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.

Patti Seymour  (pseymourbptccom)  , Senior Consultant, will deliver a pre-conference short course entitled Supply Chain Management for Vaccines on August 15th at CHIs 6th Annual Immunotherapeutics and Vaccines Summit to be held in Boston, MA from August 15-18, 2011. In addition, Susan Dana Jones   (sjonesbptccom)  will be presenting a talk entitled “Quality by Design in Influenza Vaccine Development and Manufacturing” in the Production and Manufacturing of Vaccines track on Wednesday, August 17.

By Patti Seymour  (pseymourbptccom)  

The recent wave of natural disasters, and likewise, counterfeiting and erratic quality from suppliers have sent tremors through biopharmaceutical supply chains. Because the industry has become increasingly complex and interconnected as companies seek service providers and suppliers worldwide, sometimes from countries with less rigorous regulatory systems or more prone to nature disasters, the need to become more compliant and secure becomes even more critical. Even the best supply chain professional cannot control Mother Nature, but s/he can proactively develop a risk-management program that includes the entire supply chain network of partners to mitigate the impact of these disruptions and protect the integrity of the chain.

There have been recent regulatory initiatives both in the US and Europe geared toward improving pharmaceutical supply chain security through a risk-management approach. The FDA unveiled a new strategy at the end of June to meet the challenges posed by complex global supply chains in a report called the "Pathway to Global Product Safety and Quality”. This report calls for the FDA to partner with global regulators to increase data gathering and sharing to ensure and improve product quality and safety, and leverage industry and third party efforts to mitigate risk. The Drug Safety and Accountability Act of 2010, introduced last year, but unfortunately abandoned after the 2010 mid-term elections, required that drug companies have quality management plans in place requiring suppliers to demonstrate that the drug and its ingredients were manufactured in a manner ensuring safety and quality. While this legislation did not become law, it, along with Pathway to Global Product Safety and Quality report, signals the FDA’s seriousness about identifying and correcting manufacturing weaknesses resulting from poorly performing suppliers and sets the expectation that Sponsors are to be more proactive in managing these suppliers to ensure product quality and to prevent breaches in supply chain security. Commissioner Hamburg solidified the FDA’s intent in the following recent statement, “Global production of FDA-regulated goods has exploded over the past ten years. In addition to an increase in imported finished products, manufacturers increasingly use imported materials and ingredients in their U.S. production facilities, making the distinction between domestic and imported products obsolete. There has been a perfect storm – more products, more manufacturers, more countries and more access. A dramatic change in strategy must be implemented.”

The European Commission published a draft revision to Chapter 7 of the EU GMP Guide, Volume 4 Good Manufacturing Practice Medicinal Products for Human and Veterinary Use Guide addressing control over contractors and the supply chain. This revision provides guidance on outsourced activities beyond the current scope of contract manufacture and analysis operations. Of particular note, the contractor cannot subcontract to a third party without the Sponsor’s prior evaluation and approval, and contractors are prohibited from making any “unauthorized” changes that may adversely affect the outsourced activities. These changes are intended to further secure pharmaceutical supply chains from indiscriminate subcontracting to unqualified or unapproved organizations and arbitrary changes to any outsourced activities without careful consideration of resultant changes. With ever-increasing pressure to decrease costs, this revision will prevent contractors from outsourcing to the lowest cost provider with questionable Quality Systems just to save money.

While we would encourage companies to maintain vigilance on their supply chains as routine good business practice rather than as a regulatory requirement, it is clear that the regulatory authorities attuned to the gravity of this issue will continue to push for changes to ensure that companies are taking appropriate measures to protect patients. Either way, the outcome will be more compliant and secure supply chains and lower risks to patients.

From Eli Lilly’s “Mission Impossible”-style high profile warehouse theft in March 2010 to contamination in heparin in 2008, supply chain issues continue to make headlines. As pharmaceutical supply chains become increasingly global and more complex, the potential risks to maintaining secure, safe, and compliant supply chains have increased causing both US and European regulatory agencies to introduce several initiatives.

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