Quality Risk
Management for GMP
Refresher Training
Fiona McIntyre
Pfizer Loughbeg Drug Product
Why do we do GMP training?
 FDA “Training in current good manufacturing practices
shall be conducted by qualified individuals on a
continuing basis and with sufficient frequency to
assure that employees remain familiar with cGMP
requirements applicable to them” (CFR, 1978).
 EU “Besides the basic training on the theory and
practice of Good Manufacturing Practices,...
Continuing training should also be given” (Eudralex,
1997).
What does it involve?
 Companies have reported that they
invest between 1 to 12 hours
annually per person delivering GMP
refresher training (Pharmachem
Ireland, 2004).
What do participants think?
What do participants think?
Why is QRM useful
ICH Q9 - Quality risk assessments can be
used either
 Reactively e.g. patient impact assessment
for a contamination issue
 Proactively e.g. ascertaining the appropriate
frequency for GMP refresher training.
Loughbeg DP Model
 240 Colleagues
 56 Contractors approx e.g. cleaners, security etc
 GMP refresher frequency –


Direct GMP impact – Twice per year (82%)
Indirect GMP impact - Once per year e.g. finance (18%)
 Total Number of hours training 1080 participant
hours/year
 GMP trainer responsible for designing, delivering,
scheduling and tracking.
QRM Risk Question
‘What is the minimum frequency of GMP refresher
training required per functional group to ensure
that all colleagues and relevant contractors are
cognisant of their responsibilities to the
regulators and to our patients in producing
product according to GMP and the SISPQ
requirements?”
SISPQ: Safety, identity, strength, purity and quality
(Reference CFR)
Out of Scope
 Training required for a specific need e.g.
human error (Deviation system), new
regulations/process/system or induction
training.
 Contractors not assigned to job functions
will be assessed through the annual
GMP plan.
Risk Assessment tool
 Risk Ranking and Filtering

Probability of trainees becoming complacent in
their knowledge of GMPs resulting in production of
product that is not GMP or SISPQ compliant?

