The biopharma industry’s continued focus on process efficiency is being fueled by advances in biosimilars, smaller volume drugs, shorter drug lifecycles (faster trials, development cycles), and high-volume product manufacturing issues.
To evaluate the trends that are shaping the bioprocessing segment today, BioPlan Associates recently surveyed 450 global subject matter experts and senior participants on its Biotechnology Industry Council panel of bioprocessing professionals and asked them to identify the most critical factors and trends they expect will need to be addressed over the coming year. While ‘process efficiency’ was a unifying thread, three clear sub-topics emerged: downstream processing; analytical methods development; and single-use system integration. (1) This year, the industry will see an increase in multi-product facilities, selective single-use adoption (both in clinical and commercial stage), a ramping up of continuous processing, and more advanced automation and monitoring. With downstream processing continuing to lag improvements in upstream, the industry will continue to look for better performing chromatography resins and consider alternatives to protein A.
Downstream purification (separation, filtration and chromatography) continues to be a culprit behind facilities’ capacity constraint problems. It counts as one of the key areas that the biopharmaceutical industry believes must be addressed to avoid short- and long-term capacity constraints, and it is where a large number of industry suppliers and end-users are developing and evaluating new technologies and other options for improving production efficiency.
Biopharmaceutical manufacturing, due to the fact that it operates in a highly regulated environment, tends to be characterized by incremental improvements rather than rapid, major technology shifts associated with other less regulated or consumer-oriented industries. The problem has been that with the significant increases in protein expression levels over the past several years, pressure has shifted squarely to downstream operations, which have not seen the same degree of improvement. This, in return, has resulted in continued bottlenecks in purification and filtration operations. The issues experienced by downstream operators have remained relatively constant over the past few years. And although there are many new technologies under investigation and consideration, few as yet, are being actively implemented.
This year’s trends study revealed 24% of industry participants named downstream processing as the single most critical trend. By contrast, 5% said the same about upstream processing. Within the rather broad area of downstream processing, the research reveals several sub-trends including:
• Process improvements in bioburden control in chromatography columns;
• Development of non-chromatographic recovery unit operations;
• Improving harvest operations through novel technologies;
• Increasing protein concentration in solution, without reducing yield; and
• Purification related to impurity profiles in biosimilars.
There is a general perception that the industry needs better-performing chromatography resins. Results from last year’s 9th Annual Report and Survey of Biopharmaceutical Manufacturers2, in which more than 300 biomanufacturers were surveyed, showed that slightly less than one-third of respondents wanted suppliers to focus efforts on chromatography products, the third-most sought after new product development area of the 21 we identified. (2)
There appears to be some consensus that alternatives to protein A will continue to be sought and developed this year. It is worth noting that while the industry has been clamoring for alternatives to protein A purification for some time, few facilities have made such a switch. For example, last year’s survey revealed 16% of respondents considering alternatives to protein A for existing projects, but less than half that proportion (7%) offer that they will actually be moving away from protein A for existing scale-up or commercial production units over the following 12 months.
In fact, the study found that the long-term trend among facilities interested in protein A alternatives appeared to be decreasing for new production units, while there was modest interest in switching from protein A for existing scale-up and existing production units. In general, though, interest appeared to be waning.
Using protein A chromatography media remains problematic because of the high-cost, limited life of the material and the cost of cleaning/validation. Alternative methods for purification of antibodies have been, and are being developed with longer lifetimes and therefore lower cost per unit of protein produced. However, according to most end-users, protein A “works.” While general interest in alternate purification methods to protein A remain high, actual switching behavior seems to be static or declining.
Still, the environment is ripe for innovative alternatives to emerge, and as long as downstream processing remains in the conversation, alternatives to protein A will be an ongoing topic of discussion.
In most biomanufacturing segments, it appears that improvements in assays and analytical capabilities are needed or desired. In addition to the continuing needs to assess and document product composition and quality, new demands for assays and analytical capabilities for biosimilars range from proving similarity to determining the unique differences between products. Assays and analytical method improvements are also needed to increase productivity in active agent design, discovery, screening and optimization, as there are too many products continuing to fail very expensively later in development. Most all can agree that it’s preferable to have products fail fast in order to move on to the next, most promising candidate in the development pipeline.