Developing an Extended-Release Opioid Class-Wide REMS

Developing an Extended-Release
Opioid Class-Wide REMS
May 6, 2009
Proposal to Industry Working Group
CONFIDENTIAL AND PROPRIETARY
Any use of this material without specific permission of McKinsey & Company is strictly prohibited
https://www.industrydocuments.ucsf.edu/docs/xfxk0255

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McKinsey & Company 2
Contents
▪ Introduction
▪ Proposed project approach
▪ McKinsey qualifications
▪ Working arrangements
▪ Appendix

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Our understanding of the challenge you face
Situation Challenges
• October 2008: FDA asked opioid manufacturers to
prepare and submit individual REMS proposals
• November 2008: King pharma proposes REMS
programs for Remoxy & Embeda at FDA AdCom
▪ AdCom members expressed desire for a single
class-wide REMS and frustration over whether
REMS would be effective
• December 2008: FDA asked the same sponsors to
NOT submit REMS proposals, and instead wait for
written guidance on a class-wide REMS
• February 2009: FDA announced that it invited
sponsors of 24 modified-release opioid drugs to
discuss the development of a class-wide REMS, as
the first of a series of different stakeholder meetings
• March 2009: FDA asked manufacturers to
collaborate on preparing a joint proposal for a class-
wide REMS for controlled-release opioids
• April 2009: Sponsors initiated regular meetings,
divided into five sub-teams and begin planning and
brainstorming how to collectively develop a mutually
agreeable REMS proposal
• No REMS has ever been created on this scale,
affecting tens of millions of patients
• There is no precedent for the manufacturers of
24 different drugs developing a joint
recommendation on such a sensitive issue:
▪ Disparate interests and concerns (e.g.,
those of generic versus branded)
▪ Wide range of resources already invested
in understanding challenges of opioid
REMS (zero to huge)
▪ Varying levels of seniority, experience, and
time commitment in each manufacturer’s
designated representatives
• Implementation of REMS may have
consequences that are difficult to anticipate
• Risk that REMS will unduly burden healthcare
system and disrupt patient access to opioids
• Coordinating the process and input from 75+
individuals is time consuming and logistically
difficult; no one participating has time to do it

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Making matters more difficult, the FDA continues to grapple with a number
of REMS-related challenges
SOURCE: The Pink Sheet; literature search
“We're still trying to learn what the process might be, what the triggers are, what
the expectations are, so that we can convey those to you in a guidance ”
– John Jenkins, Director, FDA Office of New Drugs
* As of 2/20/2009
Uncertainty over
how broadly to
apply REMS
Legal
implications
Burden on the
healthcare
system
Quotes
To date*, the FDA has yet to issue official guidance on REMS
The vagueness of the language in FDAAA raises questions on the scope of FDA’s
legal authority (e.g., Can the FDA mandate a class-wide REMS?)
“There are some complex legal issues based on the way FDAAA is written”
The severity of burden on various stakeholders is unclear
“We can’t keep trying to come up with an individual system each time…
Eventually, the system [healthcare system] is going to collapse under the
weight of multiple programs”
Logistical
challenges
The current healthcare infrastructure is inadequate to support REMS
“What ideally we need to achieve…is a health care system that can
accommodate any of the REMS programs. We need a system where a
pharmacy doesn’t need to call the iPledge program or the new opioids program
to decide whether or not the doctor who wrote the prescription is enrolled and
registered”

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REMS implementation will have unintended as well as intended
consequences
Total population
Eligible patient population
Potential patient pool
after REMS
Eligible patients with
optimal risk profile
Effects of REMS on
patient population
• REMS will restrict
inappropriate use (e.g.,
through enforced lab test)
and off-label prescription
(physician education/
certification)
• REMS might also cause
patient access issues due
to complicated and
burdensome compliance
programs
Patients who don’t
receive drug due
to increased
administrative
burden on
prescribers,
pharmacists and
patients
Additional high-
risk populations
filtered out by
REMS to avoid
known or potential
risks
Patients ineligible
for drug by
definition, e.g.,
label,contra-
indications
(increased
enforcement
through REMS)
Patient population
CONCEPTUAL
SOURCE: McKinsey analysis
In addition to the unintended
consequences for patient access, REMS
can also create additional burden on
the health system

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Costs of different elements of REMS will vary significantly
with type of program and complexity of design
1 Vendor administrated survey: $1.9 per mailed survey and $0.75 per processed response
2 Self administrated survey: $0.98 per mailed survey and $4.30 labor cost per processed response
3 In office survey: $1.57 per survey for survey printout, office staff incentive, and data entry
4 International Medical News Group
SOURCE: BioMed Central; Psychiatric Services; JGIM; Mgmt & Tech. Consultants LLC.;
Cost of running a patient survey for 100 responses
In USD
Annual cost of patient registry system per provider
In USD
10251
Mailed
survey by
vendor @
20% resp.
rate
7081
Mailed
survey by
vendor @
30% resp.
rate
10442
Self-admin
mailed
survey @
30% resp.
rate
1573
Written
survey run by
office staff in
a clinic
650
WellCentive
registry
system
1000+4
Misc.
comprehensiv
e systems
EXAMPLES

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Participating manufacturers must answer a number of critical questions in
order to successfully navigate class-wide REMS hurdles together…
Critical questions
Strategic
Operational
Organizational
▪ What is the optimal design for the REMS?
▪ Will pending approvals be delayed by ongoing REMS discussions? (e.g., Remoxy, Embeda)
▪ What are alternatives to REMS measures authorized by the FDAAA?
▪ What will the ultimate cost of the REMS proposal be (and how will it be split between
branded and generics manufacturers)?
▪ How can the effectiveness of REMS be measured?
▪ Who will be responsible for measuring impact?
▪ How can the REMS be implemented to achieve risk management goals, while minimizing
adverse impact on patient access, and on the business?
▪ How will you take into account input from other non-sponsor stakeholder groups (e.g.,
patient advocacy groups, pharmacists, wholesalers, etc)
▪ Who should be responsible for operating the REMS program? (e.g., sponsors vs. States vs.
the FDA)
▪ What technical/IT infrastructure is required to support a REMS that would cover 21 million
prescriptions per year?
▪ How can sponsors of 24 products, who are competitors, work together to most effectively
and quickly develop a common REMS proposal?
▪ Is there sufficient experience on the components of REMS within the “consortium”?
▪ Which functions should be included for input into REMS design and at what stages?
▪ How will decisions be made by the “consortium?
▪ How will disagreements be resolved?
▪ Will you introduce a Steering Committee?

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…and plan a clear path forward
Potential actions
Strategic
▪ Design strategy
– Assess potential alternatives for REMS design that would meet risk management goals
– Benchmark proposed or solicited REMS against existing REMS for drugs with similar risk profiles
▪ Communication strategy
– Define a clear communication plan for influencing FDA on design and implementation of REMS
– Define communication plan for reaching relevant stakeholders (prescribers, patients, pharmacists)
– Define communication plan for reaching other sponsors for “Class-wide” REMS
▪ Determine generic versus branded sponsor role and responsibilities
– Assess potential for establishing IP around REMS processes (e.g., Celgene’s registry patents)
Operational
▪ REMS implementation:
– Assess impact of REMS design on patient access and burden on healthcare delivery system
– Assess potential compliance / reception to various REMS requirements by healthcare stakeholders
▪ Clearly define process and dynamics for cross-sponsor w”consortium” working norms
– Align quickly on program requirements and implementation
– Assess and plan for potential positions / perspectives of other sponsors based on their situation
(e.g., products / revenue impacted, relevance to business, etc.)
– Determine dispute resolution procedures between sponsors and with other stakeholders
– Assess potential cost-sharing arrangements for shared programs
▪ Potential impact and re-design
– Incorporate specific assessments to determine impact of REMS on meeting goals
– Proactively communicate findings to FDA
Organizational
▪ REMS team design
– Create cross-functional REMS subteams, define objectives of each
– Include personnel from Regulatory, Risk Management, Legal, IT, Distribution, Marketing
▪ Internal “consortium” capabilities
– Assess Regulatory and Risk Management capabilities / experience
– Assess potential project management leads given need for cross functional team
1 Generic and innovator manufacturers required to share single system for Elements to Assure Safe Use unless FDA determines 1)
burden of single system outweighs benefit or 2) aspect of Elements to Assure Safe Use is protected and unable to be licensed
NOT COMPREHENSIVE

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Contents
▪ Introduction
▪ Appendix

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As part of this effort, McKinsey would provide project
management support during an 18-month period
Phase I –
Develop initial
manufacturers proposal
Phase II –
Syndicate with external
stakeholders and test
operational feasibility
Phase III –
Finalize recommendation
to be submitted to FDA
~3-4 months ~9-12 months ~1-2 months
Timing
• Coordinate efforts
among the 15
manufacturers
• Develop an initial
integrated proposal that
• Conduct preliminary
feasibility assessment
• Syndicate initial
proposal with key
external stakeholders
(e.g., physician groups,
patient advocacy
groups, pharmacy
groups, distributors)
• Ensure alignment and
validate operational
feasibility
• Refine initial proposal
including input from
• Finalize proposal to be
submitted to FDA
Description
PRELIMINARY

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At a high level, McKinsey’s support would span 4 key areas…
Work planning
Meeting
coordination
Communications
Budget and
payments
management
1
2
3
4
▪ Develop and track project workplan, including key milestones, using
appropriate tools (e.g., Microsoft® Project)
▪ Schedule, coordinate and facilitate all relevant team meetings and
teleconferences
▪ Provide relevant materials to all team members prior to meetings or
teleconferences
▪ Prepare and Distribute meeting minutes within 3 business days of any
project team meetings and/or teleconferences
▪ Manage all critical project communications, including communicating
goals, deadlines, issues and progress to the team in a timely fashion
▪ Manage budget and provide a budget status update on a monthly basis.
▪ Disperse payments to other IWG vendors, as needed.
PRELIMINARY

