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OPERATION C.L.E.A.N. OPERATION C.L.E.A.N. Compounding: Leveraging and Elevating Awareness in a New Era

Presented by:Audrey B. Johnson, BPharm, CPh, MSM

#FSHP2018

Disclosure: I do not have a vested interest in or affiliation with any corporate

organization offering financial support or grant monies for this continuing education activity, or any affiliation with an organization whose philosophy could potentially bias my presentation.

Objectives:Objectives:• Recognizing issues in sterile procedures and

compounding • Recognize trouble shooting and steps that need to be

taken to fix problems in both aseptic and extemporaneous compounding

• Explain the steps that need to be taken before and after aseptic and extemporaneous compounding

(referencing USP 795, 797, and 800)

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What do you mean by “Clean”?What do you mean by “Clean”?

Compounding requires a host of Procedures, practices, and processesIncluding skills, techniques, documentation, testing, and most of all your “Integrity”!

How do we guard against what we cannot see?

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The 2018 Florida Statutes

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Florida Pharmacy Law64B16-27.797Adoption of USP Chapters

797 – Sterile Compounding71 – Sterility Tests85 – Bacterial Endotoxins

www.floridapharmacy.govFLORIDA DRUG AND COSMETIC ACTChapter 499.0121Storage and handling of prescription drugs; recordkeeping

USP Chapters United States Pharmacopeia

Provides guidance for safety, quality, and efficacy of products compounded for human consumption or use • USP 795 Provides guidance of compounding

utilizing Non-Sterile componentscompounded preparations for consumption/use

• UPS 797 Provides guidance for compounding utilizing Sterile products

• USP 800 Provides guidance for compounding Hazardous products both Sterile and Non-Sterile (hazard levels)

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Improvements in Compounding Compliance increased from 77% in 2011 to 87% in 2018

We still have improvement steps to make (+/- 20%)

“Prevent Contamination”

How? Follow the Guidelines (Policy & Procedure)

When? Always

Why? Product & Patient Safety

Deviation from process creates opportunities for Harm

Objective 1: Recognizing issues in sterile procedures and compounding

ASHP Time line of Events for Sterile compounding

Issues identified in Sterile Compounding:

www.CDC.gov

Event Trends from 1970 – 2012753 injured

64 Deaths in 753 injured….more reported /many unknown-and recent reporting's have been added –although delayed occurrences secondary exposure and residual injuries

Response: Federal & State levelsRapid and Aggressive changes in Regulations and Guidance standards for the Compounding of Medications

Changes in Agency oversightSeparation of ActivitiesRequirements of PerformanceStandards for PracticeFacility conformance General Requirements

2019 Release of New Guidelines for USP 797, 800, 795 and FDA (503A- 503B)

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The Impact of “Issues”…. 2012 event

#FSHP2018Time: 02:00

General causes of issues: • Inadequate Training• Inadequate Equipment• Deviation of process • Improper Cleaning• Failure to follow procedure• Improper Storage • Using beyond established time• Contaminations • Use of Out dated/Expired contents• Improper Storage & Stability data

• Beyond Use / dating• Inadequate gowning• Stretching Guidelines • Non-compliance• Personnel Activities• Poor Environmental Conditions• Compromised Air Quality• Inadequate Aseptic Technique

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Example of an Exterior environment exposures

Example of Improper Gowning exposure:

Types of Contamination

Touch(aseptic

techniques)

Cross(technique-practice)

Exposure(personnel/product/air)

Viable Non-Viable

“Prevent Contamination”

How? Follow the Guidelines (Policy & Procedure)

When? Always

Why? Product & Patient Safety

Deviation from process creates opportunities for Harm

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How does contamination occur?

How do we trouble shoot?

What Measures should be taken?

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Follow the Guiding Rules:

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Objective 2:

Recognize trouble shooting and steps that need to be taken to fix problems in both aseptic and extemporaneous compounding

RCA & CAPA:

•What Happened?•Where Happened?

What was the impact?

(How many defects)

•What was the impact? •How many defects/errors?

Analyze:

•What was involved? •Who was involved?

