Enterprise Regulatory Information Management

Industry, Health Authority, and Vendor Trends

Gens and Associates Whitepaper

Fall 2012 Edition







Prepared By:

Steve Gens: Gens and Associates Inc.
Greg Brolund: Chicopee Falls Consulting LLC





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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
Int roduct ion
Our annual industry white paper is written to give a current state of Regulatory Information
Management (RIM) along with key trends and projected change. This is based upon many
biopharmaceutical benchmark studies, client work, and our professional experiences. RIM
continues to grow in importance and in our opinion, is at an inflection point. Many organizations
have or are conducting strategic reviews of their Regulatory capabilities (systems, process,
policy, data quality) driven by a combination of what we consider are core 2012 themes:

1) Realization that Regulatory Information is an enterprise corporate asset used by many
functions (see Figure 1) and needs to be managed as
such
2) Desire to deploy and maintain a trusted Regulatory
Information authoritative source containing reliable
product and registration life-cycle information for
analysis and decision-making; replacing many
niche systems and spreadsheets
3) Increased complexity due to expanding Health
Authority requirements and Industry initiatives
4) Dilemma of obtaining transparency of affiliate
Regulatory activities versus the need to simplify
local data entry and deliver tangible business benefit
5) Expanding processes and systems to include key markets
that support both commercial and R&D activities
6) Mandatory operational efficiency gains and an end-to-end view of regulatory processes

The following opinions and perspective are based upon 10 of our industry benchmarks and key
learnings from client work. The studies focused primarily on Top 50 biopharmaceuticals as
defined by Pharmaceutical Executive. The structure of this years whitepaper is:

Regulatory Information Management Overview
Collaboration / Information Exchange
Product Information and Registration Management
Publishing and Submission Management
Content Management and Authoring
Vendor Landscape
Health Authority Trends / Impact
Conclusion: Key Questions

We hope this information is insightful and valuable. Please contact us with any questions.


Figure 1 - Functional use of RI


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012

Regulat ory Informat ion Management (RIM) Summary
Having tracked the Regulatory Information space for over ten years, we believe we are at an
inflection point for a number of strategic reasons. First and most importantly, critical regulatory
information is utilized throughout the value chain for important development, corporate, and
commercial decision-making. The effort and time to find and verify information to answer what
should be relatively simple questions has become unacceptable. Secondly, this information is
scattered across many information silos and secondary systems leading to a significant cost of
complying with the growing number of health authority requirements. Finally, regulatory
organizations have increased budget constraints leading to critical review of business processes,
data governance practices, productivity, resource allocation, and the cost/effectiveness of
information silos. Most organizations need
to become much more efficient supporting
the global environment. We strongly
believe increasing organizational
efficiency and effectiveness drives down
the cost of compliance without introducing
any undue risk. Figure 2 depicts the scope
of RIM and representative operational and
strategic value propositions.

Our 2011 themes of increased
collaboration, emerging market support, and growing
operational complexity (formats and number of
markets) continue to be important for most organizations. However, the subtle but significant
shift is the review of regulatory capabilities from an enterprise, not functional perspective with
an increased focus on realizing an enterprise authoritative source for critical Regulatory
Information such as product, registration, commitment and health authority questions and
answers. This has brought necessary focus on data governance models or the way critical
regulatory information is entered, verified, managed, consumed, and expressed (reported in
forms of dashboards, portals, mobile devices etc.). Several organizations have taken steps to
ensure information entry is part of everyday routines and is tied directly into individual / team
performance reviews.

The shift to an enterprise orientation, along with efficiency goals, brings the importance of a new
level of performance metrics. Traditional metrics focused on reporting activity volume or
quantity such as number of submissions, percent projected versus actual submission date,
number of commitments outstanding, etc. The new priority is to add efficiency and effectiveness
metrics to understand the true cost of compliance without introducing risk and to increase
organizational effectiveness.

We have been tracking the best of breed versus an integrated approach to regulatory systems
for many years. At a spring 2012 polling session of 52 companies; roughly one third had a clear
integrated approach, one third had best of breed approach, and the other third did not have a
Figure 2 - Regulatory Information Management


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
clear RIM strategy. These averages greatly varied by tier of company as shown in Figure 3. We
believe a consolidation and integration of capabilities will
support a greater amount of regulatory activities to better
achieve the vision of one source of the truth at a reduced
cost. This consolidation and simplification follows an
integrated approach and allows more scalability and
flexibility in our opinion.

