Bioprocessing Trends: Annual Survey Results - Pharmaceutical Technology

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Bioprocessing Trends: Annual Survey Results
Readers share their views on bioprocessing challenges, equipment use, and outsourcing trends in our annual bioprocessing equipment and processing survey.


Pharmaceutical Technology
Volume 36, Issue 5, pp. s6-s12

Past and future innovation




Even though the use of disposable technology is well established, it continues to impress. When asked to identify the single most important innovation of the past year responsible for improving process efficiency, many respondents said increased number of disposable options and new types of equipment had been the biggest contributor. Some were quite specific, mentioning the development of disposable stirred bioreactors, increased disposable bioreactor size, and single-use sensors as being important innovations. In addition to disposables, others said that QbD and PAT, including a greater range of available analytical tools, had increased bioprocessing efficiency, while improved cell lines resulting in greater yields were also mentioned.

While users obviously find the disposables they have to be useful, they still feel there are improvements that could be made. Readers were asked what specific innovations could be made to improve process efficiency, and again, disposables earned prominent mention. Readers asked for harmonization among disposables suppliers, disposables for microbial culture, disposable pressure sensors, and disposables for large-scale culture of adherent cells. Others were looking for better purification techniques—an alternative to protein A, cheaper disposable tangential flow filtration equipment, or a method for decreasing the number of steps in the purification process. To improve product quality, readers asked for better monitoring tools, and a broader application of PAT.

Survey

The MIT CBI Biomanufacturing Product Quality Survey
- Reuben D. Domike, Jeffrey T. Macher, Paul W. Barone, Stacy L. Springs, Anthony J. Sinskey, and Scott Stern

The Center for Biomedical Innovation (CBI) at the Massachusetts Institute of Technology (MIT) has conducted a survey asking in-depth questions of product life-cycle history, current manufacturing site characteristics, and site quality activities. The survey is part of a larger initiative at CBI to understand the impact of globalization and regulation on quality, both of which have increased in importance and cost within the biomanufacturing industry (1, 2). An additional intent of the initiative is to understand similarities and differences of quality between biomanufacturing and manufacture of small-molecule pharmaceuticals, the latter which has been analyzed previously from the regulator perspective (3). The initiative is primarily funded by a grant from the Alfred P. Sloan Foundation located in New York, NY.

Products surveyed

The survey collected information on 31 unique products, that were diverse in the following dimensions: geographic location of current manufacture (48% North America, 32% Europe, 19% Asia); processing (71% by mammalian cell culture, 29% by microbial fermentation); perceived manufacturing complexity (45% perceived to be of above average complexity); and consistency in manufacturing (45% of products regularly manufactured). Using cross-tabulation analysis of the product-specific survey data and statistical significance at the 0.10 level, the following quality issues at the commercial scale of manufacture of biopharmaceuticals are apparent:
• Life-cycle dependence: products that have had quality issues during development are more likely to experience quality issues in commercial manufacture.
• Geographic region dependence: products that have had critical quality issues in commercial manufacture are more likely to be manufactured in Asia and less likely to be manufactured in North America than products that have not had these issues.
• Contract manufacture dependence: products that are currently manufactured in a facility that does 40% or more of its manufacture for others are less likely to have had quality issues in development and are more likely to have critical quality issues in commercial manufacture. In other words, lack of development issues is more likely to lead to contract manufacture and contract manufacture is more likely to lead to critical commercial issues.
Product quality issues in commercial manufacture were found to be uncorrelated to process type, site-reported processing complexity, and whether the product was regularly manufactured (based on the available survey data and statistical significance levels of 0.10). An insufficient number of the commercially manufactured products had undergone quality by design to incorporate that into the analysis.

Sites surveyed

The products were manufactured at 15 sites. These sites were diverse in terms of geographic location, age, and extent of contract manufacture activity. Of the 15 sites, five each are located in North America, Europe, and Asia. Five of the 15 sites are 10 years of age or less and the sample average age is 12 years. Six of the 15 sites do less than 20% of their production volume for others on contract and five do greater than 80% of their production volume for others as contract manufacturers.
The survey results of the sites suggest the following regarding the drivers of quality and ongoing quality activities:
• Past drivers of quality efforts: Change initiated due to the regulator was the top reason for a quality effort at the sites; new technology, cost reduction, and pursuit of new markets were each identified as a past driver of efforts by less than 25% of the sites.
• Future drivers of quality efforts: Most past drivers are expected to continue, while new drivers are expected to be novel technology, cost reduction, and the pursuit of new markets were each identified by more than 50% of the sites
• Quality personnel and activities: Wide variation was evident between the sites in the fraction of technical personnel in quality assurance and control (15–45%); use of multidisciplinary teams in quality initiatives (range: low/med to high); and the frequency of third-party inspections (1–10 over past 5 years)
• Perception of inspection variation: Overall, there was no consistent perception from the sites of strong variation between inspections either within the FDA, within the EMA, or between the two.

Sources
1. J. Woo, S. Wolfgang, and H. Batista, Clin. Pharmacol. & Therapeut. 83 (3) 494–497 (2008).
2. D. Vogel, Governance 11 (1) 1–22(2002).
3. J.T. Macher, J.M. Mayo, and J.A. Nickerson, Jrnl. of Law and Econ. 54 (1) 25-54 (2011).

To learn more about this ongoing survey, the broader research initiatives, and/or CBI at MIT, please contact CBI at cbi@mit.edu or tel. 617.253.0257.

About the Authors:
Reuben D. Domike is affiliated with the Center for Biomedical Innovation, Massachusetts Institute of Technology (CBI, MIT) and the School of Business, University of Prince Edward Island; Jeffrey T. Macher is affiliated with CBI, MIT, and the McDonough School of Business, Georgetown University; Paul W. Barone and Stacy L. Springs are affiliated with CBI, MIT; Anthony J. Sinskey is with the MIT Department of Biology; and Scott Stern is with the MIT Sloan School of Management.

Reference

1. PhRMA, "Biotechnology Medicines in Development," http://www.phrma.org/sites/default/files/1776/biotech2011.pdf, accessed Apr. 2012.

For additional resources and online exclusives on this topic, visit http://www.pharmtech.com/.


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