1. <USP 800> Avoiding the Hazards of Non-Compliance
Dustin Ezell, PharmD, BCPS Baptist Health – North Little Rock

2. Learning Objectives
Compare <USP 800> requirements to current guidelines and practices
Identify NIOSH risk categories and corresponding safe handling guidelines
Review strategies for implementing a successful compliance program
Effectively perform hazardous drug risk assessments
This is not intended to be a comprehensive review of the USP 800 standard. A sufficient review would take 8 hours or more. The goal of this presentation is to provide the framework and tools for compliance.

3. What is 800?
USP (United States Pharmacopeia) is an independent standard setting body
No inherent regulatory or enforcement authority
Considers standards <1000 “enforceable”
Standards set by Expert Committee
USP <800> defines processes intended to minimize exposure to hazardous drugs in healthcare settings.

4. Abbreviations
Organizations: USP – United States Pharmacopeia ASBOP – Arkansas State Board of Pharmacy EPA – Environmental Protection Agency DEA – Drug Enforcement Agency ISO – International Organization for Standardization ASTM – American Society for Testing and Materials OSHA – Occupational Safety and Health Administration NIOSH – National Institute for Occupational Safety and Health

5. Abbreviations
Terminology: SCA – Segregated Compounding Area BSC – Biological Safety Cabinet CACI – Compounding Aseptic Containment Isolator HEPA – High Efficiency Particulate Air HD – Hazardous Drug(s) CSTD – Closed System Transfer Device PPE – Personal Protective Equipment API – Active Pharmaceutical Ingredient AoR – Assessment of Risk SOP – Standard Operating Procedure ACPH – Air Changes Per Hour

6. Why? 3Valanis BG, et al. Am J Hosp Pharm. 1993 Mar;50(3):455-62.
4Hansen J, Olsen JH. Scand J Work Environ Health Feb;20(1):22-6
5Connor TH, et al. J Occup Environ Med Oct;52(10):

7. Enforcement USP is not an enforcement body
Arkansas State Board of Pharmacy regulations:
– HOSPITAL PHARMACEUTICAL SERVICES PERMIT
All hospitals shall have adequate provisions for pharmaceutical services regarding the
procurement, storage, distribution, and control of all medications. All federal and state
regulations shall be complied with.
USP “Should” = recommendation
USP “Shall” = requirement

8. Current HD Standard USP <797> USP<800> Dec 2019
Sterile Compounding Only
“Low volume exemption”
No SCA for Hazardous drug compounding
Sterile and non-sterile compounding
No exemptions
Provision for SCA
BSC/CACI
Minimum 12 ACPH
(-0.01”) w.c. pressure
USP 797 addresses hazardous drugs currently. Many times people refer to USP 800 as a new standard, but many of the practices are covered in USP 797.

9. Current HD Standard USP <797>
“Shall”
PPE
minimal variation
Compounding
ISO 5 hood, negative pressure room*
Env Monitoring
pressure monitor
Training/Personnel
didactic, technique, acknowledgement of risk
Storage
separate
*low-volume exemption (use CSTDs)
“Should”
Compounding
12 ACPH
Facility
external exhaust
Env Monitoring
wipe sampling every 6 months
Storage
negative pressure, 12 ACPH
USP 797 addresses hazardous drugs currently. Many times people refer to USP 800 as a new standard, but many of the practices are covered in USP 797.

10. What does USP <800> cover?
Handling of Hazardous Drugs
Facilities and Equipment
Personnel
Receiving and Storage
Personal Protective Equipment
Cleaning
Dispensing and Administration
Spills and Disposal
Environmental QC

11. What does USP <800> not cover?
• Hazardous waste disposal
Refer to EPA p-listed & u-listed chemicals
(warfarin, phentermine, phenobarbital, nicotine, etc)
Controlled drug waste
Refer to DEA guidance
21 CFR Part 1300
Sterility & stability Assurance
Refer to USP<797>

12. Pop Quiz
The numerical chapter designation (> or < 1000) of USP standards indicates:
<1000 means state boards must enforce
<1000 means sterile vs. >1000 non-sterile
<1000 means USP considers standard enforceable
<1000 contain requirements only, >1000 contain recommendations only

13. Facilities Designated HD handling areas Signs and Restricted Access
Away from food (break room)
Receipt, storage, nonsterile HDs, sterile HDs
Signs and Restricted Access
HD Sterile Compounding - ISO 7
Ante Area – ISO 7 (note: different than IV Buffer)
Minimum 30 ACPH HEPA filtered air
+0.02” w.c. to unclassified adjacent areas
Facilities standards in USP 800 have not changed drastically from USP 797 standards with regard to compounding. But 800 broadens the scope to include receiving, storage, handling, and even administration of HDs. Additionally, 800 includes non-sterile HDs. These are many times

