PROMOTING BEST PRACTICES FOR THE SAFE HANDLING OF HAZARDOUS DRUGS A CONTINUING EDUCATION WEBINAR

PROMOTING BEST PRACTICES FOR THE SAFE HANDLING OF HAZARDOUS DRUGS A CONTINUING EDUCATION WEBINAR

PROMOTING BEST PRACTICES FOR THE SAFE HANDLING OF HAZARDOUS DRUGS Firouzan Fred Massoomi, PharmD, FASHP Nebraska Methodist Hospital Department of Pharmacy Services Omaha, Nebraska 68114 Fred.Massoomi@nmhs.org

Objectives Outline the latest policies and recommendations about the safe handling of HDs Identify state legislation in regards to HD handling Explore the landscape changes for practice sites and the need to meet identical standards throughout

Who Is at Risk of Occupational Exposure? 8 million US healthcare workers o Pharmacy, nursing personnel, physicians o Operating room personnel o Veterinary personnel o Shipping and receiving personnel o Laundry workers, waste handlers, maintenance workers NIOSH. http://www.cdc.gov/niosh/docs/wp-solutions/2009-106/pdfs/2009-106.pdf. Accessed April 14, 2015.

Risks of Hazardous Drugs Exposure 7,094 nurse and pharmacy personnel pregnancies Compared to peers not at risk Observed risks to handling hazardous drugs Increased risk for miscarriages by 40%-50% Increased risk for low birth weight by 17-fold Increased risk for congenital malformations by 5-fold Valanis B, et al. J Occup Environ Med. 1999;41(8):632-638.

Quantifying Exposure Worker Day Number of Urine samples Positive CP samples Positive IF samples Pharmacist 1 1 6 3 0 Pharmacist 2 1 10 3 9 Technician 1 1 8 8 1 Technician 2 1 6 000 0 Technician 3 1 9 0 0 Nurse 1 1 5 1 0 Nurse 2 1 4 3 0 Control 4 0 0 N(pos)=7 48 18 (N=5) 10 (N=2) CP =cyclophosphamide; IF=ifosphamide Wick, C, et al. Am J Health Syst Pharm. 2003;60(22):2314-2320.

Legacy of Current Practices Source: ASHP Study Guide: Safe Handling of Cytotoxic and Hazardous Drugs. 1990.

Defect: Compounding Inconsistencies Source: Nebraska Methodist Hospital Department of Pharmacy Services

A Decade Towards Safety 2004 2014 CDC & NIOSH. http://www.cdc.gov/niosh/docs/2004-165/. Accessed April 1, 2015. US Pharmacopeial Convention. http://www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handlinghealthcare-settings. Accessed April 1, 2015

Guidelines for Hazardous Drugs Source Year American Society Heath-System Pharmacists 1982, 1984, 1990, 2006 Occupational Safety Health Administration 1986, 1995, 1999 American Medical Association 1985 Oncology Nursing Society 1988, 2003, 2010 NIOSH* Alert 2004, 2010, 2012, 2014 Hospital Oncology Pharmacists Association 2009 United States Pharmacopeia <797> 2004, 2008 United States Pharmacopeia <800> 2014 (for comment) *NIOSH = National Institute for Occupational Safety and Health 33 years of safe handling guidelines

Defect Compliance NIOSH survey of nursing practices findings Failure to wear nonabsorbent gown (42%) Intravenous (IV) tubing primed with antineoplastic drug by respondent (6%) or by pharmacy (12%) Potentially contaminated clothing taken home (12%) Spill or leak of antineoplastic drug during administration (12%) Failure to wear chemotherapy gloves (12%) Lack of hazard awareness training (4%) Boiano JM, et al. J Occup Environ Hyg. 2014;11:728-740.

State Health Departments State regulations for compounding Board of pharmacy or health departments Most states have USP 797 specific regulations Specific hazardous drug compounding regulations Washington 2011(Bill 5594) California 2013 (Bill 1202) North Carolina 2014 (H644) Maryland 2014 (Bill 1108) Michigan March 2015 (Bill 237) -Washington State: http://search.leg.wa.gov/combineddocument.aspx. -California: http://www.leginfo.ca.gov/pub/13-14/bill/asm/ab_1201-1250/ab_1202_cfa_20130422_121250_asm_comm.html. -North Carolina http://www.ncleg.net/sessions/2013/bills/house/html/h644v0.html. -Maryland: http://dhmh.maryland.gov/regs/documents/sb1108%20-%20safety%20standards%20wg_ REVISED_Final%20Signed_12-16-14_OGA%201547.pdf. -Michigan http://legislature.mi.gov/documents/2015-2016/billintroduced/senate/pdf/2015-sib-0237.pdf. -All accessed: Accessed 04/20/15

The Joint Commission Is Concerned To reduce the incidence of hazardous drug contamination by and exposure to workers, a health care organization should have a comprehensive safety program. The Joint Commission. March 2014: volume 7; issue 3.

