U.S. CONGRESS

No overarching federal policy, strategy, or consensus currently exists on how to reduce the amount of discarded drugs that result from weight-based dosing of medicines contained in single-dose vials. However, actions by Congress have focused attention on specific aspects of this issue.

Several versions of draft congressional bills introduced in the 115th Congress (2017–2018) and the 116th Congress (2019–2020) that focused on discarded drug related to single-dose vials have proposed rebates from manufacturers to be directed to health care providers and payers for discarded drug amounts. Box 4-1 presents a summary of some of these bills. Most bills, however, did not propose rebates directed to patients, who would continue to have cost-sharing responsibilities for the cost of discarded drugs that were not used in their care. As discussed in previous chapters, Medicare beneficiaries without supplemental private or public health insurance coverage are responsible for up to a 20 percent coinsurance of the cost of drugs used in their treatment, including any discarded portion of a vial.

BOX 4-1

Select Draft Bills Focused on Waste Related to Single-Use Drug Vials.

Based on the committee's assessment, it is not feasible to use rebates for discarded drugs to recoup significant funds that could be spent on other health care services, so manufacturer rebates for unused drug are unlikely to achieve the intended aim. Also, given the variety of ways that drugs are priced and reimbursed, a rebate system for clinician-administered drugs is likely to be quite complex. However, if the rebates that have been proposed in legislation are implemented, the committee asserts that patients need to be included in those rebates.

PROFESSIONAL ORGANIZATIONS

As the costs of expensive infusible and injectable drugs and biologics continue to rise, research and professional organizations have called for developing and adopting innovative solutions to reduce the amount of discarded drugs or increase efficiency in dispensing such drugs.

The American Society of Clinical Oncology (ASCO), a leading professional organization, has urged the Centers for Medicare & Medicaid Services (CMS) to consider better ways to identify the sources and costs of discarded chemotherapy drugs. The organization has called for such data to be made public and encouraged private payers to consider similar strategies (ASCO, 2018). ASCO, the U.S. Oncology Network, and the Hematology/Oncology Pharmacy Association (HOPA) have encouraged clinicians to adopt clinical practices such as dose rounding, dose capping, or dose banding (discussed later in this chapter). These practices are intended to reduce the amount of drug discarded when single-dose vials are used, while ensuring patient safety. HOPA has called on the relevant regulatory agencies to reconcile regulatory policies governing sterile compounding and on pharmaceutical manufacturers to increase the availability of medications in multi-dose vial formulations (HOPA, 2019). (See Box 4-2 for more on multi-dose formulations.)

BOX 4-2

Multi-Dose Formulations.

The American Society of Health-System Pharmacists (ASHP), an organization that represents pharmacists who serve as care providers in acute and ambulatory care settings, has taken a position on the availability and use of appropriate vial sizes, advocating that pharmaceutical manufacturers provide vial sizes that reduce the amount of drug discarded and enhance safety. Additionally, ASHP has called on regulators, manufacturers, and other health care providers to collaborate to develop best practices on the safe use of single-dose vials (ASHP, 2019).

CLINICAL PRACTICES

Because of the rapidly increasing number of specialty medications coming to the market in single-dose vials (Lotvin et al., 2014; Watanabe et al., 2018), health systems and health care providers are being increasingly challenged to address the issues that these medications raise. These are not low-stakes considerations, given that the acquisition price and reimbursement amount for these medications can markedly affect a clinical practice's finances. Furthermore, clinicians and health care systems are increasingly burdened with making decisions about approaches to reduce the amount of medications they discard.

This section explores the various mechanisms and approaches that clinicians, physician offices, hospitals, and clinics currently employ to reduce the amount of discarded drugs and examines the consequences for health systems. Many clinicians, for example, have embraced strategies that several Organisation for Economic Co-operation and Development (OECD) countries currently use, although these are not yet well established in the United States; these strategies include vial sharing, drug vial optimization, closed-system drug transfer devices (CSTDs), dose banding, dose rounding, and dose capping, or a combination of these approaches. It is important to recognize that implementing these strategies requires a certain amount of health care worker time to plan and perform.

Vial Sharing

One suggested approach to dealing with the issue of discarded drugs is to discontinue the one vial per patient approach. To illustrate how this approach can decrease the amount of discarded drugs, Figure 4-1 shows the sort of situation that occurs in today's medical practices, with three patients who are receiving the anticancer drug bortezomib from single-dose vials, with each patient getting a different dosage and no vial sharing possible. The bortezomib comes in 3.5-mg vials. Patient 1 receives a dose of 2.45 mg (70 percent of a vial), with the remainder discarded. Patient 2 requires 50 percent of the vial, with the remainder discarded. And Patient 3 receives 60 percent of the vial, so 40 percent of the vial is discarded. This means that for the three patients, 30 percent of one vial plus 50 percent of a second vial plus 40 percent of a third vial—or 120 percent of a single vial's contents—would be discarded.

By contrast, with vial sharing, the remainder from each vial is retained and can be used for the next patient. Thus, by sharing two vials, the total discarded amount would be 20 percent of a single vial instead of 120 percent—or an entire vial saved (see Figure 4-2).