14. Facilities IV Buffer Room (ISO 7) HD Buffer Room (ISO 7) BSC Ante Area
Air flow
Air Flow
Ante Area
(ISO 8)
Ante Area
(ISO 7)
Air flow
Air flow
BSC

15. Equipment Class II BSC (Biological Safety Cabinet)
CACI (Compounding Aseptic Containment Isolator)
Externally Vented

16. Equipment Closed System Transfer Devices (CSTDs) • Controversial
1Gurusamy KS, et al. Closed-system drug-transfer devices plus safe handling of hazardous drugs versus safe handling alone for reducing exposure to infusional hazardous drugs in healthcare staff. Cochrane Database Syst Rev. 2018
“There is currently no evidence to support or refute the routine use of closed-system drug transfer devices in addition to safe handling of infusional hazardous drugs, as there is no evidence of differences in exposure or financial benefits between CSTD plus safe handling versus safe handling alone (very low-quality evidence).1”
2 Power LA, et al. Cohrane Review on CSTDs Misses the Mark. Pharmacy Practice News 2018
“…acceptance of the authors’ blanket rejection of all CSTDs, regardless of effectiveness, will continue decades of avoidable exposure to HDs.2

17. USP 800 CSTDs (aka Containment Supplemental Engineering Controls)
All CSTDs are not equal
CSTDs are no substitute for BSC/CSCI
MUST be used when administering antineoplastics when dosage form allows
Tubing must be primed prior to transport

18. PPE Highlights
Gloves - ASTM standard / sterile / powder-free / double gloves
Gown – recommends coated gown; must be back-closing, long sleeved, and have closed cuffs with no seams that could allow HDs to pass
Head/Hair - no difference from USP <797>

19. PPE Highlights
Shoe Covers - double shoe covers / outer doffed on exiting (doffing line inside buffer room)
Eye/Face - protection MUST be worn when there is a risk for spill or splash
Respiratory - should: fit-tested elastomeric half-mask with multi-gas cartridge and p100 filter if unpacking HDs not contained in plastic
ALL PPE is “contaminated.”
No reuse of gown
Dispose in HD waste

20. Pop Quiz USP<800> dictates the use of CSTDs when:
compounding HDs in a BSC/CACI outside of ISO 7 Buffer Room
administering HDs when dosage form allows
convenient and cost-effective
All of the above
A and B

21. Communication and Training
Establish a Hazard Communication Program
Standard Operating Procedures
Labeling, transport, storage, and disposal
MSDS
Documented and assessed training at least every 12 months
Information and training for staff prior to assignment
Personnel of reproductive capability MUST confirm IN WRITING that they understand the risks of handling HDs

23. Receiving / Disposal
Possibly the biggest change to most existing practices
Storage in negative pressure area
PPE worn when unpacking
Spill kit in receiving area
damaged containers
transport
NO pneumatic tubing of HDs
Disposal of waste
“Comply with federal, state, and local regs”
Don’t try to manage this out of pharmacy

24. Deactivate Decontaminate Clean Disinfect
Step
Purpose
Examples
Deactivation
render HD inert or inactive
oxidizers: peroxide formulations, sodium hypochlorite*
Decontamination
remove HD residue
alcohol, water, peroxide, sodium hypochlorite*
Cleaning
remove organic and inorganic
material
germicidal detergent
Disinfection
destroy viable microorganisms
sterile alcohol or other EPA registered disinfectant
*sodium hypochlorite is corrosive and MUST be neutralized with sodium thiosulfate or followed with an agent to remove

25. Spill Control
Training of personnel – specific qualified spill responders
Use of PPE
Signs restricting access to the area
Spill kits readily available
Immediate evaluation of personnel exposed
Document event and response

26. Medical Surveillance
Handlers of HDs should be enrolled in a medical surveillance program
Symptom complaints, physical findings, blood counts, etc.
Program highlights:
Identification of those at risk
Records of handling and estimated exposure
HIPAA
Baseline physical assessment
Follow up for any health changes suggesting toxicity
Exit exam

27. Hazardous Drug List
National Institute for Occupational Safety and Health (NIOSH) maintains a list of antineoplastics and other HDs used in healthcare
An entity must maintain a list of HDs – must include NIOSH drugs that the entity handles
Must be reviewed at least every 12 months
New agents or dosage forms should be reviewed
Use NIOSH provided criteria

28. Hazardous Drug List NIOSH GROUP Why hazardous? examples Group 1
Antineoplastics
• cytotoxic
• teratogenicity
• genotoxic
cisplatin, doxorubicin, tamoxifen, megestrol, hydroxyurea
Group 2
Non-Antineoplastics
• carcinogenicity
• organ toxicity
valgancyclovir, progestins, risperidone, mycophenolate
Group 3
Primarily Reproductive
Risk only
oxytocin, temazepam, valproic acid, warfarin, ziprasidone

29. Risk Assessment 1. Review NIOSH list
2. Which drugs / dosage forms do you handle?
3. Is it worth it to do a risk assessment for each drug?

