Quality Management in the IVF Laboratory

Quality Management in
the IVF Laboratory
By
Raj Joshi
Manager of IVF
Reproductive Medicine Unit
Objectives
Understand:
 What is quality?
Components of a Quality Management
System (QMS)
How useful is it in an IVF lab?
Risk managment
Quality Managementintroduction
The definition of quality is:
– a standard or grade of something
– excellence referring to the highest or finest
standard
International
Organisation
for
standardisation (ISO) defines quality as:
“Degree to which a set of inherent
characteristics fulfils requirements”.
Quality Managementintroduction
The introduction of the European Union
Tissue Directive (EUTD) in 2006 led to all
European IVF centres implementing a
mandatory QMS.
QMS is also mandatory for clinical IVF
practice in Australia.
Quality Managementintroduction
QMS ensures that an organisation delivers
a product meeting customer requisites
and
improves
their
satisfaction
consistently.
The
world
leader
in
standards
development is the ISO.
ISO 9001:2008 is the most common QMS
certification for IVF units
Quality Managementintroduction
 QMS covers the whole organisation:
Management structure
Training and Standard Operating
Procedures (SOPs) for all practices
Manuals (reference)
Forms
Monitoring of equipment
Audit
Basic principle of QMS
Plan
Improve
Act
Evaluate
Quality Managementintroduction
 facilitates:
Repeatability
Traceability
Accuracy of results
provides an auditable system
Quality Managementintroduction
QMS encompasses:
 quality assurance (QA)
 quality control (QC)
 quality improvement (QI)
Quality Assurance
 Comprehensive method for monitoring and
evaluating the entire process
 Focuses on all activities and system
processes
 Standard operating procedures (SOPs) for
every procedure performed
 All documents to be version controlled and
reviewed annually
 Includes all QC processes
Quality Control
Encompasses all activities ensuring that
procedures and equipment function efficiently
Allows :
Uniformity
Standardisation
Monitoring:
Environment; temperature: light; humidity
Accuracy of equipment by validation
Patient satisfaction
Consistent performance
Safety program
Corrective actions to allow conformance
Quality Control
 Define the processes: establish referenced SOPs
 Set safe conditions: record all non-conformities
 Define operational parameters for laboratory
 Monitoring of:
Environment: temperature (incubators &
surfaces); humidity; air quality; light intensity
Equipment (Incubators, fridges, hotplates)
Set upper and lower limits for:
Temperature
Gas levels
Quality Improvement
Methodological enhancement of process with
the aim to improve outcome
Increase the effectiveness and efficiency
Goal is to satisfy requirements and improve
the outcome and patient experience
How useful is quality
in an IVF Lab
The IVF laboratory is a crucial part of all IVF
Units as it is where the embryos are created
It has a high number of variables that need to
be monitored and controlled
QC should run concurrently with all laboratory
activities
QI should enhance all laboratory performance
Errors should be detected and corrected by
periodical assessment and audit
How useful is quality
in an IVF Lab
Laboratory environment
Air quality
Temperature
Humidity
Lighting
Equipment
Consumables
Staffing
Audit
Laboratory Environment
 Air Quality: positive pressure in lab
 EUTD states requirements of Grade A in critical work
areas; Grade D in background. HFEA allows for grade C
in critical work areas and grade D in background
 Class II hoods: it protects the sample and the operator
 Air filtration:
 HEPA; Carbon; Coda Towers; Zander Air Filtration systems
 Particle counting (<0.5 particles/feet3 for a clean room)
 Volatile Organic Compounds (VOC) are toxic agents and
need monitoring as will adversely affect gametes and
embryos
 VOCs released by new equipment; plastics; cleaning
agents; paints; sealants; felt pens; perfumes (alcohol
based); ethylene oxide (sterilising agent).
