USP : New Regulations to Protect Health Care Workers from Hazardous Drugs

Pharmacists need to be aware of the ways in which draft regulations developed by the United States Pharmacopeia are likely to affect the handling of potentially hazardous drugs.

Currently, approximately 8 million health care professionals are exposed to hazardous drugs (HDs) each year, increasing the burden of chromosomal abnormalities, reproductive risk, and the incidence of cancer among those handling antineoplastic drugs. According to the US Centers for Disease Control and Prevention, since 1994, more than 100 studies have been published documenting worksite contamination with HDs, and more than 50 studies have documented health care worker exposure resulting from this contamination.^1-4

As early as 1983, HD handling guidelines were developed by several organizations, including the American Society of Health System Pharmacists, the Occupational Safety and Health Administration, the National Institute of Occupational Safety and Health (NIOSH), and the United States Pharmacopeia (USP). Of these guidelines, USP regulations have become the most broadly accepted across the United States. The current USP <797> guidelines were issued in 2004 and revised in 2008. New USP <800> regulations will build on the USP <797> and USP <795> guidance. As of March 2015, a draft version of USP <800> is available for public comment.^1-3

Specialty Pharmacy Times discussed the new regulations with one of the foremost experts on USP <800>, Patricia C. Kienle, RPh, MPA, FASHP, director of accreditation and medication safety at Cardinal Health, member of the USP Compounding Expert Committee, and chair of the USP Hazardous Drug Subcommittee and Expert Panel. Kienle’s statements are her own and are not official statements from USP.

The draft USP <800> regulations focus on the importance of protecting health care workers from HDs. These HDs include drugs that are carcinogenic, teratogenic, or genotoxic, but may also include medications that have the potential for causing organ damage at low doses (either in humans or in animals) and new drugs that have structural similarities to existing HDs. NIOSH publishes a list of HDs, with the most recent update published in 2014 (Table 1). Paying attention to this list and going through it carefully will be a first step in adopting USP <800>.^5-8

“Each organization will have to go through the list and identify if there are nonantineoplastic and reproductive hazard only drugs, and organizations need to look not only by drug, but also by dosage form,” Kienle said.

Unpacking and Storage

Per draft USP <800> regulations, HDs must be unpacked either in a neutral or a negative-pressure environment, never in a positive-pressure or sterile compounding environment. Unpacking should occur in a clearly marked area with spill cleanup kits readily available during the unpacking process. Additionally, HDs must be stored in a negative-pressure environment with at least 12 air changes per hour. In the storage area, HDs that require refrigeration must be stored in a separate designated refrigerator from those used to store nonhazardous products.^5,6

Draft USP <800> regulations specify that nonsterile compounding with HDs must occur in a negative-pressure environment, preferably with external venting, or alternatively with redundant HEPA filtration.^5,6

“The hood is in a negative-pressure area. Negative pressure is what contains that drug,” Kienle stated. “If you drop a vial of Cytoxan in your chemo room, you would not want that Cytoxan getting out.”

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Nonsterile Compounding

A powder cabinet may be designated for nonsterile compounding, although a biological safety cabinet (BSC) or compounding aseptic containment isolator (CACI) that is normally used for sterile compounding may be used, provided it is decontaminated, cleaned, and disinfected before resuming sterile compounding. Under USP <800> draft regulations, sterile compounding must occur in a BSC or CACI. As well as the existing requirements in USP <797>, draft USP <800> regulations mandate compounding of HDs in a specific area intended for that purpose. This rule also applies to institutions that prepare low volumes of HDs.^5,6

Eliminating the Low-Volume Exception

“Right now, <797> allows places that prepare a small number of chemo treatments to place their chemo hood inside the same room where they do the rest of their preparation,” Kienle said.

