Inventing new GMP peptide manufacture
By Alastair Hay, PhD, MBA
Account Manager – Peptides, Almac Sciences
“Necessity is the mother of invention” is a quote attributed to the Greek philosopher, Plato. The phrase has become something of a proverb, and is pretty self-explanatory – when we face challenges, we need to find new ways to get things done. Today, we are globally living this philosophy as we tackle the devastating COVID-19 pandemic. In the more mundane world of GMP peptide manufacture, the challenge is no less real. As researchers find new ways to tackle human disease, manufacturing methodology must adapt in order to make the research ideas a reality.
In a recent article(1) we described how we tackled the question posed to us in 2012, “Can you make 20 mg each of 20 GMP peptides in <4 weeks?”. Researchers were wanting the rapid manufacture of neoantigen-derived peptides for use as individualized cancer vaccines. Speed was crucial. Quality was crucial. We spent a long time mapping the GMP process, and building an appropriate GMP quality system. We built the approach from the ground up as there was no guidance to work with. Almac’s high throughput NeoPeptide™ offering was born. We started the journey in 2014, and using a few stepping stones, we brought full GMP online in 2018. We now have multiple GMP manufacturing lines. Our processes undergo continuous improvement, and there are many more upgrades in the pipeline.
Nothing stands still. The interest in peptides as vaccine modalities has increased dramatically in the last few years, and there are numerous promising clinical trials underway. As typified by the NeoPeptide™ world, vaccines are by definition low dose, and limited treatment regimens, and so the quantities required are dramatically lower than for conventional therapeutics. It is also the case that multiple peptides are required in order to ensure that patient epitope coverage is maximised. Developing product-specific processes for multiple peptides is a time-consuming and costly task. A Phase I trial is likely to require less than a gram of material for each peptide, so adopting a conventional approach to development and manufacture is a large burden to bear in order to generate preliminary clinical data.
At Almac, we have looked at projects requiring GMP manufacture of multiple peptides for early phase trials in a different way. We have adapted our NeoPeptide™ principles to create a robust, fully GMP compliant approach. Instead of taking many, many months, or even years of upfront development and manufacturing time, we can produce a gram of multiple peptides in a matter of weeks – around 10% of the time of the conventional approach. There are no short-cuts. This isn’t “GMP-light” (not a philosophy Almac subscribes to). It is a fully GMP-compliant process built around a quality system designed to deliver requirements of the high throughput niche.
The result? Researchers get to the clinic faster and cheaper than they would otherwise have been able to achieve. It may also be the difference between programmes reaching the clinic or not in circumstances where conventional approaches are prohibitive. As later clinical phases are reached, and scale up is required, a conventional development/manufacturing approach will be adopted, but that stage is reached in a more streamlined manner and with more clinical data under the belt.
(1) www.chemicalsknowledgehub.com October/November 2019View Resource
Almac API, Chemical Development, Analytical & Solid State Services
Almac Sciences provides integrated services from development to commercial scale of advanced intermediates and Active Pharmaceutical Ingredients (API).
We provide a range of services for small molecules (including highly potent) and peptides. We have a proven track record of saving time and cost through the integration of our services and application of innovative biocatalysis and technology solutions.
We offer a full suite of analytical testing for a range of different product types including small molecules, peptides, biologics, conjugates, potent and controlled substances.
Our vast pool of scientific knowledge can help to overcome the analytical challenges that typically arise during drug development.