Air filtration
Portable
Fitted to air conditioning
unit (HVAC)
Laboratory Environment
Temperature: Incubators; hotplates; warmers
Temperature fluctuations will disrupt the
meiotic spindle
< 330C :
embryo metabolism slowed; delayed development
Gamete / embryo organelles altered
Spindle depolymerisation within 10 minutes
>380C:
spindle disruption; spindle microtubule
disorganisation
Increase in embryo mortality
Humidity and Light
 Humidity reduces the evaporation of water from
media in the incubator thus maintaining pH and
osmolality
 The laboratory has to be 30-60% relative
humidity to prevent static charges
 Lighting has to be incandescent with UV
protectors over fluorescent tubes as fluorescent
light causes formation of toxic products in media
 Light wavelength has to be >500nm to prevent
harm to gametes and embryos
 Use of green filters minimises the harmful effects
Equipment
 The lab must have all the necessary equipment for best service
 All user manuals should be available in lab
 Validation SOPs must exist before equipment first used
 All must be labelled with unique identifier; date of last and
next service
 All must be validated using calibrated instrumentation (usually
on installation) e.g. temperature and gas levels
 All critical equipment must be monitored daily or weekly;
connected to an alarm system that will autodial users out of
hours if any problems encountered
 All critical equipment must be on uninterrupted power supply
(UPS) or come fitted with battery back-up should the power
fail
 Maintainence and service must be periodically performed and
records kept for future reference
Incubators
Larger ones maintain temperature
for longer as have double doors or
individual inner doors
Benchtops have a rapid recovery of
temperature and gas
The air quality inside the incubator
is important too
The gas supplying the incubators
needs filtration
Equipment
 The incubators will need to be validated for
temperature and gas levels so the reading on the
display is the actual reading
 Hotplates and warmers will need to be validated for
temperature
 This can be accomplished using calibrated meters
and should be performed during the installation by
the engineer.
 The engineer should be able to supply a calibration
certificate for that meter for your reference.
Temperature and Gas
monitoring
Consumables
All should be CE marked (European Confirmation)
and for IVF use only
All plasticware that is used for gamete and
embryo manipulation should be mouse embryo
assay (MEA) tested
Perform sperm survival testing as an in-house QC
Record all batch numbers and keep all certificates
of analysis for future reference
Consumables
Consumables
All media and oil must have a high degree of
temperature control
Transport must be refridgerated and storage in
a monitored, pharmaceutical fridge
Record all batch numbers and keep certificates
of analysis for future reference
Keep warmed oil for maximum 5 days in
incubator then discard
Staffing
All staff must have the necessary
qualifications, experience and training to
perform their roles
Detailed job descriptions
Defined
and
documented
individual
responsibility and lines of responsibility within
the lab
Documented orientation/induction and training
Competencies
CPD
Regular clinical meetings
Audit
“Measure what is
measurable and make
measurable what is not.”
The father of science,
Galileo Galilei
16th Century
Audit
Internal audit should demonstrate UNIFORMITY
in lab personnel methodology
External audit e.g. Gamete Expert; NEQAS
ensures lab procedure inline with other labs
Both internal and external audits demonstrate
inter/intra lab variations
Discoveries of non conformities after audit is
positive as confirms that system is working and
our ability to recognise faults and weakness and
correct them
Audits should be performed periodically and
findings and actions documented
Audit
 The RMU will be auditing a variety of areas:
 nursing
 laboratory to ensure that it maintains the
QMS
 Patient satisfaction
 The laboratory will be the main focus as it
will be where the embryos are created.