For instance, under USP <797>, HDs may be prepared if 2 tiers of containment are used, such as a closed-system transfer device (CSTD) system within a BSC or CACI. Under proposed USP <800>, the low-use exception will be eliminated and all HD compounding must occur in a negative-pressure environment.^5,6

Some organizations, such as small hospitals or oncology clinics, may not have a negative-pressure clean room. Proposed USP <800> offers an alternative: organizations may use a separate, negative-pressure room called a containment segregated compounding area (C-SCA) that is vented to the outside and has at least 12 air changes per hour but does not need to meet International Organization for Standardization clean room standards. Importantly, treatments prepared under C-SCA conditions have a beyond-use date of only 12 hours.^5,6 Kienle noted the importance of the provision for many organizations, stating, “This provision is not necessarily limited to small hospitals. For instance, some university centers may use this approach for their oncology satellite or oncology clinic.”

Supplemental Engineering Controls: CSTD Systems

Draft USP <800> regulations continue to recommend use of CSTD systems during HD compounding, consistent with USP <797> recommendations. However, unlike USP <797>, draft USP <800> regulations require the use of CSTDs during administration of HDs to patients, provided that the dosage form is compatible with CSTD systems. This new requirement will have an important effect on nurses who administer HDs to patients.^5,6 Kienle added that the changes are necessary to ensure the safety of nurses.

“Right now in pharmacies, we have these engineering controls to protect us,” she said. “The nurses have nothing. They have nothing to contain that drug.”

The draft USP <800> regulations will also mandate that an organization has policies and procedures for medical surveillance purposes and recommend specific issues, such as testing and monitoring of staff for exposure to HDs through their medical history, physical examination, laboratory studies, and biological monitoring.^5,6

Kienle clarified that these are recommendations, stating, “Proposed <800> says that wipe samples should be done, but doesn’t mandate it. As that industry develops and becomes more robust, more and more people will be doing those kinds of tests.”

CSTD Selection

It is important to understand that not all CSTD systems are equally capable of protecting health care workers. Currently, there are 5 CSTD devices available on the US market: the PhaSeal system by Becton Dickinson, SmartSite/Texium by CareFusion/Becton Dickinson, On-Guard/Tevadaptor by B. Braun, ChemoClave/Spiros/ChemoLock by ICU Medical, and Equashield/Equashield II. Although all of these devices have been cleared by the FDA, only 3—the BD PhaSeal system, the Equashield/Equashield II system, and the ICU Medical ChemoLock system&mdash;are cleared with the ONB product code requiring data to demonstrate the systems are truly closed.^9-14

Unlike other medical device product codes, the ONB code is specific to CSTD systems. Using an ONB product code indicates that CSTD systems have data to support the performance of these systems in reducing health care worker exposure to HD contamination and requires proof that the CSTD system is closed. These studies are relevant to USP <800> regulations, which recognize the importance of studies to support the use of CSTDs and do not simply consider CSTDs as a single category of interchangeable products. In recognition of these differences, NIOSH is currently developing a performance protocol to evaluate CSTDs.^9-14

According to a joint position statement issued by the Oncology Nursing Society, the American Society of Clinical Oncology, and the Hematology/Oncology Pharmacy Association, organizations that handle HDs must establish evidence‐based policies and procedures for safe handling of HDs and evaluate the utility of supplemental engineering controls such as CSTDs. These evaluations are difficult, if not impossible, for systems that have not been validated in studies. Some of the important studies substantiating the performance of CSTD systems in protecting health care workers from HD contamination are summarized in Table 2.¹⁵

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Final Thoughts

The USP <800> comment period will last until May 31, 2015, and may be finalized in 2016. Finally, full enforcement of USP <800> requires acceptance by regulatory bodies, including state boards of pharmacy. Enforceability, however, will not be instantaneous.

“Once published, there is a lag time before it is enforceable—6 months from the time of publication, and this may need to be a longer time period for USP <800>,” Kienle said. However, she added, “The biggest message is that people should not be paralyzed by this. Some say, ‘I’m going to wait until it’s absolutely done and then I’m going to start to react.’ These are personal safety issues that need to be addressed now.”

State legislatures are concerned about the issue of HD contamination and are already adopting stricter rules for HD handling. An October 2013 bill from the California legislature approved a bill that addresses the handling of antineoplastic drugs. Other states, including Washington, Maryland, and North Carolina, have adopted stricter standards for the storage, handling, and transport of HDs in advance of the final USP <800> regulations.^1-3,14

With the ultimate approval and adoption of USP <800>, health care professionals can expect more regulations in the handling, transport, storage, administration, and compounding of HDs. However, it is important to remember that CSTD systems help protect health care workers from chromosomal abnormalities, reproductive risk, and cancer.

