Cytotherapy and Regenerative Medicines – New Parenterals for a New Era in Medicine
Regenerative medicines represent a new approach to human medicine that promise to provide treatments for diseases that are presently considered incurable. These products rely on human cells and tissue to prepare treatments that are personalized for each patient. The source of cells or tissues, which are used in cytotherapy and regenerative medicine is typically the patient himself or herself. The use of autologous cells mitigates issues with immune rejection of foreign tissues. Replacement cells or even tissue sheets can be grown from cells harvested from a patient and then re-introduced to that patient within the clinical setting. There are presently more than 50 regenerative medicine systems/approaches approved for marketing globally and another 150 or so in clinical study.
These technologies, which are evolving rapidly and becoming more technically sophisticated each year, represent a very different approach to therapy than traditional drug or biological preparations. Regenerative medicine products unlike the parenterals that PDA members, standard setters and regulators are familiar will present new and unique challenges. These products will not be made in large factories with timelines that stretch into weeks or months. They will not rely on bulk products formulated in batches of hundreds or even thousands of liter and then processed, containerized and packaged on high-speed production/packaging lines.
Instead these products will be made in small quantities for individuals and manufacturing will occur in cell or tissue factories located in many cases right in a clinic or laboratory. Regenerative medicine products will be in every case high risk products in terms of microbiological contamination and they will be expensive to produce. There will be no way that these products can follow the same rigid microbiological analysis approach used for traditional parenterals. Time will be of the essence and there is no practical way that 14 day incubation periods for sterility testing or five day environmental monitoring cycles will be applicable (sterility testing) or beneficial (monitoring). On the other hand well-defined and standardized methods for physical sterilization, decontamination and disinfection will be applicable and can be used based upon existing standards and precedence.
Evidence is emerging that the best way to manufacture regenerative medicines will be in the implementation of modular isolator technology able accommodate cell harvesting, modification, growth, and preparation for delivery to the patient. I’ve had the privilege over the last few years of working with a Japanese affiliate manufacturing advanced automated cell processing systems. These systems can be customized to meet specific regenerative medicine manufacturing requirements and are being delivered to regenerative medicine laboratories/producers at this time. Data indicate that these advanced aseptic systems promise to reduce the cost and increase the efficiency of regenerative medicine production by up to 10-fold or more over traditional clean room approaches.
It is important for intelligent standards and regulations to be applied to regenerative medicine manufacturing globally. The recovery and growth based microbiological assessment programs that have been applied with increasing intensity to large-scale parenteral manufacturing will not work for these new therapies. Asepsis and safety must be engineered into these systems there will be no reason or value in attempting to test or monitor these attributes into regenerative medicine products.
Applying validation concepts from the 1980s to 21st century medicine will not enable these products to reach those they can help at reasonable cost. Perhaps lessons can be learned from this effort that will help us take a more modern scientific approach to large-scale parenteral production as well.
Those interesting in seeing what a regenerative medicine factory will look like in practice may enjoy the non-commercial video,which can be found at this link regarding work done at Tokyo Women’s Medical University: