Medications in Single-Dose Vials Implications of Discarded Drugs (2021) / Chapter Skim
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2 Single-Dose Vials of Weight-Based Drugs
2 Single-Dose Vials of Weight-Based Drugs
Pages 31-60
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From page 31... ...
2 As noted in Chapter 1, for the purposes of this report, weight-based dosing includes dosing based on body surface area. 3 The phrase vial size used throughout this report refers to the volume per vial of a drug.
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From page 32... ...
This chapter offers an overview of the factors in the U.S. biopharma ceutical supply chain that interact or compete to influence the amount of discarded drugs from weight-based dosing of medicines contained in single-dose vials including the drug discovery and development process, drug dosing approaches, vial sizes, guidance from federal and non governmental organizations, and clinician acquisition of and payment for drugs.
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FIGURE 2-1 A typical time line for drug discovery and development in the United States.
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Establishment of Weight-Based Dosing in the Drug Development Process As noted above, drug doses are established during early clinical trials to demonstrate that the drug is both safe and effective (FDA, 2005; Musuamba et al., 2017)
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Therefore, an adult dose for many injectable or infusible drugs is frequently weight based because of the early drug development process. DRUG DOSING The dosing regimen for a given drug can contribute to the discarding of drugs.
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From page 36... ...
To address such issues, earlyphase clinical trials need, to the extent possible, to include bodies at the extremes of the weight continuum in order to provide the necessary data for determining the appropriate modifications to the strictly body-weight dosing or to dosing determined according to body surface area (BSA) , which is a variant of weight-based dosing.
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From page 37... ...
. Fixed-dose prescribing has been used for newer targeted therapies covered under Medicare Part B that are highly selective for specific cellular pathways and molecular targets, that demonstrate different relationships between exposure and effect on the molecular target, and that display quite different dose-limiting toxicities than cytotoxic chemotherapy.7 Fixed dosing of these targeted agents has become standard despite wide inter individual variation in plasma concentrations following standard dose regimens and substantial interindividual variability in plasma concentration throughout the dosing interval.
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From page 38... ...
. In brief, because of convenience, safety, and the potential cost savings in the manufacture, packaging, and storing of fixed doses, fixed dosing for all patients regardless of body size characteristics has become the standard for essentially all oral targeted therapies.
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From page 39... ...
An added complication is that even if a medication has been given regulatory approval for multiple vial sizes, there is no guarantee that drug manufacturers will produce or that drug distributors will carry all the approved sizes. Finding the optimal balance between too many and too few vials has been a topic of debate for researchers and policy makers in recent years.
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From page 40... ...
In addition, managing multiple vial sizes of the same product may add complexity to manufacturing and distribution logistics, such as inventory and administrative costs. Each new vial size must be sent to regulatory agencies in multiple countries for validation and approval in order to manage a global supply chain or inventory.
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From page 41... ...
FDA has limited influence over the vial sizes that an individual manufacturer markets or over the design of the foundational clinical trials that sponsors submit as a prerequisite to obtaining regulatory approval. This also includes the oversight of clinical trials undertaken by companies that seek to obtain new drug labels or modify existing drug labels, although there are evidently some aspects of FDA oversight that clearly influence what manufacturers do.
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From page 42... ...
Currently, Medicare reimburses health care providers up to the amount of drug indicated on the vial or package label of a single-dose product, including what is discarded, and patients have cost-sharing responsibility for both the portion they receive and the portion that is discarded. Health care providers must use the smallest package size available from the manufacturer or the package size that is the closest to the patient's prescribed dosage amount (CMS, 2016)
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From page 43... ...
• Consumers and/or health care providers should not be routinely required to use more than one vial to administer a typical single dose of the drug product." According to CMS (2012) , "it is permissible for health care personnel to administer repackaged doses derived from a single-dose vial to multiple patients, provided that each repackaged dose is used for a 10 An ISO 5 environment is a primary engineering control, such as a laminar airflow workbench or compounding aseptic isolator, that allows for no more than 100 particles per cubic foot of air, which acts to minimize the chances of a vial being contaminated by envi ronmental microorganisms (USP, 2009)
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44 FIGURE 2-2 Comparison of FDA, CMS, and CDC guidance on the use of single-dose vials. NOTE: CDC = Centers for Disease Control and Prevention; CMS = Centers for Medicare & Medicaid Services; FDA = U.S.
