Regulatory Intelligence: what is it? & How can it help your company's

Regulatory Intelligence:
what is it?
&
How can it help your company's
drug development?
15 April 2010
Sybille L. Sauter, Ph.D., R.A.C.
Senior Regulatory Scientist
Cato Research, Ltd.
[email protected]
Copyright © 2010. Cato Research
Agenda
•
What is regulatory intelligence, and why is it
important?
•
Where can you find information for regulatory
intelligence (RI)?
•
How to use, interpret and present RI information?
•
Final thoughts
•
Questions
Copyright © 2010. Cato Research
What Is Regulatory Intelligence?
Copyright © 2010. Cato Research
Definition of Regulatory Intelligence
“The act of gathering and analyzing publicly available
regulatory information.
This includes communicating the implications of that
information, and monitoring the current regulatory
environment for opportunities to shape future regulations,
guidance, policy, and legislation”
•
Definition as per the DIA’s Regulatory Intelligence Network
Group – a special interest area community
Copyright © 2010. Cato Research
The Regulatory Intelligence Process
Research Question
Search and collect
applicable documentation
Surveillance
Review new information
Summarize information
Analyze information
Interpret - new information
in light of current systems
Integrate - modify current
practices, regulatory strategy or
SOPs based on new information
Source: RA Focus, December 2007
Copyright © 2010. Cato Research
RI Includes Three Categories of
Intelligence
•
Regulatory landscape
– Research agency review recommendations and
opinions about previous approval/rejection of products
•
Existing and/or emerging competitor products
– Analyze competitor information to devise development
programs and assess the relative position of the
product to existing/emerging products
•
Submission routes
– Analyze legislation/guidance documents to identify
potential routes of submission, procedural steps of the
submission process, and agency requirements needed
for approval
Copyright © 2010. Cato Research
RI Allows a Regulatory Professional to..
•
Generate a development plan
•
Investigate precedence and update for current regulatory
landscape
•
Advise personnel of various disciplines
•
Generate a marketing application compliant with all Agency
requirements
•
Adjust marketing application to global needs
•
Create a regulatory strategy for a product
Copyright © 2010. Cato Research
Regulatory Intelligence Is…
•
Key duty of the RA department
•
Vital to maintain compliance
•
Critical to successful product development
•
Highly interactive with other disciplines
Interpretation of RI information shapes
company’s regulatory strategy
Copyright © 2010. Cato Research
Regulatory Strategy
•
Regulatory strategy incorporates the drug development
plan, an outstanding issue or question, background
information, regulations and/or guidance documents,
strategic advice and recommendations on implementation
•
Regulatory strategy could be seen as the adaptations a
company makes to move its product from the development
state to achieving marketing approval
Source: Meredith Brown-Tuttle, Bay Area Clinical Roundtable, 2006
Copyright © 2010. Cato Research
Why Is Regulatory Intelligence
Important?
Copyright © 2010. Cato Research
…Because RI Provides the
Regulatory Professional with
Information to:
•
Identify opportunities
– Broader indications
– Roadmap to product approval
•
Identify possible hurdles
– Compliance issues
– Change in requirements for specific indication
•
Predict Agency approval requirements
•
Predict Agency review times
•
Answer specific development questions raised by team
Copyright © 2010. Cato Research
Benefits of Regulatory Intelligence
•
Increase compliance
•
Decreased time to approval
•
Decreased costs of product development
•
Maximize target market(s)
Copyright © 2010. Cato Research
Successful RI Is a Powerful
Business Driver
•
RI identifies competitive advantages in a increasingly
complex regulatory landscape for global drug development
•
RI is now recognized as more than just a strategic driver
RI is a key business success differentiator!
Copyright © 2010. Cato Research
Remember…
•
Working in RI does not mean that you are acquainted with
everything
•
It’s more important to know where to look and how to use
the information that has been gathered
Copyright © 2010. Cato Research
Where to Mine for RI Information?