From an investment standpoint, we see continued activity
in submission, registration, and commitment management
capabilities and some resurgence in the content
management / authoring area. Dossier outsourcing
continues to expand along with the use of contractors / consultants to supplement internal staff.

Finally, most companies are continuing to explore ways to lower their overall Total Cost of
Ownership (TCO). This has resulted in aggressive publishing outsourcing in the pasts two years
and analysis of alternative solution hosting concepts such as Software as a Service (SaaS) and
Cloud Computing. We find a significant increase in the investigation and use of the SaaS model
in small and mid-tier companies, but not yet in large bio-pharmaceuticals. While several vendors
are heavily investing in Cloud Computing for the RIM space and many biopharmaceutical
companies are interested, few are making the strategic decision to adopt.


Collaborat ion / Informat ion Exchange
Collaboration continues to be at the center of many organizational, technological, and process
initiatives and has increased significantly as seen in
firgure 4. We first started discussing our view of the
collaborative centric model in 2009 that was and
continues to be driven by significant co-
development and co-marketing relationships,
outsourcing of core activiteis (clinical Trials,
Manufacturing etc.) and increased usage of external
services for day to day operations (e.g. Dossier
Publishing). This requires change to operating
policies, information and content structures,
technologies, team/organizational competencies, and
business process.

The new normal is working in a global virtual workplace requiring global systems, 24x7
mobile access to key information / content, seamless and secure content exchange, and the
implementation of global information standards. The good news is several industry standards are
maturing (e.g. TMF Reference Model) and several current (EVMPD) and projected (IDMP)
Health Authority standards for Product Information are evolving making standard information
platforms more achievable. This has driven the need for organizations to invest in enterprise
Figure 3 - RIM Strategy by Tier
Figure 4 - Degree of Collaboration Change


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
information architectures (see Figure 5) that will ultimately make accessing and exchanging
information more efficient and reliable.

Salient Points:

Information exchange effectiveness continues to improve with
Health Authorities due to the realization of ICH standards,
adoption of HL7 and other standards, and the use of electronic
information exchange gateways
Significant challenges continue for business to business
information exchange (60% cite as ineffective) as authoritative
sources and enterprise standard data structures are still in an
infancy stage
Affiliate collaboration levels have dramatically increased since
our 2009 and 2011 studies due to the focus on risk
management (did an affiliate make the label update or was the
annual report submitted etc.) and forecasting (affiliate requires
better submission planning data to drive their local operations)
Organizations continue to open their internal authoritative document management
systems for third party collaboration
Organizations are increasing training and coaching to help staff be successful in both a
global and highly virtual environment
Social networking tools continues a slow adoption outside of Sales and Marketing

We believe significant investment will continue in this area for the next 2 4 years as companies
adapt to the collaborative centric environment where global virtual teaming and instant
mobile access to content is the norm.

Product Informat ion and Lifecycle Regist rat ion Management
We see significant activity in this area as many companies are investing in establishing a global
authoritative source for the first time or modernizing their existing capability. There was a major
wake-up call with EVMPD requirements and the difficulty companies had with complying with
this regulatory requirement quickly and efficiently. We also think Health Authorities were
perplexed at the difficulty industry communicated as the information exist; they didnt realize
how the product information is scattered across many databases so obtaining a complete list by
country was a difficult task for some. We believe a strategic view of registration management is
from a product life cycle orientation that combines a product dictionary with many core
regulatory activities that are part of a registration life cycle (submissions, correspondence,
question and answers, and commitments). These need to be managed by a global common
process and have an authoritative source to manage it for regulatory and other functional areas
(manufacturing, supply, business development, R&D etc.). Our 2011 survey found greater than
60% of top 50 companies will initiate or continue registration / submission tracking projects over
Figure 5 - Information Architecture Status


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
the next 24 months. We also note most active projects are taking significantly longer than
planned due to the gross underestimation of the time to locate and validate the registration and
product information from affiliates globally and finalize data governance rules to ensure the
central database is considered authoritative.

What we find extremely interesting is most companies share common project goals or expected
outcomes of a registration / product information initiative while the implementations are vastly
different. We have found no clear trend on project scope and implementation practices. Some
companies utilize a central model for data entry while others leave it to the affiliate or regional
hub. Some utilize links into the authoritative submission document management system to
complete the story by viewing the content (e.g. health authority correspondence) while others
do not. Some have introduced commitment tracking and correspondence management while
others utilize other systems.

