CASE STUDY

Leveraging the CGT process maps

9 May 2022
Advanced Therapy Medicinal Products

The context

Current technology for cell and gene therapies (CGTs) is unsuitable for large-scale production. This is partly because there is no common standard for the industrial manufacturing of CGTs nor any common reference frame for designing a company-specific production facility.

To help fill this gap, BioPhorum’s Cell & Gene Therapy Commercialization Workstream has published a set of process maps for cell therapy and gene therapy. These represent example processes, unit operations, and platform technologies being used in CGT manufacturing. They can be used as an educational tool and will accelerate collaboration projects, process improvements, and product commercialization.

Here, Jørgen Magnus, Strategic Program Manager at Bayer’s Cell and Gene Therapy Unit, describes the BioPhorum process map project, which leveraged an internal Bayer engineering study, and how the new maps can benefit companies when they are considering investing in a facility.

The story

“I brought some internal process maps to the team, which then developed them into comprehensive process map documents for cell therapies and gene therapies,” said Magnus adding that the wide expertise of the team was crucial to their development. “The BioPhorum team consisted of experts from different fields who brought their experience to the project. These included specialists in GMP requirements, bio-safety levels, architecture, processing, and cost calculations.”

We used our internal process maps in 2019 when we wanted to build a production facility for bioreactors
Jørgen Magnus, Strategic Program Manager at Bayer’s Cell and Gene Therapy Unit

The outcomes

“At that point, we did not know what future programs we would have or where this facility would be – in the US, Europe or wherever. So our first step was to conduct a feasibility study where we calculated the cost and timeline to build it.

“Of course, we had to design it according to what we thought our requirements would be, i.e., how many patients we would treat, which was around 4,000 patients. At a high level, the results were a projected $100m capital cost and a three-year build time, based on our Berkley, California site.” Magnus said these figures were critical to making an investment decision and allowing a proper engineering study to take place before building the facility.

“As a basis for this type of decision, you need a complete overview of the different processes that you will have. For example, if the equipment you’re buying is specific for one type of expression system or whether you can use it for the different types of processes, and how flexible your facility will be with a certain type of equipment.”

After deciding on the equipment you need, Magnus added that the next step is to design the facility, e.g., the processing floors for the bioreactors, the downstream equipment, filling rooms, buffers, media preparations etc. “This is how the BioPhorum process maps can be used, as the starting point of an engineering study.”

Benefits

“The maps give you a complete overview of the different types of processes and help you go into more specific design details, e.g., what type of equipment and its scale,” said Magnus. Example process maps include those for cell bank and plasmid preparation for transient transfection in gene therapy, and autologous and viral gene editing in cell therapy.

“They also help users connect the number of patients that need treatment with the size of your equipment and, ultimately, your facility. For example, if you want to treat 4,000 patients per year, the size of the bioreactor is one of the main design criteria for the facility because everything else is sized according to that. In that whole calculation, the process maps are very helpful.”

He suggested that it is hard to quantify the cost savings from using the process maps, other than to say that time is money, and the maps will definitely speed up the early phase of engineering projects.

At the start of a new project, there are always a few months when the team is just trying to understand it. This phase goes much faster when you can put the process maps on the table as they let you understand how a process works without having to do extensive research
Jørgen Magnus, Strategic Program Manager at Bayer’s Cell and Gene Therapy Unit

Lessons learned

Magnus said that the first step should always be to understand the facility design process. “Some people might say they have a piece of land and they want to put a facility on it, so let’s see what we can fit into that building. But this is the wrong way to do a feasibility study. Instead, you should start with what you need the building for. So the question is, how many patients would you like to treat and with what kind of processes?”

He added that you should always start with your core process then design everything around that, e.g., your utilities and other requirements. “Then you go into the facility requirements, cleanroom classification, bio-safety levels, etc. After that, you go to the next layer, which is the building itself. So, you should go from the inside to the outside.”

The process maps now use improved navigation, e.g., clicking on a high-level process box that takes you to a detailed process map. “Looking ahead, I can see that the process maps could be made even better by including more detail on the processing steps and the equipment that we suggest for each one. At the same time, a second version could include more simple presentations to make them easier to read.

“BioPhorum’s CGT process maps can be used for designing a company-specific process and production facility,” said Magnus, “and are a great first step towards industry standardization.”

NEWS
A view from industry on the implication of the new Annex 1 requirements on visual inspection process
NEWS
Maine and Minnesota – the BioPhorum responses to US state PFAS consultations
NEWS
BioPhorum Supply Partner has become Supply Resilience
NEWS
BioPhorum’s sustainability ambition – let’s move out of the holding pattern
NEWS
Building a resilient business means adopting water stewardship

Advanced Therapy Medicinal Products

Advanced Therapy Medicinal Products support the quest for better and faster development of cell, gene and RNA therapies​ through connecting therapy developers, contract manufacturing, and testing organizations to gain an understanding and respond to the challenges faced by the advanced therapeutics industry.

