Disposables crucial in future of patient-specific meds

Using information about a patient's genetic profile to create tailor-made treatments specific to the individual has become a hot topic of conversation in drug development circles. However, the seismic shift in production practices that would be needed to successfully create such treatments is proving a daunting prospect to drug manufacturers. Singh's key message, driven by decades of experience with disposable technologies and bioreactors, is that these personalised medicines simply will not happen without the use of disposable equipment. "Disposables are ultimately going to be the way forward,"​ Singh told in-PharmaTechnologist.com. "Any kind of patient-specific therapy will be based on disposable equipment." ​ As the founder and former president of Wave Biotech and recently installed as general manager of the Wave Products Group at GE, Singh can speak with some authority on the role single-use manufacturing equipment could have in the future of healthcare, and sees it as a critical enabler for patient-specific meds and cell therapies. While disposable bioreactors are currently de rigueur​ in biopharmaceutical manufacturing, their application in the development of personalised medicines will be a significant transition for the pharmaceutical industry to make, moving from a few large, commercial scale processes to numerous smaller projects. "In the biopharmaceutical industry the trend has been to produce maybe a gram or a kilogram of protein to produce millions of doses,"​ Singh explained. "But with patient-specific production, each reactor may only [have a capacity of] one or five litres to produce a single dose. It's a much smaller scale, but would involve thousands of separate reactors." ​ This switch in scale could potentially be an uneasy one for manufacturers, used to dealing in terms of vats or tanks to manufacture their products. Despite the fact that one might only be producing a single dose to treat a single patient, Singh emphasises the fact that the procedure can't be carried out in a flask or dish - the nature of the process means that five or ten litres of cells will be required and, therefore, a bioreactor. In addition to this, patient-specific manufacturing will bring its own production puzzles and risks, particularly in terms of the potential of cross-contamination. While in the past instruments such needles and syringes were routinely autoclaved and reused, this is now practically unheard of in the Western world with single use products today the norm in most healthcare settings. This concern regarding the risk of cross-contamination and infection clearly and critically extends to the production of patient-specific medication, albeit in a slightly more distinct way. This, again, is where disposable bioreactors step in to play a vital role. "Some guidelines developed for the biopharmaceutical industry don't really apply as the main issue in that instance is validating the cell lines that are being used,"​ said Singh. "But by using a patient's own cells the process is like an autologous graft, so any regulatory framework will be directed more at preventing mix-ups between patients." ​ Personalised medicines will undoubtedly draw a string of unique manufacturing, regulatory and economic issues, but some companies haven already taken steps towards these next generation treatments. According to Singh there are a number of firms that have reached Phase III trials with therapies destined for the patient-specific market, and as these smaller companies test the water and help establish a base of proven products, larger manufacturers are more likely to follow suit, buying up the small fry along the way. Initial applications are most likely to be cancer treatments, as it is somewhat easier from a regulatory standpoint to work with new potential treatments for serious diseases for which there is no real cure according to Singh. In his opinion, activated T-cell therapies are likely to be the first patient-specific treatments that we see, emerging in the next two to three years. Other viral vectors for patient-specific gene delivery could be around in five to ten years, and tissue and organ replacement therapies in the next ten to twenty years. These customised treatments, however, will be coming with a hefty price tag, with a single dose costing perhaps $10,000 to $15,000 (€7,500 to €11,200). Despite this, if there is a new and possibly more effective way of treating a disease, experience has shown people are prepared to pay. US firm Genzyme for example, currently markets a treatment for Gaucher's Disease, a rare condition caused by an enzyme deficiency. Despite Genzyme's Cerezyme (imiglucerase) enzyme therapy costing each patient hundreds of thousands of dollars a year, they are prepared to pay the premium rate to get the treatment. "The field is still in its infancy, and still fairly academic,"​ said Singh of patient-specific therapies. "The technology to do this on a mass scale will make it economic, but it doesn't exist just yet… now is the time to raise awareness and start thinking about a whole new generation of disposable technologies." ​ Look to the East ​ It's possible that the Far East could hold the key to the foundation of the patient-specific drug market, leaving behind some of the restraints holding back the sector's development in the west. Certain political constraints that can hamper research and development activities in the west are les of a problem over in Asia, giving companies the opportunity to off-load R&D activities to these less restricted locations. In Singh's opinion, Singapore could well end up as a hub for the development and production of personalised medicines, having already established itself as a base for biopharmaceutical manufacture. "Singapore invested a lot in biotech, but it didn't give it as much of an edge over India and China as it had hoped,"​ said Singh, speaking of Singapore's position in relation to other low-cost manufacturing destinations. "Applying itself to patient-specific therapies could give Singapore an edge over India which is already well-established in the pharmaceutical market, and China which is more focused on its own internal market." ​ With these regions keen to boost their presence and reputation on the global stage, and the possibility of personalised medicines becoming a more prominent theme in the industry, wide-spread use of patient-specific therapies - manufactured in low-cost areas using disposable technologies - could be a reality sooner rather than later.