CHEMOTHERAPY/HAZARDOUS DRUGS PRECAUTIONS, PREPARATION, ORDERING

CHEMOTHERAPY/HAZARDOUS DRUGS PRECAUTIONS, PREPARATION, ORDERING Naser Z. Alsharif, PharmD, PhD Professor, School of Pharmacy and Health Profeesions Creighton University, Omaha, NE Selected Slides Courtesy Karen K. O Brien, B.S. Pharm, Pharm.D. Associate Professor, Pharmacy Sciences School of Pharmacy & Health Professions Creighton University The 20th Congress of the Scientific Association of Colleges of Pharmacy in the Arab World November 8th, 2017 1

OUTLINE Define hazardous drugs and identify healthcare areas and personnel where hazardous drugs are encountered Discuss the different types of exposure Identify activities that may result in exposure Discuss guidelines for handling hazardous drugs Discuss best practices in ordering chemotherapy Identify ethical considerations in chemotherapy Discuss implications for Jordan 2

WHAT ARE HAZARDOUS DRUGS? Drugs that pose a potential health risk to workers who may be exposed to them This can include chemotherapeutic, cytotoxic, antiviral, immunosuppressant, hormonal and bioengineered drugs. Not all hazardous drugs are cancer chemotherapeutic agents! 3

WHAT ARE HAZARDOUS DRUGS? The National Institute for Occupational Safety and Health (NIOSH) defined hazardous drugs as those that exhibit one or more of the following characteristics: Carcinogenicity: cancers usually develop after many years; often occurs as a type of leukemia Teratogenicity: damages developing fetus Reproductive toxicity May be related to increased miscarriages & birth defects A concern for women and men of child bearing age Organ toxicity Genotoxicity New drugs with structure and toxicity profiles that mimic existing hazardous drugs 4

WHERE DOES ALL OF THIS APPLY TO? Protection against hazardous drugs apply to facilities where they are used and to personnel who may become in touch with them: Facility Examples Hospitals Pharmacies Physician s offices Patient treatment clinics Wholesalers Other health care facilities and institutions 11/28/2017 5

WHO DOES ALL OF THIS APPLY TO? Workers may be exposed to a drug at any point throughout its life cycle: receipt, transport, storing, preparation, administration, or disposal Personnel Examples: Shipping & receiving personnel Pharmacists, Interns, Technicians Physicians Nurses Custodial staff, Environmental services personnel Delivery Personnel Any one involved in preparing, handling, or, stocking hazardous substances 11/28/2017 6

TYPES OF EXPOSURES Inhalation (frequency unresolved) Skin contact/absorption (may be a primary route) Ingestion : unintentional exposure from hand to mouth contact/ingestion of contaminated foodstuffs Injection: unintentional exposure through a needle stick or sharps injury (less common) The likelihood that a worker will experience adverse effects from hazardous drugs increases with the amount and frequency of exposure and the lack of proper work practices. 7 Source: NIOSH Alert 2004 ASHP Guidelines on Handling Hazardous Drugs

ACTIVITIES THAT MAY RESULT IN EXPOSURES Reconstituting powdered drugs; further dilution of reconstituted drugs/concentrated liquids Expelling air from syringes filled with hazardous drugs Administration of hazardous drugs by IM, SQ or IV routes Contacting measurable concentrations of drugs present on drug vial exteriors, work surfaces, floors & final drug products (Bottles, bags, syringes, cassettes) Generating aerosols during administration of drugs (IV push/iv infusion) Priming the IV set with a drug-containing solution at the patient bedside (should be done in Pharmacy) 8 Source: NIOSH Alert 2004

ACTIVITIES THAT MAY RESULT IN EXPOSURES Handling contaminated wastes generated at any step of the preparation or administration process Handling unused hazardous drugs or hazardous-drugcontaminated waste Decontaminating and cleaning drug preparation areas Transporting hazardous waste containers Removing and disposing of personal protective equipment (PPE) after handling hazardous drugs or waste 9 Source: NIOSH Alert 2004

