15-A Prescription for Infection Prevention Rounding in the.ppt

A PRESCRIPTION FOR INFECTION PREVENTION ROUNDING IN THE

PHARMACY

EVELYN COOK

Thanks and acknowledgement to Pamela Isaacs for the content and slides in this presentation.

OBJECTIVES:

1. Discuss recent outbreaks related to medication contamination and practice breaches associated with them.

2. Identify similarities and differences in state and national pharmacy practice guidelines

3. List specific items to include in Infection Prevention rounds in their pharmacy

Then & Now

OUTBREAKS

Serratia marcescens – betamethasone 2001

Esophiala – steroid injectables 2002

Serratia marcescens – TPN 2011

Bacterial & Fungal – betamethasone, cardioplegia and

triamcinolone injectables 2013

SERRATIA MARCESCENS INFECTION FROM MPA INJECTION (2001)

11 patients identified with S. marcescens infections 4 patients initiated investigation Facilities involved include

Community Pharmacy Ambulatory Surgery Center

Final outcome: Meningitis – 5 patients, 3 deaths Epidural abscesses – 5 patients Hip infection – 1 patient

S. marcescens recovered from cx of medication vials, stock solution, pharmacy surfaces, multiple parenteral materials at ASC.

Deficiencies found at Compounding Pharmacy Inadequate autoclaving temperatures Failure to perform terminal sterilization

Clin. Infect Dis. 2006 Oct 1;43(7):831-7 Epub 2006 Aug 22

EXOPHIALA INFECTIONS FROM CONTAMINATED INJECTABLE STEROIDS (2002)

5 cases investigated for fungal infection after receiving epidural injections for pain management77yo female, chronic lower back pain

MPA injections 100 & 35 days pta

CSF + for Exophiala dermatitidis

51 day LOS, died

61yo female, chronic lower back pain MPA injections 84 & 34 days pta


70 day LOS, survived

MMWR Dec 13, 2002/51(49);1109-1112

EXOPHIALA INFECTIONS FROM CONTAMINATED INJECTABLE STEROIDS (CONT)

71 yo female, chronic lower back pain MPA injections 82, 55 & 35 days pta


Unknown outcome

65yo female, chronic lower back pain MPA injections 116 days pta


Unknown outcome

52yo female, chronic lower back pain MPA injections 152& 103 days pta


Unknown outcome

MMWR Dec 13, 2002/51(49);1109-1112

EXOPHIALA INFECTIONS FROM CONTAMINATED INJECTABLE STEROIDS (CONT)

Pharmacy findings One pharmacy involved

Supplies 5 states with MPA

Inspection findings

Improper performance of autoclave

No written policies, SOP

Lack of testing for sterility

Lack of monitoring of quality indicators

Inadequate clean room policies

CDC cultures + for 3 lots of MPA

MMWR Dec 13, 2002/51(49);1109-1112

SERRATIA MARCESCENS INFECTION ASSOCIATED WITH TPN (2011)

Six hospital outbreak

To date 19 cases bacteremia Age range 38 ‐94 years of age

11 of 19 cases died

Compounding Pharmacy deficiencies Tap water used to clean equipment

Amino Acid filter/sterilization process suboptimal

Inadequate sterility testing of compounded product

Compound machine tubing not changed q 24 hrs.

Serratia cx from: Tap water, AA powder, Carboy, Impellor and TPN bags

www.infectioncontroltoday.com, www.adph.org/epi/assets/Serratia_Outbreak_Investigation_05042011.pdf

BACTERIAL & FUNGAL INFECTIONS FROM INJECTABLE STEROIDS

Largest reported outbreak June, 2013

745 confirmed infections

58 deaths

One New England Pharmacy

MPA ‐ > 17,000 vials (3 lots)

>13,000 people received

www.infectioncontroltoday.com, www.cdc.gov/medicationsafety/recalls/necc

BACTERIAL & FUNGAL INFECTIONS FROM INJECTABLE STEROIDS (CONT)

Compounding Pharmacy Deficiencies found:Release of product prior to results of sterility testingSterility testing techniques suboptimal

Autoclaving practices suboptimal Sterility procedure

Equipment testing and maintenance

Powder hoods cleaning insufficient

Inadequate protection of clean room from outside debris

Standing water from boiler with floor and wall intrusion

Visible particulates found in medication vialswww.infectioncontroltoday.com,

www.cdc.gov/medicationsafety/recalls/necc

OUTBREAKS NOT JUST THERE AND THEN…. THEY ARE OCCURING NOW

AND HERE TOO!

