January / February 2017

Drug Shortages Theory into Practice

John C. Berridge, PhD, CChem, FRSC

After much focus at recent conferences and in publications on understanding the manufacturing- and quality-related causes of drug shortages, delegates at the 2016 ISPE Annual Meeting & Expo in Atlanta, Georgia, had the opportunity to hear from a panel of speakers how the current range of tools can be used practically to prevent and mitigate those shortages.

Peter Bigelow from xCell Strategic Consulting opened the session by inviting Rafael Lander and Carl Finamore from PriceWaterhouseCoopers (PWC) and Wes Schmidt from AbbVie to explore supply chain resilience, looking at how the risks to the product supply have increased in concert with complexities, especially as more players become involved in the pharmaceutical supply chain. One surprise was hearing that 80% of companies across industries cannot check whether their suppliers have business continuity plans, according to the results of a PWC/Massachusetts Institute of Technology (MIT) survey conducted in 2014. Homing in on pharmaceutical supply chains, we saw that there are unique operational and regulatory risks, including regulatory approval delays, changing regulations, and quality or compliance failures in addition to the more widespread risks such as natural disasters and political risks. Of course, should one of these risks occur, both the business and the patient will suffer.

Again, referencing the PWC/MIT survey, we heard that biopharmaceutical companies are struggling to master the increasing complexity while simultaneously responding to progressively more diverse customer and country requirements. And, it was asserted, avoiding this complexity is not an option for growing companies. Other challenges were seen to be the expansion of novel product types and delivery systems, cost pressures, and the demands of payers.

Looking at real-life examples of major drug shortages, we heard of uncorrelated causes such as product sabotage, cross-contamination, natural disasters, and shortages resulting from quality problems arising at a CMO. While some of the problems can be resolved quickly, sometimes recovery time is measured in years.

The solution is to invest in understanding the end-to-end supply chain risks and proactively develop resilience (business continuity) plans. The resource needed to develop such plans is not to be underestimated. Fortunately, help is at hand and we heard how not-for-profit consortia can help. Identified in the ISPE Drug Shortages Prevention Plan was the key enabler of “Robust Quality System” and organizations such as Rx360 can undertake supplier audits that test the robustness of the quality system(s) from raw materials to the pharmacy.

Other tools for shortage prevention include risk maturity and resiliency models, web data analytics, and ISPE’s Drug Shortage Assessment and Prevention tool.

ISPE’s tool has within it a self-assessment maturity model. PWC showed that maturity models can also help companies evaluate themselves against their peers: Companies with more mature resiliency practice outperform their counterparts. We were introduced to a resiliency model that is based on third-party data and uses simulation techniques to drive a probabilistic view of how supply chain risks impact key metrics. These can then inform resource and investment decisions. For example, the model might show that an industrial dispute in a port could have a major disruptive effect on product distribution and an alternative shipping mechanism might be appropriate. In a similar way, web analytics can provide near-real-time monitoring of risks such as a natural disaster.

The ISPE Drug Shortages Prevention Plan and the ISPE Drug Shortage Assessment and Prevention Tool together provide a holistic six-dimensional approach to the prevention and mitigation of shortages. The tool is an easy-to-use self-assessment approach that translates theory into practice and is globally applicable.

In the subsequent panel discussion, which included Larry Kranking (Commissioning Agents), Lance Minor (Medimmune), and Peter-Jost Spies (Janssen), we were treated to candid feedback from early adopters of the ISPE prevention tool who had practical experience with its use. While implementing it across all six dimensions demands significant resource investment, this is not always necessary as one can “pick and choose” the areas of most importance to the user. The holistic approach was seen to be very powerful, although it was recognized that other, perhaps more limited product-specific tools are available. Members of the ISPE Drug Shortages Task Force welcomed the feedback and heard that the use of the tool could be facilitated by its conversion to an electronic spreadsheet format. Readers, what are your views? Have you used the prevention tool? Would making it electronic improve its utility?

Attendees were also alerted to recent regulatory developments, including the new law enacted in France that requires that essentially all products have shortage-prevention plans available. While at the time of the conference the full requirements had still to be published, the ISPE shortages prevention tool was proposed as a cost-effective way of assessing a site or an organization’s product portfolio and demonstrating that plans to prevent or mitigate a shortage are available.

Finally, we were given a taste of ISPE’s latest contribution to the understanding and prevention of shortages—a collaboration with Pew Trusts. The joint ISPE/Pew research study, due for publication in early 2017, will examine the drivers that inform and influence companies’ decisions about whether to invest in areas such as new facilities, contingency production capability, or backup stock to mitigate a potential shortage, with focus on sterile injectable products.