Written by:
Senior Vice President, Global Head of Oncology Regulatory Science, AstraZeneca
Senior Director, Cell Therapy, Oncology R&D, AstraZeneca
Head of Clinical Development, Cell Therapy Unit, AstraZeneca
Cell therapies are transforming the treatment of cancer; however, their revolutionary status leads to unique challenges for existing regulatory frameworks designed primarily to assess synthetic molecules and established biologics such as therapeutic antibodies. We are committed to the future of cell therapy—this means partnering with regulators to pioneer new techniques for engineering these ‘living medicines’, and bringing them to more patients.
Cell therapies present unique regulatory challenges
As ‘living medicines’, cell therapies require a separate regulatory framework that has been evolving over recent years.
Manufacturing requirements for cell therapies are complex, requiring specialised clean rooms and Good Manufacturing Practice (GMP)-compliant facilities, stringent quality control and additional regulatory considerations.
Autologous cell therapy products are created from a patient’s own immune cells, which are inherently more variable than other products synthesised at large scale in a laboratory, such as small molecules and antibodies. Therefore, key steps in cell therapy development—from collecting a patient’s cells, through to engineering and manufacturing a product—are even more important to regulators.
Additionally, cell therapies are often administered as a single, long-lived infusion. This means regulators are extremely interested in close monitoring of long-term effects, because they can be hard to predict.1 As a result, requirements for long-term patient follow-up are more stringent for cell therapies than for other drugs—with a mandated follow-up period of 15 years.2 This can have important implications for long-term patient care.
Working with regulators to evolve research regulations
We see the conversation between regulators and industry as an evidence-led, collaborative process. Both parties share the goal of transforming the regulatory environment so that it can facilitate the development of potentially life-changing medicines for patients.
We are working with regulators to simplify and streamline cell therapy manufacturing. This involves implementing new technologies designed to shorten the process and keep autologous cell therapies ‘stem cell-like’, with the aim of optimising the safety profile of cell therapies.
The emergence of allogeneic or “off-the-shelf” cell therapies taken from healthy donors, could mitigate cellular variability, and conversations are ongoing around rejection prevention, focusing on tissue compatibility and learning from transplantation and other therapy areas.
Finally, we are researching molecular ‘control switches’ to turn cell therapies on and off after administration—should this be required—with the goal of mitigating long-term safety risks of cell therapy.
Regulators are taking the lead in outlining a pragmatic and patient benefit-focused approach to these strategies, building on the successes of the first generation of cell therapies approved for clinical use, and helping forge a path to bring these potentially transformative medicines to more people living with cancer.
Global cell therapy regulation standards are converging
There is a comprehensive regulatory framework for ‘advanced therapies’, such as cell therapies, though specifics can vary by geographic location.3,4 There is an increasing need to develop consistent, precise and timely regulatory guidance, addressing the nuances unique to cell therapy. Efforts are in motion to align standards worldwide, with the aim of simplifying cell therapy development and improving access to these medicines.
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has formed a cell therapy group to provide a platform for technical discussion of issues related to cell and gene therapies.5 This group has now been joined by Chinese regulators, greatly expanding the area covered, to help build a truly global regulatory paradigm.6
Stakeholders are aiming to unify and streamline the global regulatory framework, embracing innovations and expertise from different countries. Simplified regulatory pathways will ensure that development teams can reduce the time taken for new medicines to reach patients.
Working in partnership with regulators and health authorities to streamline regulatory pathways is paramount for the successful development and deployment of cell therapies to fight cancer. At AstraZeneca, our global reach and in-depth knowledge of health service policies globally and at country level means we are well placed to collaborate with regulators within the new framework.
Future direction for cell therapy regulation
Highlighting our joint aspiration of improving access to new, transformative treatments, and based on close collaboration with industry, regulators are facilitating the development of a framework, to support new technologies and development pathways for the rapidly evolving world of cell therapy.
There is a positive recent trend towards more collaborative, partnership-based and open-source research and development (R&D), which promises to accelerate and diversify the industry. We are a global leader in this kind of open-source innovation, with experience from over 400 R&D collaborations, including in cell therapy.
The wider shift to greater collaboration, while it has the potential to accelerate scientific innovation, may come with regulatory challenges. Our extensive and varied experience means that we are ideally positioned to help evolve regulatory policies related to collaborative R&D.7
Through the digitisation revolution, R&D is advancing using virtual experimentation and simulation, digital collaboration, and big data.8 ‘Digital’ has the potential to change and accelerate all regulatory processes, including the traditional ways of developing and submitting data to regulatory agencies. For example:
- Through the ‘Real-time Oncology Review’9 FDA reviewers are gaining earlier access to data, to identify potential data-quality and review issues, aiming to provide early feedback to allow for a more efficient review process.
- Project Orbis,10 a pilot programme initiated by the FDA, provides a framework for concurrent submission and review of oncology products among international partners, allowing earlier registrations in countries outside the US.
- We are partnering with organisations such as Accumulus Synergy11 to create digital regulatory submissions while adhering to, and allowing for, the different processes of regulators across the world.
Our oncology cell therapy group was formed to transform the treatment of hard-to-treat solid tumours, and our acquisition of the pioneering T-cell receptor engineering company Neogene has accelerated our research in this area. Partnering with regulators to facilitate effective R&D, employ cutting-edge engineering and manufacturing, and develop solution-focused approval processes is a vital part of the solution. We are deeply proud of our progress so far, and excited to continue the collaboration to bring the best possible treatments to patients.
