Development with the End in Mind – Overcoming Early-Phase Challenges

A drug must be safe and effective. Manufacturing of a drug product should consistently yield a predetermined quality. These are the undisputed goals for commercialization of a drug within our industry. Why do so many companies struggle in achieving these goals while following anticipated timelines?

Drug development from lab-bench to commercial production is a lengthy and costly process, that knows many challenges. These challenges can have many dimensions such as, impurity levels, scalability of physical processes, internal or external manufacturing, safety parameters, and cost of unit.

One of the causes for start-up failure is the highly regulated industry that often struggles to keep up with process development direction of the drug product versus the clinical development direction. The production process solidifies quickly during development and, in parallel, clinical development must remain open to options for different indications. But different indications could mean different volumes, different final products, different modes of administration, and maybe even different impurity levels.

High quality preparation is required to bring your case to the EMA or FDA. But how do you know, with resources being limited, where to focus. In this blog, we will explain this further to reduce the risk of failure of potential drug candidates, minimize financial risks, and accelerate development timeline.  

The Challenges in Drug Development Processes

So, what are the hurdles and challenges when it comes to early drug development and taking the product to the next milestone?

• Setting priorities – Coming from an academia/startup environment with limited resources, the experience needed to set priorities from a commercial drug development perspective can be limited.
• Strategic partnership – Finding the right partners as CDMOs, CROs, and investors might be a challenge if you don’t have the right experience and network.
• Decision making – Decisions made early in drug development will have impact on the journey as a whole, and can be a deal breaker. Lacking drug development experience will make it harder to predict the consequence of each decision.
• Costs – As you progress in product development, the costs will increase significantly. Clinical trials, formulation development, and supply chain will be more complex at each phase. If you don’t have a good understanding of your future development costs, this could lead to hesitation from investors.
• Practical knowledge - It’s one thing to have theoretical understanding of drug development, but lessons learned from having completed the journey before can help avoid many common mistakes.
• Market access - At early-stage development it can be hard to visualize a commercial product, many years ahead. But it is truly important to understand who your patient will be, what the population will look like, who the payers will be, and what they are willing to pay for the product? This is incremental for getting funding for your development and have the numbers widely endorsed in the end.
• Development focus - With the end point in mind, it’s important to stay focused on your development plan. If the development is not in focus for what you planned (and need), your development can take another path into a dead end or get terminated due to increasing costs.

Data shows that most drug development ideas fail even before Phase I, and only a handful make it to clinical research. From those that make it to clinical Phase II and III, even less make it to launch. Before moving to the clinical phases, start-ups are required to begin documentation around the quality, safety, and efficacy of their product. Research shows that probability of success from research to market is below 10%. This is called the “Valley of Death”. Failures relating to nonclinical and clinical issues with your product often remain unresolved because they are inherent related to the idea of your therapy. However, failures around quality aspects and documentation can be prevented. Anticipating quality issues with your product and setting up proper documentation with the right future in mind, is something you can control.

So how do you prevent these quality issues in your drug development process?

Drug development planning means beginning with the end in mind. Ask your team and yourself the relevant questions. What is really needed in the development phase to enable commercialization?

Begin with the Target Product Profile (TPP). A TPP outlines the desired ‘profile’ or characteristics of a target product that is aimed at a disease, and what you want to achieve with your product, your end point. This involves aligning within your company what it is that you are going to do and how you are going to achieve it. This TPP will determine the next phase in development. Questions you need to ask, are:

• What is the supposed working mechanism of the product in the patient?
• Which nonclinical studies are needed to support MoA and TPP claim?
• What characteristics should the product meet?
• Which clinical studies or clinical program is needed to support MoA and/or indication?

Do not be afraid to estimate and adjust later on. This will not be the last version of a TPP.

The TPP can be divided in 4 different profiles: drugs characteristics, use, safety, and business profiles. Based on these main profiles, TPPs further state the key elements of intended use, target populations, cost, and other desired attributes of products, including, stability, dosing frequency, safety, and efficacy-related characteristics.

Characteristics – The physical parameters of the product (quality attributes), formulation, potency, dosage, product container, etc.

Safety – How to ensure safety of the product, microbial, manufacturing process, contamination, impurities, and safety profile.

Usage – Indication for use (efficacy), pharmacokinetics and dynamics. What to have in mind is that a wide indication will increase the complexity regarding clinical trials (number of trials, recruitment of patients, different populations, different formulation etc.).

Business – How to meet the financial target of the product, based on the above profiles. The more the characteristics/safety/user profile has been defined the easier it is to predict financial/business profile of the product.

Handling All Aspects of Drug Development

Drug discovery is an expensive, slow, and risky business and requires many disciplines. The biggest chances start-ups have of preventing failure of bringing your product to market, is to resolve any issues relating to quality. Because that is the factor you can control. Defining your TPP will play a big role in this as you will have a clearer vision and expectation of the product.

It helps minimizing risk of failure, and financial or development risks, as well as provide an efficient and effective control program. TPP embodies the notion of beginning with the end (goal) in mind. Define the goal to develop a drug development process that is safe and effective, and its development and commercialization is supported by a sound financial strategy.

To ensure your company has the resources, required competencies, and experience to handle all aspects of drug development, start-ups can rely on ProPharma Group’s experts to support them along the way. We will help you deliver quality, efficiency, and resources to ensure you have clinical trial material with the appropriate documentation dossier for MAA application.

To overcome the challenges during drug product development including the "Valley of Death”, we offer start-ups a bridge between academia and commercialization based on defining and development of Target Product Profile (TPP) and creation of a tailored Drug Development Roadmap to reach the end goal of TPP.