Bacterial & Fungal contaminated MPA injectionsMay 22, 2013

Two pts w soft tissue abscesses One clinic MPA injections Steroid compounded at Newbern, TN pharmacy. 5 similar cases in Illinois the month prior (April)

July 25,2013 81 facilities, 15 states (including NC) 26 pt with soft tissue abscesses (at injection site) 1,045 pts contacted in NC

FDA identified both bacterial and fungal contamination in recalled MPA from the TN pharmacy

http://www.fda.gov/Drugs/DrugSafety/ucm355575.htm

COMPOUNDED MEDICATIONS

COMPOUNDED MEDICATION

Bulk Medications/Non‐InjectablesOrals

Solids

Liquids

Topical Creams, Ointments & Powders

Compounding/repackagingHand Hygiene

Gloves (when working with orals)

Clean work surface prior to batching

Label – to include product name, concentration, volume, beyond use date (based on manufacturer), initials

COMPOUNDED MEDICATION (CONT)

Injectables (sterile) Best Practice is purchase in most Ready‐to‐Use state.

Issues that affect this are:

Feasibility

Cost effectivenessOphthalmic medications ‐ Same practice as Injectables

Irrigation solutions ‐ Same practice as Injectables

TPN, Epidurals – same practice as Injectables

COMPOUNDED MEDICATION (CONT)

Injectables (sterile)

Preparing/Reconstituting Hand Hygiene

Don gown & gloves

All work done under LAFH (laminar airflow hood)

Vial & bag ports to be cleaned with alcohol after removing manufacturer’s protective cap and allow to dry before entering.

All syringes used during process are single use

Filtered needle used when drawing out of ampoule, needle changed before injecting med into container/solution

Seal is placed on finished medication port prior to removal from LAFH

LAMINAR AIR FLOW HOOD (LAFH)

Filtered air uniformly supplied in one direction at a fixed velocity in parallel streams (generally recirculated)

Should remain on 24/7/365

If turned off, should be turned on at least 30 min prior to beginning an aseptic batch

Scheduled cleaning – Work surface and interior prior to each batch and at end of day

with sterile isopropyl alcohol

Cleaning log must be maintained

What is your organizations PM Schedule?? Pre‐filter visual inspection, air exchanges

Inspection Service qualification

Adequate functioning

HEPA filter

LAMINAR AIR FLOW HOOD (LAFH)

Product placement in hood Do not place in front of or on top of vent (airflow obstruction)

All work items to be at least 6 inches from outer edge of hood and 2 inches from other objects under hood

Only ONE batch of medication to be handled under LAFH at any time.

VERTICAL LAFH

HORIZONTAL LAFH

CLEAN ROOMS

Standard requirements ISO 5

ISO – International Standards Organization

ACR + FFU + Airflow Velocity(air change rate)+(Filter/Fan units)+Speed

CLEAN ROOMS (CONT)ACR – air change rate

Home = 0.5 to 2 times/hr

Clean room = 10 to 600 times/hr (determined by ISO Class)

Affected by External contaminants (trying to get into room)

Internal contaminants

Equipment (cleanliness/volume)

Staffing (garbing effectiveness/access frequency)

Operations

A range for ACR is acceptable to meet needs of “at rest” and operational needs

CLEAN ROOMS (CONT)

FFU – Filter/Fan Units

– Ceiling HEPA filtered fans required to remove contaminated air

– Speed of removal determined by ISO class

CLEAN ROOMS (CONT)

Airflow Velocity – speed of filtered air moving through a clean room. Positive Pressure – greatest from clean to dirty

Clean Room Activity & Attire

Clean Room Activity & Attire

Sources of Contamination during Aseptic Activities

Aseptic processing: A review of current industry practice. Agalloco J, Akers J, Madsen R. Pharmaceutical Technology. 2004;28(10, Oct):128

