QUALITY ASSURANCE & AUDIT Birinder Kaur Senior Pharmacist Pharmacy Dept National University Of Malaysia Medical Centre Kuala Lumpur birin@ppukm.ukm.edu.my
LEARNING OBJECTIVES To define quality assurance and state the importance of implementation in cytotoxic preparation and handling the products. List factors and procedures involved in cytotoxic preparation To ensure that end-product results acceptable quality and the adequacy of staff safety when handling these cytotoxic products To identify relevant references and tools that can be incorporated in your practice
Quality Assurance (QA) Refers to a program for the systematic monitoring and evaluation of the various aspects of a service or facility to ensure that standards of quality are being met. Gives CONFIDENCE in a product.
Quality Assurance (QA) 2 KEY PRINCIPLES Fit for Purpose The product should be suitable for the intended purpose Right First Time Error-free
Why QA is needed? Healthcare Personnel s Perspective Occupational exposure - Dermal contamination - Airborne contamination - Oral contamination Signs and symptoms - Skin rashes - Infertility, miscarriage, birth defects - Leukemia, other cancers
What can Affect Quality? Drug Procedures/ Work Processes Audit Personnel Facilities & Equipment
Factors Involved Policies & Procedures Facilities & Equipment Aseptic Technique& Product Preparation Personnel education, training & evaluation Storage & Handling within the pharmacy Process validation Expiration dating Labeling Documentation End-product evaluation
Policies & Procedures Up to date Available to all involved personnel Should be updated when changes occurs Specific to handling cytotoxic drugs Personnel education & training requirements Preparation technique Process validation Labeling Use & maintenance of facilities & equipment Product acquisition Storage & handling of products & supplies
Policies & Procedures Master formula and worksheets Personnel Garb Describe environmental monitoring devices & techniques such as air velocity, temperature & pressure meters Cleaning materials & disinfecting procedures
Facilities & Equipment
Facilities & Equipment Laminar Airflow/Biohazard Safety Cabinets Laminar Flow Cabinets (LFC)s are not suitable for the preparation of hazardous drugs. Biohazard safety cabinets (BSCs) should be used instead,with a vertical downward airflow exhausting vertically from the cabinet and not towards the operator PIC/S Guide to good practice for preparation of medicinal products in healthcare establishments-april 2008 http://www.picscheme.org/.
Facilities & Equipment Biological Safety Cabinets (BSC) Re-circulation in BSC of air :0/30/70% Running 24h/day:7 day/week Alarm for insufficient exhaust Alarm for insufficient internal flow External exhaust.pressure BSC Validation 6-12 months - DOP - Leak - Air velocity - Smoke -Temp -Microbiology - Noise - KI disk DOP=dioctyl phtalate KI= potassium iodine ISOPP Safe Handling Standards
Facilities & Equipment Pharmaceutical Isolator A containment device which utilises barrier technology to provide an enclosed controlled workspace Positive or negative pressure Running 24h/day:7 day/week Alarm for insufficient exhaust Alarm for insufficient internal flow Double HEPA air filtration (inlet/outlet) Preparation with attached rubber gloves/half suit Validation 6-12 months - DOP -Leak - Air speed - Microbiology PIC/S Guide to good practice for preparation of medicinal products in healthcare establishments-april 2008 http://www.picscheme.org/. ISOPP Safe Handling Standard
Surface Environmental Sampling Recommendation USP<797>2008 Frequency: - Initially - At least every 6 months If measurable level of Contamination: - Identify cause of contamination - Document - Contain - Retraining - Cleaning (high ph soap & water) - Improving engineering controls Sample localizations: - Working area of BSCs and CACIs - Counter Tops (finished preparation) - Areas adjacent to BSCs/ CACIs (Floor) - Patient administration areas BSC: Biological Safety Cabinets CACI: Compounding Aseptic Containment Isolator Engineering controls improvements Venting BSCs/CACIs 100% to outside Implement CTSD Re-assessing type of BSCs /CACIs CTSD= Close System Transfer Device USP United States Pharmacopeia. Pharmaceutical compounding sterile preparations (general chapter 797) in: second supplement to UPS 31-NF 26: 2008
