ISPE, Baltimore, Maryland Wednesday, 4 June 2014

Drug ShortageOne year after the ISPE released the results of its Drug Shortages Survey which focused on technical manufacturing issues and their potential role in causing drug shortages, an update on the drug shortage issue was the subject of a three hour session at the Third Annual ISPE-CGMP Conference. The morning included a Plenary Session, a Drug Shortage Update session and a roundtable discussion offered by the ISPE Drug Shortage Task Force and others, followed by a question and answer period.

The drug shortage issue was called a “vexing problem” by Thomas Cosgrove, JD, Acting Director, FDA/CDER/OC/OMPQ.  However, he rejected the idea that FDA enforcement is a primary cause of drug shortages.  “FDA is a public health agency,” said Cosgrove. “In that regard, drug shortages challenge the agency. We can’t sit back and hope that problems will resolve themselves. We are engaging everyday with this issue.”

Francois Sallans, Vice President and Chief Quality Officer, Johnson & Johnson, said preventing and mitigating drug shortages are “critically important to public health.”  He noted the causes of drug shortages have just recently been identified but the problem has not been solved, although the curve of the number of drug shortages is bending downward. “ It needs to be zero,” he said.  Among the elements that contribute to eliminating drug shortages are a good corporate quality culture, a robust quality system, metrics, a business continuity program, communication with regulators and capacity building. These elements will form the backbone of ISPE’s Drug Shortages Prevention Plan which is in development.

In outlining the FDA’s response to drug shortages, Douglas Throckmorton, MD, Deputy Director, Regulatory Programs/FDA/CEDR, delivered two messages:  “we are making progress on drug shortage problems but we are not finished  and solving drug shortages has to be linked to quality manufacturing.”  He listed some current shortages, such as those with IV normal saline, zinc and doxorubicin for cancer treatment.  The central problems continue to be sterility, particulates, crystallization and impurities. He stressed the need for “early notification” by manufacturers and told attendees that FDA prevented 280 drug shortages in 2012.

Gerald Heddell, Director, Inspection Enforcement and Standards Division, MHRA, discussed the UK’s response to the drug shortage problems and added that although drug shortages are being reduced in the UK the problem was growing in the Netherlands and France. In part, the problem is the result of the “complexity of the global supply chain” where there are more links in the chain and more opportunities for things to go “awry.” “There are more actors and greater distances,” said Heddell, emphasizing that what patients want is “safe, effective and available medicines when they need them.” He also discussed the dilemma of whether it was better for patients to get drugs that were potentially defective rather than get no drugs at all.

Sam Venugopal, Director, PricewaterhouseCoopers, suggested that firms should put the right emphasis on building capacity to avoid drug shortages, and that problems in the supply chain needed to be addressed.  He offered 3 Rs that could focus the effort: Robust, Redundancy and Resilience.  Robustness comes with metrics, Redundancies look toward needs, and Resilience means evaluating the system for agility. These factors also will be further explored in the ISPE Drug Shortages Prevention Plan.

European initiatives to prevent drug shortages in Europe were discussed by Sabine Haubenreisser, PhD, EMA Liason to FDA, FDA/OC/OGROP/OIP. She noted that drug shortages in Europe were national problems as well as problems at the wider European level, with the European Union having a legal framework and related powers to mitigate shortages by maintaining a legally enforced continuity of supply.  She added that the EU also considered making potentially defective drugs available rather than restrict their use in critical needs. “Public health comes first,” she concluded.

John Berridge, PhD, Strategic Advisor to ISPE, told attendees that while enhancing the corporate quality culture is important, some companies struggle to get a robust quality system. Karen Hirschfield, RPh, Senior Compliance Specialist, Genetech, Inc.,  spoke on the issue of upgrading or acquiring new equipment as part of an effort to further quality and prevent the kinds of manufacturing problems that contribute to poor product quality and subsequent drug shortages, as identified by the 2013 ISPE Drug Shortage Survey. She admitted that purchasing new equipment might be a tough sell to senior company management.