HANDLING CHEMO DRUGS COMPONENTS 10

BEFORE PREPARING AN ORDER What are key things to put in place before preparing a chemo order? 11

I. GUIDELINES FOR HANDLING HAZARDOUS DRUGS American Society of Health-System Pharmacists (ASHP) National Institute for Occupational Safety and Health (NIOSH) National Occupational Research Agenda (NORA) Occupational Safety and Health Administration (OSHA) Environmental Protection Agency (EPA) Stated goals vary somewhat from source to source, but the general purpose is to protect health care workers by providing recommendations for the safe handling of hazardous drugs. What is the equivalent in Jordan? 12

II. SAFETY PROGRAM Whose Responsibility? Every institution that works with hazardous drugs should have a comprehensive safety program in place. This covers ventilation controls, training and monitoring staff for safe handling of hazardous drugs, and personal protective equipment (PPE). The goal is: These programs should help to keep the workplace safe. Chemo room set up 13

III. PRE-PRINTED ORDERS (PPO) 14

HANDLING CHEMO DRUGS COMPONENTS 15

IN THE PROCESS OF PREPARING AN ORDER What are key things to put in place in the process of preparing a chemo order? 16

I. STORAGE AND LABELING Wear PPE when unpacking hazardous drugs in case damaged containers are found. Hazardous drugs should be stored separately from other drugs. All hazardous drugs must be labeled to identify them for special handling. 17

II. PERSONAL PROTECTIVE EQUIPMENT Gloves Only gloves that have been tested against the American Society for Testing and Materials (ASTM) standard for resistance to chemotherapy should be worn. Includes latex, nitrile, neoprene, and polyurethane gloves Gloves need to be worn at all times when handling hazardous drugs. Double gloving is required; change gloves a minimum of once every 30 minutes when compounding hazardous drugs. 18

II. PERSONAL PROTECTIVE Gloves EQUIPMENT Place inner glove under the knitted cuff of chemo gown; place outer glove over the cuff. There should be no exposed skin. The outer pair of gloves should be removed after compounding is complete and the final preparation has been wiped off. The inner gloves should be worn while the labels are affixed and the preparation is placed into a sealable containment bag for transport. When gloves are removed, only touch the outer uncontaminated surface of the gloves. Gloves should be placed in a sealable plastic bag for disposal. 19

II. PERSONAL PROTECTIVE EQUIPMENT Gowns Use disposable gowns made of materials tested to be protective against hazardous drugs. Coated gowns should not be worn longer than 3 hours during compounding. Remove gowns carefully and contain and dispose of gowns as hazardous waste. Always wash hands after removing gowns. 20

II. PERSONAL PROTECTIVE EQUIPMENT Eye and Face Protection Should be used whenever splashing or aerosolization of hazardous drugs is possible A face shield provides better skin protection than safety goggles/ glasses. A surgical mask only protects the preparation ; a respirator fit to the individual is needed to protect both the worker and the preparation. This worker is wearing a face shield, but not a respirator 21

II. PERSONAL PROTECTIVE EQUIPMENT Shoe and Hair Coverings These should be worn Gloves should be used to remove shoe and hair coverings and the contaminated coverings should be discarded as hazardous waste. 22

III. VENTILATION CONTROLS Hazardous drugs should be stored in a negative pressure environment Cleanroom should be separate from other preparation areas & possess negative pressure Access to areas where hazardous drugs are stored & prepared should be limited to protect persons not involved in drug preparation All transfers of hazardous drugs should be carried out in an ISO Class 5 BSC or (Compounding Aseptic Containment Isolator (CACI) Optimally 100% vented to outside air via HEPA filtration 23 Source: USP Chapter <797> Revision Bulletin, 2008 http://www.dynamicdesignpharma.com/chemosafe_classic.html

III. BIOLOGICAL SAFETY CABINETS (BSCS) Class II BSC use vertical flow HEPA filtered air Inward airflow for personal protection HEPA-filtered laminar airflow for product protection HEPA-filtered exhaust air for environmental protection OSHA, ASHP, and NIOSH recommend Class II BSCs for compounding sterile preparations of hazardous drugs Four types of Class II BSCs Type A1, Type A2, Type B1, and Type B2 24

