Designing a cell and gene therapy GMP cleanroom

As cell and gene therapy developers progress through the clinical trial phases to commercial manufacture, the strain on the production process increases, testing the limits of scalability and robustness.

During these stages additional capacity may be required to transition through clinical trials and move to commercial manufacture, which may result in the need to move to a new facility or invest in a build programme.

Challenges in cell and gene therapy production

The cell and gene therapy industry has a number of specific challenges which may introduce additional complexity into the development path and manufacturing scalability of these products. The key challenges include:
The challenges in cell and gene therapy manufacturing diagram

The range of challenges in cell and gene therapy production

Early implementation of manufacturing technologies and practices can help ease the transition to a GMP manufacturing facility. However, additional process development activities may still be required in order to meet the target cell dose and release specification requirements, achieving increases in cell yield as well as product purity. The technologies implemented for manufacture at the early clinical phase may need to be changed to achieve an end to end closed manufacturing process in later phases. Alternatively, appropriate aseptic technologies and practices must be put into place (e.g., isolator technologies, lamina flow cabinets with appropriate room background).

When completing the route to commercialisation, allogeneic therapies can have a higher resource and investment requirement due to the need to implement new, larger scale equipment. Autologous cell and gene therapy development can benefit from implementation of automated scale out technologies during the process development stages, reducing the time and investment when transferring to a manufacturing facility.

Designing a GMP lab for cell and gene therapy manufacture

The process of designing your GMP cleanroom can benefit from working closely with operational, quality and facility management teams to build in operational quality and ensure facility fit. Key activity areas at this stage include:

Equipment

Selection of suitable equipment which will allow you to achieve the scale-up/scale-out of the target cell therapy. The following tools and activities can help to identify the most suitable equipment for your facility cleanroom:

Producing a detailed equipment list including equipment manufacturer, part numbers and utility requirements

Defining software requirements and integration needs for each piece of equipment

  • Assessing the need for Code of Federal Regulation part 11 compliance
  • Assessing the need for integration with electronic batch manufacturing records
  • Assessing the need for integration with laboratory information management systems
Moving from use of needles, luers and biosafety cabinets to adopting closed systems
Defining equipment installation and operational qualification work packages required
Writing user requirement specification documents for the required equipment
Scheduling

Scheduling of materials, product and waste movements ensures robustness of manufacturing activities as well as helping to optimise equipment utilisation during operation. In order to help with the scheduling task, the following activities can be considered:

Mapping the movements of materials, people, waste, product and QC samples with the facility
Ensuring suitable movement, intermediate and holding times are supported by development work to avoid deviations and ensure product quality
Planning for cold chain supply as well as product distribution
Integration of the process schedule with a detailed process modelling tool. Performing a “what if analysis” can allow you to identify potential risks to the manufacturing operation
Process layout

The manufacturing process must be arranged appropriately in order to increase facility utilisation, increase operational robustness and identify additional equipment of facility needs. The following activities may help with creating process and cleanroom layouts:

Deciding on equipment positioning within the lab using layout modelling or VR tools including Hakobio

Mapping of utility supplies to ensure their availability for equipment operation using layout modelling or VR tools including Hakobio

Mapping air flows and assessing impact of people and equipment on cleanroom environmental compliance

Designing operational space and mapping necessary movements within the facility including process flow and work flow mapping

Mapping the segregation of product, material and waste flows
Running through the SOPs and BMR procedures using the layout, ensuring procedural compatibility with equipment positioning
Technology transfer

The technology transfer process to a manufacturing facility or cleanroom requires the preparation of appropriate level of documentation and detailed planning of the technology transfer activities, including clear definitions of roles, responsibilities, expectations and success metrics. 

Find out more about technology transfer methods on this scientific poster.

The scale up of cell and gene therapy manufacturing is a major driver of industry growth and is a key theme for CGT Catapult’s industrialisation team. To find out more about the team and their work, visit the industrialisation team webpage. To support companies in developing their manufacturing processes we are opening a fully flexible, innovative large-scale manufacturing centre, where companies can secure their own manufacturing futures in their own production modules. To find out more about CGT Catapult’s approach to manufacturing visit the manufacturing centre webpage. 

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