USP <800> Raises Awareness of an Obscure Concern
Hazardous Drugs in Veterinary Medicine
Veterinary care workers encounter a plethora of hazards in their daily work. In addition to the animals themselves, which need to be restrained so they don’t inflict injuries, veterinary care workers can be exposed to infectious organisms, bloodborne pathogens, hazardous chemicals, musculoskeletal disorders, workplace violence, fire, radiation, waste anesthetic gases, and noise. Recently, the promulgation of the United States Pharmacopeia (USP) General Chapter 800 standard has led to increased interest in preventing exposure to hazardous drugs in veterinary medicine providers. 
When most people hear the term “hazardous drug,” they usually think of chemotherapy drugs administered to patients within a human healthcare setting. Veterinary care workers also administer a fair number of hazardous drugs, albeit to furrier patients with two (or more) legs in some rather unorthodox environments. The potential for exposure to hazardous drugs, and the challenges related to minimizing it, are quite similar in veterinary and human healthcare settings. USP is a nonprofit organization that develops standards for the uniform preparation of drugs to ensure their quality, potency, and purity. USP <800> was developed with the goal of protecting the health and safety of all healthcare workers and patients who may be exposed to hazardous drugs. On December 1, 2019, USP <800> became official, yet informational only until updates to USP chapters <795> and <797> become official. The effective dates for those chapters have yet to be determined. The unique aspect of USP <800> is that its scope is not limited to the pharmacy space: USP <800> is applicable to personnel handling hazardous drugs in all healthcare settings, including pharmacists, nurses, veterinarians, and technicians. USP <800> provides an 18-section framework to help veterinarians protect their staff from exposure to hazardous drugs from the moment the drug enters an organization to the time it leaves, encompassing preparation, administration, use of engineering controls, personal protective equipment, training, and disposal.  ENFORCEMENT OF USP <800> The enforcement of USP standards is unclear and varies across local, state, and federal agencies as well as veterinary medicine and pharmacy licensing boards. Veterinary medicine may be practiced by veterinarians licensed by the Board of Veterinary Medicine at private clinics within the local community; veterinary hospitals that offer more specialized services such as oncology, orthopedics, cardiology, and dermatology; and research facilities at universities and specialty schools of medicine, which may employ pharmacists licensed by a separate Board of Pharmacy. If the state Board of Pharmacy has adopted USP standards, the pharmacy licensure process offers opportunities for enforcement, but according to Emily Sorah, director of clinical pharmacy services at North Carolina State College of Veterinary Medicine and president-elect of the Society of Veterinary Hospital Pharmacists, “this would be rare and likely to occur only in a university setting.”  Another avenue of enforcement of USP standards would be through the Board of Veterinary Medicine, but according to an article from the Veterinary Information Network Services, as of February 2018 only four states—Delaware, Georgia, New Mexico, and Washington—had confirmed that they will either be amending or have already incorporated USP <800> language into their state’s veterinary practice act. In Alaska, Missouri, Nevada, New Hampshire, and Virginia, USP <800> was “under review.”  Many states have adopted or are in the process of adopting their own OSHA standards related to hazardous drugs—for example, North Carolina and Washington have adopted OSHA standards, while California has a rule pending—which would impact veterinary care workers. If your state does not have a local OSHA standard specific to hazardous drugs, there is always the OSHA Hazard Communication standard (29 Code of Federal Regulations 1910.1200), which requires employers to provide information about the hazards of each chemical in the workplace; and the OSHA General Duty Clause, which stipulates that each employer furnish to each of its employees a workplace that is free from recognized hazards that are causing or likely to cause death or serious physical harm. DEFINING “HAZARDOUS DRUG”  The foundation for a successful and comprehensive program for safe handling of hazardous drugs is a complete and accurate inventory of hazardous drugs used within the veterinary setting. According to USP <800>, “an entity must maintain a list of hazardous drugs, which must include any items on the current National Institute for Occupational Safety and Health (NIOSH) list that the entity handles.” NIOSH defines a drug as hazardous if it causes cancer or embryonic malformations, interferes with the development of the fetus, impairs reproduction, damages organs at low doses, or mutates genetic information within cells. NIOSH regularly reviews drugs approved by the Food and Drug Administration and publishes a list of hazardous drugs that meet the agency’s criteria. The list released in 2016 contains 266 hazardous drugs grouped into antineoplastics; non-antineoplastics that meet one or more of the  NIOSH criteria for a hazardous drug; and non-antineoplastic drugs that primarily have adverse reproductive effects. (Ed. note: NIOSH released its most current hazardous drug list for public comment on May 1, 2020, too late to be considered for this article.)
