of pharmacy and new roles for the pharmacist in patient care. The roundtable will address these issues through a discussion of future alternative models of drug distribution, the information-specialist role of the pharmacist in the new drug distribution channels, and the impact of new drug distribution channels on the pharmaceutical industry's relationships with physicians, pharmacists, and patients.

Moderator
Prasanna R. Gore, Ph.D.
Gore & Company, a Division of PharmaCompany, Inc.

Emerging Technologies and Their Impact on Drug Distribution in the New Millennium
Thani Jambulingam, Ph.D.
St. Joseph’s University

Influences of Emerging Methods of Drug Distribution on Pharmacy and Patient Care in the New Millennium
William Doucette, Ph.D.
University of Iowa

Perspectives in Powder Flow Characterization

Roundtable
Tuesday, October 23, 2001
9:00 am - 11:00 am

The quality of pharmaceutical solid dosage forms can be impacted by the flowability of the materials using the specified production process. From the design of clinical and market formulations through production support, multiple opportunities are presented for measurement and observation of flow properties/flowability of the mixture. Given the multivariate systems encountered, what measures are useful for solving problems related to flow of the material? From historical measurement techniques to compendial procedures, the choice of test method for generating flowability data can add clarity or confuse the problem solving process. This roundtable will use case studies to illustrate investigative processes and measurement techniques for powder flowability. New techniques, established testing procedures and proposed compendial methods will be discussed.

Moderator
Samir Mehta, Ph.D.
GlaxoSmithKline, Inc.

Powder Flow in Formulation Development
Dwayne A. Campbell, Ph.D.
GlaxoSmithKline, Inc.

Powder Flow in Process and Equipment Design
James K. Prescott, M.E.
Jenike and Johanson, Inc.

PQRI Proposal on Blend Uniformity Analysis

Tuesday, October 23, 2001
1:30 pm - 5:00 pm

Teambuilding and Communication are Essential for the Effective Performance of Pharmaceutical Organizations

Education Committee Roundtable
12:00 pm - 1:30 pm

Pharmaceutical product development is a complex process and involves effective communication, co-operation between the members of different functional areas for accelerated development and global registration of the product. Many times this may involove out-sourcing of work and/or a joint venture between two multinational companies with different cultural backgrounds. The roundtable will discuss the recent trends in high performance team building and effective communication approaches taken by the industries. The presentation will be helpful for graduate students, academic and industrial scientists.

Moderator
Prakash Parab, Ph.D.
Bristol-Myers Squibb Company

Application of Multiplexing Binding Assays in the Quantification of Biomarkers

Symposium
Tuesday, October 23, 2001
1:30 pm - 5:00 pm
ACPE Program Number: 073-999-01-224-L04

Quantification of biomarkers can provide important information regarding the activity, efficacy and toxicity of a candidate drug. This information is often combined with traditional pharmacokinetic data to develop an understanding of the drug’s concentration-effect relationship that aids in drug development. However, the potential positive impact of biomarkers is often not realized fully, as issues of sample volume and analytical costs often limit investigation and assessment of biomarkers during preclinical and clinical development. Thus, analytical strategies that overcome these limitations have the potential to increase the utility of biomarkers.

Multiplexed binding assays comprise a novel nonisotopic binding assay technology that permits the simultaneous determination of multiple analytes within biological specimens. This technology, which combines the principles of flow cytometry and binding assays into one analytical methodology, utilizes an array of distinct sets of microspheres. The beads serve as the solid phase for conducting the binding assay usually employing either an antibody or a DNA/RNA primer. Each bead set is impregnated with a unique fluorescent spectral address that serves to identify the binding reaction specificity. Detection is achieved by means of a fluoresecent labeled reporter, usually a secondary antibody, avidin or DNA/RNA primer. Since multiplexed binding assays offer the advantage of simultaneously measuring multiple analyses within a biological specimen, this technology should facilitate the identification and application of in vitro assays for biomarkers within the pharmaceutical industry.

Moderator
Brian T. Edmonds, Ph.D.
Eli Lilly and Company

Application of Multiplexing Binding Assays in the Quantification of Biomarkers: An Emerging Flow Cytometry Based Technology
Francis F. Mandy, B.Sc.
Health Canada, Canada

The Luminex LabMAP ^™ System: A Rapid, Homogeneous, Multiplexed Assay Platform
Lekha Patel, M.S.
R.W. Johnson Pharmaceutical Research Institute

Multiplexed Quantitation of Signal Transduction Pathways in Drug Discovery
Brian T. Edmonds, Ph.D.
Eli Lilly and Company

Microsphere-Based Studies of Nuclear Receptor Interactions
Marie A. Iannone, M.S.
GlaxoSmithKline, Inc.

