Introduction to USP General Chapter <800> How Will It Affect Federal Pharmacy?

CPE Information and Disclosures Introduction to USP General Chapter <800> How Will It Affect Federal Pharmacy? MAJ Jonathan Bartlett Moncrief Army Health Clinic CPT(P) Seth Mayer Walter Reed National Military Medical Center MAJ Bartlett declares stock ownership in Walmart. CPT(P) Mayer declare(s) no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this program, including grants, employment, gifts, stock holdings, and honoraria. The American Pharmacist Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. CPE Information Target Audience: Pharmacists & Technicians ACPE#: 0202-0000-16-163-L04-P/T Activity Type: Knowledge-based Learning Objectives At the completion of this activity, participants will be able to: List the elements of USP <800> and the purpose of its creation Identify what processes will be affected by the implementation of USP <800> Outline an action plan to ensure compliance with the elements of USP <800> Question 1 The list of current medications covered under USP<800> are on the list developed by which organization? a) NIH b) NIOSH c) APhA d) OSHA Question 2 SOPs for all of the following processes must be written or modified in order to meet USP <800> standards except: a) New employee training standards b) Pharmacy supply procedures c) Nursing Administration guidelines d) Civilian hiring practices 1

Bottom Line Question 3 Sterile compounding of Hazardous Drugs must be performed under conditions that meet all of the following standards except: a) C-PEC must maintain an ISO 5 or better environment b) Room that contains C-PEC must be negative pressure relative to adjacent rooms c) C-PEC must be in an ISO 7 buffer room connected to an ISO 7 ante room with 30 Air Changes Per Hour d) C-PEC can be in a Containment Segregated Compounding Area for low or medium risk Compounded Sterile Products. USP Chapter <800>, like <795> and <797>, will be an enforceable standard Joint Commission Accreditation Implementation poses both short and long-term challenges Coordination, cost, training, surveillance, work flow, etc. Early organizational support and planning USP Chapter <800> becomes official 1 July 2018 Background Background Cont Regulation of hazardous drugs is complicated! OSHA NIOSH DoT EPA DoD Etc. All define specific rules regarding the handling, use, and disposition of hazardous drugs No single enforceable federal standard exists to protect healthcare workers Evolutionary standard for management: USP <795>: HDs shall be stored, prepared, and handled under conditions that protect the healthcare workers and other personnel USP <797>: HDs shall be prepared under conditions that protect healthcare workers and others in preparation and storage areas USP <800> applies to both sterile and non-sterile compounding Key Elements of USP <800> List of HDs Responsibilities of Personnel Facility Design and Engineering Controls Environmental Quality and Control Personal Protective Equipment (PPE) Hazard Communication Training Receiving Labeling, Transport and Dispensing Compounding Administering Cleaning Documentation Medical surveillance Key Element - Hazardous Drugs List A comprehensive list of all HDs maintained by the entity Items on current NIOSH list utilized by entity Any new HD or investigational drug in use at facility since NIOSH list update Other agents identified through local risk assessment. Additional institution-wide list High Alert Medications; Look-Alike / Sound-Alike; Hazardous Drugs Reviewed annually and upon additions 2