Copyright © 2010. Cato Research
RI Information for Drugs, Biologics or
Devices
•
Sources of information differ
•
Surveillance resources differ
•
Consultants/CROs used differ
•
Analysis of information is similar
Goal is the same:
Approval of marketing applications
Copyright © 2010. Cato Research
Sources of Regulatory Intelligence
•
Common
–
–
–
–
Regulations
Guidance documents
Panel meetings
Previous approvals
•
Less Common
– Warning letters
– Interactions with Agency
reviewers
– Interactions with other
regulatory professionals
– Agency presentations
– Competitor information
– FOI requests
Copyright © 2010. Cato Research
Additional Sources for RI
•
•
•
•
•
•
•
Discussion groups/blogs/twitter
Global regulatory agency websites
Harmonization and standardization efforts
Professional journals and newsletters*
Labels, SPCs (summary of product characteristics)
Specialized RI software*
Regulatory alerts/updates/newsletters/subscriptions and
services*
Educational resources
RI/Research providers and RI sites*
Business intelligence websites*
Pharmacopeias
Advisory Committee Update Information*
Industry and trade associations – Regulatory
•
•
•
•
•
•
*may require a fee
Copyright © 2010. Cato Research
FDA Has a Twitter Site
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Regulatory Affairs Discussion
Groups/Blogs
www.pharmalot.com
www.cafepharma.com
www.eyeonfda.com
www.biotechblog.com
www.organgebookblog.com
blogs.wsj.com/health
www.patentbaristas.com
www.fiercepharma.com
www.patentlyo.com/patent
www.invivoblogspot.com
carl1anderson.wordpress.com
www.fdalawblog.net
www.fiercebiotech.com
www.piperreport.com
druganddevicelaw.blogspot.com
www.ask-cato.com
pharmagossip.blogspot.com
Copyright © 2010. Cato Research
How to Access FDA Approval
Information?
•
[email protected] includes most of the drug products approved
since 1939
•
The majority of patient information, labels, approval letters,
reviews etc. available for drug products approved since
1998
•
Product approved between 1939 and 1998?
– Search for publicly available SBA (summary basis of
approval)
– If SBA not available, go to FOI website (some
documents can be purchased for a fee)
Copyright © 2010. Cato Research
Access to EU Approval Information?
•
EPAR: European Public Assessment Report
– EPAR reflects the scientific conclusion reached by the
Committee for Medicinal Products for Human Use
(CHMP) at the end of the centralized evaluation
process
– The summary, list of authorized presentations and the
product information (SPC, labelling and package
leaflet) are provided in all EU languages
– A-Z listing of EPARs
http://www.ema.europa.eu/htms/human/epar/a.htm
Copyright © 2010. Cato Research
Betaferon EPAR Site
Copyright © 2010. Cato Research
RI Databases for Drugs, Biologics,
and Devices
•
Several database providers
•
Provide worldwide regulatory information
•
Explanatory documents guide you through a country’s
drug/device registration process
•
Conduct focused research and surveillance, some
summarize and integrate
•
Can set up for daily or weekly e-mail updates
•
Key word or full text searches
•
$1-8+K annually per module or country per user
Copyright © 2010. Cato Research
RI and Competitive Intelligence
Providers (Fee Databases)
Companies
Websites
Tarius
www.tarius.com
IDRAC
www.idrac.com
PharmaPendium
www.pharmapendium.com
Compliance Control
www.compliance-control.com
Clinivation
www.clinivation.com
Adis R&D Insight
www.wolterskluwerhealth.com
BioPharm Insight
http://www.biopharminsight.com/biopharm_in
sight.html
MedTRACK
www.medtrack.com/research/default.asp
Pharmaprojects
www.pharmaprojects.com
Copyright © 2010. Cato Research
Globalization of RI
•
More and more companies are conducting trials and filing
marketing applications worldwide (Pfizer example)
– Norvasc launched in 1990: 9 years to market in 60 countries
– Viagra launched in 1998: 2 years to market in 60 countries
•
Staying abreast of worldwide regulatory information is
increasingly important as a change in the global landscape
can affect the global regulatory strategy
Copyright © 2010. Cato Research
Considerations of Global RI
•
Familiarity with international regulations (RAC)
•
International agency websites
– Language barrier
•
Paper vs electronic submissions
•
Consider cultural differences
•
Country-specific reimbursement systems
•
Cross-talk between international regulatory agencies (e.g.
