A more efficient approach to regulatory maintenance of marketed products

White paper The Hub & Spoke model: A more efficient approach to regulatory maintenance of marketed products Redeploy regulatory assets to profit drivers Peter Lassoff, PharmD, Vice President and Head of Global Regulatory Affairs, Quintiles Executive summary Managing the maintenance of marketed products on a global scale is an increasingly complex and costly endeavor. Ensure compliance and quality by leveraging technology Even the largest companies are investigating ways to streamline operational infrastructure, yet they need people on the ground to deal with licensing, variations, renewals, label updates and other tasks that are required to maintain the regulatory status of their product portfolio. This is particularly challenging in Europe, where fragmentation of markets means they may need to maintain multiple teams across the wider region (East and West). But now they have another option.

Executive summary (continued) Quintiles Hub and Spoke model provides a cost-effective solution to these regulatory pressures by focusing on integrated solutions, optimized processes, flexible technology and a blended resource model that drives value while minimizing cost and variability in the parent organization. Through this strategic partnership model, Quintiles takes responsibility for all of a company s global regulatory administration needs, enabling them to minimize remote staff and related infrastructure, while creating a more sustainable system for information management that efficiently and transparently accommodates their regulatory requirements worldwide. This paper outlines how the Hub and Spoke model for regulatory management helps companies reduce overhead, cut costs and achieve greater oversight of their global regulatory affairs. 2 www.quintiles.com

Introduction We believe one of the most effective strategies biopharma companies use to reduce costs is outsourcing non-value driven tasks to industry partners who can deliver them with greater agility, lower costs and increased consistency. The decision to outsource makes the most sense, we believe, when it enables these companies to reduce investment in fixed human and capital resources, while tapping into the depth and breadth of expertise they need. Nowhere is that business case more evident than in dealing with maintenance of marketed products. Regulatory affairs work requires localization, which translates to employees, offices and other overhead in markets in which a biopharma company sells its products. Despite harmonization efforts, such as The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), the regulatory agencies in target markets still retain a largely regional and country specific focus. It is important to have, for example, high-level Food and Drug Administration (FDA) experts located in the U.S., and there are similar scenarios in Western and Eastern Europe, Latin America, Asia Pacific and elsewhere. Regulatory affairs work requires localization, which translates to employees, offices and other overhead... but there is little added strategic value associated with the work. This means that biopharma companies need to maintain teams in these locales whose jobs involve filing paperwork, reviewing labels and renewing licenses on established drugs. These regulatory tasks are mandatory, but we think there is little added strategic value associated with the work. These regulatory tasks do not improve sales, add efficiencies, or impact the top or bottom line in any significant way in our opinion. They also do not tap into unique corporate skill sets or knowledge capital which is why they are ideal for outsourcing. Quintiles Global Regulatory Affairs (GRA) division has created a scalable, sustainable framework, called the Hub and Spoke model, to conduct these regulatory steps for clients. This adds transparency, efficiency, and standardization to the process while providing greater insight and control over localized regulatory decisionmaking. Through this model, clients are able to tap into Quintiles extensive global talent, infrastructure, technology and regulatory expertise to oversee their regulatory tasks worldwide. One of the unique value propositions of this model is that Quintiles can transition much of the regulatory work to places where it can be conducted more efficiently, with greater economies of scale and to the same high quality standards required. Those benefits and local knowledge are then translated to Quintiles clients, who are able to eliminate or shift fixed-assets while still allowing older cash cow products to fund newer developmental products. How it works Using the model of regional hubs, the Quintiles team provides biopharma companies with a more effective way of handling maintenance work for marketed products. Instead of having dedicated regulatory personnel in each country, regional hubs are used (e.g. Argentina for Latin America). These hubs are responsible for tailoring the regulatory dossier/file for regional acceptability in terms of language and content. Actual submission of the filings are completed directly from the regional hub or, where required, from within the country itself as a postbox/mailbox service. The regional hub approach avoids the need for most individual country work. Instead, work on the core dossier for each product is largely conducted in an off-shored site (Quintiles uses India), where the basic file is produced and published. This is then available electronically through the use of a Records Information Management (RIM) system with secure portals for each hub to tailor for their specific markets/countries. This solution potentially eliminates biopharma companies need for whole layers of in-country personnel who traditionally take core dossiers and tailor them for each country. It also adds a higher level of transparency, 3 www.quintiles.com