Application Issues for Clinical Multiplexing Immunoassays of Cytokines
Chad A. Ray, M.S.
Eli Lilly and Company

Oral Dosage Form Development for Poorly Water-Soluble Drugs: Challenges and Opportunities

Symposium
Tuesday, October 23, 2001
1:30 pm - 5:00 pm
ACPE Program Number: 073-999-01-225-L04

Sponsored by Zeneca Pharmaceuticals Group

Combinational chemistry and high-throughput screening are commonly used in the discovery of new drug molecules. Both of these techniques favor the selection of highly lipophilic and poorly water-soluble drug candidates, and dosage form development of such compounds has become very challenging. Questions arise during the drug development process: Does a compound have adequate solubility to ensure dissolution under gastrointestinal (GI) pH conditions? What roles might GI physiology play in its dissolution and bioavailability? What are dose-to-solubility ratios in biorelevant media? What should formulation strategies be to ensure oral absorption at preclinical and early clinical development stages where dose requirements are relatively high? What are technological challenges and limitations in the development of marketable dosage forms for poorly water-soluble drugs? Can physiochemical properties of drug substances be modified by particle engineering to enhance dissolution and bioavailability? Are special drug delivery systems required? Is solid dispersion a viable approach, and, if so, what are some of the new opportunities in this approach? What are the challenges and opportunities in the development of lipid-based drug delivery systems? The speakers will attempt to answer most of these questions. Various developability issues with poorly water-soluble drugs, as well as strategies for overcoming them by dosage form design, will be presented.

Moderators
Abu Serajuddin, Ph.D.
Novartis Pharmaceuticals Corporation

Dharmendra Singhal, Ph.D.
Pfizer Global Research & Development

Assessing the Developability of Poorly Soluble Compounds
Jennifer B. Dressman, Ph.D.
Johann Wolfgang Goethe-Universität, Germany

Drug Candidate Selection and Early Development Strategies
Yatindra Joshi, Ph.D.
Novartis Pharmaceuticals Corporation

Molecular Pharmaceutics and Particle Engineering of Poorly Soluble Drugs
Peter York, Ph.D.
University of Bradford, United Kingdom

Bioavailability Enhancing Solid Dispersion Formulations Using Hydroxypropyl Methyl Cellulose Acetate Succinate (HPMCAS)
Ravi Shanker, Ph.D.
Pfizer Global Research & Development

Lipid Formulations: Why, When and How?
Colin Pouton, Ph.D.
University of Bath, United Kingdom

Process Control of Solid Dosage Form Unit Operations

Symposium
Tuesday, October 23, 2001
1:30 pm - 5:00 pm
ACPE Program Number: 073-999-01-226-L04

This symposium will review and emphasize the critical controls for different unit operations commonly involved in the manufacture of solid dosage forms. The identification and illustration of critical control systems and their impact on technology transfer, regulatory acceptance, and manufacturing process capabilities will be discussed. Additionally, case studies of unit operations will be presented, with the focus on identification and control of critical process variables to ensure robust manufacturing operations.

Moderators
Colleen E. Ruegger, Ph.D.
Novartis Pharmaceutical Corporation

Metin Celik, Ph.D.
Pharmaceutical Technologies International, Inc.

Overview of Process Control Systems for Solid Dosage Forms
Bhogi Sheth, Ph.D.
University of Tennessee

Control of Fluid Bed Wet Granulation Processing
David M. Jones
Glatt Air Techniques, Inc.

New Trends in the Production of Pharmaceutical Granules: Batch vs. Continuous Processing
Hans Leuenberger, Ph.D.
Swiss Academy of Engineering Science, Switzerland

Optimization and Control of Roller Compactor Operating Parameters
Roman T. Dec, Ph.D.
K.R. Komarek Research, Inc.

Film Coating: Process Control During Pan Coating
Stuart C. Porter, Ph.D.
Pharmaceutical Technologies International, Inc.

Role of Drug Transporters in the Brain

Symposium
Tuesday, October 23, 2001
1:30 pm - 5:00 pm
ACPE Program Number: 073-999-01-227-L04

Little is known about the cellular and molecular mechanisms of drug transport between blood and brain. This is unfortunate since the presence of tight junctions between the endothelial cells that form the blood-brain barrier (BBB) and the chorod plexus epithelial cells that form the blood-cerebrospinal fluid barrier (BCSFB) limit paracellular movement. Thus, specific transporters are required for the transcellular transport of hydrophilic compounds whether for the movement of nutrients into the brain or toxins out of the brain. By taking advantage of the unique structural and functional characteristics of these barriers (i.e., asymmetry of carriers on the blood-facing and CSF-facing membranes), it may be possible to target certain drugs to the brain. Alternatively, it is possible that transporters mediate the efflux of ligands from the brain, thus restricting their entry into the CNS from the circulating blood. In addressing fundamental questions of drug transporter activity, expression and significance, this symposium will have important implications for the treatment of serious CNS disorders and for providing new strategies in drug design, delivery and targeting to the brain.

