Christopher D.

Breder, MD PhD
Division of Neurology Products
Food and Drug Administration
 Disclaimer

The views expressed in this talk represent

my opinions and do not necessarily
represent the views of the FDA.
 Introduction
• By way of …
– Small
– Medium and
– Large Pharma

– the FDA
• OND\CDER\DNP (Div Neurology Products)
– Johns Hopkins University, Center for
Biotechnology Education
 Objectives
• By the end of this lecture, you should be
able to:
– Describe the role of and skill sets needed for
the Project Manager (PM) position
– Appreciate the different tools used by the PM
 Recommended Reading

“…is not a simple process” “..depends on the quality of the

development strategy”
So lets start at square one
6
 What is Pharmaceutical
Development
…and why do we need a 
Project Manager?

How many of you have had a manager as a ‘Boss’ (functional or otherwise)

How many of you have had a ‘bad Boss’

A PEEK UNDER THE HOOD OF
THE PHARMACEUTICAL
PROJECT TEAM
 What is
Pharmaceutical Development
• Unmet • Market
Medical Need Potential

• Innovation

R&D COMMERCIAL

REGULATORY
Corporate
Infrastructure

• Statutory • Resource
Constraints Limitations
 What is a
Pharmaceutical Project Team
CLINIC
AL

NON
Regula
Business
CLINIC
AL
Drug tory
Marketing

CMC
 The team at the first level
Clinical
Reg Ops
Research

Safety Clinical
Clin CLIN Reg Regul Med
Pharm Affairs atory Writing
ICAL

Medical CMC
Affairs NON Reg
Regul
CLINI
CAL
Drug atory

Pharm
Chemi
stry

Non CMC ANAL

Manufa
Tox Clinic Path cturing CMC YTICA
al L

CLIN
PKDM SUPPLY
 What is a Clinical Development
ClinicalProject Team Clin
Pharm
Research

Clin Bio Clinical PK

Clin Biome
Clinical Pharm trics
OPS Stats Research

Data Modeling
Mgmt
Clin
Safety Clinical Pharm
Med
Early Devt
Affairs

Medical
Safety Epidemi Affairs Med Medical Health
Team Safety ology Comm Affairs Econ

Post
Marketing Liasons
Surveillance
 The Matrix Model for Project
A
Recommended
Teams
1. Higher Efficiency and Ownership
Approach to
2. Managing by Influence (No Line Authority)
International
Project
Management

Functional Managers

Primary Representatives

Objectives/
Decisions
Project Team
 INTERNAL FORCES
Evaluation Team
Turf
Quality
YOUR Strategic
Time PROJECT Intent

Decision Marketing
Making Selection
 EXTERNAL FORCES

Competition Commercial
Potential
Time YOUR
FDA/BoH
PROJECT

Activists Congress
Reimbursement
Pharmaceutical Project
Management
What is Project Management?

PMBOK
“Project management is the
application of knowledge, skills,
tools, and techniques to project
activities in order to meet or exceed
stakeholder needs and
expectations from a project.”
 Cost of Poor Management
• 27,400,000
• $ 899 MM/Each New Drug
• Opportunity Costs
• Failed Drugs
• Marketing & Sales Costs
• The Patients are Still Waiting
In other words…
 Benefit of Good
Management
• Higher NPVs
• More Products per $
• Identify Losers Sooner
• More Successful Projects
• Faster Reviews
Shrinking time to second in class requires
that you get out of the gates fast & hard
Years Between Drug Launch and First Competitor

Years 0 2 4 6 8 10

Inderal 1968
(hypertension)
Tagamet 1977
(ulcer)
Capoten 1980
(hypertension)
Seldane 1985
(hayfever)
• Increased competitiveness
AZT 1987 • Must maximize opportunity
(AIDS) from day one
Mevacor 1987
(cholesterol)
Prozac 1988
(depression)
Diflucan 1990
(fungal infections)
Recombinant 1992
(hemophilia)

Source: A.T. Kearney, The Economist 09/20/97

The Role of the PM
 PM EVOLUTION
Project/Venture

PROJECT DRIVEN
LINE DRIVEN

Portfolio P/M
Resource Allocation
Facilitate
Plan/Integrate
Resource Constraints
Track
Monitor Status
Notes
1975 1980 1985 1990 1995 2000
The Faces of Clinical Development
Project Management

