About a year and a half ago, we were asked by a client in the US to help them implement capacity planning & detailed scheduling for manufacturing and quality operations in a CAR-T cell & gene therapy production plant. What are the insights that we have gained since then? And what have we discovered as game-changing elements in the end-to-end supply chain orchestration?
What is cell & gene therapy?
Every human being consists of cells. Each cell holds genetic material or DNA. Unfortunately, things can go wrong with that DNA.
A part can be missing, which is commonly known as a genetic disease. Or certain parts of the DNA might be weak, unable to fight effectively against aggressive diseases like cancer. The basic premise of cell & gene therapy is that it cures diseases by modifying (strengthen) or correcting (cut & paste) parts of the patient’s DNA.
A new, very promising & high-value technology
Today, there is a limited number, 4 to be exact, of such therapies approved. But it is expected that as of 2025, up to 20 new therapies will be approved every year. The first therapy that was launched commercially in 2017, is called Kymriah. Kymriah is a therapy that strengthens the patient’s body to more effectively fight Leukaemia.
Kymriah and other cell & gene therapies are considered as very effective for very complex diseases. This is because CGT therapies are very targeted: manufacturers create a unique treatment for every individual patient. But the fact that these are one-patient treatments also means they are costly to produce (=low volume, high value).
It’s a game-changing market
Cell & gene therapy supply chains are substantially different from traditional pharmaceutical supply chains, where the most stretched case is autologous therapies that use the patient’s specimen as the raw material for the on-patient batch production. This approach requires a fundamentally different supply chain management and operations planning approach.
The need for robust supply chain processes already starts in the clinical trial phase, making it an even bigger challenge in a domain where supply chains are still very immature. Phase III CGT trials supply chains cannot be managed with Excel and paper.
So, what are those ‘unique challenges’?
Looking at the end-to-end process, it consists of different steps that are unique to cell & gene therapies.
Organizing market access
- Forecasting the number of patients is tough to forecast because it strongly depends on market access decisions and reimbursement policies.
- Typically companies know how many to-be-treated patients there are in each country, but it’s hard to predict when they will be able to treat them. This, because it depends on if / when / where the therapy will be included in the reimbursement policy.
- Companies are organizing market access, but the actual green light of the therapy is out of their hands.
- This results in high variability in any forecasting effort and is, therefore, quite a challenge: companies need to build up capacity but by when? That exercise is expensive, and all the more challenging when done blindfolded.
Request for a treatment
- A supply chain, as the traditional life science companies know it, is ‘push-based’: they produce a product, put it in inventory, and distribute it through the different market layers.
- In CGT, it’s not a ‘push’ but a ‘pull’ supply chain: the demand is generated by an individual patient, for which an on-demand treatment needs to be made. Push & pull supply chains are literally opposites, and bring their own set of specific challenges.
The manufacturer has to confirm the request
- As there are multiple patients requesting treatment at the same time, and CGT manufacturers have a limited capacity, they now need to decide: who will we treat? And who will we treat first?
- These are very complex decisions to make, which require factoring in a series of aspects such as the medical condition of the patient, the regulatory environment, the reimbursement policies and ethical considerations.
- Once a patient is entitled to the treatment we enter the capable-to-promise step:: to which site will we allocate this patient batch? What makes sense? Will we have enough capacity and is it utilized in the most optimal way?
Specimen is collected
- The specimen is collected at a treatment center (hospital) by nurses & doctors.
- What if the nurses & doctors that are responsible for the collection are not available? What if the patient is too weak to travel to the treatment center on the day of the specimen collection? The appointment gets rescheduled, which in turn has a significant impact on the rest of the supply chain.
- As soon as the specimen is collected, the clock starts ticking. There is a fixed ‘vein-to-vein’ time, which means that in order for the treatment to be successful, it has to be delivered within x number of weeks after the specimen was collected.
Transported to and from the treatment
- Specimen & treatments are very sensitive and therefore have very specific and validated conditions to transport.
- This is what we call ‘cryogenic transportation’ (specific conditions + low temperatures) which is expensive and has a limited capacity.
- Traditional life science production processes are known to be quite sequential or linear in nature: you produce, do quality control and release the product to the market. CGT on the other hand is highly interactive: every hour there are interactions between production, quality control, quality assurance, regulatory affairs, … in a constant re-evaluation of the patient batch.
- Organizing capacity is also a whole different ball game in CGT: manufacturers have to ramp-up capacity to tackle the initial backlog, but then have to dismantle it again once they reach steadier waters. All while it’s hard to predict: when will the therapy be approved? What about the re-imbursement policies?
Follow-up and after-care
- The journey does not stop when the therapy is delivered. There needs to be a process of patient follow-up, done by skilled staff, … not for a couple of weeks, but often several years!
How can Binocs help? Our vision!
It’s clear, there are a lot of unpredictable variables linked to each patient batch. And, as the number of treatments and patients is growing rapidly, CGT manufacturers need to make sure there are scalable business processes in place that can handle the high variability in the supply chain: they need to become more agile and have the ability to react in real-time to changing circumstances.
Binocs is a digital planning & scheduling software for knowledge workers (scientist, lab analysts, …), and we are currently implementing specific modules in our product, in co-creation with some of our customers, to better support CGT manufacturers in dealing with the high variability in the supply chain. The 6 modules in our Binocs product, specifically for CGT:
Binocs continuously synchronizes with patient journey platforms like Trakcel, Vineti, in-house platforms, … as well as seamlessly integrates with the production shopfloor (LIMS, ERP, AMS, …).
Dynamic site & slot allocation
Binocs can automatically allocate patient batches to sites & slots, based on configurable assignment rules, optimizing utilization rates.
This process is dynamic (updated & optimized constantly), as Binocs continuously synchronize with patient journey platforms, treatment centers (CRA), and the rest of the supply chain.
Projected slot capacity management
Slot capacity management in Binocs helps you to generate visibility on what you project as available capacity in (slots/day) for patients’ batches.
This in turn allows you to handle exceptions better (cancellations, non-availabilities, holidays) and optimally utilize backup slots when needed.
Binocs can automatically create a day-to-day schedule across all teams. And can be re-shuffled in a click of a button to deal with changes in the planning.
The digital schedule board makes your planning transparent & easy to distribute to your teams.
As we are tracking progress, you get real-time visibility across your different patient batches. You can then zoom in on the status of individual patient batches and ACT.
Operating model management
Incoming patient batches are automatically translated into sequenced and integrated production steps, QC operations, …
This means that it is easily scalable: from scheduling one team to scheduling a multi-site supply chain. Or from handling a couple to a lot of patient batches at once.
In summary: 3 key take-aways
A new market
We are looking at a completely new market where demand is exploding, but the supply chains are immature.
Complete mind shift in the way we look at and organize the supply chain. Even if the processes become more robust in the future, there will always be a high level of variability (patient condition, …).
Need to be agile
Companies need to react in real-time, they need to become more agile: immediately capture varieties/events and react to them in real-time.
So, are you eager to find out more about how we can help you in orchestrating cell & gene therapy supply chains?
Fill in the form below and we’re happy to share you with some more insights.
Check also how to increase planning adherence in QC Labs.