A very recent trend noted by several vendors is companies who have successfully completed
their registration management projects are finding other business functions want to integrate
additional functional systems. This is an attractive option as the registration information is now
considered an authoritative source. We expect this trend to pick up momentum as other
companies complete their projects and look to increase the value of their system throughout the
company.

Salient Points:

Common goal to achieve an authoritative source of product and registration information;
significant work in common terminology and naming standards
Significant endeavor to convert and maintain quality product and registration data,
especially in mergers & acquisitions or multi-system consolidations
Significant focus on Data Governance model (entry and data validation)
Commitment management criticality has increased for inspection support and risk
management (status of work-in-progress vs. deadline)
Consistency in Q&A responses is a growing concern and focus of work
More Health Authorities are conducting more data reviews (instead of referring to lead
ICH regions) leading to more questions
Typical business case to justify these projects are compliance and efficiency

Submission Management and Publishing
This area continues to see significant change as global submission planning, improved efficiency
in production planning, and dossier outsourcing are common initiatives for most companies. The
typical Regulatory Operations function is managing growing complexity as individual country
filing requirements continue to evolve and no central authoritative source of these filing
requirements is easily available. The pressure to drive cost out of the operation is pushing


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
organizations to functional outsourcing although the cost difference between off shore and on
shore is starting to close as the individual publishing rates are rising and the cost of project
management on both the vendor and sponsor sides actually increases cost. Some organizations
are investigating on shore publishing apprentice program utilizing low-cost entry staff.
Publishing tools continue to be relatively static as patches and minor releases keep
Regulatory Operations busy. There is a desire to have less change as the time to re-validate is
considerable. In addition, most are waiting to see the vendor RPS strategy and what impact
(small or large) it will have on their publishing platforms.
Global submission planning has a heighten priority as most companies understand the resource
requirements of big marketing applications, but dont appreciate the high volume of smaller
submissions managed behind the scenes supporting a large percentage of the revenue base.
The reality is Publishing Operations spends a
majority of its available time and resources on the
thousands of daily small submissions to respond
to health authority requests and to keep individual
country registrations current.

The publishing resourcing trend is dramatic (see
Figure 6) as companies are moving aggressively
with outsourcing or internal work redistribution to
internal sites in India and China. Several large
companies have entered into different outsourcing
agreements such as functional outsourcing, offshore
utilizing internal systems, and rebadging. The trend
in our outsourcing benchmarks is very interesting as 2008 and 2011 were key decision point
years as industry determined whether to outsource more (new or expanded) or not. Our 2012
benchmark (see Figure 6) finds 75% of top 50 doing
some type of project or functional outsourcing with
21% in analysis mode. What we do know is the
outsourcing deals are much larger and are shifting to
more strategic relationships (see Figure 7).

Our benchmark data shows high vendor satisfaction
with publishing outsourcing partners. While the
vendor satisfaction level is good news, there are mixed
results in achieving internal goals. We asked 8
companies that have outsourced for at least 6 months
to report four key performance metrics (cost
realization, complexity, efficiency, and turn-around
time). 50% stated meeting outsourcing business goals while 50% had several or many goals not
realized.

Salient Points:

Multiple e-submission formats, validation tools, and electronic gateways are increasing
Regulatory Operations complexity
Figure 6 - Dossier Outsourcing Trends
Figure 7 - Dossier Outsourcing Direction


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
National affiliate support for electronic submissions is a growing need and often satisfied
through a regional / central operation or outsourcing
Regulatory is evolving to a true global regulatory business model resulting in a more
distributed regulatory strategy group and in centralized operations groups
Resourcing models (outsourcing or work redistribution to low cost regions) are in flux
Off-the-shelf solutions providing an authoritative source of planning / tracking
information are maturing
Core Dossier Programs continue to focus on minimum builds

Cont ent Management / Aut hor St at us and Trends
Content Management programs have seen little change since our 2011 survey in our opinion.
Many organizations now consider it back office technology and part of the operational
infrastructure. We do see a renewed interest in Structured Content Authoring (SCA) and our
view has not changed: it is still in learn mode with a significant change management hurdle.
This is comprised of: 1) authors writing in chunks or components instead of broad themes
based on the data and 2) the virtualization of the authoring community making it hard to
implement this type of technology. We also believe the lack of a clear and substantial economic
business benefit makes it hard to justify the degree of change required. The only exception is
within label operations were the volume and structure of information would warrant the
investment in SCA.

