Standards-Setting in the
Context of Regulatory
Harmonization
Carolyn Compton, M.D., Ph.D.,
CEO and President
Critical Path Institute (C-Path)
IOM Workshop International Regulatory
Harmonization
Washington, DC
February 13, 2013
The Global Challenge
 It takes 12 - 15 years to develop a new drug
 Costs now exceed $1B USD*
 The process is broken
 Solutions require collaborative approaches that:
 Include both the public (regulatory) and the private
(industrial and academic) sectors
 Are applicable on a global level
* “The average drug developed by a major pharmaceutical company costs at least $4 billion, and
it can be as much as $11 billion.” The Truly Staggering Cost of Inventing New Drugs. Forbes
2/20/12
Drug Development Process
• Throughout the domestic and global drug development
enterprise, both between and within companies:
o
o
o
Data to demonstrate efficacy & safety are defined and
collected differently
Measurements of efficacy and safety are based on
differing criteria
Methodologies for design of clinical trials for new drugs
differ widely
Standards As Solutions
There is a fundamental need for global standards
across the developmental and approvals procedures
for regulated medical products.
Effective Standards Save Time, Money
and Headaches
A good standard = A global solution
A bad standard = A global problem
5
Standards Are at the Center of
Process Improvement
Effective standards require:
•
•
Widespread consensus
•
Widespread compliance
•
Widespread availability (free not proprietary)
•
Cost effective applicability
•
Endorsement/enforcement by authoritative sources
•
Global application
6
The Importance of International
Standards
•
Current technologies and modes of transportation erase
international boundaries, allowing companies of any size to
market products around the globe.
•
Differing regulations and standards from country to country
continue to cause delays and create barriers.
•
The costs and logistics associated with this are high.
•
A manufacturer may need to produce multiple versions of
the same product in order to distribute that product to
countries where standards and regulations differ.
•
For medicines, differing standards and regulations are both
medically and ethically unacceptable.
7
Moving Toward the Use of
International Standards
•
For international standardization to be successful,
Standards Development Organizations, regulatory bodies,
and industries around the world need to work together.
8
Moving Toward the Use of
International Standards
Other regulated industries such as information technology,
telecommunications, finance have lead the way
International Standards Development Organizations:
•
International Organization for Standardization (ISO)
•
American Society for Testing and Materials (ASTM)
•
National Fire Protection Association (NFPA)
•
Telecommunications Industry Association (TIA)
•
International Electrotechnical Commission (IEC)
•
International Telecommunications Union (ITU)
9
International Organization for
Standardization
What is a standard?
Provides requirements, specifications, guidelines or characteristics
that can be used consistently to ensure that materials, products,
processes and services are fit for their purpose.
What are the benefits of international standards?
•
They ensure that products and services are safe, reliable and
of good quality.
•
They are strategic tools that reduce costs by minimizing waste
and errors, and increasing productivity.
10
C-Path In A Nutshell
Critical Path Institute functions as
an orchestrator for development
of new tools, approaches, and
standards
created through collaboration,
reviewed and qualified by the FDA
(EMA, PMDA), and subsequently
made available to the community.
11
C-Path and Standards Development
International Scientific Standards for Drug Development: “Drug
Development Tools”
• Measurement standards
o
Molecular biomarkers for efficacy and patient classification
o
Molecular biomarkers for toxicity
o
Imaging biomarkers for efficacy and patient classification
o
Patient-, observer-, clinician- reported outcomes
• Methods standards
o
Disease models and clinical trial simulation tools
o
In vitro models
Regulatory Qualification
•
Recognition, approval for a given context of use
FDA and EMA Qualification: A Formal,
Rigorous Process of Review and Acceptance
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM230597.pdf
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004201.pdf
13
C-Path: A Public-Private Partnership

Act as a trusted, neutral third party

Convene scientific consortia of industry, academia, and
government for pre-competitive sharing of data/expertise
 The best science
 The broadest experience
 Active consensus building
 Shared risk and costs

