CMC Project Team Leadership – In Person

Attendees view introductory lecture prior to the start of the course

Continental Breakfast/Networking

Welcome and Introductions

Eric Buxton, PhD
Clinical Professor, Program Director: MS Applied Drug Development, Chair, Division of Pharmacy Professional Development, School of Pharmacy, University of Wisconsin-Madison

Anatomy of the Common Technical Dossier ("CTD"): and Clinical Trial Applications in US and EU

Speaker: Sharon Graham, Regulatory Affairs, Chemistry Manufacturing and Controls (RA CMC), AbbVie

Overview of the common technical document format for submissions of IND's, NDAs, BLAs, ANDAs, and DMFs. US Clinical trail applications: types of INDS, US laws, regulations and guidance and IND submission and review process. Overview of international clinical trial applications in the EU.

Physical & Chemical Factors in Candidate Selection and Optimization

Speaker: Rick Pyter, PhD, Development Consultant and Adjunct Professor
School of Pharmacy, University of Wisconsin – Madison

The key physicochemical factors that distinguish "lead compounds" from "development candidates" will be addressed.

Technical Overview: Drug Substance Synthesis and Process Development

Speaker: Ashok Bhatia, PhD, Director, Pharmaceutical Development, Associate Research Fellow, Process Chemistry, AbbVie

Synthesis/process chemistry challenges; starting materials, intermediates, reagents, solvents, catalysts; particle isolation step; salts, crystal forms and polymorphs; impurity profiles of toxicological and clinical batches including: chirality; genotoxic impurity assessment; working with contractors; elucidation of structure and physical-chemical properties; reference standard; level of detail provided in an IND.

Analytical Challenges with Testing Drug Substance

Speaker: James Bernstein, PhD, Pharmaceutical Consultant
Live Oak Pharmaceutical Consulting, Inc.

Overview of analytical chemistry role in DS development; analytical methods used for raw material, intermediates and final DS; analysis of DS; associated release tests, the C of A; method validation requirements; specifications; stability assessment and protocol example; initial retest period and extension; typical level of detail provided in an IND or IMPD for DS.

Team Exercise #1: Calculation of drug requirements thru FIM-Introduction

Moderators: Ashok Bhatia and other faculty create teams.

Technical Overview: Oral & Parenteral Drug Delivery and Dosage Form Development

Speaker: Ed Elder, PhD, Director, Zeeh Pharmaceutical Experiment Station
School of Pharmacy, University of Wisconsin – Madison

Overview of major oral and parenteral dosage forms; formulation development stages (excipient compatibility, selection and level optimization, prototype formulation development); DS requirements and development time requirements for different dosage forms; technical considerations with placebos and packaging (container and closure) selection.

Analytical Challenges with Testing Drug Product

Speaker: James Bernstein, PhD

Overview of the role of analytical chemistry in DP development; analytical methods used for raw materials, intermediates, and DP; support of DP development; analysis of DP (content, impurities, etc.), associated release tests, the C of A; method validation requirements for Phase 1; specifications; stability assessment and protocol example including packaging; assignment of DP expiration dating; typical level of detail provided in an IND or IMPD for DP.

CMC Project Management Tools

Speaker: James Bernstein, PhD

Elements of project planning; timing and interdependencies of DS and DP tasks; critical path identification, determining DS and staffing requirements for development, clinical trial supply manufacture & scaleup; project reviews, strategy documents, progress reports and other communication vehicles; CMC team meeting management ( agendas, minutes, decision making approaches, conflict management and other aspects of project team meetings).

Biotechnology Talk-Large Molecules and CMC
What's Different About Project Planning for NBEs and NCEs?

Speaker: Eugene McNally, PhD, PPD

Key differences between CMC activities associated with NBEs and NCEs will be explored.

Continental Breakfast/Networking

Team Exercise #2 Working Session

Quality Assurance and Quality Control for GLP and GMP Materials

Speaker: James Bernstein, PhD

Overview of the regulatory aspects of release and testing of supplies for GLP toxicology and GMP clinical trials.

