Stuart R. Gallant, MD, PhD
How A Drug Development Plan Originates
Keller and Schnell suggest that there are five challenges to a pharmaceutical startup: 1) gathering clinical evidence, 2) transforming data and features into a value proposition, 3) ensuring market access and sufficient funding, 4) designing a profit-optimal pricing and contracting scheme, and 5) preparing the launch and the sales organization [1]. But, adopting this time-linear paradigm, is both inaccurate to the startup’s method of working and imprisoning to the thought process of its founders.
A better way to think about a startup is by beginning with the value proposition. The management team engages with patients, families, healthcare providers, regulatory agencies, insurers, and others to understand what medical problem they are trying to solve. Everything about the drug development program flows from that initial engagement with stakeholders.
The drug development plan is the embodiment of what was learned from that engagement and also the mechanism which ensures alignment of all the efforts to realize the drug development goal. As such, it is a living document that adapts to the changing circumstances of the drug lifecycle.
Another way of saying the same thing is that a drug development plan doesn’t proceed as ”1-2-3-4-5”, it proceeds “1 then everything else together.” The plan starts with the value proposition and moves forward in parallel with the pre-clinical and clinical planning at the same time as the regulatory and marketing plans emerge and preparations are made for launch/exit.
In researching the value proposition (or the “drug concept”), the pharmaceutical company must engage with patients and families to understand their needs. Sometimes apparently small things have real value to patients (e.g., reducing the “pill burden” to cystic fibrosis patients). At the same time, the needs of healthcare providers must be considered (e.g., for medications with mild or minimal side effect profiles and low risk of toxicity). And, regulators of course want to see demonstration of safety and efficacy, even though demonstration of these characteristics may be difficult in orphan indications with small patient populations. Insurers want to understand the economics of the treatment and how paying for a new treatment won’t prevent them from paying for existing treatments (i.e., they don’t want a drug to break the bank). Also, insurers don’t want to look like the bad guys—denying life-saving treatments to patients. There are even internal stake holders at the pharmaceutical company—as companies start to consider lifetime monitoring of treated patients that may be required for some new gene therapy treatments.
What a Drug Development Plan Does
Once the drug concept has been vetted by the stakeholders, the drug development plan supports the drug concept in four ways:
- Communication: A pharmaceutical company contains many specialized departments (regulatory, pre-clinical, clinical, CMC, business development, finance, etc.). They often speak different languages and have different assumptions. For instance, the marketing team may have a plan for dosage form, storage condition, and shelf life. If the CMC team develops data that shows that the marketing team’s goals cannot be met, then that fact needs to be communicated back to marketing rapidly so that another plan can be developed.
- Decision making: The drug development plan facilitates decision making. Consider the case of a Phase 2a proof of concept study. By making the criteria of success explicit and relating them back to the value proposition of the drug, it becomes easier to make a Go/No Go decision following the return of data.
- Risk management: By listing out each element of the drug development plan and assessing it for risk, the program can be risk ranked and strategies for minimizing risk to the program can be devised. For instance, if improved efficacy compared to a competitor is essential for licensure, studies to demonstrate efficacy can be pushed forward (proof of concept studies) to reduce project risk.
- Investors and management needs: If investors see a clear plan and understand the risks, they are more likely to invest. Similarly, senior management is more likely to have confidence in the program.
Elements of the Drug Development Plan
The drug development plan is a document of hypnagogic complexity. For that reason, an outline is provided (rather than listing every bullet point in this post):
Some ideas to bear in mind as the drug development plan is prepared include:
- Engagement with stakeholders is critical. If the drug development team develops a clear idea of what drug they are trying to bring to market, many critical decisions will be much easier to address as the program proceeds. For instance, not a few development programs have proceeded to an unsuccessful Phase 3, when clear-eyed examination of the Phase 2 data (in light of the drug development plan) would have indicated a flawed drug concept. Using a well written drug development plan, a management team in that circumstance actually has two choices: 1) they can cut bait and return the remaining investment capital to the investors or 2) they can return to the stakeholders and reinvent the drug concept.
- The target product profile (TPP) serves as a starting point for discussions with regulatory agencies, but also as a starting point for the dialog with the pre-clinical, clinical, and CMC teams. Once those teams clearly understand the TPP, they have their “marching orders” to a great extent.
- The Risk Management plan is of great help both to the project manager and the management team. The project manager knows which elements of the Gantt require special focus, and the management team can monitor progress of the high-risk items and consider adding resources before risks become actual problems.
- The nonclinical plan is an important element of the project because nonclinical work provides the first indication if the drug concept has legs. Special attention should be paid to nonclinical work, and it is not uncommon to have even several false starts in the nonclinical work. Some dosage forms may be found to have poor bioavailability or stability, and the team may have to iterate on the drug concept before they get forward momentum. Nevertheless, taking time to get this stage right pays big dividends later. In the case of uncertainty regarding which of two dosage forms is superior, it is even possible to bring both forward into human Phase 1/2 to manage risk (typically staggering the lead and follow-on dosage form by six or nine months because of the large resources required by FIH trials).
- CMC is often rate limiting to filing of an IND but then has a lull in intensity prior to Phase 3. This pause should be used intelligently to address issues like: scalability of manufacturing technology, selection of manufacturing sites for commercial launch, and critically, planning a successful validation and Phase 3 manufacturing campaign.
In this writer’s experience, a drug development program usually proceeds smoothly, unless the drug development plan is not adequately prepared in advance. So, build your house on solid rock, not sand, and prepare a good drug development plan.
[1] Keller M. and Schnell G. “Marketing and Sales for LS Ventures Four Key Areas for Successfully Launching New Life Sciences Products,” in J. Becker und T.R. Villinger (Hrsg.), Life Science Venturing, DOI 10.1007/978-3-658-06382-5_6.
Disclaimer: PharmaTopoTM provides commentary on topics related to drugs. The content on this website does not constitute technical, medical, legal, or financial advice. Consult an appropriately skilled professional, such as an engineer, doctor, lawyer, or investment counselor, prior to undertaking any action related to the topics discussed on PharmaTopo.com.