According to the evaluation study’s results, almost one-quarter (24%) of industry experts tabbed analytical methods development as the top trend of 2013, on par with the percentage citing downstream processing. Common micro-trends within this area included:
• Convenient, high-throughput assays that assess physicochemical properties IgG clones for high level expression and therapeutic efficacy;
• Demonstration of biosimilarity to reduce costs of biologics manufacturing, and analytics to demonstrate equivalent product quality;
• Development of better characterization tools for upstream analysis and optimization; and
• Improved high throughput, high resolution glycoslylation analysis.
Clearly, there are multiple addressable dimensions to this topic, and we found a similarly wide net in last year’s Annual Report study where we inquired as to which assay areas most urgently required new or improved testing methods. That is, of the 29 “areas” we identified, 10 were cited as urgent by at least 20% of respondents. These included:
• Bio-assays to assess potency for release of drugs (41%),
• Biophysical characterization during process development (35%),
• Glycosylation (33%),
• Better stability assays (32%), and
• Biotech drug comparability (in-house manufacturing changes and biosimilars (31%).
Preliminary data from our 10th Annual Report and Survey of Biopharmaceutical Manufacturers3 (due to be released in April) indicate that the industry is looking for innovation in this area, ranking it near the top of the list in terms of new product development areas of interest among respondents.
Single-Use System Integration
Although analytical assays rank towards the top of biomanufacturers’ new product development interests, single-use, disposable products are at or near the top of the list. Preliminary data from the study reveals that end-users are interested chiefly in disposable products, bags and connectors (49%), while also expressing a desire for improvements in disposable probes and sensors (30%), disposable bioreactors (29%), and disposable purification (29%). These areas have been consistently in demand for several years now.
Disposable devices continue to make advances in manufacturing and are becoming increasingly common in most areas of biopharmaceutical production. Although, as yet, there are few non-rigid single-use devices (e.g., bioreactor bag liners) used in commercial scale GMP applications, it is likely this will change quickly as new products move through the development pipeline and out of clinical-scale manufacturing. Further, as regulators gain familiarity with the safety profiles and materials used in such devices, necessary approvals for product manufacture are apt to accelerate as well. When this occurs, the market volume for single-use devices is likely to increase significantly.
This year, 22% of the Biotechnology Industry Council members surveyed believed that single-use system integration would be the key trend for the year. Within this burgeoning area, participants identified several sub-trends. These include:
• Building quality into single-use operations to further reduce regulatory activities/oversight;
• Fixing disposable bioreactors that create inconsistent growth due to changes in resins, films, gamma irradiation, and cell line specificity;
• Downstream operations using membrane adsorbers;
• Emergence of flexible and modular biomanufacturing facilities;
• Establishing leachables and extractables guidance for testing;
• Improved upstream contamination investigations from a QA perspective;
• Introducing single-use devices at GMP commercial scale manufacturing; and
• Leachables and extractables [standardization] at clinical and commercial scale.
There are two interwoven trends worth an additional look. The first regards leachables and extractables. Last year, there were reported problems with the reliability and performance of available disposable solutions, with leachables and extractables a key factor. As Rick Johnston, Ph.D., CEO of Bioproduction Group Inc. noted, these issues “undermined confidence in the ability for … manufacturers to supply material in a timely manner to support production. This led many biomanufacturers to aggressively pursue dual-sourcing and risk-mitigation strategies like holding large inventories, both of which raise overall production costs. It is hoped that in the 2013 time period these issues can be resolved to allow the promise of disposables to be realized in the biomanufacturing setting.”
Indeed, the emergence of flexible and modular facilities, as well as the adoption of single-use devices at GMP commercial scale manufacturing (something already underway) depends in part on resolution of leachables and extractables (L&E) problems. In our 9th Annual Report, we asked respondents to identify the factors that may restrict their use of disposables in biopharmaceutical manufacturing. Fully 7 in 10 (69%) either agreed or strongly agreed that L&E problems were a concern, beating out bag breakage and single-source issues as the most common factor restricting further adoption of disposables. And when respondents were asked about identifying the single most important reason for not increasing their use of disposable technologies, concern regarding L&E headed the list again.
The debate over L&E data continues, but a major concern that end-users struggle with is that the raw material sourcing sometimes is unregulated, putting them at a disadvantage. Because vendors deal directly with raw material providers, end-users feel they are in a better position to test and provide the necessary L&E data as supporting documentation for their products. The desire for this type of data is strongest among scale up/clinical development organizations that do not have the resources to conduct such tests in-house. On the other hand, late-stage manufacturing organizations that are in phase III or commercial production are unwilling to take a chance with vendors and would rather generate L&E data themselves to minimize regulatory risks.
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