1. USP 800 Implementation Tips
Joanna Robinson, PharmD, MS
Inpatient Operations Manager

2. Objectives Describe how to develop a Hazardous Drug (HD) list
Develop a USP 800 Compliance Plan
11/22/2019

3. USP 800 Overview
USP 800 is an enforceable standard aimed at minimizing the risk of hazardous drug exposure to healthcare personnel, patients and the environment
Employees must know which drugs are hazardous
Employees must understand the risks of hazardous drugs
Employees must know how they should keep themselves safe when handling hazardous drugs
Compliance deadline is December 1, 2019!
It’s not just chemotherapy
Must use the NIOSH Hazardous Drug List and have a plan for all drugs on this list
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4. Before we jump in…
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5. Two Paths to Compliance
Complete Risk Assessments & Decide how WE want to handle Hazardous Drugs
All NIOSH List Agents Must Follow USP <800> Requirements

6. Understanding what makes a drug “Hazardous”
NIOSH Hazardous Drug Criteria
NIOSH Hazardous Drug List
Hazardous Drug Criteria
Definition
Carcinogenicity
May cause cancer
Teratogenicity or other developmental toxicity
Can alter the development of an embryo or fetus
Reproductive toxicity
May interfere with normal reproduction or fertility
Organ toxicity at low doses
May cause damage to organs or organ function
Genotoxicity
May cause mutations to genes
Table 1
Antineoplastic Drugs
Table 2
Drugs that meet one or more NIOSH Criteria for a HD
Table 3
Reproductive Risk Only Medications

7. Understanding the Hazard
It’s important to know why the drug is hazardous
Case reports describe congenital anomalies in infants exposed to in utero maternal fluconazole during most or all of the first trimester
But we also must consider the dosage form and how we’re going to manipulate it at our institution. USP 800 allows us the flexibility to do this.
Priming tubing on IV fluconazole may lead to more employee exposure than opening a unit dose container to administer to a patient
Crushing a tablet of fluconazole may lead to more employee exposure than not crushing it
Preparing an IV fluconazole in a clean room may lead to more employee exposure than buying pre-made bags

8. Risk Assessments for Non-Antineoplastic Parenteral Dosage Forms
Parenteral Dosage Form Risk > Oral Dosage Form Risk
Determine Alternative Safe Handling
Treat like Chemotherapy = Full USP 800 Precautions
IVPB Drug
Hazardous Criteria
Fosphenytoin
Metabolized to phenytoin. Phenytoin is an IRAC Group 2B carcinogen = possibly carcinogenic
Fluconazole
Case repots of congenital abnormalities in infants exposed in utero, same effects as seen in rats, preg category C
Mycophenolate mofetil
Black box warning for embryo fetal toxicity
Oxytocin
Hazardous only for women in the third trimester,
preg category C
Pamidronate
Embryo-fetal toxicity
Phenytoin
IRAC Group 2B carcinogen = possibly carcinogenic
Tacrolimus
At therapeutic doses in patients receiving tacrolimus there is increased risk of lymphomas and other malignancies. Toxicity of IV > oral in rats / baboons. Preg category C
Valproic Acid
Black box warning for teratogenicity, congenital malformations, preg category D
Zidovudine
Zoledronic Acid
Increase in stillbirths and decrease in neonate survival in lab studies
Drug
Hazardous Criteria
Chloramphenicol
IARC Group 2A carcinogen = probably carcinogenic
Cidofovir
Manufacturer Safe Handling Guidance
Cyclosporine
IRAC Group 1 carcinogen = carcinogenic
Dexrazoxane
Ganciclovir
Inhaled Ribavirin
Pregnancy Category X
IRAC 2B or greater
Manufacturer does not require
Pregnancy Category C,D
Hazardous data is at therapeutic doses (Black box warnings) or in animals
IRAC Group 1 or 2A
Pregnancy Category X
Manufacturer Requires (MSHG)

