leblanc - compounding updates · 2019. 7. 10. · 7/10/2019 2 acknowledgements •dr. joann gibbs,...

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Compounding UpdatesJoseph G. LeBlanc, Jr., Pharm.D., R.Ph., M.H.A., M.B.A., D.P.L.A.

Director of Pharmacy

Heart Hospital of Lafayette

Louisiana Pharmacist Association Annual Convention

July 19, 2019

Disclosures

• I have no financial interest regarding the topics discussed to disclose.• The views & opinions expressed in this presentation are the views &

opinions of the presenter and are not those of any other governing body.

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Acknowledgements

• Dr. Joann Gibbs, PharmD, BCPS• Director of Pharmacy at Byrd Regional Hospital

• Kevin LaGrange, RPh• Quality Control Director at Professional Arts Pharmacy

Pharmacist Objectives

• Identify challenges and minimum requirements for maintaining USP 795, 797, & 800 standards

• Identify important dates and significant updates to USP 795, 797, & 800 • Introduce challenges associated with initiating USP 800 standards and

complying with USP 795 & 797 standards

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Pharmacy Technician Objectives

• Identify and discuss approaching USP 795 & 797 standards updates• Recognize and understand personnel competency requirements for preparing

compounded sterile preparations in accordance with USP standards

• Analyze the intent of USP 800 guidelines and discuss metrics for making value-adding contributions towards compliance with these standards

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Important dates for USP

• July 27, 2018: The proposed revision was pre-posted online for public comment

• September 4, 2018 was formally published in the Pharmacopeial Forum• September 5, 2018- Open Microphone Session

• August 5, 2018- Registration for Open Microphone Session opened• November 30, 2018- Public Comment Period for closed• June 1, 2019- Intended Publication Date of in USP-NF• December 1, 2019- Established Official date for

• A standardized methodology used to assist pharmacists in producing compounded sterile products that are free of deficiency or defect

• Applies to pre-administration manipulations of compounded sterile preparations including compounding, transportation, and storage

• Applies to all compounding personnel without distinction to site or profession- all patients deserve to be protected from errors and contamination

• The current published version of General chapter in USP-NF is official until the new Chapter becomes official

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• Notes that direct contact is the principal source of contamination in CSPs• Applies to CSPs given via application, implantation, inhalation, injection,

insertion, instillation, and irrigation

• Provides minimum standard for practice and quality for compounded sterile preparations of drugs and nutrients based on current scientific information and best sterile compounding practices.

Quality Monitoring

• The practices in place to ensure the desired outcome and includes:• Environmental Controls

• Temperature• Humidity• Cleanliness• Airflow

• Personnel Control• Training• Technique

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ISO Class 5 Sources, Buffer Areas, and Ante Areas

Direct Compounding Area

• The DCA is only the portion of the Primary Engineering Control dedicated to the task of Aseptic manipulation.

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Environmental Control Thresholds

ISO Class U.S. FS 209E ISO, m3 FS 209E, ft3

3 Class 1 35.2 1

4 Class 10 352 10

5 Class 100 3,520 100

6 Class 1,000 35,200 1,000

7 Class 10,000 352,000 10,000

8 Class 100,000 3,520,000 100,000

• ISO Classification of Particulate Mat- ter in Room Air (limits are in particles of 0.5 ìm and larger per cubic meter [current ISO] and cubic feet [former Federal Standard No. 209E, FS 209E])*

Environmental Controls

• Aimed at creating ISO 5,7, & 8 environments• ISO 5- LAFW, BSC, CAI, CACI are “Primary Engineering Controls• Unidirectional airflow for exposure of critical sites is required• Must maintain ISO 5 during dynamic (in use) working conditions

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• ISO 7 buffer and ISO 8 ante area- are “Secondary engineering controls”• They Utilize HEPA filter air sources• Must maintain ISO 7 or 8 during dynamic (in use) working conditions• Minimum of 30 air changes per hours of HEPA filtered air (15 ACPH with

recirculating ISO 5 device)

• Airflow balance testing required at the installation site


• ISO 5 Primary engineering control (LAFW, BSC, CAI, CACI) to be in an ISO 7 environment

• Exception: CAI if its design provides ISO 5 and isolation from the room during dynamic operating conditions as placed at your site (including transferring materials in and out) when tested by CETA Guidelines

• Only personnel and materials essential for compounding and cleaning are permitted• Performing appropriate daily and monthly cleaning are

VITAL to risk reduction.

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Staff Errors

• Does staff have appropriate attention to detail?• Alcohol swabs being used only once (No longer a concern)• Products wiped with sterile IPA prior to putting inside the compounding chamber?• Hand washing complied with?• Garbing requirements complied with?