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…and coordinate the efforts of all three committees and execution sub-
teams
Steering
committee
Content
committee
Public Relations
committee
McKinsey
Project
Management
support
Sub-team 2
Sub-team 1 Sub-team 4

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Each phase will have specific activities and deliverables
Phase I –
Develop initial manufacturers
proposal
Phase II –
Phase III –
Finalize recommendation to be
submitted to FDA
▪ Develop detailed project work
plan with key milestones and
deliverables
▪ Help form sub-teams that will in
charge of execution
▪ Schedule and facilitate regular
meetings with IWG members to
develop and refine initial
proposal
▪ Track overall progress of all sub-
teams and send out regular
updates
▪ Ensure coordination among all
different sub-teams
▪ Identify all relevant external
stakeholders (e.g., physician
groups, patient advocacy groups,
pharmacy groups)
▪ Conduct literature review of
existing position papers to
capture current thinking and
understand stakeholder positions
▪ Schedule and facilitate meetings
with all relevant stakeholders
▪ Help incorporate feedback from
external stakeholders into update
REMS
▪ Initiate dialogue with the FDA on
planned approach to align
expectations and secure
participation
▪ Incorporate FDA and other
stakeholder input and feedback
to finalize the REMS
▪ Follow-up interviews with
stakeholders and experts as
necessary to finalize the
document
▪ Draft a white paper to publish
the consensus perspectives, if
appropriate
Activities
▪ Detailed project workplan in
appropriate tool (e.g., Microsoft®
Project)
▪ Detailed meeting schedule with
proposed agendas
▪ Meeting materials and minutes
▪ Regular updates to teams
▪ List of all relevant external
stakeholders
▪ Literature review with likely
position of key stakeholders
proposed agendas
▪ Materials for discussion with the
FDA
▪ Finalized REMS for FDA
submission
proposed agendas
Deliverables
PRELIMINARY

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McKinsey has extensive project management experience and can use a
series of tools to facilitate the management process
Project
follow up
Project initiation
Project idea Study
Project start-up
Approval
Detailed
preparation
Project in running
Business
implement.
IT implement.
1. Project Charter
To define up-front in sufficient detail:
▪ Project scope and goal
▪ Top-level business case
▪ Top-level project plan and
staffing needs
▪ Potential Risks
Critical
project
tools
2. Project work plan
▪ To plan detailed structure of the
project, including phases,
milestones, tasks, end
deliverables, and resource
requirements
2.1. Kick-off document
▪ To create a kick-off presentation
2.2. Project resource plan
▪ To show resource utilization
along the project
3. Project reporting
To monitor project status, including
▪ Targets achieved, deliveries made
▪ Risks in the project
▪ Actions / decisions in order to
overcome obstacles
Special
project
tools
1.1. Business case tool
▪ To assist estimating total
investment, business and IT
impact
1.2. Key stakeholder analysis
▪ To ensure involvement of key
stakeholders who are not part of
project team
1.3. Project risk assessment tool
▪ To identify and address
potential risks in the project
3.1. Change request form
▪ To change of scope or other
major changes in the problem
has to be addressed
3.2. Risk monitoring tool
▪ To identify arising risks of
project failure while running the
project
4.1. Project-end
document
To wrap the project
up, including
▪ Project summary
▪ Project evaluation
▪ List of related
project
documents
3.3. Budget management tool
▪ To track budget over time and
compare actual vs. planned cost

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Project charter
Project opportunity: Detailed description of opportunity that project will address
Sponsor(s): Steering committee:
Project manager: Stakeholders:
Project objectives
▪ What are the specific objectives (e.g., growth, market
share)?
▪ Are the objectives measurable?
▪ Are the objectives realistic?
▪ What are the nonquantitative objectives?
Major milestones/
activities
▪ What are the known
final deliverables?
▪ What major milestones
or interim deliverables
exist?
Timing
▪ When must the project
be completed?
▪ When must certain
critical path objectives
be reached?
Project background
▪ What is the rationale/history for the project?
▪ What decisions have already been made?
Key issues/risks
▪ What solution constraints exist?
▪ What are the concerns of the stakeholders?
▪ Do conflicting agendas exist?
Cost/benefit analysis
▪ What is the potential value of the project?
Resources
Team members Skills required Time commitment
Cross-functional support (e.g., information
technology, purchasing):
Project cost: $__________
▪ What resources can we leverage?
▪ Who controls the resources?
▪ Which members are under the project leader
and which are outside the project leader’s control?
▪ Do we have a dedicated, cross-functional team?
1 ILLUSTRATIVE EXAMPLE

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Business case tool
BUSINESS CASE
Project Name Build new credit card system
Project Leader Mr X
Date 9/2/2004
Key assumptions Risk (H/M/L)
Business Assumptions
¶ No entry of large foreign credit card players M
¶ No significant entry of competitors into our new untapped
target segments, i.e. low income young men outside
Seould
H
¶ No significant competitor for VISA payment system in the
coming 2 years
L
¶ No "price-war" of credit cards in the coming 2 years H
IT Assumptions
¶ Smooth integration between new system and current
legacy system and its database
L
Business requirements Operational KPI
Quantified financial impact
(NPV)
Expected timing of
realization
¶ Increase in number of credit cards + 10,000 cards + US$15,000 in
revenue/month
3 months after
implementation
All
¶ Reduction in application processing error rates 25% reduction n/a 1 month after
implementation
Application
50% reduction n/a 3 months after
implementation
¶ Shorten application time Application time : 2 days =>
4 hours
n/a 1 month after
implementation
Application
Total cost estimated according to resource plan US$441,600 million
Overall business case
NPV improvements = +US$600,000
RoI = 16.5%
Impact Estimated
Related functional
blocks
Assumptions (both business and IT)
underlying the business case are
clearly laid-out and assessed in risk
to provide vigor in estimation
Timeline for realization of benefits is
estimated and subsequently tracked
Both operational and financial
impacts are clearly laid out to justify
the business case
1.1 ILLUSTRATIVE EXAMPLE

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Key stakeholder analysis: mapping (1/2)
1.2
High
Medium
Low
Opponent Neutral Supporter
Ability
to
impact
success
Level of support
Most preliminary analysis tends to be overly optimistic,
mapping stakeholders further to the right than they actually are
A stakeholder’s position may
change as a result of:
• Change in role
(promotion, demotion,
reassignment, etc.)
• Change in scope or timing
of initiative
• Stakeholder management
activities
Stakeholders that are not formally managed as part of the process tend to “drift to the left”

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Key stakeholder analysis: mapping (2/2)
1.2
Ability to impact success
High:
• Stakeholder support is critical to success; without
required support, initiative will be unable to
deliver its objectives
Medium:
• Stakeholder support is important; absence of
support will have strong impact on some
objectives and may inhibit achieving others at all
Low:
• Stakeholder support will impact several of the
objectives, reducing the overall effectiveness of
the initiative
Level of support
Supporter:
• Stakeholder has or will undergo change in mindset
and behavior required by the initiative
• Will “say good things” about the initiative
• Those further to the right in the supporter column
are willing to actively advocate for the initiative
Neutral:
• Stakeholders are either unsure about the change
(either because they do not know enough or
because they are “waiting to see”) or they are
ambivalent because there are some positive
aspects resulting from the initiative, but there are
also some elements they would like to see
changed
Opponent:
• Stakeholder will not undergo change in mindset
and behavior required by the initiative
• Those further to the left in the opponent column
are likely to actively undermine the initiative and to
seek to persuade others to do likewise

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Project risk assessment tool
1.3
Risk category
Scope/size
IT
People and
organization
implementation
Financial
Legal/regulatory
Type of risk Risk level Category weight
Percent
Alarm signal Mediation for risk
▪ State of risk
based on
‘Project risk
assessment
checklist’
specifically for
the project
▪ Type of the
risk need to be
as project
specific as
possible
▪ Estimate risk
level based on
‘Project risk
assessment
checklist’
▪ Grade 1-3, use
0.5 distinction
if needed
▪ Category
weights
estimate
relative
importance of
different risk
categories on
overall project
risk
▪ The weights
are project
specific and
can be
changed in
different
phases of
project
▪ Value
threshold or
signal specific
to type of risk
when project
comes into
large troubles
▪ Outline of
action to be
taken when
given type of
risk achieved
and signed

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Project work plan: overview
2 Focus
over time
End of
project
▪ Top-down targets set
by top management
▪ Iterative planning
process
– Within subprojects
– Across subprojects
(coordinated by
PMO)
▪ Definition of critical
milestones for each
subproject
Necessary revisions due to delays
or changes in requirements
Initial project
work plan
Planning
▪ Mainly up front
but revisions
typically
necessary in
long projects
▪ Potentially
very complex
due to inter-
dependence
of subprojects
Week 1
▪ Milestones and status
▪ Risks and issues
▪ Budget
Week 2
…
Final week
…
…
▪ Subprojects aggregate their module reporting
▪ PMO aggregates subproject reporting, checks consistency
▪ Project leader approves/rejects, triggers corrective action
▪ PMO distributes weekly reporting to top management and subproject
▪ Regular task,
e.g., on
weekly basis
▪ Potentially
very time-
consuming
due to large
number of
reporting
sources
Reporting
Project setup Implementation start
Update

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Project work plan: key elements
2
Phases
What is it?
Why to
have it?
Have
frequently
use it?
Milestones Tasks End product Timing
Respon-
sible
Depend-
encies
▪ Parts which are
– Comprehens
ive
– Logical
– Self-closed
▪ Could be treated
as separate small
project
▪ Significant events
showing progress
▪ Different from
progress reviews
since not given
by time but
results
▪ Smallest pieces
of work plan
with clearly
defined results
to be
measurable
▪ Tangible
task result
▪ End results allow
for project re-
direction or re-
scoping
▪ Allow tracking of
project progress
▪ Divide project
into more
manageable
parts
▪ Drive project
team
organization and
planning process
▪ Drive
accountability of
team/project
manager
▪ Allow for
effective team
resources
allocation
▪ Drive
accountability of
team members
▪ Up to 3 months ▪ 1-3 months
▪ Always sub-part
of phase
▪ 1-3 weeks
▪ Always sub-part
of milestones
      