Project
Management

Project Analyst Project Leader

(timelines, (Voice to Upper
budgets) Mgmt)
 Project Management
Who They Are and What They Do:
From a Project Manager
• Masters of Business Process
• Business = Commercial +
Technical
• Facilitators of Interpersonal
Interaction

26
What is Project Management?:
• Broad Knowledge
– Experience
• Interpersonal Skills
– Facilitating
– Human Factors
• Ability to get the most
out of tools / technology
– Innate analytic
• Communication Techniques
 What is Project Management?:
Facilitating decisions
• Selecting Clinical Candidates
• Implementing
• Tracking
• Reporting
• Completing /Terminating

Adapted from “How to Keep R&D Projects on Track!”--Robert Szakonyi

What is Project Management?:
Human factors
• Leadership
• Team Building
• Matrix/ Heavy-weight Teams
• Communication
• High Performance
• Education
What is Project Management?:
Communication Techniques
• What if analyses • Cajoling
• Critical path • Nagging
analyses • Begging
• Brainstorming
• Challenging
(devil’s advocate)
Suddenly, a heated exchange took place between
the king and the moat contractor!
What is Project Management?:
Tools
• Planning • Decision trees &
software network
• PERT charts • Meeting minutes
• Gantt (bar) • Spreadsheets
charts
• Dashboards • e-Mail
• Budgets • Word processor
• Teleconference
• Videoconference
 “Sure, we need more research in alchemy,
necromancy, and sorcery, but where is the money
going to come from?”
 Tools for the Project Manager
• Don’t Leave Home Without It!!
– The Team Minutes
– The Target Product Profile
– The Draft Structured Product Label
– The Strategic Development Plan
– The GANNT Chart
– The Probability Analysis
Why are these tools important
to everyone?!
• “…Even if you do not lead a team,
you lead a team of 1”.
 Team Meeting Minutes
• What they are good for
– Exquisitely organized progress review
– Concise communication tool for Senior
Management
• Brings priorities and timelines up front
– Documentation of accountabilities and
responsibilities
– Drives the agenda of the team meeting
 Team Minutes Template
• Issues (Boxed)
– Things that will cause delay, cost overrun, or that may
impact a Go/No-Go decision
– Background, impact, proposals
• Timelines
– With key milestones, e.g., final protocol, first patient,
database lock, topline data, final report
• Some Mgmt like planned /projected (while ongoing)/actual

• Financial Summary
• Progress by Dept
– Nonclin, Clin Pharm, Clin, Regulatory, CMC, Clin Supplies
– More granular, yet concise progress report, including
finances, timelines, key deliverables met and forthcoming
 Target Product Profile
• A contract with the Corporation regarding
the desired attributes of the Product
– Determines estimate of Net Present Value
– Forms the basis of Go-No Go Criteria
– Forms the basis of the clinical development
plan (CDP;and probably all other DPs) and
draft label
Target Product Profiles
The low case may be the 
same or reasonably lower 
You may not want any of 
than the GS if there are 
a particular GS attribute, 
other attributes in favor of  It is not uncommon to 
even in the low case
your drug incorporate intellectual 
property positions in the 
TPP

Differences in numerical 
results are tricky to 
assign; be reasonable; 
What is clinically 
significant?

Same point as efficacy; 
This is my common 
tolerability strategy
 Product Labeling: New Format
Highlights Section
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Imdicon ---------------------DOSAGE FORMS AND STRENGTHS----------------------
safely and effectively. See full prescribing information for Imdicon. Capsules: 50 mg (3)

IMDICON® (cholinasol) CAPSULES -------------------------------CONTRAINDICATIONS------------------------------

Initial U.S. Approval: 2000  Hematopoietic disorders or a history of TTP or aplastic anemia (4)
 Hemostatic disorder or active bleeding (4)
WARNING: LIFE-THREATENING HEMATOLOGICAL ADVERSE  Severe hepatic impairment (4, 8.7)
REACTIONS
See full prescribing information for complete boxed warning. -----------------------WARNINGS AND PRECAUTIONS------------------------
Monitor for hematological adverse reactions every 2 weeks for first 3  Neutropenia (2.4 % incidence; may occur suddenly; typically resolves
months of treatment (5.2). Discontinue Imdicon immediately if any of the within 1-2 weeks of discontinuation), thrombotic thrombocytopenic
following occur: purpura (TTP), aplastic anemia, agranulocytosis, pancytopenia,
 Neutropenia/agranulocytosis (5.1) leukemia, and thrombocytopenia can occur (5.1)
 Thrombotic thrombocytopenic purpura (5.1)  Monitor for hematological adverse reactions every 2 weeks through the
 Aplastic anemia (5.1) third month of treatment (5.2)