• Jewelry worn• Artificial nails• Talking, eating, chewing gum

• Restocking by bringing cardboard into compounding area, increasing particulates.• Pharmacists not gowning prior to going into the compounding area.

Leadership

• Educate compounding staff to• Understand• Believe• Buy in to the importance of standards

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Microbiological Beyond-Use Dating Prior to 12/19

Risk Category

Room Temp

Refrigerator

Freezer (-25 C & -10 C)

ImmediateUse

1 hour 1 hour N/A

Low 48 Hours 14 days 45 days

Low w/12-hr BUD

12 hours or less

12 hours or less

N/A

Medium 30 hours 9 days 45 days

High 24 hours 3 days 45 days

CSP Risk Categories

• Prior to 12/19 • 12/19• Immediate Use CSPs• Low-Level• Low-Risk Level w/12

hour or less Beyond Use Date • A subsection of Low-

Risk Level

• Medium-Risk Level• High-Risk Level

• Category 1• Category 2

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Defining Category 1 & Category 2

• Category 1 CSP- based on facility configuration (SCA/C-SCA)• BUD of 12 hours or less at controlled temperature• BUD of 24 hours or less when refrigerated• Only if made in accordance with acceptable requirements for Category 1 CSPs

• Category 2 CSP- based on facility configuration (ISO classified ante and buffer rooms)• BUD of greater than 12 hours at controlled room temperature• BUD of greater than 24 hours when refrigerated • Only if made in accordance with acceptable requirements for Category 2 CSPs

• Table 1 provides a summary of the minimum requirements for each category but many requirements are not in the table because they apply to ALL CSPs.

Determination of Risk Category

• Responsibility of the compounding personnel…. Think about the risk• No single rule to determination• Requires professional judgment• General descriptive statements to aid in compounding personnel• Study criteria for each risk level… no prescriptive way.

• Example: Reconstitution of sterile powder before injection versus TPN. What is the risk level?

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BUDs 12/19

• BUDs for Category 1 CSPs

Controlled Room Temperate (20-25 C) Refrigerator (2-8 C)

BUD

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BUDs Category 2 CSPs

• Category 1 & Category 2 Requirements are the same

Requirement Frequency

Visual Observation of Hand Hygiene Every 6 Months

Gloved Fingertip and Thumb Sampling Every 6 months

Media Fill testing Every 6 months

Requalification Every 12 months

Other Personnel Qualifications

• Training is not just for compounders• Other personnel handling CSPs or accessing the compounding area• Must demonstrate competency in proper behavior to maintain the

environment

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Dressing Properly

• Head and facial hair covers• Shoe Covers• Face masks• Sterile gloves• Non-shedding gowns• No makeup• No externally visible piercings• No long fingernails

Garbing and Hand Hygiene

• Disposable nail cleaner must be used• Garbing order is not specified

• Up to the facility to decide• Define in SOP

• Gowns cannot be reused• CAI and CACI

• Disposable gloves under gloves under gauntlet gloves• Sterile gloves over gauntlet gloves

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Gloved Fingertip & Thumb Sampling

• No changes to the number of times• Clarifies that initial GFS is done after “separated and complete hand hygiene

and full garbing”

• Box 2-1 indicates that fingers and thumb are rolled over the surface• Gives multiple options for devices to use• Provides incubation parameters that are longer and require two temperatures

Reevaluation, Retraining, Requalification

• Failure of the following will require successful reevaluation before personnel can resume compounding.• Hand Hygiene/Garbing• GFS• Media Fill Testing

• How will this effect your ability to care for patients if you need to wait 14 days for media fill results?

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Facility Requirements

Compounding Category Compounding Environment

Category 1 CSP Cleanroom Suite or SCA

Category 2 CSP Cleanroom Suite

You can no longer compound in a CAI or CACI in a SCA and get full dating

Defining Cleanroom Suite

• ISO-classified ante-room with fixed walls and doors• Controls to minimize the flow of lower-quality air into he more controlled

areas• Supply Air introduced through HEPA filters located in the ceiling• Low wall returns unless a visual smoke study is performed • Pressure differential monitoring system• Line of demarcation in the ante-room

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Important “Shoulds”

• Design of the facility should take into account• Number of personnel and their movements• Equipment, supplies, and components

• The cleanroom suite should• Be at a temperature of 20º C or cooler at a relative humidity below 60%• Provide comfortable conditions for personnel in required garb

• Pass-through doors• Should be interlocking• That are not interlocking MUST never be opened at the same time

