KNOWLEDGE SHARING

MANAJEMEN RESIKO MUTU

QUALITY RISK MANAGEMENT

AN IMPLEMENTATION

Rakhmat Budi Yuwono (Pharmacist)

06 September 2017
Pekan Ilmiah Tahunan (PIT) IAI 2017
 Australian Code of GMP for Medicinal Product

45 words RISK

European Guide to GMP

54 words RISK

WHO WHO : Annex 4 GMP For Pharmaceutical Products,

16 words RISK
In various words
Various words : risk due to inadequate safety, quality and efficacy,
risk to quality, risk of error, risk of mix-up, risk of cross
contamination, risk of microbial contamination, risk of manipulations,
risk to the product, etc
Regulatory Requirements
 Product Life Cycle Risk - Patient

US

Sister Friends

Patients

Brother Parents

Pharmaceutical Technology Commercial Product

Development Transfer Manufacturing Discontinuation
 Introduction..(1)

Manufacturing and use of a drug product

involve some degree of risk.
Effective Quality Risk Management (QRM)
ensure the high quality of the drug product
Proactive means to identify and control
potential quality issues
improve the decision making if a quality
problem arises.
facilitate better and more informed
decisions
Provide regulators with greater assurance of
a companys ability to deal with potential
risks
 Introduction..(2)

Basic Principles
The evaluation of the risk to quality
should be based on scientific knowledge
and ultimately link to the protection of
the patient; and
The level of effort, formality and
documentation of the quality risk
management process should be
commensurate with the level of risk.
 Advantages as Process

Improves decision making

Identifies what gives most benefit to the
patient
Is scientific & data-driven
Reduces subjectivity
Ranks risk - allows prioritization
Better use of resources
Means of building in Quality
Improves transparency - inside organisation
and builds trust with competent authorities
Enables regulatory flexibility
Benefits apply throughout product lifecycle
7 | Q-Risk
Management | April
 What is RISK ?

Risk:
The combination of the probability of
occurrence of harm and the severity of
that harm (ISO/IEC Guide 51).

Harm:
Damage to health, including the damage
that can occur from loss of product
quality or availability (ICH Q9).
 What is (QUALITY) RISK MANAGEMENT ?

Risk Management (ISO 14971, 2007):

A systematic APPLICATION of management
policies, procedures, and practices to the tasks of
analyzing, evaluating, controlling and monitoring
risk.

Quality Risk Management (ICH Q9):

A systematic PROCESS for the assessment, control,
communication and review of risks to the quality of
the drug (medicinal) product across the product
lifecycle.
Quality Risk Management -
General

10 | Q-Risk
Management | April
 SEVERITY
Level People
Membahayakan jiwa
5 High Customer/Employee atau
menyebabkan cacat permanen
Menyebabkan cacat sementara
4 pada employee/pasien menderita
namun masih dapat disembuhkan
Menyebabkan penurunan fungsi
3 Medium
tubuh pasien/employee
Berefek terhadap
2 ketidaknyamanan
pasien/karyawan
Tidak ada resiko kepada
1 Low
Customer/Employee
Compliance
Menyebabkan Recall & izin edar
dicabut/perizinan perusahaan
dicabut
Menyebabkan Recall namun
masih memiliki izin edar/major
variation
Menyebabkan produk tidak dapat
digunakan/minor variation-prior
approval
Menyebabkan Complaint dari
Customer/minor variation-
notifikasi
Tidak ada resiko perizinan
 PROBABILITY

Level Kemungkinan Frekuensi Kegagalan

1 kejadian dari 2 f > 1/10

5 High
cycle
4 Sering terjadi 1/10 f > 1/100
Mediu 1/100 f >1/10.000
3 Terjadi beberapa kali
m
1/10.000 f > 1/100.000
2 Terjadi kadang-kadang
1/1.000.000
1 Low Jarang sekali terjadi
 DETECTABILITY

Level Kemungkinan Terdeteksinya Kegagalan

5 High Tidak dapat dideteksi melalui sistem/visual

4 Berisiko tidak terdeteksi melalui sistem/visual

Dapat dideteksi melalui sistem/visual setelah
3 Medium
terjadi
2 Selalu terdeteksi pada saat terjadi

1 Low Selalu terdeteksi sebelum terjadi

 RISK EVALUATION EXAMPLE A

S 5
e
4
v
e Risk Control
3
r
i 2 Accept w/ Risk Control
t
y 1 Accept w/ Risk Control based on Priority

1 2 3 4 5 6 7 8 9 10
Occurrence : Probability + Detectability
RISK EVALUATION EXAMPLE B
 BE AWARE OF .(1)

Not a means of removing industrys obligation

to comply with regulatory requirements
Justification of product or process failures
People have to think and not simply follow
black and white rules
Pre-determined outcome of assessments
Not applicable in situations where decisions
allow no flexibility (regulatory requirements)
Not embedded in an overall quality systems,
stand alone activity

16 | Q-Risk
Management | April
 BE AWARE OF .(2)

Lack of training on tools

Improper composition of teams performing
the risk assessments lack of scientific
knowledge, relevant data not assessed, lack
of process knowledge
Decision makers and stakeholders not
informed
Writing half of (or hiding) facts or information

