Regulatory Science In Therapeutics Development
Henrietta Ukwu, MD, FACP, FRAPS
Senior Vice President, Global Regulatory Affairs
Changing Landscape, Changing Needs
Regulatory Demands and Responsibilities
Regulatory
Science
Demands
1980s
1990s
Biotech / Pharma
Blockbuster Boom
1980 – 1990s
Orphan Drug
Act
1983
2000
2002
Mergers and
Acquisitions
1990s – 2000s
Outsourcing
(CRO, CMO)
2000s
2004
Drug Safety
Concerns
2004
(ex. Vioxx)
Emerging
Markets
2004 - 2005
2006
2008
PERFECT
STORM!
Decline in
Productivity;
Rise in Product
Failures;
Unsustainable
Paradigm
2010
Current
EMERGING REGULATORY
TRENDS:
ICH to Local Heterogenicity
Collaboration amongst Regulatory
Agencies
Adaptive Trial Designs
CV Outcomes Studies
REMS Development
Advanced Therapeutic Pipelines
Personalized Medicine
Orphan Drug Indications
Gundersen LE. Careers in regulatory affairs: from practitioner to professional. Nature biotechnology. (20) Apr 2002:409-410
Freedman TB. Career Opportunities in the Life Sciences. www.careersbiotech.com. 2007
Ukwu H, Malone H. Blueprint – Driving Regulatory Excellence. Regulatory Focus Mar 2009:40-45
Regulatory Science in the Drug Development Process
Chemistry
Synthesis
Chemical and analytical
characterization
Development
pharmaceutics
Research and development activity
Pharmaceutical
Pharmacology
Screening
Side
effects
Acute
toxicology
Toxicology
Analytical
specifications
Interaction with
other drugs/Genomics
Subacute
toxicology/
teratology
Chronic toxicology
mutagenicity
carcinogenicity
Absorption
distribution
metabolism
excretion// Biomarker
Pharmacokinetics
R
RxX
Phase I
studies
Clinical trials
Regulatory affairs
Scale up
manufacture
Advice on
regulatory
strategy
Phase II
studies
Preclinical / Biomarker strategy
Orphan drug, pediatric,
Regulatory agency/ IND/
Regulatory agency –
early pharmaceutical
novel technologies
strategy
Phase III
studies
TA expertise,
Innovative CT ;REMS
HE; Tools validation,
SPA; SA/B-R
On the average, ~8-12 years to develop a drug at a cost of ~£464 million or ~$900 million
" Knowing is not enough ; we must apply..." Goethe
Phase IV/V
studies
Product
approval / Safety
& PMS/ Life cycle
optimization
Emergence of Regulatory Science
•
Bridge the scientific, translational and clinical knowledge into
regulatory development planning
− Become the liaison between multidisciplinary groups
− Bring clinical reasoning and scientific methodology to a processdriven field
− Continually educate themselves on international regulations that
govern scientific discovery
•
Need for precision, prediction, and intelligence in adapting
the Regulatory Process to product development
− Introduce pragmatic methods to proactive approaches to
complex situations
− Incorporate analytical process to improve operational execution
•
Infuse business doctrine into strategy
− Business Development- licensing opportunities, outsourcing
strategies and CRO partnerships
“Regulatory science is the science of developing new tools,
standards and approaches to assess the safety, efficacy,
quality and performance of regulated products…” FDA
Strategic Elements of Regulatory Contribution
TPP / Product inception
Competitive,
Globally acceptable,
Value-adding, Sustainable
Product
Global CTA / IND filings
Clinical trial design & conduct
Fast track; Orphan drug;
Opportunities for
acceleration;
Manufacturing strategies
TPP-Driven Regulatory
Agency meetings /
Consultations & scientific
advice
Post Approval / Life cycle
optimization
Special Protocol
Assessment Pivotal studies/
Endpoint assessment; SRI
Stakeholder
Engagements
KOL; HTA / Experts
Data review; Competitive
Benchmarking; Product label;
REMS; Benefit /Risk
Assessment
Global Filing & Review
of Marketing
Ukwu, H. (2011). Chapter 2: Global regulatory affairs – role in bio-pharmaceutical industry.
