Quality Risk

Management
Presented by: Gerik D. Placido
John Lemuel T. Pacil
APE - Technical Services

21 MAR 2016
AmPI Conference Room

Objective
Quality Risk Management
Risk Management Plan
FMEA Risk Management Tool
WORKSHOP!

Amherst Parenterals, Inc.

Vision

We shall be the leader and Sterile

Manufacturer of choice for Liquid Products in
the Philippines.
We shall do this by strictly adhering to
current Good Manufacturing Practice (cGMP)
and Global Quality Standards, complemented
by a globally competitive and highly
motivated workforce.

Hazard, Harm & Risk

Hazard potential source of Harm
i.e. Expired
Food

Harm damage to health, including the damage

that can happen from loss of product quality
i.e. Food Poisoning

Risk - combination of the probability of

occurrence of HARM and severity of that

HARM
i.e. Death

HAZARD

RISK

RISK

HAZARD

Risk Management Plan

(RMP)

- RA 9711

Risk Management Process

Risk Assessment
What might go wrong?
Risk Identification knowing the hazards
Risk Analysis estimation of the risk
Risk Evaluation reduce or accept the risk

Risk Category of
Manufacturers

HIGH

Manufacturer of Sterile Medicines

Manufacturer of OTCs MEDIUM
Manufacturer of Vitamins - LOW

Risk Control
Reduce the risk to an acceptable level
Provide additional controls/action to minimize

the risk

Risk Management Tools

Basic Flowcharts, Fishbone Analysis
Risk ranking and filtering
HACCP Hazard Analysis and Critical Control Points

FMEA Failure Mode and Effects

Analysis

FMEA
Identify potential failure
Prioritize risks and monitor effectiveness of risk

control activities
Applied to equipment and facilities and to analyze

a manufacturing operation and its effect on the

product or process

FMEA
Severity a measure of the possible

consequences of a failure
Occurrence frequency of specific failure
Detectability - likelihood of detecting a failure

or the effect of the failure before it occurs

FMEA Model
Risk Assessment
Process

Risk

Cause

Risk Mitigation

O Current D RPN
Control

List the Identify List the Identify

the current
process,
the
causes
controls
systems potentia of failure
made to
or
l risks
the
functions
process

S Severity
O Occurrence
D Detectability
RPN Risk Priority Number

Risk
S O* D* RPN
Control
*
Provide
additional
risk
mitigation
action

RPN = S x O x D

Risk Analysis
Column

Description

Severity

Based on numeric values of 1, 3, 5, 7, and 10, the

severity of the risk is assessed.

Potential Causes

A list of causes of the failure. There may be multiple

causes in which case the effect of failure and the
severity is repeated.

Occurrence

Value based on the actual or assessed rate of

occurrence

Current Controls

Identify the current control method by which the

event is controlled if at all.
manual
automatic
procedural

Detection

If the failure is not detectable, the score is 10 and if

the failure is obvious the score is 1.

RPN (Risk
Priority Number)

Severity x Occurrence x Detection

Rating
RPN, Severity, Occurrence, Detection
Value

Severity

Occurrence Detection

10

Injury to a patient/ Death More than

once per
batch

Not detectable by
current methods

Cause extreme
customer dissatisfaction

Once per
batch

All manually
inspected

Something likely to
result in a complaint

Once per 6
months

Statistical
sampling

Minor nuisance resulting Once every 1

in no loss
3 years

100% inspection

Be unnoticed and not

affect performance

Obvious or
monitored and
alarmed

Once every 6
100 years

Risk

RPN

Ok

Minor

27

Mid

125

Major

343

10

10

1000

Critical 10

Acceptance
Criteria: RPN < 125

AmPI Process Flowchart

Receivin
Receivin
g
g of
of
RM/PM
RM/PM

Delive
Delive
ry
ry to
to
FPDI
FPDI

Testing
Testing
of
of
RM/PM
RM/PM

FG
FG
Release
Release

Issuanc
Issuanc
e
e of
of
RM/PM
RM/PM

Packagi
Packagi
ng
ng

Batchi
Batchi
ng
ng

Visual
Visual
Inspecti
Inspecti
on
on

Contain
Contain
er
er
Preparat
Preparat
ion
ion
Solution
Solution
Preparat
Preparat
ion
ion

LT
LT
M
M

Filli
Filli
ng
ng

Terminal
Terminal
Steriliza
Steriliza
tion
tion

1. Receiving of RM/PM

Receiving of RM/PM
Initial Checking
SAP
Unloading to Quarantined Rooms

Critical
Steps

Risks

RM/PM
Receiving

Receiving of
damaged
PMs

Effects
Product
recall and
rework

Cause
Human
error: overlooked due
to random
inspection

Controls
Initial
Checking,
QC
Inspection

2. Testing of RM/PM
Area Preparation
RM/PM Sampling
Transportation from SVP Sampling Room to
Laboratory
RM Testing (pH, assay, identification test, potency)
PM Testing
Critical
Steps
RM/PM
Transfer

Risks
Inappropriat
e handling
of samples

Effect

Cause

Controls

Cross
Not following Personnel
contaminatio operating
Training,
n
procedures
SOPs

3. Issuance of RM/PM

Area Clearance
Issuance of Picklist
SAP Confirmation
Releasing
RM Issuance (Loading to ante room)

Critical
Steps

Risks

Effect

Cause

Controls

Releasing

Releasing of
sub-quality
RMs

Bulk
rejection

Improper
testing

Sampling and
Testing SOP

RM
Issuance

Expired RM
issued

Batch
Rejection

Over-looked
RM details

Counterchecking
of expiry date.

