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

Transcription

1 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.

2 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

3 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 Oct 1;43(7):831-7 Epub 2006 Aug 22

4 EXOPHIALA INFECTIONS FROM CONTAMINATED INJECTABLE STEROIDS (2002) 5 cases investigated for fungal infection after receiving epidural injections for pain management 77yo 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 CSF + for Exophiala dermatitidis 70 day LOS, survived MMWR Dec 13, 2002/51(49); EXOPHIALA INFECTIONS FROM CONTAMINATED INJECTABLE STEROIDS (CONT) 71 yo female, chronic lower back pain MPA injections 82, 55 & 35 days pta CSF + for Exophiala dermatitidis Unknown outcome 65yo female, chronic lower back pain MPA injections 116 days pta CSF + for Exophiala dermatitidis Unknown outcome 52yo female, chronic lower back pain MPA injections 152& 103 days pta CSF + for Exophiala dermatitidis Unknown outcome MMWR Dec 13, 2002/51(49);

5 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); SERRATIA MARCESCENS INFECTION ASSOCIATED WITH TPN (2011) Six hospital outbreak To date 19 cases bacteremia Age range 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

6 BACTERIAL & FUNGAL INFECTIONS FROM INJECTABLE STEROIDS Largest reported outbreak June, confirmed infections 58 deaths One New England Pharmacy MPA > 17,000 vials (3 lots) >13,000 people received BACTERIAL & FUNGAL INFECTIONS FROM INJECTABLE STEROIDS (CONT) Compounding Pharmacy Deficiencies found: Release of product prior to results of sterility testing Sterility 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 vials

7 OUTBREAKS NOT JUST THERE AND THEN. THEY ARE OCCURING NOW AND HERE TOO! Bacterial & Fungal contaminated MPA injections May 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, 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 COMPOUNDED MEDICATIONS

8 COMPOUNDED MEDICATION Bulk Medications/Non Injectables Orals Solids Liquids Topical Creams, Ointments & Powders Compounding/repackaging Hand 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

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11 COMPOUNDED MEDICATION (CONT) Injectables (sterile) Best Practice is purchase in most Ready to Use state. Issues that affect this are: Feasibility Cost effectiveness Ophthalmic medications Same practice as Injectables Irrigation solutions Same practice as Injectables TPN, Epidurals same practice as Injectables

12 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

13 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

14 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

15 HORIZONTAL LAFH CLEAN ROOMS Standard requirements ISO 5 ISO International Standards Organization ACR + FFU + Airflow Velocity (air change rate)+(filter/fan units)+speed

16 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

17 CLEAN ROOMS (CONT) Airflow Velocity speed of filtered air moving through a clean room. Positive Pressure greatest from clean to dirty

18 Clean Room Activity & Attire

19 Clean Room Activity & Attire

20 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

21 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 USP 797 COMPOUNDING STERILE PREPARATIONS (CAPS) Guidance on Staff proficiencies Aseptic technique in med prep Hand cleaning Don/Doffing of PPE Evaluate by Testing Observation Fingertip sampling Media fills

22 USP 797 COMPOUNDING STERILE PREPARATIONS (CAPS) Guidance for Monitoring the work environment Temperature Humidity Lighting Air flow, pressures, filtration USP 797 COMPOUNDING STERILE PREPARATIONS (CAPS) 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

23 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

24 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 USP 797 CONTAMINATION RISK LEVELS FOR CSPS 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

25 USP 797 CONTAMINATION RISK LEVELS FOR CSPS 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 USP 797 CONTAMINATION RISK LEVELS FOR CSPS 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

26 USP 797 CONTAMINATION RISK LEVELS FOR CSPS High Risk Level Prepared 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. USP 797 CONTAMINATION RISK LEVELS FOR CSPS High Risk Level FAILURES Prepared with sterile ingredients but exposed to < ISO 5 for > 1hr. Improper garb & glove personnel > 6 hr delay from compounding to sterilization of watercontaining 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.

27 STANDARDS AND GUIDELINES What is required? What is recommended?

28 STANDARDS HISTORY 1906 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 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 GUIDES FDA 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 Pharmacy Compounding (Reissued 05/29/2002)

29 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 ASHP Discussion Guide on USP Chapter 797, American Society of Health System Pharmacists (1-22) THE JOINT COMMISSION HOSPITAL ACCREDITATION Medication Management Chapter Twenty Standards MM 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

30 MM (cont) THE JOINT COMMISSION HOSPITAL ACCREDITATION 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 The ASHP Discussion Guide on USP Chapter 797, American Society of Health System Pharmacists (1-22)

31 STANDARDS HISTORY (CONT) The Pharmacy Compounding Accreditation Board (PCAB) Voluntary system of standards for compounding pharmacies The ASHP Discussion Guide on USP Chapter 797, American Society of Health System Pharmacists (1-22) NORTH CAROLINA BOARD OF PHARMACY (NCBOP) 21NCAC Req/Pharmacies dispensing sterile pharmaceuticals Designated 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

32 NORTH CAROLINA BOARD OF PHARMACY (NCBOP) 21NCAC Responsibility of Pharmacy Manager Knowledgeable of pharmacy practices Current Policy & Procedures Staff Training QA Projects Appropriate disposal of waste/drugs NORTH CAROLINA BOARD OF PHARMACY (NCBOP) 21NCAC 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

33 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

34 NCBOP REPORT & RECOMMENDATIONS 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) NCBOP REPORT & RECOMMENDATIONS 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.

35 WHAT TYPE OF COMPOUNDING IS DONE IN YOUR PHARMACY? ISO Class 5 Clean room Or LAFH ISO Class 5 Clean room Or LAFH Designated work area away from other activity Storage area

36 WHAT YOU NEED TO DO TO ENSURE THE SAFETY OF COMPOUNDING? WHAT YOU DO? IP ROUNDS IN ISO CLASS 5 CLEAN ROOM Daily 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, (797) Pharmaceutical Compounding Appendix V

37 IP ROUNDS IN ISO CLASS 5 CLEAN ROOM Monthly 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. United States Pharmacopeial Convention, June 1, (797) Pharmaceutical Compounding Appendix V 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, (797) Pharmaceutical Compounding Appendix I

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

39 IP ROUNDS IN COMPOUNDING PHARMACY Compounding 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, (797) Pharmaceutical Compounding Appendix IV IP ROUNDS IN PHARMACY PPE DONNING Know appropriate sequence for garbing and hand hygiene No cosmetics or jewelry Shoe covers Beard cover Head cover no hair exposed Face 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, (797) Pharmaceutical Compounding Appendix III

40 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. United States Pharmacopeial Convention, June 1, (797) Pharmaceutical Compounding Appendix III IP ROUNDS IN PHARMACY NC BOP Inspection Forms can be found at: United States Pharmacopeial Convention, June 1, (797) Pharmaceutical Compounding Appendix III

41 WHAT DO YOU SEE?

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46 IS YOUR PHARMACY SAFE?

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