To understand the causes of drug shortages, it is useful to explore the creation of a medication from the manufacturing and distribution points of view (Fig. 9.2). A pharmaceutical company needs to acquire raw products and then combine them to create the finished medication. Problems with the procurement of raw materials, such as civil unrest or a labor strike could be the initial hurdle. Despite the fact that 80% of the active ingredients used in pharmaceuticals come from outside of the United States, disruptions in delivery accounted for less than 10% of shortages from 2010 to 2011 [5]. Transportation of these materials to the factory could result in delays. Once all necessary materials are in the factory, reliable equipment is crucial. Machinery malfunction, loss of sterility, contamination with particulate matter, and other unacceptable outcomes can arise (Fig. 9.3). Once packaged, the medication is then transported to regional distribution centers across the United States. It is possible that due to inadequate planning or a sudden change in regional demand, one such center may be without the medication while other distribution centers have ample stock. These regional variances in supply could still result in national shortages. For example, when an anticipated shortage is announced, 89% of hospital purchasing agents buy excess inventory, which could increase the duration of a shortage [6]. From these regional distribution centers, the medications find their way into health care pharmacies for dispensation.

The story is also valuable from the procurement side. Clearly, a health care facility’s pharmacy staff doesn’t call multiple factories to obtain pricing and place orders for the thousands of products used. Rather, group purchasing organizations (GPOs) have been developed to handle this complex task. The GPOs then negotiate pricing and place orders with factories on behalf of their customers. What’s important to understand is that health systems, since they are businesses, want to pay the lowest possible price for their products. While this sounds intuitive (nobody goes shopping and offers to pay higher prices), it has led to unintended consequences. Because there are few GPOs that handle the vast majority of health care systems, they have tremendous negotiating power with the manufacturers. In fact, they have so much power that the profit margins of most medications in short supply are razor thin. This has many effects: (1) with such small profit margins, there is no value for competing manufacturers to enter the market; (2) with GPOs controlling such large swaths of the market, it would be equally challenging and risky for a new manufacturer to enter the market without guaranteed contracts [7]; (3) when a machine breaks down for one of the low-profit generics, there is less incentive to repair the machinery; (4) because drug manufacturers make multiple products, if machinery breaks down for one of the more profitable medications, a manufacturer will often move this product to a generic line’s equipment, when possible, to reap greater rewards; and (5) there is minimal incentive to provide more than the basic necessary maintenance of the equipment on the generic lines.

The other challenge is the practice of just-in-time inventory. Because the health care pharmacy and the regional distributors do not want cases of medications stored on site (lack of space and too much capital tied up), factories have followed suit. Therefore, medications are made and shipped rapidly. There is no “extra fat” built into the system. Thus, when a product manufacturing line goes down for whatever reason, existing stores of medications are used up at their normal rate, but there is no replacement forthcoming. All of the above issues lead to the major cause of drug shortages: lack of redundancy in the manufacturing supply chain [8]. Three manufacturers account for 70% of the sterile injectable market in the United States, and in some cases, one company is responsible for 90% or more of a drug [9]. For these critical medications, that’s just not safe.

One of the key issues with drug shortages is to define exactly how front-line physicians are affected by shortages (Fig. 9.4). At least one professional society, the American Society of Anesthesiologists, has addressed this topic [10]. Anesthesiologists are often faced with the challenge to use medications that are less familiar, have more side effects, may be less efficacious, and in some circumstances may result in less than optimal patient outcomes. One example is a case in which propofol was unavailable, so the hospital ordered multidose vials of methohexital. The operating room pharmacist dispensed an inappropriate dose to the anesthesiology department, and the anesthesiologist incorrectly diluted the medication giving the patient an eight-fold overdose leading to cardiac arrest and death [11]. In addition to these potential and real tragedies, these adaptations need to be done minimizing the production pressures involved with operating room throughput. To frame this from a different perspective, imagine if a vascular surgeon needed to perform a distal bypass, but successfully do so without bulldogs, without three of the most commonly used sutures, without the correct blades, and still complete the operation in the usual amount of time. You can bet that surgeon wouldn’t remain silent about the deficiencies but complain to every person with ears. Because of the direct effect on the practice of anesthesia, anesthesiologists do have an ethical and professional responsibility to participate in the development of solutions to this societal problem.