December 22, 2021

Small batch manufacturing & fill-finish in cell and gene therapy

In these years, we are witnessing the advent of a new era in medicine and pharma. Recent breakthrough advances in life sciences such as immunotherapy, next generation sequencing and cell and gene therapies have sparked an unbelievable acceleration of biotechnology development. The COVID-19 pandemic forced the biotech field to even higher productivity and catalyzed much needed progress in regulatory processes. With the first approvals by the US Food and Drug Administration (FDA) and several hundreds of such advanced therapies in early to late stage clinical trials, there is no slowing down on the horizon.

But this progress is not easy to achieve. Biopharma companies face unprecedented challenges that pertain to the cost of goods, formulation, supply chain and logistics of large-scale commercial production of cell and gene therapies (CGT). With biopharmaceutical drug products becoming more personalized, the supply chain must change from traditional manufacturing to keep an inventory, towards a manufacturing process that commences very close to the actual treatment process.

A great example is the treatment of insidious cancers with chimeric antigen receptor T-cells, in short CAR T-cells, that relies on modifying the patient’s own T-cells to instill them with a targeted way to fight cancer cells. The notion of keeping an inventory of such therapies is absurd, yet the benefits of personalized medicines drive biotech companies to form strong partnerships with contract development and manufacturing organizations (CDMOs) and supply companies to find and optimize innovative ways to solve these challenges.

The difference between cell therapy and gene therapy

What is cell therapy and what is gene therapy? What are the differences?

Cells are small building blocks of organisms that come in many shapes and functions, e.g. liver cells, muscle cells, nervous system cells and skin cells. Genes are regions of DNA molecules inside cells and carry genetic information, much like a blueprint or a program. Every person carries approximately 20 thousand genes and two copies of each that stem from each parent.

If a gene is altered (mutated) at a critical region, this could lead cells to malfunction or perish, ultimately leading to a genetic disease. This might be caused by environmental influences or hereditary.

Gene therapies aim at either silencing destroyed genes or restoring malfunctioning genes by repairing them or replacing them with a working copy.

Cell therapies work through replacing missing cells or altering a class of cells to carry out their normal function. Moreover, some cell therapies rely on modifying cells to carry a therapy into the patient’s body. For cell therapy, cells are first cultivated or modified outside the body in manufacturing facilities and then introduced into the patient through an injection. The cells could be derived from the patient (autologous cells) or from a donor (allogeneic cells).

For CAR T-cell therapy, the patient’s own T-cells are harvested and subsequently genetically modified and subjected to validation, before being reintroduced into the body. Therefore, CAR T-cells are autologous cells and both cell therapy and gene therapy.

Hurdles in CGT manufacturing

The manufacturing of cell and gene therapies is a fledgling field that is continuously evolving with developments in bioprocessing, filling, robotics, process development and quality control. The production and logistics in small batches for initial clinical trials is becoming a solved problem but the scale-up to batch sizes suitable for large clinical development trials and ultimately commercialization in accordance to (current) Good Manufacturing Practice (GMP and cGMP) is challenging biotech companies.

A key part of the solution to manufacturing and logistics hurdles is the formation of strong partnerships with companies that are experienced in the development of single-use equipment for batch production filling lines and fill-finish of injectable final products, e.g. biologics. Their experience has direct carryover to emergent novel cell culture and cleanroom methodologies and facilitates innovative solutions for automated systems performing aseptic fill into vials and syringes.

Fully automated and high accurate fill and draining system for small single-use bags as used for CGT

With the onset of commercialization and hence massive scale-up of CGT production volumes, innovative companies foresee the regulatory and CMC challenges and are actively seeking scalable solutions and product development to bring these novel therapies to patients.

With RoSS.FILL CGT, Single Use Support developed a fully automated filling & draining system for parallel use of small single-use bags at highest accuracy down to few g. It allows the use of 36 single-use bags with volumes from 10 mL to 500 mL, with filling times of down to 20 seconds for 250 mL bags. This system is ideal for studies on the laboratory scale and small volumes in cell and gene therapies or seed train intensification. RoSS.FILL for CGT is fully compatible with the protective shell RoSS.KSET that makes transporting highly valuable goods convenient and secure.

 

Conclusion

We are experiencing exciting times in medicine and the life science sector. Breakthrough therapeutics are entering the broad market, curing and treating previously devastating diseases. The key players face big challenges in the commercial manufacturing of cell and gene therapy products but forming collaborations with strong partners in the field of drug substance logistics will solve many issues that accompany the accelerating speed of CGT commercialization. Single Use Support is excited to contribute to these developments.

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Michael Mühlegger

Marketing Manager

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