Vial sharing presents several challenges, however. Each shared vial must be unpackaged, appropriately logged, and stored, and its sterility must be ensured for later use (Smith, 2015). Multiple patients who are treated with the same drug must be scheduled to come in on the same day, a process known to some as batching (discussed in detail in Box 4-3). Because two or more patients are treated from a single vial, microbial contamination is possible. Sharing a single vial can be complicated temporally, as consistently forecasting the amount of compounded product even over a few days is not simple, and the decision to puncture any individual vial will affect the usage pattern to follow. Vial sharing also demands additional attention and documentation by staff to prevent accidentally exposing multiple patients to a medication after its beyond-use date.¹ Finally, vial sharing is generally unrealistic for small clinics and facilities that do not have enough patients to make it consistently feasible.

BOX 4-3

Batching.

Nonetheless, the advantages of vial sharing are great enough that it has come into regular use in various places around the world. It is common in Australia (Gilbar, 2020), where the Therapeutic Goods Administration—which plays a role similar to FDA in the United States—provides guidelines for the use of partial vials. The Pharmacy Board of Australia provides guidelines on assigning beyond-use dates on compounded sterile injectable products. The Society of Hospital Pharmacists of Australia supports vial sharing as long as it is carried out in specialized aseptic pharmacy facilities and follows rigorous standards of practice (Gilbar, 2020). The situation is similar in New Zealand and the United Kingdom, both of which endorse vial sharing (Gilbar, 2020). A number of studies have examined the practice of vial sharing in these and other countries and found that it reduces the amount of discarded drugs and cost of treatment (Gilbar et al., 2019; Hall et al., 2020; Rustemi et al., 2019).

Drug Vial Optimization

Certain difficulties associated with vial sharing can be ameliorated by a practice called drug vial optimization, which relies on extending the length of time that a drug remains sterile and stable up to as much as 7 days by using a closed-system drug transfer device (CSTD) (Amerine et al., 2019). Generally, once the sterility of the vial is breached by a puncture, the remaining drug is no longer considered safe and effective and is thus unusable. However, CSTDs make drug vial optimization possible by moving drugs from one place to another—such as from a vial into a syringe—without letting the drug or its vapor escape into the environment or introducing any contaminants into the vial or the syringe. As a result, CSTDs can ensure the stability and sterility of injectable drugs after vial puncture for much longer than the United States Pharmacopeia (USP)specified 6 hours and safely preserve the remaining volume for later use. Manufacturers of these devices have demonstrated that the punctured vial contents remain stable and sterile for as much as a week after the beyond-use date (Gilbar et al., 2019; Juhász et al., 2016). Furthermore, CSTDs protect pharmacy personnel from exposure to those otherwise hazardous drugs (McMichael et al., 2011; Simon et al., 2016; Spivey and Connor, 2003; Wick et al., 2003). (See Box 4-4 for a detailed discussion on CSTDs.)

BOX 4-4

CSTDs.

Though the United States was the first to implement drug vial optimization, this strategy is not supported by recent guidelines from the USP or some state boards of pharmacy (Amerine et al., 2019). Sterility is a vital criterion in drug vial optimization due to the chance of microbial contamination, which is the most common reason for policies regarding a safe duration of use (Suzuki et al., 2019). Good manufacturing practices call for the drug to be discarded after the USP's 6-hour beyond-use date (Amerine et al., 2019), which could be why current guidelines do not support drug vial optimization. However, drug vial optimization is widely accepted globally. A 2019 survey found 10 of the 12 countries surveyed had implemented this model (Suzuki et al., 2019).

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES PARTNERSHIPS WITH FEDERAL AND NONFEDERAL PARTNERS

The U.S. Department of Health and Human Services (HHS) has an opportunity to effectively coordinate and collaborate with other federal agencies and nonfederal partners to identify and develop technological systems that allow single-dose vials to be used safely across multiple patients. Over the past decade, HHS has partnered with other government agencies, private organizations, and public entities to address diverse health-related issues, including developing strategies for effective solutions to address and mitigate the public health impact of diseases and strategies to improve patient care and health outcomes through the efficient and effective use of data.

An example is the HHS partnership to facilitate the rapid deployment of prefilled syringes for quick response to widespread health emergencies. The Rapid Aseptic Packaging of Injectable Drugs (RAPID) will enable the Strategic National Stockpile to rapidly fill and finish hundreds of millions of syringes to respond quickly and efficiently to widespread health emergencies (HHS, 2020). The RAPID consortium will identify and use technologies that eliminate the inefficiencies and difficulties of drawing medicines from glass vials to ensure that drugs are available to patients when needed.

Another example is the Accelerating COVID-19 Therapeutic Interventions and Vaccines partnership, which has brought together several agencies within HHS, including the Biomedical Advanced Research and Development Authority, the Centers for Disease Control and Prevention, and FDA, other federal agencies, including the U.S. Department of Defense and the U.S. Department of Veterans Affairs, representatives from nonprofits, including the Foundation for the National Institutes of Health, more than a dozen biopharmaceutical companies, and an international partner, the European Medicines Agency. The stated purpose of the partnership is to “develop an international strategy for a coordinated research response to the COVID-19 pandemic” (NIH, 2020). The partnership will develop a coordinated research strategy for prioritizing and allow for harmonizing and sharing preclinical evaluation methods to speed the development of the most promising treatments and vaccine.

