Process analytical technology (PAT) integrates analytical technologies into the biomanufacturing process to achieve the timely measurement of process parameters and product quality attributes. For new and emerging complex biologics – such as cell, gene, and RNA therapies (CGTs) designed for patients with high medical needs and typically manufactured in small batch sizes with short shelf lives – there is a need for speed and deeper process understanding. CGTs stand to benefit greatly from employing PAT.
However, with unique critical quality attributes, complex mechanism of actions and heterogenicity issues, developing PAT approaches for CGTs will likely present additional new challenges than those encountered with PAT for more established biologics (e.g., monoclonal antibodies). These may be best addressed by industry working collaboratively.
This is why BioPhorum Cell and Gene Therapy brought together 198 subject matter experts from 40 different CGT companies for a two-day virtual event in March 2023. This focused on understanding the challenges and opportunities for PAT in the CGT space, performing industry benchmarking activities, and sharing case studies and suggestions that may ultimately accelerate the implementation of PAT.
The output from the event is summarized in A commentary on the current process analytical technology status and opportunities for cell and gene therapies.
Our commentary summarizes the CGT industry views on PAT articulated during the virtual event and documents key takeaways on the benefits and barriers to PAT. It also notes the unique considerations for PAT in the context of CGTs and highlights some near-term options to help you accelerate these important therapies to patients before implementing PAT.
To look at the application of PAT tools for CGT modalities, we conducted a pre-event benchmarking survey that gathered feedback from 28 experts from 21 different CGT companies. The findings include:
- Only 25% of respondents have started to implement PAT, while 50% intend to implement PAT in the near future (of which, the majority currently focus on in vivo gene therapy and in the non-GMP environment)
- Only two had initiated any regulatory discussions related to PAT implementation
- Where PAT is being used, it is mostly seen in upstream processing steps – there is more work to do to achieve its widespread adoption in both upstream and downstream processing.
The event also featured a PAT lab of the future virtual tour and the opportunity for attendees to discuss quality system improvements that could provide options to reduce batch release turnaround times irrespective of the PAT status.
The consensus from the event is that, for these complex modalities where process understanding is inherently poorer than for more established biologics, PAT adoption has the potential to transform CGT process characterization and manufacturing, expediting these life-changing therapies to patients. Our paper is a great contribution to the debate and lays the groundwork for future collaborative work with industry, regulators, and suppliers working together to advance PAT integration to realize improvements in process control that are fit for CGTs.