Barkey withing the C&G Process

Cell and gene therapy (CGT) development is an extremely complex and small-step process. From discovery through development to clinical and commercial manufacturing, cryopreservation and thawing of cells play critical roles, to which the impact is essential to consider.

The conditions of the thawing process affect the critical quality attributes (CQAs) of CGTs. These thawing parameters must be determined, identified, and established early in development:

Standardization

Standardization of thawing process and minimization of human error potential.

Flexibility

The maximum flexibility in container types and volumes.

medical devices

Shortened time to market by using compliant and locally approved medical devices in over 80 countries.

1 - 2 | R&D - Process Development + Pre-GMP

Laboratory equipment used for research and subsequent process adaptation should meet these requirements:

  • Adaptable, gentle, and uniform dry thawing process that uses sealed, water-filled temperature-controlled heating cushions for heat transfer.
  • Cell recovery and viability rates equivalent to water bath protocols, but without the associated contamination risks, with better reproducibility and sustainable water consumption.

3 | GMP Manufacturing

Used for both autologous and allogenic platforms, Barkey varitherm and Barkey plasmatherm C&G support the GMP manufacturing, scaling-up and scaling-out strategies of CGT products globally.

Compatible with installation in controlled environments and easy to clean due to the absense of inaccessible surfaces. They ensure “standardized, temperature-controlled, aseptic thawing” [1] of cryopreserved starting materials in bags and vials, including thawing of multiple containers simultaneously.

The use of both devices simplifies the technology transfer to GMP manufacturing or to other sites. Temperature profiles and other critical process parameters (CPPs) can be recorded and further transferred, made possible by the data logging software and user-friendly interface.

In addition, Barkey varitherm has a wider, programmable temperature range, extending its use beyond cell thawing applications to include various heating protocols, such as, in-house GMP compliant serum inactivation.

Alternative solutions to fetal bovine serum (FBS) serum, such as human serum, (huS) demonstrate similar or even superior results concerning cell expansion [2] and T-cell function [3]. These facts, coupled with initiatives to better secure supply chains, have prompted CGT developers to internalize the serum inactivation process.

4 | Administration of drug products

The plasmatherm C&G is a unique device on the market, securing compliant, global CGT drug product administration preparation. The C&G system has obtained medical device clearance in over 80 countries, a crucial advantage for multinational clinical trials and the commercialization strategies of CGT developers.

Being suitable for use in both a centralized hospital pharmacy and for patient bedside thawing, the device provides user-friendly process integrity for every CGT product, regardless of the quantity or style of container, thereby simplifying SOPs and training procedures for clinical sites and certified treatment centers.

Automated thawing of the CGT drug products with Barkey plasmatherm C&G effectively eliminates variability related to operator error or inconsistency.

Sources:

[1] Autologous cryopreserved leukapheresis cellular material for chimeric antigen receptor T cell manufacture Seshu Tyagarajan, David Schmitt and others, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA, and Novartis Pharma AG, Basel, Switzerland Cytotherapy 21(12):1198-1205, 2019

[2] Human-derived alternatives to fetal bovine serum in cell culture. Karin Witzeneder, Andrea Lindenmair, Christian Gabriel and others, Red Cross Blood Transfusion Service of Upper Austria, Linz, Austrian Cluster for Tissue Regeneration, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Linz/Vienna, Austria. Transfus Med Hemother 2013; 40:417–23.

[3] Heat-Inactivation of Human Serum Destroys C1 Inhibitor, Pro-motes Immune Complex Formation, and Improves Human T Cell Function, Matthias A. Fante, Sonja-Maria Decking, Christina Bruss 1, et al., Department of Internal Medicine III, University Medical Center Regensburg, Regensburg Center for Interventional Immunology, Department of Dermatology, University Medical Center Regensburg, Germany. Int J Mol Sci 2021; Mar 5; 22(5): 2646.