enterprise regulatory information: industry, ha, and...

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

2

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 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 year’s 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

3


Regulatory Information 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

4


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. Collaboration / Information 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

5


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 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 were perplexed at the difficulty industry communicated as the information exist; they didn’t 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

6


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

7


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 don’t 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

8


• 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 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

9


Regulatory Information Management Vendor Landscape

The vendor space has experienced many changes since last year’s 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 CRO’s 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

10


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. CSC’s 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

11


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 CRO’s 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. Registration 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

12


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 EMA’s 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 won’t 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. Health Authority Submission Formats and Emerging Standards

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

13


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.

14


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 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 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

15


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 FDA’s regulatory review process

• Publish a draft guidance document for comment describing FDA’s intended approach to the use of meta-analyses in the FDA’s 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 PlanPublic Workshops (2)

Enhance Structured Benef it / Risk Assessments

Develop review capacity for complex issues related to biomarkers and pharmacogenomics

FDA’s 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 Stds Plan Update Stds Plan Update Stds Plan Update Stds Plan Implementation Plan

4

Public Meeting: Sentinel Feedback Interim AssessmentSentinel: Evaluating

Drug SafetyInterim 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 Ef fectiveness and Healthcare

Integration

Guidance and Strategy & Assessment Mtgs

Priority Project Identification

Assessment Guidance

project completion TBD

16


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 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 FDA’s 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, 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 regulatory information sharing agreements with 26

17


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:

– Japan participates in annual pharmacovigilance conferences and staff exchange among 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 data mining.

• 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: 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.

18


Conclusion: Key Questions 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 Associates Inc. Benchmark References for this edition

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.

White Paper Authors

Steve Gens has 25 years of business experience with the majority in the biopharmaceutical and healthcare industries. His early career was spent at Johnson 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

19


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. [email protected] 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 FDA’s 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

mailto:[email protected]�

enterprise regulatory information: industry, ha, and...

Documents