Monoclonal-antibody (MAb) manufacture presents substantial current and upcoming challenges to the biopharmaceutical industry. This is true both from an economic point of view and from a technical perspective. The goal of producing sufficient quantities of high-dose antibodies, and the concurrent pressure to reduce cost-per-treatment, is culminating in a vigorous public debate. Recent presentations and publications suggest that manufacturing costs are particularly critical for scientists and engineers. So, where is the biopharmaceutical industry heading?
MULTITON MANUFACTURING: WILL WE NEED IT?
Multiton scale manufacturing is on the horizon. Or is it? There's considerable doomsday talk about future demands in downstream processing and the industry's lack of preparedness. Yet industry trends suggest a need for reduced, rather than increased, production scales.
In a recent case study of large-scale MAb manufacturing, Kelley investigated a single-branded product need of up to 10,000 kgs per year.1 He concluded that such production is possible with current technology. In addition, he saw little need to turn to unproven alternatives simply for cost reasons. Indeed, in his analysis, cost was not a major driver away from current technology. The caveat with Kelley's study may be that he assumed access to a facility planned and built for the production in question, and clearly not everyone has such access. He also assumed that downstream processing technology would make some evolutionary progress (e.g., in capacity) before such a hypothetical case would become reality, yet large-scale MAb manufacturing is already taking place. Finally, Kelley concluded that it was unlikely that this scale of production would ever be required.
Gunter Jagschies, PhD
It is important to note that Kelley was undertaking a case study to make a point. He was not intending to create a blueprint for the biopharmaceutical industry.
A study conducted by GE Healthcare BioSciences began by examining the production scale of currently marketed biopharmaceuticals (Figure 1). Investigators identified four general trends that could reduce the average production scale for novel protein drugs. These trends are: diminished likelihood of discovering blockbuster drugs, increased competition, dosage reductions, and diagnostic improvements.
Diminished Likelihood of Finding Blockbuster Indications
The chances of finding blockbuster indications are not improving. Many major medical indications are already served by several protein drugs, and more drugs are coming through the pipeline. Rheumatoid arthritis is one example; anemia and diabetes also fall in this group.
Perhaps more important than the diminished need for blockbuster drugs is the issue of competition. Competition in the biopharmaceutical industry has increased significantly over the past decade. For example, in the early days of the industry, the first competitor to a first-to-market drug appeared, on average, eight to 10 years after the drug's market introduction.2 Today, the first competitor typically appears much sooner—within 1.5 years. As a result, few individual branded biopharmaceuticals are likely to enjoy high market shares.
MAb-based medicines are high-dose drugs, and intensive research is underway to reduce dosages. This is being done to minimize patient risks and reduce drug manufacturing costs. Examples of this include the targeted manipulation of glycosylation patterns and the replacement of MAbs with smaller proteins (such as antibody fragments), with the desired effect of improved efficacy (for example, an enhanced ability to penetrate solid tumors).