BioProcess Blog |

By Patti Seymour  (pseymourbptccom)  

With shortages of life saving medicines making headlines recently, President Obama signed an Executive Order on October 31 to ease pressure on health care providers and reverse this dangerous trend. Drug shortages, primarily involving generic sterile injectables, have been increasing in frequency and severity in recent years with roughly half of the approximately 80 manufacturers experiencing shortages in 2011.

FDA has reacted to this situation by issuing “A Review of FDA’s Approach to Medical Product Shortages,” detailing the existing drug shortage, summarizing actions FDA is taking both to prevent and respond to drug shortages, and the unique drivers causing these shortages. While the problem is complex and caused by a variety of contributing factors, quality issues at the drug manufacturing facilities seem to be a leading cause of the drug shortages, accounting for 43% of all shortages. As discussed in my previous post on this topic, FDA is focused on identifying and correcting supplier performance as part of their overall risk-based approach to inspections, which has translated into numerous 483 citations at sterile product contract manufacturers. The expectation is that Sponsors will be more proactive in managing these suppliers to ensure product quality, but clearly this is not happening. A leading manufacturer of sterile injectable oncology products, Ben Venue Laboratories, announced in August that the company was exiting the contract manufacturing business while it dealt with multiple FDA 483s at their manufacturing facility in Bedford, Ohio. Unfortunately for Sponsors and patients relying on medicines manufactured there, Ben Venue temporarily suspended all drug manufacture and distribution just before Thanksgiving, putting further pressure on already stressed supply chains.

Unfortunately, Ben Venue is not an isolated case. When using a CMO for any part of your supply chain, it is important to ensure that the CMO is operating in full compliance of all cGMP regulations to avoid supply disruptions. This diligence begins with the initial selection of the CMO but should continue through periodic GMP compliance audits. Without question, any quality issues identified either during a Sponsor audit or a regulatory inspection should routinely be addressed immediately and the CMO monitored to ensure appropriate corrective actions have been implemented and compliance is maintained or restored. Proactive supply chain monitoring can provide early warning signs of potential supply chain issues, enabling Sponsors to implement risk-mitigation plans to head-off potential catastrophes. For all links in the supply chains, a risk-management plan which identifies all elements that could contribute to a breakdown in supply and outlines risk-mitigation strategies, such as second source manufacturing for key links in the supply chain, that will ensure continuity of supply.

While some of the current drug shortages could not have been predicted, many of them could have merely by connecting the dots through vigilant supply chain oversight and robust risk-management plans. It’s not too late to thoroughly analyze your supply chain and inspect it for any chinks or weak links that could disrupt continuity of supply. Make this your New Year’s resolution.

​Join Dr. Howard L. Levine  (hlevinebptccom)  , President and Principal Consultant, at the Eight Annual BioProcess International European Conference, April 18-19, 2012 in Prague to learn more about manufacturing strategies for biologics, biosimilars and novel therapies. Drawing from BPTC’s proprietary Biopharmaceutical Product database and recently published report “The State of Mammalian Cell Culture Biomanufacturing,” Dr. Levine will speak on the “Global Demand and Utilization of Mammalian Cell Culture Manufacturing Capacity. His presentation will highlight the expected 50% growth in industry-wide capacity utilization between now and 2016 as well as the impact of recent technological advances in manufacturing processes, improvements in expression levels, widespread acceptance of single-use bioreactors, and the increased interest in biosimilars throughout the world. As with its sister event, the BioProcess International Conference held last October in Long Beach, CA, BPTC is pleased to be a part of BPI Europe. To pre-arrange a meeting with Dr. Levine at the conference, please click here  (hlevinebptccom)  .

By Tom Ransohoff  (transohoffbptccom)  

BPTC’s inaugural bioPULSE^TM survey focused on perceptions and trends in the development of antibody-drug conjugates (ADCs). The responses to three of the survey questions foreshadow significant growth in the ADC field. First, a vast majority of respondents (83%) expect to see a significant increase in the number of ADCs entering the biopharmaceutical pipeline in the coming five years. Second, as many respondents (24%) indicated that their company is not currently developing ADCs but planned to do so in the future as those indicating that their company is already developing ADCs (also 24%). Finally, an overwhelming number of respondents expect this field to be very large (95% selecting either “massive – as big as MAbs” or “important – but not as large as MAbs”) compared to only 5% who felt that ADCs would be limited to niche markets only. Although we recognized ADCs as an important emerging class of biopharmaceutical products, we were honestly surprised at the strength of opinions from respondents related to the potential of this area.

Along with the optimism for growth in the ADC area, the survey indicated some concerns related to remaining CMC development hurdles and the adequate availability of critical outsourcing services to support development and supply of these products. The results of the survey clearly indicated that conjugation technology and linker chemistries were among the greatest CMC development hurdles for these products. Additionally, a number of potential areas likely to experience increasing demand for service providers, such as CMOs with the ability to handle biologic-cytotoxic conjugates, were identified by survey participants. It will be interesting to see how the CMO/CRO world responds to the increasing demand for services to support ADC products.

The objective of all bioPULSE^TM surveys is to obtain relevant and focused feedback on topics of interest to the biologics manufacturing community. The web-based surveys are quick, short, and rewarding (everyone who participates will be emailed a summary and analysis of the aggregate results). The topic of the second bioPULSE survey, which is currently open and accessible at www.bptc.com/biopulse, focuses on vaccine manufacturing and supply. Your input is encouraged, appreciated and rewarded!

Join Dr. Susan Dana Jones  (sjonesbptccom)   at the second annual Cell Culture World Congress to be held in Munich, Germany from February 28 to March 1.  At the conference, Dr. Jones will provide insights into the benefits of focusing on product quality early in cell line development in her talk entitled, “Enabling cost-effective product quality focus in early biopharmaceutical development.” Email  (sjonesbptccom)   Dr. Jones to set up a meeting.