Moderator
David E. Smith, Ph.D.
The University of Michigan

Drug Transporters at the Blood-Brain Barrier
William M. Pardridge, M.D.
University of California, Los Angeles

Role of Efflux Transporters for Organic Anions in the Blood Brain Barrier and Blood CSF Barrier
Yuichi Sugiyama, Ph.D.
The University of Tokyo, Japan

Role of Organic Cation Transporters in the Brain
John B. Pritchard, Ph.D.
National Institute of Environmental Health Sciences

Peptide Transporters: Role in the Choroid Plexus
David E. Smith, Ph.D.
The University of Michigan

Role of MPR/MDR Transporters in the Brain
A .G. “Bert” de Boer, Ph.D.
Leiden University, The Netherlands

The Success and Challenges of Bioinformatics and Pharmacogenomics in Drug Discovery and Development

Symposium
Tuesday, October 23, 2001
1:30 pm - 5:00 pm
ACPE Program Number: 073-999-01-229-L04

The pharmaceutical drug discovery process is continuously challenged to market innovative and effacious drugs. Critical to improving and enhancing this process and to reduce the cost of drug discovery and development, will be the know how of using the latest development in technologies. Recent advances in genomics and bioinformatics have led to the widespread utility of high throughput screening methods to increase the success rate. However, they also pose tremendous challenges for companies to continually improve their discovery methods, and to tease out the most valuable information that is important in drug discovery and development. The sciences that are involved in the translation of a biological obervation to the creation of a new drug are also ever-changing.

Symposium topics will include DNA-microarray platforms to identify new disease markers and targets, and to characterize lead compounds, the utility of gene expression arrays for novel target identification in the central nervous system, expression profiling of cancer cells and treatment with anticancer agents using DNA microarray, DNA-array technology to assess induction of genes encoding drug metabolizing enzymes, and DNA-array technology to assess toxicological response of xenobiotics and potential drug candidates in the pipeline, will be presented. This information may have significant impact in pharmaceutical drug discovery and development in the near future.

Moderator
A.-N. Tony Kong, Ph.D.
Rutgers University College of Pharmacy

Employing an Integrated RNA and Protein Expression Platform to Identify New Disease Markers and Targets, and to Characterize Lead Compounds
Mark Egerton, Ph.D.
Incyte Genomics Ltd.

Using Gene Expression Arrays for Novel Target Identification in the Central Nervous System
Lillian W. Chiang, Ph.D.
Millennium Pharmaceuticals

Gene Expression Studies Involving Functional Genomics and Informatics Approaches to Categorize Anticancer Agents and Drug Resistance of Tumor Cells
Khew-Voon Chin, Ph.D.
The Cancer Institute of New Jersey

Molecular Biological Approaches for High-Throughput Screening of Cytochrome P450 Induction in Drug Discovery
Thomas H. Rushmore, Ph.D.
Merck and Company

Using Gene Expression Profiles for Studying Signaling Mechanisms and Responses of Xenobiotics
A.-N. Tony Kong, Ph.D.
Rutgers University College of Pharmacy

Utility of Various Commercial Software Packages to Expedite Clinical Drug Development

Symposium
Tuesday, October 23, 2001
1:30 pm - 5:00 pm
ACPE Program Number: 073-999-01-228-L04

Clinical drug development for a typical New Chemical Entity (NCE) normally takes between four and seven years and costs an estimated $100 to $400 million. The attrition rate is around 80%, even after NCEs have been shown in animals to be safe and possess desirable pharmacological activity. Recent advances in clinical study design, laboratory automation and robotics, and new initiatives by regulatory agencies have decreased clinical development time and costs to some extent. However, computer technology advances have also resulted in very significant paradigm changes in how pharmaceutical companies conduct, execute, and complete regulatory submissions of NCEs.

Over the past 25 years, the computation tools used to support pharmacokinetic and pharmacodynamic analysis have evolved freeing the pharmaceutical scientist from the burden of cutting and weighing AUCs, sorting through stacks of cards, and/or loading magnetic tape. The advent of the PC and its continued maturation have brought computationally-intensive modeling techniques to the desktop and removed some of the coding burden. With these advances, the desire to assemble data across the lifetime of a chemical entity has become attainable. In addition, the necessity to mine historical data within a compound’s development and across compounds within a therapeutic area has become a current challenge for many companies as they seek to streamline development costs and eliminate redundancy. These efforts directly coincide with the regulatory and document management efforts to provide data for an electronic submission. Several attractive solutions are available to meet the needs of today’s pharmaceutical companies in this arena. They differ in scope, data management backbone, and interface. This session will examine and critically evaluate a number of approaches that use computer systems and applications to address the growing pressures to shorten development times and improve success rates from a variety of perspectives including data management/mining resources, modeling and simulation methods, and regulatory compliance with 21 CFR part 11. As these technologies evolve, forums such as these are an invaluable way for the scientist/consumer to voice opinions about the current status of these products and for the commercial vendors to learn how the scientific community feels about their products.