NIOSH List National Institute of Occupational Safety and Health s List of Antineoplastic and Other Hazardous Drugs Used in Healthcare Three groups with corresponding tables Group 1 Antineoplastic drugs Group 2 Non-antineoplastic drugs that meet 1 or more NIOSH criteria for a hazardous drug Group 3 Drugs that pose reproductive risk to men and women who are actively trying to conceive and women who are pregnant or breast feeding Provides criteria to determine HD placement on list Key Element Personnel Responsibilities Hazardous Drug Officer: Each entity must have a designated person who is qualified and trained to be responsible for: Developing and implementing appropriate procedures Overseeing entity compliance with this chapter and other applicable laws, regulations, and standards Ensuring competency of personnel Ensuring environmental control of the storage and compounding areas Managing risk-prevention policy and reporting functions Providing oversight of facility monitoring, including testing/samples and acting upon results Personnel Responsibilities Cont Key Element Facility Design Training Initial and annual refresher training HD List and risks Proper use of PPE and engineering controls Responses to HD exposure or spills Documentation of training Responsible and Accountable Practice standards Notice of risk in position description Medical Surveillance Facility must be designed to protect the patient, the preparation, healthcare personnel, and the environment. Designated activity locations: Receipt and Unpacking (receiving) Storage Compounding (sterile vs. non-sterile) and power specific Neutral/normal vs. negative pressure Uninterrupted power sources (UPS) for all ventilation equipment Facility Design - Receiving Facility Design Storage Specific location must be designated where unpacking occurs Refers specifically to removal from external shipping containers Segregated from non-hds Neutral/normal or negative pressure to the surrounding areas HDs must not be unpacked from their shipping containers in sterile compounding areas or in positive pressure areas Layout with spill prevention and breakage consideration Storage layout by Group and manipulation requirement: NIOSH Group 1 requiring manipulation (beyond counting or repackaging) and any HD Active Pharmaceutical Ingredient (API) must be stored separately. NIOSH Group 2 and 3 + final dosage forms of Group 1 may be stored with other inventory. 3

Facility Design Guess That Drug Which of these needs special storage? Facility Design - Storage Layout with spill prevention and breakage consideration Storage layout by manipulation requirement: Non-antineoplastic, reproductive risk only and final dosage forms of antineoplastic HDs may be stored with other inventory. Antineoplastic HDs requiring manipulation other than counting final dosage forms and any HD API must be stored separately. Storage Cont. Facility Design - Compounding HD separate storage Separate room, buffer room, Containment Segregated Compounding Area (C-SCA) Sterile and non-sterile HDs may be stored together Negative pressure Twelve (12) air changes per hour (ACPH) Refrigerated HDs Stored in designated refrigerator Within HD separate storage Supplemental to <797> and <795> Controls divided into: Primary Engineering Control (C-PEC) ISO 5 or greater Secondary Engineering Control (C-SEC) Room where C-PECs are placed Supplemental Engineering Control Adjunct controls to offer additional levels of protection Careful attention to should vs. must Primary Engineering Controls (C-PEC) Certified Biological Safety Cabinet (BSC) Class II Type B2 Compounding Aseptic Containment isolator (CACI) Secondary Engineering Controls (C-SEC) Minimum requirements: Negative pressure Externally vented 12 ACPH Variable requirements dependent upon sterile vs.. non-sterile compounding Additional physical requirements Ante-room, sink, eye wash station 4

Supplemental Engineering Controls Adjuncts to offer additional levels of protections Closed System Transfer Devices (CSTDs) Should be used when compounding Must be used for administration Antineoplastic HDs If dosage form allows Check compatibility between drug and device Sterile Compounding Two different options for facilities: Full cleanroom setup C-PEC within an externally vented buffer room Negative relative pressure to connected ante-room Both rooms ISO 7 with 30 ACPH Containment Segregated Compounding Area (C- SCA) C-PEC within an unclassified space with fixed walls, relative negative pressure and 12 ACPH. Facility Diagram Current Facility Example Supply Cart Positive Supply Cart Supply Cart Supply Cart HD Fridge Negative Supply Cart Non-HD BSC WIRE RACK WIRE RACK MEDICATION WORK TABLE MEDICATION FRIDGE HD BSC MEDICATION Sink Current Facility Example Current Facility Example Non-HD BSC Positive Sink MEDICATION HD MED Negative HD BSC HD FRIDGE Negative HD MED MEDICATION Positive Non-HD BSC MEDICATION HD FRIDGE MEDICATION HD BSC Sink 5