30. Risk Assessment
• Assess: Drug – Dosage Form – Risk – Package - Manipulation
• Decide: alternate (to USP 800) handling strategy
• Train: personnel about the list and the Risk Assessments
• Review: every year and when new drugs are added to
formulary
• Document, Document, Document

31. Risk Assessment
Risk assessment alternative handling is not allowed for:
• Any HD API (active pharmaceutical ingredient) OR
• Antineoplastic that requires manipulation (compounding)

32. Risk Assessment
“Drugs on the NIOSH list that do not have to follow all of the
containment requirements of USP <800> if an assessment of risk
Is performed and implemented:”
• Finished form of HD CSPs or HD counting/repack only
• Each drug and dosage form must have a separate AoR
• You need an SOP for how you will perform AoR
• Drugs not handled do not require AoR

33. Sample Assessment of Risk
Date of Assessment:
Oct 11, 2018
Oxytocin
Drug:
NIOSH Table:
Dosage Form/Route:
Origin:
Packaging:
Table 3: Reproductive Risk Only
IV Solution
Outsource 503B (DGE Compounding)
Oxytocin 20 units in 0.9% Sod Chl 1000mL in PVC Bag
Alternative Containment Reason:
Oxytocin is a hormone that is used in labor to stimulate uterine contractions. Risk from exposure is limited to pregnant women in the late stages of gestation. Handling does not pose a risk of exposure in a quantity significant to produce uterine contractions.

34. Sample Assessment of Risk
Alternative Handling
Receiving:
Storage:
Handling:
Administration:
Disposal:
Non-HD procedure
Non-HD procedure
Pharmacy employees and unit staff who are pregnant
will be given specific information regarding risk and
alternatively assigned if requested.
Spills may be contained using non-HD procedures.
(see handling) gloves will be worn during
administration preparation by any of above
Trace waste disposed in standard trash.
large volume waste will be disposed via reverse
distribution vendor. (Drugs-Back ‘R Us)

35. Personnel “Designated Person” PPE SOPs Acknowledgement of Risk
“There is no acceptable level of personnel exposure to HDs.” USP <800>
“Designated Person”
“Qualified and trained to be responsible for developing and implementing appropriate procedures, overseeing compliance, ensuring personnel competency and environmental control.”
PPE
Don’t go cheap
SOPs
“hit by a bus”
Acknowledgement of Risk
Free template:

36. Personnel
“There is no acceptable level of personnel exposure to HDs.” USP <800>

37. Summary
Compare <USP 800> requirements to current guidelines and practices
USP 797 HD handling vs. USP 800 handling
Non-sterile HD included
No low use exemption
Storage requirement
Identify NIOSH risk categories and corresponding safe handling guidelines
Table 1 – Antineoplastics
Table 2 – non-Antineoplastics (toxicity)
Table 3 – Reproductive Risk only
This is not intended to be a comprehensive review of the USP 800 standard. A sufficient review would take 8 hours or more. The goal of this presentation is to provide the framework and tools for compliance.

38. Summary
Review strategies for implementing a successful compliance program
Facilities/Equipment
Personnel
PPE
Effectively perform hazardous drug risk assessments
Evaluate NIOSH list against formulary
Identify candidates for alternative containment
Written strategy for handling
Review yearly
This is not intended to be a comprehensive review of the USP 800 standard. A sufficient review would take 8 hours or more. The goal of this presentation is to provide the framework and tools for compliance.

39. Special Thanks Baptist Health Medical Center – North Little Rock
Grace Marable, PharmD, BCPS
Don Garner, PD
Clinical Pharmacy Staff reviewed and provided feedback and edits
Patricia C. Kienle, RPh, MPA, FASHP – USP <800> Expert Committee
Provided reference supplements

41. references
American Society of Health-System Pharmacists. ASHP guidelines on compounding sterile preparations. Am J Health-Syst Pharm. 2014;71(2):145– 166.
Connor TH, Mackenzie BA, DeBord DG. Clarification about hazardous drugs. Am J Health-Syst Pharm. 2012;69(22):1949– 1950.
NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, Cincinnati, OH: Department of Health and Human Services, CDC; 2016.
University HealthSystem Consortium. UHC consensus statement: model hazardous drug safety plan for institutions. Chica-go, IL: UHC; October 2009, revised January 2011.
dg.pdf (accessed Sept 24, 2018)

42. references
USP Convention, Inc. <800> Hazardous Drugs-Handling in Health care Settings. USP 40-National Formulary 35. 1st supp. Rockville, MD: USP Convention, Inc , 2017.
mixed-radiological-wastes. Accessed Sept 24, 2018
Perform an Assessment Of Risk To Comply with Usp : March Pharmacy Purchasing & Products Magazine.