compliance and control over regulatory submissions through the use of a centralized data management system and standardized processes, combined with a RIM system. The Hub and Spoke model is fully scalable even for very large projects. Technology as enabler Modern RIM systems and associated information technologies, such as structured content management (SCM), enable sponsors to derive the full benefit of the Hub and Spoke model. The RIM system, as the single source of truth, provides accurate and reliable information about all regulatory activities. Fortunately, past challenges to populating the RIM system with definitive information have been overcome by best in class innovations in RIM technology. This has come about as a result of improvements to direct information capture and intelligent integration, as well as advances in usability and ease of access and deployment. These systems facilitate coordination and collaboration between the sponsor and Quintiles, to simplify and make the regulatory affairs process more efficient. For example, the strategy and specific regulatory tasks for outsourced activities can be viewed within the system, and input that leverages the specific knowledge of each party is then captured and tracked. These updates are subsequently readily available to the team carrying out the work. Thus, the technology serves as a powerful tool, used to guide the execution and tracking of those tasks. In other models, where types of activities in a geography are not outsourced in total but rather Quintiles is augmenting in-house capacity, the RIM is essential to coordinating a smooth ramping up and down of work to Quintiles. The regional hub approach potentially eliminates biopharma companies need for whole layers of incountry personnel. RIM technology also enables the sponsor to further leverage the scale benefit of the Quintiles Hub and Spoke model. Not only is the sponsor accessing the hard regulatory intelligence about current local regulations, processes, and the like, but it benefits from the soft intelligence the RIM system harvests from the high volume of work Quintiles is conducting in each country. Such intelligence has a direct positive impact on efficiency and cycle times. Where RIM technology is enhanced by SCM technology, applied to such activities as submission document writing, labeling, routine submissions and similar, additional significant benefits accrue to the sponsor. Finally, by providing the sponsor views into workflows, dashboards, reporting tools and other RIM management tools, sponsors and Quintiles can easily be on the same page about all outsourced activities. 2,000 applications in six months Recently, Quintiles took over the regulatory work for an international pharma organization, providing global maintenance support for the company s portfolio of multi-therapy products. Through the partnership, Quintiles took full responsibility for all regulatory submissions, including variations, renewals, line extensions and roll-out dossiers/ndas in new markets. The Quintiles team provided regulatory intelligence, centralized management of publishing tasks in India and support for all regulatory requirements in regional hubs. To validate the benefits of the partnership, the project team tracked key performance indicators (KPIs), which demonstrated increases in volume processing, reduced cycle times across every stages of the regulatory process, increased productivity, with no submissions failing to clear the validation phase. Within six months the project team completed 2,000 regulatory applications. During that time, all of the company s dossiers were updated to current registration standards, continuance of products in these markets was approved, MAs were maintained in all countries, and Quintiles successfully represented the company in Health Authority negotiations and local market support. This is just one example of how biopharma companies are achieving higher levels of efficiency through this innovative regulatory approach. Since rolling out the Hub and Spoke model, we have seen a large upturn 4 www.quintiles.com

in clients asking for Quintiles to handle their maintenance work for marketed products globally, whether as standalone regulatory work or combined with pharmacovigilance/safety activities. Some projects involve new submissions in global markets as well as maintenance. Conclusion One of the primary reasons biopharma companies choose Quintiles to support their regulatory needs is that we offer a unique combination of skills, infrastructure and deep industry experience. Quintiles has a strong strategic regulatory presence with true expertise in the markets of interest to biopharma companies, aligned with processing staff in off-shored regions. Moving forward, we are increasing our infrastructure in India while continuing to build our regional hubs to add further value to these companies. Biopharma companies are able to reduce overhead and redirect their assets into more profit-driving projects that will enhance their product portfolio and add value to the bottom-line. This is the obvious next step toward a more agile and flexible biopharma business model. By relying on a trusted partner like Quintiles to manage these regulatory maintenance steps more efficiently, biopharma companies are able to reduce overhead and redirect their assets into more profit-driving projects that will enhance their product portfolio and add value to the bottom-line. Lessons learned: Getting the most value from the Hub and Spoke model As with all collaborative outsourcing relationships, biopharma companies achieve the greatest benefits from the Hub and Spoke model when they are willing to operationalize the transition, and address the concerns that often exist in their current regulatory submission process. Many global biopharma companies today have decentralized regulatory offices, where localized staff report to country leaders rather than to global regulatory affairs headquarters office. This fragmented approach means the regulatory affairs group can lack control and clarity over what local teams are doing, which potentially puts the organization at risk. Country fiefdoms will often have different priorities for regulatory work than headquarter functions, and in many countries the label (especially indications) can be tailored for country-specific requirements without the knowledge and buy-in of the headquarters function. Shifting to the Hub and Spoke model enables companies to gain control and consistency over in-country regulatory transactions. This drives improved efficiencies, reduces the risk of errors, increases the likelihood of approval ratings and leads to better relationships with local regulatory stakeholders. Some companies take things a step further and centralize their regulatory structure. When localized regulatory teams report to country leaders, the corporate office has little control over their performance, which can add risk to the regulatory process, and makes it difficult to implement a standardized approach and ensure compliance. It can also make it difficult to outsource maintenance work, as this can cause local teams to fear for their jobs and create unnecessary obstacles to the change management process. Therefore, some companies have taken the major step of changing the functional reporting structure to have all regulatory personnel report to headquarters instead of to local operating companies. This important but difficult change facilitates maintenance work and simplifies working with our Hub and Spoke model. We have found the following very useful in terms of lessons learned: 1. Don t forget the technology. A centralized regulatory information management (RIM) system with state of the art reporting and translation tools is important to the success of large-scale global regulatory affairs models. Yet, in many cases, localized teams rely on spreadsheets or multiple nonintegrated legacy systems that are less efficient to track and manage regulatory submission efforts. This can lead to missed deadlines and potential compliance and even legal issues when errors are inadvertently allowed to move through the system unchecked. continued on page 6 5 www.quintiles.com

