Cell and gene therapies hold the promise of cure for a wide range of life limiting diseases. Until recently these therapies could only be found in academic laboratories being produced on laboratory equipment. However, they are now being commercialised at pace, often with equipment with a laboratory heritage. In parallel to this advancement, regulatory frameworks and guidance documents for this nascent sector are being developed.
In the last few years, in response to this growing need, automation in closed systems is gaining momentum.
Why are ATMPs so challenging to manufacture?
Advanced Therapy Medicinal Products (ATMPs) as they are known in Europe, or cellular and gene therapies (C>) products in the US, offer innovative treatments for a variety of complex diseases and conditions. Many of these products can be administered as one-off treatments, offering life-long benefits or curing a potentially life-limiting disease.
When compared to conventional solid oral dose or injectable therapies, ATMPs are significantly more complex to produce. The variability and fragility in starting material and the overall number of processing steps presents significant opportunity for error.
Overlaid upon this are further complications around manual processes that were recently developed in academic laboratories and that now need to be carried out aseptically. These products are typically delivered as infusions or injections and being cellular in nature, they cannot be terminally sterilised.
This adds an additional layer of complexity, namely the need to ensure that the product is not contaminated by any viable or non-viable particulate. Unlike with orally delivered therapeutics, the body struggles to defend against contaminants delivered into the bloodstream via injected therapeutics: poisoning a patient with a viable particulate into the bloodstream is not an option!
These products should therefore be produced according to Annex 1, which states that “The manufacture of sterile products is subject to special requirements in order to minimise risks of microbial, particulate and endotoxin/pyrogen contamination”.
Currently, manual production involves skilled technicians using aseptic techniques in biosafety cabinets; difficult, manual work where humans pose the greatest contamination risk due to shedding skin cells and respiratory droplets. However, to meet regulatory requirements and reduce contamination risks, the industry is shifting towards “closed” or “functionally closed” systems and automation using robotics.
Currently, manual production involves skilled technicians using aseptic techniques in biosafety cabinets; difficult, manual work
Functionally closed systems
Many of the therapies have elected to use what are known as “functionally closed” systems. So-called “bag-sets” are
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