Air Exchanges

Compounding Area ACPH Requirements(HEPA-filtered supply air)

Pressure Requirements

Unclassified SCA None None

Unclassified C-SCA >= 12 ACPH (exhaust)No HEPA air required

Negative 0.01 to 0.03”

ISO Class 7 Non-HD Buffer Room

>= 30 ACPH (supply) Minimum Positive 0.02”

ISO Class HD Buffer Room >= 30 ACPH (supply) Minimum Positive 0.02”

ISO Class 7 Anteroom >= 30 ACPH (supply) Minimum Positive 0.02”

ISO Class 8 Anteroom >= 20 ACPH (supply) Minimum Positive 0.02”

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Air Exchanges

• Highly controversial part of certification• Chapter only prescribe minimum ACPH based on HEPA-filtered supply air for C-SCA

(based on exhaust)• ACPH may need to be higher to maintain a state of control• Factors effecting needed ACPH

• Number of personnel in the area• Number of particulates generated from processes in the area• Room pressure• The effects of temperature

Air Change Specifics

ISO Class 7 ISO Class 8

>= 30 ACPH >= 20 ACPH>= 15 of the total air change rate must come from the HVAC through HEPA filters located in the ceiling

Clarified requirement , Previous chapter did not specifythis requirement, FDA Aseptic Processing Guidance required this minimum value

If the PEC is used to meet the minimum total ACPH requirements, the PEC must not be turned off except for maintenance

All ACPH must be supplied from the HVAC through HEPA filters located in the ceiling

Certification report must have the ACPH from the HVAC, ACPH contributed from the PEC, & the total ACPH

Certification must have total ACPH

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Sink

• Should be hands free• Cleanroom Suite

• Inside the anteroom• Outside the anteroom

• SCA• Accessible • At least 1 meter from the PEC• Must not be in the SCA perimeter

Viable Environmental Sampling

Viable Air Sampling Surface Sampling

Every 6 months Monthly

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Section 5 Retitled

Environmental Monitoring

(2015)

Microbiological Air & Surface Monitoring

(2018)

Media & Incubation

• No longer required to sample in the SCA, only the classified areas• TSA still the only type of media listed

• Option given to use two pieces of media for each sample location• Open for SDA, MEA, etc.

• One plate of TSA • 30ºC to 35ºC for no less than 48 hours &• 20ºC to 25ºC for no less than 5 days

• Two plates• TSA: 30ºC to 35ºC for no less than 5 days• TSA, MEA, SDA: 20ºC to 25ºC for no less than 5 days

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Action Levels

Classification Air Sample (CFU/m3) Surface Sample(CFU/sample)

ISO Class 5 >1 >3

ISO Class 7 >10 >5

ISO Class 8 >100 >50

• Only if the Action Level is exceed, the genus of any microorganism recovered must be identified with the assistance of a microbiologist

Exceeded Action Levels

• Cause must be investigated and corrective action must be taken.• Corrective action plan must be dependent on the CFU count and the

microorganism recovered.

• The extent of the investigation should be consistent with the deviation and should include an evaluation of trends

• The corrective action plan must be documented

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These are NOT Cleaning Agents

Sodium Hypochlorite (Bleach) Isopropyl Alcohol (IPA)

Bleach is not a cleaning agent IPA is a disinfectant

Has sporicidal properties Does not have surfactant or detergent

Does not have a surfactant or detergent Is a disinfectant when applied immediately after cleaning

Has undesirable effect on most finishesover time

Is a sanitizer when applied throughout the day but not immediately after cleaning

Cleaning Tools

• Material should be disposable• Reusable MUST be

• Cleanable • Cleaned before and after each use• Dedicated for use in the classified area or SCA

• Tools must be in good condition and replaced as needed

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Clean Vs. Sterile

• Cleaning• A mechanical process• Uses detergent and water• Removes dirt, debris, and germs• Prepares the surface for disinfecting

• Sanitizing• A Chemical process

• Decreases the number of microbes to “safe” levels

• Disinfecting• A Chemical process• Destroys 100% of harmful bacteria, viruses, and fungi• Does not always kill spores

• Sporicidal Agents• Kill microorganisms• Kill spores

Cleaning the PEC (Table 8)

• Cleaning• Horizontal work surface at the beginning and end of each shift, and when surface contamination is known or

suspected.• Ceiling, walls, bars and any equipment inside the PEC on each day that compounding is performed and when

contamination is known or suspected.

