AFG Venture Group Dispatches

Corporate advisory and consultancy in Australia, South East Asia and India.

Cell Therapy Commercialisation

David James
Director Life Sciences and Pharmaceutical, Invetech

Introduction

Cell therapies are being investigated for an ever increasing range of applications to treat infectious diseases such as AIDS, repair spinal cord injuries, repair cartilage, strengthen immune systems, and treat neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and epilepsy. Other potential applications include treating arteriosclerosis and other cardiovascular diseases, congenital defects, breast reconstructions, and liver insufficiency.

Successful commercialisation of a cell therapy requires more than proving safety and efficacy to the regulators. Ultimately the therapy must be commercially viable, allowing enough patients to be treated with an adequate financial margin to justify the investment.

Barriers to cell therapy production scale-up.

A critical issue with cellular therapies is the means to scale up production once registration is achieved. Conventional methods are typically expensive, labour intensive and involve high degrees of process variability.

During Phase 3 trials of a cellular therapy, perhaps 100 patients per year will be treated. If the process runs longer than two weeks, a common occurrence, it is probably acceptable to lock down clean rooms for the duration of each patient lot.

In such a case, four clean rooms would be required to complete the trials without fear of cross contamination. However, for many cell therapies, commercial success requires a significant number of patients to be treated, with 10,000 patients per annum being common. Scaling up this manual process would require a large number of clean rooms and an even larger number of trained personnel to work the rooms. Even if clean rooms were built, and the staff hired and trained, maintaining the level of consistency and quality to satisfy the regulatory requirements and process demands would be challenging.

A paradigm shift in thinking is required.

What if you automated and closed the process?

A “closed”, automated solution requires cell therapy processes including centrifugation, incubation, media addition, cell selection, cell washing and final fill and finish, to be performed within a “closed” consumable. A machine is used to automate the processes and replicate many of the qualitatively controlled manual processes. The machine also provides consistent and operator-independent quality.

Because the process is “closed”, automated machines producing therapies for different patients can be placed side-by-side in a processing room whereas conventional “open” processing would require a separate clean room for each batch.

The benefits delivered from an automated, closed cell processing system include:

–        Significant reduction in the cost of therapy (typically 25 – 90%)[1].

–        Significant reduction in the number of operators required (typically >70%).[2]

–        Reduced dependence on skilled labor.

–        Significant reduction in capital investment through better facility utilization (typically 30 – 50%).[3]

–        Improved quality and reduced number of quality events

–        Ability too more rapidly scale-up and scale-out to match demand.

A roadmap to commercial scale cell therapy production.

The overall commercial success of a safe and efficacious therapy will depend on its cost and scale-up.

Funds are typically precious during early stage clinical trials. Until there is a clear indication that the therapy is safe and efficacious, and the process reasonably mature, investment in a highly customised system should be kept to a minimum.

Once Phase 3 clinical trials are complete using a specific process, changes to the process can be extremely difficult and will require proof of bioequivalence or additional clinical trials -“in cell therapies, the product is the process”. Developing a customised cGMP system will typically take 2 – 4 years, depending on the complexity of the process and the time taken to progress through the various development stages, clinical trials and capital raising.

When to Act.

Plan

During Clinical Trials and Phase 1, companies should invest a relatively small amount of money and effort to identify the most appropriate manufacturing process and system design and plan the development strategy including cost and timing. This identifies core technologies that can be used for initial trials and aligned to a scalable process.

Develop & Prove

During Phase 2 Trials, or earlier, companies should develop the commercial production system that can then be used during the critical Phase 2/3 clinical trials. This helps to ensure that the clinical trials are conducted with a process representative of final production. Rapid scale-up is possible once the therapy is approved.

Rollout

Investing in production systems early in the development phases allows production capacity to be rapidly increased to match demand by installing additional, automated machines in the original facility or in facilities that are located closer to the market (“scale-out”).

Conclusion

Cell therapy companies face many challenges when managing the journey from early clinical trials to commercial production. Apart from satisfying regulatory requirements and demonstrating that the therapy is efficacious and safe, commercialising such therapies also requires the therapy to be cost effective and scaleable.

These requirements are particularly challenging where the therapy is manufactured in small batch sizes (eg specific to an individual patient such as autologous). Traditional small volume cell processing is largely manual and only partially closed. Whilst this approach is appropriate for research and early stage clinical trials, it introduces several significant commercialisation challenges

For the cell therapy industry to reach its full potential, it must have commercially viable small-batch processing — and ideally the ability to deal with a batch size of one (patient). Several cell therapy companies have already invested in developing innovative closed, automated systems for small-batch cell therapy manufacturing. Those systems have delivered significant cost, quality, and scale-up benefits over existing manual, cleanroom-based processing strategies. They have also provided valuable insight into the needs of the industry and a demonstration of what is possible

Cell therapy is an extremely exciting and rapidly advancing field of medicine that could have a significant impact on how we treat a vast array of diseases. Closed and automated cell-processing systems provide an opportunity to change the paradigm and deliver these therapies at a cost that was not previously thought possible.

About the Author

David James is responsible for the strategy, sales and delivery of automated production systems for clients spanning diagnostic, medical device and cell therapy industries.

David has been with Invetech for more than 20 years and during that time has grown the Manufacturing Innovation division to serve a global client base across a range of industry segments.

Prior to Invetech, David was with Lewis Australia where he managed custom automation for the industrial sector in automotive and metals.

David has a bachelor’s degree in Engineering from the University of Melbourne.


[1] Figures based on Invetech research and external project work completed 2005-2010

[2] Figures based on Invetech research and external project work completed 2005-2010

[3] Figures based on Invetech research and external project work completed 2005-2010