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 Audit Personnel
Processes

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
 Sample localizations:
 Frequency:
- Working area of BSCs and CACIs
- Initially
- Counter Tops (finished preparation)
- At least every 6 months - Areas adjacent to BSCs/ CACIs (Floor)
- Patient administration areas
• If measurable level of BSC: Biological Safety Cabinets
•Contamination: CACI: Compounding Aseptic Containment Isolator
- Identify cause of contamination
- Document Engineering controls improvements
- Contain
- Retraining
• Venting BSCs/CACIs 100% to outside
- Cleaning (high pH soap & water)
• Implement CTSD
- Improving engineering controls
• 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
Choice Of Device Dependant on
eg:Phaseal, ICU Medical 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 CYTOTOXIC DRUG
 Identification of pharmacist/staff in HANDLE WITH CARE
charge
 Contact numbers
ASHP Guidelines on Quality Assurance for Pharmacy Prepared Sterile Products
ASHP: American Society Of Health-System Pharmacists
 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

Improve
Negative
Corrective
Report Actions
Highlight &
Positive
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

Figure 4: Flow chart on the

Printing of cytotoxic drug prescriptions
recruitment and exclusion
of DayCare Oncology
Preparation of worksheet and labeling of cytotoxic Cases
drugs
Verification & confirmation by pharmacists if the dose
or regimen in prescription is ambiguous 3 cases
excluded
Filling of cytotoxic drugs into cytotoxic drug bags

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

44.64
45

40

35

30
Duration (min)

25

20

15

10
7.63
6.28
5
1.97 2.69
1.27
0.09
0

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 ± 14.71 ± 7.28 ± 5.15 ± 3.17 ± 48.02±
10.732 15.617 10.019 6.515 4.691 22.510
Median (min) 1.00 2.00 10.00 3.00 3.00 1.00 45.00
Minimum 0 0 0 0 0 0 0
(min)
Maximum 101 78 103 55 40 30 145
(min)
 Figure 4: Comparison of median of time taken from one
process to another process
50

45.0
45

40

35
Duration (min)

30

25

20
Trolley
15 Collection

10.0
10

5 3.0 3.0
2.0
1.0 1.0
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