APR September/October 2020 - 132

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BIOPHARMACEUTICAL PROCESSING

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Figure 2. Considerations for scaling manufacturing and supply.

multiple processes and provides enough "slack" in the schedule to
effectively manage multiple projects along different timelines.

Early Phase Clinical Trial Design
While not the remit of manufacturing and supply, one additional
factor that can impact the ability to scale out across multiple processes
and products for early phase trials is the trial design. For instance,
when managing trials across our three wholly-owned products, we
have learned that smaller trials implemented across a smaller number
of clinical sites and in a more limited number of countries, creates
strategic relationships with investigators. This helps facilitate rapid
iterations and changes, making them easier to manage. It also means
less manufacturing capacity required for a broader range of clinical
trials, reduced investment in materials, CapEx, personnel, etc. And
given that clinical signals of efficacy (or not) often emerge in a limited
number of patients, having smaller, more focused trials can speed the
"time to insight" from each new trial.

Scaling Up to Manage the Larger and
More Geographically Diverse Patient
Population of a Commercial Product
Manufacturing Process Execution
Once a company is preparing for a later stage trial, considerations
for commercial scale and the need to "lock" the process becomes
the priority. Any changes to the process in a potential registration
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enabling trial will be challenging to implement. The requirement for
comparability between processes or manufacturing sites is high for
any pharmaceutical company, but even higher for autologous cell
therapy companies given the complexity and the "one patient, one
batch" reality.
This is where automation comes into its own, including electronic
batch records, automated environmental monitoring, laboratory
information systems, and software to manage the cell Chain of Custody
(CoC) and Chain of Identity (CoI) requirements. We want to close as
many open steps as possible to reduce the contamination risks to the
product. Applying Lean Sigma principles at this stage is a good way to
improve performance while reducing waste, especially as you move
into higher patient numbers where reducing costs will be imperative.
Unlike large or small molecules where one batch may provide enough
drug product for thousands of patients, with autologous cell therapies
small improvements in operational effectiveness can have a dramatic
impact when doing thousands of individual batches per year.
Within the supply chain it is essential to ensure your supply base can
scale up for higher volumes as well as meet commercial GMP quality
standards. Much of the supply base in cell therapy is also growing from a
research scale and there is high demand for their products and services,
all of which make supply chain planning in an emerging therapeutic
field very challenging. Adaptimmune has pursued a strategy to
build an integrated company so that we can optimize the number of
suppliers with whom we need to work to manage volume and quality.
One example has been how we have evolved our vector supply chain,
starting with material coming from academia during our initial trials,
then moving to CMOs, and finally adding our own in-house vector
manufacturing capabilities in the UK. Our journey started over two years

| September/October 2020

10/2/20 11:46 AM
APR September/October 2020

Table of Contents for the Digital Edition of APR September/October 2020