9. IARC and Pregnancy Risk Classifications
IARC Classification
Group 1
Carcinogenic to humans
Group 2A
Probably carcinogenic to humans
Group 2B
Possibly carcinogenic to humans
Group 3
Not classifiable as to its carcinogenicity to humans
Group 4
Probably not carcinogenic to humans
An agent is classified based on scientific evidence derived from human and experimental animal studies and from mechanistic and other relevant data
FDA Pregnancy Risk Classification A
No fetal risk B
No risk to human fetus despite possible animal risk / studies C
Risk cannot be ruled out, human studies are lacking D
Positive evidence for risk to human fetus, but benefits may outweigh risk of drug X
Contraindicated in pregnancy, studies demonstrate evidence of risk to fetus
FDA has decided to eliminate the pregnancy categories because they are often viewed as confusing and overly simplistic and don’t effectively communicate the risk a drug may have during pregnancy and lactation and in females and males of reproductive potential.

10. What is KU planning on doing?
11/22/2019

11. KU HD Risk Levels Communication about the hazardous risk level will be
In a MAR message
On the label (if there is a label)
Communication will be something like
“Level 1 Hazardous Drug”
Staff will need to know what they must do to protect themselves when handling a “Level 1 Hazardous Drug”
Education will be provided; Policies will be available
EMR will not tell them

12. KU HD Risk Levels: PPE and Safe Handling
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13. The HD List
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14. Assessment of Risk Must consider (at a minimum):
Type of HD (antineoplastic, non-antineoplastic, reproductive risk)
Dosage form
Risk of exposure
Packaging
Manipulation
Must document what alternative containment strategies and/or work practices are being employed for specific dosage forms to minimize occupational exposure
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15. KU Assessment of Risk Export of all drug records from EMR
Ensured all dosage forms were captured
Foundation for AoR
Excel spreadsheet with columns for each consideration
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16. USP 800 Compliance Plan

17. Compliance Plan 101 Know your compliance gaps
Several gap analysis tools available:
ASHP (
Critical Point LLC (
IJPC (
TJC (
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18. Compliance Plan Prioritize (and delegate) your tasks
Evaluate Effort vs. Impact
Buckets of work
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19. Policies and Procedures
Buckets of Work
Supply Chain
Disposal and Cleaning
Chemotherapy decontamination agent for floors
Spill kits
Other nursing supplies (e.g. cream applicator / prep mat)
Black vs. Yellow vs. Red Buckets
Cleaning non Pharmacy Areas
Human Resources
Policies and Procedures
PAPR clearance
Employee attestation
Write all USP 800 required P&P
Tag in Policy Stat with “USP 800” for easy retrievability
Education
Spill Management
TLC creation – 3 levels of training depending on intended interaction / exposure to hazardous drugs
Spill kit
PAPR
Spill Response Team

20. HD Risk Level Implications
Risk Assessments determined that we will treat chloramphenicol, cidofovir, cyclosporine, dexrazoxane, ganciclovir, and inhaled ribavirin like chemotherapy
RNs cannot crush or open tablets / capsules of oral anti-neoplastic agents on the floor (must be manipulated per USP 800 requirements – in BSC)
Policies and Procedures will be written with HD Level 1 and Level 2 in mind
E.g. PPE for HD Level 1 will be as required by USP 800 whereas PPE for HD Level 2s will be decided internally based on risk assessment

21. HD Risk Level Implications
Antineoplastic drugs can not go through automatic packaging devices
Must be packaged in BSC
Once in final dosage form (unit dose), may be stored with other non-hazardous inventory
Pharmacy cannot draw up oral liquid anti-neoplastic agents outside of USP 800 requirements
Doses will be drawn up in BSC
Spill response team Haz Mat team + volunteers
Deployed for spills greater than 1L
Hazardous Drug Precautions PPE Cart
All PPE and cleaning products for inpatient on Level 1 HD

22. Remember… Employees must know which drugs are hazardous HD List
Labeling (MAR, products, storage areas)
Employees must understand the risks
TLC Education on Hazardous Drugs
Employees must know how to keep themselves safe when handling HDs
P&P
PPE, CSTDs, Negative Pressure storage / compounding, BSCs, Decontamination, Spill management… and more!

23. Learning opportunities are endless!
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24. USP 800 Implementation Tips
Joanna Robinson, PharmD, MS
Inpatient Operations Manager