USP <800> A practical approach to compliance. Ryan W. Naseman, PharmD, MS, BCPS Michael Storey, PharmD, MS, BCPS

Transcription

1 USP <800> A practical approach to compliance Ryan W. Naseman, PharmD, MS, BCPS Michael Storey, PharmD, MS, BCPS

2 Learning Objectives Explain the need for USP <800> from an employee safety standpoint Describe facility needs to comply with USP <800> Apply practice changes needed to be compliant with handling provisions in the chapter Adapt the intent of the chapter to your practice setting Note: All learning objectives are applicable for both pharmacist and technician continuing education.

3 Agenda Brief overview of occupational hazardous exposure literature Review of USP <800> Hazardous medication lists Requirements and strategies to manage hazardous medications throughout the medication use process at your institution Closed System Transfer Devices Environmental quality and control Deactivating / decontaminating / cleaning Spill control Medical surveillance

4 NIOSH Hierarchy of Industrial Controls

5 Occupational Hazardous Exposure Chemotherapy has been detected in the urine of nurses and pharmacists Mitigated by use of a Closed System Transfer Device (CSTD) Evidence exists for mutagenicity, carcinogenicity, and reproductive risks There are documented cases of specific exposures with short term and long term adverse effects

6 USP <800> Released: February 1, 2016 Sections: Hazardous drug (HD) list Types of exposure Responsibilities of Personnel handling hazardous drugs Facilities and engineering controls Receiving Storage Compounding Environmental quality control Personal Protective Equipment Hazard communication program Enforceable: July 1, 2018 Personnel training Receiving Labeling, packaging, transport and disposal Dispensing final dosage forms Compounding Administering Deactivating, decontaminating, cleaning, disinfecting Spill control Documentation of SOPs Medical surveillance

7 NIOSH list National Institute for Occupational Safety and Health (NIOSH) Maintains a list of HDs Provides the criteria used to identify HDs Group 1: Antineoplastic drugs, including those with the manufacturer s safehandling guidance Group 2: Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug, including those with the manufacturer s safehandling guidance Group 3: Non-antineoplastic drugs that primarily have adverse reproductive effects

8 Selected Medications on the NIOSH List Group 2 Estrogen / progesterone combinations Conjugated estrogens Esterified estrogens Phenytoin / fosphenytoin Group 3 Oxytocin Temazepam Testosterone Valproate / valproic acid Voriconazole Warfarin Zonisamide

9 So What s required? Absolutely required to follow all USP <800> requirements Any/all HD active pharmaceutical ingredients (API) Any/all antineoplastic HD requiring manipulation (Group 1 Medications) Required to follow some USP <800> requirements - if an assessment of risk has been performed and implemented Final dosage forms not requiring additional manipulation If the entity has determined alternative containment strategies and work practices

10 Hazardous Drug Lists Each entity MUST maintain a list of HDs MUST include any item on the NIOSH list that the entity handles MUST review at least every 12 months Or when a new agent OR dosage form is used MUST use the NIOSH criteria to evaluate any drug that enters the market after the most recent NIOSH list or an investigational agent Hazardous drugs defined as having any of the following characteristics: Carcinogenicity, teratogenicity or developmental toxicity, reproductive toxicity, organ toxicity at low doses, or genotoxicity Structure and toxicity profiles of new drugs that mimic existing drugs determined hazardous by the above criteria Special consideration to the dosage form purchased and type (if any) or manipulation performed within the institution

11 Assessment of Risk If an assessment of risk is NOT performed ALL HDs MUST be handled with all containment strategies in USP <800> Assessment of risk MUST include (at a minimum): Type of HD (antineoplastic, non-antineoplastic, or reproductive risk only) Dosage form Packaging Manipulation Risk of exposure Assessment of risk must be documented and reviewed at least every 12 months

12 Assessment of Risk Example Oral mercaptopurine tablet Type: antineoplastic HD Dosage form: tablet Packaging: purchased in unit dose packaged tablets Manipulation: none RN must open package at bedside to administer Risk of exposure Inhalation? Skin? - will RN touch tablet Dust from tablets/capsules may present a risk of exposure by skin contact and/or inhalation

13 Types of Exposure Routes into the body Dermal and mucosal absorption Inhalation Injection Ingestion Opportunities of exposure Drug containers (i.e. outside of vial) Spills/breakage Nebulization (i.e. inhaled ribavirin) Compounding waste

14 Medication Use Process Nadzam. Medication Use: A Systems Approach to Reducing Errors. 1998:5-17.

15 Receiving Antineoplastic HDs and all HD APIs MUST be unpacked Removed from external shipping containers neutral/normal or negative pressure NOT in positive pressure areas (i.e. ante room) Receive in impervious plastic Wear chemo gloves when unpacking Deliver to HD storage area immediately after unpacking If damage is detected, discard entire bag*

