USP 797 & USP 800: Updates Are Coming… Are You Prepared? Alexandra Sible, PharmD NMPhA Mid-Winter Meeting January 28, 2018

Objectives Upon completion of this activity, participants will be able to… 1. Describe the background and purpose of USP General Chapters 797 and 800 and explain key differences between the two chapters. 2. Describe proposed changes to USP 797 and USP 800. 3. Outline the proposed timelines for implementation of new USP 797 and USP 800 standards. 4. Identify challenges that pharmacies and pharmacy personnel may face in implementing new USP 797 and USP 800 standards.

https://PollEv.com/multiple_choice_polls/Lf8NWU92DsCnB2X/web

A History Lesson

Background USP = United States Pharmacopeia The United States Pharmacopeial Convention (also called USP) is a non- profit organization Founded in 1820 by a group of 11 physicians Sets standards for identity, strength, quality, and purity of medicines Chapters <1> through <999> are enforceable by the Food & Drug Administration (FDA) USP is not an enforcement agency Source: ASHP Discussion Guide on USP Chapter <797> Available at: www.medrepinc.com/index.php/download_file/view/12/

USP 797 USP <797> sets standards for preparing compounded sterile drugs (intravenous, ophthalmic, etc.) Early 1970s – thousands of sepsis cases and deaths from contaminated parenteral products 1970s and early 1980s – National Coordinating Committee on Large Volume Parenterals (NCCLVP) developed recommended standards for quality assurance of parenteral products NCCLVP dissolved in the 1980s 1990s – American Society of Health System Pharmacists (ASHP) and USP issued practice recommendations No formal accountability, regulation, or enforcement Source: ASHP Discussion Guide on USP Chapter <797> Available at: www.medrepinc.com/index.php/download_file/view/12/

USP 797 January 1, 2004 – First official and enforceable sterile preparation compounding standard in the U.S. published  USP 797 Last official revision released June 1, 2008 Revision proposed for public comment from September 25, 2015 to January 31, 2016 Intended for publication on May 1, 2017 A second revision is planned to be published September/October 2018 for a second round of public comments Revision will be harmonized with USP 800 Anticipated to be published June 1, 2019 Becomes official on December 1, 2019 Source: http://www.usp.org/frequently-asked-questions/pharmaceutical-compounding-sterile-preparations

Waiting for USP 797 Updates

USP 800 USP <800> sets standards for handling of hazardous drugs in healthcare settings In 2004, National Institute of Occupational Safety & Health (NIOSH) published an alert on hazardous drugs in healthcare settings – after USP 797 was released USP 797 revision in 2008 included a specific section for hazardous drugs (but only as it relates to sterile compounds) Based on published reports of adverse effects in healthcare personnel from exposure to hazardous drugs, USP 800 was developed Source: http://www.usp.org/frequently-asked-questions/hazardous-drugs-handling-healthcare-settings

USP 800 First published for public comment in March 2014 Revised and presented for further public comment in December 2014 Revised again and published in February 2016 Will be harmonized with USP 797 Becomes official on December 1, 2019 Source: http://www.usp.org/frequently-asked-questions/hazardous-drugs-handling-healthcare-settings

https://PollEv.com/multiple_choice_polls/BzFRYrrYfB6HyPf/web

USP 797 vs. USP 800

USP 797 The purpose of USP 797 is to describe conditions and practices that prevent harm, including death, to patients that could result from compounded sterile preparations due to microbial contamination, excessive bacterial endotoxins, variability in intended strength of the product, unintended chemical and physical contaminants, or ingredients of inappropriate quality.

USP 797 Compounded sterile preparations Compounded biologics, diagnostics, drugs, nutrients, and radiopharmaceuticals that must be sterile when administered to patients Aqueous bronchial and nasal inhalations Baths & soaks for live organs and tissues Injections (emulsions, solutions, suspensions, etc.) Irrigations for wound & body cavities Ophthalmic drops and ointments Tissue implants

USP 797 Includes Methods for sterilizing products and verifying sterility of products Responsibilities of compounding personnel Storage and beyond-use dating Requirements for personnel cleansing and garbing Suggested standard operating procedures Requirements for cleaning and disinfection procedures Dispensing, packaging, and transportation of CSPs Training and evaluation for compounding personnel Patient/caregiver training Patient monitoring and adverse events reporting Facility design Environmental quality & control Sample forms for assessments Microbial contamination risk levels Suggested actions for deficiencies Official information available at: http://www.usp.org/compounding/general-chapter-797

