2015 PFIZER PHARMACEUTICAL MEDICINE ELECTIVE. Last Update: November 17, 2015

Transcription

1 2015 PFIZER PHARMACEUTICAL MEDICINE ELECTIVE Last Update: November 17, 2015

2 Table of Contents I. Medicines Regulation... 3 A. Introduction to Regulatory Strategy: Shira Rohde, PhD... 3 B. Introduction to Medical Device Regulation: Mario Mendoza, MD, MS... 3 C. Regulatory Concerns: Advertising & Promotion, USPI overview: Diane Rocco, MBA, MS... 3 D. Overview of Generic Nomenclature Process: Michael Quinlan, BA... 3 E. Overview of Project Management: Amy Novina, PharmD... 4 II. Drug Safety Surveillance... 4 A. Principles of Case Review: Gregory G. Gribko, PharmD, MPH... 4 B. How Epidemiology Adds Value to Drug Safety: Rachel Sobel, PhD... 4 C. Risk Evaluation and Management: Gary G. Wilson, PhD... 4 III. Clinical Pharmacology... 4 A. Clinical Pharmacology in Drug Development: Bimal Malhotra, PhD... 4 B. Drug Metabolizing Enzymes & Pharmacogenomics: Bimal Malhotra, PhD... 5 C. Clinical Pharmacology: Drug-Drug Interaction and Special Population Studies: Manoli Vourvahis, PharmD... 5 IV. Clinical Development... 5 A. Good Clinical Practices: Joan Mackell, PhD... 5 B. Understanding Clinical Trials: Ana Maria Jorga, MD, PhD... 6 C. Phase 3 & 4 Clinical Trial Design: Thomas McRae, MD, MS... 6 D. Statistical Considerations in Clinical Trials: Glenn Pixton, PhD... 6 E. Clinical Trials: TRIAD: Bimal Malhotra, PhD... 6 F. Molecular Epidemiology: Geoff Makinson,... 7 G. Application of Population Pharmcokinetic/Pharmacodynamic Modeling and Simulation in Drug Development: Ellen Q. Wang, PhD... 7 V. Medical Affairs... 7 A. One Physician s Journey in Industry: Julia Perkins, MD... 7 B. Medical Affairs: Konstantinos Tsilkos, MD... 7 C. Publications at Pfizer: Shirley Lam, PharmD... 8 D. Why are you a Physician working at Pfizer?: Denis Keohane, MD, MS; Mike Wajnrajch, MD, MPA; Kevin Williams, MD, JD, MPH... 8 E. Basics of the Pharmaceutical Industry and Why We are Where We Are: How d We Get There: Andrew Clair, PhD

3 F. Investigator Initiated Research: Margaret Essex, PharmD... 8 G. Health Economics & Outcomes Research: Christine Baker, JD, MPH... 9 H. Medical Science Committee for Opioids: Bimal Malhotra, PhD... 9 I. Overview of External Medical Affairs: Paula DeCola, Michael Flesher, Nisith Kumar, Bob Miglani, Charles Thompson... 9 J. Medical Affairs: Phase I-IV studies: Mabel Woloj, PhD... 9 K. Overview of interactions with FDA prior to approval, in label negotiations, and regarding initial promotional materials, Laura Cisar, PhD, MPH

