These are heady days for vaccines, which are enjoying a rebirth of interest. Crawford Brown, Ph.D., CEO of Eden Biodesign, discussed the challenges of viral vaccine production at the meeting.
“The technical and regulatory demands are greater for vaccines than for antibodies, so we are seeking to overcome these barriers and build a platform similar to the CHO/protein A production method currently used in antibody production,” Dr. Brown explained. “Our aim is to build our products through the application of good science one day at a time.”
According to Dr. Brown, monoclonal antibodies have become more small molecule like in that they are moving into a mainstream product class. This means that they are treated from a commercial point of view more like small molecules, their manufacture is easily outsourced to a range of CMOs, regulatory agencies are quite comfortable in the evaluation of these entities, and scale-up is now a routine process.
In order to move vaccine production to this level, a number of problems unique to this discipline must be addressed. Currently, there is no dominant production platform, there is a limited transferability of skills and knowledge between products, and there is a high level of risk involved in the development process. New approaches are required including more platform-like strategies, new analytical tools and innovative facility design. “We are aiming for a platform that is robust, transferable, reproducible, and scalable,” said Dr. Brown.
Disposables play a major part in the Eden vaccine program, a feature shared with many CMOs. Disposable columns are now widely available and entail less contamination risk, faster turnaround, and reduced validation. The familiar stirred tank bioreactors, widely used in therapeutic biologics production, are used whenever possible, as they provide increased control of cellular physiology during the viral production process.
“Vaccine development still faces challenges that have been largely overcome for mAbs and other recombinant products,” he claimed.
Protein-based therapeutics have mushroomed into a vast industry. The overall market for biologics (including antibodies) was $63 billion in 2007 and is expected to reach $87 billion by 2010, according to Kalorama Information. Moreover, the biologics market, although much smaller than the entire pharma industry, continues to grow at a more rapid pace. This phenomenal growth is a powerful incentive to the industry to optimize its production capabilities.
Points to Consider
- The production of high-quality biologics raises a number of significant challenges whose resolution may be different from those that have been so successful in ramping up antibody yields to kilogram quantities.
- Although mammalian cell expression systems still dominate the industry, there is great interest in alternatives, including yeast expression systems. At Merck, Pichia has been successfully engineered to produce appropriately glycosylated proteins.
- Amunix has developed biosuperiors, recombinant proteins that, it claims, perform better than the original pharmaceutical.
- Knottins, cysteine-containing peptides of small size and limited immunogenicity, reportedly make effective scaffolds for protein engineering.
- Long ignored by pharma companies, vaccines are enjoying a rebirth of interest. Eden Biodesign is developing a platform that is robust, transferable, reproducible, and scalable in order to speed vaccine production.
- The biologics market, although much smaller than the entire pharma industry, continues to grow at a rapid pace, providing a powerful incentive to the industry to optimize its production capabilities.