USP 800 Proposed USP 800: Timeline First Release March 2014 Comment Due Date July 31, 2014 Second Release December 2014 Comment Due Date May 31, 2015 Goal Publish Date February 2016 Official Compliance Date August 2016 Source: USP Open Mic Session; Open-Microphone Web Meeting for General Chapter Hazardous Drugs Handling in Healthcare Settings: February 20, 2015

USP 800 The objective of this chapter is to protect personnel and the environment when handling hazardous drugs (HDs). Sterile and non-sterile products US Pharmacopeial Convention. www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handlinghealthcare-settings. Accessed April 1, 2015.

USP 800 The Hazardous Drug Team Primary Pharmacist Pharmacy technicians/interns Pharmacy purchasing Nursing Surgical services Risk management Employee health Environmental services Secondary Administration Safety officer Physician office managers Home health managers Primary Goal: Establish a hazardous drug safety program Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Visual Hazard Mapping Tool Hazardous Drug Process Pre-Hospital Hospital Post-Hospital RX Company $ $ Waste Hauler Waste Management Delivery Wholesaler Packaging Delivery Dock/Pharmacy Receiving Pharmacy Compounding Patient Unit Delivery Nurse Administration Patient Housekeeping Linen Haulers Linen Management Massoomi 2012 Hazardous Drugs products should always be considered contaminated on the packaging and vials until properly decontaminated. Connor T, et al. AJHP 2005;62:475-582 Hazardous Drug NOTE: Red Indicates Contamination points Without a total hazardous drug safety program in place the drug products, the patient, the linen from patients, the pharmaceutical wastes provides multisourced contaminated risk to healthcare providers. NIOSH Safety Alert 2004 Source: Nebraska Methodist Hospital Department of Pharmacy Services.

The Contaminated Environment 1. More than 70 published studies 2. Surfaces that come in contact with hazards A. Primary engineering control spaces B. Storage locations C. Patient linen 3. Some with in-direct contact with hazards A. Floors B. Patient bed rails C. IV ump buttons

USP 800 Environmental Quality Control Routinely = every 6 months Approximate cost is $250 to $400 per sample Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 NIOSH Hazardous Drug List September 5, 2014 NEW Group 1: Antineoplastic drugs 97 drugs listed Group 2: Non-antineoplastic drugs 48 drugs listed Group 3: Reproductive risk Men and women 39 drugs listed 12 drugs removed from the 2004/12 lists Guide to handling based on formulation CDC. http://www.cdc.gov/niosh/docs/2014-138/. Accessed April 1, 2015.

USP 800 Formulary Assessment Application of NEW NIOSH of Hazards Antineoplastic Non-Antineoplastic Reproductive Class 1 Class 2 Class 3 Continuously stratify with new formulary drugs Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 #1 Safety Concern The Source The Vial and Packaging EVIDENCE: 11 Published studies Drug vial exteriors Not due to damage during shipping & handling Source: Nebraska Methodist Hospital Department of Pharmacy Services.

Wholesaler Process Limitations Source: Nebraska Methodist Hospital Department of Pharmacy Services. Limitations on hazardous drugs Cytotoxic only No NIOSH stratification Site trick Set up departments Order based off the department Antineoplastic HD Non-antineoplastic HD Reproductive HD

USP 800 Segregated Handling of Vials Good Distribution Practices Totes from wholesaler Gloves to handle Shall not Store Unpack Compound Manipulate Drugs left in baggies Not a + pressure area Equi-pressure Negative pressure Handle in compounding space Source: US Pharmacopeial Convention. www.usp.org/usp-nf/notices/generalchapter-hazardous-drugs-handling-healthcare-settings. Accessed April 1, 2015. Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Personal Protective Equipment (PPE) Training Documentation Goal Minimize Contamination From product to employee and visa versa Proper demonstrative use of PPE Methodist notes per guidelines Hand washing technique No make-up No jewelry No artificial finger nails No ipods or personal devices No exemptions from garbing requirements Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Donning and Doffing PPE Donning Sequence Doffing Sequence Source: Fred Massoomi visit. Taipei Veterans Hospital; Taipei, Taiwan: 2012.