4 I. Medicines Regulation A. Introduction to Regulatory Strategy: Shira Rohde, PhD Medicines Regulation is a key foundation for the Pharmaceutical Medicines Elective. The FDA regulates all aspects of the pharmaceutical industry from early drug development through to post-approval maintenance. The first section of this module introduces the student to global regulatory agencies (with a focus on the U.S. FDA), drug development timelines, the electronic Common Technical Document (ectd), and New Drug Applications (NDAs). B. Introduction to Medical Device Regulation: Mario Mendoza, MD, MS Introduction and general overview of the FDA medical device regulation and clearance pathway. Includes definitions of a medical device, examples of medical devices, FDA CDRH infrastructure and medical device clearance applications (510k, PMA, De Novo, HDE). C. Regulatory Concerns: Advertising & Promotion, USPI overview: Diane Rocco, MBA, MS Provide an introduction to the U.S. Prescribing Information (USPI). Specifically, the format is reviewed and the process by which the content is developed internally and negotiated, and ultimately approved, by the FDA is presented. The NDA/BLA submission process is reviewed in the context of label creation and approval. The importance of the USPI content is discussed relative to the document s use in Advertising and Promotion activities. The process for the development, review, and approval of promotional materials is discussed. Real-product examples of promotional materials are discussed to highlight regulatory considerations in the creation and execution of promotional materials. D. Overview of Generic Nomenclature Process: Michael Quinlan, BA Using real world examples, the overview will explain the purpose of generic names, how they are derived and screened, and the process steps involved in gaining successful outcome on the review of the name. It will take the colleagues on the process journey from name development through the USAN Council & the WHO INN Programme approvals. 3

5 E. Overview of Project Management: Amy Novina, PharmD To gain an understanding of project management, and the the role of the project manager. To provide a brief overview of RU / BU structure. Define governance, decision points, and lastly what data/information is necessary for a DP presentation. II. Drug Safety Surveillance A. Principles of Case Review: Gregory G. Gribko, PharmD, MPH Appreciate how to approach and prepare for a case review as well as understand when they are applied and when case series reviews are useful. Understand terms such as adverse events, adverse reaction, dose response, temporal association, de-challenge, re-challenge, and confounding, and individual case assessments. Understand how to assess drug/adverse event causality. B. How Epidemiology Adds Value to Drug Safety: Rachel Sobel, PhD Understand how pharmacoepidemiological study data is utilized in safety signal management, drug development decision-making, and regulatory strategy. C. Risk Evaluation and Management: Gary G. Wilson, PhD Provide an overview of Risk Evaluation and Mitigation Strategies (REMS-U.S.) and Risk Management Plans (RMP-European Union). III. Clinical Pharmacology A. Clinical Pharmacology in Drug Development: Bimal Malhotra, PhD Provide an overview of Clinical Research during various stages of drug development from Firstin-Human (FIH) to Proof-of-Concept (POC) studies; as well as transition to late-phase 4

6 development (Phase 2) and registration (Phase 3) studies. Understand the importance of Knowledge Management in applying the principles of Enhanced Quantitative Drug Development (EQDD), in practice at Pfizer over the last several years to improve the probability of success of each of our clinical studies through efficient and well-informed study designs. To understand the critical role of clinical pharmacology in traditional areas such as pharmacokinetics/ pharmacodynamics aspects of clinical programs, selection of doses for FIH/POC and Phase 2/3 studies, bioavailability/bioequivalence and drug-drug interactions and special population assessment. Provide an understanding of the application of modeling & simulation to the Phase II/III clinical study design process. B. Drug Metabolizing Enzymes & Pharmacogenomics: Bimal Malhotra, PhD Provide an overview of drug metabolizing enzymes with specific focus on cytochrome P450 (CYP) enzymes. Discuss, specific examples of drugs used to treat overactive bladder (tolterodine and fesoterodine) and depression (venlafaxine and desvenlafaxine) as well as attention deficit hyperactive disorder (atomoxetine), where CYP2D6 activity is implicated in the metabolism of the parent drug. C. Clinical Pharmacology: Drug-Drug Interaction and Special Population Studies: Manoli Vourvahis, PharmD Provide an overview of drug metabolizing enzymes and drug transporters with a detailed discussion on special population and drug-drug interaction study strategy, study design, and analysis. Examples of special population studies discussed include assessing pharmacokinetics in pediatrics, hepatic impairment and renal impairment populations. Provide an overview on how to interpret the drug-drug interaction and special population sections of the product label. IV. Clinical Development A. Good Clinical Practices: Joan Mackell, PhD Discuss the various clinical and historical events that led to the evolution and development of Good Clinical Practices (GCPs), including laws, regulations, the Declaration of Helsinki and the contemporary international perspective, as developed through the International Conference on Harmonization (ICH) Guidelines. Provide an understanding of the rationale for these laws, regulations and guidelines, ensuring that clinical research is consistently performed to high 5