between the ICH regions US, EU, Japan)
Copyright © 2010. Cato Research
Information Sharing Agreements
Between Regulatory Agencies
•
•
FDA and China: since 2007
FDA and European Medicines Agency: since 2003
– All legislation and guidance documents governing
medicinal products
– Post-authorization pharmacovigilance data and safety
concerns arising from periodic safety update reports
and post-authorization obligations and commitments
– Information on quality defect or product recalls
– Information in applications for scientific advice, orphan
medicine designation, marketing authorization or postauthorization activities
– GMP Inspection reports and product sample results
– GCP Inspection reports
Copyright © 2010. Cato Research
Consequences of Information
Sharing for Regulatory Strategy
•
Critical issues that surfaced during review of your
application with FDA may also be known to the European
Medicines Agency
•
If FDA identified a problem with request for orphan, it’s
possible that the reasons for request denied were shared
with European Medicines Agency
Copyright © 2010. Cato Research
Global Regulatory Agency Websites:
Language Barrier
Country/Region
Information
in English
Comment
European Union
(28 Member
States)
Some Member Information on products
States
approved via the centralized
procedure by the European
Medicines Agency is in English
Switzerland
Yes (partial)
Some documents available in
French and German only
Japan
Yes
-
China
No
-
India
Yes
-
South Africa
Yes
-
Brazil
No
-
Israel
Yes
-
Copyright © 2010. Cato Research
Global Regulatory Agency Links
Global Regulatory Websites
www.clinicalresearch.com/Professionals/Pages/GlobalR
egulatoryAgencies.aspx
www.rainfo.com
www.drw-research.com/resources.html
www.globepharm.org/links/resource.html
www.fda.gov/oia/agencies.htm
Copyright © 2010. Cato Research
Regulatory Information/Research
Providers and RI Sites
Provider
Contact Information
Biologics Consulting Group
www.bcg-usa.com/regulatory/reglib.php
Clinivation
www.clinivation.com/worldview/index.php
Datamonitor
www.datamonitor.com
DRW Research&Info Services
www.drw-research.com
European Regulatory Intelligence
www.eraconsulting.com/eri
Global Regulatory Affairs Consultants
www.globalregulatory.com
Graematter, Inc.
www.graematter.com
Noblitt & Rueland
www.fdaconsulting.com
Prous
http://integrity.prous.com
Reg123
www.reg123.com
RegIntel Ltd
www.regintel.com
RegSource
www.regsource.com
RAPS
www.raps.org
RA Info
www.rainfo.com
Regulatory Intelligence Centre
www.ric.d-target.com
VerveHealth, LLC
www.vervehealth.com/services.html
Source: RA Focus, December 2008, December 2009
Copyright © 2010. Cato Research
Business Intelligence Websites
www.biospace.com
www.hoovers.com
Social.eyeforpharma.com
www.biotech-intelligence.com
www.bna.com
www.cbinet.com
www.centerwatch.com
www.datamonitor.com
www.datamonitor.com
pharmalicensing.com
www.espicom.com
www.imshealth.com/portal/site/imshealth
www.pipelinereview.com
www.pharmalive.com
Source: RA Focus, December 2009
Copyright © 2010. Cato Research
Pharmacopeias and Advisory
Committee Update Information
Pharmacopeia
Website Address
US Pharmacopeia
www.usp.org
European Pharmacopeia
www.edqm.eu/site/page_628.php
Japanese Pharmacopeia
http://jpdb.nihs.go.jp/jp14e
Codex Alimentarius
www.codexalimentarius.net/web/index_en.jsp
Advisory Committee Update
Contact Information
AdComm Bulletin
www.idrac.com
Advisory Committee Updates
https://secure.iian.ibeam.com/events/fdcr003/
20100/index.jsp?autoLogin=
FDA Advisory Committee Website
www.fda.gov/ohrms/dockets/ac/acmenu.htm
FDA Live
www.fdalive.com
Source: RA Focus, December 2009
Copyright © 2010. Cato Research
New: Portal for Rare Diseases and
Orphan Drugs (www.orpha.net)
•
Searchable database of >5,600 rare diseases
•
Lists disease prevalence (# cases/100,000)
•
Provides descriptions (with literature references) of
– Cause of disease
– Clinical and biochemical features
– Diagnosis
– Clinical management
– Molecular and population genetics
– Animal models
– History
Excellent resource for the production
of orphan designation requests!
Copyright © 2010. Cato Research
Monitoring RI Information:
Surveillance
Copyright © 2010. Cato Research
Definition of Surveillance
•
“Worldwide monitoring of regulatory information looking
for changes in the regulatory landscape”
Source: Meredith Brown-Tuttle, Bay Area Clinical Roundtable, 2006
Copyright © 2010. Cato Research
How to Keep Up With the Constantly
Changing Regulatory Landscape?
•
Monitor Agency’s websites
•
Subscribe to relevant journals, newsletters
•
Get daily e-mails from regulatory websites, commercial
information provider websites
•
Attend relevant conferences/advisory meetings
•
Talk to colleagues and consultants
•
Employ a regulatory information database
Copyright © 2010. Cato Research
Surveillance
Copyright © 2010. Cato Research
Copyright © 2010. Cato Research
Surveillance: How Often?