Containment Segregated Compounding Area (C-SCA) Non-sterile Compounding Secondary engineering control for sites with limited HD compounding C-PEC is placed in a room with fixed walls and: Negative pressure Externally vented At least 12 air changes per hour (ACPH) Only low and medium risk HD sterile products C-PEC must be: Externally vented Class I BSC or Containment Ventilated Enclosure (CVE) or better Located within a C-SEC with at least 12 ACPH & negative pressure For occasional non-sterile HD compounding C-PEC for sterile compounding may be used Requires decontamination, cleaning, and disinfection afterwards Key Element Labeling, Packaging, Transport Labeling Warning label to identify HD Clear administration instructions Packaging Sufficient to protect personnel and product Safety over bag Light protection Pre-primed Transport In accordance with federal/state/local regulations No tubing of liquid HDs Key Elements - Personal Protective Equipment Gloves ASTM-tested chemotherapy gloves Powder free Gown Disposable, back-closure, long sleeved with cuffs, non permeable Must change gown: Per manufacturer recommendation Every 2-3 hours After splash Key Elements - Personal Protective Equipment Shoes Double covered Donned and doffed when entering C-SEC Eye and Face Must be worn when risk of spill or splash is present outside C-PEC (spill cleaning, etc.) Face shield with goggles recommended PPE Based on function being performed Key Elements - Personal Protective Equipment Respiratory Unpacking HDs not contained in plastic Elastomeric half-mask with multi-gas cartridge and P100-filter Any manipulation of HD with splash, droplet, or spray risk Fit-tested NIOSH-certified N95 or greater Gaseous or vapor risk Full face piece chemical cartridge respirator or powdered airpurifying respirator (PAPR) Equipment must be maintained in accordance with manufacturer requirements Any HD spill > 1 spill kit / cleaning underneath C-PEC Also requires protection equivalent to gas/vapor risk 6

Key Elements Cleaning Cleaning Steps Extension of <795> and <797> Robust procedures for workspace preparation Occurs wherever HDs are handled Deactivation / Decontamination + Cleaning: Receiving, compounding, transport, administering, and disposal Additional Disinfection for: Sterile compounding and devices Facility Must must develop SOP Cleaning Step Purpose Agents Deactivation Render compound inert or inactive Sodium hypochlorite 2% followed by sodium thiosulfate; EPA-registered oxidizer; or as listed in SDS Decontamination Cleaning *Disinfection Remove inactivated residue Remove organic and inorganic material Destroy microorganisms Surface wipe with sterile alcohol or water Germicidal detergent and sterile water Isopropyl alcohol 70% (sterile) *only necessary for sterile compounding Key Elements Cleaning Key Element - Spills When to conduct cleaning: Daily when in use (work surfaces, C-PEC) Between compounding different HDs Any time a spill occurs Before and after certification As indicated in <795> or <797> Organization-wide policy Spill prevention and clean up Location of kits and instructions for use Who will respond/manage? Training in spill management PPE and respirator use Must be available whenever HDs are in use Practice and execute spill drills Designate the team Key Elements - Administering Staff administering HDs Must: must: Utilize appropriate PPE Discard PPE at site of administration Utilize Closed-system drug-transfer devices if treatment allows Staff administering HDs should: Should: Avoid manipulation of HDs (relocate process to HD compounding room whenever possible) Key Elements Environmental Quality Control Wipe Sampling Initial and every 6 months Include: Interior of C-PEC Staging or work areas near C-PEC Areas adjacent to C-PECs Areas immediately outside HD buffer room or C-SCA Patient administration areas If measureable contamination is found: Identify, document and contain Repeat sampling after decontamination to validate 7

Key Elements - SOP and Training Key Elements - SOP and Training Standard Operating Procedures (SOPs): Maintain SOP(s) for all aspects of HD handling Reviewed at least annually by Hazardous Drug Officer Mechanism for communication of changes Departmental and Hospital/Clinic SOPs will be required Employee file documentation Initial and ongoing assessments for personnel Overview of facility s HD list and risks Review of facility s HD handling SOPs Proper use of PPE Proper use of equipment and devices (e.g., engineering controls) Spill management Response to known or suspected HD exposure Personnel that transport, compound, or administer HDs Documentation must be IAW OSHA Standard 1910.120 Hazardous Waste Operations and Emergency Response Key Elements Medical Surveillance Implementation Challenges Part of a comprehensive exposure control program Organization-wide management and support Should include: Identification of personnel exposed Initial baseline and periodic assessment Monitoring of data to identify process failures and prospective health Follow-up plan for personnel with health changes suggestive of toxicity or acute exposure Exit exam including medical documentation Facility Design HD compounding services Sterile Non-Sterile Physical changes to pharmacy for receiving, storage, compounding, and work flow Design options vs.. current pharmacy footprint Funding Implementation Challenges The Way Ahead (Action Items) Cross-organization support requirements SOP generation and implementation Communication and training Hazardous Drug Officer position development Medical Surveillance and Environmental Quality Control Evolve current hazardous medication programs Recurring mechanisms to review SOPs, conduct training, maintain HD list and risk assessment Consider HD Committee USP <800> Staff Familiarization Organization subscription to USP Develop subject matter experts Site-specific assessment Identify current compliance; key areas of focus Perform gap analysis Online tools available Consultants 8