•Establish correction which will prevent reoccurrence (aka: Action Plan)

Trouble shoot & Fix problems

RCA: Root Cause Analysis• Define/Identify the issue• Evaluate Magnitude/Impact• Identify Cause• Analyze and Document Cause

• Procedure/Process• Persons/People• Product ? –recalls, storage, shipping• Equipment • Environment• Microbiology test –growths/samples

CAPA: Corrective And Preventive Action• Correct the issue

• Identify the cause and corrective action needed

• Establish the Preventive action• Establish a redesign of the

process • Re-educate or Re-train• Service-Update- or Replace

systems/equipment

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Calibrations Validations

Training AssessmentMonitoring

Workflow design

Validate

Calculations Calibrations

Testings

EngineeringMonitoring

CertifyAir Quality

Viable-NonViable

CleaningExposure

Aseptic Processes AnalysisSterility

VerificationDocumentation

?What is all of this???

Activities of involvement for Safe compounding of pharmaceutical products for use:

Product

EnvironmentPEC/SEC

Air

EquipmentTested

Calibrated

Material & Supplies

Storage&

Stability

Quality

PersonnelTraining

The Elements for Controls in Safe Compounding:

Essential Areas for Compliance Practices: Personnel • Aseptic Training • Compounding Skills• PPE- Personnel Protective• Hand Hygiene

Environmental Controls• ISO Classifications • Air Quality

(Particles/Temperature/Pressure) • Cleaning

(supplies/solutions/frequency)

Engineering & Equipment: • Cleanroom Designs• Primary & Secondary• Hoods /BCA & BCC• Equipment –Supplies Cleaning

Quality Assurance: • Environmental Monitoring• Product Testing • Personnel –Process Validations

Personnel Training & Awareness: Required Training with Documentation:

Aseptic Technique Media Fill Validation-Touch Plate Proper Garbing & Gowning – Touch PlatesHand Hygiene Cleaning practices

Written Assessment & Observational are required

Annually or Semi-Annually for Hazardous or High Risk

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Aseptic Techniques: Sterile Cmpd <797>

Application of technique utilizing methods, manipulations, and process to prevent the introduction of bacteria, virus or micro-organism contamination1st line of defense for safe preparation

Some steps in Aseptic practice include:• Hand washing and application of antimicrobial agent with persistent activity• Sterile IPA for swabbing and wiping • Proper use Sterile Gloves• Cleaning workspace, outer containers with Sterile IPA• Use new supplies with each unique compound/batch • Replace compromised items- gloves, needles, garb• Work 6 inches within the PEC (hood/box) • Do Not touch critical sites• Do Not block first air flow from hood

Common Cleanroom Micro-Organisms

• Micrococcus spp.• Staphylococcus spp.• Corynebacterium spp.• Bacillus spp.• Aspergillus spp.• Pencillin spp.

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Techniques : Non-sterile Extemporaneous <795>

• Apply techniques of Sterile- Hand Hygiene/Gloves/Gowning • Use Clean sanitized equipment and supplies• Prepare workspace with only necessary items • Do NOT share Compounding workspace• Clean workspace after each preparation • Label and store properly• Place used supplies in appropriate area• Ensure measures are correct• Equipment calibrated• Use cleaning units properly – sanitizing, sterilizations, incubation• BUD- expiration date factoring all components used*

Common Organisms: Extemporaneous

•

Cleanings & Solutions:

Anti-sporicidalBroad SpectrumQuintenary Bleach 2% measured accurately for concentration valueSterile IPA (not 70% Isopropyl basic) – Sterile with COAPeroxide Fungicidal

Room Design & Engineering:

• Room design- layout

• Segregated by Activity

• HVAC –designated with access

• HEPA Filters- High Efficiency Particle Air

• Temperature Monitoring

• Humidity Monitoring

• Ceiling Tiles - Lightings

• Walls/Floors

Engineering & Equipment:

Air Duct external exhaust

HEPA Filters

Work bench

Waste bins

Pharm Waste

Control Particles: Non-lint sheading wipes

Product Wipe down before entry

Air Quality Testing Minimize In/Out – Product Introduction – Misc.