7 ethical and scientific standards, with the primary considerations being to protect the rights and safety of clinical subjects and ensure quality, integrity, consistency and reproducibility of data. B. Understanding Clinical Trials: Ana Maria Jorga, MD, PhD Provide an understanding of different clinical trial designs, basic study terminology, phases of drug development, protocol design, and aspects of study participation (informed consent, patient safety and protection). Provide an understanding of late stage clinical trial design (Phase 3 & 4). Protocol design and considerations including: demographics of study population, regulatory considerations, cultural aspects (local studies), and statistical considerations. C. Phase 3 & 4 Clinical Trial Design: Thomas McRae, MD, MS Provide an understanding of late stage clinical trial design (Phase 3 & 4). Protocol design and considerations including: demographics of study population, regulatory considerations, cultural aspects (local studies), and statistical considerations. D. Statistical Considerations in Clinical Trials: Glenn Pixton, PhD Introduce statistical concepts and how they relate to study design. Understand how study design affects data analysis. Provide an introduction to basic terms such as Type I and II error, randomization, bias, types of comparisons, sample size, and interim analysis. E. Clinical Trials: TRIAD: Bimal Malhotra, PhD Provide an introduction to Pfizer design and conduct of clinical research and how it is enabled through study teams comprised of a TRIAD at the core, representing three critical and essential functional lines: Clinical Sciences, Clinical Pharmacology, and Statistics. Discuss the role and responsibilities of the TRIAD study team; the TRIAD is expected to consider multiple study design options and is encouraged to use quantitative tools such as modeling & simulation exercises to choose an option that provides optimum probability of success. A clinical program or trial may be endorsed to proceed only when the TRIAD has demonstrated application of EQDD best practices. 6

8 F. Molecular Epidemiology: Geoff Makinson, Provide an introduction to the role of molecular epidemiology and its function across Global Health & Value, Outcomes & Evidence, and R&D. G. Application of Population Pharmcokinetic/Pharmacodynamic Modeling and Simulation in Drug Development: Ellen Q. Wang, PhD Provide an example of how population pharmacokinetic/pharmacodynamic (PK/PD) modeling is used to establish the quantitative relationship between drug dose, plasma concentration, and pharmacodynamic response. Provide an understanding of how clinical trial simulations were used (using the final population PK/PD model) to help select the most appropriate dose and regimen for a global Phase 3 program. V. Medical Affairs A. One Physician s Journey in Industry: Julia Perkins, MD Provide an overview of how much clinical training one needs to work in industry, how to apply it and which areas within industry are available to a physician for career development. Understand the pros and cons of working in pharmaceutical medicine versus clinical medicine. Deck entitled: Fellows Career Day: Fellowship to Industry B. Medical Affairs: Konstantinos Tsilkos, MD Provide a clear overview of the role of medical affairs within an industry setting. Including, but not limited to: providing a medical perspective to drug product development, provide support for marketed products (ie, RC committees), ensure adherence to relevant scientific and legal guidelines, and provide general as well as specialized expertise per therapeutic area as required internally and externally. Finally, to act as the company subject matter expert in a given therapeutic area/areas and interface with all sectors of the medical profession. 7