The enforcement of USP standards varies across local, state, and federal agencies as well as veterinary medicine and pharmacy licensing boards.
However, as Sorah noted, “The [2016] NIOSH hazardous drug list focuses on human drugs and does not list veterinary-specific drugs.” Jenny Cassibry Fisher, director of education at Practivet, a provider of veterinary equipment, agreed that “the lack of a veterinary-specific hazardous drug list makes it challenging for veterinary providers to identify all the hazardous drugs used within veterinary medicine and that smaller practices do not have the bandwidth to evaluate new drugs to determine if they meet the NIOSH criteria.”  Jerald Ovesen, a NIOSH pharmacologist who coordinates the agency’s hazardous drug list, indicated that “although the [2016] NIOSH hazardous drug list is undergoing revisions, it will not contain veterinary-specific drugs at this time, but NIOSH does consider input from the public concerning potential changes to the list.” In lieu of a NIOSH veterinary hazardous drug list, Cassibry Fisher recommends “using the current NIOSH hazardous drug list as the foundation of the facility-specific list and add veterinary-specific drugs that have similar toxicological profiles to the human drugs” on the NIOSH list. BRIDGING THE IMPLEMENTATION GAP Although USP <800> provides an 18-section framework to manage hazardous drugs, the requirements surrounding implementation can be quite overwhelming, especially for small veterinary practices that have limited safety resources. No doubt, Section 5 on facilities and engineering controls is the most challenging section to implement. Section 5 requires substantial capital investment to renovate existing spaces to meet USP <800> containment primary engineering control (C-PEC) requirements such as the installation of appropriate biological safety cabinets within an appropriate containment secondary engineering control (C-SEC). (An example of a C-SEC is a negative-pressure room to protect the worker from exposure to hazardous drugs and protect the preparation from microbial contamination.)  Overcoming the renovation hurdle to achieve protection for workers and drug preparation is enough to give even the most experienced design consultant pause. Sorah recommends focusing on low-hanging fruit to minimize exposure to hazardous drugs and consider outsourcing areas or processes where you may not be able to achieve compliance. Many online tools are available to assist in the identification of program gaps; some are listed in the Resources section at the end of this article.  CLOSED SYSTEM DRUG-TRANSFER DEVICES Closed system drug-transfer devices, or CSTDs, are readily available supplemental engineering controls that offer an additional level of protection by limiting the aerosolization of hazardous drugs during compounding and administration. Cassibry Fisher recommends “checking with the CSTD distributor to determine if they offer education and training services as part of the product roll-out.” PERSONAL PROTECTIVE EQUIPMENT PPE such as chemotherapy-tested gloves, impermeable gowns, head/hair/shoe/sleeve covers, goggles, face shields, and respirators protect workers from surface residues and aerosols generated from handling hazardous drugs during receipt, storage, transport, compounding, administration, deactivation/decontamination/cleaning/disinfection, spill management, and waste disposal. PPE varies by risk of exposure and activity performed. To determine the appropriate PPE, conduct an exposure assessment that reviews dosage, formulation, route of exposure, and frequency and duration of exposure. USP <800> stipulates that “disposable PPE must not be re-used. Reusable PPE must be decontaminated and cleaned after use.”  Gloves. Gloves used for compounding and administration of chemotherapy drugs must meet the ASTM International D6978 standard, which tests the permeation (breakthrough) of nine chemotherapy drugs through the glove material over a certain period of time. Although ASTM D6978 gloves are not required when handling non-chemotherapy drugs, it is a best practice to use the ASTM D6978 gloves. If you are uncertain whether your current gloves meet the ASTM D6978 requirements, look on the glove box for the symbol indicating ASTM D6978 testing or contact your distributor or manufacturer for the glove specifications. Users should change gloves every 30 minutes or when torn, punctured, or contaminated, and wash their hands with soap and water after removing gloves.  