Overcoming manufacturing and financial challenges of personalized cell therapies

Apr 01, 2010
By Pharmaceutical Technology Editors
Volume 4, Issue 22

Person-specific cell therapy could potentially offer a cure as opposed to ongoing treatment, but it is also a disruptive technology that doesn't currently fit into traditional therapeutic manufacturing processes.

There's already a lot happening on a small scale; a huge amount of research on every possible therapeutic angle is being conducted across the globe, but as yet there are few routine therapies. The big question is where do we go next?

There's not much happening on the process development side and there isn't a lot of manufacturing capacity. This is a particular issue for personalised therapies because one batch is one process for one patient, which means that the research scale is the same as the production scale; however, manufacturing processes are not the same as research processes. Although the equipment still looks like research equipment, the regulatory environment applies to full scale manufacturing. There is also the issue of clinical trials; trials as we know them are expensive. It's difficult to get funding for them and there is also the question of whether the traditional trial structure is suitable for personalised cell therapies.

There are also additional hurdles:
  • approvals are complex
  • large scale manufacturing doesn't exist
  • there's nothing in place for purchasing these therapies into national health services
  • cell therapies are "living" and don't have a long shelf life
  • the therapy also includes both donation and delivery.

Personalised medicines do not fit into the supply chain currently in place so at the moment there's a lot of research with nowhere to go. However, if personalised treatments were to come to fruition then what we would see is a decrease in caring for patients with long-term chronic conditions and an increase in smaller, local diagnostic and treatment centres.

Manufacturing solutions

At the moment, manufacturing equipment technology for cell therapies is very expensive: the disposables are very expensive, the reagents are very expensive and the equipment is expensive, but this partly reflects the clever technology that has gone into their development.

For example, when developing T-cell therapies, the initial purification can be done completely manually using a centrifuge to separate the white blood cells from everything else; however, another option is to use a Cobe 2991 cell processor (Gambro, Sweden), which can handle larger volumes. Unfortunately, this system is expensive and, as with many other equipment involved in this space, requires a lot of aseptic operations to put it together. It is also not a closed system.

Moving into the cell selection stage of T-cell development, one of the most widely used systems is the CliniMACS (Miltenyi, Germany) system, which relies on magnetic separations. Although this is a closed system when it's running, putting it together at the beginning requires an aseptic environment. A newer system, which is generating a lot of interest, is the BD Influx (BD Biosciences; CA, USA), which is the first system based on fluorescence-activated cell sorting.

For cell expansion, there is everything from 24-well plates through to WAVE bags and cell expansion bags with multiple areas that can be expanded into. Recently, there has been quite a lot of interest in the WAVE system, which is widely used in biopharmaceutical processes to culture cells.

The ideal facility

The standard facility for cell therapy manufacturing is currently a grade A/B environment where only one therapy can be worked on per room. The next generation of facilities, however, would include grade D rooms with isolators for aseptic manipulation. This would enable a much higher throughput. Ultimately, it would be beneficial to use facilities that are fully automated where thousands of therapies can be run simultaneously. eXmoor pharma is currently working on these next generation facilities and processes with a number of clients.

In summary, cell therapy manufacture currently involves manual processes, a lot of aseptic connections, grade A/B rooms, a small number of vendors selling highly specialised equipment, and high costs for reagents and consumables. Much of the work is also currently being conducted by researchers.

Ideally, we would like to get to closed robust systems, grade D rooms that can accommodate many therapies, a large number of vendors with validated manufacturing equipment, readily available GMP reagents and GMP operators.

Achieving this is a bioprocessing challenge, but it is not impossible.

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