USP 797 Applies to all persons who prepare CSPs and all places where CSPs are prepared, and all personnel who prepare, store, and transport CSPs Compliance with USP 797 required in New Mexico (not in all states) Enforced by Board of Pharmacy Title 16, Chapter 19, Part 36 Enforced by FDA Enforceable standards currently based on June 1, 2008 version

USP 800 The purpose of USP 800 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. Receipt, storage, compounding, dispensing, administration, and disposal of sterile & non-sterile preparations.

USP 800 Hazardous drugs Any drug defined as hazardous by NIOSH on the basis of at least one of six criteria Carcinogenicity Teratogenicity or developmental toxicity Reproductive toxicity in humans Organ toxicity at low doses in humans or animals Genotoxicity New drugs that mimic existing hazardous drugs in structure or toxicity

USP 800 Applies to all healthcare personnel who handle hazardous drug preparations and all entities that store, prepare, transport, or administer hazardous drugs Including but not limited to: pharmacists, pharmacy technicians, nurses, physicians, physician assistants, home healthcare workers, veterinarians, and veterinary technicians Ensuring compliance after standards become official on December 1, 2019 will be the responsibility of FDA, states, and other government authorities Official information & a free download available at: http://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare

PROPOSED REVISIONS

USP 797 Original proposed revisions (September 2015) are available for review at: http://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/usp-gc-797- proposed-revisions-sep-2015.pdf USP also held an “open mic” forum; slides available here: http://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/usp-nf- notices/797-open-mic-slides.pdf USP received more than 8000 comments from more than 2500 stakeholders New revision to be posted September/October 2018 in Pharmacopeial Forum and will be open for comment until November 30, 2018 Sources: http://www.uspnf.com/notices/general-chapter-pharmaceutical-compounding-sterile-preparations-will-be-posted-second-round-public-comments?_ga=2.86118488.1573374732.1515011589-332876994.1512593742 http://www.usp.org/frequently-asked-questions/pharmaceutical-compounding-sterile-preparations

https://PollEv.com/multiple_choice_polls/JiIFZ4NpQxCob1B/web

USP 797: Major proposed changes General reorganization of chapter USP 800 will be used to outline hazardous drugs requirements A new “Beyond-Use-Date (BUD)” paradigm BUD cannot exceed 45 days, regardless of sterility testing “In-Use Time” – describes time to use a manufactured product or compounded dilution bag after it has been punctured Changes to terminology Microbial contamination: low, medium, high risk  Category 1 & Category 2 “No such thing as a low-risk CSP” Immediate-Use CSPs  Urgent-Use CSPs “For rare circumstances when a CSP is urgently needed”

USP 797: Major proposed changes Primary engineering controls – new terminology Laminar airflow system (LAFS) Restricted Access Barrier System (RABS) Isolator Placement of primary engineering control: Category 1 – may be placed in an unclassified Segregated Compounding Area Category 2 – LAFS, biological safety cabinet, or RABS must be placed in ISO class 7 or better area; isolater must be in ISO class 8 area

USP 797: Major proposed changes Requirement for sterile sleeves for some compounding activities Quarterly observation of compounding personnel’s hand hygiene and garbing Quarterly gloved fingertip sampling and media-fill testing Currently semi-annually or annually Changes to environmental monitoring requirements: Nonviable air sampling – every 6 months Viable air monitoring – monthly Surface sampling – monthly (currently “periodic basis”) Increased documentation requirements for batch compounding Master formulation records Compounding records

USP 800: Sections Requirements for maintaining an internal list of hazardous drugs Types of hazardous drug exposure Responsibilities of personnel handling hazardous drugs Facilities & engineering controls Environmental quality and control Personal protective equipment Hazard communication program Personnel training Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5057202/ https://www.specialtypharmacytimes.com/publications/specialty-pharmacy-times/2017/september-2017/Key-Points-From-USP-800 http://www.usp.org/frequently-asked-questions/hazardous-drugs-handling-healthcare-settings

