Demographics & Responses

Vectors, Manufacturing and Supply Chain

Demographics

Representatives from biotech companies made up the majority of participants with 39% and medical device companies/regulatory agencies were the lowest.

VP/Head/Directors were the most popular job titles for this survey with 33% whilst investor and research were the least popular job titles.

The majority of participants of this survey were based in North America at 48% and 35% of participants were from Europe.

Over 52% of the companies that participated in the survey focus on oncology. Rare diseases is also a popular area of focus.

Gene therapy and CAR-T are the main focus areas or are in the pipeline for the participants of this survey.

Over 37% of our participants are in Phase I of their cell or gene therapy clinical trials and another 33% of the participants are in Phase II.

Over 32% of the survey participants are working with AAV vectors.

What are the main vectors types you are working with?

50% of the participants use Real-Time PCR when characterizing their vectors. DNA Hybridisation Assays is the least popular tool amongst the participants.

Majority of the participants thought the greatest need for emerging tools is for monitoring quality throughout.

There was a range of opinions regarding the importance of Critical Quality Attributes. Safety and potency were considered the most important.

Viral vectors used in production and plasmids were voted to be the most limiting when considering raw and starting materials used in viral vector manufacturing whilst buffer components were considered the least limiting.

When considering raw and starting materials used in viral vector manufacturing where are the biggest limitations?

The participants considered inefficiency in downstream processes and effects on potency as well as volume of supply to be the critical pain points in the transition.

This open question received many different responses from the participants – however, the most common theme was scalability. The responses ranged from ‘scalability on same platform to enable rapid scale up from lab to commercial supply’, ‘scalable flexible manufacturing platforms are necessary’ and ‘scale up of animal free high quality component’. Other common answers included switching to non-viral vector solutions, GMP compliance, improved yield, higher titers and industrial standardization.

As the demand for vectors in the space grows, where do you think the biggest changes need to be made with regards to current manufacturing platforms? (Selected responses)

“Yield, large scale and rapid manufacturing, turnaround time for autologous therapeutic products.”

“Better tools for purification and characterization of vectors.”

“Process efficiency and robustness need a quantum leap. Current processes are clunky, expensive and unreliable.”

“Scalable flexible manufacturing platforms are necessary. More work has to be invested to also target such cell types efficiently which are not addressed by current vector surface proteins (such as VSV-G).”

“True scaling up with AAV rather than scaling 'out'.”

"Lack of coordinated and standardization of processes for intellectual property considerations. The field is evolving from a less populated / collaborative approach to a more crowded / competitive mindset with its growth."

"We are currently switching to non-viral DNA delivery systems. The manufacturing of vectors is becoming cost-prohibitive for us to do ourselves and also to purchase from other vendors."

"Clarity on allowable use of animal derived components such as FBS."

"More stable cell lines- need for less complicated plasmid process where possible process intensification- to suspension platforms (linked to point 1) reduction in COGs also ensuring high purification yields and less freeze/thaw losses."

"Small footprint, flexibility and analytics."

"Higher titres / downstream; flexible cell lines; inline monitoring re. CQAs - real time release."

"The viral vector production should be manufactured only in GMP approved site."

"Size and number of genes each vector can carry."

In response to current bottlenecks in supply chain, more than half of applicable respondents had considered or have previously worked on potential cryopreservation of viral vectors, whilst the rest have not.

Encountering stability issues is the main hurdle that 61% of the respondents see when cryopreserving their vectors. Meanwhile, almost a third see a lack of good protocols for this process. The remaining 10% reported that they experienced no issues in their cryopreservation.

59% of the participants are working with viral methods when considering viral gene therapy delivery.

Out of non-viral methods, most of the survey respondents are working with messenger RNA and plasmids.

Non-viral solutions

Irrespective of which method you are currently using which of the below do you think non-viral has the potential to address?