Technical Overview: Preparation of Toxicology and Clinical Trial Supplies

Speaker: Ed Elder, PhD

Overview of the strategies and other factors associated with design and production of supplies for GLP toxicology and human clinical trials.

Lunch

FDA-Industry Meetings

Speaker: Sharon Graham

Overview of the types of formal FDA meetings, pre-IND, pre-NDA, end of phase (EOP), preparation of questions and briefing documents, meeting conduct.

CMC Project Manager's Responsibilities Part 1: Deliverables and Optimization of Team Performance

Speaker: Rick Pyter, PhD

Key deliverables and leadership responsibilities will be defined; reporting responsibilities will be discussed; important attributes of an effective leader will be described. The composition of Global Project and CMC teams will be discussed as a function of project stage. The pros and cons of various team structures will be addressed. Teams will conduct a self-assessment of their overall effectiveness.

Project Management of Life Cycle Management and Drug Device Combination Products - CMC Considerations

Speaker: Pamela Swatkowski
President, PLS Consulting, LLC, Adjunct Associate Professor, School of Pharmacy, University of Wisconsin – Madison

Differences in the science, associated project planning and tasks for life cycle management programs, including drug device development and line extensions, will be highlighted.

Team Exercise #3 - Introduction and Working Session: Creation of a CMC Project Plan for a Drug/Device Combination

Moderators: Faculty

Assemble the appropriate tasks into a coherent CMC project plan that includes timing, key dependencies, responsibilities, etc. One team member will be elected by the team to present the plan to the entire group.

Adjournment

Evening free to explore Madison

Continental Breakfast/Networking

Challenges with An Outsourcing Model

Speaker: James Bernstein, PhD

Out-sourcing of various CMC activities creates new challenges for CMC team leaders, with additional differentiation occurring between large integrated pharmaceutical organizations and small or virtual pharmaceutical organizations. The different requirements of CMC leaders in these situations will be explored; participant experiences will be of particular value to the discussion.

Phase Appropriate Strategies for CMC Development

Speaker: James Bernstein, PhD

A regulatory and strategic framework for phase-appropriate CMC development will be discussed; valve drivers for early development identified; impact of drug properties on development activities will be considered.

Assessing CMC Changes During Phase 3 and After Primary Stability
Speaker: Sharon Graham

Assessing CMC changes that occur late in development (during or after Phase 3 and after primary stability batches have been manufactured). Using post approval change guidance to determine what additional data need to be included in the initial NDA to support changes. 

Team Exercise #4 - Assessing Changes to Drug Substance and Drug Product: Introduction and Working Session

Moderator: Sharon Graham

Team Exercise #4: Sub-groups report to entire group

Sub-groups present their constructed project plans, highlighting key features, assumptions, and critical success factors.

Team Exercise #5: Introduction and Working Session: Creation of a CMC Project Plan for A Line Extension

Moderator: Rick Pyter and other faculty

Assemble the appropriate tasks into a coherent CMC project plan that includes timing, key dependencies, responsibilities, etc. One team member will be elected by the team to present the plan to the entire group.

Continental Breakfast/Networking

Team Exercise #5 - Sub-groups Report to Entire Group

Sub-groups present their constructed project plans, highlighting key features, assumptions and critical success factors.

CMC Project Manager's Responsibilities Part II: Skills and Key Attributes

Speaker: Rick Pyter, PhD
Important skills and attributes of an effective leader will be described.

Alternative Emerging Therapeutic Approaches - Antibody-Drug Conjugates (ADC): Basic CMC Concepts
Speaker: Ashok Bhatia, PhD

Course Summary and Assessments

Rick Pyter, PhD, & Eric Buxton, PhD
Key concepts will be summarized and integrated in closing comments. Attendees will be asked to fill out a course assessment form to help the faculty improve future offerings.