Once a biotech or pharmaceutical company defines their product development objectives including business strategy, global filing objectives, and program plans to reach key milestones in the drug development lifecycle, they must focus on designing the timeline to propel the program forward.
There is a lot to unpack. For example:
Once the strategy is outlined and the timeline is established, pushback from internal stakeholders often arise. Common questions often asked include:
This got me thinking of the ideal timeline – the critical roadmap where all the essential deliverables are fused together to keep a company focused on their mission as quickly as possible – and one that is appropriate for companies regardless of size.
Based on my experience, here is my point of view on timeline basics and responses to common questions asked.
Timeline Basics
Timeline Components
Timeline Types
Timeline Creation
Understanding the components, types, and the process of the development objectives helps to put things in perspective to address the common questions asked by companies.
Q: Why does this take so long? And is this timeline inflated to include potential issues?
A: When the timeline is mapped out to review a document, such as a Type B Pre-IND meeting package, time to draft, review, address comments, repeat this cycle twice, quality control review, finalize, approve, and prepare for submission is taken into consideration. These steps take time, and most often, there may be late-breaking information that can change the trajectory of the timelines. In addition, there is a human prediction component to the timelines since the internal Subject Matter Experts are estimating how long it will take to run a preclinical experiment, manufacture drug substance or drug product, and clinical study start up and enrollment based upon their previous experience, competitors doing similar studies, and/or how long it takes to run the lab experiments.
However, a development timeline must be balanced with the timelines required by various vendors to execute a particular task. Since there are various stakeholders involved in all of the tasks, this all adds additional levels of complexity.
Q: Shouldn’t we be able to develop faster because we are a small, nimble company?
A: There is a perception that in a larger organization there are multiple levels of review, and a longer runway to align on key decisions due to an escalation process or sign off involved many individuals. However, large organizations have established processes, ready-made templates, and an army of resources who are experts. For smaller biotech companies with less than 100 people or even less than 20 people, there are issues with pipeline prioritization, people wearing multiple hats in terms of responsibility, and the various levels of experience that span from never having filed an NDA, to those who have done it multiple times.
In theory, a small company may be able to create a faster timeline, however, there are roadblocks or considerations that need to be analyzed to see if activities can be accelerated. Sometimes, companies are waiting for the in-life data of a Good Laboratory Practice (GLP) tox study, waiting for a certain number of responses to produce the desired safety or efficacy profile, waiting for manufacture of a drug product since the Phase 1 site may not be able to scale up for Phase 2 or Phase 3 registrational batches, or FDA review times for specific Type A, B, C, or D meetings. There are certain tasks that may be fixed and other areas that may be accelerated. Critically assessing these risks is a key part of establishing a realistic timeline.
Q: What can we do to accelerate the timelines since we publicly announced reaching milestones by a certain date?
A: Some of the issues mainly stem from using so-called ‘industry standards.’ For example, there is a misperception that it should take three- or four-months from top-line pivotal data to file an NDA for smaller companies, but it takes, on average, six months. While this might be true if the indication is an ultra-rare disease, I would like to challenge this idea.
The reason why is because the duration can be dependent on the indication type, number of clinical studies in the development program, FDA feedback that may require a change in strategy, or late breaking or ad hoc data that prevents clinical summaries from being completed against original timelines.
I suggest understanding if acceleration can (and should) happen alongside building the critical path towards a particular goal. The critical path is defined as the longest path to get to the goal such that if an activity moves out by one day, the overall major goal moves out by one day. Creating and analyzing the critical path can help companies understand which tasks can truly be accelerated. I highly recommend not publicly announcing a specific date for a target goal until the detailed timeline has been verified by the Subject Matter Experts and there is dedicated time to ensure the timeline has been properly discussed with the program or core team. Involvement by the team helps before committing to a goal that might be missed or changed.
While a timeline may be accelerated depending on the task or milestone, I recommend dedicating time with the team to develop, validate, and pressure test assumptions. One would not write a clinical overview without the clinical summary or write a clinical summary without the source clinical study report. As such, it starts with the source, and in this case, that is the functional leads.
In summary, it’s critical to understand that a timeline builds from the source because if the detailed project plans are accurate, they roll up nicely to produce a Gantt chart visual, then roll up again for the key milestones, and finally compile together for an all-encompassing dashboard. Then the next step is to establish a timeline analysis by evaluating the critical path, seeing which tasks can be done in parallel or sequentially, or if activities may be accelerated with more incentives or additional resources.
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