To get new products to market faster, pharmaceutical companies are increasingly looking to their regulatory submissions not only for opportunities for improvement but also as a focus area for strategic capability building. A submission is a multidisciplinary endeavor, and it requires careful orchestration across R&D and commercial functions over the year—or longer—that it takes to develop a filing strategy and prepare the dossier for a regulatory agency.
We define submission excellence as the ability to prepare, in industry-leading time frames, high-quality regulatory submissions that accurately represent relevant data and maximize the likelihood of first-cycle approval with a favorable label for a medical product. Submission excellence can bring benefits for patients and companies alike: the ability to launch products more quickly can shorten waiting times for life-enhancing therapies, yield more days of peak sales, and simplify and streamline an organization’s ways of working.
The value of being first to market has been thrown into sharp relief by the COVID-19 pandemic (see sidebar, “Estimating the value at stake”). Organizations sprinting to develop vaccines and therapeutics have dedicated enormous resources to getting to market as quickly as possible. Those companies have demonstrated how effective collaboration with regulators can expedite the approval process and how coordination among internal teams can improve submission quality. Other pharma companies under pressure to accelerate submission timelines will be looking to those experiences for signals on what has gone well and any pitfalls to avoid.
This article looks at the benefits that submission excellence can bring, examines six areas that companies can focus on to achieve it, and suggests how to get started on optimizing the path to approval. By following the approach outlined here, some pharma companies have been able to reduce their timelines radically—from last patient, last visit (LPLV) to submission in as fast as 12 to 16 weeks (for their entire portfolios) rather than the more typical six to eight months (exhibit).
The goals and benefits of submission excellence
A shorter timeline to market is an important goal for companies pursuing submission excellence, but it isn’t the only one. Another key objective is to produce a high-quality dossier that improves the likelihood of regulatory approval for a medical product by succinctly articulating a scientific narrative that accurately reflects the product’s safety and efficacy. Yet another is to implement a consistent approach across a company’s whole portfolio to increase predictability and efficiency. Submission excellence also helps increase the chances that a product will receive its proposed label, thereby contributing to a robust strategy.
Within a pharma company, submission excellence delivers several additional benefits beyond those goals. Having every part of a multifunctional submission team moving in unison to deliver a shared global strategy helps surface risks early so that they can be addressed quickly. More timely and better-coordinated submissions can help clarify and align expectations, reducing last-minute churn and stress for the teams working on product filings. In turn, greater clarity on strategic priorities—which will involve deprioritizing some products—can reduce the strain on teams and help leaders keep their top talent focused on what matters most. For submissions related to life-cycle management or change control, improving efficiency can deliver substantial savings and enable an organization to redirect resources to high-priority novel assets.
Several upstream enablers, such as clinical-trial design and global regulatory strategy (including order of market entry), also play important roles in submissions excellence but fall outside the scope of this article because they take place outside the context of submission preparation. In addition, high-speed, high-quality submissions require meticulous coordination across clinical, nonclinical, and chemistry, manufacturing, and control (CMC) functions, but the approach described here focuses mainly on the critical path involving clinical and CMC work.
Six areas to target for impact
Leading pharma companies are already rethinking their submission process and starting to identify a mix of asset-level quick wins and portfolio-wide longer-term initiatives to help them get to market more quickly. Their experience suggests that there are six key areas to target in submission excellence.
Individually, each of the areas is fairly straightforward to address. However, achieving consistent excellence in submissions calls for action on all six fronts, as well as intense coordination across functions. With those elements in place, along with a flexible way of working suited to a pandemic-conscious world, organizations may be able to reduce their submission times to as few as 12 to 16 weeks portfolio-wide.
Present a compelling narrative
By developing a clear, concise storyboard that incorporates all relevant data without being overloaded with unnecessary detail, a pharma company can ensure that it presents the regulatory agency with a high-quality, user-friendly dossier to review. This approach also enables leaders to streamline and simplify the workloads of their submission teams. Each storyboard needs to be readily understandable by someone with a degree of technical expertise but no prior knowledge of the product’s development program.