Salient Points:

Implementation of Clinical eTMF continues to be a significant are of focus with 80%
implementing or planning to change
More companies provide ECM access for external partners; this continues to be a key
priority
Structured Content Authoring is still in learn mode. Tool vendors continue to invest,
but struggle to gain enough business to justify the investment
Authoring continues to focus on writing in a global context to minimize regional or
country specific re-writes
A common challenge is to provide appropriate access to mobile users and partners while
managing the content management platform as a commodity






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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
Regulat ory Informat ion Management Vendor Landscape
The vendor space has experienced many changes since last years edition including several
significant mergers and acquisitions. Our views of the landscape are:

Vendor consolidation continues within the Regulatory solution space and we expect
further vendor merger & acquisition activity. Larger organizations are buying the smaller
niche providers as the addressable market for combined services / solutions is growing
R&D Content Management and Registration Management have clear market leaders with
several newcomers trying to penetrate these markets
Submission and Resource Management vendor market share is predicted to change
significantly over the next 1 2 years
Robust Regulatory Information Management capabilities are still maturing and buying
cycles are longer due to the strategic nature of vendor/partner decisions
Most vendors realize the importance of mobility and are aggressively investing
Dossier outsourcing competition is growing past the traditional players as CROs are
aggressively pursuing this space. Deals are much more substantial as opposed to just
traditional one-off projects.
Labeling vendors are struggling after the PIM program cancellation: we are expecting an
industry investment pick-up for 2013 / 2014
Several vendors are offering cloud solutions; we believe this will mature significantly by
2015

Vendor competition is heating up as RIM concepts are seen as viable and companies are making
significant investments to update their processes, technology, and data governance practices.
What we believe to be critical is how an organization views
their Regulatory capability as this will orient them to a subset
of vendors. We see RIM vendors aligned to one of three
orientations based on process, marketing, or architecture
drivers:

1. Tightly Integrated: Fewer solutions tightly integrated
2. Best of Breed: Top market tools supporting individual
capabilities
3. Independent Solutions: Solo components with little or
no information sharing / integration (or no strategy)

Many biopharmaceutical companies would like to make
significant improvements to their overall RIM practices and solutions but are deterred by the cost
of the change. Some companies have been able to leverage a major event such as a merger or
acquisition to justify an overhaul to their RIM capability. In other cases, a well designed
strategic roadmap and business case is needed to gain approval for the change.

Figure 8 - RIM Triangle of Truth


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012

Document Management
Since our 2011 report, small but significant changes have emerged and we believe the next two
years will be very interesting in this space. We see incremental improvements in authoring and
electronic signature along with a renewed interest in digital records management functionality.
The next big wave in document management will be cloud-based and the solutions sets are still
in a maturing phase, although some significant deployments have occurred in the Promotional
Material Management area.

We have been tracking the top 50 bio-pharmaceutical movement of internally developed
document management solutions to off-the-shelf (OTS) capabilities over the past seven years.
The industry has flipped from a 75% / 25% (custom to OTS) to 77% having a true OTS solution
and we expect this to continue as several early adopters are modernizing their capabilities and
will go OTS.

Our market-share is based on an 2011 industry survey and we expect
only minor share changes over the next three years. CSCs First Doc
retains market leadership with a 46% market share while customized
Documentum is second at 41%, but declining for R&D document
management. We believe that NextDocs (based on the SharePoint
platform) is becoming an important player and has some success in
the manufacturing and clinical areas along with Veeva Systems that is
pushing a pure cloud solution set. Clearly the NextDocs solution set
advantages are ease of use at a reduced cost. Veeva could potential be
a game-changer with some initial success and should be attractive
for smaller organizations for enterprise content management or functional for larger
organizations.

We also see a shift in organizations considering leaving traditional Documentum based systems;
our 2011 survey found 20 30 % of participants citing the potential to change their
Documentum based systems within the next 2 years. What we find interesting is that
Documentum announced a solution set for Life Sciences that will compete directly with CSC,
NexDocs, and Veeva Systems, and are hiring seasoned industry consultants to help support this
new offering. This raises some interesting questions:

What does this mean for CSC and its relationship with EMC?
Has EMC entered this market too late or is it perfect timing for customers who are
frustrated with minimal solution sets available?
Will Sharepoint be able to scale to gain market-share from Documentum based solutions?



Figure 9 - Top 20 Documentum Share


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012

Publishing
Publishing vendors have had relatively little software change since the transition to the eCTD
format. Although 2010 and 2011 saw several significant
mergers (Liquent/ Datafarm and CSC/ISI); little change
in the market has resulted. Each of the primary
publishing vendors (ISI, Liquent/Datafarm, Extedo, and
Lorenz) are closely monitoring and preparing for the
new FDA format RPS. It is yet to be seen if this will
create a new software solution or just an enhancement
to their current eCTD capabilities.

