“How can we submit sooner?” It’s long been the most common question a regulatory submissions team hears. Executive leaders have ambitious goals in mind for sound business reasons: beat the competition to market, retain investor confidence, and, of course, get life-enriching therapies to the patients who need them.
While aggressive deadlines might seem daunting, regulatory submissions teams would do well to embrace the mandate, work closely with leadership and other functions to weigh the risks, control what you can, and together set—and achieve—ambitious timelines.
This piece explores why to embrace the “submit sooner” mandate, how to work better with management and relevant functions, and considerations for accelerating regulatory submission timelines.
For specific ways different regulatory roles can work faster, as well as real-world examples of how they did so, download the complete article.
To many regulatory submissions teams, partnering with management will be a new way of working. But there are benefits to responding to a timeline challenge with creative solutions and a spirit of partnership.
The regulatory submissions team is in a unique position to bridge the gap between strategic goals and the realities of operations. On one hand, you can assist and encourage functional teams (clinical, nonclinical, CMC, etc.) to expedite their work. On the other hand, you can provide management with the information they need to make tough decisions about budgets, resources, and risks.
Of course, to help accelerate a timeline—and provide relevant information to management—a solid foundation must be in place. Outline all the requisite activities, interdependencies, and functional handoffs between deliverables. Clearly define roles and responsibilities. Identify and mitigate potential risks. And research and pursue opportunities like new regulatory pathways.
Once the foundation is in place, you can work with functional teams to identify how they can go faster and what they would need to be successful. Then, you can present those needs to executives, who make decisions based on the organization’s priorities, budget, and risk tolerance.
For instance, Integrated Project Management Company, Inc. (IPM) led an investigational new drug (IND) submission for a biotech startup. Collaborating with CMC, they decided they could begin studies sooner if they commissioned just 150g of the 400g drug substance needed for in vivo studies, then follow up with a second batch. Doing two batches cost more, but it reduced risk (if the initial study failed, they could have canceled the second). So, they were able to justify the investment to management.
On another project, IPM was working with a global biopharma company’s regulatory submissions team on a supplemental biologics license application (sBLA) with an aggressive deadline just six months after the BLA approval. The management team asked regulatory, “what do you need to make this happen?” Together, they decided to add several medical writers to the team. They also streamlined the document review process by getting executive feedback and buy in upfront to avoid changes late in the process. And they agreed to one- or two-day reviews rather than the usual week or more.
Each organization—and even submission—may require unique methods to accelerate the process. And each functional team likely can help. (For specific ways different functions can work faster, as well as real-world examples of how they did so, download the complete article.) If the teams work together, they’ll be more likely to come up with a goal and timeline that everyone can stand behind and ultimately achieve.
IPM has found there are several things cross-functional teams should consider as they are collaborating to accelerate regulatory submissions processes.
Competitive pressures and other market forces may require a faster submission. However, factors like other strategic priorities, particularly complex regulations, and limited competition may mean your customary timelines are good enough.
Your team may be working on multiple submissions. But every submission can’t be the most important. Management must provide guidance and back it up by investing the appropriate time, budget, and resources. And they may have to make the tough decisions to narrow the label scope, to target fewer market areas, or to suspend or postpone other submissions. Adding to teams’ work, rather than reassigning resources to the most important work, will dilute efforts and lead to burnout and possibly turnover.
IPM helped support a new drug application (NDA) for a biopharma company whose patient enrollment was delayed due to the war in Ukraine. When it was ready to begin a trial in a new market, its timeline encroached on another submission. The company chose to pursue both submissions, so it prioritized them over other programs to provide the required resources and worked with IPM’s program manager to identify ways to streamline the process.
Acceleration often means doing only what’s required and nothing more. But it’s easy to do too much. For example, scientists want to get the most from the data they receive, so they may ask for analyses that aren’t required for the submission. Called in to help an NDA get back on track, IPM found more than 70 unnecessary tables, listings, and figures (TLFs) in an appendix.
But to accelerate, you might consider a larger scope. For example, for a global strategy, identify which countries to submit to and in what order. Too often, organizations are overly focused on getting approval in the first country and miss the opportunity to produce a single dossier that supports multiple country submissions.
Be sure the submission scope aligns with the commercial strategy. IPM has seen instances where the trials and data supported dosing intervals that patients couldn’t meet (every 48 hours, though clinics aren’t always open on weekends, rather than three times a week) or modes that doctors didn’t want to administer (approved for intermuscular, but not intravenous).
And pursue opportunities to align with health authorities. While this might seem like an additional step, the Federal Drug Administration (FDA) and other agencies can clarify requirements. Leading a recent IND submission, IPM recommended that the company request an INTERACT (initial targeted engagement for regulatory advice on CBER products) meeting with the FDA. The intention was to learn if their nonclinical strategy was good enough going into the first in human study and to avoid extra work.
There are tradeoffs involved with any method of accelerating submissions timelines. It may just be an additional investment, such as manufacturing product at risk, running studies in parallel, hiring experienced resources, or adding clinical sites.
Using the FDA example above, you may identify a fast-track program to accelerate approval. The risks include that they typically require evidence of substantial benefits over existing treatments and post-market studies. In the dosing example, reducing the drug’s label may speed up approvals, but it will limit its market potential.
Even tactics that seem benign can have a negative impact. You may motivate a team to work through weekends and holidays to meet an ambitious deadline. But if they have to work above and beyond for every submission, they’ll burn out or leave. Running clinical trials in multiple countries not only costs more; you risk delays due to political instability (the war in Ukraine delayed hundreds of studies, for example). And there are ethical considerations around testing in countries where you don’t intend to market the drug.
When Covid-19 hit, nearly all clinical trials around the world stopped. But it doesn’t take a global pandemic to delay a submission. A CMO may be subject to a surprise audit. A shortage of animals may prevent safety testing. As noted above, an unexpected invasion of a sovereign country can halt clinical trials.
Leave room to adapt. For example, you might agree in advance that ad hoc decision-making meetings will be prioritized and that teams who encounter unexpected delays of more than seven days will report them immediately.
And always document assumptions. For instance, “The team assumes the FDA agrees to the proposed approach outlined during the pre-submission meeting.” Or, “We assume pivotal clinical study enrollment will be complete by the specified date.” When the unexpected occurs, you can point to these assumptions to explain the impact to the timeline.
Communicate often and openly. A dashboard can show both progress and complexity of the work. Sharing information helps teams to be ready for handoffs and management to be prepared to make decisions when problems occur.
Communication will also help to avoid changing priorities or scope revisions. Assuming you’ve asked for input early in the process and been keeping everyone in the loop, there should be no surprises or new ideas during reviews or approvals. If you’ve agreed to what “good” looks like and how long a person can review, you can hold each other accountable.
Every submission is unique, but there may be acceleration tactics that you can repeat or even make part of your regular process. If you track progress and take time for an objective review—and include your management partners—you’ll identify scalable improvements for future submissions.
You’ll also demonstrate your ability to align your efforts with the broader organizational goals, streamline regulatory submissions processes and decision-making, identify and mitigate risks, and help ensure compliance.
For specific ways different regulatory roles can accelerate submissions and real-world examples of how they did so, download the complete article.
Authors:
Susan Carino, FRAPS, MBA, MS, PMP, RAC, Principal Consultant
Rani Maloney, MBA, PMP, RAC, Senior Consultant
Integrated Project Management Company, Inc.
Services: Regulatory Submissions
Industries: Life Sciences