16 Storage MUST be stored in a manner that prevents spillage or breakage Not on the floor If manipulation is required (i.e. not just counting or repackaging) Antineoplastic HD and HD API Stored separately from non-hds Externally ventilated, negative pressure room 12-air changes per hour (ACPH) Non-antineoplastic HD, reproductive risk only HD, and antineoplastic final dosage forms May be stored with other non-hd inventory if permitted by policy (Risk Assessment) Sterile and nonsterile HDs may be stored together HDs for nonsterile compounding SHOULD NOT be stored in sterile compounding area Refrigerated MUST be stored in a dedicated refrigerator Negative pressure, 12-ACPH If in negative pressure buffer room - CONSIDER exhaust adjacent to compressor

17 Compounding / Dispensing Primary engineering controls Secondary engineering controls Containment supplemental engineering controls Sterile compounding Non-Sterile compounding Final dosage forms

18 Secondary Engineering Controls (SEC) MUST Be externally vented* Physically separated Negative pressure between 0.01 and 0.03 inches of water column relative to all adjacent areas Water sources/drains MUST be > 1 meter from PEC Sink available for handwashing Eye wash station

19 Primary Engineering Controls (PEC) MUST operate continuously If it supplies some or all of the required negative pressure for the SEC Is used for sterile compounding (<797>) MUST be externally vented (prefered) OR have redundant-hepa filters in series Examples: Class I BSC - (nonsterile only) Containment Ventilated Enclosure (CVE) - (nonsterile only) Class II BSC A2-30% exhausted (sterile or nonsterile) B % exhausted (sterile or nonsterile) B2-100% exhausted (sterile or nonsterile) Compounding Aseptic Containment Isolator (CACI)

20 Sterile vs. Nonsterile Compounding If performing both PECs MUST be located in separate rooms UNLESS SEC can maintain ISO 7 continuously throughout nonsterile compounding AND Nonsterile PEC is 1 meter AND Particle-generating activity (i.e. nonsterile compounding is not performed when sterile compounding is being performed. <797> and <795> must be followed, respectively

21 Non-Sterile Compounding Dedicated compounding equipment PEC must be placed in SEC with at least 12 ACPH Surfaces (i.e. ceilings, walls, floors, etc) MUST be smooth, impervious, nonshedding For occasional nonsterile HD compounding A PEC used for sterile compounding may be used IF Decontaminated, cleaned, and disinfected before resuming sterile compounding If a dedicated PEC for nonsterile is used: Does not need unidirectional airflow PEC to be exhausted ideally; alternative is two in-line HEPA filters

22 Example - Dual HEPA-Filtered Hood HEPA #2 HEPA #1

23 Sterile Compounding PEC must provide ISO class 5 or better BSC Type IIA2, BSC Type IIB1, BSC Type IIB2, BSC Type III, CACI Non-HD sterile compounding? Place in protective outer wrapper during removal (i.e. bag) Label to require PPE handling precautions PEC must be placed in a SEC Plastic-backed mat placed on work surface of PEC Changed if spill occurs, regularly during use, and discarded at end of shift

24 Sterile Compounding - SEC ISO class 7 buffer room WITH an ISO class 7 ante-room Buffer room: Externally vented 30 ACPH of HEPA-filtered air Negative pressure to adjacent areas ( inches of water column) Ante-room: 30 ACPH of HEPA-filtered air Positive pressure (at least 0.02 inches water column) to adjacent unclassified space Unclassified containment segregated compounding area (C-SCA) Externally vented 12 ACPH Beyond-use date (BUD) as defined in <797> for segregated compounding area 12-hours

25 Ideal Room Configurations Nonsterile Sterile

26 Sterile configurations with limitations

27 HD Buffer Room Through Non-HD Buffer Room Line if demarcation within the negative-pressure buffer room for donning and doffing PPE A method to transport HDs, HD CSPs, and HD waste into and out of the negative pressure buffer room to minimize the spread of HD contamination

28 Closed System Transfer Devices Definition: Drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of HD or vapor concentrations outside the system Why: Vial pressurization (escape of vapors / aerosols) Droplets from stopper puncture Accidental needle sticks USP <800> requirement when dosage form allows: Should be used when compounding MUST be used when administering antineoplastic HDs Accessed: 4/16/17

29 Closed System Transfer Devices Considerations Containment vs. Air Cleaning Functionality/usability Drug compatibility Cost NIOSH CSTD protocol Protocol version 2 Comment period open through June 2017 Utilizes substrates that mimic hazardous drug Detects levels of substrates to determine if system is closed