III. CLASS II BIOLOGICAL SAFETY CABINET Work surface of BSC Note Glass Shield Note intake grills in front and back of cabinet BSC certification is required once every 6 months, or with each physical move whichever is shorter 25

III. BSCS CLASS II Type B2 26 Image from: http://www.bakerco.com/resources/intro.php

HORIZONTAL AIR FLOW HOOD: DIFFERENCE Note placement of the HEPA filter Note filtered intake vents in front Venting directly at the operator Horizontal laminar airflow workbenches (LAFWs) must not be used to compound hazardous Compounded Sterile Products Note: Protective metal grid in front of HEPA filter Note white filter material beneath metal grid Supported by corrugated metal strips between the HEPA filter material 11/28/2017 27

III. WORK PRACTICES IN BSCS CLASS II Appropriate PPE should be worn A plastic-backed absorbent preparation pad can be used Avoid leaving and reentering the work area of the Class II BSC, NO DISTRACTION Wipe down all vials with moist gauze after placing them in the BSC It should not block airflow and should be replaced and discarded after each batch. Discard the gauze as hazardous waste. A small waste/sharps container may be placed towards the back corner of the BSC Wipe the final preparations with a moist gauze Remove your outer gloves before labeling the final preparation 28

IV. ASEPTIC TECHNIQUE USP 797, Control for contamination from: Personnel Materials Environment 29

IV. ASEPTIC TECHNIQUE Fingernail Pickings Coughing Uncovered hair head shake 30 Blood agar cultures courtesy of Dr. O Brien.

IV. ASEPTIC TECHNIQUE Medication Vial Blood agar cultures courtesy of Dr. O Brien. 11/28/2017 31

IV. ASEPTIC TECHNIQUE BASIC CLEANROOM RULES Keep hands and face clean Keep fingernails trimmed and clean Never comb your hair in the room Never wear makeup or jewelry Never carry personal items into the room No eating or chewing gum in the room Wear specified clothing/gloves AS SPECIFIED Don t walk around unnecessarily Wipe down items with isopropyl alcohol before placing in the ISO Class 5 environment Use good aseptic technique 11/28/2017 32

IV. ASEPTIC TECHNIQUE Closed-system vial-transfer devices (CSTDs) are preferred Vial-transfer systems that allow no venting or exposure of hazardous substance to the environment 33

IV. ASEPTIC TECHNIQUE When drawing out the contents of the vial small, amounts of air should be exchanged for small amounts of drug solution to avoid creating a high positive pressure in the vial. Maintain a small negative pressure to avoid accidental dribbling or aerosolization of hazardous drug from the vial The exact volume of drug required should be measured out before the syringe is removed from the vial After the drug is measured, turn the vial upright and pull back a small amount of air before removing the needle 34

IV. ASEPTIC TECHNIQUE Do not re-cap needles Dispose of needles and syringes in a specially marked Chemo Sharps Container The CSP must bear proper labels for use and a warning CHEMO label 35

V. PREPARATION FOR DELIVERY TO THE NURSING UNIT OR PATIENT All chemo preps should be by pharmacist and doubled checked by a pharmacist before it goes up to the floor To supply chemo in LVPs or IVPBs: Send to nursing unit with an administration set attached Tubing of the administration set should be primed with nonchemo containing fluid Add chemo agent only after priming the administration tubing with container fluid 36

V. DELIVERY TO THE NURSING UNIT OR PATIENT Chemo product delivered to floor or home should be contained in multi-layered, leak proof packaging Never send through pneumatic tube system; hazardous medications must be hand delivered Should have a spill kit available at the pharmacy, nursing unit, home, and with delivery courier to cover any emergency spills All individuals trained in clean-up and appropriate disposal All individuals trained and aware of risk of exposure to these 37 agents