• Disinfecting• All interior surfaces of the PEC at the beginning and end of each shift, after spills and when surface

contamination is known or suspected• The horizontal work surface at least every 30 minutes while compounding if the compounding process takes

30 minutes or more

• Sporicidal Application• Monthly

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Disinfecting the Critical Site

• Specifies sterile 70% IPA and wiping in one direction • No mention of the type of water• Revision reads as long as wiper is sufficiently wet, it can be used on multiple

sites.

• The critical site must be dry before puncturing the stopper/septum or breaking the necks of ampules

Beyond Use Date

• Defined as….• Must be established based on Table 11 and table 12 in the chapter• Tables are based on microbial contamination risk, assuming the compound

will be physically and chemically stable, and will maintain package integrity

• BUD will not exceed shortest remaining expiration date

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Important Dates for USP

• March 30, 2018- The proposed revision posted for public comment• April 20, 2018- open Microphone Session- Recorded Session• May 1, 2018- formally published in the Pharmacopeial Forum• July 31, 2018- Public Comment Period for concluded• June 1, 2019- Publication Date of in USP-NF• December 1, 2019- Anticipated Official Date for

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General Chapter USP

• USP Introduction & Scope Defines Nonsterile Compounding as:• Combining, admixing, diluting, pooling, reconstituting other than as provided in the

manufacturer package insert, or otherwise altering a drug or bulk drug substance to create a nonsterile medication. Reconstituting a conventionally manufactured nonsterile product in accordance with the directions contained in the approved labeling provided by the product’s manufacturer is not considered compounding as long as the product is prepared for an individual patient and not stored for future use.

USP Chapter Updates Introduction

• Newly revised draft made available for download and review on 3/30/2018• 24 pages in length (previous chapter 16 pages)• Better organized and easier to read• HD Preparations & CSPs removed and replaced in USP 800 & 797 respectively

• The Nonsterile Compounding Consensus Group (NCCG) strongly all nonsterile urges compounders and other interested parties to engage by reviewing and submitting comments

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Comparison of current & Proposed Chapter

• Introduction• Categories of Compounding• Responsibilities of the compounder• Compounding Process• Compounding Facilities• Compounding Equipment• Component Selection, Handling, & Storage• Stability Criteria and Beyond-use Dating• Packaging and Drug Preparation Containers• Compounding Documentation• Quality Control• Patient Counseling• Training• Compounding for Animal Patients• Glossary

1 Introduction and scope

2 Personnel qualifications-training, evaluation, and requalification

3 Personal Hygiene and Garbing

4 Building and facilities

5 Cleaning and Sanitizing

6 Equipment and components

7 SOPs and master formulation and compounding records

8 Release testing

9 Labeling

10 Establishing beyond—use dates

11 Quality assurance and quality control

12 CNSP handling, packaging, storage, and transport

13 Complaint handling and adverse event reporting

14 Documentation

• Glossary• Appendix

• Current USP 795 Chapter • Revised USP Chapter

High-Level View of Proposed Changes/ Observations

• Proposed sections are numbered, current sections are not• “Scope” of the chapter has been added• “Categories of Compounding” has been removed• “Responsibilities of the Compounder” has been changed to “2.

Personnel Qualifications-Training, Evaluation, and Requalification”

• “3. Personal Hygiene and Garbing’ section added• “Compounding Facilities” has been changed to “4. Buildings and

Facilities”

• The proposed chapter appears to be closely patterned after

• “Compounding Processes” has been removed

• “Compounding Equipment” and “Component Selection, Handling, and Storage” sections have been combined into “6. Equipment and Components”

• “Patient and Counseling” has been removed and possibly replaced with “Complaint Handling and Event Reporting”

• “Compounding Documentation” has been expanded into two sections: (1) SOPs and Master Formulation and Compounding Records”, and “92) Documentation”

• The section “Compounding for Animal Patients” has been removed with only limited information in the “1. Introduction and Scope” section.

• A new section “8. Release Testing” has been added• Some sections have been renamed• An “Appendix of Acronyms” has been added• There is a lot of duplication and basic teaching in this proposed

chapter that can be said more briefly and concisely as standards

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Compounder Responsibilities

• Preparations must be of acceptable:• Strength• Quality• Potency

• Appropriate packaging and labeling• USP Chapters

• 797, 1151, 1160, 1163, 1176, 1191• Applicable state laws • General Principles of Compounding as stated in USP

Compounding Process

• Criteria• 1. Dose, safety, and intended use of the preparation is suitable• 2. Master Formulation and Compounding Record• 3. Ingredients have expected identity, quality, and purity• 4. Clean and Sanitized Area• 5. One preparation at a time • 6. Appropriate equipment• 7. Reliable BUD• 8. Hygiene and PPE