UNITED STATES PHARMACOPEIA (USP) STANDARDS

USP 17 Prescription Container Labeling

USP 795 – Compounding Non‐Sterile Preparations

USP 797 – Compounding Sterile Preparations

USP 71 – Sterility Testing

USP 797 COMPOUNDING STERILE PREPARATIONS (CAPS)

Provides guidance on Mixing, Diluting, Reconstituting to prevent: Microbial contamination

Excessive bacterial endotoxins

Variability in the intended strength of correct ingredients

Unintended chemical & physical contaminants

Ingredients of inappropriate quality


Guidance on Staff proficiencies Aseptic technique in med prep

Hand cleaning

Don/Doffing of PPE

Evaluate by

Testing

Observation

Fingertip sampling

Media fills


Guidance for Monitoring the work environment Temperature

Humidity

Lighting

Air flow, pressures, filtration


Responsibilities of the Supervisor (Qualified licensed healthcare professional) Personnel training, performance, documentation thereof Ingredients quality, purity, identity

Storage of open/partially used containers

Sterilization w/in 6 hrs of nonsterile CSPs

Proper & adequate sterilization practices

Appropriate packaging for sterility & stability

Compounding environment maintains sterility or purity of items

Labels appropriate & complete

Correct compounding procedures are used

USP 797 COMPOUNDING STERILE PREPARATIONS Includes Exemptions and Exceptions of Clean Room requirements Immediate use exemption (OR, ER, Card. Cath, RT)

Pharmacy Satellites & Outpt Treatment Cntrs

Low risk preps allowed without anteroom or segregated compounding areas

“The use of technologies, techniques,

materials or procedures other than those

described in this chapter is not prohibited

so long as they have been proven to be

equivalent or superior with statistical

significance to those described”

USP 797 CONTAMINATION RISK LEVELS FOR CSPS(COMPOUNDED STERILE PREPARATIONS)

Immediate Use

Low Risk

Low Risk within 12 hrs or less of BUD (beyond use date)

Medium Risk

High Risk

USP 797 CONTAMINATION RISK LEVELS FOR CSPS

Immediate use CSP Emergency situation or one where pt would have additional risk if therapy

delayed

No storage/batching

Does not include medium & high risk level CSPs

Can be exempt from ISO 5 conditions

Compounding process < 1hr

Aseptic technique

Admin within 60 min prep


Low Risk level CSP Sterile commercial drug compounded using sterile device

ISO 5 environment within ISO 7 buffer area

Limited # products, transfers and

manipulations that can occur

Garbing and visual inspection release

check procedures must be followed

Annual media‐fill and other competencies

for staff


Low Risk level within 12h or less BUD (beyond use date)

All Low Risk Level CSP criteria met

ISO 5 environment but does not require ISO 7 buffer area

Pt specific prescription

Administer w/in 12 hrs of prep

Segregated area but not isolated

Away from sink area


Medium Risk Level Multiple sterile commercial products for multiple pts or one pt multiple

times

Complex aseptic manipulations (i.e. TPN)

Compounding procedure – prolonged time

No bacteriostatic agents added to prep

Environment and Quality testing same

as low risk

Annual evaluation of personnel


High Risk LevelPrepared from NON sterile ingredients or with non sterile device

Prepared with sterile ingredients in ISO 5 within ISO 7 buffer area.

Proper garb & glove personnel

Purity and content strength must be verified

Requires semi‐annual media‐fill evaluation

of personnel

Requires simulation of high‐risk level

compounding using dry non‐sterile media by

personnel.

High Risk Level FAILURESPrepared with sterile ingredients but exposed to < ISO 5 for > 1hr.

Improper garb & glove personnel

> 6 hr delay from compounding to sterilization of water‐containing product

Purity and content strength not verified

No semi‐annual media‐fill evaluation

of personnel

No simulation of high‐risk level

compounding using dry non‐sterile media by

personnel.


STANDARDS AND GUIDELINES

What is required?

What is recommended?

STANDARDS HISTORY1906 ‐ the official standards for drugs in the US

Food & Drugs Act (The Wiley Act) AN ACT For preventing the manufacture, sale, or transportation of

adulterated or misbranded or poisonous or deleterious foods, drugs, medicines, and liquors, and for regulating traffic therein, and for other purposes.

USP To improve global health through public standards and related

programs that help ensure the quality, safety, and benefit of medicines and foods.

