Roadmap to commercialization success: Build agility into drug development plans
By Dr. Diane Seimetz
We know the lifechanging impact that gene, cell and tissue-based therapies can have and how they’re poised to steer us toward more personalized medicine. But for these advanced therapies, the road from research and development to the clinical stage can be a bumpy one, filled with detours and potential obstacles. Hitting product development milestones can be a challenge without a carefully planned, multi-disciplinary approach that provides adaptability as development progresses and knowledge is gained. With this in mind, it’s clear that organizations would benefit from an integrated product development plan (IPDP) as a key part of the commercialization process.
Diane Seimetz delves into the value of an agile, multidisciplined development plan in bringing advanced therapies to market.
Transformative therapies need a non-traditional, more nimble path to market
The development of advanced therapy medicinal products (ATMPs), as they’re called in the European Union and the UK, or cell and gene therapy products (CGTPs) as they are called in the United States, has exploded over the last few years. More than 980 organizations are involved globally, the majority in North American and Europe. At the end of 2019, over 1,000 clinical trials were in progress worldwide.1 With those numbers only growing, the value of an IPDP is obvious. But as critical as an IPDP is, it’s surprising how underestimated it can be as a planning tool.
We know that ATMPs are complex products with specific risks, challenges and considerations. For the organizations involved, the “traditional” clinical development paradigm simply may not work. Agility is crucial as key decision points pop up along the way, which is why the IPDP must be an organic document, spanning key organization disciplines and evolving as development progresses. This ability to be nimble promotes organizational prioritization and decreases time-to-decision.
And while we’ve watched regulatory agencies develop and apply tools for accelerated approval of vaccines and treatment during the pandemic, this won’t always be the case. That’s why it’s imperative that the IPDP be devised in a way that explores, from early on, how its set-up can also expedite the development from a regulatory perspective.
A target product profile is key
Beginning with the end goal may sound contradictory, but in the case of an IPDP, the focus must be on getting to a target product profile. Using quality, nonclinical, clinical and regulatory components, the profile defines:
- The value proposition under consideration of the competitive environment
- Target indication(s)
- Target countries or regions and pricing
- Identified population(s) for development, including desired efficacy and safety profile, route of administration, and dosing strategies
This is a starting point that will likely fluctuate as learnings are gained. Organizations that circumvent this critical step do so at their own peril, given the potholes in the process.
Robust and predictable manufacturing processes are needed to drive quality
Let’s go into the four components that comprise an IPDP. The first and possibly most important is quality. Unlike traditional drug reviews where 80% of the focus is on the clinical portion of the application, scrutiny for advanced therapies centers on product manufacturing and quality.2 For a patient to have a consistent, replicable experience with a therapy, uniform quality is crucial.
Advanced therapies pose a challenge due to the inherent variability of the starting materials, especially where viable cells are used. Additionally, the manufacturing processes are complicated and may need innovative and intricate analytical solutions to control consistency, product quality and comparability. Companies may consider contract manufacturing organizations (CMOs) in order to address these. The IPDP should outline the proposed manufacturing approach, as well as the control strategy, for the drug substance and the drug product.
Nonclinical involves safety, pharmacology and toxicology assessments
The next component is nonclinical. Looking at nonclinical evidence helps convince regulatory agencies and oversight committees or review boards that the advanced therapy is suitable for administration to people at the planned dose levels. Nonclinical studies may also present obstacles, as suitable disease models are rarely available. The IPDP should spell out the proposed in vitro and in vivo studies planned to address pharmacology, safety and toxicology. In vitro data can provide insights that may prove useful further down the road.
With clinical studies often the most expensive part of development, special care should be taken.
The clinical component is an essential part of the IPDP. We recognize the special challenges that advanced therapies present in terms of smaller studies that may not deliver a sufficiently strong basis for a benefit/risk evaluation. Also, clinical development can often outpace chemistry, manufacturing and control (CMC) development, making meeting development needs and regulatory compliance and timelines difficult. The IPDP must define at least the first-in-human study. Then, depending on the stage of development, it should call for further clinical studies—up to approval and beyond for potential follow-up commitment.
Regulatory makes the difference between a hope and reality.
Regulatory is the fourth and final component of an IPDP. Early and frequent dialogue with regulatory agencies is important, since they can provide valuable input and advice. The function of the IPDP is to present the regulatory tools available in the target territories and assess the suitability and most favorable timing of these tools for the advanced therapy. The regulatory interaction strategy dedicated regulatory programs, as well as submission strategies, are key parts of the IPDP.
Having an IPDP in place can help an organization successfully navigate the often treacherous scientific, clinical development and regulatory issues that can complicate the translation from research into patient access. A strategically designed IPDP is an essential tool for improving efficiency, reducing costs, shortening timelines, and increasing the probability of success for advanced therapies.
Interested in learning more about how to identify and mitigate risks early in development? Download our white paper, The Future of Advanced Therapies: Strategies to Evolve Global Health in a Post-COVID World.
Dr. Diane Seimetz is a renowned expert with decades of global drug development, regulatory affairs and partnering experience in the biopharmaceutical industry.
- Institute for Clinical and Economic Review. Integrated product development for ATMPs. Available at: https://icer.org/news-insights/journal-articles/integrated-product-development-for-atmps/. Accessed November 9, 2021.
- 2. Statement from FDA commissioner Scott Gottlieb, M.D. and Peter Marks, MD, PhD, Director of the Center for Biologics Evaluation and Research on new policies to advance development of safe and effective cell and gene therapies. US Food and Drug Administration, 2019; https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-and-peter-marks-md-phd-directorcenter-biologics.
The Key to Successful Drug Approval: An Effective Regulatory Strategy, Diane Seimetz; Life Science Venturing, 2017
Approval of First CAR-Ts: Have we Solved all Hurdles for ATMPs? Diane Seimetz, Karl Heller, and Jan Richter; Cell Medicine, Volume II: 1-16, 2019
From fiction to science: clinical potentials and regulatory considerations of gene editing; Maria Schacker and Diane Seimetz; Clinical and Translational Medicine, 2019