Gowns. Compounding and administration (via injection) of chemotherapy drugs requires the use of a gown that resists the drugs’ permeability. Unfortunately, there is no current test for permeability of chemotherapy drugs on gowns, so manufacturers tend to use chemotherapy drugs as surrogates for ASTM F739, Test Method for Permeation of Liquids and Gases Through Protective Clothing Materials Under Conditions of Continuous Contact. USP <800> recommends using “disposable gowns made of polyethylene-coated polypropylene or other laminate materials [that] offer better protection than those made of uncoated materials.” When in doubt, review the manufacturer specifications, especially for isolation gowns, which typically are not made with polyethylene-coated polypropylene or other laminate materials. As with gloves, gowns are required when handling non-chemotherapy hazardous drugs. The use of gowns made with polyethylene-coated polypropylene or other laminate materials, though not required, is a best practice. Change gowns per manufacturer recommendations or every two to three hours in the absence of manufacturer recommendations.  Eye and face protection. USP <800> states that “appropriate eye and face protection must be worn when there is a risk for spills or splashes of hazardous drugs or hazardous drug waste materials when working outside of a C-PEC (e.g., administration in surgical suite, working at or above eye level, or cleaning a spill).” Use of eye and face protection is especially important when veterinarians administer electrochemotherapy (delivery of chemotherapy drugs through electric pulses to tumors) on large animals, as this work tends to be above eye level.  A common misconception when working with hazardous drugs that present a potential splash hazard to the eyes and face is that the use of safety glasses is adequate. Safety glasses are similar in shape to prescription glasses and sunglasses—they have open sides that allow a splash to reach the eyes above, under, or around the lenses. Chemical safety goggles that seal to the face on all sides are the appropriate type of protection from splash hazards coupled with a face shield to prevent splashes to the face. Another misconception is that a face shield is adequate protection in lieu of eye protection. As with safety glasses, a splash can enter the eyes and face through the openings above, under, and around the face shield. Respiratory protection. An exposure assessment should be conducted to determine which tasks require respiratory protection and which type is appropriate. In addition, ensure that you follow the OSHA respiratory protection standard (29 CFR 1910.134), which requires medical clearance, fit testing, and training for those tasks that require respiratory protection. EDUCATION AND TRAINING The OSHA hazard communication standard (29 CFR 1910.1200) requires that all employees who may be exposed to hazardous chemicals must be trained prior to their initial assignment on how to work safely with the hazard. USP <800> essentially reinforces this requirement, but it is specific to working with hazardous drugs and requires reassessment at least every 12 months. Sorah tackled the training dilemma by developing online learning modules to provide quick and efficient training with standardized content for many staff who handle hazardous drugs. “Boards of pharmacy typically also prefer an observational checklist demonstrating understanding and skills,” Sorah said, adding that, at North Carolina State, the observational checklist is independent of online training. But she cautioned that “training through staff meetings is likely more efficient in small clinic settings.”  Quick wins with low-hanging fruit can also be achieved through labeling of hazardous drugs, obtaining safety data sheets, and procuring spill kits. Sorah recommends “focusing on the ‘must’ versus the ‘should’ language of USP <800>, and remember that the implementation of USP <800> is a learning process and to remain flexible in workflows to achieve proper compliance.”    SHELLEY R. CARRY, CIH, CSP, is principal consultant at Kaiser Permanente. She can be reached at . Acknowledgments: The author thanks Jerald L. Ovesen, PhD; Jenny Cassibry Fisher, RVT, VTS-Oncology; and Emily Sorah, PharmD, RPh, DICVP, FACVP, FSVHP, for their contributions to this article. Send feedback to The Synergist.

