Cell and gene therapies (CGTs) are transforming the way we treat, and even cure, disease. Since the first CAR-T therapy was approved in the United States five years ago, there has been significant growth in the number of companies focussed on developing CGTs. However, CGTs are complex products and this complexity gives rise to unique manufacturing challenges compared to traditional small molecules.
The difficulties associated with CGT manufacturing were amongst the topics discussed at the One Nucleus event last night (15 November 2022) held at the Royal Veterinary College in London. Sitting on the panel was:
- William Raimes, Head of Process Development, Ori Biotech
- Michael Kyriakides, Life Sciences Investor, Synconca
- Dirk Werling, Director, Centre for Vaccinology and Regenerative Medicine, Royal Veterinary College
- Bams Abila, Visiting Professor (Clinical Pharmacology; Biologics & ATMPs), Kings College London
Panellists discussed how biotech companies have not tended to pursue the fully integrated manufacturing model traditionally favoured by big pharma and have instead tended to prefer an outsourced manufacturing model forming partnerships with CMOs. Michael Kyriakides (Syncona) noted than an outsourced manufacturing model makes sense for early stage companies, particularly as it is cheaper in the early stages of development (noting however, that this may not be the case in the long term). The alternative, building out an integrated in-house manufacturing capacity, necessarily requires a significant amount of capital and as a result has not been viable for early stage biotech companies.
As well as the technical manufacturing issues associated with the complex nature of CGTs, over the past few years there have also been a squeeze on manufacturing capacity with some CDMOs booking out capacity years in advance. In part this is due to the increasing number of companies working in the CGT space, each of whose capacity requirements grow as their products progress through the development pipeline. There have also been widely reported shortages of viral vectors (we examined some of the reasons in this article earlier this year see: https://www.bristows.com/news/viral-vectors-shortages-and-innovation/).
While CDMOs have been rapidly building out capacity, CGT manufacturing remains a small part of the CDMO market compared to large scale manufacture of more traditional drugs. These issues mean that CGT companies need to take potentially difficult, long term strategic decisions regarding manufacturing earlier than ever.
With more CGT products progressing through clinical trials to approval it seems clear that manufacturing will continue to be a key focus area for the CGT industry. William Raimes (Ori Biotech) highlighted the potential for growth in the CAR-T market in particular (with 15,000 patients currently, compared to an addressable patient population of 900,000). Raimes also gave a glimpse into some of the innovative solutions the industry is exploring to address manufacturing issues associated with CGT products. He proposed a decentralised platform manufacturing model using manufacturing pods and making greater use of automation and data. This could enable companies in early development to use one device for process development and to scale up by adding multiple devices in clinical manufacturing. Such an approach may also enable developers to iron out out technical issues earlier on, potentially saving time and money and making for a more efficient development process. Raimes suggested the devices could be located at hospitals, potentially addressing logistical manufacturing issues, in particular avoiding the need to freeze and ship cells internationally.
As the industry grows and matures over the next few years it will be interesting to see how it adapts to address manufacturing issues. We expect CGT companies will continue to need to take early strategic decisions regarding manufacturing, but it seems that the options available to CGT companies are likely to grow.