Teams typically begin by developing a storyboard of the dossier to set the direction and then working through submessages on safety, efficacy, and risk–benefit assessment. As the storyboard takes shape, it needs to be agreed upon by a cross-functional leadership team and shared with functional subteams to ensure that they are fully aligned. When teams are compiling a submission before all the data are available, it can be helpful to sketch out scenarios to illustrate options under a range of expectations. For instance, some companies prewrite sections of clinical-summary documents based on high-potential scenarios to save valuable time on the critical path.
Streamline the dossier
Pharma-product submissions have expanded in size and scope over time. Biologics License Applications (BLAs) often run to more than ten million pages, creating huge workloads for teams and cluttered, hard-to-follow storylines for regulators. Trimming down what goes into the dossier and simplifying the presentation of key messages can reduce the burden for the teams preparing submissions and the agencies reviewing them.
Breaking down dossiers into modules is one way to streamline both the submissions themselves and the processes for creating them. By drawing on historical filings and expert perspectives, companies can develop a set of “minimum viable products”: reusable outlines or templates that illustrate what should be included in each module or section of the dossier, with variants tailored to specific therapeutic areas or new molecular or biological entities. Creating a library of standard dossier sections is a significant undertaking. But once the library is complete, it will provide teams with a stock of best-practice elements that they can populate with relevant data and refine as needed. That will save considerable time and resources from being expended on writing lengthy documents from scratch for each submission.
In one example, a company revaluated its analysis plan for patient-reported outcomes with its vendor. They determined that some analyses were critical for the core dossier and that others were focused on potential US Food and Drug Administration (FDA) follow-up requests. To accelerate the company’s submission preparation, it streamlined the first set of analyses delivered by the vendor. That allowed medical writing to start approximately five days earlier, while the vendor finished up the second batch of analyses in parallel.
Optimize submission processes
By adopting best practices, teams working on product submissions can speed up dossier production, avoid wasteful use of resources, and reduce errors. The key steps include simplifying processes, aligning on a project plan and timeline, making regular updates, and sharing details with all members of the submission team.
Defining cross-functional optimization of key processes to enable teams to brainstorm possible acceleration levers, such as challenging legacy processes to remove unnecessary steps, front-loading activities, adopting parallel processing in selected areas, and simplifying reviews, is critical to optimize filing timelines. Teams can decide which levers to target, how to apply them, and who is the owner (usually a regulatory-process or project manager) of each lever who will be responsible for determining how it is applied and tracking its impact on the timeline. To pursue speed without sacrificing quality, risk needs to be managed systematically and all trade-offs balanced appropriately.
Working together through agile sprints can help optimize processes. One submission-excellence team started by building an integrated baseline timeline. It then held “jam sessions” to ideate and prioritize acceleration levers, followed by focused small-group sprints to evaluate the impact and feasibility of each. From there, the team reconvened to map out a detailed process design.
Put capabilities in place
Today’s regulatory professionals for pharma and medical products need to be cross-functional leaders with broad experience in the relevant topics and effective communication and collaboration skills. Retaining people with the historical knowledge of an organization and its development programs can give companies a head start in crafting an effective narrative for the dossier. Having an individual recall why a particular decision was made can save an organization churning through years’ worth of documents. Similarly, it is an advantage to employ practitioners who are aware of past successes and failures and know how to get things done within an organization’s specific culture and dynamics.
Organizations naturally ensure that their teams have technical skills in fields such as regulatory science, statistics, and labeling. But as new modalities emerge and big data becomes more fundamental to development programs, the nature and number of core knowledge areas will increase. Given the intense competition for top regulatory talent, companies will need to build or enhance many capabilities by upskilling their current teams.
Given the intense competition for top regulatory talent, companies will need to build or enhance many capabilities by upskilling their current teams.
Companies have leveraged a wide range of resources to build submission-excellence capabilities. Empowered change champions for each function can serve as go-to experts for future submission teams. A central office can enable continuous improvement by owning and curating submission-excellence materials. Also, tools such as standard timelines and playbooks give teams an advantage for each new submission.