ASTM International: ASTM D6978 - 05(2019), Standard Practice for Assessment of Resistance of Medical Gloves to Permeation by Chemotherapy Drugs (2019).  ASTM International: F739-12e1, Standard Test Method for Permeation of Liquids and Gases through Protective Clothing Materials under Conditions of Continuous Contact (2012). California OSHA: Occupational Exposure to Antineoplastic Drugs. CriticalPoint: 2020 USP <797> & <800> Compliance Study and Gap Tool. “Self-Assessment of Safe Handling Practices for Hazardous Drugs,” NIOSH: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, 2016 (2016). North Carolina OSHA: 13 NCAC 07G.0101, Handling of Antineoplastic Agents. OSHA: Occupational Safety and Health Standards, Personal Protective Equipment, Respiratory Protection. OSHA: Occupational Safety and Health Standards, Toxic and Hazardous Substances, Hazard Communication. USP: United States Pharmacopeia General Chapter 800, Hazardous Drugs — Handling in Healthcare Settings (PDF, 2016). VIN News Service: “Veterinary Profession Mulls Implementing USP 800 (February 2018). Washington OSHA: WAC 296-62-500 Hazardous Drugs (PDF).
Veterinarians and COVID-19

In April, CDC issued interim guidance to protect veterinary providers from COVID-19. Although CDC is aware of a small number of animals reported to be infected with SARS-CoV-2 after close contact with people who have COVID-19, at this time there is no evidence that animals play a significant role in spreading the virus. Review the interim guidelines on CDC's website.

Although the print version of The Synergist indicated The IAQ Investigator's Guide, 3rd edition, was already published, it isn't quite ready yet. We will be sure to let readers know when the Guide is available for purchase in the AIHA Marketplace.
My apologies for the error.
- Ed Rutkowski, Synergist editor
Disadvantages of being unacclimatized:
  • Readily show signs of heat stress when exposed to hot environments.
  • Difficulty replacing all of the water lost in sweat.
  • Failure to replace the water lost will slow or prevent acclimatization.
Benefits of acclimatization:
  • Increased sweating efficiency (earlier onset of sweating, greater sweat production, and reduced electrolyte loss in sweat).
  • Stabilization of the circulation.
  • Work is performed with lower core temperature and heart rate.
  • Increased skin blood flow at a given core temperature.
Acclimatization plan:
  • Gradually increase exposure time in hot environmental conditions over a period of 7 to 14 days.
  • For new workers, the schedule should be no more than 20% of the usual duration of work in the hot environment on day 1 and a no more than 20% increase on each additional day.
  • For workers who have had previous experience with the job, the acclimatization regimen should be no more than 50% of the usual duration of work in the hot environment on day 1, 60% on day 2, 80% on day 3, and 100% on day 4.
  • The time required for non–physically fit individuals to develop acclimatization is about 50% greater than for the physically fit.
Level of acclimatization:
  • Relative to the initial level of physical fitness and the total heat stress experienced by the individual.
Maintaining acclimatization:
  • Can be maintained for a few days of non-heat exposure.
  • Absence from work in the heat for a week or more results in a significant loss in the beneficial adaptations leading to an increase likelihood of acute dehydration, illness, or fatigue.
  • Can be regained in 2 to 3 days upon return to a hot job.
  • Appears to be better maintained by those who are physically fit.
  • Seasonal shifts in temperatures may result in difficulties.
  • Working in hot, humid environments provides adaptive benefits that also apply in hot, desert environments, and vice versa.
  • Air conditioning will not affect acclimatization.
Acclimatization in Workers