Can be
easily set
up in
Microsoft
Project
ILLUSTRATIVE EXAMPLE

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Project work plan: planning tools
ID Task Name
1 Phase 1
2 Task 1
3 Task 2
4 Task 3
5 Milestone
6 Phase 2
7 Task 4
8 Task 5
9 Review meetings
Anna[50%]
Bogdan
Anna
10-30
T F S S M T W T F S S M T W T F S S M T W T F S S M T W T F S S M T W
'01 Oct 08 '01 Oct 15 '01 Oct 22 '01 Oct 29 '01 Nov 05 '01 Nov 12
Task
completion
indicator
Resource or
responsible
person
Holidays
You can
explicitly point
dependencies
There is a
function to insert
a recurring task
One can apply
structure
(hierarchy)
2
▪ Microsoft® Project allows for
- Resources planning
- Budget depletion control (through designated rates)
- T&M cost calculation
- Reporting

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Resource support plan (1/2)
Purpose Structure Use
Format
▪ Plan needed internal and external
resources
▪ Define the budget
▪ Task description
▪ Needed material resources
▪ Time of resource allocation
▪ Relevant financial resources
▪ Execution units make a list of resources
needed to accomplish the task
▪ The PMO (jointly with the Finance) makes
a consolidated schedule of needed
resources and actions to detail them (e.g.
rent of space, involvement of
subcontractors, etc.)
Date by which
the required
resource must be
allocated
Stage and tasks
requiring resource
allocation
Type of required resources
▪ Human (man/hours)
▪ IT
▪ Financial
▪ Etc…
Stage
Task
No
Descrip-
tion
Time
Required physical resources
Type
Relevant financial
resources
Unit of
measure
Quantity
Price per
unit of
measure
Financial
result
▪ Required financial budget
▪ Result of multiplying the
quantity of the resources
by their price

|
Resource support plan (2/2)
Employees involved clearly listed
with their grades, time of involvement
and % of time involved
Each employee is given a
“charge back” rate to reflect the
true cost of a project, and make
“apple-to-apple” comparison with
external vendors
PROJECT PLAN - RESOURCE PLAN
Project Name Class wide REMS proposal – Subteam 1
Project Leader Mr X
Time and duration of
resource utilization is laid
out clearly to facilitate
resource planning
Week 0 is the week starting
Time (weeks)
Resource # Working group leaders Function
Cost
equivalence
per day (US$)
Involvement 0 1 2 3 4 5 6 7 8 9 10 11 12 13
H-1 Mr A Regulatory TBD 100% 1 1 1
H-2 Mr B Clinical TBD 100% 1 1 1 1 1 1 1 1 1 1 1 1 1 1
H-3 Mr C Regulatory TBD 100% 1 1 1 1 1 1 1 1 1 1
H-4 Ms D Safety TBD 100% 1 1 1 1 1 1
H-5 Mr E Safety TBD 50% 1 1 1
H-6 Mr F Project Mgmt TBD 50% 1 1 1
Resource # External Parties Cost (US$)
V-1 ABC Co (Programming support) TBD
V-2 XYZ Co (Testing environment provision) TBD
Resource # Others Cost (US$)
O-1 Pilot testing TBD
Total project budget TBD
9/2/2004

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Project reporting: 3 key elements
3
A project-wide status overview
summarizes the key points …
"Overview project status"
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
a
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
… and the corresponding mile-
stone overview
c
Milestones subproject A
… based on the more detailed
reporting for each subproject …
▪ Compiled by PMO for project
leader/top management
▪ Objective comparison of
planned milestones and
actual status – can be
automated to a large degree
▪ Prepared by subprojects
▪ Ideally presented to top
management by subproject
leaders
b
"Subproject A: …"
Results Current issues
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
▪ ...
Decision needs
▪ ...
▪ ...
▪ ...
▪ ...
▪ "Traffic lights" logic to trigger
necessary action, e.g., at core
team or steering committee
level
▪ Persistent, transparent
tracking is key
▪ Highlights need for action

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Project reporting: overview project status
▪ Business Case
drafted and
accepted by
steering
committee
▪ Location of
customer care
center
determined
▪ Process des-
cription on hold
due to IT deploy-
ment delay
▪ IT-Deployment
delayed, next
deployment
window in week
44
▪ Requirements
Doc Version 1.1
checked and
accepted
▪ Product
roadmap
redefined to
remove legal
risks
▪ Marketing cam-
paign ready for
roll-out
▪ National roll-out
campaign
planned
▪ Advertisement
trucks for
ranger
campaigning
ordered
▪ Roll-Out of
cable in 7 of
150 cities
delayed
▪ Boxes with
quality issues
Products/
Marketing
M. Shipman
Customer
Service
L. Hersh
System
Integration
J. Westin
Sales and
Distribution
T. Cochran
Finance
L. Cullum
Technical
D. Angel
3a
Quality & Testing
R. Zander
▪ Product pilot planning finished
▪ KPI definition on-going
B. Smith
Project Owner
F. Cunningham
Project Leader
G. Beecham
Project office

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Project reporting: Week 42
3c ILLUSTRATIVE EXAMPLE
Dec
Nov
Oct
2007
2006
Jan
End products
▪ Release 1.0 with
features A, B, and
C (deployment)
▪ Release 1.1
– Testing finished
– Finishing require-
ments-doc
– Deployment
▪ Support team for new
IT landscape
– Planning phase
finished
– Hardware setup
– Skilled employees
recruited
Activity
Plan
Forecast
Forecast changed

|
Risk monitoring tools: risks and proposed measures
3.2
Responsible
Overall project
leader
Subproject
leaders
Sales and
distribution
Technical
workstream
Project office
Description
▪ Product roadmap
interferes with new
governmental
regulation plans
▪ Insufficient project
management and
progress control
▪ Legal danger to
product sales by
loopholes in
distributor contract for
Points of Sale
▪ Cities obstruct cable
construction works by
delaying permissions
▪ Integration of
employees
▪ Competitors are
pushing quickly
to market
Proposed measures
▪ Set up meetings with regulatory
board
▪ Review project plans/milestones
▪ Revise contracts and set up a
task force for negotiations with
distribution channels
▪ Initiate talks with political
leaders
▪ Check project plans for speed-
up potential
▪ Launch marketing campaigns
Date
10/30/06
10/31/06
11/15/06
12/15/06
ongoing
Issue
Regu-
latory
Environ-
ment
Project
manage-
ment
PoS
contracts
Construc-
tion Per-
missions
First
mover
advan-
tage
A
B
C
D
E
FROM OTHER INDUSTRY

|
Risk monitoring tools: risk matrix
3.2
Low: Keep in mind
Medium: Action required
High: Urgent measures
required
Risk Factor
(Importance = Impact x Probability)
High(4)
Low
(1)
Low(1) High(4)
Importance
Urgency
A
B
C
D
E
A Regulatory
Environment
B Project
management
C PoS contracts
D Construction
Permissions
E First mover
advantage
FROM OTHER INDUSTRY

|
Budget management tool ILLUSTRATIVE EXAMPLE
Cumulative
cost
Project week
number
Today
Actual cost
Planned cost
Work-
streams
15
20
18
20
13
14
35
A
33
B
32
C
Budget over time Budget expenditure as of xx/xx/06
▪ Actual cost exceed planned cost by EUR10mn
▪ Actual cost will stay in budget, because trans-
gression of planned cost was caused by earlier
start of testing
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
3.3

|
Sample project planning checklist
▪ Nominate project sponsor
Parties involvement
▪ Decide on Steering
Committee composition
▪ Appoint Project Manager
▪ Complete the Staffing of
the Project Team
▪ Involved outsourcers
(contractors)
▪ Describe principal risks
Risk factors analysis
▪ Approve project budget
Budget
▪ Define the management
instruments
Methodology
▪ Overall project
duration ?? phases,
deadlines

Time plan
▪ Clear, reviewable
milestones

▪ Measurable task
deliverables with
deadlines and
responsibilities

▪ Overall project
duration ?? phases,
deadlines

Time plan
▪ Clear, reviewable
milestones

▪ Measurable task
deliverables with
deadlines and
responsibilities

▪ Define total duration,
phases, deadlines
Schedule
▪ Mark clear and consistent
milestones
▪ Approve end products with
responsible people and
deadlines
▪ Set authority limits on
altering the deadlines
▪ Define the procedure of
internal information
exchange
Communication
▪ Make a schedule of
expenses and payments
▪ Set authority limits on
altering the budget
▪ Develop ways to mitigate
risks and contingency plans
▪ Define the weight and the
probability of the risks
▪ Identify the critical path
▪ Define the procedure of
external information
exchange
▪ Approve the frequency of
the events (meetings of
the Project Manager, the
Steering Committee)
▪ Approve the instruments
– With the Steering
Committee
– With the Project team
▪ Approve the mechanisms
of making adjustments to
the project approach

|
Contents
▪ Introduction
▪ Appendix

|
We believe McKinsey brings distinctive capabilities to support you in this
effort (1/2)
• Established track record of successful collaboration with multiple companies
participating in the class-wide opioid manufacturer consortium
• Appreciation for your organizations, cultures values, and how to help shape
decision-making
• Experience serving multiple pharmaceutical companies (large and small) on
REMS design and implementation, capability building, external influencing
through consortia and strengthening relationships with stakeholder groups
• Convened and facilitated discussions among diverse groups of stakeholders
(including but not limited to creating consortia) to drive productive
discussions, generate alignment, create consensus perspectives. Examples
have included:
▪ Facilitated a discussion between FDA experts, pharma industry leaders
and McKinsey experts on Critical Path Initiative to share perspectives on
the progress, observations, issues and opportunities for to drive impact
▪ Facilitated the creation of a consortium of stakeholders and supported
discussions of multiple stakeholders as part of a joint effort to ensure a
proposed class REMS meets its stated objectives
Strong past
collaborations with
participating companies
Recent and relevant
experience with REMS,
stakeholder engagement
Experience facilitating
similar forums with FDA
and other stakeholders