VI. DECONTAMINATION AND WASTE DISPOSAL Personal Decontamination Immediately removing the gloves or gown Immediately cleanse the affected skin with soap and water Flooding an effected eye at eye wash fountain or with water or isotonic eyewash for at least 15 minutes Obtaining medical attention Documenting the exposure in the employee s medical 38

VI. DECONTAMINATION AND WASTE DISPOSAL Alcohol does not deactivate hazardous drugs Hazardous drug waste should be placed in thick sealable plastic bags before being placed in an approved hazardous-waste container. Strong oxidizing agents such as sodium hypochlorite bleach are effective deactivators of many hazardous drugs. Should not be mixed with biological waste Waste containers should be puncture proof and have a sealed lid. 39

Chemo Spill Kit http://www.kendallhq.com/imageserver.aspx?contentid= 31229&contenttype=application/pdf 40

PRE-PRINTED ORDERS Safety Includes dose amount and parameters (mg/m2, mg/kg, flat dose) Lists infusion order for multi-drug regimens Includes all pre- and post-drugs, labs and other testing Key to eliminating errors Consistency Streamline the process of ordering for physicians Addresses protocols based on diagnosis/physician Eases understanding/communication for nursing Supports practice guidelines for appropriate premeds and prn drugs

PRE-PRINTED ORDERS Best Practice Regimens appropriate for disease state Continuous modifications based on evidence based practice Maximizes patient well-being Maximize cost control Patient Education Identifies key information to relay to patients

PHARMACOGENOMICS Variations in the genome that affect drug activity May cause abnormal activity of metabolizing enzymes Tests are available (blood or cheek swab) Oncology examples results in dosage change UGT1A1 metabolism of irinotecan DPD metabolism of fluorouracil and capecitabine Additional panel of 20 medications used for supportive care

ETHICAL ISSUES IN CHEMOTHERAPY Physicians are bound by Respect for autonomy Nonmaleficence (do not harm) Informed consent Justice make standard of care available to all Drug shortages Shared decision making Patients who select alternative care (cultural competency) Educate Continue to communicate Support (LEARN)

IMPLICATIONS FOR JORDAN Guidelines and regulations Best practices in handling chemo drugs IV room set up, ordering, preparation, dispensing, labelling, delivery, storage, decontamination Safety guidelines and procedures. Personnel training (KSA) Chemotherapy knowledge Patient Education Cultural competency, Ethical Considerations, palliative care 45

SUMMARY Hazardous drugs are part of community and hospital practice Exposure to such drugs is a possibility Safe handling guidelines should be followed to decrease any possible exposure to such drugs Pharmacist training plays a major role in preventing exposure to themselves and others 46

SUMMARY Establishing best practices in hazardous drugs: Ordering Preparation Handling Disposal is essential to optimize patient care and address ethical considerations. 47

QUESTIONS?

CHAPTER <800> USP Chapter <800> (Feb, 1, 2016), extended official implementation date for July 2018. Some states have elected to require earlier compliance) Focus on protecting healthcare workers and environments from exposure to hazardous drugs in the healthcare settings where they are handled State boards of pharmacy are in the process of being trained extensively on this regulation American Society of Health System Pharmacists American Society of Clinical Oncology National Institute for Occupational Safety and Health Oncology Nursing Society 49

COMPLIANCE STUDY Conduct a gap analysis to identify areas that require improvement 2016 compliance Study 26% of the hospitals report using the low volume exemption contained in Chapter <797> relative to HD compound Chapter <800> removes that exemption 27% of hospitals report they do not comply with the physical plan requirements of Chapter <800> and have no plans to comply Containment Primary Engineering Controls (CPEC) Containment Secondary Engineering Control 50

NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH Designate a knowledgeable individual to be responsible for all aspects of HD Compile list of HD s handled using the 2016 NIOSH HD list Consider performing an assessment of risk for those drugs (chemo that need to be packaged or counter, non-chem and reproductive only hazard) that may be eligible for alternative containment strategies and work practices Assess current physical plan (CPED, CSEC) Evaluate current work practices and identify gaps between required and desired work practices and actual work practices Revise written standard operating procedures (SOPs); Changes to: Hazardous PPE donning and doffing practices; HD inventory receipt and handling Organization of compounding steps (improve containment of HD residues) 51