Applications e-CTD
In Global Regulatory Systems: A strategic primer for biopharmaceutical product
development and registration. Center watch Publishing www.store.centerwatch.com
Opportunities for Regulatory Science
REGULATORY SCIENCE DEMANDS
... Differentiation is the name of the game!
Strategic Regulatory Expertise
Competitive Regulatory Intelligence
Therapeutic Expertise
Regional / Local Expertise
Operational Excellence
OPPORTUNITIES
Redefinition of Stakeholders;
Heightened Regulatory Approval Threshold;
Increased Patient Access;
Product Value Proposition / Differentiation;
Increased Competition;
Transformation Initiatives
Simultaneous Global Development /
Registration;
Cost Containment Measures; Rigorous
Regulatory Reviews
CHALLENGES
Redundancy vs. Complementarities to
Clinical/Medical/Scientific Affairs teams;
Clarity of Value-added roles;
Positioning and Development of Career
Advancement vs. Traditional Model
Ukwu H, Malone H. Blueprint – Driving Regulatory Excellence. Regulatory Focus Mar 2009:40-45
Position Profile of a Regulatory Scientist
Profile
•
Combination of strategic and operational
excellence
−
−
−
−
−
−
Program development planning
Strategic regulatory intelligence
Regulatory authority meetings
Clinical trial methodologies
Global awareness & understanding
Matrix-organization supervisory experience
ing
P
La rod
be uc
lin t
g
ertis
Ad v
and
otion
Su
bm
i ss
ion
s
Strategic
Excellence
Operational
Excellence:
Regulatory Compliance
Ukwu, H. (2011). Chapter 2: Global regulatory affairs – role in bio-pharmaceutical industry. In Global Regulatory Systems: A strategic
primer for biopharmaceutical product development and registration. Center watch Publishing www.store.centerwatch.com
Ukwu, H. Role of Regulatory Scientist in BioPharmaceutical Industry. RAPS Focus perspectives.. March 2003
Th Cl
in
Ex era ica
p
pe e l
rti uti
se c
Regulatory
Affairs
Scientist
d
an y
y or
l i c l a t n ce
Po g u i g e
e
R tell
In
Responsibilities
C MC
•
•
Local / Regional Expertise
l&
na
i o i cs
a t st
sl ati ise
an st rt
Tr Bio xpe
E
•
Usually terminal clinical and/or scientific degrees (MD,
PhD, PharmD, DDS) with post-doc/fellowship
experience
Active participation in professional organizations and
publications
Background in translational research/medicine
Therapeutic Area and technical/data review
Capabilities are strong assets
Prom
•
od
Pr
uc
t
v
De
elo
e
pm
nt
Industry Model: Regulatory Development
Regional Strategy &
Operational excellence:
Executing on Milestones
Regulatory submission
BOH correspondence
Physician / Scientific
Application of Therapeutic Area
expertise and
Strategic Regulatory Intelligence
Associate/Principle/Senior
Associate/Principle/Senior
Specialist / Analyst
Coordinator/Specialist
Associate/Senior
Associate/Senior
Manager / Scientist
Manager / Liaison
Associate/Senior/Executive
Director
Therapeutic Area
Head
Associate/Senior/Executive
Vice President
Associate/Senior/Executive
Director
Career Development of a *PPD Regulatory Scientist
Associate/Principle/Senior
Specialist / Analyst
Associate/Senior
Regulatory Scientist (Thought Providers)
Integrate Regulatory Intelligence
Support Consultants and Directors
Develop and plan strategy
Direct Liaisons for Operations and Teams
Problem solvers
PPD Global Regulatory
Intelligence
(GRI)
Manager / Scientist
Associate/Senior/Executive
Director / Consultant
Regulatory Consultant (TA experts/ Thought Leaders)
Apply Regulatory Science and Intelligence
Advise Client Development Strategy
Oversee Planning and Implementation
Direct Liaisons for Company and Regulatory Bodies
PPD Global Regulatory
Consulting
(GRC)
Associate/Senior/Executive
Vice President
*Ukwu, H. (2011). Leading a CRO paradigm shift at PPD from operational to strategic regulatory science application to enhance quality
of services to clients