4. Batching

BPR Issuance
Transfer of RM from Ante room to Batching room
Area Preparation and Clearance
Weighing balance verification
Weighing of RMs
Container Handling
Sampling Booth Operation

Critical
Steps
Weighin
g of RMs

Risks
Insufficient
quantity of
batched RM

Expired RM
used

Effect
Low Assay

Cause
Wrong
computation
(w/ potency)

Controls
Personnel
Training,
Operating
Procedure,
BPRs

5. Solution Preparation

Cleaning and Sterilization of Mixing Tanks

Loading of WFI
Sampling of WFI
Preparation of Contact Parts
Bulk Preparation
pH checking
pH adjustments

Critical
Steps

Risks

Effect

Cause

Controls

Preparati
on of
Contact
Parts

Wrong
Low / High
Sterilizatio accumulate
n
d lethality
program/
setting
used

insufficient
sterilization
of contact
parts

Checking of BPR for

sterilization
settings,
Familiarization to
operating
procedures

Bulk
Preparati
on

Over
volume

Low Assay

Miscalculated
stud reading

Counterchecking ,
BPRs

Filter
Preparati

Inappropri
ate filter

High
bioburden

Human error

Re-training of
operator,

6. Container Preparation

Receiving of Containers
Set-up of Washing Unit
Set-up of Depyrogenating Tunnels
Change parts
Loading of containers

Critical
Steps

Risks

Effect

Cause

Controls

Receiving
of
Container
s

Wrong
quantity of
received
containers

Shortage of
containers/
prolonged
filling
operation

Human
error:
Miscalculatio
n

BPR, Operating
Procedures

Set-up of
Depyro
Tunnels

Wrong input
of
parameter
settings

High/Low
accumulated
lethality (FH)

Human error

BPR, Operating
Procedures,
Visual Aids

7. Filling Operation

Area Preparation and Clearance

Set-up of Contact Parts
Unloading of cart with cassettes
Loading of RS and FOC
Filling operation
Volume check
Loading of product

Critical
Steps

Risks

Effect

Cause

Controls

Area
Preparati
on

Wrong
disinfectant
used

Microbial
Growth

Human
Error

Disinfectant
Schedule

Set-up of
Contact
Parts

Non-aseptic
Handling

Contaminati
on

Human
Error

Personnel
Training

Filling
Operation

Wrong dosing
pump size

High/ low
volume

Human
Error

Familiarization
with Operating
Procedures

8. Terminal Sterilization

Autoclave Set-up
Loading of charts and printer papers
Monitoring
Unloading of Product

Critical
Steps

Risks

Effect

Cause

Controls

Sterilizatio Low steam

n
supply

Low
accumulated
lethality

Malfunctionin
g steam
generator

Preventive
Maintenance

Unloading
of Product

Inaccurate
temperature
readings

Misplacement Personnel
of autoclave
Training
probes

Damage on
autoclave
temp probes

9. LTM Operation

Transfer of Product to staging area

Machine Set-up
Change parts
Unloading of products
Transfer to visual/quarantine

Critical
Steps
LTM Setup

Risks
Wrong
parameter
settings

Effect

Cause
Human error

Substandar
d quality of
LTM output

Controls
Checking of
BPK

10. Visual Inspection

Unloading of SFG
Inspection of individual SFG
Accounting of rejects
Inspected SFG transfer to Quarantined Area

Critical
Steps

Risks

Effect

Cause

Controls

Unloading of
SFG

Product
Mixed-ups

Product
Rework/
Rejection

Mishandling of
SFG batches
with same
containers

Labels, SOPs

Visual
Inspection

Acceptanc
e of reject
SFG

Substandar
d quality of
SFG

Human Error:
Fatigue

Double
checking of all
SFGs,
Personnel
Training, Eye
breaks

11. Packaging Operation

Receiving of Packaging Materials

Coding of Individual Box
Machine Set-up
Labelling Operation
Weighing (counterchecking)
SAP
Transfer to Quarantined FG

Critical
Steps
Coding of
Individual
Box

Risks
Wrong Three
Line printed

Effect
Rework

Cause
Human
error

Controls
Checking of BPK,
Personnel Training

12. Releasing
Receiving of Samples
Testing of samples
Sterility testing
Critical
Steps

Risks

Effect

Cause

Controls

Testing of
Samples

Improper
dilution of
test samples

False
Results

Human Error

Counter
checking,
Review of
SOPs

Review of
BPRs

Over-look
OOS in BPRs

Product
Complaint

Human Error

Counter
checking and
review

13. Delivery to FPDI

Critical
Steps
Loading of
FGs to
Container
Vans/Trucks

Risks
Nonqualified
forklift
operator

Effect
Mishandling
of Finished
Goods

Cause
Lack of
training

Controls
Personnel
Training

Engineering and Maintenance

Calibration
Maintenance

Critical
Steps
Maintenan
ce

Risks
Defective
quickconnect
valve

Effect
Injury

Cause
Poor/
insufficient
maintenance

Controls
Preventive
Maintenance
schedule, SOP