<USP 800> Avoiding

<USP 800>

Avoiding the Hazards of Non-Compliance

Dustin Ezell,

PharmD

, BCPS

Baptist Health – North Little Rock

Learning Objectives

Compare <USP 800> requirements to current guidelines and practicesIdentify NIOSH risk categories and corresponding safe handling guidelinesReview strategies for implementing a successful compliance programEffectively perform hazardous drug risk assessments

What is 800?

USP (United States Pharmacopeia) is an independent standard setting bodyNo inherent regulatory or enforcement authorityConsiders standards <1000 “enforceable”Standards set by Expert Committee USP <800> defines processes intended to minimize exposure to hazardous drugs in healthcare settings.

Abbreviations

Organizations:USP – United States PharmacopeiaASBOP – Arkansas State Board of PharmacyEPA – Environmental Protection AgencyDEA – Drug Enforcement AgencyISO – International Organization for StandardizationASTM – American Society for Testing and MaterialsOSHA – Occupational Safety and Health AdministrationNIOSH – National Institute for Occupational Safety and Health

Abbreviations

Terminology:SCA – Segregated Compounding AreaBSC – Biological Safety CabinetCACI – Compounding Aseptic Containment IsolatorHEPA – High Efficiency Particulate AirHD – Hazardous Drug(s)CSTD – Closed System Transfer DevicePPE – Personal Protective EquipmentAPI – Active Pharmaceutical IngredientAoR – Assessment of RiskSOP – Standard Operating ProcedureACPH – Air Changes Per Hour

Why?

4Hansen J, Olsen JH. Scand J Work Environ Health. 1994 Feb;20(1):22-65Connor TH, et al. J Occup Environ Med. 2010 Oct;52(10):1019-27.

3

Valanis

BG, et al. Am J

Hosp

Pharm. 1993 Mar;50(3):455-62.

Enforcement

USP is not an enforcement bodyArkansas State Board of Pharmacy regulations:04-05-0001 – HOSPITAL PHARMACEUTICAL SERVICES PERMITAll hospitals shall have adequate provisions for pharmaceutical services regarding theprocurement, storage, distribution, and control of all medications. All federal and stateregulations shall be complied with.USP “Should” = recommendationUSP “Shall” = requirement

Current

HD StandardUSP <797>Sterile Compounding Only“Low volume exemption”No SCA for Hazardous drug compoundingUSP<800>Dec 2019 Sterile and non-sterile compoundingNo exemptionsProvision for SCA BSC/CACI

Minimum 12 ACPH

(-0.01”)

w.c.

pressure

Current

HD StandardUSP <797>“Shall”PPEminimal 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

What does USP <800> cover?

Handling of Hazardous DrugsFacilities and EquipmentPersonnelReceiving and Storage Personal Protective EquipmentCleaningDispensing and AdministrationSpills and DisposalEnvironmental QC

What does USP <800>

not cover?• Hazardous waste disposalRefer to EPA p-listed & u-listed chemicals(warfarin, phentermine, phenobarbital, nicotine, etc)Controlled drug wasteRefer to DEA guidance 21 CFR Part 1300Sterility & stability AssuranceRefer to USP<797>

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

Facilities

Designated HD handling areas Away from food (break room)Receipt, storage, nonsterile HDs, sterile HDsSigns and Restricted AccessHD Sterile Compounding - ISO 7Ante Area – ISO 7 (note: different than IV Buffer)Minimum 30 ACPH HEPA filtered air+0.02” w.c. to unclassified adjacent areas

IV Buffer Room

(ISO 7)Ante Area (ISO 8)Air flowHD Buffer Room(ISO 7)

Ante Area

(ISO 7)

Air Flow

Air flow

Air flow

BSC

BSC

Facilities

Equipment

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

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

Equipment

USP 800

CSTDs (aka Containment Supplemental Engineering Controls)All CSTDs are not equalCSTDs are no substitute for BSC/CSCIMUST be used when administering antineoplastics when dosage form allowsTubing must be primed prior to transport

PPE Highlights

Gloves - ASTM standard / sterile / powder-free / double glovesGown – 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>

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 splashRespiratory - should: fit-tested elastomeric half-mask with multi-gas cartridge and p100 filter if unpacking HDs not contained in plasticALL PPE is “contaminated.” No reuse of gownDispose in HD waste

Pop Quiz

USP<800> dictates the use of CSTDs when:compounding HDs in a BSC/CACI outside of ISO 7 Buffer Roomadministering HDs when dosage form allowsconvenient and cost-effectiveAll of the aboveA and B

Communication and Training

Establish a Hazard Communication ProgramStandard Operating ProceduresLabeling, transport, storage, and disposalMSDSDocumented and assessed training at least every 12 monthsInformation and training for staff prior to assignmentPersonnel of reproductive capability MUST confirm IN WRITING that they understand the risks of handling HDs