1938 ‐ Federal Food, Drug & Cosmetics (FD&C) Act is established as a revision of 1906 Act standards of strength, quality, purity, packaging, and labeling

FDA responsible for enforcement of FD&C Act

The ASHP Discussion Guide on USP Chapter 797, American Society of Health System Pharmacists (1-22)

FDA COMPLIANCE POLICY GUIDESFDA Modernization Act 1997

Compounded drug products by pharmacist/physician on customized basis for individual patients. Protected pharmacy from

Adulterization of medication

Misbranding

New drug provision

Concerns that ensued: Compounding in anticipation of prescription

Receiving products from non FDA registered facilities

Using non industry equipment for compounding

Compounding commercially available medications

FDA Compliance Policy Guides CPG Sec.40.200 Pharmacy Compounding (Reissued 05/29/2002)

STANDARDS HISTORY (CONT)

July 1, 2004 TJC used USP Chapter 797 to survey health system pharmacies

2006 TJC no longer required implementation of USP 797 as a condition of accreditation.

TJC “will expect to see structures and processes that ensure safe practices for compounding sterile medication”


THE JOINT COMMISSIONHOSPITAL ACCREDITATION

Medication Management Chapter Twenty Standards

MM.05.01.07 The hospital safely prepares medications

All compounded sterile preps done by Pharmacist except in emergent/urgent/life threatening situations

Prep areas clean, neat, uncluttered, separated areas that prevent contamination

THE JOINT COMMISSIONHOSPITAL ACCREDITATION

MM.05.01.07 (cont) The hospital safely prepares medications

Visual inspection for particulates/discoloration

ISO Class 5 or LAFH for sterile IV preps not used within 24 hrs.

Prescription required for all preparations released for patient care

Radiopharmaceutical preps are done by trained registered Pharmacist

STANDARDS HISTORY

The National Assoc. of Boards of Pharmacy (NABP) supports USP 797 chapter incorporating it into its Model State Pharmacy Act and Model Rules

Enforced to the extent they are adopted by individual states


STANDARDS HISTORY (CONT)

The Pharmacy Compounding Accreditation Board (PCAB)

Voluntary system of standards for compounding pharmacies


NORTH CAROLINA BOARD OF PHARMACY (NCBOP)

21NCAC46.2803

Req/Pharmacies dispensing sterile pharmaceuticalsDesignated area – isolated and restricted from rest of pharmacy

Restricted personnel

Used only for prep of specialty products

Size sufficient for clean room, equipment & supply storage

ISO 5 category


21NCAC46.2804

Responsibility of Pharmacy Manager Knowledgeable of pharmacy practices

Current Policy & Procedures

Staff Training

QA Projects

Appropriate disposal of waste/drugs


21NCAC46.2808 Quality Assurance

Personnel performance

Equipment performance

Facility performance

Finished product oversight Microbial contamination testing

Recall procedure

Storage/dating procedure

Logs Refrigerator/freezer

Maintenance (cleaning) of LAFH and/or clean room

Filter inspections and replacements

North Carolina Board of Pharmacy (NCBOP)

Response to Recent Sterility Issues

NCBOP REPORT & RECOMMENDATIONS

Pharmacy Compounding Work Group, April 16, 2013 Identification of pharmacy as sterile compounding facility and risk

category of compounding

High (non sterile to sterile)

Medium (complex sterile to sterile)

Low (sterile to sterile)

“Office Use” clause clarification to reduce manufacturing of products commercially available


Incorporate and enforce USP 795 and 797 standards

Offered no recommendations on how to enforce

Encourage but not require accreditation from NCBOP approved accrediting body

Update existing inspection and investigation policies of the NCBOP to comply with USP standards. Also provide training of new policies and procedures to investigators (Investigations occur usually only with complaints/requests)

Require out of state pharmacies to hold NC permit and/or comply with USP standards

Need to determine how to monitor this.

Encourage pharmacists to obtain CE for compounding. NCBOP should identify/develop accredited training for compounding.


WHAT TYPE OF COMPOUNDING IS DONE IN YOUR PHARMACY?

ISO Class 5 Clean room Or LAFH

ISO Class 5 Clean roomOr LAFH

Designated work area away from other activity

Storage area

WHAT YOU NEED TO DO TO ENSURE THE SAFETY OF COMPOUNDING?