We also see vendors creating simple converter tools to
combat the complexity of multiple e-submission formats
such as eCTD to NeeS and eCTD to ACTD for ASEAN
block submissions.

The most significant growth will be in the services side
of the business as many vendors are projecting growth
of 30 50% as more companies adopt partial or full
dossier outsourcing. The momentum is significant and
a key question for service vendors is one of
organizational scale. With a significant increase of
business, how can their organizations scale effectively
AND keep quality and turn-around times equal to
customer expectations. We believe
Accenture/Octagon, Liquent, CSC (ISI), and several
CROs to be the main players moving forward. We
find that large organizations prefer a global outsourcing
partner while the mid-tier and small organizations
might partner with a regional niche player.


Regist rat ion and Submission
Management
This area is experiencing significant activity with
Liquent the clear market leader and gaining share
since our 2011 review. Many organizations will
make vendor decisions late 2012 and 2013 and
we expect the market-share story to evolve with
much of the internally developed (see Figure
12) to shift to OTS solutions. Liquent continues
to build on their strength and we believe they
Figure 10 - 2012 eCTD Market Share
Figure 11 - eCTD 2007 - 2012 Market Share
Figure 12 - Registration Market Share


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
will be the market leader for the foreseeable future. CSC is pushing hard to gain industry
acceptance of their Total Regulatory Solution that brings the data and document side together.
They will need several significant wins with their Registration module to demonstrate relevance.
Mission 3 and Oracle PLM are trying to make inroads and we will know within 12 months if
they have success or not.

The Submission Management space is very
interesting as companies see this as either an
add-on to their publishing capabilities or a
separate solution set. Liquent, CSC, and Extedo
have natural, but limited extensions into
Submission Management. Both Planisware and
Accenture/Octagon have mature solutions that
address more of the total resource management
combined with the classical submission planning
and scheduling modules.

We believe that looking at Registration
Management independent of the overall regulatory information management picture is
shortsighted. Companies need to determine their overall RIM strategy and be very intentional in
their adoption of a niche or information integrated strategy. Registration, Approval Status,
and Product Information are core to any RIM capability.


Labeling
This area has remained relatively static since EMAs announcement to cancel the PIM program.
This announcement has had significant ramifications in our opinion. First, several important
label management solution vendors are distressed and fighting for survival as significant
investments were made with limited revenue to recoup their expenses. Secondly, many
biopharmaceutical companies made preliminary investments and oriented their global label
programs to the PIM paradigm. They were left empty-handed and probably wont stomach future
risky investments for potential health authority programs that should benefit both the
competent authorities and industry; it is truly a shame this has happened.

As the PIM situation fades, many organizations and the remaining vendors are working again on
the global label paradigm where: a) full transparency to what was submitted, b) Core Data Sheet
conformance, and c) translation continue to be primary goals. We expect investments to increase
in 2013 in global labeling and XML based solutions to streamline the label operation.


Healt h Aut horit y Submission Format s and Emerging St andards
Health Authorities and the pharmaceutical industry are engaged in initiatives to develop and
expand the use of electronic submission formats and standards for data and content. These
initiatives provide opportunities to take advantage of emerging standards and updated internal
Figure 13 - 2008 - 2012 Market Share


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
processes to reduce operational complexities. At the same time, an unintended result of these
global activities is an increasingly complex environment for managing regulatory data and
submissions.

Electronic submissions and standards initiatives continue to be actively pursued by both the US
Food and Drug Administration (FDA) and the European Medicines Agency (EMA). A good
example of the progress in this area is the eCTD which is the only marketing application
electronic format allowed by the FDA and by the EMA for the EU Centralised Procedure. In
Europe, extension of the eCTD to the Mutual Recognition Procedure and Decentralized
Procedure submissions is expected by 2014.

FDA is planning to make the submission of marketing applications (New Drug Applications and
Biologics Licensing Applications) and investigational drug applications (IND) in eCTD format
mandatory by the end of 2017. This is one of the goal statements in the US Prescription Drug
User Fee Act V renewal (see FDA PDUFA V below).

