CMC and staffing must be resolved if CGTs are to go ‘supersonic’

CMC deliverables must be addressed to continue CGT momentum, but overcoming talent gaps will give firms the competitive edge, says former Spark Therapeutics CTO Cynthia Pussinen.

With 10 approvals in the US and Europe last year, there is little doubt the cell and gene therapy (CGT) sector is blossoming. Consultant Cynthia Pussinen described the sector as having “lifted off and in flight” at Phacilitate’s Advanced Therapies Week earlier this month, with much progress including “truly rewriting how patients are treated and how disease cured.”

However, having reached this inflection point and poised for a wave of more significant advances in the field, she told delegates: “We’re trying to figure out how do we now go supersonic.”

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With around 2,500 therapies in clinical studies, more than 3,500 products being evaluated, and more than 50 products expected to be approved by 2024, “the bottom line is that the landscape is rapidly evolving in front of us.”

But to keep up with momentum and realize the full potential of CGTs, industry must address numerous challenges, though according to Pussinen, CMC (Chemistry, Manufacturing, and Controls) is key in enable scaling-up and the reliability of products while simultaneously lowering the cost of goods (COGs).

“There’s an increasing awareness that CMC is a hot space to be in, she said. “CMC is the cause for far more disruptions and delays in the cell and gene therapy development compared to mAb programs,” or 43% of all CGTs – 52% of viral vector-based and 50% CAR-T programs – vs 28% monoclonal antibodies, according to a 2021 McKinsey report. Of these, CMC issues caused 12% of CGT disruptions, compared to 3% for mAbs. And of these CMC issues, comparability/analytical issues represented the bulk of the problems, followed by manufacturing site issues (e.g., 483s and inspection delays).

Other pressing challenges include: Increasing expectations from regulators coupled with a lack of clarity, required advancements in process and analytical development, better comprehension of potency assays and characterization, a lack of consistency of raw materials and batches, and problems surrounding clinical trial design and recruitment.

Talent search

But one of the main issues that has gone under the radar is the talent shortage being felt in the CGT space.

“People are your greatest asset and your competitive edge in this business,” she said. While there have been layoffs of late, “there’s still a war for talent.”

An aging life sciences workforce, workforce exits, and the advent of new modalities is leaving the US biomanufacturing sector short across the board and with growth in industry outpacing the arrival of new talent, Pussinen pointed to research from Evolution Search Partners indicating Q2 2023 will mark the inflection point when demand outstrips supply.

“[The CGT sector is] part of the challenge because as we’re growing, we’re creating that need for more and more talent. Some estimates indicate that we’ll face somewhat of a supply demand equilibrium depending on how quickly the people pipeline fills or refill.”

Pussinen’s not alone in highlighting the need for talent in the CGT space. McKinsey & Company wrote about it in a blog post last year, while SwedenBio highlighted the issue in 2021. Meanwhile, several initiatives are looking to bridge the gap, including virtual reality and frontline worker training programs.