Maintenance of Premise More GMP related but important for the patients safety!! Validation tests for cleanrooms should be performed once a year and pass standards Some parameters: - Grade of room (B or C) and workstation (A) - Air changes/hour: 20 - Pressure difference: 10-15 Pa Tests included: - Particle Count Test - HEPA Filter Patency Test - Temp Test - Humidity Gradient Test - Lighting Level Test - Sound Test - Bacteriological Test GMP= Good Manufacturing Practice Singapore Guidelines for Safe Handling of Cytotoxic Drugs ISOPP Safe Handling Standards
Microbiological Monitoring Premises environmental monitoring cleaning and disinfection People operator broth transfer tests hand cleaning and disinfection
Environmental Control and Monitoring Evaluated by measuring the viable particles in the environment Count reported as colony forming unit (cfu) per cubic metre is a measure of microbial contamination Air sampling carried out at least once a month using an air sampler set for sampling 320 litres for 8 minutes Each sampling exercise must be carried out using two types of agar strips/plates: - TSA for total count at 30 35C for 48 hours - Rose Bengal-Agar for yeast and mould 28 30C for 120hours If counts >1cfu per cubic metre no preparations to be done in that cabinet Remedial actions to be carried out and cause of contamination traced Singapore Guidelines for Safe Handling of Cytotoxic Drugs www.asia4safehandling.org
Personnel Education, Training & Evaluation Basic concepts of cytotoxic reconstitution Written and practical training Clinical, Pharmaceutical & Chemical drug properties Facilities, Equipment & supplies Cytotoxic Reconstitution Documentation ASHP Guidelines on Quality Assurance for Pharmacy Prepared Sterile Products ASHP: American Society Of Health-System Pharmacists
Personnel Education, Training & Evaluation Proper gowning & gloving technique General conduct in the controlled area Principles of GMP Cleanroom design Aware of safety measures on handling CD GMP: Good Manufacturing Practice ASHP Guidelines on Quality Assurance for Pharmacy Prepared Sterile Products ASHP: American Society Of Health-System Pharmacists
Cytotoxic Drug Reconstitution Drug Reconstitution With Needle and Syringe Drug Transfer With Needle and Syringe Chemospike Filter Needles Dispensing Pin Closed System Drug- Transfer Device eg:phaseal, ICU Medical Choice Of Device Dependant on Degree of Safety & Quality of Device ISOPP Safe Handling Standards: Must Be Air Tight & LeakProof
Safety Devices/Terminology Closed system drug transfer device (NIOSH) A device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drugs or vapor concentrations outside the system US ASHP Guideline QA sterile products Closed system = aseptic transfer of sterile nonpyrogenic finished pharmaceuticals (e.g. from vials or ampoules) obtained from licensed manufacturer into sterile final containers NIOSH= National Institute for Occupational Safety and Health, available at www.cdc.gov/niosh
Expiration Dating Should be done on a product by product basis & be based on currently available drug stability information & sterility considerations consider all aspects of sterile product, drug reservoir, drug concentration & storage conditions methods should be documented Should be evidence based with reference ASHP Guidelines on Quality Assurance for Pharmacy Prepared Sterile Products ASHP: American Society Of Health-System Pharmacists
Documentation Training & competency evaluation of employees in sterile product procedures Refrigerator temperatures Certification of cabinets Dispensing records for cytotoxic products Documentation of dose calculations & batch preparation record Worksheet preparation ASHP Guidelines on Quality Assurance for Pharmacy Prepared Sterile Products ASHP: American Society Of Health-System Pharmacists
Labeling Patient name and identification Batch no if batch prepared All solution & ingredient names, amounts,strengths & concentrations Expiration date ( and time when applicable) Volume of regimen, flow rate and route Appropriate auxiliary labeling Storage requirements Identification of pharmacist/staff in charge Contact numbers ASHP Guidelines on Quality Assurance for Pharmacy Prepared Sterile Products ASHP: American Society Of Health-System Pharmacists CYTOTOXIC DRUG HANDLE WITH CARE
End Product Evaluation container leaks container integrity solution cloudiness particulates in the solution appropriate solution colour solution volume when preparation is completed verification that product was reconstituted accurately ASHP Guidelines on Quality Assurance for Pharmacy Prepared Sterile Products ASHP: American Society Of Health-System Pharmacists
Audit Verify the effectiveness of a quality management system Hands-on management tool for achieving continual improvement