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Compounding Process

• Criteria cont’d• 9. Preparation made in accordance with USP and all other scientific data and

information• 10. Critical processes verified• 11. Final Preparation Assessed• 12. Appropriate final package for preparation• 13. Proper labeling of final product• 14. Master Formulation and Compounding Record reviewed• 15. Appropriate patient consultation

Compounding Facility

• Adequate space neatly arranged

• Potable water VS Purified water

• Clean and Sanitary Condition• Well-lighted w/ proper heating & cooling to maintain appropriate temperature and humidity

control

• Adequate Storage

• Hazardous Drug storage-USP-800

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Equipment

Powder Hood and Balance

Equipment & utensils shall be of appropriate design and capacity

Equipment-Routinely inspected, calibrated & checked to ensure proper performance

Cleaned after each use

USP 800 Dedicated utensils and equipment

Component Selection, Handling, and Storage

• USP 795• USP, NF or FCC• Purchased from FDA registered facility• Obtain Certificate of Analysis

• FDA-503a • Compound with Bulk substances with USP or NF monograph• If no monograph, drugs substance must be FDA human approved component • FDA Approved list (under development)• FDA “DO NOT COMPOUND LIST”

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Component Selection, Handling, and Storage

• Component Selection• SDS Safety Data Sheets previously know as MSDS-Material • Certificate of Analysis

• Handling Components• Original Container vs Repackage Container• Adequate space

• Appropriate Temperature and Humidity• Controlled Room Temp• Refrigerator• Freezer

Sterility, Stability, and Beyond-Use Dating

• Conservative• Considerations:

• Nature of Drug• Dosage Form and its components• Potential for microbial proliferation• Container • Storage Conditions• Intended Duration of Therapy

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Sterility, Stability, and Beyond-Use Dating

• General Guidelines for Assigning BUD (in the absence of stability information):• Non Aqueous- not later than the time remaining until the earliest expiration date of

any API or 6 months, whichever is earlier

• Water-Containing ORAL- not later than 14 days when stored at controlled cold temps• Water- Containing TOPICAL/DERMAL and MUCOSAL Liquid and SEMI

SOLIDS- not later than 30 days

Packaging and Drug Preparation Containers

Packaging containers and enclosures used in packaging compounded preparations meet USP requirements

Containers must be suitable material in order not alter the quality, strength, or purity of the compound

Containers & closures Shall be stored off the floor to permit inspection and cleaningNeat and orderly as not to prevent contaminationRotate stock

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Compounding Documentation

• Systematically TRACE, EVALUATE, and REPLICATE all steps of the process

• Comply with state boards requirements for record keeping• Master Formulation Requirements• Compounding Record Requirements

Quality Control

• Correct ingredients and calculations• Accurate and precise measurements• Appropriate formulation conditions and procedures• Prudent pharmaceutical judgment• Review:

• Observe finished preparation• Investigate any discrepancies• Corrective action before prescription is dispensed

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Patient Counseling

• Proper use

• Storage and handling

• Proper disposal

• Report adverse events

• Report/Notify the pharmacist of any changes in physical characteristics

Looking Ahead to December 2019

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USP 800 Timeline

• First Release: March 2014• Comment Due Date: July 31, 2014• Second Release: December 2014• Comment Due Date: May 31,2015• Approval: February 1, 2016• Initial Compliance Date: July 2, 2018• Official Compliance Date: December 1 ,2019

• USP is:• A Standardized methodology for handling hazardous drugs (HDs) with the intent of promoting:

• Patient Safety• Worker Safety • Environmental Protection

• USP includes:• Receipt, storage, dispensing, administration, & disposal of sterile and non-sterile products/preparations

• USP

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Hazardous Drugs

Carcinogen Genotoxin Teratogen

Reproductive Toxin

Organ Toxicity at Low Doses

New agent that mimics known HD in structure or toxicity

Preparing for USP 800

• Responsible Person• Acknowledgement of Risk• Facility Design• Personal Protective Equipment• Training• Environmental Monitoring

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Hazardous Drugs

• Sections Extensively revised in 2008• USP 800 implementation date set for December 1, 2019

• Brought into concert with NIOSH Guidelines• BSC vented to the outside is recommended for optimum conditions• Must be located in separate negative pressure ISO Class 7 with ISO Class 7 ante

area

• Low-volume HDs doses exempted (a limit of 5 per week was indicated in the proposed revision)

Hazardous Drugs

• Personnel protection specified• Use of closed-system transfer devices must be within BSC or CACI, only in

an ISO class 5 environment

• Disposal according to state and federal regulations• Consistent with NIOSH guidelines as of 2008

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Hazardous Drugs

• USP • Uses NIOSH list of Antineoplastic and other Hazardous drugs in healthcare

setting.

