The Course

The Medical Product Development Enterprise: Past, Present, and Future Perspectives

Learning Outcomes
At the end of Session 1, the course participant should be able to:

• Summarize the history of the pharmaceutical enterprise
• Discuss the principles and organization of global pharmaceutical research and label-driven product development
• Discuss the future directions of global pharmaceutical, health economics and business environments, and their implications for drug selection, drug development, regulatory and business evaluations
• Identify innovation in discovery and development as a response to patient, medical and market needs
• Develop a Target Product Profile to set the strategy for medical product discovery and development programs and projects
• Explain US Food and Drug Administration regulatory pathways for drugs, biologics, biosimilars, cellular and gene therapies and combination products

Topics

• History of the pharmaceutical enterprise
• Development timelines
• Principles of contemporary drug development and regulatory science
• Patient perspectives in medical product development
• Pharmacoeconomics, health technology assessment, and methods for comparison of economic value for different products
• Global health trends, disease management, and their effect on health outcomes
• Regulatory pathways for drugs and biologics
• Regulatory landscape and development challenges in pediatric, cell and gene therapies, and novel treatment modalities
• Special topics based on cutting edge science, changing regulations, controversies, etc.
• Decision points in development of small and large molecules
• Management science: Portfolio, projects, and teams
• Target product profile: A key strategic tool in product development

Learning Trials: From Discovery to First in Humans

Learning Outcomes

At the end of Session 2, the course participant should be able to:

• Describe the principles of drug discovery including in vitro and in vivo techniques used to identify and characterize the chemical, biological, and pharmacological properties of drug candidates
• Explain the fundamentals of pharmacokinetics (PK) and describe the use of preclinical data to predict human PK
• Identify the methodology for selecting, optimizing, formulating, assessing the safety, and protecting the intellectual property of small molecule and biologic preclinical drug candidates
• Apply clinical pharmacology principles for the early assessment and development of clinical candidates
• Describe how biomarkers are integrated into and used to accelerate the drug development process
• Discuss the principles of and regulations for conducting nonclinical and first-in-human clinical studies

Topics

• PK, pharmacodynamics (PD) and absorption, distribution, metabolism, and excretion (ADME)
• Discovery chemistry
• Discovery of biologics
• Chemistry, manufacturing, and control (CMC)
• Selection criteria for therapeutic monoclonal antibodies
• Strategies and approaches for preclinical to clinical translation
• Intellectual property in drug discovery and development
• Strategies for predicting human PK, exposure-response, and safety
• Determinants of human PK variability
• Guidelines and Beyond for nonclinical toxicology
• Strategies for successful toxicology investigations
• Devices to support early drug development

Learning and Confirming Trials: Finding and Confirming the Right Dose

Learning Outcomes
At the end of Session 3, the course participant should be able to:

• Discuss strategy for taking drugs into humans and through proof of concept in patients
• Discuss the appropriate use of preclinical data for estimating safe and potentially effective dosing in early human clinical studies, especially the limitations of such predictions
• Discuss the pros and cons of early trial designs, the safety management of subjects in these studies, and the decisions required on limited data
• Discuss model-informed drug development (MIDD)
• Address approaches to measuring change in disease, drug efficacy, and safety as generally modulated by dose-exposure-response
• Discuss and plan strategies for determining dose-response prospectively and finding individual dose-exposure-response by exploratory analysis
• Explain the various aspects of the conduct of a clinical trial

Topics

• Choosing doses/exposures for first in human studies, and the role of pharmacokinetics-pharmacodynamics (PKPD) modeling and simulation
• Biomarker strategy and qualification for efficacy and safety
• Developing drugs from first in human dosing to understanding dose-exposure-response in patients – efficacy and safety
• Regulatory perspective: Utilizing pharmacodynamic biomarkers in drug development
• Quantitative principles for drug development decision-making
• Dose-exposure ranging in early drug development
• Exposure response and drug-drug interaction
• Optimization of clinical trial design
• Conundrums of the learning phase of drug development
• Proof of concept
• Data utilization for decision making at the end of the learning phase

Statistics: Design, Analysis, and Interpretation of Clinical Trials

Learning Outcomes
At the end of Session 4, the course participant should be able to:

