ADVANCES THERAPIES USING GENES, CELLS AND TISSUES
Scalable manufacturing brings personalized cures and treatments to those in need
Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues or cells. They offer ground-breaking new opportunities for the treatment of disease and injury. ATMPs embrace gene therapy medicines, somatic-cell therapy medicines, tissue-engineered medicines. Gene therapy medicines contain genes that lead to a therapeutic, prophylactic or diagnostic effect and are injected into the body. Somatic-cell therapy medicines contain cells or tissues that have been manipulated to change their biological characteristics or cells or tissues not intended to be used for the same essential functions in the body. Tissue-engineered medicines contain cells or tissues that have been modified so they can be used to repair, regenerate or replace human tissue. ATMPs are exciting new areas of medicine that are just starting to gain regulatory approval. They cover a wide range of individual treatments from CAR T cell cancer therapies (e.g. Kymriah against leukemia and Yescarta against lymphoma), gene therapy (e.g. Zolgensma against spinal muscular atrophy) to regenerative medicine for rare genetic diseases, degenerative disorders such as Parkinson’s or other defect disorders (e.g. Carticel for repairing cartilage defects). In all its diversity, mastering the entire manufacturing process from source to patient is key for ATMPs.
ATMPs jump into the gap where classical medicine alternatives are scarce, of low effectiveness or simply non-existent: Autologous treatments with cells obtained from the patient him/herself and re-injected after therapeutic modification offer new avenues to more effective treatments and even cure of diseases (however at a cost of $400k to $2M per patient). Tissue engineering can improve effectiveness of organ and tissue transplantations or replace it by generated tissue, overcoming today’s shortage of donor material (about 20% of patients on the liver transplant waitlist die or become too sick to be transplanted). Today, broad adoption of ATMPs is hampered by its cost, not bearable by public health systems and thus by far not reaching all those in need. Automation of ATMP processes are critical to broader adoption and require significant efforts to develop appropriate, safe and scalable platforms and processes.
Relevance for the Electronic Components and Systems (ECS) industry
ATMP biomanufacturing must be transformed from artisanal manufacturing towards high yield/high quality production yet keeping the promise of personalized treatment. The ECS industry can enable ATMP 4.0 by leveraging its expertise on Process Analytical Technology (PAT) for pharmaceutical manufacturing and its efforts towards Industry 4.0. ATMP 4.0 needs to address the inherent variability of the biological cell, gene and tissue material with technology. The convergence of size between biological components and the ECS technologies (nanometer to micrometer) is of great interest for automated systems, possibly decentralized at bedside, and compatible with the scarcity of resources.
The ECS industry can contribute to ATMP 4.0 with
Microfabrication technologies for embedded microfluidics (materials such as silicon or polymer and compatible with biological systems) for production, sorting and manipulation of cells and cell culturing in scaffolds;
Miniaturized sensor and actuator components for bioprocess monitoring and control;
Real-time embedded process control and monitoring platforms (energy efficient, secure and connected);
AI-support through efficient (edge-)AI computing hardware / software.
Enabling technology platforms
Essential capabilities for ATMP 4.0 relate to embedded process control and monitoring and embedded microfluidics. The ECS industry can contribute here with open technology platforms for manufacturing and assembly of embedded microfluidics devices, ideally on a foundry service base. Additionally, it can drive standardization of the physical interfaces and testing. Equally important, it can establish systems control, interconnectivity and data standards and contribute the necessary sensors and actuators, embedded systems, and edge AI hardware and software enabling embedded process control and monitoring.
Synergies exist with other domains. Organ-on-chip, point of care diagnostics, bioelectronic medicines and smart drug delivery also draw on sensors and actuators and miniaturized microfluidic devices. ATMPs may also contain one or more medical device as an integral part of the therapy administration (combined ATMPs).
European Medicines Agency (EMA) – overview ATMP - https://www.ema.europa.eu/en/human-regulatory/overview/advanced-therapy-medicinal-products-overview.
Alliance for Regenerative Medicine (ARM) - Annual Report 2019 – https://alliancerm.org/sector-report/2019-annual-report/.
The three obstacles stopping cell therapy becoming mainstream – labiotech, July 13, 2020 - https://www.labiotech.eu/in-depth/cell-therapy-obstacles-widespread-use/
Raising the bar in manufacturing cell therapy products – imec, white paper 2018 - https://www.imec-int.com/en/expertise/lifesciences/cell-and-gene-therapy
OrganTrans – Organoids transplantation – project web site https://organtrans.eu