This eighth in the series of annual evaluations by BioPlan Associates, Inc. yields a composite view and trend analysis from 352 responsible individuals at biopharmaceutical manufacturers and contract manufacturing organizations (CMOs) from 31 countries. The methodology also encompassed an additional 186 direct suppliers (vendors) of materials, services and equipment to this industry. This year's survey covers such issues as: current capacity, future capacity constraints, expansions, use of disposables, trends and budgets in disposables, trends in downstream purification, quality management and control, hiring issues, employment and training. The quantitative trend analysis provides details and comparisons by both biotherapeutic developers and CMOs. It also evaluates trends over time, and assesses differences in the world's major markets in the U.S. and Europe.
The need for better analytical equipment in biopharmaceuticals is a major and increasing concern within the industry. In fact, over 30% of biomanufacturers and CMOs are demanding better assays and products . This is up significantly from last year (see Figure 1). The recent 8th annual survey of biopharmaceutical manufacturers (with 352 global respondents) by BioPlan Associates shows that, after disposable devices, the industry is demanding newer, better, more relevant assays.
Improved analytic technology is recognized as supporting better biomanufacturing processes, improving product quality and reducing costs. The study shows that the industry is turning its focus on process improvement, and product quality. This is driving the demand for more and better analytical technologies and equipment at every stage in biopharmaceutical R&D and manufacturing. Survey results parallel and confirm a number of trends leading to increasing use of chemical analysis of biopharmaceuticals. These include advancing technologies, and expectations of regulatory agencies who, with more data available, will likely increase their expectations for more extensive and diverse analytical information. In addition, the global growth in biosimilars, whose approvals are largely dependent on analytical data, is facilitating the focus on improved analytics.
New Technologies Becoming Available
Analysis of bioprocess intermediates and end-products is becoming an integral part of biomanufacturing, from R&D through product manufacturing. Advancing technologies present opportunities for product improvement, cost-savings, and streamlined manufacturing. But technological improvements also pose a quandary: not only do analytical costs increase, but the possibility of finding problems not identified using prior technology also grows. Difficult decisions need to be made, including what technologies and equipment to use, when to adopt, how much testing should be done, and where should it be done—in-house, or with contract testing laboratories.
Advancing technology is making an array of analytical testing more available, yet much of this is new and has yet to be considered by regulatory agencies. And while adopting new analytical technologies may provide some ultimate cost-savings, the acquisition of new expensive equipment and expertise may become a requirement, based on what regulatory agencies expect. Regulatory uncertainties are bound to arise as agencies come to request more and more analytical data, which can either speed up or delay approvals.
Industry Views of Analytical Bottlenecks
This year’s survey shows that analytical equipment remains a major concern. In addition to finding that 31% of the industry is demanding improvements in analytical assays, 26.2% cited “Analytical testing and drug product release” as a major factor likely to constrain their organization’s production capacity over the next five years.
We found industry concerns regarding production constraints, which were mirrored when we asked about factors creating improvements in production operations. Of the 15 areas we evaluated, the largest portion, 72.6%, cited “overall better control of the process.” We also found that 60.6% cited “better analytical testing and release services” as being responsible for improved performance (Figure 2).
The study also compared European vs. U.S.-based manufacturers’ responses. We found Europeans reported greater performance improvements from “Better analytical testing services” (64% of European respondents, vs 57% of U.S.); in addition, we found that 83% of Europeans indicated “Better process control” was “improving” or “significantly improving” biomanufacturing performance, vs 66% of U.S. respondents.
The Need for Improved Analytical Methods
Improved assays and analytical methods were cited by a majority of biomanufacturers as creating capacity constraints, and reducing productivity. We measured 26 assays and testing methods, and the top concern this year was for glycosylation assays (Figure 3). This is related to the ability to prove drug comparability between manufacturing batches/lots as well as biosimilarity between different products. For both these areas, nearly half, 44.8%, of industry respondents noted them as needing improved testing methods. This was followed by host cell protein assays (39.4%), biophysical characterizations during process development, and in-process testing methods. Other key areas of interest for improved single use assays included dissolved oxygen, cell density and cell viability.
When we compared responses from biomanufacturers and CMOs, we found that CMOs were more concerned with glycosylation, pre- calibrated disposable sensors, pH disposables, and qPCR. Biomanufacturers’ focus is on biotech drug comparability (in-house manufacturing changes and biosimilars), biophysical characterization during process development and better stability assays.