USP 800 Choosing the Right Glove IMPORTANT: ASTM D6978 and not ASTM F739 due to permeability limits 35.2 +2 C 25 C temperature delta US Pharmacopeial Convention. www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handlinghealthcare-settings. Accessed April 1, 2015.

TJC is Concerned About the Glove Joint Commission Resources: (Environment of Care News). Oakbrook Terrace, IL: Joint Commission on Accreditation of Healthcare Organizations (2014) Vol. 7, Issue 3. Reprinted with

USP 800 Primary Engineering Controls Biological Safety Cabinet Class II Type B2 BSC Isolator Glove Box Compounding Aseptic Containment Isolator (CACI) Source: Nebraska Methodist Hospital Department of Pharmacy Services. Total Exhaust

USP 800 Secondary Engineering Controls Low Volume Compounding Exemption ELIMINATED from USP 797 Attributes of the room: Separate Room 12 Air Changes Per Hour (ACPH) HEPA filtered air to ISO 7 Standard Negative Pressure to -0.01 to -0.03 inches of water column Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 C-SCA Containment Segregated Compounding Area Non-HEPA room 12 ACPH Negative pressure NO USP 797 dating Not for high risk Max 12 hours dating Line of demarcation Primary Engineering Control: Cabinet Dual HEPA HEPA= High-efficiency particulate arrestance. US Pharmacopeial Convention. http://www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handling-healthcare-settings. Accessed April 1, 2015

USP 800 Supplemental Environmental Controls Closed system transfer devices (CSTDs) Compounding : Recommended Administration : Required Currently 7 US products PhaSeal : BD VialShield /Texium : Carefusion: BD On-Guard : B.Braun ChemoLock : ICU Medical ChemoClave /Spiros : ICU Medical Equashield All devices FDA cleared Four have FDA ONB device code

Uptake in CSTD Use in US

CSTD Drug Incompatibilities N,N-Dimethylacetamide Amsacrine VUMON (teniposide) BUSULFEX (busulfan) TREANDA (Bendamustine) Listed CSTD On-Guard TM ChemoClave PhaSeal TM CAUTION, no testing with others! ISMP Medical Safety Alert. February 26, 2015. FDA ALERT. March 10, 2015.

Users Comments on CSTDs FDA. accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm. Accessed January 5, 2015.

Repetitive Strain Injury 19% 81% Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Bacille Calmette-Guerin (BCG vaccine) Indication: Bladder CA WARNINGS Live biological hazard BCG infections in healthcare workers have occurred Case studies of deaths due to cross contamination of Total Parenteral Nutritional products Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Compounding Competency ChemoChek Fluorescence test Nursing certification program www.covidien.com ChemoTEQ Red dye and broth test Videos and training materials online www.valiteq.com Source: Nebraska Methodist Hospital Department of Pharmacy Services.

Assuring Safety Compliance Compounding efficiency Protocol driven Remote verification ISMP highly recommends Volumetric, gravimetric, barcode scanning

USP 800 Pre-primed bags Line naïve fluid Proper labeling Clear instructions Warning labels Line labels Final Product Preparation Not USP 800, but good practice Safety overbag Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Delivery of Hazardous Drugs Yes to Hand Delivery NO to Pneumatic Delivery Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Hazardous Drug Spill Kits/Policy Develop a collaborative policy Define volume limits Who is responsible DATE KITS!!!!!!!!! We do 5 years on the date receipt Develop or purchase spill kits Location of kits USP 800: Warehouse Training on kits Dating on kits Drill spills Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Proper Workspace Preparation Deactivation 1 2% sodium hypochlorite solution Sodium thiosulfate 2 Decontamination Physical wiping of surface 3 Cleaning Tri- or quadrivalent detergent Peroxide 4 Disinfection Sterile isopropyl alcohol 70% UV light Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Medical Surveillance Program First Step Work with Human Resources, Employee Health, and Legal Tier One: Education and Self Surveillance Tier Two: Employer/Supervisor Surveillance Annual reproductive questionnaire Trending of sick calls Tier Three: Comprehensive Medical Surveillance At hire and annually CBC, urinalysis, LFT Urine drug testing by www.exposurecontrol.nl Tier-Four Post-exposure Surveillance Notation in medical record with date and drug CBC=complete blood count, LFT=liver function. test Massoomi F, et al. Implementing a personnel surveillance program for hazardous drug safety. Pharmacy, Purchasing & Products. April 2008: 2-5.

