Cell and gene therapies (CGTs) are rapidly gaining popularity as proof-of-concept data becomes available. This has resulted in an increase in the number of biotech companies that are investing in developing their own products. With five different cell and gene therapies gaining FDA approval in 2023 alone, there has been a steady influx of potentially life-changing treatments for patients with a wide range of disease indications.1
Although cell and gene therapies may have the potential to revolutionise the pharmaceutical market, they are still relatively novel and come with unavoidable and complex challenges that must be overcome; these extend all the way from discovery to commercialisation. Therefore, outsourcing manufacturing has become increasingly appealing for CGT developers, who are beginning to outsource the process to contract development and manufacturing organisations (CDMOs).
With so many CDMOs offering a range of services at different price points, quality levels and development timeframes, picking a suitable partner can be a daunting experience for any biopharma organisation — small or large. So, what makes a good CDMO? To find out, Annabel Kartal-Allen spoke with Andrew Frazer, Associate Director of Scientific Solutions at Charles River Laboratories.
Outsourcing can provide ... access to the best technologies without having to commit to buying bespoke equipment
Why use a CDMO?
There are many steps involved in the commercialisation of a cell and gene therapy product, so getting one to market requires companies to surpass many milestones. Here are a few reasons why businesses should consider outsourcing their CGT operations.
The cost and associated risk of development/manufacture: There are many costs associated with the manufacture of cell and gene therapies — including raw materials, development costs and clinical trials, as well as testing and quality control. Small mistakes can have big impacts, so utilising an experienced CDMO to cover all these bases can save developers significantly in the long-run.
To manufacture complex therapies such as CGTs in-house, companies must also have access to advanced, often specialist equipment. This can be a costly investment for pharmaceutical companies — many of which will not focus entirely on cell and gene therapies. Therefore, outsourcing can provide companies with access to the best technologies without having to commit to buying bespoke equipment.
Specialist expertise: Although CGTs haven’t been around for as long as small molecules or more traditional biologics, there is a growing base of field specialists, with many of them currently working in the CDMO space. Gaining insider know-how from specialist teams who have worked with a large number of CGT products can make a huge difference in terms of kick-starting a programme and getting the product to market as quickly and efficiently as possible. 
Production efficiency: As CDMOs often have extensive experience in their respective fields, they will have a more detailed understanding of associated development and manufacturing hurdles and how to mitigate them before they become major issues. An experienced CDMO will have the capability to reliably deliver with respect to cost, timelines, compliance, sustainability and yield.
The perks of having one partner
Although there are many CDMOs on the market who are able to serve clients in the cell and gene therapy market, development and manufacturing is just one piece of the puzzle, meaning that companies typically have to enter into and manage partnerships with multiple contractors to commercialise their therapeutic. Because of this, Andrew advises companies to find a partner with expertise in all stages of the CGT development process.
According to Andrew, a big differentiator between a good and a great CDMO is their ability to offer an end-to-end service: “Having a CDMO on side that has a strong history in discovery, safety assessment and testing — as well as manufacturing solutions — creates efficiencies and can add significant value to the partnership.”
“At Charles River, we have developed extensive capabilities in contract development and manufacturing, complimenting the success of our development and safety assessment services. This allows customers to select a provider that can support them through their full product life-cycle, rather than having to manage multiple partnerships.”
A key consideration ... is a CDMO’s ability to support analytical development, while also offering an established suite of quality control testing
Considering early stage manufacturing
Production of representative and compliant materials is a key element involved in the overall success of a therapeutic product. “Typically, developers won’t want to invest heavily — particularly at the early stages — to generate compliant materials for use in preclinical development or early stage clinical trials,” states Andrew. “That’s why many choose to outsource this aspect of the CGT development process — with the potential to then move operations back in-house post-approval. A CDMO is there as a specialist manufacturer with a full range of capabilities and production scales that a drug developer wouldn’t necessarily have.”
Having proven and compliant manufacturing platforms, as well as testing for plasmid and viral vector production ready to incorporate into your model can speed up the process by avoiding laborious development times.” Andrew says.
Incorporating analytics
There are many elements to the cell and gene therapy manufacturing process. One key consideration, Andrew notes, is a CDMO’s “ability to support analytical development while also offering an established suite of quality control testing to support development and manufacturing activities.” A previous article from Manufacturing Chemist highlighted the importance of developing potency assays early on in the process, so companies would be wise to find a CDMO who can assist them with this.2 
"With the majority of CDMOs outsourcing analytics, finding a partner with fully in-house analytical testing capabilities can save time, money and effort,” Andrew emphasises. “When another level of complexity is added to the development chain, it can cause a bottleneck in the speed of manufacture and create major challenges with scheduling for complex programmes. It also requires a developer to place their faith in a company they may not directly interact with. By working with a single provider for manufacture and testing, developers have the opportunity to recognise more reliable timelines and reduce overall complexity and risk associated with manufacturing activities.”
Building a relationship with your CDMO
One of the most important aspects of a development and manufacturing collaboration is the relationship between a contractor and their client. By forming a close working relationship with your CDMO, you can ensure that all the processes in their remit are being conducted how you want them. Not only do you have better control of your therapeutic’s success, but you can also work with them to adapt and make changes if necessary — which is significantly easier if you’re on good terms.
Andrew believes that companies should prioritise building relations: “Effective collaboration between a CDMO and a customer is incredibly important and anyone who’s entered into this type of activity will know that managing manufacturing activities — particularly if a number of separate companies are involved — can be particularly challenging.”
To overcome the logistical challenges of managing multiple CDMOs, Dr Frazer recommends that businesses aim to find a partner that can support all stages of the development journey. “By partnering with a CDMO with end-to-end capabilities, developers can have one point of contact and develop long-term relationships, helping them to reduce the organisational burden associated with managing the activities of multiple research, manufacturing and test sites.”
“Developers have an extensive range of activities they’ll need to split their time and effort between. Simplifying outsourced activities like contract development and manufacturing can significantly reduce the labour burden while also creating opportunities for improved timelines and reduced risk.”
References
1 www.nature.com/articles/s41587-024-02166-7.
2 https://manufacturingchemist.com/why-potency-assays-are-a-crucial-consideration-for.