By Dr. Satish Tadikonda
Today’s life sciences industry faces many challenges as drug development costs continue to climb, pricing pressures mount, and new global markets gain critical importance. At the same time, the FDA, EMA, and other regulatory bodies are expanding and amending requirements, clinical trials are becoming more complex, and public disclosure demands are increasing. This increases the importance, complexity and risk related to managing regulatory information assets.
According to analyst firm IDC Health Industry Insights, a new drug costs from $800 million to $1.2 billion to bring to market, and a quarter of this cost is regulatory content requirements. The means that the life sciences industry spends several billion dollars a year on the management of content and regulatory information.
In response to this hyper-competitive global market, many pharmaceutical companies have undergone radical transformations to become more agile in developing new drugs to address unmet medical needs. This has included massive restructuring, reengineering of key R&D processes, new models of partnering and outsourcing key development activities to CROs. These moves to a more agile enterprise must not be hobbled by cumbersome regulatory information management (RIM) paradigms based on legacy thinking and systems.
This article will explore new RIM approaches and technologies for better management of and access to regulatory information. Regulatory data and the related information are important corporate assets, supporting many cross-functional processes such as manufacturing, R&D document authoring and clinical trial submissions. New approaches in content management can improve regulatory authoring and publishing. This is defined by a move from a document-centric to a content-centric approach to information.
Regulatory professionals (RP) face a shifting landscape while struggling with proliferating information sources, variable data quality and heterogeneous data. Too often information management strategies and systems are not designed to cross organizational boundaries. Regulatory document creation and information management in a life sciences company cannot be seen as a discrete activity. Indeed, such data is used by many departments within the enterprise for such activities as business development, marketing, labeling, supply release, local affiliate tracking, and for third party information exchange and collaboration. Without a holistic view of regulatory information management as an enterprise-wide process, the company is greatly hampered.
One problem is the overwhelming amount of data, documents, and tasks RPs deal with, much of it redundant. A typical regulatory affairs department can deal with 2,000 submission documents in a given quarter, and many more at larger companies. Minor changes in documents, labels, statistical analyses, etc. are the norm, creating a ripple effect through thousands of documents over many years. The document tracking and processing is massive. Equally significant is the wide range of different departments and individuals contributing to these “regulatory” activities. Regulatory professionals need visibility into critical information which is too often isolated in local, departmental data and document silos, negatively affecting regulatory and operational compliance, strategic planning, innovation, timelines and productivity.
Smaller companies face similar challenges at a smaller scale. Many feel the problems acutely at particular inflection points – an expanding product portfolio, submission deadlines, or geographic expansion. They then recognize that the scope of the regulatory information management challenge has expanded exponentially at a time when there is no bandwidth by key personal to put new processes and systems in place.
New Approaches to Regulatory Management
Regulatory strategists and operations professionals alike can benefit from an information management approach that integrates comprehensive global regulatory information into a single, role-based view. Life science companies that maximize and leverage organizational information across all operations, including R&D, submissions, labeling and marketing, gain a strategic advantage. Achieving this, however, is a tall order.
What is needed is a transformative, regulatory information management system that helps RPs better track and manage complex global regulatory data and processes including correspondence, commitments, approvals and management. This can help the RP better plan, coordinate and execute their regulatory activities and achieve superior compliance. What should RPs look for in such a system?
Key regulatory information should be gathered and presented in roles-oriented (e.g. Executive, Regulatory, CMC, etc.) dashboards through an intuitive web based system. The system brings together data used to plan regulatory activities, including commitments, filing plans and milestones, to operational information, including, correspondence, regulatory timelines, contacts, licenses, reporting, product partners, maintenance and CMC changes.
Each activity is tracked and managed. With commitments, for example, the RP can monitor all obligations to health authorities and be notified of upcoming requirements. RPs should expect a filing plan management ability for submissions from inception to end. This includes creating the initial plan, gathering required submission data from multiple sources, and tracking output and registration. By coordinating multiple contributors in a timely way in the workflow, filing plan functionality can eliminate the need to constantly monitor submissions. RPs resources can be deployed to more value added activities with such efficiency gains.
Benefits of Holistic Approach
An actionable dashboard can provide transparency on the status of regulatory activities and intuitive information access for the entire drug portfolio. This is useful considering that RPs source data and coordinate activities across multiple departments including Regulatory Affairs, R&D, Supply, Commercial, and others. It is also helpful for preparing for inspections and audits or facilitating partnerships. The “one source of truth” platform provides the regulatory professional with one click intelligence from any location for audits and inspections from regulators. CAPAs, follow-ups, fines, and wasting money on redoing work is greatly reduced.
User-specific dashboards should, at a minimum, track the relationships between relevant correspondences, commitments, and submissions all in one system and view. This will ensure users at different levels and with differing responsibilities can be empowered with the information needed to stay on course daily while pushing forward with improvements to enhance compliance, productivity and competitiveness.
A view into a regulatory information management system dashboard, showing the regulatory timeline and related submissions for a given drug. Drill down capabilities provide detail for each entry.
In an example of improving global regulatory practices, one top global life science company instituted an international regulatory information management system to support more than 1,000 users in 80 countries. The system tracks global product submissions, contacts, commitments, milestones, registrations and on-going maintenance submissions. This standardizes global regulatory processes and provides executives with timely reporting. The system allows multiple contributors to work in parallel on content creation and review, providing more real-time collaboration. Among the benefits gained were reduction in redundant data entry, including time spent duplicating information in local trackers, and reduction (or elimination) of time required to respond to redundant queries from regional hubs.