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There are at least two ways to avoid this incentive: produce vial sizes that are better calibrated to the average single dose or refine the reimbursement system to allow the health care system to charge partial amounts. The latter possibility is hindered by the lack of harmonization across agencies as to whether repackaging is appropriate.
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From page 46... ...
Distributors may choose not to stock all available sizes of the same product, as this would require additional storage space, suppliers, and transportation expenses and impose a risk that the products may exceed their allowable shelf life before leaving the distribution center. PBMs negotiate contracts and drug prices with drug manufacturers and wholesalers on behalf of payers and pharmacies (NASEM, 2018; Schulman and Richman, 2018)
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From page 47... ...
from intermediaries, such as wholesalers or specialty pharmacies; they then store them in their practices, administer them as needed, and submit a claim to either Medicare or the patient's health insurance. This means that the provider decides which vial sizes to buy and stock, often with no or little knowledge of the types of patients the physicians' practices and hospital outpatient departments serve.
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From page 48... ...
FIGURE 2-5 Flow of payments and drugs under "brown bagging." NOTES: For drugs in single-dose vials, physicians are reimbursed for the drug administration fee plus an amount for the quantity of drug that is discarded. The process reduces the opportunity for the physician office, hospital, or clinic to earn margin on the medication itself.
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From page 49... ...
An unintended consequence of the current ASP payment model is that it has the potential to incentivize use of higher priced drugs because administration-related payment to clinicians increases with the price of the drug (Jacobson et al., 2010; OIG, 2012; Werble, 2017) , many of which have been identified as those with the JW modifier used to indicate discarded drug from single-dose vials.
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From page 50... ...
Furthermore, the JW modifier does not comprehensively capture the scope of discarded drugs. Cur rently, according to CMS, the modifier should not be used for drugs or biologicals administered in a rural health clinic or a federally qualified health center, claims for hospital inpatient admissions that are billed under the Inpatient Prospective Payment System, and drugs or biologicals in multi-dose vials.
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From page 51... ...
Thus, in an era where Medicare Part B drug spending is growing faster than drug spending in other federal health care programs, the United States has a tremendous opportunity to realign incentives to encourage health care providers to make the most efficient choices for their patients and to decrease the amount of drugs discarded. Realigning Incentives for Clinician Administration of Infused or Injected Drugs In the past decade, proposals from the federal government -- from both the U.S.
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From page 52... ...
As described later in this chapter, to the extent that these practices become widespread, drug manufacturers are likely to adjust prices of their drugs upward to reflect the fact that more patients are being treated by the same amount of a given drug. Raising drug prices combined with the costs associated with developing methods to allocate drugs to multiple patients from single-dose vials would likely not result in any actual financial savings to payers and patients.
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From page 53... ...
This section examines patient safety and quality-of-care issues related to weight-based drugs, with a particular focus on the implications for small practices and rural hospitals. Changing Roles of Health Care Providers Peeling away all the layers of the drug manufacturing process, public policy, and health care financing, the clinician writes a prescription for a patient for whom a particular dosage of a weight-based drug is expected to treat that patient's disease or condition.
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KEY FINDINGS 1. When a dosing regimen based on body size (e.g., body surface area, weight)
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From page 55... ...
early in the drug development process could help to determine if dosing based on a patient's body size (e.g., weight or body surface area) provides greater benefit than a fixed dose for a given therapeutic agent.
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From page 56... ...
Department of Health and Human Services should require the Centers for Medicare & Medicaid Services (CMS) to uncouple add-on payments to clini cians for infused or injected drugs under Medicare Part B from the drug average sales price, focusing the add-on payment instead on CMS's assessment of the time and complexity of drug management and safety monitoring.17 16 These recommendations will be discussed fully in Chapter 6.
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From page 57... ...
2016. "Brown bagging" and "white bagging" of chemotherapy drugs.
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2015b. Allowable excess volume and labeled vial fill size in injectable drug and biological products: Guidance for industry.
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2007. Flat-fixed dosing versus body surface area based dosing of anticancer drugs in adults: Does it make a difference?
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2015. Narrow therapeutic index drugs: A clinical pharmacological consideration to flecainide.
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