The Way Ahead (Action Items) Key Points Begin Mission Analysis Lean-Six-Sigma PI project; engage peers Create information brief for leadership Develop diagrams and workflow concept Required facility changes Process changes Hazardous Drug Officer SOP development Training USP <800> provides practice and quality standards for handling of HDs in healthcare settings Significant changes in facility design and engineering controls may be required to meet the standards SOPs and training will need to be updated and/or implemented to meet the new standards prior to the Chapter becoming official Beginning early is important to ensure facilities meet standards by the Chapter s go live date Question 1 The list of current medications covered under USP<800> are on the list developed by which organization? a) NIH b) NIOSH c) APhA d) OSHA Question 2 SOPs for all of the following processes must be written or modified in order to meet USP <800> standards except: a) New employee training standards b) Pharmacy supply procedures c) Nursing Administration guidelines d) Civilian hiring practices References Question 3 Sterile compounding of Hazardous Drugs must be performed under conditions that meet all of the following standards except: a) C-PEC must maintain an ISO 5 or better environment b) Room that contains C-PEC must be negative pressure relative to adjacent rooms c) C-PEC must be in an ISO 7 buffer room connected to an ISO 7 ante room with 30 Air Changes Per Hour d) C-PEC can be in a Containment Segregated Compounding Area for low or medium risk Compounded Sterile Products. 1. <795> Pharmaceutical Compounding Nonsterile Preparations - Revision. (2014, January 1). United States Pharmacopeia. Retrieved from http://www.uspnf.com 2. <797> Pharmaceutical Compounding Sterile Preparations Second Supplement to USP 31-NF26. (2008, June 1). United States Pharmacopeia. Retrieved from http://www.uspnf.com 3. <800> Hazardous Drugs - Handling in Healthcare Settings First Supplement to USP 39-NF 34. (2016, February 1). United States Pharmacopeia. Retrieved from http://www.uspnf.com 4. A Vapor Containment Performance Protocol for Closed System Transfer Devices Used During Pharmacy Compounding and Administration of Hazardous Drugs. (2015, August). Retrieved August 23, 2016, from http://www.cdc.gov/niosh/docket/review/docket288/default.ht ml All images published under Free use with modifications or Public Domain license through Creative Commons 9

References Cont. 5. Badry, N., Fabbro, J., & Lemos, M. L. (2013). Hazards in determining whether a drug is hazardous. Journal of Oncology Pharmacy Practice, 20(4), 312-315. doi:10.1177/1078155213496675 6. Kastango, E. S. (n.d.). The USP Compliance Study. Retrieved May 20, 2016, from http://800gaptool.com/ 7. Massoomi, Firouzan. "USP <800> And The Expected Impact On Health Systems". 2014. Presentation. 8. National Institute for Occupational Safety and Health [NIOSH]. NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2014. Retrieved from http://www.cdc.gov/niosh/docs/2014-138/pdfs/2014-138_v3.pdf Questions? MAJ Jonathan Bartlett, CPT(P) Seth Mayer, PharmD PharmD, BCACP PGY2 Pharmacy Resident Chief of Pharmacy, Walter Reed National Military Moncrief Army Health Clinic Medical Center Jonathan.S.Bartlett5.mil@mail.mil Seth.A.Mayer2.mil@mail.mil All images published under Free use with modifications or Public Domain license through Creative Commons 10