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

2. 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.

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

4. A History Lesson

5. 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:

6. 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:

7. 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:

8. Waiting for USP 797 Updates

9. 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:

10. 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:

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

12. USP 797 vs. USP 800

13. 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.

14. 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

15. 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:

16. 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

17. 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.

18. 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

19. 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, will be the responsibility of FDA, states, and other government authorities
Official information & a free download available at:

20. PROPOSED REVISIONS

21. USP 797
Original proposed revisions (September 2015) are available for review at: proposed-revisions-sep-2015.pdf
USP also held an “open mic” forum; slides available here: 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:

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

23. 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”

24. 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

25. 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

26. 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:

27. 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

28. 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

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

30. 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

31. 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

32. 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

33. 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.

34. Challenges

35. 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?

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

37. 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

38. 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

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

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

42. Resources USP 800 Gap Analysis Tool: http://www.800gaptool.com/
Joint Commission Resources Self Assessment for Hazardous Drug Handling:
Sign up for USP updates:
USP 800 FAQs: handling-healthcare-settings
Free download of USP 800:
USP 797 FAQs: compounding-sterile-preparations
Sign up to download USP 797: compendium

43. 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

44. Questions?