Development Group

Development Group accelerates and improves the development process of biopharmaceutical medicines for the benefit of the patient. Replacing isolation with collaboration by providing a “safe” space where subject matter experts can work on sharing solutions and best practice on emerging industry trends, implementation of new technologies and common issues whilst ensuring their intellectual property and confidentiality is protected.

Drug Substance

Drug Substance advances excellence in drug substance manufacturing and testing, acting as an industry voice to accelerate technology adoption, implement post-approval change more rapidly and increase confidence in maintaining compliance.

Fill Finish

Fill Finish accelerates development and acceptance of sustainable world-class filling and packaging operations for drug product which meets the future needs of patients. Through innovative solutions resulting from the sharing of expertise, we can overcome common performance challenges and deliver on quality and regulatory compliance.

Information Technology

Information Technology accelerates digital maturity across the ​global pharmaceutical manufacturing industry.

Quality

BioPhorum Quality provides a dedicated, safe space for quality professionals from biomanufacturers and contract organizations to coalesce and enhance effective collaboration to address shared industry challenges.

Regulatory-CMC

Regulatory CMC brings leaders together who have a common goal – to improve access to medicines through innovation in the Regulatory ecosystem. It provides a dedicated space for strategic leadership and a coordinated industry voice, to move from divergence to convergence.

Supply Chain to Patient

Supply Chain to Patient transforms the performance of global pharmaceutical clinical and commercial outbound supply chains through industry collaboration by creating transparent patient-centric, resilient and agile E2E supply chains, that consistently deliver high-quality medicines ensuring an uninterrupted supply to patients.

Supply Resilience

Supply Resilience is a trusted advisory group and collaboration that is the engine for driving change across the global industry for all things relevant to the inbound supply chain. Addressing the challenges of complexity, resilience, cost, sustainability, and innovation.

Sustainability

Sustainability enables the industry’s transition to a low carbon, circular future – supporting members to improve patient health while respecting the planet. We activate multi-disciplinary teams drawn from our network to deliver environmental sustainability improvements across the value chain.

Technology Strategy

Technology Strategy acts as one voice of the industry to define strategy, accelerate technology transformation and support technology translation and adoption. With a purpose of enabling the future state of flexible, resilient, sustainable end-to-end biomanufacturing.

DOWNLOAD
An industry perspective on understanding AAV capsid content variants
Needle On Yellow Background
EXTERNAL-RESOURCE
An intercompany perspective on practical experiences of predicting, optimizing and analyzing high concentration biologic therapeutic formulations
DOWNLOAD
The Drug Substance 2.0 Strategic Value Framework
Coloured dots on teal, next to vial
DOWNLOAD
BioPhorum’s holistic approach to container closure integrity
Magnifying glass over a tablet all coloured blue
DOWNLOAD
Digital Plant Maturity Model 3.0
NEWS
Inaugural BioPhorum Quality face to face – get involved
PODCAST
The next step in building regulatory as a capability to enable strategic innovation across the BioPhorum community
NEWS
A launchpad for an improved CGT outbound supply chain
DNA and Earth on blue background
DOWNLOAD
A vision for the biopharmaceutical industry’s inbound supply chain
NEWS
Building a resilient business means adopting water stewardship
Technology Roadmap V 2.0
DOWNLOAD
BioPhorum Technology Roadmapping roadmap vision 2.0

Publications

Documents including best practices, vision statements and peer reviewed papers to help you take value back to your business.

Webinars

Discussing all aspects of the biopharmaceutical industry, from digitization and knowledge management to raw materials, supply chain, sustainability and more. Learn from the perspectives of those at the forefront of the industry.

Podcasts

BioPhorum Connect is our podcast series that keeps you up to date with the latest news and trends in the biopharmaceutical industry. From experienced professionals to thought leaders, these podcasts bring you the insights and perspectives of experts from around the world.

Tools

A variety of resources including design tools and user requirement specifications to help you improve and streamline your business processes.

Benchmarks and Surveys

Research conducted among the BioPhorum membership providing evidence to support change and identify best practice.

Browse all

Access a variety of free tools and papers and other resources designed to provide you with up-to-date information and insights to help you make informed decisions and maximize your success. Access our resources today and start making improving and streamlining your business processes.

WEBINAR
Bioreactivity testing in single-use system biomanufacturing
WEBINAR
Bioreactivity testing in single-use system biomanufacturing
WEBINAR
Bioreactivity testing in single-use system biomanufacturing
Magnifying glass over a tablet all coloured blue
DOWNLOAD
Digital Plant Maturity Model 3.0
WEBINAR
Bioreactivity testing in single-use system biomanufacturing