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USP General Chapter <800> Hazardous Drugs Handling in Healthcare Settings

Introduction

Most healthcare workers are aware that antineoplastic drugs (medications used to treat cancer; also referred to as chemotherapy drugs), such as

cisplatin, methotrexate, mercaptopurine, or cyclophosphamide, have significant side effects and must be handled with care. However, other

meds that require special handling to avoid hazardous exposure, such as fluconazole or phenytoin, may not be that obvious.1 In addition, even if

a healthcare worker can identify a hazardous med, they still may not know how to safely handle it to prevent toxic exposure. For example, if a

box of antineoplastic vials dropped to the floor and broke, would you know how to handle the spill?

United States Pharmacopeia (USP) Chapter <800> was created to provide better guidance on how to safely handle hazardous meds in all

settings, including both inpatient (hospitals, nursing homes, etc.) and outpatient (pharmacies, physician offices, etc.) sites. It includes safe

handling of hazardous meds for ALL employees, such as those receiving the product, compounding the medication, or transporting it to the

patient. In addition, USP Chapter <800> focuses on minimizing the risk of contamination not only to the patient but also to the healthcare worker

and the environment.1

USP Chapter <800> was drafted in June 2014. After receiving input, the draft was updated and officially released in February 2016. However, a

delay in implementation was approved until December 2019 to allow time for facilities to prepare to meet the standard.1,2 USP Chapter <800> is

designed to complement USP Chapter <797> on sterile compounding and Chapter <795> on nonsterile compounding. It will not replace them.

Because it is a chapter below 1000 in the USP manual, it will be enforceable. Expect to hear more about the safe handling of hazardous meds at

your pharmacy. Start preparing yourself by reviewing the basic concepts of USP Chapter <800>.

Identify Hazardous Meds

Facilities handling hazardous medications are responsible for reviewing and making sure they are compliant with USP Chapter <800> standards.

So how do you know which meds are considered hazardous? The National Institute for Occupational Safety and Health (NIOSH) releases a list

of hazardous medications periodically, with the most recent list published in 2016(https://www.cdc.gov/niosh/docs/2016-161/). In addition,

NIOSH provides advice for how to review the hazardous potential of new medications that become available.3

NIOSH defines hazardous meds using the definition first published in the 1990 American Society of Health-System Pharmacist's guidance concerning hazardous

drugs. A med is considered hazardous if it has one or more of the following characteristics in humans or animals:3

• Carcinogenicity (cancer causing)

• Teratogenicity or other developmental toxicity (causing harm to an unborn baby)

• Reproductive toxicity (interference with normal reproduction such as effects on fertility in either sex)

• Organ toxicity at low doses (harming organs, such as heart, liver, lungs, etc.) • Genotoxicity (damaging the genetic information in a cell, which could lead to cancer)

• Structure and toxicity profiles of new drugs that are the same as drugs considered hazardous by the above criteria

Examples of medications with at least one of these characteristics:3

Carcinogenicity Anastrozole (Arimidex) Leuprolide (Lupron)

Teratogenicity or other developmental toxicity

Valproic Acid (Depakote) Fluconazole (Diflucan)

Reproductive toxicity Colchicine (Colcrys) Dutasteride (Avodart) Paroxetine (Paxil)

Organ toxicity Carbamazepine (Tegretol)

Genotoxicity Abacavir (Ziagen) Mycophenolic Acid (Myfortic)

Other examples of hazardous medications on NIOSH's list that may surprise you include:

• Estrogens

• Clonazepam (Klonopin)

• Dronedarone (Multaq)

• Phenytoin (Dilantin) and fosphenytoin (Cerebyx)

• Oxcarbazepine (Trileptal)

• Raloxifene (Evista)

• Risperidone (Risperdal)

• Spironolactone (Aldactone)

• Topiramate (Topamax)

• Voriconazole (Vfend)

Most pharmacies are likely to stock at least one of the medications on NIOSH's hazardous med list and will need to ensure they are meeting

USP Chapter <800> standards. Any antineoplastic drug or hazardous active pharmaceutical ingredient (API; a substance or mixture of

substances intended to be used in compounding) that undergoes manipulation, such as IV compounding, will need to meet all of USP Chapter