• Evaluate clinical trial designs and statistical analysis plans to generate credible evidence about a treatment effect
• Interpret clinical trial data to evaluate whether the data constitute substantial evidence of a treatment effect for a regulatory approved label
• Understand the concepts underlying frequentist and Bayesian inference, including hypothesis testing, p-values and Bayesian posterior probabilities
• Recognize the impact of multiple testing in clinical trials and methods to reduce false positive findings
• Construct an appropriate estimand for a clinical trial using the ICH E9(R1) framework
• Compare the pros and cons for various clinical trial designs, including adaptive designs and enrichment designs, and understand how modeling and simulation play an important role in trial optimization
• Discuss considerations for sample size, power, false positive and false negative decisions emanating from interim analyses and final analyses of clinical trials
• Apply statistical considerations for a confirmatory study design and design an analysis plan for a tailored subgroup for phase 3

Topics

• Role of confirmatory phase in drug development
• Statistical principles for clinical trials
• Choice of control groups in clinical trials
• Study objectives, hypothesis testing, sample size, and probability of study success
• Multiplicity in clinical trials
• Missing data and estimands
• Interim analysis
• Bayesian statistics
• The design, analysis, and interpretation of a clinical endpoint trial
• Modeling and simulation
• Adaptive design in clinical trials and optimization
• Design and analysis of adaptive clinical trials
• Enrichment designs
• Perspectives for developing a targeted medicine
• Co-development of a diagnostic and targeted medicine
• Statistical issues related to design, analysis, and reporting of gene therapy clinical trials
• Multi-regional clinical trials
• Safety assessment and surveillance
• Pharmacovigilance

Global Clinical Trial Authorization and Marketing Authorization Processes

Learning Outcomes
At the end of Session 5, the course participant should be able to:

• Explain the requirements for various regulatory applications, including documentation and possible avenues for receiving advice from regulators
• Discuss the procedures for regulatory oversight in the US, the European Union (EU), and China, including processes for starting a clinical trial and for marketing authorization in these jurisdictions 
• Discuss social corporate responsibility and its impact on low- and middle-income countries
• Discuss special US regulatory procedures, regulatory strategies, and crisis management
• Recall and apply the benefit-risk framework used by the US FDA for assessment of new drug applications

Topics

• US FDA applicable laws, regulations, and guidance documents
• FDA’s new drug clinical trial and marketing authorization review processes
• US benefit-risk methodology and considerations
• US labeling requirements
• US regulatory actions and outcomes for NMEs, NDAs, and BLAs
• US regulatory approaches to post-marketing
• US regulatory requirements for rare diseases, pediatric therapeutics, and cell & gene therapies
• Challenges with and approaches to multi-country clinical trials
• US FDA advisory committee meetings and CHMP oral explanations
• CMC section of regulatory applications
• FDORA, PDUFA VII, and their impact on US FDA-regulated industry and US FDA
• Starting a clinical trial and obtaining scientific advice in the EU, Japan, China, and the US
• Procedures and approaches to obtain marketing authorizations from the European Medicines Agency (EMA), Pharmaceutical and Medical Devices Agency of Japan, National Medical Products Administration (NMPA) of China, and US FDA
• Enhancing diversity in clinical trial populations
• Real-world data and real-world evidence
• Artificial intelligence and machine learning

Integrated Product Development, Project Management, Portfolio Management, and Preparing for Transition to Market

Learning Outcomes
At the end of Session 6, the course participant should be able to:

• Discuss the principles of project and portfolio management, including aspects of planning, project evaluation, and decision making
• Explain the limitations of traditional portfolio management and propose innovative methods to improve portfolio management
• Apply the principles of portfolio management to drive decision making in medical product development
• Discuss the principles of business development, partnering, and alliance management throughout the lifecycle of a product
• Apply the principles of regulatory requirements for advertising and promotion of a prescription drug
• Practice leadership strategies for team interactions and other decision making

Topics

• Portfolio management: principles, challenges, applications, and strategies
• Role of licensing in portfolio management
• Project management: principles, challenges, and strategies
• Judgment under uncertainty
• Integrated global strategy
• Turning strategy into plans
• Co-development and alliances
• Strategic marketing (commercial) role in development

• How to launch a new drug successfully into the market

• Risk communication and prescription drug promotion
• Promotional committee review simulation
• Leadership strategies in drug development and regulation