Lee Madrid, Ph.D., Head of Global BioPharm Center of Excellence
MilliporeSigma Corp, Burlington, MA
A business of Merck KGaA, Darmstadt, Germany
Geoffrey Rule, Ph.D., Principal Scientist
MilliporeSigma, Bellefonte, PA
A business of Merck KGaA, Darmstadt, Germany
In general, what tools and services does MilliporeSigma provide to biopharmaceutical companies that develop or manufacture protein therapeutics?
As a global provider, MilliporeSigma offers a wide range of products and services to biopharma. On the analytical side, we have a growing selection of chromatography and sample preparation products for development and QC laboratories. This includes enzymes for protein digestion and glycan release, reagents for derivatization, consumables (including SPE and MWCO filtration products), and high purity solvents. In analytical chromatography we offer a range of wide-pore, superficially porous particle (SPP) chemistries, both in UHPLC and HPLC particle sizes, that we call BIOshell™. These particles improve separations of peptides and large therapeutics like mAbs and other biomolecules. In addition to SPP we offer monolithic silica column chemistries, including a high-resolution version, as well as a new line of carbon-based HPLC columns we call Supel™ Carbon.
On the services side, we provide flexible, custom solutions for biologics manufacturing, including solutions for viral therapies, and biosafety testing under the BioReliance® brand. We enter into comprehensive partnerships with companies to support their entire journey from development to commercialization, with product characterization, lot release, and stability a focus. Our laboratories are equipped with a wide range of analytical instruments, all installed and maintained in compliance with cGMP requirements and operated with validated methods.
How has the growth of protein-based biopharmaceuticals impacted the market and the technologies you offer to the industry?
Protein-based therapeutics and prophylactics have consistently seen double-digit growth over many years. The stream of new biological medicines has transformed many debilitating diseases into manageable and, in some instances, curative outcomes. This has been highlighted by novel monoclonal antibody therapeutics and recently, the surge of mRNA-based vaccines to combat the COVID-19 pandemic. This growth in the market has fueled many innovations in our industry. We have responded by launching innovations in process and manufacturing science, including aseptic, tangential, and nano (viral) filtration; purification technologies like chromatography resins and membranes; cell culture production and media technologies; single and multi-use systems for process fluid management; CDMO services, and formulation innovations. Our approach is to work with customers to identify innovative processing solutions that we can bring to market.
The role we played in supplying manufacturers with technologies and services to combat the COVID-19 pandemic highlights this approach. We pivoted quickly to supply urgently needed manufacturing equipment, single use, and formulation products and services to help vaccine manufacturers produce in a timely fashion and with consistently high quality.
What is your approach in developing new strategies to analyze protein biopharmaceuticals?
We keep our eyes and ears open, attend conferences, and constantly track new developments in the industry. Automation, speed, accuracy, precision, and lowering the risk of errors are key considerations in our approach.
Some of our current advancements are in the area of multi-attribute methods, or MAM, which are based on peptide mapping and high-resolution mass spectrometry (MS) data. MS-only methods carry the potential to replace older methods in QC release testing. At the moment, we are evaluating how this may impact the future use of chromatography in product release testing. What is essential when using MAM for peptides is that the method provides high resolution separations across a run. To ensure this we have developed columns with pore sizes of 160 Å. For separating intact proteins, or IgGs, we suggest using the particles of 400 and 1000 Å pore size.
Advancements are also expected that further automate sample preparation for protein digestion and peptide mapping. In turn, automation is an important consideration when developing reliable, multi-site MAM methods. So, we are looking at new ways for us to use our protein A and enzyme products in ways that are amenable to automation.
What advice can you give to companies developing mAbs? Which tools, technologies and expertise should they have in place to make the process as efficient as possible?
Companies that develop and produce mAb therapeutics and other biologics are constantly looking for innovative ways to improve. Speed to market, quality, and robust supply are essential in the industry. Our advice is to look at the entire development and manufacturing process and find where technology can increase quality and yield. Bottlenecks can be alleviated by careful process development and introducing technologies that are fit for purpose and have been proven to reduce cost and increase yield and speed-to-market. Many emerging biotechnology companies do not have the resources to study processes in detail but, with our knowledge of the industry and relevant technologies, we can assist and be an extension of any process development and manufacturing team.
We also produce thought leadership and applications content to support clients who want to improve speed-to-market and efficiency. This includes laboratory-based process modeling at lab, pilot, and manufacturing scale, and customer-specific troubleshooting. To assist in these studies, we have a global network of M Lab™ Collaboration Centers where customers can simulate their processes with our equipment and technologies.
You’re referring to the M Lab™ network – can you tell us more about this?
Our M Lab™ Collaboration Centers, the largest global network of scientific experts, innovative technologies, and non-GMP facilities, empower drug developers of all sizes to achieve manufacturing excellence and innovation through collaborative exploration and learning. Customers can expect to come in person or virtually to any of our M Lab™ Collaboration Centers around the world and work with our process engineers to demonstrate processing capabilities and/or troubleshooting. All interactions are confidential and specifically designed for the customer experience. In a nutshell, the M Lab™ Collaboration Centers are there to demonstrate how MilliporeSigma technologies can serve our customers.
Looking ahead, how will protein therapies evolve and how will you meet the needs of pharmaceutical companies as this market segment grows?
Continued growth of biological medicines like vaccines, monoclonal antibodies, and other recombinant proteins have accelerated our drive to offer innovative analytical and manufacturing solutions. We have expanded our supply chains and capacities to meet the growing demand and are looking to increase service offerings to help companies achieve market supply consistency. Investments will continue to be a driver and fuel our innovation pipeline and will strengthen our position as a key collaborator for next generation processing, digitalization, and supply robustness.
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