Severity of impact to product/process/patient if a
trainee were to deviate from requirements that
ensure GMP and SISPQ compliance due to
insufficient training?
Probability
Factor
Weighting
Description
Low
1
no GMP impact, not responsible for making GMP decisions or performing GMP
tasks, they may have read only access to GMP system or infrequent access
to GMP areas e.g. HR
Med
2
not responsible for making GMP decision or for conducting routine GMP tasks,
they may however have access to GMP areas and/or perform GMP related
tasks on a on a relatively frequent basis (number of times a week but not
daily). e.g. DCC
High
3
responsibility for managing GMP systems or involved in GMP decision making,
however do not work directly in production or with analysis of
product/materials and/ or the operating or cleaning of production
equipment. They are responsible for governing systems related to the
facility, utilities or process equipment. e.g. PAT
Very
High
4
responsibility for making GMP related decisions or is directly involved in
production and analysis of product or materials and/ or the operating or
cleaning of production equipment e.g. QA/ QC/ Manufacturing.
Severity
Factor
Weighting
Description: Error or mistake would involve….
low
1
minor nuisance, no effect on quality or GMP, it would be
unnoticeable by the customer and have no regulatory impact
Moderate
2
low GMP or business impact that could be easily detected or
rectified on site immediately. GMP actions performed are
verified or controlled by another job function with a higher risk
ranking.
High
3
possible minor rework or re-inspection; customer may raise a
complaint but the error will not result in serious GMP issue or
patient safety issue.
Very High
4
could lead to adverse patient reaction or non compliance and or
serious customer complaint with regulatory implication or recall
scenario.
Risk Score = Severity x Probability
Increasing
Probability
4
4
8
12
16
3
3
6
9
12
2
2
4
6
8
1
1
2
3
4
1
2
3
4
Increasing Severity
13-16 Critical –
Twice per year
9-12 Major –
Once per year
5-8 Minor –
Every 18 months
1-4 Non Critical
– Every 2 years
Category Description
 1-4
Non Critical
These employees have a
low probability of impacting GMP/quality of the product as
they are not responsible for GMP decisions or conducting
routine GMP tasks. Any errors they could potentially make
would have little of no effect on GMP or quality. They
generally work in admin roles or roles such as Finance or HR.
 5-8
Minor
These employees generally have a
GMP aspect to their job; however those GMP tasks are
verified or controlled by another job role classified as
major or critical impact. Employees in this category generally
work in roles such as DCC, purchasing etc.
Category Description (cont.)
 9-12
Major
These employees work in a GMP
role; however, they work indirectly with product. They are
responsible for the GMP systems governing; the facility,
utility or equipment used for manufacturing of product.
They generally work in roles such as process engineering,
calibration etc.
 13-16
Critical
These employees work directly
with manufacturing or testing of product and have the
potential to cause serious GMP or quality impact. they work
in roles such as Tablet Technician or QC Specialist etc.
Worked example….
QC Chemist/Analyst
Step 1: Assess ‘what is the probability of
colleagues/contractors producing product that is not
GMP or SISPQ compliant?’
Result:
Very High
Score= 4
Rationale: A QC Chemist works directly with the
testing and analysis of product on a daily basis and
has a very high probability of GMP impact on the
product.
QC Chemist…
Step 2
Assess ‘severity of impact to product/process/patient
if a colleague/contractor were to deviate from
requirements that ensure SISPQ compliance due to
insufficient GMP refresher training?’
Result:
Very High
Score= 4
Rationale: A QC Chemist has the potential to cause
serious quality issues in the course of their work e.g.
quality issues as a result of releasing a material with
an OOS result.
QC Chemist ….
Step 3: Calculate risk classification by multiplying the probability
score by the severity score (4 x 4 = 16)
Step 4: Assign Refresher frequency requirement – Critical
classification.
Functional
Group
Probability Severity Result
Classification
QC Chemist
4
Twice per
year
4
16
Assessment of other Job roles
Functional Group
Probability
Severity
Result
Classification
Frequency of
GMP
Tablet Technicians/Operators
Operations Manager
QC Specialists
QA Specialists
4
4
16
Critical
Twice per
year
AIT Engineers
Process Engineers
Warehouse Colleagues
VTS Specialists
3
4
12
Major
Once per
year
Buyer & Planner
QC Assistant
Document control Coordinators
2
3
6
Minor
Once every
18
months
Department Administrators
Security
EHS
HR
1
1
1
Non Critical
Once every 2
years
Probability
Factor
Weighting
Description
Low
1
no GMP impact, not responsible for making GMP decisions or performing GMP
tasks, they may have read only access to GMP system or infrequent access
to GMP areas e.g. HR
Med
2
not responsible for making GMP decision or for conducting routine GMP tasks,
they may however have access to GMP areas and/or perform GMP related
tasks on a on a relatively frequent basis (number of times a week but not
daily). e.g. DCC
High
3
responsibility for managing GMP systems or involved in GMP decision making,
however do not work directly in production or with analysis of
product/materials and/ or the operating or cleaning of production
equipment. They are responsible for governing systems related to the
facility, utilities or process equipment. e.g. PAT
Very
High
4
responsibility for making GMP related decisions or is directly involved in
production and analysis of product or materials and/ or the operating or
cleaning of production equipment e.g. QA/ QC/ Manufacturing.
Severity
Factor
Weighting
Description: Error or mistake would involve….
low
1
minor nuisance, no effect on quality or GMP, it would be
unnoticeable by the customer and have no regulatory impact
Moderate
2
low GMP or business impact that could be easily detected or
rectified on site immediately. GMP actions performed are
verified or controlled by another job function with a higher risk
ranking.
High
3
possible minor rework or re-inspection; customer may raise a
complaint but the error will not result in serious GMP issue or
patient safety issue.
Very High
4
could lead to adverse patient reaction or non compliance and or
serious customer complaint with regulatory implication or recall
scenario.
Challenges
 Devising the descriptions
 Tracking of the requirement
Benefits of the QRM
 Old requirement = 1080 participant hours/year
 New requirement = 892 participant hours/year
= saving of 18%
= 188 participant hours
 Time – TNA for department specific GMP refreshers.
Improved quality of GMP refresher training
courses.
 Shared & implemented across other Pfizer sites
increasing the benefit to Pfizer.
Questions