The International Conference on Harmonisation (ICH) is depending on the development and
approval of the HL7 Regulated Product Submission (RPS) standard to be the basis of the next
major version of the eCTD eCTD 4. FDA is proceeding with the effort to make the eCTD
mandatory using eCTD V3.2.2 with the idea of updating to eCTD V4 when the RPS standard has
been approved and eCTD V4 implementations have been tested. A possible timeline for these
two events is shown in Figure 14. We expect RPS implementation will take at least 3 to 5 years
and even longer in some regions where ISO approval is also required and the pace of change can
be affected by technology, regulatory, budget and political considerations. The electronic
submission landscape will be even more complicated, if as expected, the FDA moves quickly to
adopt the RPS standard for its submissions while the other ICH regions take a prolonged period
of time to adopt.


Figure 14 - Mandatory eCTD for FDA and eCTD v4 / RPS
In addition to the eCTD and traditional paper submissions, the Non-eCTD Electronic Submission
(NeeS) is still the most commonly accepted electronic format for National Procedure
submissions in Europe and a recent survey found 10 years to be the average life expectancy of
the format. NeeS will be accepted, as at least a temporary format, in other countries including
Saudi Arabia and Australia. In Europe, industry groups and National Competent Authorities
(NCA) support the eCTD but still see a long term future for NeeS for mature nationally approved
products.


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012

We know regulators adopt new submission formats and standards but rarely fully retire existing
ones. The acceptance of electronic submissions and the elimination of paper submissions
continue to grow in the US and in Europe. But there has been relatively little adoption of
electronic only submissions in other regions and the adoption of a global, single electronic
submission standard has not been accomplished. For most of the world, it will continue to be
paper and business as usual for the foreseeable future.

In most companies there is a relatively high cost to implement new standards for submission
format, content and data. It is also expensive to update existing policies and procedures to
implement new requirements. Therefore, many companies adopt a reactive strategy in which
adoption and implementation is undertaken only after it is clear that there will be a regulatory
requirement.

We believe proactive implementation of standards for processes and content across the
regulatory enterprise provides an opportunity to simplify operations and integrate information
resources. The ROI from global standards will only be realized when data, content and format
standards are fully adopted for internal and partner processes. Waiting for regulatory mandates
will continue to place the industry in a reactive mode, reducing the ability to capitalize on
opportunities to improve capabilities for regulatory information management, and internal and
external collaboration.

FDA Prescript ion Drug User Fee Act V
The reauthorization of the Prescription Drug User Fee Act (PDUFA) includes goals for FDA
from Fiscal Year (FY) 2013 through FY 2017. There are many opportunities for industry to
participate in the development and implementation of the FDA activities to achieve these goals.
This includes attending FDA public meetings, providing comments on proposed regulations and
guidance, and participation in standards development organizations. Active involvement
increases the awareness and readiness of individual companies and allows industry to influence
timing and content. Figure 15 lists these key goal areas and Figure 16 shows the key milestones
across the 5 year PDUFA V authorization period.

Goal Area Summary Highlights
Improving the efficiency of
human drug review through
required electronic submissions
and standardization of electronic
drug application data
Required Electronic Submissions IND, NDA, BLA Final guidance shall
be binding on sponsors, applicants, and manufacturers Mark Gray, FDA ,
April 2012
Develop standardized clinical data terminology through open standards
development organizations
Development of terminology standards for data other than clinical data
Sentinel: Evaluating Drug
Safety
Determine the feasibility of using Sentinel to evaluate drug safety issues that
may require regulatory action
Enhance Structured Benefit /
Risk Assessments
Develop a five-year plan to further develop and implement a structured
benefit/risk assessment in the new drug approval process


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
Goal Area Summary Highlights
Risk Evaluation & Mitigation
Strategies (REMS) Effectiveness
and Healthcare Integration
Develop techniques to standardize REMS and with stakeholder input seek to
integrate them into the existing and evolving (e.g. increasingly electronic)
healthcare system
Meta Analysis Methodologies
Evaluate different scientific methods and explore the practical application of
scientific approaches and best practices, including methodological
limitations, for the conduct of meta-analyses in the context of FDAs
regulatory review process
Publish a draft guidance document for comment describing FDAs intended
approach to the use of meta-analyses in the FDAs regulatory review process
by the end of FY 2015
Advance Use of Biomarkers and
Pharmacogenomics
Develop staff capacity to review submissions that contain complex issues
involving pharmacogenomics and biomarkers
Advance use of Patient Reported
Outcomes & Other End Points
Initiate a public process to nominate a set of disease areas that could benefit
from a more systematic and expansive approach to obtaining the patient
perspective on disease severity or unmet medical need
Enhanced IND Communication
Develop and publish draft guidance for review staff and industry describing
best practices for communication between FDA and IND sponsors during
drug development
Figure 15 Selected FDA PDUFA V Goals


