The Biotechnology Industry Organization (BIO) thanks the Food and Drug Administration (FDA or Agency) for the opportunity to submit comments on the Food and Drug Administration Drug Shortages Task Force and Strategic Plan. BIO appreciates that FDA opened this comment period in an effort to obtain public insight as it seeks to develop and implement the drug shortages strategic plan as per Section 1003 of the recently enacted Food and Drug Administration Safety and Innovation Act (FDASIA, Pub. L. 112-144).
BIO represents more than 1,100 biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products, thereby expanding the boundaries of science to benefit humanity by providing better healthcare, enhanced agriculture, and a cleaner and safer environment.
The biotechnology industry is committed to the discovery and development of new, novel treatments for serious and life-threatening diseases, and drug shortages that prevent patient access to needed treatments stand counter to our driving mission to extend and enhance the life of patients. BIO shares the FDA and public’s interest in the recent documented increase in prescription drug shortages, as these shortages can create significant concerns for patients seeking to maintain a treatment regime for their disease or condition. These shortages can even delay or halt clinical trials necessary to bring new therapies to market.
BIO applauds FDA’s commitment to finding new tools and approaches to prevent and mitigate drug shortages. Currently, critical shortages are most acute for off-patent sterile injectable products, including certain chemotherapy agents, total parenteral nutrition (TPN) electrolytes, and anesthetics, and therefore most resources and analysis have been focused on these products and markets. The factors contributing to drug shortages are complex and multi-faceted, and the relevant economic, logistical, and scientific factors can vary significantly among different sectors of the pharmaceutical industry, including branded and generic manufacturers. Consequently, there is no one-size-fits all solution to this issue and only a sustained multi-faceted approach that engages all stakeholders will advance the goal of preventing or mitigating shortages.
While biotechnology products represent a small minority of overall drug shortages, BIO recognizes that, in recent years, there have been shortages of a handful of these products. Companies invest, on average, more than $1 billion over a decade or longer to produce a new biologic and have a limited time (patent life) to recoup this investment. A manufacturing delay can cause significant adverse economic impact to companies, secondary to lost or reduced production of patented biologics. These economic realities incentivize biotechnology companies to invest in highly qualified manufacturing experts, top-of-the-line manufacturing facilities, robust quality systems, and extensive quality control.
We agree with Janet Woodcock, et al.’s recent article in Nature cautioning against applying the conclusions of sterile injectable drug shortage analysis to other drug shortages as “branded manufacturers have a greater incentive to invest in quality systems and to maintain spare capacity in case production unexpectedly has to be shut down.” Many of the current biologic shortages are either due to increases in demand, leading to the need to ramp up production, or unanticipated manufacturing problems. Given the complexity of biologic manufacturing processes, addressing either of these causes takes time. When a manufacturer had difficulty ramping up the process or encounters unexpected difficulties producing a pure and potent final product, it works exhaustively to address the issues and restore manufacturing capacity.
In the experience of many biotechnology companies, FDA staff work constructively and collaboratively with the manufacturer in the event of a shortage to help resolve the problem and restore patient access to needed therapies as soon as possible. In our December 2011 comments, BIO proposed several additional steps that the Agency could take to help further bolster the ability of both FDA and manufacturers to prevent and respond to drug shortages. These include expedited review of manufacturing supplements, prioritized re-inspections of facilities, joint and harmonized inspections, and guidance on continuity of supply chain and risk mitigation. BIO also offers the following specific responses to questions posed by the FDA in the Federal Register Notice and would welcome the opportunity to serve as a resource to the Agency as it continues to enhance its efforts to work with manufacturers to prevent and mitigate shortages.
Tufts Center for the Study of Drug Development, “Average Cost to Develop a New Biotechnology Product is $1.2 Billion, According to Tufts Center for the Study of Drug Development,” November 9, 2006, www.csdd.tufts.edu.
J. Woodcock and M. Wosinka, Economic and Technical Drivers of Generic Sterile Injectable Drug Shortages, Nature, Vol. 93, No. 2, February 2013.
See ibid, noting that “when production disruptions occur [with branded products], they tend to be resolved faster.”