Take advantage of technology and automation
Although senior leaders at pharma companies often express interest in exploring tech- and automation-use cases in regulatory affairs, adoption has been slow to take off. In a benchmarking exercise involving 11 leading pharma companies, only two reported having implemented automated solutions to accelerate their submissions. The range of solutions available is wide and includes the following:
- packages for autogenerating data sets for tables, listings, and figures with standardized metadata
- automated drafting tools that can analyze the components of a study and generate a summary
- dashboards to inform safety and clinical reviews
- quality-control software that can validate terminology, ensure consistent formatting, and check graphics against source data
- tracking solutions that monitor progress across functions in real time
In addition to those targeted solutions, companies also have access to more transformative approaches, such as migrating to cloud-based solutions and adopting enterprise-wide, structured content-management tools. Many companies could pursue step-change improvements in productivity and submission quality by investing in core technology and infrastructure and, in some cases, placing thoughtful bets on automation solutions.
One way that technology can be applied to submissions is the auto-update and quality control of in-text tables, listings, and figures (TLF) against source data. Whenever changes are made to the underlying source tables, an automation bot uses the table-corresponding row and column titles to update in-text TLF accordingly. That helps reduce overall work hours, save time on the critical path, and improve data accuracy.
Treat regulatory agencies as thought partners
Working collaboratively with regulatory agencies in the time leading up to a product submission can expedite the approval process by months, as recently seen in the case of COVID-19 vaccines. Teams could, for instance, take advantage of milestone meetings to bring regulators along with them on innovations in rare diseases, new technology, and so on. They could also take active steps to elicit comments from agencies throughout the development process rather than waiting until the end of the review period for feedback. For the best results, teams can adopt a collaborative approach to agency interactions as part of their regular ways of working instead of relying on leadership to drive those conversations.
Pharma companies leverage several approaches when working with regulatory agencies. Some focus on strengthening a relationship with an FDA regulatory liaison (for example, a regulatory project manager) to communicate the submission plan, get clarification, and address any potential questions. Others rely more heavily on meetings prior to pre–New Drug Application (NDA) meetings (for example, Type C meetings to review a statistical analysis plan [SAP]). Both can help accelerate the submission process.
Starting out on the path to submissions excellence
Once a pharma organization has decided to focus on its submission process and practices, it needs to decide the best path forward. Companies should consider four main options:
- Undertake a holistic transformation of submissions across the entire portfolio. The company starts by identifying opportunities across all functions and activities in the submission process and then addresses them via agile sprints for process redesign, automation, and capability and mindset shifts. This approach calls for considerable effort and commitment from leadership, but it can also deliver the most impact and be sustainable over the long term.
- Adopt a cross-functional, asset-led approach. Like option one, this has the benefit of supporting full-team collaboration. But in this case, the transformation starts with a subset of assets rather than the whole portfolio. Processes are redesigned within the context of the assets, allowing leaders to develop multiple proofs of concept with various types of filings before they invest in embedding capabilities, tools, and lessons learned from the pilots into the broader portfolio. Once organizations have seen tangible impact from multiple pilot submissions, they are often much more enthusiastic about investing in scale-up.
When identifying suitable pilots, leaders may want to target assets with an expected filing in eight to 15 months’ time. That will give teams enough time to redesign the submission approach, optimize processes, and plan implementation before the countdown begins on the critical path. To improve the odds of success, teams can look at examples of acceleration from the past and identify any resource constraints that might hinder current efforts.
- Take a functional view and transform everything that falls within the remit of the regulatory organization. This approach will streamline regulatory processes. However, given the cross-functional nature of submissions, it is not likely to have a material impact on timelines. It could still represent a viable alternative to options one and two if other functional leaders are not heavily invested in pursuing submission excellence as a priority.
- Invest in one capability, such as automation, and deploy it across the pipeline of submissions. Since taking a single capability in isolation generates only a limited impact, teams should adopt this approach only if they believe the investment will deliver positive returns.
Option one or two is likely to be the best choice for most companies, and we have seen several organizations achieve successful outcomes with those approaches. However, if there are barriers to deploying them, option three or four may provide a good alternative starting point for an organization’s transformation journey.
A pharma company that can make a 12- to 16-week timeline (from LPLV to submission) its standard for regulatory submissions could capture tremendous value. As submission complexity and competitive intensity increase, investing in turning the approval process into a source of advantage offers the prospect of significant returns.