Figure 16 - PDUFA V Goal Milestones

Goal Area FY 2013 2014 2015 2016 2017
Public Stakeholder
Meeting
Publish Draft
Guidance
Publish Final
Guidance
Meta Analysis
Methodologies
Public Meeting:
Current Status &
Strategies
Advance Use of
Biomarkers and
Pharmacogenomics
Public Meeting
Advance use of
Patient Reported
Outcomes & Other
End Points
Publish Draft Plan
Public Workshops
(2)
Enhance Structured
Benefit / Risk
Assessments
Develop review capacity for complex issues
related to biomarkers and
pharmacogenomics
FDAs qualification of standards for drug development
tools, measurement theory and implications for multi-
national trials
Disease area specific public meetings (4 / year)
e-Submission Draft
Guidance
Final Guidance NDA / BLA Requirements IND Requirements:
REQUIRED
eSubmissions
Publish StdsPlan Update StdsPlan Update StdsPlan Update StdsPlan
Implementation
Plan
4
Public Meeting:
Sentinel Feedback
Interim Assessment Sentinel: Evaluating
Drug Safety
Interim Assessment
Multiproduct / class safety signal evaluation (4-6)
Internal Drug Dev
Communication &
Training Staff
Train Internal
Review Staff
Publish Draft
Guidance
Publish Final
Guidance
Enhanced IND
Communication
Clinical Terminology
Standards
REMS Effectiveness
and Healthcare
Integration
Guidance and
Strategy &
Assessment Mtgs
Priority
Project
Identification
Assessment Guidance
project completion TBD


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
Healt h Aut horit y Audit and Collaborat ion Trends
Since 2011, Health Authorities continue to increase collaboration programs with other Health
Authorities and are trending toward increased scrutiny of electronic records and promotional
material. Health Authorities are raising the bar for compliance especially in manufacturing
and pre and post approval safety programs. At the same time, individual countries like China
and South Korea are raising their health authority regulatory profiles in order to exert more
influence: others nations may follow this trend. For example, several countries in Central
America and South America have recently begun the process of updating their drug approval
regulations.

In the US, FDA statements and industry experience suggest that FDA is shifting compliance /
enforcement practices from relatively collaborative to more punitive model. Some believe that
risk based enforcement is shifting from Identify the Risk to No Risk Tolerated.

In the last few years, FDA public statements suggest a possible increase in the level of
enforcement activities and identified possible changes that would hold sponsor companies more
accountable for the manufacturing processes of outside contractors and for verifying that
contractors have followed FDA standards, including the possibility that companies may be
required to conduct on-site audits at outsourced manufacturing facilities. According to FDA, the
total number of product recalls across all Centers increased by 16% from 2009 to 2010. CDER
and CBER recalled a combined total of 3592 products in 2010 and 3816 products in 2011. We
are interested in the 2012 FDA report-out.

In 2010, FDA announced its intention to make 21 CFR Part 11 inspectional assignments to help
further assess how to proceed with the possible modification of Part 11 regulation and guidance.
As of 2012, there is still very little information available about FDAs findings and the best
method to comply with the regulation continues to be debated within and among companies.

The EMA approach to audits and inspections also continues to evolve. For example, the EU
GCP Inspectors Working Group reflection paper (i.e. guidance) effective August 2010, provides
a detailed description on the characteristics and processes expected for the use of electronic data
capture in clinical trials.

At the same time there is a clear trend of increasing collaboration among health authorities
around the world. Major regulatory agencies have entered into regional and cross-regional
agreements to share information at each stage of the drug development process.

The EMA has formal agreements with other Health Authorities including FDA, Health Canada,
J apanese Ministry of Health, Labour and
Welfare (MHLW) and the Pharmaceuticals
and Medical Devices Agency (PMDA),
Swissmedic and others.

As of 2012, the FDA has over 61 regulatory
information sharing agreements with 26


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
individual countries and the European Union. In the biopharmaceutical area, formal agreements
include information sharing regarding inspections of manufacturing and clinical trial sites as well
as reviews of pharmaceutical products and medical devices.

There is especially close cooperation with the EMA through
the exchange of confidential information (advance drafts of
legislation and regulatory guidance documents) as well as
non-public information related to ensuring the quality, safety
and efficacy of medicinal products for human and veterinary
use.

