TIDES TV: Achieving GMP Quality in Protein Manufacturing

August 31, 2021 / by Justin Byers

Justin Byers, Client Relations Senior Manager, GMP Custom Protein Services at Aldevron discusses important considerations for achieving GMP quality protein manufacturing for advanced therapeutics and vaccines.

He was interviewed by Michael Dunnet for TIDES TV.

Can you describe Aldevron's protein manufacturing experience?

Aldevron has been manufacturing recombinant proteins since 2009. Our focus is on delivering a seamless pipeline of products and services from research use to GMP. That includes gene editing nucleases, ribonucleic proteins and IVT enzymes that fully support mRNA production.

We also offer a dedicated process development team to generate optimal manufacturing methods for research grade or clinical manufacturing of our clients' protein of interest, most commonly client programs start in development and manufacturing at our ISO 13485 certified facility, followed by design and technical transfer to our GMP operations.

For your custom manufacturing services, do you have a specific area of focus and what does the client need to provide as a starting point?

The specific area of focus we work on spans a wide variety of proteins, including enzymes, growth factors and nucleases to fully support an area of gene and cell therapy. We do have a special area of focus on the manufacture of gene editing enzymes and ribonucleic proteins. As part of that focus, we are also committed to the production of enzymes that synthesize and cap mRNA. And while we do have the capabilities to express proteins in mammalian and insect cell lines for research use, our primary production vehicle is E. coli. We can produce proteins from research use through clinical applications.

To answer the question regarding what does a client need to provide, we accept projects at any starting point, as Aldevron has the expertise to develop a robust manufacturing process with as little as an electronic DNA sequence. We routinely generate expression and purification procedures and quality control packages that are suitable for both and in terms of quantity and quality.

When developing a protein production process for GMP manufacturing, what are the most important considerations they take into account?

There are several important factors to consider. We think scalability and robustness are at the top of the list. What works well at a lab scale may not be feasible or economical in a large manufacturing environment. This could be something as simple as a dilution step or chromatography method that does not scale up easily. For example, size exclusion chromatography works great with small samples, but it's not suitable for manufacturing due to the restriction on sample size and the slow processing time it requires.

The production process also needs to be robust so that the specified critical quality attributes can be achieved the first time and every time. That is why it is important to partner with the CDMO that has the experience developing processes that will be robust and economical at the large scale needed to support pre-clinical through commercial stages.

As a CDMO producing therapeutics and vaccines, what are some important considerations?

Above all, clear communication with our clients. That is the most important way in which we can deliver excellent service in support of therapeutics or vaccine programs. We work hard to make sure that we are providing information that is both accurate and timely. We have a dedicated project manager to support the client throughout the process.

It is also crucial that we deliver meeting the client specifications and on time. Our clients rely on us to meet timelines so that they can advance their programs and ultimately get vital therapeutics to patients.

What support does Aldevron provide to clients from its GMP quality assurance and regulatory teams?

Our quality assurance team supports the client starting with the client quality agreement, which defines a process associated with the quality partnership. In addition, our quality assurance team ensures that every aspect from raw material inspection through product release complies with Aldevron's quality systems.

In the past year, Aldevron recently expanded our regulatory support team, which has been well-received and supported our clients with IND and other regulatory filings. Our quality assurance and our regulatory teams are an integral part and our client partnerships and instrumental to our client's success.