Surface CleaningSterile IPA- Sterile Water

Cleaning requirementsDaily: Compounding Surface/Floors

Weekly: Daily + Cleaning Solution changeMonthly: Ceiling –Walls- Surface-Carts-Bins

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ISO Classifications (Air Quality)ISO Classifications (Air Quality)International Science Organization for Standardization

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According To USP 797, What Levels of Viable Colony Counts Are Considered Elevated?

The following table lists the action levels adapted from the Pharmaceutical Compounding - Sterile Preparations <797>,

that when exceeded must initiate further investigation.

ISO Class

Active Airborne (cfu*/m3)

Glove Fingertip (cfu/contact plate)

Inanimate Surfaces** (cfu/contact plate)

5 > 1 > 3 > 3

7 > 10 not required > 5

8 > 100 not required > 100

 

Quality Assurance: Monitoring & Maintenance:

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Pressure Monitoring: ACH –air changes per hour

Temperature Monitoring: below 70

Quality Assurance: Air –Surface-Product testing's Viable (micro organisms) & Non-Viable (particles)

Cleaning: Solutions and Microbial coverage required

Case Study: 2011: Multiple Patients Blinded Due to Avastin Contamination6

Patients in California, Florida, and Tennessee were blinded after receiving Avastin that had been contaminated during medium risk level compounding. Additionally, one patient suffered permanent brain damage.

How did the contamination occur? A. Process:

B. Product:

C. Environment:

D. Container/Supplies:

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Techniques : Non-sterile Extemporaneous <795>

• Apply techniques of Sterile- Hand Hygiene/Gloves/Gowning • Use Clean sanitized equipment and supplies• Prepare workspace with only necessary items • Do NOT share Compounding workspace• Clean workspace after each preparation • Label and store properly• Place used supplies in appropriate area• Ensure measures are correct• Equipment calibrated• Use cleaning units properly – sanitizing, sterilizations, incubation• BUD- expiration date factoring all components used*

Steps to take Before & After Compounding:

Before: 1. Prepare in proper attire – follow Garbing – Gloving requirements2. Clean and Prepare the workspace 3. Review required materials – correct, intact, pure4. Review Date opened/ Use date/expiration date)5. Evaluate supplies for use- (do not use6. Review Compounding Procedure prior and review after completion 7. Aseptically prepare only 1 compounded product in a session*

After Completion: 1. Label Properly2. Conduct proper cleaning between sessions3. Reverify contents used- “as a post-compound review” 4. Package Properly 5. Clean work space with Sterile IPA 6. Change gowning/glove if necessary

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Tips for Success not provided in Guidance and Rules: • Train Properly – Assess Abilities • Evaluate compliance of personnel• Adequate Staff for Workload• Design Workflow processes • Review and Update processes• Allow proper time for compounding • Establish sound procedures• Avoid deviations from process • Conduct random evaluation • Inspect frequently (watch out for Shortcuts and Work arounds) • Provide adequate resources and supplies• Replace broken and defective equipment • Invest in a Compounding Documentation Software Program*

“Prevent Contamination”

How? Follow the Guidelines (Policy & Procedure)

When? Always

Why? Product & Patient Safety

Deviation from process creates opportunities for Harm

The Acronyms:The Acronyms:PEC: Primary Engineering ControlsSEC: Secondary Engineering controlsPPE: Personnel Protective Equipment BUD- Beyond Use Date API-Active Pharm. IngredientHEPA- High Efficiency Particle AirCFU’s- Colony Forming Units

PEC

SEC

PPE

BUDIPA

HEPA

CFU

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References: • USP-NF Compendium ; Chapters 797, 795, Assessments• www.USP.org• Florida Pharmacy Law; 64B26.797 • ASHP Trends –trending; Journal April 2011• Pharmacy Products & Purchasing; April 2018• Pharmacy Today • Carter Health –catalog image• Florida Cleanroom – production image• Compounding Pharmacy Today• PDA Journal of Pharmaceutical Science & Technology; 2011

Operation C.L.E.A.N.Operation C.L.E.A.N.

Questions & Answers?

Thank you for your participation!

“Follow the Guidelines”

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