Standards-Setting in the Context of Regulatory

HarmonizationCarolyn Compton, M.D., Ph.D.,

CEO and PresidentCritical Path Institute (C-Path)

IOM Workshop International Regulatory Harmonization

Washington, DCFebruary 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 Data to demonstrate efficacy & safety are defined and collected differently

o Measurements of efficacy and safety are based on differing criteria

o 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.

5

Effective Standards Save Time, Money and Headaches

A good standard = A global solution

A bad standard = A global problem

6

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

7

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.

8

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.

9

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)

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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.

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.

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C-Path and Standards Development

International Scientific Standards for Drug Development: “Drug Development Tools”

• Measurement standardso Molecular biomarkers for efficacy and patient classificationo Molecular biomarkers for toxicityo Imaging biomarkers for efficacy and patient classificationo Patient-, observer-, clinician- reported outcomes

• Methods standardso Disease models and clinical trial simulation toolso 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

13

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM230597.pdfhttp://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004201.pdf

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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

15

Consortia: Cooperation, Collaboration, Consensus7 global consortia collaborating with 1,000+ scientists and 41 companies

C-Path’s Global Landscape

16

Partners

17

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

Facilitates Global Drug Developer Interaction and Dialog with Global Regulators

Close FDA/EMA/

PMDA/SFDA Interaction

Collaboration

Open Dialogue

Diverse Expertise

Efficiency

ResourceSharing

Data SharingDiverse

Expertise

Qualification Processes for Regulatory Agencies Not Fully Harmonized

FDA EMA PMDA Process Start 2006 2007 2009 Scope ← Regulatory Review/Acceptance → Fees 0 $100,000 $30,000 Minimum # Steps 24 12 11

Months to Decision 24 6 6

Qualification Decisions 3 6 1Modified from Frederico Goodsaid 2012

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What About Data Standards ?

A Data Standard ≠ A Common Data Element

Date of Birth= 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

Gender = CDE

Male:Female

M:F

0:1

1:2

Mal:Fem

ML:FM

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

22Charles Cooper, Computational Science Center, CDERPresented at CDISC European Interchange, April 18, 2012

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Standards Change the Focus of Effort in Regulatory Review

Demographics, Adverse events, Disposition, Toxicity

Standards Shift Emphasis to Interpretation and Decision-making – “Thinking”

Data Standards As Drug Development Tools

For clinical trials, there is value in using

standards from the start 60%

70-90%

Benchmark With CDISC

time

in m

onth

s0

5

1

0

15

24http://www.cdisc.org/business-case

Time savings: 8 months

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, FDA25

C-Path and International Standards Development

DATA STANDARDS FOR DRUG DEVELOPMENTTherapeutic (Disease) Area Data Standardso 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

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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

FDA Safety and Innovation Act (FDASIA):

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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?

Moving Toward Global Regulatory Harmonization Through Standards

STANDARDS

EMAEurope

PMDAJapan

Diverse Expertise

TPDCanada

FDAUSA

TGAAustralia

SFDAChina

Standards-Setting in the Context of Regulatory

HarmonizationCarolyn Compton, M.D., Ph.D.,

CEO and PresidentCritical Path Institute (C-Path)

IOM Workshop International Regulatory Harmonization

Washington, DCFebruary 13, 2013