30 Dispensing Final Dosage Forms If no manipulation required Counting and repackaging is not considered manipulation May be prepared for dispensing without any requirements for containment MUST be performed carefully To prevent HD dust generation or leakage Use clean equipment dedicated for use with HDs Decontaminate after each use MUST not be placed in automated counting or packaging machines

31 Administration MUST use protective devices and techniques IV administration: CSTDs required Spike in pharmacy, prime with non-hd solution Wear PPE Oral (non-manufactured tablet or capsule) Oral solution (prepared in pharmacy) only. Bladder irrigation, transcatheter chemoembolization, cavity administration

32 Inhaled Ribavirin Inhalation as a route creates unique risks for exposure Staff inhalation risk Family inhalation risk Surface contamination risk Risk minimization strategy: Prepare in a ready-to-administer syringe for nebulization Use scavenger tent to capture drug Captures >99% of drug not inhaled Negative pressure room Full chemotherapy garb with addition of N-95 mask Staff education

33 N-95 Masks Not your typical surgical mask Most commonly used in hospitals for airborne precautions Must be fit-tested for each person Must block at least 95% of small particles NIOSH maintains a comprehensive list of qualifying masks

34 Transport All HDs that require special handling MUST be clearly labeled Packaged to maintain integrity/stability/sterility during transport Prevent from damage, leakage, contamination, degradation Transported in containers that minimize risk of breakage or leakage Do not tube Any liquid HDs Antineoplastic HDs

35 Waste / Disposal Black - RCRA waste Any unused or partially used HDs IV Bags, tubing, etc. Visibly soiled PPE Yellow - trace chemotherapy Any trace remainders of HDs Empty IV bags, tubing, syringes, etc. Consider all PPE to be contaminated, at minimum, trace quantities of HDs Red - needles

36 Environmental Quality and Control Wipe testing should be done at baseline and periodically (i.e. at least every 6 months) Interior of PEC and area around PEC Pass-through chambers Surfaces in staging areas for medication preparation Near, adjacent to, under the PEC Patient administration areas If contamination is found MUST identify, document and contain the cause Re-evaluation of work practices Retraining Re-Cleaning Repeat the wipe study

37 Deactivating / Decontaminating / Cleaning Agents applied through the use of wipes wetted with solution and not delivered by spray bottle Deactivation Goal: render compound inert or inactive Examples: peroxide, sodium hypochlorite Decontamination Goal: remove HD residue Examples: alcohol, water, peroxide, sodium hypochlorite Cleaning Detergent Disinfection Sterile alcohol

38 Spill Control Must be contained and cleaned immediately Spill kits must be kept in all areas where hazardous drugs may be located Must use N-95 mask/respirator for spill cleanup Spill materials are hazardous waste Spills must be documented Circumstances and management Personnel and non-employees exposed Completion of an incident form

39 Medical Surveillance SHOULD not MUST Identify workers with exposure risk Nurses Pharmacy staff Providers Unit support staff Environmental services/housekeeping Waste handling Baseline, periodic, and exit testing Tracking of employee exposure Spills - follow-up plan for possible exposures Quantities, types, and frequency of HDs handled

40 Selected Medications on the NIOSH List Group 2 Estrogen / progesterone combinations Conjugated estrogens Esterified estrogens Phenytoin / fosphenytoin Group 3 Oxytocin Temazepam Testosterone Valproate / valproic acid Voriconazole Warfarin Zonisamide

41 Assessment of Risk / Strategies for Compliance Estrogen / testosterone API for compounding into a cream ALL <800> requirements (HD API) Phenytoin / fosphenytoin Tablet: No containment storage requirements Dedicated equipment for counting Must split / crush in pharmacy (nonsterile PEC) IV: Could store with non-hd Compound in PEC in negative pressure SEC Prime in pharmacy w/ base solution Bag / label as HD CSTD (optional) PPE?

42 Assessment of Risk / Strategies for Compliance Oxytocin Temazepam Valproate / valproic acid Voriconazole Warfarin

43 Review / Strategies to Start... Responsible person Three pronged approach: SOPs Facilities Process compliance (every time, every day) Utilize the assessment of risk to document / develop SOP for handling each dosage form of each HD handled at your institution Collaborate with nursing, employee health, environmental services, etc.

44 USP <800> A practical approach to compliance Ryan W. Naseman, PharmD, MS BCPS Michael Storey, PharmD, MS, BCPS Reference: First Supplement to United States Pharmacopeia and National Formulary (USP 39-NF 34). Rockville, MD: United States Pharmacopeia Convention; 2016.