• Requires the healthcare organization assign a compounding supervisor• Covers storage requirements, compounding facility design, supplemental

engineering controls.

• http://www.usp.org/usp-nf/notices/compounding-notice

Acknowledgement of Risk

• OSHA: Hazard Communication Standard (HCS) is based on a simple concept that employees have both a need and a right to know the hazards and identities of the chemicals they are exposed to when working

• Personnel of reproductive capability must confirm in writing that they understand the risks of handling HDs

• Applies to all personnel who handle HDs

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• USP Uses and coordinates pharmacy practice into concert with the NIOSH list of Antineoplastic and other Hazardous drugs in healthcare setting.• https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf

• NIOSH categorizes HDs into 3 groups:• Antineoplastic Drugs• Non-Antineoplastic Drugs that meet at least one of the aforementioned NIOSH criteria for

an HD.

• Drugs that pose a reproductive risk only to men and women who are actively trying to conceive and women who are pregnant or breast feeding.

NIOSH List of Hazardous Drugs

• Table 1- Antineoplastics• Table 2- non-antineoplastics• Table 3- Reproductive- only hazards• Table 4- Items removed from previous

list • Table 5- Recommended PPE

• Your Options • Option #1

• Handle all drugs and dosage forms with all containment and work practices listed in

• Option #2 • Perform an assessment of risk to

determine alternative containment strategies for work practices

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NIOSH Approach to Risk

Your Hazardous Drug List

• Review the NIOSH list of hazardous drug• Identify the drugs and dosage forms you needle• Perform an Assessment of Risk

• Risk of exposure• Packing• Manipulation

• Implement alternative containment strategies and work practices• Document review of the list annually

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Your HD List

Require ALL containment strategies detailed in

Alternative containment strategies can be considered and implemented

Active Pharmaceutical Ingredient (API) of any HD on the list

Antineoplastics you only need to count or package

Antineoplastics that require manipulation Non-antineoplastics

Dosage forms that don’t fir your Assessment of Risk

Reproductive only hazards

Product Risk Assessment

• An assessment of risk must consider the following characteristics:• Type of HD (what NIOSH category)• Dosage form• Risk of Exposure• Packing• Manipulation

• Documentation of what alternative containment strategies and/or work practices are being applied to respected HDs to minimize occupational and environmental exposure is of essence.

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Approach to Risk Assessment

• The NIOH list has links and information concerning why the drug is on the list

• Look at the information and evaluate based on your circumstances• If you exempt specific drugs and dosage forms in your entity, you must

identify the alternative containment strategies and/or work practices

• Some are situational hazards• Hazards in third trimester

Question for the Audience

• Once an assessment of risk has been performed and policies/procedures have been developed/implemented for alternative work practice and containment for the specified HDs how often showed this policy be reviewed and documented to remain valid?• A. Quarterly• B. Bi-annually• C. Annually• D. On a periodic Basis• E. None of the above

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• Once an assessment of risk has been performed and policies/procedures have been developed/implemented for alternative work practice and containment for the specified HDs how often showed this policy be reviewed and documented to remain valid?• A. Quarterly• B. Bi-annually• C. Annually• D. On a periodic Basis• E. None of the above

Receipt, Storage, Compounding of HDs

• A designated area must be dedicated towards:• Receipt & Unpacking

• Neutral or normal pressure room relative to surrounding• Not to be unpacked in positive pressure or sterile compounding areas

• Storage of HDs• Separate from non-HDs in a negative pressure externally ventilated room with NLT 12 ACPH (this goes for

refrigerated HDs as well)/

• Non-sterile HD compounding (if performed)• Sterile HD compounding (if performed)

• ECs required to prevent product cross-contamination and microbial contamination.

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Receiving

• Can you tell from outside of your package that a hazardous drug is inside?• Do you have any antineoplastics that must be manipulated other than

counted or packaged?

