What should be considered when designing a biotech product for clinical trials?

In my experience collaboration is key and you have to remember you are ultimately designing the asset to be commercialized. Every step should ladder up to optimal label language. Consult (early) with regulatory, medical, commercial, legal, and marketing experts to think about where you want to be once you are done phase 3. This helps you ensure you are both optimized for swift and effective trial recruitment and execution, and ultimately you will have an asset that can be commercialized.

While most drug developers will (rightly) state the importance of the target product profile (TPP) as the foundation of any asset strategy or clinical development program, the manner by which a TPP is developed can be easily overlooked. Principled evidence based approaches should be at the core of any TPP. A triad of clinical, commercial and regulatory rationale should support each component of a TPP from indication selection through to target efficacy / safety assumptions with appropriate pressure tests. Negating the above can lead to the illusion of data driven decision making and thus over confident bets. In my experience it's the molecules with the rushed TPP that end up with unfortunate challenges later down the road.

- Frequent regulatory meetings and consultation helps in speedy development of new investigational drugs. - Requirements & compliance : Ensure that product development process adheres to the regulatory requirements of the target markets ( consider atleast 3 major regulatory bodies & their requirements i.e., USFDA, EMA, PMDA) - Selection and sourcing of excipients or raw materials including cell culture media, growth factors, and purification reagents, play a crucial role in ensuring the quality, safety, and efficacy of the drug product. Ensure that the selected components not only has compatibility with biological API but also comply with regulatory requirements & adherence with specific pharmacopoeial standards

Clearly define the unmet medical need, target population and indication, mechanism of action, and expected benefits and risks. Conduct a thorough literature review and market analysis to evaluate the existing and potential competitors, the current standard of care, and the gaps and opportunities in the field. Consider intellectual property, regulatory requirements, and development strategy. Be specific, focused, realistic, innovative, and collaborative. By following these principles, biotechnology companies can develop well-designed product concepts that are more likely to succeed in clinical development and commercialization.

Consider that there is a lot of research out there, hence a lot of potential biotech products that did not receive funding, but could be the next life-saving and/or life-extending product. Unmet needs could be "Quality Of Life", so consider challenging an extremely good drug, but with a lot of/too many side-effects. Your biotech product might not be better, but it will increase the patient's quality of life during and after the treatment. To be discussed between R&D, Regulatory & Commercial if you want to go down that/any route! Keep thinking outside of the box and you'll find your niche in the Biotech world.

Consider that you've potentially just developed a biotech product that only works on a human receptor, what preclinical model are you going to use that can be accepted by Regulatory authorities? Your Regulatory expertise will be important here. There is a lot of literature out there as well.

Preclinical development is constantly changing, nevertheless, if you develop a compounds (in-silico or on the bench) which proved to inhibit, stimulate, etc on a dish, you need to develop a road map on which models need to be used to prove efficacy and safety. Regulatory expertise is a must to navigate the Pre-IND process. After the modernization act from the FDA, many other pre-clinical models will be available besides the animal. I´m talking about organs on a chip and more, which, showed better sensitivity (close to 80%) vs the animal one (close to 50).

You should have involved your clinical development department (or CRO) as early as possible in the development process so they would have developed the clinical development plan. Linked to the next point, in the timelines linked to the plan, the manufacturing is an important parameter, so involve your R&D and/or Production (or CDMO) as early as possible as well! Clinical trials is the ultimate team effort. Know at each moment who needs to be involved in what and who needs to be consulted for what.

The clinical development plan is key here, many assets fail in phase 2 or 3 because they don't show significance on their primary outcome or have safety issues. For the efficacy part, this could be for 2 reasons, the compound lacks efficacy or the primary outcome chosen is not the correct one. Sample size calculation and using the correct statistical models are key.