----------------------------RECENT MAJOR CHANGES-------------------------- ------------------------------ADVERSE REACTIONS-------------------------------

Indications and Usage, Coronary Stenting (1.2) 2/200X Most common adverse reactions (incidence >2%) are diarrhea, nausea,
Dosage and Administration, Coronary Stenting (2.2) 2/200X dyspepsia, rash, gastrointestinal pain, neutropenia, and purpura (6.1).

----------------------------INDICATIONS AND USAGE--------------------------- To report SUSPECTED ADVERSE REACTIONS, contact

Imdicon is an adenosine diphosphate (ADP) antagonist platelet aggregation (manufacturer) at (phone # and Web address) or FDA at 1-800-FDA-1088
inhibitor indicated for: or www.fda.gov/medwatch.
 Reducing the risk of thrombotic stroke in patients who have experienced
stroke precursors or who have had a completed thrombotic stroke (1.1) ------------------------------DRUG INTERACTIONS-------------------------------
 Reducing the incidence of subacute coronary stent thrombosis, when  Anticoagulants: Discontinue prior to switching to Imdicon (5.3, 7.1)
used with aspirin (1.2)  Phenytoin: Elevated phenytoin levels have been reported. Monitor
Important limitations: levels. (7.2)
 For stroke, Imdicon should be reserved for patients who are intolerant of
or allergic to aspirin or who have failed aspirin therapy (1.1) -----------------------USE IN SPECIFIC POPULATIONS------------------------
 Hepatic impairment: Dose may need adjustment. Contraindicated in
----------------------DOSAGE AND ADMINISTRATION----------------------- severe hepatic disease (4, 8.7, 12.3)
 Stroke: 50 mg once daily with food. (2.1)  Renal impairment: Dose may need adjustment (2.3, 8.6, 12.3)
 Coronary Stenting: 50 mg once daily with food, with antiplatelet doses
of aspirin, for up to 30 days following stent implantation (2.2) See 17 for PATIENT COUNSELING INFORMATION and FDA-
Discontinue in renally impaired patients if hemorrhagic or hematopoietic approved patient labeling
problems are encountered (2.3, 8.6, 12.3) Revised: 5/200X
 Product Labeling: New Format
Full Prescribing Information
Boxed Warning 10 Overdosage
1 Indications & Usage 11 Description
2 Dosage & Administration 12 Clinical Pharmacology
3 Dosage Forms & Strengths 13 Nonclinical Toxicology
4 Contraindications 14 Clinical Studies
5 Warnings & Precautions 15 References
6 Adverse Reactions 16 How Supplied/Storage &
7 Drug Interactions Handling
8 Use in Specific Populations 17 Patient Counseling
9 Drug Abuse & Dependence Information

44
 Why is Labeling Important
• It is considered the preferred method to
convey information about your drug
– Has profound impact on advertising, claims,
compensation
– Often the first source of information for
doctors and consumers
• If you want claims in your label, you need
to study it
– Sometimes things you don’t want get put in,
e.g., class labeling
Strategic
Development
Plan

Adapted from
Kennedy’s
“Pharmaceutical
Project Management”
GANNT Chart
 GANNT Chart
• Allows review of timetables
– Allows one to double check assumptions
• Identification of resources
• Allows recognition of critical interdependencies
– e.g., need to clear product with QA before shipping
– Forms the basis of Go-No Go Criteria
• Identifies critical path tasks
– a critical path is the sequence of activities which add up to
the longest overall project duration. This determines the
shortest time possible to complete the project. Any delay of
an activity on the critical path directly impacts the planned
project completion date. Those activities that can be done at
anytime are “not on the critical path”
Critical Path Analysis: GANTT Chart
50
Probability Exercises for Project
and Portfolio Planning
 Summary
• Clinical Development is complex, both in
its science and relationships
• The CDPM plays a pivotal role facilitating
the planning and execution of CD
• Various tools are at the
disposal for organization
and communication
• Project Leader is the
one who takes the reins!