Audit











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Number mature oocytes (>80%)
Fertilisation Rate (>70%)
Patients with no fertilisation (FTF) (<5%)
Damaged oocytes after ICSI (<5-10%)
Cleavage rate (>96%)
Number of uncleaved embryos (<5%)
Number of good quality embryos on day 3 (40%)
Blastocyst formation rate (>40%)
Implantation rate (>25%)
Miscarriage rate per clinical pregnancy (<20%)
Clinical pregnancy rate (>30%)
Multiple pregnancy rate (<10%)
Audit
 Can also look at differences between operators (<2
standard deviation point difference) e.g. fertilisation
rates between ICSI practitioners; clinicians pregnancy
rate per ET
 If there is a drop in fertilisation rate or higher FTF this
indicates problems with:
Sperm preparation
Insemination concentration
 If the cleavage rate is also decreased then maybe a
problem with toxicity in culture attributed to:
plasticware
media and/or oil
incubator
Audit
Monitoring over time will allow long term
evaluation of all parameters and overall lab
performance
Factors below the benchmark inform us where to
discover problems
Charting the data in graphical form will aid
trouble shooting in the lab by providing additional
information
Shewhart Chart
Upper
warning limit
Target value
(benchmark)
Lower
warning limit
UCL= Upper control limit
LCL= lower control limit
Control limits based on previous years data
Shewhart Chart
 This could be used for plotting :
the percentage monthly clinical pregnancy rate per ET
where the control limits are based on the previous
years results and the warning limits set by the team
The proportion of good quality embryos on D3 per
month
The fertilisation and cleavage rates per month
The blastocyst formation rate per month
 If the lab benchmarks are high and control charts
show stable performance then clinical factors
may attribute to lower pregnancy rates
Risk management
There are 2 types:
Prospective: failure modes and effects
analysis (FMEA)
Retrospective: Root cause analysis
FMEA
 FMEA is a proactive method addressing the risk
 Involves process mapping of all processes involved in
IVF
 Brainstorming all potential failures and their effects
 A worksheet is used and everything that could go
wrong with that step is recorded
 All solutions to avoiding these failures from
happening are added
 Grading the seriousness of the incident between 1
and 5 (1= no effect and 5= critical)
 Process redesigned and tested
 Resdesigned process is monitored
FMEA
 Process mapping
Prospective
Retrospective
Failure Modes and effects analysis (FMEA) is a
FMEA worksheet
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Step number e.g. 1.
Description:
witness called
Failure Mode:
witness unavailable
Failure Causes:
delay to checking fertilisation
Failure Effect:
may miss fertilisation (Pns disappear)
Likelihood of Occurrence (O) 1-5: 1
Likelihood of Detection (D) 1-5: 5
Severity (S) 1- 5:
5
Risk Priority number is calculated (OxDxS): 1x5x5=25
Actions to mitigate risk: ensure adequate staffing in morning
Responsible Person: Lab director
Reference number for evidence
Risk Score after actions have been taken
FMEA
 Improves process knowledge
Saves time and resources
Reduces errors as risks identified and
solutions in place
All staff participate and are made aware of
the risks
Root Cause analysis
 Is a reactive method used for risk assessment
when the incident has occurred or there has been
a near miss
Analysis for the reason why the incident occurred
Solutions sought and used to prevent risk from
happening again
It forms the structured basis for trouble shooting
Quality Managementsummary
Establishing a QMS system is labour intensive
Everyone must be involved
Implementation allows efficient and stable
operation of the Unit by providing structure
and standardisation
With the ultimate aim of continuously
improving service to the patients
Quality Managementsummary
10% Clinical skills
30% Scientific skills
60% Organisation
The organisation is provided by the QMS
Thank you
“Quality is doing the right
thing when nobody else
is looking”
Henry Ford, Industrialist
References
 Quality Management and regulation in the ART laboratory, K. Tilleman etal,
Human Reproduction, 28:Supplement 1:101-102
 Quality Control: Maintaining stability in the laboratory, D. McCulloh,
Textbook of Assisted Reproductive Techniques, 4th edition, 2012.
 The ART Laboratory: Current Standards, C. Sjoblom, Textbook of Assisted
Reproductive Techniques, 4th edition, 2012.
 Quality management systems for your in vitro fertilisation clinic’s
laboratory: Why bother?, J.Olofsson etal, Journal of Human Reproductive
Sciences, November 2012
 Quality Management Issues in the Assisted Reproduction Laboratory, Boone
etal, Journal of Reproductive and Stem Cell Biotechnology, 1:1:30-107, 2010
 To QC or not to QC: the key to a consistent lab?, M. Lane etal,
Reproduction, Fertility and Development, 20:23-32, 2008
 Revised guidelines for good practice in IVF laboratories, M. Magli etal,
Human Reproduction, Vol 23:6:1253-1262, 2008
 Quality and Risk management in the IVF laboratory, D.Mortimer, 2005

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