Audit Tools Can be developed and tested in cancer centres (with cytotoxic drug preparation service) Can be used to assess current procedures complies to established standards Areas to look into: - microbiological testing of facility (air sampling every month) - checking procedures ( drug and dosage errors) - facility maintenance ( cabinets and cleanrooms every 6 months) - staff validation - safety measures among staff ( nurses, pharmacists)
ISOPP Audit Tool
Audit Report Negative Positive Improve Corrective Actions Highlight & Share
Audit on Work Process to Complete Prescription Orders In CDR Unit 1. Chemotherapy prescriptions from Daycare Oncology ward from Sept 2011 to Nov 2011 2. Parenteral chemotherapy prescriptions which require preparation in clean room 3. Prescriptions received during office hours on weekdays (Mon-Fri)
Receive indent from doctors in ward Printing of cytotoxic drug prescription Preparation of worksheet and labelling of cytotoxic drugs Verification & confirmation by pharmacist if the dose or regimen in prescription is ambiguous Filling of cytotoxic drugs into cytotoxic drug bags Preparation of cytotoxic drugs in clean room Dispensing of cytotoxic products on trolley Collection by staff nurse from wards Fig1: Summary of the processes involved from prescription indenting in the Pharmacy system to completion of chemotherapy prescription order
September November 2011 All Daycare Oncology cases were evaluated (N=218) Receive indent from doctors in ward Printing of cytotoxic drug prescriptions Preparation of worksheet and labeling of cytotoxic drugs Verification & confirmation by pharmacists if the dose or regimen in prescription is ambiguous Filling of cytotoxic drugs into cytotoxic drug bags Figure 4: Flow chart on the recruitment and exclusion of DayCare Oncology Cases 3 cases excluded Preparation of cytotoxic drugs in clean room 9 cases excluded Dispensing of cytotoxic products on trolley Collection by staff nurse from wards Only 206 cases were analyzed in the study 32
50 45 44.64 40 35 Duration (min) 30 25 20 15 10 6.28 7.63 5 0 1.27 1.97 2.69 0.09 Tindent Tprint Twsheet Tverify Tfilling Tprepare Tdispense Figure 3: Comparison of mean of time taken for each process
Table 2: Time taken from one process to another process Indent Worksheet Filling Dispense 1 2 3 4 5 6 7 8 Print Verify Prep Collect 1to 2 2to3 3to4 4to5 5to6 6to7 7to8 n 206 206 206 206 206 206 206 Mean (min) 2.97 ± 1.00 6.30 ± 10.732 14.71 ± 15.617 7.28 ± 10.019 5.15 ± 6.515 3.17 ± 4.691 48.02± 22.510 Median (min) 1.00 2.00 10.00 3.00 3.00 1.00 45.00 Minimum (min) Maximum (min) 0 0 0 0 0 0 0 101 78 103 55 40 30 145
50 45 Figure 4: Comparison of median of time taken from one process to another process 45.0 40 Duration (min) 35 30 25 20 15 Trolley Collection 10 10.0 5 0 3.0 3.0 2.0 1.0 1.0 1-->2 2-->3 3-->4 4-->5 5-->6 6-->7 7-->8
Findings of the Audit: 1. Time of preparation Only one technician reconstituting drugs. Drug reconstitution is a highly skilled procedure. Requires full concentration to prevent errors. 2. Time of filling NF drugs (purchase from kedai farmasi) 3. Time of worksheet >1 cytotoxic drugs per patient Change of dose by prescriber, time taken to redo worksheet 4. Trolley to Collection Delay of collection from ward staff Only one PK involved in collection 5. Worksheet to Verify Only one CDR pharmacist to verify all worksheets Error in labeling done by inexperienced personnel (student & PRP)
Conclusion - The pharmacy should have written policies and procedures which is - available to all personnel involved in cytotoxic drug preparation - important for personnel to understand before being allowed to prepare cytotoxic preparations - allows personnel competency to be assessed periodically - ISOPP Standard of Practice for Safe Handling of Cytotoxic Agents is a powerful instrument because of its global acceptance and distribution. - The audit tool completes the standards and helps the hospital to evaluate and progress.
References: ASHP: ASHP technical assistance bulletin on quality assurance for pharmacy - prepared sterile products:am J Hosp Pharm. 1993; 50:2386-98 Brier K Leo. Evaluating aseptic technique of pharmacy personnel. Am J Hosp Pharm. 1983;40:400-3 Buchanan E. Clyde, et al. Principles of sterile product preparation. Bethesda, MD: American Society of Health-System Pharmacists, 1995 National Institute for Occupational Safety and Health, available at www.cdc.gov/niosh USP United States Pharmacopeia. Pharmaceutical compounding sterile preparations (general chapter 797) in: second supplement to UPS 31-NF 26: 2008