IM_Executive RIM Whitepaper_Gens and Associates_V_Fall 2012 Edition

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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

Introduction

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 organizationshave 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 RegulatoryInformation 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 asdefined 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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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 betterachieve the vision of one source of the truth at a reduced

cost. This consolidation and simplification follows an

integrated approach and allows more scalability andflexibility 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) andCloud 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 biopharmaceuticalcompanies are interested, few are making the strategic decision to adopt.

Collaboration / Information Exchange

Collaboration continues to be at the center of many organizational, technological, and processinitiatives and has increased significantly as seen in

firgure 4. We first started discussing our view of thecollaborative centric model in 2009 that was andcontinues 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 arematuring (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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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 withHealth 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 businessinformation 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 sinceour 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 instantmobile access to content is the norm.

Product Information and Lifecycle Registration 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 wereperplexed 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 bycountry was a difficult task for some. We believe a strategic view of registration management isfrom 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 commonprocess 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 Sta


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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 thecentral database is considered authoritative.

What we find extremely interesting is most companies share common project goals or expectedoutcomes 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 tocomplete 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 nowconsidered 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 efficiencyin 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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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 organizationsare 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 isconsiderable. 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 appreciatethe 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 respondto health authority requests and to keep individual

country registrations current.

The publishing resourcing trend is dramatic (seeFigure 6) as companies are moving aggressively

with outsourcing or internal work redistribution to

internal sites in India and China. Several largecompanies have entered into different outsourcing

agreements such as functional outsourcing, offshore

utilizing internal systems, and rebadging. The trendin 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 with21% 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 thevendor satisfaction level is good news, there are mixed

results in achieving internal goals. We asked 8

companies that have outsourced for at least 6 monthsto report four key performance metrics (cost

realization, complexity, efficiency, and turn-aroundtime). 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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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

Content Management / Author Status 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 ourview 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 toimplement 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 theinvestment 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 whilemanaging the content management platform as a commodity


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Regulatory Information 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 expectfurther 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 withseveral 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 buyingcycles 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 areaggressively pursuing this space. Deals are much more substantial as opposed to justtraditional 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 by2015

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 threeorientationsbased 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 oracquisition 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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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 expectonly minor share changes over the next three years. CSCs First Doc

retains market leadership with a 46% market share while customizedDocumentum 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 inthe 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 bea 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 thatDocumentum 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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Publishing

Publishing vendors have had relatively little software change since the transition to the eCTD

format. Although 2010 and 2011 saw several significantmergers (Liquent/ Datafarm and CSC/ISI); little change

in the market has resulted. Each of the primarypublishing 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 willcreate a new software solution or just an enhancement

to their current eCTD capabilities.

We also see vendors creating simple converter tools tocombat the complexity of multiple e-submission formats

such as eCTD to NeeS and eCTD to ACTD for ASEANblock submissions.

The most significant growth will be in the services side

of the business as many vendors are projecting growthof 30 50% as more companies adopt partial or full

dossier outsourcing. The momentum is significant and

a key question for service vendors is one oforganizational 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 believeAccenture/Octagon, Liquent, CSC (ISI), and several

CROs to be the main players moving forward. We

find that large organizations prefer a global outsourcingpartner while the mid-tier and small organizations

might partner with a regional niche player.

Registration and Submission

Management

This area is experiencing significant activity withLiquent the clear market leader and gaining sharesince our 2011 review. Many organizations will

make vendor decisions late 2012 and 2013 and

we expect the market-share story to evolve withmuch 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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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 Extedohave natural, but limited extensions into

Submission Management. Both Planisware and

Accenture/Octagon have mature solutions thataddress 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 intheir 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 importantlabel management solution vendors are distressed and fighting for survival as significantinvestments 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 futurerisky 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 increasein 2013 in global labeling and XML based solutions to streamline the label operation.

Health Authority Submission Formats and Emerging Standards

Health Authorities and the pharmaceutical industry are engaged in initiatives to develop andexpand 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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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 goodexample 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 formatmandatory 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 andapproval 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 hasbeen 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 canbe 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 periodof 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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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 submissionscontinue to grow in the US and in Europe. But there has been relatively little adoption of

electronic only submissionsin 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 bepaper 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 toimplement 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 formatstandards 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 andexternal collaboration.