WHAT YOU DO?

IP ROUNDS IN ISO CLASS 5 CLEAN ROOMDaily cleaning tasks

Use disinfectant or sterile 70% IPA, lint free wipe

Clean all counters and work surfaces, air dry

Clean all bins and products on shelves, counters

Mop floors (mop labeled “floors only”) starting with corner opposite of egress. Carts moved as needed to clean

May us microfiber cloth in place of mop

Clean all work stations at beginning & end of each shift (walls, IV Bar, machinery & work surface) as well as after every batch

Ante room Clean sink

All contact surfaces

Mop floor or use microfiber starting at clean room and work to egress

United States Pharmacopeial Convention, June 1, 2008. (797) Pharmaceutical Compounding Appendix V

IP ROUNDS IN ISO CLASS 5 CLEAN ROOMMonthly cleaning tasks – designated day

Use disinfectant or sterile 70% IPA, lint free wipe

Clean all buffer area and ante room ceilings, walls, storage shelving counters and work surfaces, air dry

Then clean the compounding area as the buffer/ante room above

Clean all bins and products on shelves, counters

Mop floors (mop labeled “floors only”) starting with corner opposite of egress. Carts moved as needed to clean

May us microfiber cloth in place of mop

Clean all under shelving of work stations, chairs, and carts starting at top and working to wheels

Clean interior/exterior of trash cans

Documentation of cleaning date and initials should be logged.


IP ROUNDS IN ISO CLASS 5 CLEAN ROOM SAMPLING

Personnel Glove Fingertip Sampling Done immediately after hand hygiene and garbing procedure. May not

disinfect with IPA prior to sampling.

Both hands, all 10 digits on agar plate

Pass = zero cfu

no less than 3x before being allowed to compound CSPs

At least annually for low & medium risk CSPs

Semi‐annual for high risk level CSPs

United States Pharmacopeial Convention, June 1, 2008. (797) Pharmaceutical Compounding Appendix I

IP ROUNDS IN ISO CLASS 5 CLEAN ROOM SAMPLING

Surface Sampling Required for all ISO 5 areas “periodic basis”

Contact plates

Swabs

Locations should be pre‐defined by pharmacy

United States Pharmacopeial Convention, June 1, 2008. (797) Pharmaceutical Compounding Appendix I

IP ROUNDS IN CLEAN ROOM WITH LAFH

Daily cleaning tasks Use disinfectant or sterile 70% IPA, lint free wipe

Clean all counters & work surfaces, air dry

Clean all LAFH work stations at beginning & end of each shift (walls, IV Bar, machinery & work surface) as well as after every batch


IP ROUNDS IN COMPOUNDING PHARMACYCompounding Personnel Demonstration (at least annually)

Verify the pharmacy has a QA process and are following it with all personnel

Garbing

Hand hygiene

Work Station preparation

Compounding Skills Assessment

Should be consistent with level of compounding performed by staff

Work station clean up

Sharps and solution management

Labeling of product at workstation

Clean all counters and work surfaces, air dry

Clean all work stations at beginning & end of each shift (walls, IV Bar, machinery & work surface) & after every batch

United States Pharmacopeial Convention, June 1, 2008. (797) Pharmaceutical Compounding Appendix IV

IP ROUNDS IN PHARMACY PPE DONNINGKnow appropriate sequence for garbing and hand hygiene

No cosmetics or jewelry

Shoe covers

Beard cover

Head cover – no hair exposedFace mask – nose to chin

Hand (and forearm) Hygiene with soap/water x 30 sec

Dries with lint free towel

Gown

Disinfect hands with waterless surgical hand scrub, air dry

Sterile gloves

United States Pharmacopeial Convention, June 1, 2008. (797) Pharmaceutical Compounding Appendix III

IP ROUNDS IN PHARMACY

Remember:

It IS appropriate for compounding staff to clean their gloved

hands with 70% Isopropyl Alcohol frequently while working in the ISO 5 environment.


IP ROUNDS IN PHARMACY

NC BOP Inspection Forms can be found at:

www.ncbop.org/resourcesfornewpermitholders.htm


WHAT DO YOU SEE?

IS YOUR PHARMACY SAFE?

Documents

15-A Prescription for Infection Prevention Rounding in the.ppt