To achieve the greatest ROI from the regulatory outsourcing process, biopharma companies should consider upgrading to a single integrated regulatory information management system. These systems drive improved productivity and reduce compliance risks by providing the corporate regulatory affairs office with a single portal through which to track every submission, label change, license deadline, compliance step and other regulatory tasks around the globe. 2. Don t add steps eliminate them. Giving up control over regulatory efforts can be a difficult change for many organizations. In response, some leaders feel compelled to create extra oversight steps. This duplication is unnecessary and can stymie productivity. Instead, take time up front to get to know the outsourced team, and then establish reporting expectations and KPIs to measure their progress. These measures may be aligned with improved volume processing, reduced cycle times, productivity gains and/or percentage of submission clearing the validation stage. Creating a formal governance process and measurable outcomes will give your regulatory group the confidence that the outsourcing team is meeting its goals without adding unnecessary oversight steps to the process. 3. Build in sufficient ramp-up but don t be tempted to go with a pilot project. With many outsourcing engagements, pilot projects are used to test the processes involved in the engagement. This works well for projects that can effectively be broken into small chunks, but it is not an applicable model for a volume approach to global regulatory affairs. Pilot projects in this realm do not allow the outsource team to adequately resource the engagement, and often forces them to rely on staff who are not completely dedicated to the project. Without long-term commitment, pilots often lack the financial or staff support within the customer and the change management necessary to deliver desired results, which can skew outcomes and instigate failure. To succeed, this level of transformation requires adequate time and resources to generate the substantial benefits you seek. Attempting to shorten this process will only reduce your likelihood of success. To make the most of the investment, dedicate at least three months ramp-up time to establish clear goals, define custom processes, and hire resources to fully support the program, then make a three-plus year commitment to generating results. 4. Have a customer champion. To get the most value and efficiency from this model, it needs a leadership-level champion who can drive through transformational change and bring the team along. These change agents will determine the success of these programs. 5. Trust, teamwork and support are keys to success. Everyone, from regulatory leadership down to front-line regional workers, needs to be on board with the transformation process for it to work. As with any change management effort, it can be painful, and those whose jobs are most affected will most likely be the hardest to bring on board. To avoid pushback and misinformation, be honest with local teams about what is happening, and base evaluations of progress on measurable KPIs and regulatory progress. Although satisfaction surveys can extremely useful, note that these can be skewed by those whose interests aren t served by the transformation. When you treat your outsourcing team as a partner and invest time and resources into making the transformation work, it will drive financial and operational benefits and deliver measurable value to your organization. 6 www.quintiles.com

About the author Peter Lassoff, PharmD Vice President and Head of Global Regulatory Affairs, Quintiles Peter Lassoff works with global clients in the pharmaceutical, medical device, cosmetic, nutrition and other industries on regulatory strategy and implementation to ensure their products are placed on the market in the fastest, least expensive manner. Dr. Lassoff has deep expertise in the development and worldwide registration of medicinal products, biotech products, borderline products, medical devices, cosmetics and cosmeceuticals, nutritional supplements and other regulated healthcare products. He has registered hundreds of products in Europe, the United States and global markets, including joint NDA/Centralised EMA submissions. He provides regulatory strategies for the development of products for global markets from preclinical to post-marketing as well as expert regulatory due diligence services for companies purchasing products or companies. Dr. Lassoff has worked in the pharmaceutical industry for 30 years. Prior to joining Quintiles, he held other leadership positions in the CRO field, and has held previous positions at BMS, ConvaTec and Stiefel. Dr. Lassoff holds a Doctor of Pharmacy (PharmD) from the University of Southern California School of Pharmacy. 7 www.quintiles.com