USP 800: Sections Receiving Labeling, packaging, transport, and disposal Dispensing final dosage forms Compounding Administering Deactivating, decontaminating, cleaning, and disinfecting Spill control Documentation & standard operating procedures Medical surveillance

USP 800 Maintaining a list of hazardous drugs: does not provide complete list; references NIOSH list; entities can use NIOSH criteria for customizing a list for their own organization Hazardous drugs must be unpacked in neutral/normal pressure or negative pressure room (cannot be unpacked in sterile compounding areas or positive pressure area) Some hazardous drugs can be stored with non-hazardous drugs; antineoplastics that require manipulation other than counting final dosage forms must be stored in negative pressure buffer area

https://PollEv.com/multiple_choice_polls/iVXyTTqJJo8dYCw/web

USP 800 Entities must designate a compounding supervisor Qualified and trained to be responsible for all aspects of hazardous drug handling No specific credentials required Does not even have to be a member of pharmacy department

USP 800 Compounding: Engineering controls are primary (containment or C-PEC – “the hood”) or secondary (C- SEC or the room where C-PEC is contained) Requirements for sterile and non-sterile compounding Stricter requirements than USP 797 USP 795 and 797 standards must be followed Compounding equipment must be designated and not intermixed with nonhazardous compounding equipment Tablet and capsule forms should not be placed in automated counting or packaging machines

USP 800 Personal protective equipment Compounding: gloves, gowns, head, hair, and shoe covers Administrating antineoplastic HDs: gloves Administering injectable HDs: gloves, gowns Double gloves and double shoe covers required for certain activities Requirements for respirators Must be used when unpacking HDs not contained in plastic Cannot use surgical masks when respiratory protection is required

USP 800 Entities must establish policies and procedures to ensure worker safety Competency assessed and documented every 12 months, when a new hazardous drug or equipment is introduced, or when a significant change in process occurs Medical surveillance program Consider confidentiality of employees’ medical information Baseline assessment of health status and medical history Records of HDs handled, including number handled & hours handling Physical assessments, laboratory values, etc.

Challenges

Think, Pair, Share Discuss with a neighbor: Are you ready for USP 797 and/or USP 800? What concerns do you have for implementing USP 797 and/or USP 800 in your practice setting?

https://pollev.com/free_text_polls/ZScu40zEejHgkFC/web

Common Concerns Cost Time New equipment Changes to facility design Separation of hazardous/non-hazardous compounding May require outside assistance/consulting More frequent monitoring – more $ if performed by outside entity Time More frequent environmental sampling More frequent personnel assessment More documentation/record-keeping

Common Concerns Training/education needed Lack of references/evidence Recommendations based on opinions of expert panels Inconsistency in enforcement of standards between states Impact on other professions Physician offices, clinics, etc. Of note – many of the same concerns were raised upon the first publications of USP 797 & 800

https://PollEv.com/multiple_choice_polls/6vZfCCo7kj4ZrJ3/web

USP 797 Compliance Study Conducted by Critical Point & Pharmacy Purchasing & Products Published in Cleanrooms & Compounding, October 2017, Volume 14, No 10., page 16 Visit http://www.800gaptool.com/ Must register to view full results (free)

Resources USP 800 Gap Analysis Tool: http://www.800gaptool.com/ Joint Commission Resources Self Assessment for Hazardous Drug Handling: https://hazmedsafety.com/en/qualify Sign up for USP updates: http://www.usp.org/hqs-signup-form USP 800 FAQs: http://www.usp.org/frequently-asked-questions/hazardous-drugs- handling-healthcare-settings Free download of USP 800: http://www.usp.org/usp-chapter-800-download USP 797 FAQs: http://www.usp.org/frequently-asked-questions/pharmaceutical- compounding-sterile-preparations Sign up to download USP 797: http://www.usp.org/products/usp-compounding- compendium

Summary USP 797 sets standards for sterile compounding; USP 800 sets standards for handling of hazardous drugs in healthcare settings New versions of USP 797 & USP 800 will become officially enforceable on December 1, 2019 You can comment on proposed revisions starting in Sept/Oct 2018 Copies of these documents are available online and should be reviewed Organizations should determine their readiness to meet standards well ahead of time Some standards will likely require significant investment of money, time, and personnel training & education

Questions?