Moderators
Henry J. Pieniaszek, Ph.D.
DuPont Pharmaceuticals

Jeffrey S. Barrett, Ph.D.
DuPont Pharmaceuticals

Use of Modeling, Simulation, and Information Technology to Improve Clinical Trials and Development Decisions
William F. Ebling, Ph.D.
Pharsight Corporation

PK Sirius as an Integrated Scientific Information Management System and Review Tool
Sasa Lu, Ph.D.
Sirius Knowledge Systems, Inc.

Accelerating Early Clinical Development and Achieving Part 11 Compliance Through Protocol-Driven, Study-Based Analysis, Management and Reporting
Richard S. Wagner
InnaPhase Corporation

A New Chemical Entity(NCE) Web Portal for Phase I and II Analysis Ready Data
Michael Roberson
Ibiomatics/SAS

Current Topics in Medicinal and Natural Products Chemistry

Poster Podium
Tuesday, October 23, 2001
1:30 pm - 5:00 pm

Authors will present papers selected from abstracts submitted for the poster sessions. Representative papers concerning drug design, computational chemistry and natural products drug discovery will be featured.

Moderator
Bruce L. Currie, Ph.D.
South Dakota State University

Recent Advances in Drug Delivery

Poster Podium
Tuesday, October 23, 2001
1:30 pm - 5:00 pm

Authors whose research in the area of drug delivery and pharmaceutical technology 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
Vishal K. Gupta, Ph.D.
Pharmacia Corporation

AAPS Graduate Symposium in Analysis and Pharmaceutical Quality

Sponsored by Celltech Pharmaceuticals, Inc.
Tuesday, October 23, 2001
1:30 pm - 5:00 pm

Graduate students whose research has been competitively judged to be outstanding will present the findings of their research efforts. Special awards will be given to the presenters at the conclusion of the session.

AAPS Graduate Symposium in Biotechnology

Sponsored by G.D. Searle and Company
Tuesday, October 23, 2001
1:30 pm - 5:00 pm

Graduate students whose research has been competitively judged to be outstanding will present the findings of their research efforts. Special awards will be given to the presenters at the conclusion of the session.

Building Credible Simulations

Roundtable
Tuesday, October 23, 2001
2:00 pm - 4:00 pm

One of the most difficult tasks for a simulation scientist is not building the model, but the conveyance to an outside audience of the simulation’s credibility or level of confidence. Simulations with low credibility are of questionable value and lead to wasted resources. This roundtable will discuss criteria that can be used to develop credible simulations which can then be used in the decision-making process.

Moderator
Peter L. Bonate, Ph.D.
Quintiles

Qualification of Models for Simulation
Hui C. Kimko, Ph.D.
Georgetown University, Center for Drug Development Science

Validating Models — One Size Does Not Fit All
Mark E. Sale, M.D.
GlaxoSmithKline, Inc.

GMP Audit Guidelines For Excipients

Roundtable
Tuesday, October 23, 2001
2:00 pm - 4:00 pm

This roundtable will define appropriate standards of Good Manufacturing Practices for the manufacture of excipients. The IPEC America perspective and views will be presented as well as a discussion on the European Community (EC) draft directive on starting materials.

Moderators
Janice Cacace
Pformulate.com

Chris Bapatla, Ph.D.
Alcon Research Ltd.

Transcriptional Regulation of Drug Metabolizing Enzymes: Novel Tools to Study Human CYP Induction

Symposium
Tuesday, October 23rd
1:30 pm - 5:00 pm

The Pregnane X Receptor: A Promiscuous Xenobiotic Receptor that Regulates Multiple CYP Genes
Bryan J. Goodwin, Ph.D.
GlaxoSmithKline

Nuclear Orphan Receptor CAR and Drug Induction of P450 Genes
Masahiko Negishi, Ph.D.
National Institute of Environmental Health Sciences

Transcriptional Control of Intestinal CYP3A4 Mediated by the Vitamin D3 Receptor
Kenneth I. Thummel, Ph.D.
University of Washington

The Use of Human Hepatocytes for Drug Induction and Metabolism Studies
Stephen Strom, Ph.D.
University of Pittsburgh

Humanized Xenobiotic Response in Transgenic Mice Expressing Human Nuclear Receptors
Wen Xie, M.D., Ph.D.
The Salk Institute for Biological Studies

An Overview of GMP Requirements for the Manufacture of Excipients

Speaker To Be Announced
FDA Speaker Invited

Excipient Industry Perspective
Irwin B. Silverstein, Ph.D.
IPEC America

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