|
We believe McKinsey brings distinctive capabilities to support you in this
effort (2/2)
• Developed distinctive expertise in Regulatory issues through supporting major
pharmacos in redesigning their Regulatory functions.
• Supported regulatory bodies directly, and as such have developed insights
into the perspectives of the regulators themselves
• Due to the large number of studies we do within pharmaceuticals, we have
developed a group of ex-regulators to counsel us during projects.
• We would leverage this group of advisors as we support you
• Multiple engagements over 10+ years in pain management
• Deep understanding of evolving changes that opioids face, including
▪ Evolving diversion and abuse problem and surveillance approaches
▪ Challenges of developing and testing “tamper resistant” formulations
• Project managed post-merger integration over a period of years for some of
the largest corporate mergers in history, inside and outside of
pharmaceuticals
• Developed a proprietary set of tools for managing highly complex processes
and webs of stakeholder groups
Proprietary Regulatory
and Pain advisory
boards
Extensive experience
managing long, highly
complex projects
Extensive experience
serving Regulatory in
industry and government
Deep expertise in pain
management, including
opioid space

|
McKinsey has experience with all aspects of REMS and in
assessing impact for drug sponsors
Regulatory submission Implementation plan
Impact on patient access Impact on business
ILLUSTRATIVE
74
REMS DOCUMENT SUBMISSION PLAN
25
Source: McKinsey analysis
ASSESSMENT OF TECHNICAL IMPLEMENTATION OF REMS REGISTRY
Coverage
Potential
capabilities Cost Time Additional Issues
System
Integrated into
fulfillment process
External options
Ease of
use
Claims processing –
Data-switch vendors
~XX% High • Registration
• Verification
$x-y /
transaction
x - y mo’s • Need to ensure coverage
of non-retail Rx
Claims processing –
PBM’s / payors
~XX%+ High • Registration
• Verification
n/a n/a • Highly fragmented market
Pharmacy management
software
~XX%+ High • Registration
• Verification
n/a n/a • Highly fragmented market
Call center - live XX% Med • Registration
• Verification
$x-y /
transaction
x - y mo’s • Potentially expensive to
scale up
Call center - IVR XX% Low • Registration
• Verification
<$x-y /
transaction
(assuming 20%
calls IVR; 80%
live calls)
x - y mo’s • Difficult to enter data; likely
needs to be used in
combo w/ live call center
Internet XX%+ Med • Registration
• Verification
<$x /
transaction
x - y mo’s • Some pharmacy chains do
not allow internet access
(intranet only)
Magnetic-card XX%+ Low • Verification n/a x - y mo’s • Requires some other
option for Registration
66
POTENTIAL AT RISK AREAS FOLLOWING REMS IMPLEMENTATION
Zip codes that may lose access to a prescriber*
Source: IMS 2008; US Census 2000; McKinsey analysis 6
OUTLINE OF VOLUME IMPACT APPROACH
%
Source: Survey data
Physician
compliance
Patient stays with
current doc: y%
Patient switches
doc: y%
.xx * (-y%)
= -yy%
% decrease in
scripts
.xx * (-yy%)
= -yy%
% of total
scripts
x%
y%
.xx * .yy
= .zz
.xx * .yy
= .zz
.xx * .yy
= .zz
% probabilities
weighted by
scripts
(xx)%
Patient response
Cumulative chg:
Comply
Doesn’t
comply
Patients do not
comply: x%
Patients comply:
x%
Patient
compliance
.xx * (-y%)
= -yy%
.xx * .yy
= .zz
.xx * (-y%)
= -yy%
Results from
patient survey
Differs by drug vs. Class-wide REMS
Differs by New vs. Continuing patients
SAMPLE CALCULATION
REMS design
Stakeholder reaction
9
PHARMACISTS COMPLIANCE WITH REMS; UNWILLING PHARMACISTS
SEE PATIENT ENROLLMENT AND VERIFICATION AS KEY OBSTACLES
Source: Survey
Percent of pharmacist survey respondents
50%
Willing
50%
Unwilling
Pharmacist willingness to comply with
ALL requirements of REMS (n = XX) 20%
Verification
20%
Enrollment
20%
Confirmation of additional
REMS requirements
20%
Training
20%
Registration of pharmacy
Obstacles against compliance cited by unwilling pharmacists
Percent of unwilling pharmacists (n = YY)
SANITIZED
44
SCHEMATIC OVERVIEW
NDC# Keyed
Gather Prescriber
Info
Script Filled or Denied
With hard-checks
Registry
Prescriber interaction with patient
Fax + Web
Phone
RX Taken to Dispenser
Gather Patient
Info

|
We have conducted over 200 engagements for healthcare clients in
the last three years on Regulatory Affairs & Risk Management
Engagements 2006-08
100% = 200+
Note: search based on ‘regulatory and medical affairs’, ‘risk management’ and ‘regulatory strategy’ for clients in Pharmaceutical and Medical Products &
Healthcare Payors & Providers
82
77
52
2008
2007
2006

|
Recent client work in Regulatory Affairs & Risk Management
Client Description
Global
Pharmaco
Global
pharmaco
European
Phamaco
Govt.
regulatory
organization
Global
Pharmaco
U.S.
Phamaco
▪ Developed high-performing Regulatory
Affairs culture including diagnostic of
current group, assessment of key
external trends, and recommendations
for required organizational changes
▪ Benchmarked Regulatory organizations
and optimized client’s model
▪ Assessed effectiveness of Legal
compliance organization and made
recommendations on how to embed
ethics-driven culture within the company
▪ Examined business process around
product safety
▪ Developed winning strategies for the
client to compete in the face of a
potential change in the U.S. legislative
landscape
▪ Conducted strategic sourcing of services
assessment for regulatory function of
U.S. activities
U.S. Pharmaco
Global
Pharmaco
U.S. Pharmaco
U.S. Pharmaco
U.S. Pharmaco
European
Pharmaco
▪ Developed REMS including design,
implementation planning, and impact
assessment
▪ Developed internal client processes to
institutionalize REMS capabilities and
planning across portfolio of products
▪ Development of risk assessment tool
including diagnostic of current approach
to risk assessment, development of new
tool, piloting tool across multiple projects
▪ Support of creation of risk management
plan (RiskMAP) for launched drug,
including diagnostic of current risk
management plans, development of risk
management framework to identify and
resolve additional risks
▪ Assisted R&D organization on clinical
trials management and risk
management framework
▪ Assessment of evolving FDA risk
management approaches and
implications for Pharmaco’s
Client Description
DETAILED EXAMPLES
IN APPENDIX

|
Detailed experience, e.g.
Maria Gordian, M.D., M.B.A. is the leader of our Regulatory Service Area
Education
• M.B.A., Wharton, University of Pennsylvania
• M.D., Tufts School of Medicine
• A.B., Harvard University
• Robert Wood Johnson Scholar
• Created REMS strategy for several large pharmaceutical meetings
• Facilitated working sessions with FDA and manufacturers on ways to enhance clinical trial
productivity
• Identified market access and commercial risks for pipeline assets of top 10 pharmaco and
designed clinical trials to address them
• Participated in FDA advisory panel to design agency position on clinical productivity enhancement
• Published multiple articles on R&D productivity and Regulatory issues
Previous Employment
• Attending, Hospital of University of PA and VA Hospital, Philadelphia, PA.
• Fellowship, Hospital of Univ of Pennsylvania
• Resident, Massachusetts General Hospital, Beth Israel Deaconess
Hospital
• Scholar, Leonard David Institute of Health Economics, University of
Pennsylvania
Dr. Maria Gordian is a Board Certified Radiologist, who is a senior partner at
McKinsey & Co. Dr.Gordian leads the Global R&D Service Area. She has extensive
experience serving clients on Regulatory issues including REMs.

|
McKinsey’s Regulatory Advisory Board is composed of leading experts in
Regulatory Affairs (1/2)
Joy Cavagnaro
▪ FDA – 10+ years
– CBER, Senior Biomedical Research Service, Biotherapeutics safety
▪ Human Genome Sciences – Former VP Regulatory Affairs
Bruce Burlington
▪ Wyeth – Former Head of Regulatory Affairs
▪ FDA – 20 years
– Former acting Deputy Director Med Affairs
– Head of Investigational New Drugs Division (Center of Biologics)
– Head of Center for Medical Devices and Radiological health
Leslie Hendeles
▪ University of Florida – Professor of Pharmacy and Pediatrics
▪ FDA
– Member, Pulmonary/Allergy Drugs Advisory Committee, 1986-1991
– Consultant, Pulmonary Division, 1991- present
Richard Lewis
– Deputy Director of the Office of Blood Research and Review (OBRR), CBER
– Chief of the Hematologic Products Branch in the Division of Blood Applications
OBRR

|
McKinsey’s Regulatory Advisory Board composed of leading experts in
Regulatory Affairs (1/2)
Ken Seamon
▪ Senior Associate, University of Cambridge
▪ Amgen – Former Vice President, Regulatory Affairs based in
London
– Director of the Office of Therapeutics Research and Review
– Associate Director for Research at the Center for Biologics
Research and Review
Anita O’Connor
– CDER
– CBER
▪ Particular expertise in pharmacology / toxicology