9 C. Publications at Pfizer: Shirley Lam, PharmD Provide an overview of External publication guidelines (ICMJE) and internal requirements (SOPs CT20 and CT37). D. Why are you a Physician working at Pfizer?: Denis Keohane, MD, MS; Mike Wajnrajch, MD, MPA; Kevin Williams, MD, JD, MPH Provides an overview of the different roles in industry as well as the paths a physician can embark on in order to begin a career in industry. It provides medical students with the opportunity to engage and interact with a number of physicians who have chosen a career in industry. Presenters discuss their backgrounds and career paths that led them to taking a position working at Pfizer. During this interactive session, students have the opportunity to ask questions and have a dialogue with Pfizer physicians working in the Medical Affairs organization. These in-depth conversations cover a variety of topics ranging from the advantages and disadvantages of choosing a career in industry and the different types of career opportunities available for physicians within the pharmaceutical industry. E. Basics of the Pharmaceutical Industry and Why We are Where We Are: How d We Get There: Andrew Clair, PhD Provide an understanding of various events which have led to the current state of the pharmaceutical industry. Other areas covered include an introduction to drug development, preclinical and clinical studies, regulatory history, origin of Good Clinical Practices and FDA warning letters due to clinical study violations. F. Investigator Initiated Research: Margaret Essex, PharmD Provide an understanding of Pfizer s commitment to fostering new relationships with scientists and nurturing top research talent. Provides an introduction to and overview of the Pfizer Investigator Initiated Research program, which serves as an incubator for research projects that 8

10 advance medical and scientific knowledge about our therapies and generates promising medical interventions. The role that Medical Affairs plays in this process is highlighted. G. Health Economics & Outcomes Research: Christine Baker, JD, MPH s Overview of health economics and outcomes research methodologies and how they are used to support Pfizer medicine market access of H. Medical Science Committee for Opioids: Bimal Malhotra, PhD s Provide an overview of the Medical Science Committee (MSC) members, role, and function within Pfizer. The Medical Science Committee (MSC) members typically include: Clinical Sciences, Clinical Pharmacology, Statistics, Regulatory Affairs, Medical Affairs, Pharmaceutical Sciences, Chemistry/Manufacturing/Controls, Project Management, and regional Medical Directors. The agenda of each meeting varies depending on the evolution of the program status. At a given MSC meeting, the team may discuss the evolving program strategy, functional line updates, clinical study design proposal(s), emerging study results, competitive updates etc. Students may be given an opportunity to attend a scheduled MSC meeting for the Abuse- Deterrent Opioids program at Pfizer. I. Overview of External Medical Affairs: Paula DeCola, Michael Flesher, Nisith Kumar, Bob Miglani, Charles Thompson s To provide an overview of Pfizer s External Medical Affairs group which supports the safe, effective, and appropriate use of Pfizer human health products across the lifecycle for all patients across the life course. This is accomplished in collaboration and partnership with the leadership of healthcare organizations, in order to shape the healthcare landscape, increase access to the Pfizer portfolio and improve patient outcomes. J. Medical Affairs: Phase I-IV studies: Mabel Woloj, PhD s Provide a basic understanding of clinical drug development phases. Including clinical and medical affairs function/roles throughout the drug development process, inclusive of drug discovery through drug approval and lifecycle management. 9

11 K. Overview of interactions with FDA prior to approval, in label negotiations, and regarding initial promotional materials, Laura Cisar, PhD, MPH s Provide an overview of how to find label information, FDA review documents, and document from Oncology Division Advisory Committee meetings: Demonstrate link to FDA label information, and how to find reviewer comments Demonstrate link to oncology advisory committee meeting materials cdrugsadvisorycommittee/ucm htm Provide an understanding of interactions with the FDA prior to approval, in label negotiations, and regarding promotional material sent in for pre-clearance: Review publication of phase 3 pivotal trial for Inlyta, and FDA guidance Good Reprint Practices for the Distribution of medical Journal Articles and medical Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices (available) Review types of information included in a briefing document prior to an ODAC (available) Review specific example (Inlyta) of label negotiations with the FDA, in parallel looking at the label Review OPDP comments on preclearance materials, keeping in mind label negotiations and publication of phase 3 study Review subsequent revisions to promotional materials 10