Enable iterative FDA involvement in the development process
 Regulatory participation and guidance
 Official recognition through “qualification” of Drug
Development Tools
14
Consortia: Cooperation,
Collaboration, Consensus
7 global consortia collaborating with 1,000+ scientists and 41 companies
15
C-Path’s Global Landscape
Partners
16
Drug Development Tool Qualification and
Implementation
Anticipated effects:
•
Shorten the time, decrease the risks, and lower the costs
of developing safe, effective medical products
•
Create stronger scientific basis for decision-making
(within both industry and regulatory agencies)
•
Engender compliance through “ownership” and official
regulatory recognition rather than “enforcement”
•
Create public resources in a pre-competitive model for
community benefit
17
Facilitates Global Drug Developer Interaction
and Dialog with Global Regulators
Resource
Sharing
Efficiency
Collaboration
Close
FDA/EMA/
PMDA/SFDA
Interaction
Data Sharing
Open Dialogue
Diverse
Diverse
Expertise
Expertise
Qualification Processes for Regulatory
Agencies Not Fully Harmonized
Process Start
Scope
FDA
EMA
PMDA
2006
2007
2009
← Regulatory Review/Acceptance →
Fees
0
$100,000
Minimum # Steps
24
12
11
Months to Decision
24
6
6
3
6
1
Qualification Decisions
$30,000
Modified from Frederico Goodsaid 2012
What About Data Standards ?
A Data Standard ≠ A Common Data Element
Date of Birth= CDE
Gender = CDE
Jan. 15, 2011
January 15, 2011
1/15/11
1/15/2011
15/1/11
15 January 2011
15-1-11
2011-1-11
Male:Female
M:F
0:1
1:2
Mal:Fem
ML:FM
20
Data Standards and Regulatory
Process Efficiency
•
In 2012, CDER at FDA received about 1280 study datasets per
week, up to 10GB in size (if electronic)
•
Extreme variability and unpredictability of data format and
content present a major obstacle to timely, consistent, and
efficient review and the use of sophisticated analysis systems
FDA Communicates the Adverse
Impact of the Lack of Data Standards
Charles Cooper, Computational Science Center, CDER
Presented at CDISC European Interchange, April 18, 2012
22
Standards Change the Focus of Effort
in Regulatory Review
Demographics, Adverse events,
Disposition, Toxicity
Standards Shift Emphasis to Interpretation and Decision-making – “Thinking”
23
10
60%
5
For clinical trials, there
is value in using
standards from the
start
time in months
15
Data Standards As Drug
Development Tools
70-90%
0
Time savings: 8 months
Benchmark
http://www.cdisc.org/business-case
With CDISC
24
How Will Clinical
Content Data Standards Help?
•
Improve efficiency of drug review
•
Facilitate use of sophisticated analytic tools
•
Enable data sharing and data pooling
•
Enhance the ability to perform complex analyses
•
Build a foundation for broader benefits in clinical research,
premarket analysis and safety signal detection
•
Establish “common language” for disease and therapeutic
areas through information models, concepts and controlled
terminologies
•
- Dr. Janet Woodcock, Director CDER, FDA
25
C-Path and International Standards
Development
DATA STANDARDS FOR DRUG DEVELOPMENT
Therapeutic (Disease) Area Data Standards
o
Coalition For the Acceleration of Standards and Therapies (CFAST)
o
Partnership between C-Path and the Clinical Data Interchange
Standards Consortium (CDISC)
o
CDISC :
•
Standards development organization for data standards for
medical research
•
Global, open, multi-disciplinary, vendor-neutral, non-profit
(SDO), founded 1997, incorporated 2000
FDA Needs for Data Standards
• 58 disease areas in 5 years to achieve the 2017 goal
26
FDA Safety and Innovation Act (FDASIA):
Section XII – Improving the Efficiency of Human Drug Review
Through Electronic Submissions and Standardization of Drug
Application Data
Clinical Terminology Standards: Using a public process that
allows for stakeholder input, FDA shall develop standardized
clinical data terminology through open standards development
organizations with the goal of completing clinical data
terminology and detailed implementation guides by FY 2017.
FDASIA Section 1136: Allows FDA to require standardized fully
electronic submissions related to marketing applications by 2017
Moving Toward Global
Regulatory Harmonization
•
For international standardization to be successful,
Standards Development Organizations, regulatory bodies,
and industries around the world need to work together.
•
It is only with collaboration among all these entities that
international standardization will become a reality.
•
Regulatory bodies have the added challenge of working
within the laws of their countries, which may restrict their
ability to act in concert with one another
• Is FDASIA an example?
28
Moving Toward Global Regulatory
Harmonization Through Standards
EMA
Europe
FDA
USA
TPD
Canada
STANDARDS
TGA
Australia
Diverse
SFDA
Expertise
China
PMDA
Japan
Standards-Setting in the
Context of Regulatory
Harmonization
Carolyn Compton, M.D., Ph.D.,
CEO and President
Critical Path Institute (C-Path)
IOM Workshop International Regulatory
Harmonization
Washington, DC
February 13, 2013