Safety continues to be a major driver for collaboration in all regions and is being facilitated by
the World Health Organization and ICH safety activities as well as individual Health Authority
initiatives. For example:

Asia Pacific:
J apan participates in annual pharmacovigilance conferences and staff exchange
among J apan, China and South Korea
Korea, J apan, and Taiwan, among others, have national pharmacovigilance systems
for collection and analysis of spontaneous reports which will be used for routine data
mining.
EMA
Promoted the establishment of the European Network of Centres for
Pharmacoepidemiology and Pharmacovigilance (ENCePP)
In J uly 2012, the EMA released two additional modules on good pharmacovigilance
for public comment, Module IV: Pharmacovigilance audits and Module XV: Safety
communication
FDA
Over the next 5 years, FDA will enhance and modernize its drug safety system by
determining feasibility of using the Sentinel program to evaluate drug safety issues
that may require regulatory action.
FDA will also expand its pharmacovigilance program beyond spontaneous reports by,
including population-based epidemiological data and other types of observational
data resources
Dubai
In 2012, the Hospital Services Sector at the Dubai Health Authority adopted an online
patient safety and risk management system across its hospitals and specialty centers
to ensure unification of processes and reporting systems which is essential to
minimize risks and further enhance patient safety
Increasing collaboration among Health Authorities coupled with the continuing trend of raising
the bar for compliance adds to the need to improve regulatory information management
capabilities and practices to be effective, efficient and agile.



In one example of EMA FDA
collaboration, the two Agencies
worked together to each send
identical language to a company
about a product under active
review.


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
Conclusion: Key Quest ions

1) Do you have the right RIM foundation (Registration Lifecycle and Product Information) to
better address growing strategic requirements?
2) Will you need a different Data Governance approach and model to achieve authoritative
source?
3) How can common processes and consolidated systems reduce the cost of compliance and
enhance usability?
4) How will you incorporate continuous improvement methods and effectively monitor
performance measures into your program?
5) What is your RIM orientation and how does this influence your vendor interactions?
6) What other stakeholders would gain value from a robust RIM environment that our outside
the traditional Regulatory Organization?


Gens and Associat es Inc. Benchmark References for t his edit ion
1) 2010 Regulatory Submission Management and Production Planning, Gens and Associates
Inc.
2) 2010 Global Pharmaceutical Regulatory Affiliate Strategy, Gens and Associates Inc.
3) 2010 COTS Market Share Analysis, Gens and Associates Inc.
4) 2010 Regulatory Information Management Industry Benchmark, Gens and Associates Inc.
5) 2011 Regulatory Trends, Gens and Associates Inc.
6) 2011 Collaboration / ECM Trends, ILSS & Gens and Associates Inc.
7) 2011 Submission Management Organizational / Outsourcing Benchmark, Gens and
Associates Inc.
8) 2011 Labeling and Promotional Material Organization Strategy, Gens and Associates Inc.
9) 2012 Regulatory Information Management and Dossier Outsourcing Trends, Gens and
Associates Inc.
10) 2012 COTS Market Share Analysis, Gens and Associates Inc.


Whit e Paper Aut hors
Steve Gens has 25 years of business experience with the majority in the
biopharmaceutical and healthcare industries. His early career was spent at
J ohnson and J ohnson and then moved into consulting where he managed several
healthcare consulting practices for Booz Allen Hamilton and First Consulting
Group. Steve has deep experience in strategy formulation and implementation,
organization development and performance, global virtual team effectiveness,
industry benchmarking, information management strategy, and leading or facilitating strategic
change. He consults for many of the largest global biopharmaceutical companies and also with


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Enterprise Regulatory Information: Industry, HA, and Vendor Trends Fall 2012
small high growth organizations. Steve has a Master of Science in Organization Development,
Bachelors of Science in Business Computer Science, and is certified in Change Management
from the NTL Institute of Applied Behavior. President of Gens and Associates Inc.
sgens@gens-associates.com or 267-614-0935


Greg Brolund is a Global Pharma management and technology consultant with
extensive experience in business processes and supporting IT for product labeling,
submission publishing, Health Authority interactions, pharmaceutical safety and
pharmacovigilance programs. He served as the Rapporteur of the ICH M2
Working Group Rapporteur from 1998 through 2002 for the development of the
initial production version of the eCTD and the implementation of the E2B ICSR
electronic submission. He has 25 years experience with the FDA leading development of FDAs
internal IT systems in support of the CDER and CBER submission review process. After leaving
the FDA, he served as the US HHS CTO and was a pharmaceutical industry consulting with
Booz Allen Hamilton. He holds a Masters of Chemistry degree from the American University in
Washington DC