ATMPs: Opportunities and Challenges | PDA’s ATMP Conference 2018

 

Earlier this month, I attended the PDA’s 10th annual Conference on Advanced Therapy Medicinal Products (ATMPs) in Amsterdam. Over the past ten years, the conference has provided a forum to discuss opportunities and challenges in the space. The topics covered were wide-ranging – from R&D and manufacturing best practice right through to the clinical application of ATMPs.

For those not familiar with the area, ATMPs consist of cell and gene therapy products, tissue-engineered products, and engineered cells combined with one or more medical devices. While there has been exciting progress in the preclinical and clinical stages in recent years, this success does not necessarily equal commercial success. The area faces a significant challenge in cost-effectively scaling up manufacture.

Below are some of the stand-out production challenges and considerations highlighted during the conference:

Production challenges:

Viral vectors act as an envelope that contains genetic material to replace or suppress a mutated gene.  However, there is currently a global shortage of viral vectors. For early-stage lab research using mice, the quantities required were enough. On the other hand, the quantities required for clinical trials are significantly greater. Furthermore, the number of manufacturers is limited, and a high degree of expertise is required. Vectors must be produced under GMP conditions and undergo several filtration and sterilisation steps. As the treatments are designed to be once-off, the manufacturing process is a custom job.  Due to the recent landmark approval of chimeric antigen receptor T-cell (CAR-T) therapies, several companies have been encouraged to enter the space and the number of clinical trials is growing. To date, the majority of applications have been in rare diseases – but there is now a shift to the treatment of more common diseases, such as cancer, putting additional pressure on vector supply.

‘GMP-in-a-Box’:

The ‘GMP-in-a-box’ concept was discussed several times at the conference. For context, there are two types of cell therapy – allogeneic and autologous. The former involves cells collected from pre-screened donors. While this means they can be mass-produced, it also frequently results in recipient immune rejection. On the other hand, autologous cells are taken from the same patient they will eventually be administered to, conferring greater tolerance. However, each production only benefits a single patient. Furthermore, small quantities of individual material must be produced under strict GMP conditions, negatively impacting cost-effectiveness. The GMP-in-a-box concept aims to resolve this issue. Autologous therapies could be produced in a closed benchtop ‘box’ modular system – ideally in the same facility where the patient is biopsied and will receive the treatment. The boxes would have all the necessary controls to ensure strict GMP compliance (temperature, cell mixing control, etc). You would simply insert the biopsy, it would perform the necessary steps to produce the cells of interest, and then release them in vials or cryogenic bags. While this technology may seem a long time off, the individual technologies necessary to build this system already exist -- but not yet in a closed and automated end-to-end system. It will be interesting to see in coming years whether the GMP-in-a-box concept can be realised. If so, it would undoubtedly improve the cost-effectiveness of these therapies, bringing them ever closer to the clinic.

In summary, the ATMP market is complex and fast-evolving. There are considerable challenges both in terms of the individual processes, scalability and cost-effectiveness. However, there are undoubtedly incredible opportunities in this sector, and with some ATMPs already receiving clinical approval, these opportunities may be realised in the not-so-distant future.

 

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