<800> standards. However, some hazardous medications on NIOSH's list may be available in dosage forms that remove some of the hazardous

potential. These medications will still need to undergo an assessment of hazardous risk. This assessment must include a review of the risk of

exposure to the patient, environment, and ALL personnel who will interact with the medication, including those receiving, storing, compounding,

dispensing, transporting, administering, and disposing of the medication. In addition, consideration must be made for those responsible for

removing medication waste, cleaning patient waste (e.g., excreted unmetabolized drug), and managing any kind of spill or damage to the dosage

form.1 For example, consider a ready-to-use fluconazole tablet that does not require manipulation. In this case, the pharmacy may not need to

follow all of the USP Chapter <800> standards provided it has reviewed the risks of hazardous exposure and completed a hazardous drug

assessment of risk. The pharmacy will still need to ensure fluconazole's safe use to mitigate any kind of hazardous exposure.1,3 For instance, a

pharmacy may have a policy in place to not allow fluconazole tablets to be manipulated or placed in devices that could crush or split the tablet,

such as a pill counter. Consider the use of electronic reminders or shelf tags for these meds to remind employees and ensure safe use.

Your facility must maintain a list of hazardous drugs that includes any items on the current NIOSH list that are handled at your facility. This list

must be reviewed and updated at least every 12 months. In addition, your pharmacy should have a process for reviewing the hazardous potential

of new medications and addressing concerns before bringing them into your pharmacy. Finally, if it's a medication that has been released to the

market after the most up-to-date NIOSH list, your facility is still responsible for reviewing its hazardous potential. If you're on the fence about the

hazardous potential of a medication, it's recommended to take precautions until more information is available.1

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USP General Chapter <800> Hazardous Drugs Handling in Healthcare Settings

Review of Equipment

Before we get into the specific instructions for handling hazardous meds, let's review the equipment that may be used. This will assist when we

get into specific requirements throughout this course.

Personal Protective Equipment1

If the personal protective equipment being used is disposable, do NOT reuse it. For example, a pharmacist or a technician leaving the IV

chemotherapy area should NOT hang up their gown to reuse later. You must dispose of it and get a new one when returning to the area.1

If your personal protective equipment is non-disposable, then you must follow your facility's policy for proper and safe cleaning. Do NOT take these items home to clean.1

o Gloves: When chemotherapy gloves are required for handling hazardous meds, they must meet the American Society for Testing

and Materials (ASTM) standard D6978-05 (or its successor).1,9

• Tips when using chemotherapy gloves with hazardous meds:1

▪ Make sure they are powder free since powder can absorb hazardous material and particulates from the

powder can contaminate the sterile compounding area.

▪ Inspect for defects prior to use and dispose if any are identified.

▪ Keep in mind the outer layer of chemotherapy gloves used during sterile compounding must be sterile.

▪ Change chemotherapy gloves at least every 30 minutes unless the manufacturer recommends an alternative

duration. Gloves should also be changed if any kind of tear or puncture occurs.

▪ Wash hands with soap and water after removing gloves.

o Gowns: Gowns for handling hazardous meds must be long-sleeved with cuffs at the end. They must be able to resist permeability by

hazardous drugs. Gowns cannot have openings in the front and must close in the back.1

• Tips when using gowns with hazardous meds:1 ▪ Change gowns according to the manufacturer's instructions. If no information is available from the

manufacturer, then gowns must be changed every 2 to 3 hours and immediately after a spill.

▪ Do NOT use gowns worn in hazardous areas in other areas.

o

o These sheets are required to contain:4

▪

▪

▪

▪

▪

▪

▪

▪

▪

▪

▪

o

▪

o Precautions while handling (commonly section 16, How Supplied/Storage and Handling)5

▪

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USP General Chapter <800> Hazardous Drugs Handling in Healthcare Settings

• Tips for handling other items accidentally exposed to hazardous substances, such as a lab coat or scrubs:1

▪ Remove the item immediately to prevent exposure to your skin.

▪ Do NOT take these items home to clean.

▪ Wash them according to your facility's policy.

o Head, hair, shoe, and sleeve covers: These provide protection from contact with hazardous residues.1

• Shoe covers worn in hazardous med areas must be removed before walking into other areas to prevent hazardous contamination.

o Eye and face protection: If there are risks of a spill or splash from a hazardous med or its waste, expect to be required to use

appropriate eye and face protection.1

o Respiratory protection: Respiratory protection may be required if unpacking hazardous meds that are not contained in plastic,

when cleaning up large spills that cannot be contained with a spill kit, during certain decontaminating and cleaning procedures, or

if vapor or gas exposure is suspected. Surgical masks and N95 masks are not acceptable because they do not prevent the

inhalation of hazardous vapors. Expect your policy to describe which respirators are acceptable and available at your facility.1

Handling Hazardous Meds

What determines the risks of handling hazardous drugs?