FDA Prescription 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 influencetiming and content. Figure 15 lists these key goal areas andFigure 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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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 ofscientific 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 StakeholderMeeting

Publish DraftGuidance

Publish FinalGuidance

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 PlanPublic Workshops(2)

Enhance Structured

Benefit / Risk

Assessments

Develop review capacity for complex issuesrelated to biomarkers andpharmacogenomics

FDAs qualification of standards for drug developmenttools, measurement theory and implications for multi-national trials

Disease area specific public meetings (4 / year)

e-Submission DraftGuidance

Final Guidance NDA / BLA Requirements IND Requirements:REQUIREDeSubmissions

Publish Stds Plan Update Stds Plan Update Stds Plan Update Stds PlanImplementationPlan

4

Public Meeting:Sentinel Feedback Interim Assessment

Sentinel: EvaluatingDrug Safety

Interim Assessment

Multiproduct / class safety signal evaluation (4-6)

Internal Drug DevCommunication &

Training Staff

Train InternalReview Staff

Publish DraftGuidance

Publish FinalGuidance

Enhanced IND

Communication

Clinical TerminologyStandards

REMS Effectiveness

and Healthcare

Integration

Guidance andStrategy &

Assessment Mtgs

PriorityProjectIdentification

Assessment Guidance

project completion TBD


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Health Authority Audit and Collaboration 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 Chinaand 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 approvalregulations.

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 moreaccountable for the manufacturing processes of outside contractors and for verifying that

contractors have followed FDA standards, including the possibility that companies may berequired 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. Weare interested in the 2012 FDA report-out.

In 2010, FDA announced its intention to make 21 CFR Part 11 inspectional assignments to helpfurther 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 datacapture in clinical trials.

At the same time there is a clear trend of increasing collaboration among health authoritiesaround 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,

Japanese 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 regulatoryinformation sharing agreements with 26


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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 oflegislation 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 Authorityinitiatives. For example:

Asia Pacific:

Japan participates in annual pharmacovigilance conferences and staff exchangeamong Japan, China and South Korea

Korea, Japan, and Taiwan, among others, have national pharmacovigilance systems

for collection and analysis of spontaneous reports which will be used for routine datamining.

EMA Promoted the establishment of the European Network of Centres for

Pharmacoepidemiology and Pharmacovigilance (ENCePP)

In July 2012, the EMA released two additional modules on good pharmacovigilance

for public comment, Module IV: Pharmacovigilance audits and Module XV: Safetycommunication

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 observationaldata 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 raisingthe 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 Agenciesworked together to each send

identical language to a company

about a product under active

review.


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Conclusion: Key Questions

1) Do you have the right RIM foundation (Registration Lifecycle and Product Information) tobetter 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 Associates Inc. Benchmark References for this edition

1) 2010Regulatory 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) 2010Regulatory Information Management Industry Benchmark, Gens and Associates Inc.

5) 2011Regulatory Trends, Gens and Associates Inc.6) 2011 Collaboration / ECM Trends,ILSS & Gens and Associates Inc.

7)

2011 Submission Management Organizational / Outsourcing Benchmark, Gens andAssociates Inc.8) 2011Labeling and Promotional Material Organization Strategy, Gens and Associates Inc.

9) 2012Regulatory Information Management and Dossier Outsourcing Trends, Gens and

Associates Inc.10)2012 COTS Market Share Analysis, Gens and Associates Inc.

White Paper Authors

Steve Genshas 25 years of business experience with the majority in thebiopharmaceutical and healthcare industries. His early career was spent atJohnson and Johnson 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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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 [email protected] 267-614-0935

Greg Brolundis 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 M2Working 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 FDAsinternal 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
mailto:[email protected]:[email protected]:[email protected]

Documents

IM_Executive RIM Whitepaper_Gens and Associates_V_Fall 2012 Edition