Develop staff training based on updated SOPs Lowest score in the 2016 compliance study were with items within the SOP Development Domain and Personnel Training Domain Establish processes to monitor for compliance with new procedures and use objective measures when possible to measure outcomes Only 10% of hospitals report performing HD environmental wipe sampling and the vast majority of these perform it by sampling of the inside of the CPEC only Should monitor the flood directly outside of these areas Keep seeking improvement, focus on moving forward 52

Compliance is a journey not a destination Develop a compliance plan that is strategic based upon your organization s needs Systemically evaluate the voyage travelled by HDs in your facility Verify current containment strategies and develop new ones Learn from the experience of others 53

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http://www.usp.org/frequently-asked-questions/hazardous-drugshandling-healthcare-settings A hazardous drug is any drug identified as hazardous or potentially hazardous by the National Institute for Occupational Safety and Health (NIOSH) on the basis of at least one of the following six criteria: carcinogenicity, teratogenicity or developmental toxicity, reproductive toxicity in humans, organ toxicity at low doses in humans or animals, genotoxicity, and new drugs that mimic existing hazardous drugs in structure or toxicity. NIOSH maintains a list of antineoplastic and other hazardous drugs used in healthcare settings. 55

The purpose of the chapter is to describe practice and quality standards for handling hazardous drugs in healthcare settings and help promote patient safety, worker safety, and environmental protection. The chapter defines processes intended to minimize the exposure to hazardous drugs in healthcare settings. The chapter was developed by the USP Compounding Expert Committee with the assistance of the USP Compounding with Hazardous Drugs Expert Panel and government liaisons from the U.S. Food and Drug Administration (FDA) and the U.S. Centers for Disease Control and Prevention (CDC) including NIOSH. The chapter was published for the first time for public comment in March 2014. Based on the public comments received, the chapter was revised and proposed for another round of public comments in December 2014. The chapter was revised again and published in the USP-NF in February 2016. 56

The public health need for developing <800> was based on published reports of adverse effects in healthcare personnel from occupational exposure to hazardous drugs.1 General Chapter <800> was developed based on existing guidance documents published by the National Institute for Occupational Safety and Health (NIOSH), American Society of Health-System Pharmacists (ASHP), and the Oncology Nursing Society (ONS). ASHP published a Technical Assistance Bulletin in 1986 and NIOSH published an alert on preventing occupational exposure in 2004. There was a known risk of hazardous drug exposure in healthcare settings from published medical reports, but there was no enforceable standard to minimize the potential risk of exposure. [1] Sessink PJ, Bos RP. Drugs hazardous to healthcare workers. Evaluation of methods for monitoring occupational exposure to cytostatic drugs. Drug Saf. April 1999; 20(4): 347-59. Venitt S, Crofton-Sleigh C, Hunt J, Speechley V, Briggs K. Lancet, Monitoring exposure of nursing and pharmacy personnel to cytotoxic drugs: urinary mutation assays and urinary platinum as markers of absorption. Jan 1984;1(8368): 74-7. (See also 57 https://www.cdc.gov/niosh/topics/antineoplastic/default.html).

Chapter <800> was written to protect all workers, patients and the general public who may be accessing facilities where hazardous drugs (HDs) are prepared. This includes but is not limited to pharmacists, technicians, nurses, physicians, physician assistants, home healthcare workers, veterinarians, and veterinary technicians. If any workers come in contact with HDs, they must receive HD training, and be assessed for an understanding of the training. All personnel who handle HDs are responsible for understanding the fundamental practices and precautions and for continually evaluating these procedures and the quality of final HDs to prevent harm to patients, minimize exposure to personnel, and minimize contamination of the work and patient-care environment. 58