The extent of risk with hazardous drugs, which determines handling requirements, boils down to two things:

• How much exposure does a person have?

• How hazardous is the med?

For example, exposure to hazardous drugs that come in ready-to-use dosage forms such as unit-dose tablets or capsules is minimal. In

contrast, compounding doses of injectable hazardous drugs increases the risk of exposure, such as from spray from a vial or accidental spills

that could lead to inhalation or absorption of drug through the skin.

Facilities must develop policies and procedures for the safe use of hazardous meds. All employees who handle these meds in any way must be

trained on how to prevent harm to themselves, patients, and the environment. Most of us think about the pharmacist or technician compounding

a hazardous med or the nurse administering it, but there are many other steps in the medication management process where employees are

handling hazardous meds.1,3

Facilities must designate a trained employee who can ensure all policies and procedures are meeting accepted standards for safe use. This

employee may lead the process of developing safe procedures and overseeing compliance to them. For example, this person will likely make

sure all employees involved with hazardous meds are adequately trained.1

All personnel exposed to hazardous meds must be trained PRIOR to performing their responsibility. There must also be some type of

competency to ensure proper understanding and demonstration of the material. Competencies must occur before a new employee can handle

the hazardous meds and reassessed at least every 12 months. Training must also occur if significant changes occur to the facility's procedures,

or if new hazardous meds are brought into the facility. All training and competencies must be documented.1

Hazardous med policy and procedures must be reviewed at least every 12 months. Any changes made to them must be communicated to all

personnel who handle hazardous meds, and evidence of these communications must be documented and maintained for the length of time as

required by the facility's state regulations.1

The policy and procedures should include standards for properly handling a medication from the minute it's delivered to your facility until its

disposal and removal. Expect the following to be included about hazardous meds at your facility:1

o Environmental monitoring to ensure hazardous exposure is not exceeding recommended standards

o How to dispose of hazardous meds and any exposed materials, such as wipes used for cleaning hazardous meds

o How to manage spills from hazardous meds

o Procedures for administration o Procedures for dispensing and transporting hazardous meds

o Procedures for safe nonsterile and sterile compounding

o Required medical surveillance of employees handling hazardous meds

o Where to receive (unpack) orders containing hazardous meds

o Where to store hazardous meds

Receipt of Hazardous Meds

Help your facility by reviewing the hazardous medications on NIOSH's list for their potential risk of exposure upon receipt. For example, the

antineoplastic agent cisplatin is available as a liquid in a vial. If the vial breaks upon delivery to your facility, then it could lead to hazardous

exposure to employees who receive the order. It's recommended to contain any potential exposure by receiving meds like this in a neutral or

negative pressure area. In addition, a spill kit should be available in this area and employees should be trained to use necessary personal

protective equipment, such as chemotherapy gloves.1

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USP General Chapter <800> Hazardous Drugs Handling in Healthcare Settings

If your facility does have a negative pressure area for compounding hazardous, sterile meds, it's important to remember that this will not be the

best place to receive a medication. Opening boxes and containers could contaminate the room and interfere with the sterility requirements

needed for compounding sterile products.1,10

Some meds on NIOSH's hazardous med list are not likely to cause toxic exposure upon receipt, such as phenytoin capsules available in their

final dosage form. Your facility's policies and procedures should explain how to differentiate between the meds that require special handling upon

receipt and which do not.1,3 For the medications that do require special handling, pay attention to packaging as it arrives. Hazardous meds

should be received from the supplier in impervious plastic (a plastic that doesn't allow fluids to pass through). If there appears to be damage to the packaging, expect your policy to provide guidance on how to handle this situation. For example, you may be instructed to reseal the container

and return it to the manufacturer.1

Storage of Hazardous Meds

Antineoplastic hazardous drugs requiring manipulation and hazardous active pharmaceutical ingredients must be stored separately to prevent

hazardous exposure to other meds. For example, cisplatin vials should be stored in a separate area designated for hazardous medications.