|
McKinsey’s Pain Management Advisory Board is similarly
composed of leading global opinion leaders (1/2)
Perry Fine
▪ Professor of Anesthesiology at the University of Utah
▪ Associate Medical Director of the Pain Management Center
▪ Chair of the ethics committee for the National Hospice and Palliative Care
Organization
Michael Doherty
▪ Clinical Professor at University of Nottingham, UK
▪ Co-author of "Osteoarthritis“, commonly used textbook and standard for OA care
Kenneth Brandt
▪ Professor of Medicine, Indiana University School of Medicine
▪ Head, Rheumatology Division Director, Multipurpose Arthritis Disease Center
Roy Altman
▪ Clinical Professor of Medicine at UCLA
▪ Participant in the NIH osteoarthritis initiative
▪ Board of directors at the Paget Foundation
Zahid Bajwa
▪ Professor, Department of Anesthesia, Harvard Medical School
▪ Director, Comprehensive Cancer Pain Service, Beth Israel Deaconess Medical Center

|
McKinsey’s Pain Management Advisory Board is similarly
composed of leading global opinion leaders (2/2)
Kenneth Kalunian
▪ Professor in the Division of Rheumatology, Allergy and Immunology at the UCSD
School of Medicine
▪ Associate Director of the Center for Innovative Therapy
Eugene Viscusi
▪ Director of Acute Pain Management at Thomas Jefferson University Hospital
▪ On the editorial board of Seminars in Pain Medicine and The Clinical Journal of Pain
Carol Warfield
▪ Edward Lowenstein Professor in Anesthesia, Harvard Medical School
▪ Director, Pain Management Center, Beth Israel Hospital, Boston, MA
Paul White
▪ Professor and Holder of the Margaret Milam McDermott Distinguished Chair in
Anesthesiology, University of Texas Southwestern Medical Center

|
McKinsey has many internal experts in Regulatory Affairs
and Risk Management…
Matthias Evers
▪ Principal in Hamburg
▪ Ph.D. in Biochemistry/Molecular Biology
▪ Regulatory Affairs
Tony Tramontin
▪ Associate Principal in New York
▪ Ph.D. in Neuroscience
▪ Regulatory Affairs and Risk Management
Kenneth Yoon
▪ Engagement Manager in Boston
▪ Risk Management - REMS
Laura Nelson Carney
▪ Engagement Manager in New Jersey
Maria Gordian
▪ Principal in New York
▪ M.D. Radiology, M.B.A.
▪ Regulatory Affairs and Risk Management
Vani Manja
▪ M.B.A.
Rachel Zhang
▪ M.B.A.
▪ Regulatory Affairs, Pharmacovigilance & Safety
Jeffrey Algazy
▪ Principal in New Jersey
▪ M.D., M.P.H.
Ron Piervincenzi
▪ Ph.D. in Biomedical Engineering
▪ Medical Affairs, Pharmacovigilance & Safety
Michele Holcomb
▪ Ph.D. in Chemistry
Petra Jantzer
▪ Principal in Zurich
▪ Ph.D. in Immunology
Lynn Dorsey Bleil
▪ Director in Los Angeles
▪ M.B.A.
▪ Regulatory Affairs - Compliance
Arif Nathoo
▪ M.D., M.P.A.
▪ Regulatory Affairs, Pharmacovigilance & Safety
Brian Salsberg
▪ Principal in Tokyo
▪ J.D.
▪ Regulatory Affairs - Compliance
EXAMPLE PROFILES
IN APPENDIX

|
… as well as Central Nervous System
diseases including pain
Ajay Bakshi
▪ M.D., Neurosurgery
Laura Blumenfeld
▪ Principal in New York
▪ Ph.D. in Biological Psychology
▪ Expertise in neuroscience/schizophrenia
Derek DuBois
▪ M.D.
▪ Expertise in anti psychotics, sleep aids, AD
Matthias Evers
▪ Principal in Hamburg
▪ Ph.D. in Biochemistry/Molecular Biology
▪ CNS signal transduction, neurodegeneration
Stephen Cho
▪ Associate in Detroit
▪ PhD in Organic Chemistry , ex-Pfizer
▪ Industry experience in CNS Med Chem
NOT EXHAUSTIVE
Gregg Caporaso
▪ Associate in New Jersey office
▪ M.D., PhD in neuroscience
▪ Attending Neurologist and Ass’ prof of Neurol
Eric David
▪ Engagement Manager in New York
▪ M.D.
▪ Clinical research on pain management
Jonathan Doogan
▪ Associate Prnicipal in London
▪ Product manager at Pfizer
▪ Launched multiple psychiatry drugs
Hiro Okayasu
▪ Associate in New Jersey
▪ M.D.
▪ Expertise in CNS landscape in Japan
Francis Lee
▪ M.D. , registrar in Psychiatry
▪ Expertise in pain
Laura Nelson Carney
▪ Ph.D. in Neuroscience, ex R&D at Merck
▪ Novel targets, psychiatry, neurology, cognition
Alexander Grunewald
▪ Engagement Manager in Los Angeles
▪ Systems and computational neuroscience
Kenneth Yoon
▪ Engagement Manager in Boston
▪ Postdoctoral work at Novartis in AD
Safa Sadeghpour
▪ M.D., Ph.D. in neuroscience

|
Contents
▪ Introduction
▪ Appendix

|
Working Arrangements
• Overall leadership by Maria Gordian (Principal, New York office)
• Consultation with other McKinsey regulatory expertise as needed
Leadership
Duration
Working team
Fees
• One full-time consultant
• Up to 18 months
• Professional fees and expenses of $65,000 per month for
facilitation/project management support.
• If the scope of work is expanded to include content support to
deliver the draft Class REMs, and McKinsey supports that work, we
will cover the fees for the full time consultant for facilitation/project
management support.
We believe McKinsey would be a strong partner to support you on “facilitation/
project management” as well as “content” to deliver and syndicate the draft Class
REMs. These working arrangements cover facilitation/project management only. We
welcome the opportunity to propose on the potential broader scope of work.

|
Contents
▪ Introduction
▪ Appendix
– Example consultant profiles with regulatory expertise
– Example McKinsey engagements in regulatory affairs

|
Detailed experience
Pasha Sarraf, M.D., Ph.D.
Education
Dr. Pasha Sarraf is a physician and researcher with expertise in preclinical
development. He has over 30 articles in peer reviewed journals including Cell,
Science, and Nature, and 15 years of problem solving experience in the biological
and medical sciences. He blends his deep expertise in the biological sciences with
experience in general and specialized medicine to bring novel insights to client
issues.
• Board Certified in Rheumatology
• Board Certified in Internal Medicine
• M.D. Harvard Medical School
• Ph.D. Cell and Molecular Biology, Spiegelman Laboratory,
Harvard University
• B.S.E Biomedical Engineering, Duke Univ.
• Developed novel approach for identification of novel binding partners of mutant proteins
• Participated in several national clinical trials at the National Institutes of Health (NIH)
• Submitted NDA for a pharmaceutical company
• Designed and managed execution of preclinical experiments with over 40,000 analytical
values for a major pharmaceutical company.
• Developed REMS for a drug prescribed to over a million patients
• Wrote a strategic FDA briefing document
• Strategically aligned and prepared clients for two critical FDA meetings
Previous Employment
• Physician, Mass. General Hospital (2 years)
• Clinical Fellow in Rheumatology, Massachusetts
General Hospital (2 years)
• Clinical Fellow in Vasculitis, NIH (1 year)
• Clinical and Research Fellow in Genetic Fevers,
NIH (2 years)

|
Detailed experience
Laura Nelson Carney, Ph.D.
Education
Dr. Laura Nelson Carney is an engagement manager in McKinsey’s New Jersey office.
She is an ex- pharmaceutical industry and academic research scientist. Her expertise is in
central nervous system diseases, both psychiatric and neurological in nature. Since joining
McKinsey she has served multiple biotech and pharma companies in R&D, including
providing support in designing in vitro experiments, clinical trials and writing NDAs.
• Ph.D. Neuroscience from Imperial College
• B.A. Human Biology from Stanford University
• Pre-McKinsey worked in Research at Merck on novel drug targets for anesthesia, schizophrenia, depression, anxiety, AD,
epilepsy (target ID to lead optimization); supported IND preparation
• 10+ peer-review papers in top science journals (Nature Neurosci, J. Neurosci, Pain, Anesthesiol.)
• At McKinsey designed large in vitro and in vivo battery of experiments to help a pharmaco respond to FDA not approvable
letter; worked with Dev’t team scientists to analyze and interpret resulting data
• Set up and facilitated expert advisory boards
• Wrote technical documents for inclusion in an NDA, coordinated submission of an NDA
• Helped multiple development teams prepare for FDA meetings, wrote multiple communications to FDA (letters, briefing
document)
• R&D transformation for a mid-sized pharmaco (organization, process performance management)
• Integrated Early Development into Research and redesigned project teams for a top-five pharmaco
Previous Employment
• Senior Research Scientist (CNS Discovery, Merck)
• Postdocotoral Fellow (Imperial College)
• Research Assistant (CNS Research, Roche)

|
Detailed experience
Felix Olale, M.D., Ph.D.
Education
Dr. Felix Olale is a physician and researcher with expertise in clinical development
and operational management of clinical studies. He blends clinical and scientific
research experience to provide deep insights into drug development and regulatory
approval
• M.D., New York University, School of Medicine
• Ph.D., Cell Biology, Developmental Genetics, New
York University
• B.A. Biology (Hons. Molecular), University of
Pennsylvania
• Conducted basic and pre-clinical research in genetics and organogenesis
• Conducted biostatical analysis on clinical trial data
• Designed clinical studies, including meta-analysis of clinical data
• Experience writing NDAs for pharmaceutical companies
• Evaluated efficacy profiles of drugs against FDA guidance in preparation for submission
• Led interactions with the CROs
• Published 6 peer reviewed articles
Previous Employment
• Skirball Institute of Biomolecular Medicine,
Biomedical Researcher (5 years)
• NYU Office of Industrial Liaison and
Technology Transfer, Venture Fund Analyst