The chapter applies to all healthcare personnel who handle HD preparations and all entities that store, prepare, transport, or administer HDs (e.g., pharmacies, hospitals and other healthcare institutions, patient treatment clinics, physicians' practice facilities, or veterinarians' offices). Yes, the chapter applies to administration of HDs. If non-antineoplastic or reproductive risk HD dosage forms do require manipulation such as crushing tablet(s) or opening capsule(s) for a single dose, alternative containment strategies and work practices as defined in the assessment of risk must be used (e.g. appropriate personnel protective equipment (PPE), use a plastic pouch to contain any dust or particles generated). If antineoplastic HD dosage forms require manipulation, the requirements of Chapter <800> must be followed. 59

The chapter applies to all healthcare personnel who handle HD preparations and all entities that store, prepare, transport, or administer HDs (e.g., pharmacies, hospitals and other healthcare institutions, patient treatment clinics, physicians' practice facilities, or veterinarians' offices). Yes, the chapter applies to administration of HDs. If non-antineoplastic or reproductive risk HD dosage forms do require manipulation such as crushing tablet(s) or opening capsule(s) for a single dose, alternative containment strategies and work practices as defined in the assessment of risk must be used (e.g. appropriate personnel protective equipment (PPE), use a plastic pouch to contain any dust or particles generated). If antineoplastic HD dosage forms require manipulation, the requirements of Chapter <800> must be followed. 60

The chapter applies to all healthcare personnel who handle HD preparations and all entities that store, prepare, transport, or administer HDs (e.g., pharmacies, hospitals and other healthcare institutions, patient treatment clinics, physicians' practice facilities, or veterinarians' offices). Yes, the chapter applies to administration of HDs. If non-antineoplastic or reproductive risk HD dosage forms do require manipulation such as crushing tablet(s) or opening capsule(s) for a single dose, alternative containment strategies and work practices as defined in the assessment of risk must be used (e.g. appropriate personnel protective equipment (PPE), use a plastic pouch to contain any dust or particles generated). If antineoplastic HD dosage forms require manipulation, the requirements of Chapter <800> must be followed. 61

From a compendial standpoint, a USP general chapter numbered below <1000> becomes enforceable through reference in the General Notices, a monograph, or another applicable general chapter numbered below <1000>. At this time, <800> is not specifically referenced in the General Notices, a monograph, or another applicable general chapter numbered below <1000>. However, states may make their own determinations regarding the applicability and enforceability of <800> to entities within their jurisdiction. Per question 8 above, USP has no role in enforcement. As a result, the specific enforceability of <800> depends on the legal fram No. USP encourages adoption and implementation of General Chapter <800> to help ensure a quality environment and protection of healthcare workers and patients when hazardous drugs are handled.ework that you are analyzing 62

Yes, there have been minimal editorial changes to the chapter. USP publishes errata if it discovers erroneously published text that does not accurately reflect the intended requirements as approved by the Council of Experts. In the errata table, enter 800 in the field Search by Monograph to view errata associated with General Chapter <800>. No. The only part of USP General Chapter <800> that is expected to change is the official date, which is expected to be changed to December 1, 2019. Yes, there are several studies demonstrating risks associated with handling HDs. Some of references are included in the References section of USP General Chapter <800>. Yes, final dosage forms of commercially available HD oral liquids that do not require any further manipulation other than pouring and repackaging may be considered under an assessment of risk. 63

No. The assessment of risk must list each drug and dosage form individually. Dosage forms of drugs within the same group might not have the same risk of exposure. For example, priming an intravenous line may have more risk of exposure than dispensing tablets without further manipulation. HDs appear on the NIOSH list based on different characterizes, such as specific reproductive risks. The facility may have the same information for several drugs or dosage forms, but the facility s list needs to be specific to the drug and dosage form. http://www.usp.org/frequently-asked-questions/pharmaceutical-compoundingsterile-preparations and http://www.uspnf.com/notices/general-chapter-797-proposed-revision http://www.usp.org/frequently-asked-questions/hazardous-drugs-handlinghealthcare-settings 64