Expect this designated area to be a negative pressure area that is vented to the outside. Sterile and nonsterile hazardous meds can be stored

together. However, it's not recommended to store nonsterile meds in your sterile compounding areas if possible. This will introduce extra traffic in

and out of these areas, which could lead to more contamination and difficulty maintaining sterility requirements.1

After an assessment of risk, your facility may determine that other hazardous meds that are not likely to cause toxic exposure upon receipt or

storage, such as phenytoin capsules, can be placed in your pharmacy's regular storage area with other non-hazardous meds. Help your facility

by reviewing NIOSH's list of hazardous meds and identifying those meds which could pose hazardous exposure risk upon receipt and storage

and which do not. For example, the oral chemotherapy agent erlotinib (Tarceva) is available as a tablet in its final dosage form and should not

pose hazardous exposure risk upon receipt or storage. Don't be surprised to see this medication stored on the shelves in your pharmacy's

regular storage area with other non-hazardous meds. Review your facility's policy to evaluate which meds require special hazardous storage and

which do not.1

Labeling, Packing, Transporting, Disposing of Hazardous Meds

As discussed earlier, each facility is responsible for determining which hazardous meds on NIOSH's list require special handling procedures.

Meds identified as hazardous should be clearly labeled at all times during transport. In addition, when placing the label onto a compounded,

hazardous med, do so in a way that will not expose others to any hazards.1

Hazardous meds that don't require any further manipulation, such as the oral chemotherapy agent erlotinib available in its final dosage form, may

not require special handling. However, your facility must make an assessment of the medication and determine what best practices need to be

put in place for its safe handling. For example, avoid anything that could damage or disrupt this final dosage form, such as automated counting or

packaging machines which can subject hazardous meds to stress and may create powdered contaminants. Review your facility's policy to

determine how to handle all potentially hazardous medications and ask questions if you have any concerns.1

Any med that may be hazardous must be packaged in a way to prevent exposure to those transporting it. Expect these details to be described in

your pharmacy's policy. In addition, the med must be transported in the safest way possible. For example, do not use a pneumatic tube to

transport liquid hazardous meds or any antineoplastic agent.1

Finally, any employee involved in removing hazardous waste must be trained on appropriate procedures to protect themselves and the

environment.1

Deactivating, Decontaminating, Cleaning, and Disinfecting

All areas, equipment, and devices handling hazardous meds must be deactivated, decontaminated, and cleaned. In addition, if it's used for

sterile compounding, it must also be disinfected.1

o Deactivating makes the compound inactive.

o Decontaminating removes hazardous residue from non-disposable surfaces and transfers it to an absorbent, disposable material, such as

a wipe or towel.

o Cleaning removes contaminants, such as soil, from objects and surfaces. o Disinfecting inhibits or destroys microorganisms. All surfaces must be cleaned before they can effectively be disinfected.

There is no one proven product or method to deactivate or decontaminate. Each facility will need to consider products that are appropriate for the

type of hazardous meds at the facility and are compatible with the equipment and devices according to manufacturer instructions. For example,

sodium hypochlorite may be used to deactivate and decontaminate, but it can cause corrosion to some surfaces. This is why you may see

sodium hypochlorite used with sodium thiosulfate. Sodium thiosulfate can neutralize sodium hypochlorite and prevent corrosion. Your facility may

use wipes or other absorbent, disposable materials to remove hazardous residue. However, expect your facility to avoid the use of spray bottles

which may spread hazardous exposure.1,9

Because this process is so complicated, it will be limited to trained personnel. These staff members must be trained on your pharmacy's

procedures, including what personal protective equipment to wear while performing the different tasks. For example, expect personnel to

decontaminate, deactivate, and clean while wearing at least two pairs of chemotherapy gloves and an impermeable disposable gown. Additional

protective equipment may also be required depending on the circumstance. For example, the space below the work tray in a primary engineering

control should be decontaminated and cleaned once a month. Cleaning and decontaminating this area may interrupt the airflow through the hood

and require the use of respiratory protection during cleaning.1

Each facility is responsible for including procedures on how to avoid spills AND procedures for how to address a spill should one occur. For

example, only trained personnel should manage a spill, and these personnel must be available any time hazardous meds are being handled at

your facility. This is important to protect the employees cleaning the spill, any person located beside the spill, and the environment. For example,

if a spill may expose vapors, the employee managing the spill should wear an approved respirator and be familiar with how to work it. Spill kits

should be readily available in all areas where hazardous substances are handled. The locations of these spill kits should be included in the

facility's procedures.1

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USP General Chapter <800> Hazardous Drugs Handling in Healthcare Settings

To summarize, the table below provides a few commonly encountered examples and some guidance for safe handling:1,3

Example Activity Personal Protective Equipment Engineering

Control

Receiving, unpacking, and storing medications determined to be potentially hazardous during these procedures

• Single chemotherapy gloves, unless spill occurs then double glove

• Special circumstances may require additional items, such as if spills occur (see handling spill example below)

