As the development of cell and gene based therapies continues to grow, we are now seeing a new, but predictable set of pressures arising soon after commercialization.
So far, most of the discussion in cell and gene has been around pre-commercial science, especially in the areas of advanced analytical techniques and in the design, execution, and conclusions from clinical trials.
Earlier this year, I had the honor of presenting at the Advanced Therapies Conference in London about how the decisions we make in early stages of development can help or hinder the achievement of the big milestone, that of product approval. I was surprised at how many of my audience were from companies in those early stages, who had only limited understanding of the later parts of that path to licensure.
At Quality Executive Partners, we are now starting to see challenges and pressures appear on the other side of the veil, beyond the licensure milestone. These challenges are predictable, at least to those who have worked in commercial biopharma, but out of a combination of necessity, prioritization, and simple naivety, have not been provided for, or even considered, during the development process. We all said, “We will fix that later, after approval”.
So, what are these not-so-new challenges? To quote Dan Aykroyd in Ghostbusters “you don’t know what it’s like out there, I’ve worked in the private sector, they expect RESULTS!” It turns out, at some point, it has to become all about the money, and COGM (Cost of Goods Manufactured) is the phrase we hear in the corridors and meeting rooms of the senior leaders. Just like Ghostbusters, we have seen this movie before.
The answers are easy to list, harder to implement, and devilishly hard to implement correctly, so that they yield sustainable benefit. Wisdom to choose targets correctly and in moderation from absolutes are key.
Areas to focus on are:
- Scale up vs scale out. Getting away from repeated manual processes in hoods and cabinets reduces variability (and potential for some types of error), reduces cost and dependence on skilled staff, and provides for per-operation costs to be reduced, or scale to be increased.
- Improved analytical performance, in terms of precision, accuracy, low invalid/failure rates, and reduced testing lag times. Assay automation, such as that used on plate assays, can do a lot here, but the assay technology needs to mature too. A robust analytical development and improvement plan is necessary. Many companies skip this important planning and just move to doing, without enough thought.
- Yield improvements and reduced batch failures. Here, we can fall back on process validation and continuous process verification practices. Take the time to understand the cause-and-effect relationships in your process. Use small scale models and DOE [(design of experiment) to develop structured data. Confirm learnings at larger scale, then make step changes. Your regulatory friends (and your regulators) will love you for this.
All of this seems a bit glib and easy to say. It is! And, as noted before, it’s much harder to do well. Many companies will say “we’ve got this, we know how to do it, we don’t need help” and that may be true. However, my experience is that good help, the kind that knows what to do and how to do it, and is focused on mutual success vs milking a client, is REALLY worth having. My experience is also that Quality Executive Partners is that good help. We’ve done this before, let’s talk.
If you would like to read the first two articles in Mark’s 2023 six-part series in Cell & Gene, click here to begin: “Cell and Gene: Article Series on CGT’s Key Drivers.”
Mark Roache, QxP VP of Cell and Gene Therapies, has spent his 30-plus year career in GXP. Mark was the Chief Quality Officer for AveXis (now Novartis Gene Therapies) at the time of Zolgensma launch. He was previously Senior VP of Quality for KBI (a CDMO with cell-therapy capabilities) and has held other senior Quality roles at Novartis, Merck and Bayer.