• Need to identify- specific to drug and dosage form- those agents that will be handled differently form and identify strategies in your Assessment of Risk

Receiving HDs

• Defined area• Not positive pressure

• Trained personnel• Gloved tested to ATM D6978• Other PPE as defined by policy• Access to spill kit• Knowledge of what to do if a spill occurs

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Containment Secondary Engineering Control-Storage and Compounding

Room with fixed walls separate

from non-hazardous storage & compounding

Vented outside the building

Negative pressure of 0.01 to 0.03

inches to adjacent space

At least 12 ACPH (30 if buffer

room)

Contains Hazard Removes Hazard

Containment Primary Engineering Control

• Containment Ventilated Enclosure (CVE)• Powder containment hood

• Biological Safety Cabinet (BSC)• Compounding Aseptic Isolator (CACI)

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What’s Allowed- What’s Not

Configuration Allowed in Allowed in

Cleanroom suite. ISO 7 positive anteroom opening into ISO 7 negative buffer room (30 ACPH)

Yes, with negative pressure of at least 0.01” negative to adjacent space

Yes, with pressure range of 0.01 to 0.03” negative to adjacent space

Low use exemption Yes No

Containment Segregated Compounding Area

Not addressed in Yes if externally vented and pressure range of 0.01 to 0.03” negative to adjacent space, but limited to 12 hours BUD CACI in negative room with 12 ACPH

Yes, optimally vented

BSC outside of cleanroom No


• Sterile and Non-Sterile HD compounding may not occur in the same room under any conditions.• True• False

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• Sterile and Non-Sterile HD compounding may not occur in the same room under any conditions.• True• False

• Sterile and Non-Sterile HD compounding may not occur in the same room if:• sterile and non-sterile compounding do not occur simultaneously• The PECs are distinguished and separated by NLT 1 meter• The PECs are encased by a negative pressure ISO 7 buffer room

HD Compounding Technique

• Negative pressure technique• Closed system drug-transfer devices• Current requires CSTD use if compounding outside of negative pressure • recommends use for compounding

• Consider for all Table 1 HDs • Consider for selected Table 2 & 3 HDs

• requires use for administering when the dosage form allows

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Stepwise Approach for Cleaning Hazardous Drugs

Deactivation • Renders HD inert (Done with bleach)

Decontamination• Removes the HD

residue • Done with an OXIDIZER

Cleaning• Removes organic &

inorganic material• Done with detergent

Disinfection• Destroys microbes• Done with Sterile

IPA

Surface Wipe Sampling

• Metric for HD Environmental and Quality Monitoring• Evaluates the ability of an entities decontamination methods for removing

HD reside from a targeted environment

• Should be performed initially as benchmarked and then every 6 months or as needed verify containment.

• Several different methods are documented (6) and the best method of choice should be selected for your facility and validated.

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Administering HDs

• What happens with:• Methotrexate for non-oncology indication• Methotrexate injection for rheumatoid arthritis• Megestrol suspension• Leuprolide injection• BCG in urology• Mitomycin in OR

Monitoring HDs

• Environmental monitoring• Still requires RM mandated by for sterile preparations• Recommends wipe sampling

• Medical surveillance• Recommended Personnel Surfaces

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To-Do List……

• Subscribe to USP Compounding Compendium• Perform Gap a gap analysis

• www.797gaptool.com• www.800gaptool.com

• Watch for final version of revised • Provide comments on 2nd version of proposed revised • Watch for the final versions of , , and • Get ready for December 1, 2019

… To Do List

• Be sure all elements are in compliance• Nonsterile compounding• Sterile compounding• Hazardous compounding

• Follow FDA compounding web site for information on outsource suppliers• https//www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyC

ompounding/ucm339771.htm

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Resources

• ASHP, www.ashp.org• Compounding Resource Center• Guidelines on Compounding Sterile Products• Guidelines on Hazardous Drugs• Compounding Sterile Preparations, 3rd edition• The Chapter Answer Book

• ASHP Foundation, www.ashpfoundation.org• Sterile Products Outsourcing Tool• Insourcing Assessment Tool

…Resources…

• Critical Point, www.criticalpoint.info• Sterile Compounding Pearls

• Oncology Nursing Society, www.ons.org• Handling Hazardous Drugs, 3rd edition

• Joint Commission, www.jointcommission.org• Standards Interpretation FAQs

• Joint Commission Resources/BD, www.hazmedsafety.com• Improving Safe Handling Practices for Hazardous Drugs

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…Resources

• Pharmacy Purchasing & Products , www.pppmag.com• February, 2015 Evolution of the CSTDs (Massoomi)• March 2017, Performing an Assessment of Risk for USP Compliance (Kienle &

Douglass)

• May 2018, Wipe Sampling (Kastango, Kienle, Fortier)

• Pharmacy Practice News• July 2018, Kienle’s 10 Building Blocks of Compounding Safety

Questions to No Longer Ponder

• What list must be used to develop an organization’s list of hazardous drugs?

• What type of solution decontaminates hazardous drug?

• What is the date when all compounding-related USP chapters is expected to be official?