•
Periodic Surveillance
– Conduct only when a question comes up
– Done when resources are limited
– Topics of interest might be missed
•
On-going surveillance
– Allows you to stay abreast of new developments that
need attention
– Can employ a database for continual surveillance
Copyright © 2010. Cato Research
How to Use, Collect, Analyze,
and Present RI?
Copyright © 2010. Cato Research
Applied RI - Example 1
•
Q: “Is it really necessary to request an EOP2 meeting
with FDA?”
Copyright © 2010. Cato Research
Applied RI – Example 1
•
FDA offers an end-of-Phase 2 meeting to discuss final
pivotal studies
•
Positive impact on first-cycle approval rates for companies
that held an EOP2 meeting (2006)
% Approval
100
Approval Rate in First Review Cycle
80
60
40
52%
20
29%
0
EOP2 mtg
No EOP2 mtg
Copyright © 2010. Cato Research
Independent Evaluation of FDA’s
First Cycle Review Performance
•
•
http://www.fda.gov/downloads/ForIndustry/UserFees/Presc
riptionDrugUserFee/ucm127982.pdf
2008 final report
– Drivers and hypothesis of multi-cycle reviews
– First cycle approval rates by year, by application type,
by review designation
– Overview of FDA sponsor communication
– Effect of meetings on approval rates
– Filing review issues
– Impact of major issues identified on approval rates
– Etc.
Copyright © 2010. Cato Research
Applied RI – Example 2
•
Q: “What do we know about the competitor
product(s)?”
Copyright © 2010. Cato Research
Applied RI – Example 2
•
Essential info to be gathered on competitor products
– Trade and INN name(s) in all countries
– Drug class
– Submission and approval dates in all countries
– Non-approval?
– Route of administration; presentations
– Pivotal clinical studies
– Label/SPC
– Submission info: standard/priority review, fast track,
accelerated review? EU: centralized, decentralized or
mutual recognition procedure?
Copyright © 2010. Cato Research
Applied RI – Example 2
•
Additional RI information that may be useful
– Overview of current regulatory landscape for that type
of product and in the markets identified for product
distribution
– Status of competitor products under development
•
Generate RI report including executive summary reviewing
competitor products on the market and under development,
the current regulatory landscape and submission routes
used by competitor products
Copyright © 2010. Cato Research
Applied RI – Example 3
•
Q: ”Does our product qualify for orphan? How
would we get orphan designation and what are the
differences between the US and the EU?”
Copyright © 2010. Cato Research
Applied RI – Example 3
FDA website
Copyright © 2010. Cato Research
Applied RI – Example 3
European Medicines Agency website
Copyright © 2010. Cato Research
Applied RI – Example 3
•
Research regulations, guidances, Agency websites,
previous orphan designations for related products and
other relevant websites
•
Summarize findings for the US and the EU such as
– Definition of orphan designation
– Regulatory requirements for orphan drug product
– Benefits for orphan drugs (tax breaks, grant
programs, reduced/waived fees etc.)
– Estimated costs/timeframe for orphan designation
request
Copyright © 2010. Cato Research
Applied RI – Example 3
•
Highlight differences between the US and the EU
•
Provide summary conclusions on
– Whether or not the product might qualify for orphan
designation
– Whether to apply in the US, the EU, or both
– Implications of orphan designation on overall
development plan
Copyright © 2010. Cato Research
Final Thoughts
Copyright © 2010. Cato Research
Objective of RI:
Identify Competitive Advantage
Business
Develop.
Regulatory
Affairs
CMC
Manufac.
Regulatory
Intelligence
Sales
Marketing
Toxicology
Preclin.
Copyright © 2010. Cato Research
Establishing a RI Project at Your
Company: Key Steps
•
Identify a need for RI activity
•
Identify internal resources for RI
•
Establish list of RI sources appropriate for your needs (e.g.,
websites, databases, consultants, CRO)
•
Discuss and clarify the scope, costs, format, and timeframe
of the RI Report
•
Collect and analyze RI information, and generate a RI
Report addressing the predefined question(s)
•
Make presentation to all Departments that may benefit from
this information
•
Update as necessary
Copyright © 2010. Cato Research
Points to Consider When
Outsourcing RI
•
Consultant or CRO?
•
Clearly define the scope
•
Clarify delivery format upfront
•
Provide timeframe and spending cap
•
Realize that one question often leads to many
more…
•
Allow for “early kill”
Outsource operational aspect of RI and use
RA Department’s time to interpret the information
and develop a regulatory strategy
Copyright © 2010. Cato Research
Questions?
Sybille Sauter
Senior Scientist, Regulatory Affairs
Cato Research
[email protected]
858-452-7271
Copyright © 2010. Cato Research
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