Not required

Handling waste of hazardous meds • Double chemotherapy gloves • Gown (impermeable to hazardous drugs) • Eye/face protection if liquid could splash • Respiratory protection if vapor or other inhalational

exposure

N/A

Handling spills • Double chemotherapy gloves • Gown (impermeable to hazardous drugs) • Certain larger spills may require eye/face protection

and/or respiratory protection (should be described in policy)

N/A

Environmental Quality and Control

When working with hazardous meds, it's important to routinely monitor your pharmacy for over-exposure or for exposure to areas designated as

non-hazardous areas. This is done by surface wipe sampling. There is no standard in regard to which wipes and how many should be used

during sampling. It's just recommended to verify the wipe sampling kit chosen for your facility has been validated to identify known hazardous

meds from various surface types.1

Surface wipe sampling should be performed on the:1

o Interior of the primary engineering control and any equipment located within it

o Pass-through chamber (if you have one)

o Areas around the primary engineering control, such as adjacent work surfaces and the floor

o Areas immediately outside the hazardous compounding area

o Patient administration areas

If surface wipe sampling shows detectable values, your pharmacy will need to identify the cause. For example, it may be an issue with training

employees or it could be that the decontamination process needs to be re-evaluated. Once the problem is identified and adjustments are made,

the wipe sampling should be repeated to ensure the adjustments did result in improvement.1

The Bottom Line

Procedures for proper handling of hazardous meds are imperative to ensure the safety of healthcare employees, patients, and the environment.

USP Chapter<800> was created to enhance the guidance for hazardous med safe use. USP Chapter <800> should complement other standards

involving hazardous meds, including USP Chapter <795> and Chapter <797>. In other words, pharmacies should make sure their procedures

are meeting all standards.

Hazardous meds include not only chemotherapy agents, but also meds that may pose other toxicities, such as organ damage and reproductive

toxicity. This is why it's so important for most healthcare workers to familiarize themselves with the standards within USP Chapter <800>. It

provides safety tips for known hazardous meds. However, it also provides advice on how to avoid toxic exposure from commonly used meds that

many may not realize have hazardous potential, such as fluconazole or phenytoin. Many healthcare workers, patients, and their family members

are exposed to these agents and need to be aware of the recommended practices to avoid hazardous contact.

References

1. <800> Hazardous Drugs - Handling in Healthcare Setting. In: United States Pharmacopeia and National

Formulary (First Supplement USP 39-NF 34).

2. United States Pharmacopeia. FAQs: <800> Hazardous Drugs - Handling in Healthcare

Setting.http://www.usp.org/frequently-asked-questions/hazardous-drugs-handling-healthcare-settings

November 3, 2017. (Accessed October 5, 2018).

3. National Institute for Occupational Safety and Health. NIOSH List of Antineoplastic and Other Hazardous Drugs

in Healthcare Setting, 2016. https://www.cdc.gov/niosh/docs/2016-161/ (Accessed October 9, 2018).

4. Occupational Safety and Health Administration. Hazard Communication Safety Data Sheets.

https://www.osha.gov/Publications/HazComm_QuickCard_SafetyData.html (Accessed October 9, 2018).

5. Food and Drug Administration. Guidance for Industry: Labeling for Human Prescription Drug and Biological

Products - Implementing the PLR Content and Format Requirements. February 2013.

https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM075082.pdf.

6. Product information for Multaq. Sanofi-Aventis U.S. LLC. Bridgewater, NJ 08807. January 2017.

7. Product information for Colcrys. Takeda Pharmaceuticals America, Inc. Deerfield, IL 60015. December 2015.

8. Product information for Sprycel. Bristol-Myers Squibb Company. Princeton, NJ 08543. November 2017.

9. Power LA, Coyne JW. ASHP guidelines on handling hazardous drugs. Am J Health Syst Pharm 2018; 75:1996- 2031 .

10. <797> Pharmaceutical Compounding - Sterile Preparations. In: United States Pharmacopeia and National

Formulary (USP 35-NF 30).

11. American Society of Health System Pharmacists. ASHP guidelines on compounding sterile preparations. Am J

Health Syst Pharm 2014;71:145-66 .

12. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on compounding nonsterile

products in pharmacies. Am J Hosp Pharm 1994;51:1441-8 .

13. Food and Drug Administration. FDA warns against using Treanda injection (solution) with closed system

transfer devices, adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene; provides

list of compatible devices. September 4, 2015.https://www.fda.gov/Drugs/DrugSafety/ucm437469.htm

(Accessed October 16, 2018). 14. Product information for Bendeka. Teva Pharmaceuticals USA, Inc. North Wales, PA 19454. April 2018.