USP 800 Implementation Tips Joanna Robinson, PharmD, MS Inpatient Operations Manager jrobinson14@kumc.edu

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

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 11/22/2019

Before we jump in… 11/22/2019

Two Paths to Compliance Complete Risk Assessments & Decide how WE want to handle Hazardous Drugs All NIOSH List Agents Must Follow USP <800> Requirements

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

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

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)

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.

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

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

KU HD Risk Levels: PPE and Safe Handling 11/22/2019

The HD List 11/22/2019

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 11/22/2019

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 11/22/2019

USP 800 Compliance Plan

Compliance Plan 101 Know your compliance gaps Several gap analysis tools available: ASHP (www.ashp.org) Critical Point LLC (http://www.800gaptool.com/) IJPC (https://compoundingtoday.com/Compliance/USPGap.cfm) TJC (www.hazmedsafety.com) 11/22/2019

Compliance Plan Prioritize (and delegate) your tasks Evaluate Effort vs. Impact Buckets of work 11/22/2019

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

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

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

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!

Learning opportunities are endless! 11/22/2019

USP 800 Implementation Tips Joanna Robinson, PharmD, MS Inpatient Operations Manager jrobinson14@kumc.edu