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NIOSH List of antineoplastic and other hazardous drugs






Oxidizer

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Oxidizer

December 1, 2019

References

• Centers for Disease Control and Prevention. Opioid Prescribing. CDC Vital Signs. July 2017. https://www.cdc.gov/vitalsigns/pdf/2017-07-vitalsigns.pdf. Accessed 10/23/2018

• Compounding Today. Pharmaceutical Compounding-Nonsterile Preparations. April 20, 2018| Volume 15| Issue 16.

• Critical Point. Sterile Compounding Boot Camp. Critical Point, LCC. 2007-2013. Accessed 6/21/2015 http://www.criticalpoint.info/boot-camp/

• Douglass K, Kastango E. Requirements and Best Practices for Sanitizing Engineering Engineering Controls. Pharmacy Purchasing and Products. September 2013. Accessed 6/21/15http://www.pppmag.com/article/1387/March_2014/Requirements_and_Best_Practices_for_Sanitizing_Engineering_Controls/

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References

• Institute for Safe Medication Practices Medication Safety Alert . Sterile Compounding Tragedy is A Symptom of a Broken System on Many Levels. Institute for Safe Medication Practices. October 18, 2012. Accessed on 6/21/2015http://www.ismp.org/newsletters/acutecare/showarticle.aspx?id=34

• Keen J, Austin M, Huang L, Messing S, et al. Efficacy of Soaking in 70% Isopropyl Alcohol on Aerobic Bacterial Decontamination of Surgical Instruments and Gloves for Serial Mouse Laparotomies. Journal of the American Association for Laboratory Animal Science. 2010 November; 49(6): 832-837. 2010. Accessed 6/20/15 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994051/

• Kupiec T. USP and Environmental Monitoring Requirements. May 2017.

References

• NIOSH List of Antineoplastics and Other Hazardous Drugs in Healthcare Settings 2016. https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf

• Okeke C. USP Chapter Update on Recent Revisions. United States Pharmacopeia. NAPB Annual Meeting 2008.

• Proposed Revision to GC . http://www.usp.org/compounding/general-chapter-797. Accessed 10/23/2018• United States Environmental Protection Agency. Ground and Drinking Water. United States

Environmental Protection Agency. April 27, 2015. Accessed 6/21/2015 http://water.epa.gov/drink/• United States Pharmacopeial Convention. General Chapter Hazardous Drugs-Handling in

Healthcare Settings. The United States Pharmacopeial Convention. Accessed 6/21/2015 http://www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handling-healthcare-settings

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References

• NIOSH List of Antineoplastics and Other Hazardous Drugs in Healthcare Settings 2016. https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf

• Okeke C. USP Chapter Update on Recent Revisions. United States Pharmacopeia. NAPB Annual Meeting 2008.

• Proposed Revision to GC . http://www.usp.org/compounding/general-chapter-797. Accessed 10/23/2018• United States Environmental Protection Agency. Ground and Drinking Water. United States

Environmental Protection Agency. April 27, 2015. Accessed 6/21/2015 http://water.epa.gov/drink/• United States Pharmacopeial Convention. General Chapter Hazardous Drugs-Handling in

Healthcare Settings. The United States Pharmacopeial Convention. Accessed 6/21/2015 http://www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handling-healthcare-settings

References

• United States Pharmacopeial Convention. Pharmaceutical Compounding-Sterile Preparations: RevisionBulletin. 2008.

• United States Pharmacopeial Convention. USP Compounding Compendium. 2015. Accessed 7/1/2015 http://www.usp.org/store/products-services/usp-compounding-compendium

• USP General Chapter Hazardous Drugs- Handling Healthcare Settings. The United States Pharmacopeial Convention. Official from December 1, 2017. http://www.usp.org/sites/default/files/usp/document/our-work/healthcare-quality-safety/general-chapter-800.pdf. Accessed 10/23/2017

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References

• USP General Chapter Pharmaceutical Compounding- Nonsterile Preperpations Proposed Revisions. The United States Pharmacopia. http://www.usp.org/sites/default/files/usp/document/our-work/compounding/usp-gc-795-proposed-revision.pdf. Accessed 10/23/2018

• Vaida A., Michalek C., McCoy A., Amerine L. Preventing Errors During Sterile Compounding: Taking the Next Steps. Institute for Safe Medication Practices. December 2017.

• Yaniv A. Considerations for Environmental and Personnel Monitoring. Pharmacy Purchasing and Products. November 2010. Accessed 6/21/15 http://www.pppmag.com/article/789/November_2010/Considerations_for_Environmental_and_Personnel_Monitoring/?surface%20sampling

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leblanc - compounding updates · 2019. 7. 10. · 7/10/2019 2 acknowledgements •dr. joann gibbs,...

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