|
Detailed experience
Tony Tramontin, Ph.D.
Dr. Tony Tramontin is an doctor of biology with expertise that spans non-clinical
research, clinical development, clinical operations and regulation. His broad
experience makes him uniquely positioned to provide deep insights across the
complete development process.
Previous Employment
▪ Experimental neuroscientist conducting neural
stem cell research at The Rockefeller
University and in The University of California
San Francisco Department of Neurosurgery
• Conducted research spanning in vitro molecular & cellular biology, in vivo animal model
research, and human subject research
• Redesigned entire late stage clinical trial organization for a global pharmaceutical
manufacturer
• Improved R&D pipeline productivity through attrition management and innovative approaches
to leveraging pipeline assets
• Created regulatory filing strategy and detailed risk management strategy (e.g., REMS)
• Designed CNS therapeutic area strategy
Education
▪ Ph.D., Biology, University of Washington
▪ B.A., Business, The University of Notre
Dame

|
Detailed experience
Jeremy Buzzard, Ph.D.
Education
• Ph.D., Molecular and Cellular Biology,
Monash University, Australia
• BSc. (SciScholProg), Monash University,
Australia
• Identified market access and commercial risks for pipeline assets of top 10 pharmaco and
designed clinical trials to address them
• Redesigned Japanese clinical development group for top 10 pharmaco to facilitate global trials
• Led team effort to generate ‘clinically compliant’ human embryonic stem cell lines would satisfy
the FDA for medical device application
• Participated in FDA advisory panel to design agency position on clinical use of human ES cells
• Published 8 peer-reviewed articles in top ranked journals
Previous Employment
▪ Post-doctoral Scientist, Harvard University
department of Molecular and Cellular Biology
▪ Research Scientist, ES Cell International,
Melbourne and Singapore
Dr. Jeremy Buzzard has extensive industry, academic and McKinsey engagement
experience in R&D. He is a firm expert in R&D, innovation-driven M&A and strategic
planning for the pharmaceutical and medical products practice.

|
Detailed experience
Kenneth Yoon, Ph.D.
Education
▪ Ph.D. Neuroscience, Yale University
– Studied nervous system development
▪ B.S. Chemistry, Stanford University
– Graduated with Honors and Phi Beta Kappa
– Honors thesis on genetic risk factors for Alzheimer’s
disease
Previous Employment
▪ Postdoctoral research, Novartis Institutes for
Biomedical Research, Functional Genomics
– Developed models of Alzheimer’s disease
▪ Bioinformatics Associate, Incyte Genomics
– Maintained cDNA libraries
Dr. Kenneth Yoon has expertise in developing risk management strategies for
pharmaceutical companies, and in assessing R&D performance. He has used his
experience to assist client companies in developing Risk Evaluation and Mitigation
Strategies and in developing R&D strategies.
▪ Experienced in leading teams that provided detailed regulatory support for client engagements
▪ Expertise in risk management strategies
– Designed and wrote Risk Evaluation Mitigation Strategy for client
– Conducted market research to assess impact of REMS on patient access and physician
prescribing preference
▪ Expertise in pharmacuetical R&D
– Conducted diagnostic on R&D performance
– Developed strategies to improve R&D productivity

|
Detailed experience
Mindy Fang, Ph.D.
Education
Dr. Mindy Fang is an expert in biostatistics with extensive experience working for
pharmaceutical companies. She has considerable experience in helping companies
develop and approve drugs globally.
• Ph.D., Biostatistics, Harvard University –
School of Public Health
• Designed and monitored over 15 global clinical trials
• Used the conventional frequency and the Bayesian adaptive approaches to clinical trial design
• Applied expertise in biostatistics to help companies improve the operations of clinical studies
• Analyzed statistical data on drug efficacy and safety
• Extensive experience working with CROs to review analyses and set performance goals
• Led the preparation for meetings with regulatory agencies to respond to clinical trial data queries
• Consulted on drug applications for the EMEA and PMDA from initial phases to final meetings
Previous Employment
• Senior Statistical Consultant, Novartis (1 year)
• Biometrical Consultant, Bayer-Schering (1 year)
• Lecturer, Kitaso University, Graduate School of
Pharmaceutical Sciences (1 year)

|
Detailed experience
Francis Lee, M.D.
Education
• M.B.A., Columbia University
• M.B.A., London Business School
• M.D., University of Birmingham
• B.Sc., Pharmacology, University of Birmingham
• Experienced writing clinical summaries for regulatory filings
• Worked with clients to file an asset for the FDA
• Hands-on experience refining clinical studies in response to weaker-than-expected earlier results
• Worked with clinical investigators to write protocols for Phase IV clinical trials
• Designed post-marketing drug (risk-mitigation) surveillance methodologies
• Experience developing plans for product launches
• Published 2 peer-reviewed articles
Previous Employment
▪ Senior Medical Advisor, Sanofi-Aventis
▪ Research Registrar, Institute of Psychiatry, London
▪ Physician NHS, Kings College Hospital (A&E);
South London & Maudsley NHS Trust (Psychiatry)
Dr. Francis Lee is an expert in clinical development and regulatory strategy with
extensive experience working for pharmaceutical companies. He has considerable
experience helping companies develop and approve drugs globally.

|
Detailed experience
Tamara Wexler, M.D., Ph.D.
Education
Dr. Tamara Wexler is a physician and researcher with expertise in clinical
development and operational management of clinical studies. She blends clinical and
scientific research experience, medical practice and clinical trial management to
provide deep insights into clinical drug development and regulatory approval.
• M.D. Medicine University of Pennsylvania - School
of Medicine
• Ph.D. Neuroscience University of Pennsylvania -
School of Medicine
• B.A. Chemistry, Public Policy, Princeton University
• Designed and led two clinical trials as a study investigator
• Managed patient recruitment for a national clinical trial
• Wrote a NDA for a pharmaceutical company
• Conducted biostatical analysis on clinical trial data
• Designed an epidemiological study, including meta-analysis of clinical data
• Evaluated safety profiles of drugs against FDA requirements in preparation for submission
• Led interactions with the Data Safety Monitoring Board
Previous Employment
• Attending Physician, Massachusetts General
Hospital (1 year)
• Clinical and Research Fellow in Endocrinology,
Massachusetts General Hospital (3 years)
• Researcher, National Institutes of Health (NIH)

|
Detailed experience
Joachim Bleys, M.D., Ph.D.
Education
• Ph.D., Epidemiology, Johns Hopkins University –
School of Medicine
• M.P.H., Epidemiology, Biostatistics, Johns Hopkins
University – School of Medicine
• M.D., Gent University, Belgium
• Expertise in observational chronic disease epidemiology (large cohort studies - survival
analysis, case-control studies, cross-sectional population studies)
• Performed analysis on clinical trial data (DASH-sodium trial)
• Created REMS strategy for multi-billion dollar drug
• Published four peer-reviewed articles on work in meta-analysis, specializing in meta-analysis of
randomized trials
• Published over 12 peer-reviewed articles
Previous Employment
▪ Graduate Research Assistant, Johns Hopkins
Dr. Joachim Bleys is a physician and scientist with expertise in observational
chronic disease epidemiology. He has extensive experience in biostatistics and has
worked with pharmaceutical companies on developing their regulatory strategies.

|
Contents
▪ Introduction
▪ Appendix
– Example consultant profiles with regulatory expertise
– Example McKinsey engagements in regulatory affairs

|
Example engagement 1:
Development of REMS proposal for US pharmaco
Situation
▪ Client with marketed compound received a letter
from FDA requiring the development of a Risk
Evaluation and Mitigation Strategy (REMS)
▪ Product represented significant fraction of client
revenue and disruption would be potentially
catastrophic
▪ REMS design required balance between
appropriate risk management elements while
preserving patient access
▪ Client lacked internal expertise to develop and
assess REMS
Impact
▪ Anticipated impact:
– Ensure that the benefits of the client’s
product outweighed the risks following
implementation of the REMS
– Deploy a REMS that would manage
risks, while preserving appropriate
patient access
– Minimize disruption to client’s business
– Assist client in developing strategies for
influencing regulatory environment
McKinsey role
▪ Coordinated internal client team composed of
requisite experts
▪ Gathered input from relevant external
stakeholders, including healthcare professionals,
risk management experts, regulatory experts
▪ Conducted quantitative market research survey to
assess business impact of various REMS
scenarios
▪ Designed and wrote REMS
▪ Will represent company at FDA interaction

|
Developed REMS strategy and capabilities for US pharmaco
Situation
▪ FDA has required REMS (Risk Evaluation
and Mitigation Strategies) for several in-
market products and NDA filings in the last
10 months
▪ Client has had to react to these FDA
requirements in short periods of time,
incurred significant costs, plan additional
clinical studies and change commercial
approach to products
▪ Several additional in-market and pipeline
products expected to require REMS in near
future
Impact
▪ Developed organization-wide capabilities to
holistically and proactively manage products in
the new REMS era and maximize their
commercial value
▪ Designed standardized processes and systems
to most efficiently handle REMS and its
implications
McKinsey role
▪ Determined the strategic questions where
REMS/ risk management thinking should
inform decision making
▪ Reviewed existing processes and governance
along the development/ commercialization
continuum to determine appropriate points to
incorporate REMs/ risk management thinking
▪ Engaged multiple internal stakeholders
(across functions) to get input, pressure-test
ideas and get buy-in

|
Developed risk assessment tool to support a risk management strategy
Situation
▪ A large multinational pharmaceutical company
had a non standardized approach to risk
management that was making it increasingly
complex to
– Perform fact-based risk assessment
– Institutionalize a rigorous risk management
approach
– Perform “apples to apples” portfolio
prioritization
▪ The culture within R&D did not embrace risk
management as a key element of each project
team member’s role
McKinsey role
▪ Develop an understanding of the current
approach to risk assessment (diagnostic)
▪ Develop a tool to standardize the approach taken
today (i.e., not imposing new, more stringent
approaches)
▪ The tool was to foster a shift in the culture
towards risk management
▪ Pilot the tool across multiple projects at various
development stages in the portfolio
Impact
▪ Extensive collaboration with representatives
from all functions in R&D led to the
development of a risk assessment tool that
detailed possible risks at all key stage-gates
in product development
▪ The tool was converted into a web-accessible
software package
▪ The approach brought together heads of all
therapeutic areas to agree on the relative
risks across disease areas, thus facilitating
all subsequent portfolio prioritization
discussions
Insights
▪ Any tools developed must be pragmatic and
developed in a process that involves not only
line function heads but project scientists
and clinicians
▪ Multiple pilots are needed to include projects
from different TAs and different risk levels
▪ Small numbers of dedicated resources
are likely required to ensure robust adoption
and implementation