Having Quality by Design principles in mind can be useful since very early on and help focus the overall development efforts around the most critical aspects of product quality. Finding the optimal balance between the development stage, quality and supply needs is critical- as overkilling CMC development can easily topple the entire budget The selection of the right partners along the ways - CDMOs and other service providers is not to be taken for granted (similarly, the decision WHAT to outsource and WHEN). Knowledge management is critical as the journey is long, people move on, and every step of the way is built on top of the prior knowledge. Use ICH Q8 to ICH Q12 as your north stars when fostering design thinking in your projects.

Scalable is often the important word, as you need to go from your R&D production badges to commercial batches during your clinical trials. Often you'll need pilot plants to help you transition slowly from one to the other. Do not underestimate this part in the budget of your clinical trials. It might be part of the R&D and/or Production's budget, but that doesn't mean it should not be part of the Product's Clinical Development budget. The question is as well how you'll be analyzing your product to be sure you produced the right amount and create a consistent output. Consider continuous methods that are continuously controlling over taking samples once in a while, as you'll win time, and might be able to release faster.

Product administration should be integrated into your initial analysis and continuously assessed during your preclinical & clinical development, as it determines many things from manufacturing until clinical protocols. Patient compliance is paramount, but some products can't be put in tablets or capsules and/or some don't survive their journey through the liver. Early on you might have to use intravenous administration because of that. An additional challenge is the temperature at which your drug needs to be kept. How do you get something to your patient while you need to store your product at -70°C/-100°F? Your R&D will work on "stabilizing" your product on the level of temperature & metabolization to provide something patient-friendly.

Regarding administrative route,considerations of competitive products availability and ease of administration shall be consider per patient’s need and therapeutic usage.

I think the point of "usage" should be anticipated much earlier in the process as it can be source of added value or a barrier for the users. it is a strateguc elements goiing along with the active substance which is often neglected as primary focus is on the disease but not on the health care provider and patients who will use the substance. The co administration has also to be consider when designing clinical trials.

When developing a biotech product, the Target Product Profile (TPP) is a critical tool. It’s not just a checklist of attributes; it's a dynamic contract within the development team. The TPP is used to define, measure, and stay accountable for the product's success. The TPP process helps to spot and resolve misalignments that could derail the project and cause costly mistakes. Regularly updated, the TPP guides the organization through critical decisions and communicates the project's progress and potential to investors, ensuring assumptions remain valid and responsive to changes in science, market, and patient needs.

- Robust supply chain management system to ensure the availability of the investigational drug throughout the trial. - Considerations include forecasting drug demand, managing drug inventory, packaging, labeling, storage, and distribution. Implement appropriate temperature controls and monitoring systems to maintain the stability and integrity of the drug during storage and transportation. - Export and import : Ensure the requirements of sending and receiving countries and their regulations for new investigational drugs

A crucial element to be considered in the development of biotech products for clinical trials is embracing a Patient-Centric Design approach. This approach involves designing the product and trial with the end-user – the patient – at the forefront. Considering factors such as ease of administration, minimizing side effects, and accommodating patients' daily routines can significantly improve patient adherence and satisfaction. Additionally, patient-centric designs can lead to more ethical and inclusive trials, ensuring diverse patient representation and considering subgroup-specific needs.

Some assessment of sizing of the unmet needs as well as sizing of volume of products needed at each step ( clinical trials, launch..) to adapt production and supply infrastructures

Supply chain forecasting, when used to compare different packaging designs or even administration methods, can have a tremendous impact on your overall drug (DS/DP) requirements and your supply chain costs. A example would be, if 6 doses are involved in the trial: - having 6 bottle sizes with 'just right' capsule counts, OR - having 2 bottle sizes to cover doses 1-2-3 and 4-5-6 may lead to completely different KPIs. First option may seem best for the patient and "looks like" it requires the least amount of DS, but that would be ignoring the overage required to cover for dose uncertainty! Each trial is different ... get your vendors involved early so they can bring their knowledge to your decisions.