The productivity gains from this technology often support increased numbers of submissions with the current regulatory affairs department headcount. The regulatory information management system can also support other divisions’ compliance (e.g. commercial product release); provide global shared transparency on upcoming regulatory activities without contacting all involved parties up front; and reduce the number and complexity of SOPs to manage compliance.
Portfolio planning also becomes much easier to do. RPs are bombarded with questions and research requests from the commercial and manufacturing sides of the company: What has been approved where, indications, commitments, etc. Whether you have 50 markets with hundreds of products, or two products in one country but a small RP staff, these requests scale to become hugely complex without a RIM system. An integrated and single platform view into regulatory and clinical data gives RPs a single, global “source” of the truth.
Content Management Helps Regulatory Authoring and Publishing
RPs repurpose, rewrite, track and manage thousands of documents for regulatory purposes every quarter. These documents become key corporate assets used across the enterprise. In light of these immense authoring, publishing, tracking and management needs, the next big advance in improving compliance while reducing cycle times and costs is the integration of source content for regulatory authoring and publishing.
To achieve this, some companies are exploring technology to deconstruct documents behind the scenes so that the core pieces of information in them can be tracked and reused. New documents are then written, often in a semi-automated fashion, in large part through the assembly of already created and approved content.
Some life science companies have attempted, unsuccessfully, to do so with electronic document management systems. These are an electronic substitution for paper counterparts. The basic problem with document management technology is that the content resides locked in the document itself, with no interconnecting network of core data or rules across the enterprise. Thus the value of the content is limited and it becomes easily lost and difficult to update.
Alternatively, a structured content management system addresses these limitation by organizing all content in documents in data components, each granularly identified, catalogued, and stored in the content library for reuse, tracking, traceability, and regular updates. This type of system enables productivity and quality gains through the reuse of core data paired with the application of specific reporting templates and business rules.
The life sciences industry is particularly well suited to marrying structured content management and regulatory information management. The development of just one drug typically generates thousands of documents comprising millions of pages. Significantly, the level of data reuse among documents is quite high – up to two-thirds of data is reused, according to an industry study at Novartis. In this study, component reuse across pre-clinical and clinical study content was analyzed. Seven documents types were examined: Pharmacokinetic Studies, Toxicology Protocols (TP), Toxicology Reports (TR), Protocol Synopses (SP), Investigators Brochures (IB), Clinical Trial Protocols (CTP), and Clinical Study Reports (CSR). The end result of this “information lifecycle” analysis was that typically up to two-thirds of data was reused across documents. (Please see the accompanying graph chart.)
This graph shows the percentage of re-used data in a given document type. The yellow bars represent reused data, while the red bars represent unique data.
Many types of information, such as a Study Objective, have a lifecycle well beyond a simple link to one or two documents. In fact, some information segments persist for many generations of document cycles and have life-spans which can be up to a decade in length. Examples can be found where information is created back in the discovery phase and persists well into Phase III and IV Clinical Trials. By reusing content, companies can dramatically reduce time to market by compressing document cycle times while improving document quality and speeding up regulatory interactions.
Value of Structured Content Approach
While many groups in the enterprise derive benefit from a structured content approach, RPs get significant value from it. First, they able to easily find and leverage company content, for example quickly building a regulatory submission document on-demand from a searchable library of core data components. Perhaps even more importantly, they also know the full pedigree of the information, thus helping to ensure that the “correct” information is being used. The information is fully traceable from final form back to its source, with all subsequent edits, reviews, comments and uses known.
An additional capability is the ability to change and validate a single document template and apply the changes to hundreds of documents. These capabilities ensure that the correct data is incorporated into the response, all submission requirements are met, electronic sign-offs are present, and the latest regulatory rules are fulfilled.
Done correctly, a life science company can set an underlying architecture required to support what will amount to millions of information segments in hundreds of thousands of regulatory documents to be created in the coming years. In an example of this, a Director of Regulatory Affairs at a life science company cited the re-usable content approach for saving his company time and money. The key to this strategy is the fact that all standards are coupled to form a continuum from content creation to use. For example, if the content is migrated to the eStability standard, it could potentially be reused in the Drug-Listing Data section of a SPL label (which in turn can be reused in both Module 1 and 3 of the CTD). Similarly, for global labeling concepts, core data sheet content is reused in SPL for U.S. labels and for labels across different European markets. Any changes in source content can be absorbed by the downstream consumers, thus resulting in significant cost savings from having to constantly change multiple content instantiations individually in light of upstream source changes.
Structured content management can help the regulatory professional respond to sudden events. For example, a large U.S. pharmaceutical company faced an emerging SAE (severe adverse event) for a new drug under development. Drawing from the core data component library, the RP auto-generated the required common forms necessary to respond to multiple regulatory authorities simultaneously. The system included only those variables and parameters that were appropriate to the specific drug, and ensured that all necessary data was present prior to submission. If clinical and regulatory data is managed in a structured content management system, then an RP can leverage these data components to automate creation of any plans for different phases of study in different countries.
In conclusion, a life science company taking a more sophisticated regulatory information management approach can better manage and automate the complex regulatory and content requirements of the drug product life cycle, leading to faster market penetration at lower cost.
About the Author
Dr. Satish Tadikonda is a 25-year life sciences industry veteran and has published and presented more than 30 articles in peer-reviewed journals and international conferences on topics in global labeling, medical imaging, clinical trial data management/disclosure, and technology in the life sciences. He is CEO/Founder of Virtify, Inc., an information management solution company for life sciences. Prior to Virtify, Dr. Tadikonda was the founder of Tribiosys, Inc., and CEO of Enmed, a clinical trial and data management systems company. Dr. Tadikonda holds a Doctorate in Electrical and Computer Engineering from the University of Iowa, and a Bachelor of Technology in Electrical and Electronics Engineering from Birla Institute of Technology and Science, India.