|
Wrote ISS and ISE components of NDA filing for US pharmaco
Situation
▪ Client received Non-Approvable (NA) letter
for key portfolio product
▪ Required timely resubmission of new pivotal
data on drug efficacy and safety
▪ Client lacked internal capacity to respond to
NA letter and resubmit product filing
▪ If fling was not executed properly, the client
faced risk of second NA letter
Impact
▪ Accelerated submission timelines by 3 months
▪ Timely submission of product filing with
potential peak revenues of USD 700 Million
McKinsey role
▪ Designed and wrote Integrated Summary of
Efficacy and Safety including associated
documents
▪ Pressure-tested scientific arguments and
rationale for each document
▪ Provided strategic and regulatory support to
in responding to individual items on NA letter
▪ Coordinated internal client team composed of
medical research and biostatistics experts
▪ Coordinated delivery and management of
data from CROs
▪ Gathered input from relevant stakeholders
(e.g., KOLs, regulatory experts)

|
Improved operational effectiveness of regulatory agency
Situation
▪ Major national regulatory agency was interested in
optimizing operational efficiency and improving the
regulatory environment in its country
McKinsey role
▪ Evaluated how best to leverage IT systems
and improve processes
▪ Developed in-depth understanding of
major regional Regulatory Agencies (FDA,
EMEA, Japanese PMDA), including
– Key processes of drug approval
– Organizational structures
– Future directions in terms of operational
improvements and global
harmonization of regulatory
requirements (ICH)
▪ Evaluated trends in global Regulatory
landscape
Impact
▪ Optimized the communications flow and
workflow between the regulatory agency and
the applicants
▪ Established mechanisms to eliminate
submission bottlenecks
▪ Perception of more transparent and efficient
regulatory climate amongst all key stakeholders
▪ Addressed internal agency blockages (e.g.,
internal organizational politics)
Insights
▪ The application of a more systematic and lean
process can result in substantial impact in
agency functioning (and consequently for all
stakeholders)
▪ Alignment around a common IT platform
although challenging significantly improves both
operational efficiency and process
▪ To enable capturing most benefit from the
implementation of IT platforms, supporting
processes need to be re-aligned

|
Re-designed Global regulatory affairs to increase effectiveness, efficiency
Situation
▪ Large pharmaco looking to redesign its Regulatory Affairs
organization prompted by recent approval challenges
– Struggling to meet timelines due to pressing regulatory
issues (e.g. label changes, safety warnings, audits)
– Weak relationships with US and other regulatory bodies
– Roles and responsibilities and decision rights unclear
▪ Asked for support to complete the detailed design, develop
new SOPs and coordinate global roll-out
Impact
▪ Dramatic improvement in bench
strength of organization
▪ Greatly reduced conflict working
cross- functionally (within global
regulatory function and with rest of
R&D)
▪ Rapidly improving relationships
with FDA and evidence of growing
trust
▪ Three major submissions on time
Insights
▪ It is key to get interfaces right:
– Between Regulatory Liaison and non-regulatory
functions (e.g. Commercial)
– Within Regulatory groups (e.g., Operations, CMC,
Administration, Liaison)
McKinsey role
▪ Developed organizational models for RA based on
benchmarks, leadership aspirations, key talent issues and
regulatory challenges
– Division of activities (global vs. local)
– Balance of focus (TA vs. regional)
– Detailed role design
– Decision rights for key roles and processes
▪ Assessed interface options between Regulatory,
Development, Marketing, and Medical Affairs functions
▪ Counseled senior R&D Leadership as they raise
performance aspirations and attract new talent
▪ Developed detailed implementation and transition plan
▪ Managed change process

|
Development of new Regulatory Affairs unit for European pharmaco
Situation
▪ Mid-size European based pharmaco was looking
to internationalize its Regulatory Affairs function
by setting up a new RA-unit outside HQ
– to attract world-class talent in new focus TAs
– to get closer to FDA
– to build an internationalization model for
the company
McKinsey role
▪ Detailed design options for US Regulatory
Affairs unit, including
– Which project to allocate to new unit
– Scope of responsibilities
– Structure and reporting lines
– Interfaces with Headquarters
▪ Preferred option was further detailed, including
– Budget estimates
– Funding models
– Implementation plans
– Implications for current organization
▪ Facilitated the set-up of new US Regulatory
Affairs unit
Impact
▪ Detailed blueprint for new unit
▪ New product advocacy function
▪ New political liaison function
▪ Alignment within senior management
▪ Important lessons for other
internationalization efforts regarding
– Ex-HQ unit design principles
methodology
– Funding model
– Responsibility allocation methodology
between new unit and HQ
Insights
▪ Real differences in registration
requirements and procedures across TAs
– need to get close to the talent pool
▪ Need for really detailed planning around
transitioning responsibilities from one
geographical location to another – must
be aligned with talent plan

|
Example engagement 8: Re-designed Global Regulatory Affairs unit to
address compliance issues and maximize strategic impact
Situation
▪ Regulatory function at a mid-size US based
pharmaco, already facing issues with regulatory
compliance, anticipates significantly increased
regulatory workload in the near term
– Unable to meet compliance timelines for
health authority queries, labeling changes
– Inconsistent documentation across
geographies (e.g. CMC dossiers)
– Inefficient processes, duplicated work
– Anticipated sharp increase in trial volume
McKinsey role
▪ Managed a large client team from all regulatory
sub functions across broad geographies
▪ Developed detailed design options for regulatory
sub functions including
– Changes in reporting relationships
– New roles with commensurate skill levels to
accomplish operational tasks
– Redesign of interface with other functions
▪ Drove implementation planning following
approval of significant organizational changes
Impact
▪ Support from other functions for Regulatory as a strategic
partner
▪ Creation of streamlined processes consistent worldwide to
improve compliance and efficiency
▪ HQ and country regulatory affairs aligned as a single function
with common goals
Insights
▪ Local business decisions may impact world wide
compliance
– Organizational design ensures that global priorities
trump local business decisions
▪ Operational regulatory tasks can be accomplished by
entry level FTE’s
▪ Experienced hires can add more value by completing
strategic tasks such as early input in clinical trial
design to maximize speed of health authority approval
▪ Health authority demands in Asia and Latin America
are increasing requiring more regulatory input in these
regions

|
Achieving excellence in Regulatory Affairs function
Situation
▪ Top-5 pharmaceutical with the vision to
build a world-class Regulatory function,
best serving internal and
external customers
▪ Currently, organization showing
mediocre performance, while demands
for Regulatory were never higher (e.g.,
safety demands, FDA’s Critical Path,
new technologies such as Biomarkers,
adaptive trial design)
McKinsey role
▪ Run internal diagnostic of global
Regulatory organization
▪ Assess external trends and distill
implications for the future organization
▪ Crafting the future development
organization (structure, processes,
talent, deliverables, governance,
jobs, interfaces)
▪ Plan and kick-off implementation
Impact (expected, still ongoing)
▪ Regulatory acting and being perceived as
strategic function – i.e., being integral
part of project teams from early on to
translate target product profiles into label
draft elements to effectively guide clinical
development (“To support, not to audit”)
▪ Having established an organization that is
well equipped to shape agenda of Health
Authorities as well as adopt to trends in
the next 1-5 years
Insights
▪ External requirements for Regulatory have
never been higher, e.g., high demands/scrutiny
on safety
▪ Regulatory functions to build a flexible and
highly talented/learning organization to address
multiple trends perhaps changing the entire
development paradigm (e.g., provisional
approval, electronic filing)

|
Re-design of Regulatory Affairs for large pharmaco
Situation
▪ Leading global pharmaco met a series of
Regulatory failures including delayed
approvals, reduced labels, non-approval
▪ Root causes identified were:
– Limited depth in health authority
relationships
– Lack of cross-functional alignment with
regulatory, marketing, clinical
– No clear process for regulatory strategy-
setting
– Insufficient regulatory skills/talent
Impact
▪ Improved regulatory success rate in EUand US
(several approvals in following 36 months, with
favorable labels)
▪ Improved relationships with regulatory
authorities, particularly at top-level
▪ Improved credibility and motivation of function
▪ Regulatory affairs gained a “seat at the table” in
cross-functional interactions
▪ Increased resources available for critical
strategy setting activities
Insights
▪ Regulatory strategy setting is critical
– Input to ClinDev plan, marketing strategy
– Advocacy planning to deliver on clinical/
marketing strategies
▪ Alignment between geographies critical for:
– Alignment between national advocacy and
EMEA/CPMP advocacy
– Strategy trade-offs, e.g., clinical strategy
between EU, US and Japan
▪ Combination of people, tools, process and
structure are required to drive change –
structure in itself not sufficient
McKinsey role
▪ Redefined functional deliverables and core
processes, including strategy-setting, health
authority advocacy and dossier assembly
▪ Implemented new regulatory functional plan
▪ Detailed organizational design including
regulatory affairs in US and EU, as well as
interfaces to local regulatory liaisons across
geographies
▪ Talent review and recruitment strategy to
identify position holders for new roles
▪ 3-day global workshop

