When the FDA recognised that the ‘orchestration’ of Provenge was Dendreon’s biggest manufacturing challenge a significant regulatory marker was placed for the management of cell therapy products.
To counter the FDA’s concerns, at great expense Dendreon developed its own IT system to manage and control the complex supply of its autologous therapy, Provenge. The system known as Intellivenge, was used to identify starting materials and intermediates using barcodes, manage shipping of starting materials and the final therapy. Without such a system in place and validated it is questionable whether the FDA would have approved Provenge.
“The major challenge in manufacturing this product is not in the manufacturing protocol…
Logistics is perhaps the more challenging aspect of producing this product due to the short shelf life of both the incoming apheresis units and the final product.
Given the tight manufacturing schedule, short process time limitations, overlapping production schedules, QC testing, and complex shipping situations.
It will be difficult to generate this product at high throughput without substantial attention paid to coordinating and orchestrating these events.”
CMC Review BLA 125197 Sipuleucel-T (Provenge®) Dendreon Corporation
Intellivenge was perhaps a portent for the current Cellular Orchestration Platforms (COPs) which are now being adopted throughout the Cell and Gene Therapy industry. These platforms manage, provide control, and base-line automation for the supply of cell therapies.
COP systems are designed to introduce efficiencies into complex, heavily regulated, supply chains. Cornerstone functions should include real time reporting, chain of identity management and chain of custody management; these features facilitate faster decision making, provide real time control, and protect each patient being treated. Chain of identity management is key when applying COPs to autologous therapies. Growing patient populations and the demands that an autologous therapy places on chain of identity and chain of custody management protocols has led to sponsor companies finding it difficult to justify the absence of COP in their supply strategy.
The COP should provide a detailed view of each therapy’s progress and a complete overview of all therapies being manufactured, including patient-specific starting materials. The control systems implemented by COP should also promote process standardisation and allow standardisation to be demonstrated to reviewers, auditors and regulatory bodies. Without using COP systems, demonstrating process standardisation is difficult, especially when the number of patients being treated increases.
The key to expedited implementation of these systems is a configurable process engine and a validated and tested core software base. The value associated with tested and validated core software should not be underestimated; this can reduce the lead time for implementing these systems by 18-36 months compared with bespoke software systems. Not surprisingly, the costs to a cell therapy company attempting to manage development of a bespoke IT system for the control of cellular therapies is significantly higher (55%-70%) than using configurable software. Indeed, developing systems in-house can introduce a litany of problems; hiring an expert to spearhead these projects is challenging enough because identifying the proficiencies required to deliver the project can be complex, separating the skilled from the charlatan is not simple.
Leveraging expertise for the implementation of a COP is vital to success, TrakCel’s team has configured its software for several different supply chains and therapies, each one being unique but with common challenges and themes. A keystone of TrakCel’s approach is to insist upon a multidisciplinary team from the sponsor, which encapsulates all business and department functions associated with the delivery of the therapy, and all touchpoints in the delivery process; this is not a simple as it sounds. Each team tends to have their own introspective requirements for a COP, however to maximise the value from COP software a harmonised, non-siloed approach is necessary, after all no man is an island.
The COP should be at the centre of your planning for commercialisation, realistically this should be introduced during the clinical assessment of the therapy to develop experience using orchestration software throughout the supply chain. All regulators will be wanting assurance that the controls detailed in licensing applications have been assessed and scrutinised before being used for commercially available treatments. A CEO and shareholders do not want to hear about delays to clinical programmes and commercialisation due to supply control problems, whether they be regulatory or control related.
By installing and using a COP system, companies developing cell therapies are sending a clear message to regulators and patient groups; process control, identity and custody management has been addressed to deliver therapies safely and efficiently.