Spiraling drug costs, drug shortages, and increasingly complex and demanding regulations are making the intravenous (IV) services business more challenging than ever. Pharmacies providing IV compounding must comply with USP 797 (and soon USP 800) and state compounding regulations requiring detailed documentation. The financial impact is obvious. Increased workloads often have required staff additions. USP 797 regulations have prompted costly remodeling to provide buffer rooms and ante rooms.
Spiraling drug costs, drug shortages, and increasingly complex and demanding regulations are making the intravenous (IV) services business more challenging than ever. Pharmacies providing IV compounding must comply with USP 797 (and soon USP 800) and state compounding regulations requiring detailed documentation. The financial impact is obvious. Increased workloads often have required staff additions. USP 797 regulations have prompted costly remodeling to provide buffer rooms and ante rooms. Furthermore, regulations on beyond use dating have restricted the utilization of medications. I have to wonder if all these changes have really added value. Have we gotten our money’s worth? What changes could we introduce to add value and maximize efficiency?
The events prompting the crescendo of regulations for IV compounding have been well documented.1 Most of these involved medium- to high-risk compounding (compounding of sterile products from nonsterile ingredients or combining multiple ingredients) or egregious breaches of aseptic technique. But most sterile compounding in the typical hospital or outpatient infusion center involves low-risk compounding in which a sterile product is diluted in a sterile IV piggyback for use within hours of preparation. Nevertheless, the regulations apply across the board. The USP 797 regulations seem to be based on these assumptions:
Researchers looked at medium-fill simulation to evaluate microbial contamination rates for USP medium-risk-level compounding.2 Contamination rates were less than 1% for manipulations using gloves (sterile = .34% and nonsterile = .96%) which were routinely disinfected with 70% IPA. Rates without gloves were as high as 6%. Low-risk manipulations (which the article states to be probably ~90% at the author’s institution) most likely have a rate just short of 0%. Conclusion: Low-risk manipulations have a very low rate of contamination assuming good aseptic technique and the importance of touch contamination can’t be overemphasized.
We all learned in microbiology that introducing a microbe to a nutrient broth will result in exponential growth. The rub is that simple drug solutions are not nutrient broths. They do not support microbial growth.3-7 They do, however, allow viability except for a few drugs with intrinsic bactericidal activity (eg, platinums, anthracyclines, 5FU). The extent and durability of this misconception is beyond explanation. The policy makers and regulatory agencies (most recently the Joint Commission in their Sentinel Event Alert issue 52, June 16, 2014) repeatedly warn of the dangers of microbial growth in single-dose vials without citing any primary references. Even when microbes are injected into dextrose 5% (a macronutrient) no growth can be detected. The probable explanation is that microbes need both micronutrients (eg, trace minerals) and macronutrients to reproduce. This means that the difference between “multiple-dose” vials with a bacteriostatic agent and "single-dose" vials is in name only. The implications are enormous. Do “single-dose” vials need to be wasted immediately after initial use? Many newer brand name IV drugs can cost thousands of dollars. All that wasted drug can add up. Investigators recently looked at the cost of discarding vials at 6 hours.8 Their stated annual budget for hazardous compounded sterile products was about $20 million and their estimated cost of discarding was about $770,000. In my experience, most vials can be completely utilized after 2 entries and within 24 to 36 hours. Assuming that the integrity of the vial’s diaphragm is maintained, beyond use dating could be extended based on stability data. Because the degree of contamination is a function of the number of entries performed without aseptic technique, the number of entries should be limited (even for “multi-dose vials”). Conclusion: Drug solutions do not support microbial growth and utilization of “single-dose” vials beyond 6 hours can conserve healthcare resources.
Besides the regulatory difficulties, efficient drug utilization can be impeded by the method of compensation. In a fee-for-service setting, incentives are lacking for conservation because it’s possible to bill for wasted drug. It’s easier to bill for the nominal number of vials and throw out the waste even when the balance is exactly what’s needed for the next manipulation. Such behavior is encouraged by attitudes that single-dose vials must be wasted immediately. Furthermore, rounding to the lowest vial size (done in some institutions when dose is within 5% of nominal) is deemed too much of a bother. In an era of astronomical prices and drug shortages, is it ethical to be so cavalier about drug waste? Can payers design systems to incentivize efficiency?
There is a disconnect on this subject between current policies and the scientific literature. These attitudes endure possibly due to misinformation and because any policy intersecting on patient safety seems to be trumped by emotion over evidence. Regulations need to be reasonable, add real value, and be evidence based. Hopefully, optimal value can someday be achieved by collaboration between policy-makers, third-party payers, and practitioners while focusing on a balanced and global perspective.
Dr Vella has been employed with Kaiser in California for 25 years, the last 18 as an oncology pharmacist working in the outpatient infusion clinic. Currently he is affiliated with Dignity Health working at two of its outpatient oncology clinics on California’s central coast.
Disclosure information: The author reports no financial disclosures as related to products discussed in this article.
1. Glassgold JM. Compounded drugs. CRS Report to Congress, June 3, 2013. fas.org/sgp/crs/misc/R43082.pdf. Accessed June 27, 2014.
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