|
Example engagement 11: Evaluated design options for globalizing the
Regulatory Affairs liaison role and supporting organization
Situation
▪ Large pharmaco with a fairly globalized RA
functions evaluating need to further globalize
▪ Specifically, believed current regional liaison
model is functioning well and did not see the
need for change to a global liaison model
▪ Also looking for opportunities to reduce
headcount by 5-10%
Findings
▪ Most pharmacos have been converging
toward one similar model, over 12-18
months
▪ Efficiency has not been a driver for this
migration
▪ Expected benefits are similar (e.g., single
point of accountability)
▪ Challenges exist in finding the right talent
and balancing between ops & strategy
▪ Beyond globalization of the regulatory
model, there are several opportunities to
increase the effectiveness of RA (e.g.,
restructure the above country support,
prioritizing focus of liaison role)
McKinsey role
▪ For pharmacos in Top 20 understood the current
reporting structure, extent of globalization in roles,
scope of shared services and key challenges/benefits
in migrating to a global model
▪ Worked with Head of RA at major pharmacos to
understand key challenges in globalizing, identifying
steps to address key issues and corroborate findings
▪ Identified key implications for respective pharmacos
to address respective challenges (e.g., organizational
structure and process implications)

|
Redesigned Regulatory Affairs for a European pharmaco
Situation
▪ National regulatory agency for human
medicines underwent scandals that led to
investigations inside the structure
▪ Investigations revealed issues in terms of
agency organization (e.g., elevated span of
control, lack of process control) leading to the
change of agency’s leadership and the
request from the Government to review the
agency’s structure and processes
Impact
▪ Allowed new leadership to have a clear picture
of the agency’s situation, i.e. strengths and
weaknesses
▪ Provided the agency with a vision for the
evolution not only in the short term but also in
the medium-long term in a complex national
contest
▪ Anticipated impact:
– Improved agency’s performance through
the redesign of the organizational structure
and of the key processes
– Allowed the agency to have a smooth and
efficacious interaction with key external
stakeholders
McKinsey role
▪ Performed an organizational assessment of
strategy, structure, processes and systems,
skills, staffing, shared values, managerial
style
▪ Defined “quick wins” to address part of the
key challenges identified
▪ Designed the new organization for the agency
in the medium and long term

|
Re-designed an Asian regulatory agency
Situation
▪ National pharmaceutical regulatory agency
for a large Asian country
▪ Agency suffered from insufficient capacity,
lack of clear standards/ guidelines and poor
infrastructure (e.g., IT systems)
▪ Slow review and approval processes causing
patients to wait many years for most leading
drugs
▪ Lack of discussion opportunities between
regulators across regions made it difficult to
enhance multinational clinical development
Impact
▪ Enabled leadership to increase number of
reviewers to accelerate the review process
▪ Developed standardized review processes
▪ Developed review policy and guidelines
▪ Created more rigorous performance
management system
▪ Developed skill building program for reviewers
▪ Created comprehensive IT strategy and
enabled significant cost avoidance for system
upgrades
▪ Improved agency’s relationship with Ministry of
Health to facilitate a more collaborative
problem solving approach
▪ Changed the mindsets and behaviors of the
agency to improve collaboration and decision-
making processes
McKinsey role
▪ Conducted a diagnostic of the agency’s
current work processes and IT systems
▪ Provided counsel for project and agency
leaders while supporting the PMO for overall
transformation effort
▪ Coordinated planning and objective setting
▪ Provided significant “hands-on” support

|
Defined new organization and strategy for an Asian regulatory agency
Situation
▪ National pharmaceutical regulatory agency of
a country with technical expertise, significant
talent resources, a large and diverse patient
pool, and growing hospital infrastructure
▪ Agency has the aspiration of significantly
enhancing the capabilities of the country in
pharmaceutical innovation
Anticipated Impact
▪ GDP growth in the range of several USD
billion
▪ Low-cost healthcare for acute as well as
chronic and life threatening ailments
▪ Creation of several hundreds of thousands of
jobs
McKinsey role
▪ Worked with agency to articulate new visions
an imperatives
▪ Regularly met and interfaced with top 10
CEOs in the country to ensure alignment with
government and industry aspirations
▪ Syndicated vision and created alignment with
the most senior elected lawmakers in country
▪ Assessed global pharmaceutical R&D
opportunity
▪ Outlined future potential aspiration
▪ Described specific opportunity areas for
developing excellence

1
Developing an Extended-Release
Opioid Class-Wide REMS
May 6, 2009
Proposal to Industry Working Group
CONFIDENTIAL AND PROPRIETARY
Any use of this material without specific permission of McKinsey & Company is strictly prohibited

2
|
Contents
▪ Introduction
▪ Appendix

4
M
s more difficult, the FDA continues to grapple w
ed challenges
erature search
“We're still trying to learn what the process might be, what the
the expectations are, so that we can convey those to you in a
Quotes
To date*, the FDA has yet to issue official guidance on REMS
The vagueness of the language in FDAAA raises questions on
legal authority (e.g., Can the FDA mandate a class-wide REMS?
“There are some complex legal issues based on the way FDA
The severity of burden on various stakeholders is unclear
“We can’t keep trying to come up with an individual system ea
Eventually, the system [healthcare system] is going to collaps
weight of multiple programs”
The current healthcare infrastructure is inadequate to support
“What ideally we need to achieve…is a health care system tha
accommodate any of the REMS programs. We need a system
pharmacy doesn’t need to call the iPledge program or the new
to decide whether or not the doctor who wrote the prescription
registered”

6
|
Costs of different elements of REMS will vary significantly
with type of program and complexity of design
1 Vendor administrated survey: $1.9 per mailed survey and $0.75 per processed response
2 Self administrated survey: $0.98 per mailed survey and $4.30 labor cost per processed response
3 In office survey: $1.57 per survey for survey printout, office staff incentive, and data entry
4 International Medical News Group
SOURCE: BioMed Central; Psychiatric Services; JGIM; Mgmt & Tech. Consultants LLC.;
Cost of running a patient survey for 100 responses
In USD
Annual cost of patient registry system per provider
In USD
10251
Mailed
survey by
vendor @
20% resp.
rate
7081
Mailed
survey by
vendor @
30% resp.
rate
10442
Self-admin
mailed
survey @
30% resp.
rate
1573
Written
survey run by
office staff in
a clinic
650
WellCentive
registry
system
1000+4
Misc.
comprehensiv
e systems
EXAMPLES

7
|
Participating manufacturers must answer a number of critical questions in
order to successfully navigate class-wide REMS hurdles together…
Critical questions
Strategic
Operational
Organizational
▪ What is the optimal design for the REMS?
▪ Will pending approvals be delayed by ongoing REMS discussions? (e.g., Remoxy, Embeda)
▪ What are alternatives to REMS measures authorized by the FDAAA?
▪ What will the ultimate cost of the REMS proposal be (and how will it be split between
branded and generics manufacturers)?
▪ How can the effectiveness of REMS be measured?
▪ Who will be responsible for measuring impact?
▪ How can the REMS be implemented to achieve risk management goals, while minimizing
adverse impact on patient access, and on the business?
▪ How will you take into account input from other non-sponsor stakeholder groups (e.g.,
patient advocacy groups, pharmacists, wholesalers, etc)
▪ Who should be responsible for operating the REMS program? (e.g., sponsors vs. States vs.
the FDA)
▪ What technical/IT infrastructure is required to support a REMS that would cover 21 million
prescriptions per year?
▪ How can sponsors of 24 products, who are competitors, work together to most effectively
and quickly develop a common REMS proposal?
▪ Is there sufficient experience on the components of REMS within the “consortium”?
▪ Which functions should be included for input into REMS design and at what stages?
▪ How will decisions be made by the “consortium?
▪ How will disagreements be resolved?
▪ Will you introduce a Steering Committee?

8
M
lear path forward
Potential actions
Design strategy
– Assess potential alternatives for REMS design that would meet risk manag
– Benchmark proposed or solicited REMS against existing REMS for drugs w
Communication strategy
– Define a clear communication plan for influencing FDA on design and imp
– Define communication plan for reaching relevant stakeholders (prescribers
– Define communication plan for reaching other sponsors for “Class-wide” R
Determine generic versus branded sponsor role and responsibilities
– Assess potential for establishing IP around REMS processes (e.g., Celgen
REMS implementation:
– Assess impact of REMS design on patient access and burden on healthca
– Assess potential compliance / reception to various REMS requirements by
Clearly define process and dynamics for cross-sponsor w”consortium” working
– Align quickly on program requirements and implementation
– Assess and plan for potential positions / perspectives of other sponsors ba
(e.g., products / revenue impacted, relevance to business, etc.)
– Determine dispute resolution procedures between sponsors and with othe
– Assess potential cost-sharing arrangements for shared programs
Potential impact and re-design
– Incorporate specific assessments to determine impact of REMS on meetin
– Proactively communicate findings to FDA
REMS team design
– Create cross-functional REMS subteams, define objectives of each
– Include personnel from Regulatory, Risk Management, Legal, IT, Distributi
Internal “consortium” capabilities
– Assess Regulatory and Risk Management capabilities / experience
– Assess potential project management leads given need for cross functiona
nufacturers required to share single system for Elements to Assure Safe Use unless FDA determ
weighs benefit or 2) aspect of Elements to Assure Safe Use is protected and unable to be license
NO

9
|
Contents
▪ Introduction
▪ Appendix

10
|
As part of this effort, McKinsey would provide project
management support during an 18-month period
Phase I –
Develop initial
manufacturers proposal
Phase II –
Phase III –
Finalize recommendation
to be submitted to FDA
~3-4 months ~9-12 months ~1-2 months
Timing
• Coordinate efforts
among the 15
manufacturers
• Develop an initial
integrated proposal that
• Conduct preliminary
feasibility assessment
• Syndicate initial
proposal with key
(e.g., physician groups,
patient advocacy
groups, pharmacy
groups, distributors)
• Ensure alignment and
validate operational
feasibility
• Refine initial proposal
including input from
• Finalize proposal to be
submitted to FDA
Description
PRELIMINARY

12
|
…and coordinate the efforts of all three committees and execution sub-
teams
Steering
committee
Content
committee
Public Relations
committee
McKinsey
Project
Management
support
Sub-team 2

Developing an Extended-Release Opioid Class-Wide REMS

Developing an Extended-Release Opioid Class-Wide REMS

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