“USP <800> is 3 things: patient safety, worker safety, and environmental protection,” Kienle said. “None of these are new, but all of those things we want to make sure we’re doing right.” SPT

References

• Gabay M. USP <800> : handling hazardous drugs. Hosp Pharm. 2014;49(9):811-812.
• Massoomi F. USP <800> and the expected impact on health systems. Pharmacy Advisor website. Published July 2014. www.pharmacyadvisor.com/resources/uploads/webinar_handouts/55/usp_800_and_the_expected_impact_on_health_systems.pdf. Accessed March 2015.
• Mixon B. USP <800>: what you need to know. http://c.ymcdn.com/sites/www.pssny.org/resource/resmgr/USP_800_presentaton_to_PSSNY.pdf. Accessed March 2015.
• Centers for Disease Control and Prevention. Occupational exposure to antineoplastic agents and other hazardous drugs. www.cdc.gov/niosh/topics/antineoplastic/pubs.html. Accessed March 2015.
• United States Pharmacopeial Convention. USP—NF General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. www.usp.org/usp-nf/official-text/revision-bulletins/general-chapter-pharmaceutical-compounding-sterile-preparations. Accessed March 2015.
• United States Pharmacopeial Convention. USP <800> Hazardous Drugs—Handling in Healthcare Settings. www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handling-healthcare-settings. Accessed March 2015.
• National Institute for Occupational Safety and Health. NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, 2014. Centers for Disease Control and Prevention website. www.cdc.gov/niosh/docs/2014-138/pdfs/2014-138_v3.pdf. Accessed March 2015.
• Traynor K. NIOSH Revamps Hazardous Drugs Update. American Society of Health-System Pharmacists website. December 15, 2014. www.ashp.org/menu/News/PharmacyNews/NewsArticle.aspx?id=4138. Accessed March 2015.
• BD PhaSeal Closed System Transfer Device. Franklin Lakes, NJ: BD Medical; January 2013. http://repconnectdocuments.s3.amazonaws.com/BD/2014/BD_PhaSeal_FDA_ONBSellSheet.pdf. Accessed March 2014.
• BD PhaSeal system receives clearance from FDA under newly created ONB product code [news release]. PR Newswire. January 15, 2013. www.prnewswire.com/news-releases/bd-phaseal-system-receives-clearance-from-fda-under-newly-created-onb-product-code-186934361.html. Accessed March 2014.
• Equashield II. Port Washington, NY: Equashield. www.equashield.com/pdf/equashield_brochure_web.pdf. Accessed March 2014.
• Equashield closed system receives FDA clearance under ONB product code [news release]. PR Newswire. May 27, 2014. www.prnewswire.com/news-releases/equashield-closed-system-receives-fda-clearance-under-onb-product-code-260765471.html. Accessed March 2015.
• ICU Medical ChemoLock is first and only needlefree CSTD to receive FDA 510(k) clearances [news release]. San Clemente, CA: ICU Medical, Inc; September 9, 2013. www.icumed.com/about-us/news-events/news-articles/icu-medical-chemolock%E2%84%A2-is-first-and-only-needlefree-cstd-to-receives-fda-510%28k%29-clearances.aspx. Accessed March 2015.
• Kastagno ES. Hazardous drugs: A New USP Chapter to Protect Patients and Practitioners and an Update to the NIOSH Alert. New Jersey Society of Health-System Pharmacists website. www.njshp.org/LinkClick.aspx?fileticket=l9jpm2y2URI%3D&tabid=1798&mid=4400. Accessed March 2015.
• Oncology Nursing Society, the American Society of Clinical Oncology, and the Hematology/Oncology Pharmacy Association. Ensuring healthcare worker safety when handling hazardous drugs. Oncology Nursing Society website. www.ons.org/advocacy-policy/positions/practice/hazardous-drugs. Accessed March 2015.

About the Author

Michael R. Page, PharmD, RPh, earned his PharmD from the Ernest Mario School of Pharmacy at Rutgers University. He has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times.