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Mitigating Regulatory Risk for a Global Product Launch

By Kristin Brooks, Contract Pharma | November 22, 2016

Addressing the critical regulatory challenges life science companies face in today's market

As regulatory standards evolve, it can be difficult for life science companies to keep track of and satisfy requirements for various countries, and failing to do so can critically impact a drug’s launch timeline and costs. 
According to BDO’s Life Science Risk Factor Report, the changing global regulatory landscape is a particular challenge for life science companies, with 97% citing FDA regulatory approvals and compliance as a risk. 
Contract Pharma recently spoke with Paul Bridges, corporate vice president and worldwide head of PAREXEL Consulting, about how companies can manage the regulatory risks of a global product launch. –KB
Contract Pharma: What are the critical regulatory challenges life science companies face today?
Paul Bridges: To be successful today, drug developers must integrate clinical, regulatory and reimbursement strategies from an early stage, and that’s a daunting challenge. Developers need to create a coherent value proposition for initial regulatory filings, and they should refine that value story continually, engaging regulatory authorities early on to pressure-test it at every phase of development.
Regulators are expanding their requirements for product quality data. They expect companies to develop systems that can monitor production, quality assurance, equipment, and facilities. They are also raising the standards for data integrity (DI); agencies, including the FDA, the EMA, and WHO, produced a torrent of new DI guidance for the industry in 2016. Companies that aren’t ready could face investigations, product recalls, reputational damage and more.
Finally, the general shift of product portfolios toward unmet needs means companies are focused on diseases that affect smaller patient populations. Nearly half of all novel drugs approved by the FDA in 2015 were orphan drugs. To maximize market penetration, sponsors need speedy global regulatory submissions and approvals. They must also ensure that a product’s label is consistent across the globe. A patchwork of different labels in various regions can undermine a product’s value story and impair a sponsor’s ability to support and maintain reimbursement and access activities.
CP: How can companies mitigate regulatory risks and challenges?
PB: You have to start with an adaptable plan and a centralized team, one that can respond quickly to different regulatory authorities. A single, centralized regulatory operations team can ensure the consistency of approvals worldwide, and create and sustain a consistent product value story across all the country product dossiers.
Also, you need a grasp of the regulatory and market nuances in every country. That can be easier said than done, especially for smaller firms that may lack experience or expertise. For example, many countries have early access programs that allow patients to start treatment before registration. The specifics vary from country to country and sponsors need to know when to utilize them.
You also need a competent nuts-and-bolts operation. Submitting applications to and fielding questions from multiple regulatory agencies around the globe is a vast undertaking. Responses need to contain the right information, communicated in a consistent manner, and be delivered on time.
CP: How can life science companies address growing global regulatory complexities and compliance demands?
PB: Despite efforts at international harmonization, drug developers must still navigate a global regulatory and reimbursement environment that’s relatively fragmented. This challenge can be exacerbated by internal fragmentation. Clinical, regulatory and market/patient access teams frequently don’t talk with each other. Or, if they do, the conversations happen too late. To navigate a complex, fast-changing regulatory environment, you need alignment of clinical, regulatory and market/patient access teams from early in the development process.
Early engagement with regulators, payers and patients can also help companies reduce their risks by achieving consensus on the basic science, clinical endpoints and patient populations that will work for both registration and reimbursement.
Equally if not more important, an enterprise-wide commitment to data quality—organized around the proper collection, analysis and application of meaningful metrics maintained by systems and procedures that safeguard the integrity of data—is the only way to achieve regulatory compliance. Regulators today are making it crystal clear how important they believe actionable quality metrics are. Some companies are improving their data systems and quality metrics not only for the sake of compliance but to gain competitive advantage.
CP: What are the benefits and risks associated with pursuing accelerated pathways?
PB: Accelerated pathways [APs] have allowed patients faster access to new medicines than ever before. And these pathways have allowed companies to gain significant commercial advantages, including shorter clinical development and regulatory review times, widespread coverage by payers, premium prices, and rapid uptake, especially where patient benefits are supported by strong evidence (for example, hepatitis C and immuno-oncology).
Using APs has become routine among drug developers; two-thirds of novel drugs now qualify for them in the United States. But companies that launch products with less clinical data due to streamlined development face significant risks. For one thing, the level of evidence needed for FDA/EMA approval may be different than what payers would like to see to demonstrate value to patients and economic value to the healthcare system. To manage the high cost of many AP drugs, some payers are imposing formulary and other restrictions on new products. They are also modifying high initial prices and coverage decisions if post-approval real world evidence does not support the initial value proposition.

Successfully mitigating the risks of APs requires companies to establish greater integration between regulatory and commercial groups; ever-earlier and more data-driven decision-making about the value of new products, and post-launch studies that demonstrate long-term value and track safety.
CP: How are the regulatory challenges that a small company faces different than those of a large company?
PB: All developers face rising regulatory requirements and market access hurdles, but emerging companies have narrower margins for error because they begin with fewer financial, technological and scientific resources. Often lacking global reach or deep regional expertise, they must husband what they have if they are to survive. But small companies also have advantages.
For example, when developing a global regulatory submissions strategy, large companies often have a set headcount, based on hard-to-change full time equivalent (FTE) budgets (approved years prior to any specific drug submission). For this reason, overhead and infrastructure tend to dictate the submission plan. But because small companies are not slaves to tradition, and have not developed rigid organizational cultures, they can be more flexible in planning and executing submissions strategies than larger companies—a definite plus.
CP: Are there different ways to prepare for the regulatory process depending on the size of the company?
PB: Emerging companies can turn their smaller size into a strategic advantage. Concentrating on science, filling in expertise and resource gaps from outside when they need them, and being flexible are all tactics that may be harder for their big pharma counterparts to match.
For example, one mid-sized biotech company with an orphan drug recently ran into unforeseen delays in its original Asia and Pacific plan. In order to avoid downtime for its regulatory team members, the company filed for approval in Malaysia six months ahead of schedule and won an early agency approval.

For larger companies, one solution might be to set up a team outside the conventional organization, staffed with insiders who can work in a flexible and fast-moving environment, and supplement them with external people who can work the same way. Some companies may need a CRO partner with a scalable global footprint, independent of the prevailing corporate culture. Other companies may be able to create the right environment in-house.

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