Risk Stratification of Employees to HDs No Contact by position with HD Or Patients on HD Direct Contact with HD or Wastes Direct Contact with Patient on HD Therapy Indirect HD contact or Hdrug patient contact No Contact allowed: Pregnancy, Breast Feeding, Attempt at Pregnancy Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Gap Pregnancy and Breastfeeding CFR Federal Register. Vol. 80. No. 15. Friday, January 23, 2015. Notices page 3601-3602.

USP 800 Non-Sterile Hazardous Drugs Segregate from non-hazardous NOT required: non-antineoplastic Simple transfers/counting Unit dose formulations Final product Negative pressure room manipulations NO automated packaging devices YES to automated dispensing cabinets Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Hazardous Waste Management Collaborative formulary assessment State and federal regulations Continuous assessment of risk and stream DRUG - GENERIC (BRAND) CLASS OF MEDICATION ROUTES/ FORMS COMPANY PREGNANCY CATEGORY SDS BSC HAZ CLASS (1-4) WASTE STREAM RCRA Y/N Aldesleukin (Proleukin ) ONC INJ Chiron C YES YES Class 1 YELLOW N Alitretinoin (Panretin ) Retinoid TOPICAL, GEL Ligand D YES Yes, if altered Class 1 YELLOW N Cyclophosphamide ONC SDS=Safety Data Sheet; BSC = Biological Safety Cabinet; RCRA=Resource Conservation Recovery Act listed drug INJ, ORAL Multiple D YES YES Class 1 RCRA BLACK Y Source: Nebraska Methodist Hospital Department of Pharmacy Services.

Legacy Home grown Hazardous Drug Training Commercially available programs ASHP videos/print material CriticalPoint web-based training lessons Covidien's ChemoPlus Training Lab Safety Corporation/Valiteq Pharmacy OneSource Baxter's Blue Book (training manual for IV admixture personnel) Germfree ideo Training Program Kendall's Chemocheck

USP 800 Gap Hazardous Drug Consideration Known CSTD Gaps NO secure bag spike system Dose size limitations: 1 ml Ampule management Specialized routes of administration Intrathecal Irrigations Ophthalmic Topical Source: Nebraska Methodist Hospital Department of Pharmacy Services.

USP 800 Gap Hazardous Drug Consideration Special Delivery Devices Elastomeric pumps On-Q pumps Syringe pumps Implantable pumps New electronic patches

USP 800 Gap Hazardous Drug Considerations Surgical Bladder installation HOT chemo baths Ophthalmic surgery = TOPICAL Esophogeal Strictures = TOPICAL Hyperthermic Intraperitoneal Chemotherapy Ophthalmology Obstetrics Ectopic pregnancy Rheumatology Rheumatoid arthritis Lupus nephritis Neurology Multiple sclerosis Source: Nebraska Methodist Hospital Department of Pharmacy Services.

What Happens After Treatment? 35 and 16 urine samples were collected from the three patients and their family members; ALL samples were positive for cyclophosphamide and 5-FU Cyclophosphamide was detected at levels of 0.03-7.34 ng/cm 2 in 8 of the 12 wipe samples obtained from the homes Study demonstrated contamination of the home setting and exposure of family members Yuki M, et al. J Oncol Pharm Practice. 2012;19:208-217.

Hazardous Drug Rounds Preparation Administration Disposal Source: Nebraska Methodist Hospital Department of Pharmacy Services.

Additional Resources 1. USP <800> Hazardous drugs Handling in healthcare settings. Briefing. www.usp.org/uspnf/notices/compounding-notice. Accessed 04/09/2015. 2. NIOSH [2014]. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2014. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014-138 (Supersedes 2012-150). 3. Davis J, McLauchlan R, Connor T. Exposure to hazardous drugs in healthcare: an issue that will not go away. J Oncol Pharm Pract. 2011;17(1):9-13. 4. Centers for Disease Control and Prevention. Workplace Safety and Health. NIOSH ALERT. Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings. DHHS (NIOSH) Publication Number 2004-165. September 2004;1-50. 5. Connor TH and McDiarmid MA. Preventing occupational exposures to antineoplastic drugs in health care settings. CA Cancer J Clin. 2006;56:354-365. 6. United States Department of Labor. Occupational Safety & Health Administration. Healthcare wide hazards: Needlestick/sharps injuries. Available at http://www.osha.gov/sltc/etools/hospital/hazards/sharps/sharps.html. 7. Pines E, Smith C. The U.S. EPA, Office of Solid Waste and Emergency Response, Innovation Initiative. Managing pharmaceutical waste: A 10-step blueprint for healthcare facilities. 2008. http://www.epa.gov/osw/hazard/generation/pharmaceuticals.htm. Accessed 04/09/2015.

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