Such effective relationships between HHS and other federal and nonfederal partners would create opportunities for developing promising and innovative systems that allow single-dose vials to be used safely across multiple patients.

INTEGRATED HEALTH CARE DELIVERY SYSTEMS, TRADITIONAL FEE-FOR-SERVICE SYSTEMS, AND THE UNDERSERVED

Different health care providers may have different incentives and barriers for reducing discarded drugs. Integrated health care delivery systems may have direct incentives to decrease the amount of discarded drugs from single-dose vials. In these systems, health care providers may be motivated to “save costs” by applying vial-sharing mechanisms or some other clinical practices for patients to reduce discarded drugs through a cumbersome and expensive process that they still view as cost-effective. Additionally, clinicians in integrated health care delivery systems are typically not paid based on the price of the drug they administer. But a traditional fee-for-service system, where health care providers are reimbursed up to the amount of drug indicated on the vial or package label of a single-dose product, including what is discarded, may have less motivation to reduce the amount of discarded drugs. And, of course, patients get little say in the matter, and it is they who may view the typical (noncapitated) approach as increasing their own costs needlessly, depending on their insurance coverage for the up to 20 percent not covered by Medicare Part B.

Rural hospitals, small clinics and physician's offices, and health care centers that serve underserved populations face additional challenges to reduce discarded drugs because of financial constraints. They may lack the appropriate resources to remove a portion of the vial contents for a given patient sterilely and return the unused portion to a refrigerator. According to a 2020 analysis, there are currently 1,844 rural community hospitals in the United States (Topchik et al., 2020). The analysis focused on the financial and operational data for 3 years before closure for closed hospitals and concluded that one in four rural hospitals are at risk of closure due to steady declines of operating margin and revenue (Topchik et al., 2020).

Even when the resources are available to keep the open vial following approved guidelines, in rural settings, it is unlikely that the vial would be fully used within the approved period, largely because the patient population is more dispersed. The sparseness of the population limits these providers' ability to share drugs among patients, as is done with batching.

Given the variety of incentives and barriers, depending on the organizational structure of the health care provider and the demographics of the patient population they serve, one single approach to reducing discarded drugs will likely not work for all providers.

KEY FINDINGS

1.

Recent legislation has been proposed to regulate payments for discarded drugs. Several of these bills proposed rebates from manufacturers directed to providers and payers for discarded drug amounts. Most bills did not propose rebates directed to patients, who would continue to be responsible for a portion of the cost of discarded drugs that were not used in their care.

2.

Technological advances, such as closed-system drug transfer devices, show promise as potential ways to reduce the amount of discarded drugs with minimal or no risk to the patient.

3.

To reduce the amount of discarded drug, clinical support staff may work to coordinate schedules so that patients requiring treatment of the same drug are scheduled within several hours of each other. This imposes logistical hurdles for practices and may create inconveniences for patients.

CONCLUSIONS

1.

Vial sharing and other clinical practices such as dose banding and dose rounding are possible mechanisms for reducing discarded drug. For small clinics and hospitals, vial sharing may be challenging to coordinate due to limited patient volume as well as the need to obtain special equipment to allow prolonged storage for safe drug use.

2.

Several technologies and clinical strategies show promise for reducing discarded drugs from single-dose vials but are not encouraged by current policies or are not feasible without reducing current practice-based constraints.

3.

Legislative initiatives proposing manufacturer rebates to providers and or payers for discarded drugs ignore the fact that a patient often would have been required to pay part of the cost of this discarded drug.

RECOMMENDATIONS³

RECOMMENDATION 4-1: The Secretary of the U.S. Department of Health and Human Services should direct the Centers for Medicare & Medicaid Services, the U.S. Food and Drug Administration, and the Centers for Disease Control and Prevention to initiate a partnership with other agencies, including the U.S. Department of Defense and the U.S. Department of Veterans Affairs, to work with health care and other organizations with expertise in areas such as industrial design and systems engineering to identify and implement technological systems that allow single-dose vials to be used safely across multiple patients.

RECOMMENDATION 4-2: The Secretary of the U.S. Department of Health and Human Services (HHS) should develop and implement policies that require drug manufacturers to produce injectable and infused drugs in multiple-dose vials when it is safe to do so. The Secretary of HHS should routinely review and evaluate the impact of such policies.

Because the committee's assessment shows that there is limited economic value to discarded drugs from single-dose vials under the current system in which drugs are developed, administered or paid for, a rebate strategy seems unlikely to achieve the intended goals. However, if the rebates that have been proposed in legislation are indeed implemented, the committee asserts that patients need to be included in those rebates.

RECOMMENDATION 4-3: In the event that legislation is enacted or regulatory action is taken to require rebates from manufacturers for discarded drugs, the U.S. Congress should require that rebates be directed first to cover the patient's out-of-pocket expense for the discarded drug and thereafter to health care providers and payers.

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