Receiving / Disposal

Possibly the biggest change to most existing practicesStorage in negative pressure areaPPE worn when unpackingSpill kit in receiving areadamaged containerstransportNO pneumatic tubing of HDsDisposal of waste“Comply with federal, state, and local regs”Don’t try to manage this out of pharmacy

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

Spill Control

Training of personnel – specific qualified spill respondersUse of PPESigns restricting access to the areaSpill kits readily availableImmediate evaluation of personnel exposedDocument event and response

Medical Surveillance

Handlers of HDs should be enrolled in a medical surveillance programSymptom complaints, physical findings, blood counts, etc.Program highlights:Identification of those at riskRecords of handling and estimated exposureHIPAABaseline physical assessmentFollow up for any health changes suggesting toxicityExit exam

Hazardous

Drug ListNational Institute for Occupational Safety and Health (NIOSH) maintains a list of antineoplastics and other HDs used in healthcareAn entity must maintain a list of HDs – must include NIOSH drugs that the entity handlesMust be reviewed at least every 12 monthsNew agents or dosage forms should be reviewedUse NIOSH provided criteria http://www.cdc.gov/niosh/topics/hazdrug/

Hazardous

Drug ListNIOSH GROUPWhy

hazardous?

examples

Group 1

Antineoplastics

•

cytotoxic

• teratogenicity

• genotoxic

cisplatin,

doxorubicin, tamoxifen,

megestrol

,

hydroxyurea

Group 2

Non-

Antineoplastics

• carcinogenicity

• organ toxicity

• teratogenicity

valgancyclovir

,

progestins

, risperidone,

mycophenolate

Group 3

Primarily

Reproductive

Risk only

• teratogenicity

oxytocin,

temazepam

,

valproic

acid, warfarin,

ziprasidone

Risk Assessment

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

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

Risk Assessment

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

Risk Assessment

“Drugs on the NIOSH list that do not have to follow all of thecontainment 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

Sample Assessment of Risk

Drug:NIOSH Table:Dosage Form/Route:Origin:Packaging:

Alternative Containment Reason:

Oxytocin

Table 3: Reproductive Risk Only

IV Solution

Outsource 503B (DGE Compounding)

Oxytocin 20 units in 0.9% Sod

Chl

1000mL in PVC Bag

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.

Date of Assessment:

Oct 11, 2018

Sample Assessment of Risk

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.

Alternative Handling

Receiving:

Storage:

Handling:

Administration:

Disposal:

Non-HD procedure

Non-HD procedure

(see handling) gloves will be worn during

a

dministration preparation by any of above

Trace waste disposed in standard trash.

l

arge volume waste will be disposed via reverse

d

istribution vendor. (Drugs-Back ‘R Us)

Personnel

“Designated Person”“Qualified and trained to be responsible for developing and implementing appropriate procedures, overseeing compliance, ensuring personnel competency and environmental control.”PPEDon’t go cheapSOPs“hit by a bus”Acknowledgement of RiskFree template:https://www.pppmag.com/documents/V8N10/CC/PDFs/HazDrugRisk_Acknowledg.pdf“There is no acceptable level of personnel exposure to HDs.” USP <800>

Personnel

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

Summary

Compare <USP 800> requirements to current guidelines and practicesUSP 797 HD handling vs. USP 800 handlingNon-sterile HD includedNo low use exemptionStorage requirementIdentify NIOSH risk categories and corresponding safe handling guidelinesTable 1 – AntineoplasticsTable 2 – non-Antineoplastics (toxicity)Table 3 – Reproductive Risk only

Summary

Review strategies for implementing a successful compliance programFacilities/EquipmentPersonnelPPEEffectively perform hazardous drug risk assessments Evaluate NIOSH list against formularyIdentify candidates for alternative containmentWritten strategy for handlingReview yearly

Special Thanks

Baptist Health Medical Center – North Little RockGrace Marable, PharmD, BCPSDon Garner, PDClinical Pharmacy Staff reviewed and provided feedback and editsPatricia C. Kienle, RPh, MPA, FASHP – USP <800> Expert CommitteeProvided reference supplements

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,

2016

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.

https://www.pppmag.com/documents/V8N10/CC/PDFs/HazDrugRisk_Acknowledg.pdf

(accessed Sept 24, 2018)

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.https://www.epa.gov/hw/defining-hazardous-waste-listed-characteristic-and-mixed-radiological-wastes. Accessed Sept 24, 2018Perform an Assessment Of Risk To Comply with

Usp

: March 2017 - Pharmacy Purchasing & Products

Magazine. https

://www.pppmag.com/article/2012