Set up Cell Clinical Trials and the Challenges
The therapeutic set up cell and Advanced Therapeutic Medicinal Product (ATMP) companies are continuing to develop. Over the last two years the focus of industry discourse groups within the UK has moved forward from homework techniques during development to the challenges of GMP producing these products. Once manufacturing issues are resolved focus could move onto the challenges of Palingen stem cell scientific trials.
The difficulties of obtaining approval from authorities that will conduct the trials will be the main focus of the bring in. With these challenges ahead, there may be little time to focus on the actual procedure for labelling, storage and distribution of the product to the trial offer sites.
Challenges of Stem Cell Clinical Trials
Phase i treatment trials are generally conducted at a single site with a solo investigator and a close relationship between the investigator and the coordinator. The investigator in these trials is often a pioneer in their niche and closely involved with the development of the product.
Trials involving autologous products require collection of cells, processing of the cells plus delivery back to the cell donor; this whole function may be conducted on a single site or alternatively it may necessitate transport to a separate site for cell processing and next return of the material to the same patient. Although the tricks of the material and the technology to process the cells is tremendously complex, the logistics of the trial are relatively simple. It does take secure traceability of the sample, obtained by following good making practice (GMP) guidelines and a validated shipper, which échange the material at the desired temperature between the patient and the application site. Following production and labelling the material will require seeking that it is GMP compliant; in the EU this is confirmed by way of Qualified Person (QP).
At Phase II the study will likely take place at more than one investigator site. For autologous cures this has the added complication of more than one patient’s treatment simply being processed at the same time. Traceability of samples is critical and the synchronisation of patients, the manufacturing site and QP variety becomes more complex. Competent project management and good considering should overcome these difficulties. Additionally tracking systems for samples using patient biometrics are being developed which would flag up an incorrect sample being returned to a patient.
Allogeneic products are derived from stem cells which are used to treat people rather than the donor. These cells are typically manufactured in batches, using a larger scale and may be intended for use in trials in various countries.
One issue faced with clinical demos of ATMP products is ensuring regulatory compliant labelling. The primary containers must be labelled during the manufacture and in advance of freezing.
Consideration needs to be given to the labelling process of the principal containers, once frozen to -80 or -196°C, the important container cannot be labelled, therefore producing bulk unlabelled amounts and then determining which trials the stock will be allocated to at a later date is not possible.
Once the product is packed around primary containers (units), it may be shipped to a second web page for secondary packaging, storage and distribution to specialized medical sites. This is similar to the logistics of more traditional pharmaceuticals.
For instance , bulk batches of labelled material could be shipped with the manufacturer to a storage site. These could then often be assembled into kits in a cryostorage box, containing more than enough material to dose one patient. Alternatively, to avoid mobile or portable wastage material could be handled with a ‘just in time’ packing method, which has proved successful in more conventional pharmaceutical trials where the drug is either very scarce or very pricey.