The market for new biopharmaceutical drugs was investigated by the Boston Consulting Group in its study "R&D Productivity 2014: A Breakthrough Year for Biopharma." 2014 was a record year in terms of approvals by the FDA: 53 new therapeutic drugs (NTDs) were approved. Conservative estimates of revenues from these drugs in 2014 are $48 billion, a figure significantly above the 25-year average of $36 billion. The numbers are even more impressive when compared to research spending. Total R&D expenditures in the industry have remained relatively constant since 2008 at $140 billion, including in 2014. Boston Consulting considers this on average an acceptable relationship between research expenditures and revenues for NTDs, an important prerequisite for sustainable and ongoing investment.1
Personalised medicine
Personalised medicine describes a wide area of individualised applications, with one point in common. The need to handle a small number of containers, often suitable only for one patient. From a fill-finish perspective, we can name some candidates for small batch sizes.
It can be a disease with only very restricted potential patients. FDA defines orphan disease as a condition that affects fewer than 200,000 people nationwide, but can be even less than one hundred.2
It might be new monoclonal antibodies (NMEs) based on individual biomarkers, suitable only for a restrict number of patients. In the last three years more than 20% of NMEs approved by CDER can be put into this category.3
The EMA (European Medicines Agency) classifies therapies based on substantially manipulation of cells, not intended to be used for the same essential function as ATMPs (Advanced Therapy Medicinal Products).4 In the US, the phrase "cell and gene therapy" is more typically used. The basic approach of gene therapy is replacing a mutated gene that causes a disease with a healthy copy. Thereby inactivating, or "knocking out," a mutated gene that is functioning improperly or introducing a new gene into the body to help fight a disease.5 Cell therapy is defined as the administration of live whole cells or maturation of a specific cell population in a patient for the treatment of a disease. Expression from specific molecules might affect a broad range of diseases or used for eliminating specific cancer cell.6
Currently we see a split between autologous and allogenic efforts. Even if we follow the allogenic path, we will make only a quite low number of treatments on an individual patient (based on the idea: "it’s a cure not a lifelong treatment"). Autologous means donor and patient are the same. So we will face a sophisticated logistic and even a much lower applications "one drug – one patient".
Personalised medicine or even cellular therapies are not a new concept. In 1907, Reuben Ottenberg reports the first known blood compatibility test for transfusion using blood typing techniques and cross-matching between donors and patients to prevent hemolytic transfusion reactions.
But rapid developments in genomics, together with advances in a number of other areas, such as computational biology, medical imaging, and regenerative medicine, are creating the possibility for scientists to develop tools to truly personalise diagnosis and treatment.7 In consequence, the "one size fits all" treatment might become less relevant in the following decades. In the end, we will have to take care of a fragile living organism (cell), with restriction to storage conditions, a limited acceptance to shear forces and a high requirement of an appropriate treatment over all.
Downstream processes
Downstream processes are most often not in the focus of R&D groups. However, fill-finish will be a focus of production, quality and regulatory. Next to all the challenges in apheresis, R&D, manufacturing, storage and logistics, we have to choose the proper container, filling a pharmaceutical and close it, for human use. Not to forget we are required to fulfil the common rules of aseptic processing and to follow cGMP guidance in a commercial process.
Fill-finish is mainly, but not in total, related to the chosen container, the adequate filling and closing itself, the added controls and checks, the (possible) grade of automation and the environment we work in...
(All Rights Reserved)