17 | Q-Risk
Management | April
 Implementation Approach

Quality Risk
Management
Existing (QRM)
internal
Documentation Where
to be in
System future?
(Mission, Policy)

What to do?
(e.g. Directives)

How to do?
(e.g. Guidelines)

Detailed instructions
(e.g. Standard Operating Procedures) Records

Rules & Procedures Records &

(internal regulations) Reports
 HOWS RISK MANAGEMENT GIVE
MEANING IN DEVIATION HANDLING

Scope
Any events where there is conditions or process
parameter or product that DOES NOT MEET the
approved requirement and specification
 INTEGRATE RISK MANAGEMENT
1 Deviation

Originator

All Process Melaporkan penyimpangan

FR-C4.0554, PT-C4.0093

Process Owner

Follow up laporan & Identifikasi

penyimpangan

DRF, PT-C4.0093

I2.07 Compliance Specialist C4.03

Register dan review Product Released & Post

Risk Management
penyimpangan Production Monitoring

RMF DRF, Database, PT-I2.0007 DRF

Apakah kategori
penyimpangan major atau Tidak 1
kritikal?

Ya 3

Process Owner

Tentukan akar masalah yg

menjadi penyebab
ketidaksesuaian yg terjadi

PT-I2.0007, PT-C4.0200

01

20
 01 Deviation

3 6

I2.07 Process Owner I2.04

Tentukan tindakan perbaikan

Risk Management Corrective & Preventive Action
yang akan dilakukan

RMF DRF, PT-I2.0007, PT-I2.0010 CAPA Form

5 4

Compliance Mgr Compliance Mgr/QM

Menganalisa kebutuhan untuk Review penyimpangan &

melakukan extended correction plan serta approval
investigation Deviation Form

DRF, PT-I2.0007, PT-I2.0010 DRF, PT-I2.0007, PT-I2.0010

Process Owner C4.09

02
Implementasi correction Change Control

DRF, Dokumen Pendukung CC Form

Compliance Mgr/QM

All Process Verifikasi hasil implementasi 1

DRF, Dokumen Pendukung,

Database

Compliance Mgr I2.04

Melakukan trending secara

03 Corrective & Preventive Action
periodik

PT-C4.0156, FR-C4.0415, CAPA Form

Database

21 2
 CLASSIFICATION IN DEVIATION

RECORD

CRITICAL INCIDENT
DEVIATION
CLASSIFICAT
ION

MAJOR MINOR

22
23
 PROACTIVE RISK MANAGEMENT

Risk Evaluation 24
 Risk Reduction

Risk Control 25
 Risk Acceptance

Risk Control 26
Risk Review 27
 Implement Deviation Record/Incident
Simplifying Minor Deviation Handling
One Day Root Cause Analysis & Finalized
Reduce Lead Time
Strengthen QA Inspector Role
Analyzed Reoccured Deviation
Finalized CAPA from deviation
Risk Analysis (Accept residual risk or not)
 HOWS RISK MANAGEMENT GIVE
MEANING IN CALIBRATION

All measuring devices Increase the amount

calibrated withouth of measuring device
risk assessment must be calibrated
Interval of calibration continuously
have defined Increase calibration
normative activities, lead to
No procedure to improper in calibration
determine either management system
risk prioritizing,
measuring devices
calibration schedule
needs to be calibrated
calibration procedure
or not by reviewing
accuracy result
criticality measuring
device based on the Risk to patient safety
influence of measuring and regulatory
device performance on compliance.
product quality
 DEVICES AND CALIBRATION ACTIVITIES

2500

2000

1500

Measuring Devices
Calibration Activities
1000

500

0
2014 2015 2016
 BACKGROUND AND PURPOSE

BACKGROUND
An organization which is not unlimited resources, so
it needs to optimize the resources for calibration
activities with improving quality risk management on
calibration policy

PURPOSE
This document describes an assessment approach
that should be applied to evaluate measuring
device criticality and define required calibration
intervals or frequencies.
 RISK EVALUATION-STAGE 1

5 4 4 4 5 5
Risk Evaluation Score :
4 3 3 4 4 5 3 : Low
3 2 3 3 4 4 4 : Medium

2 1 2 3 3 3 5 : High

1 1 1 2 3 3
1 2 3 4 5

Needs to be calibrated

No needs to be calibrated but verification, include

in Preventive Maintenance

No needs to calibrated
 RISK EVALUATION-STAGE 2

3
stability calibration result extended calibration
period
4th calibration pass 2 period calibration
1 2 3 4 5
3rd calibration pass 1 period calibration

Level Calibration Frequency

Innitialy, monthly and verification before used

Innitialy and every 3 months

Innitialy and every 6 months

Innitialy and every 12 months

Innitialy and every 24 months

 RESULT

Man Hour
6800 6685.5
6700
6600
6500
6400
6300 6183.5 Reduce 6%
6200 man hour/year
6100
6000
5900
w/o RA with RA
 HOWS RISK MANAGEMENT GIVE
VALUE IN TRAINING MANAGEMENT

Kategori Materi Evaluation Training

High 1 tahun 2 tahun
Medium 2 tahun NA
Low 3 tahun NA
Operator
N Competency Matrix Type S P D Risk
o Level
1 5R, Sanitation & Hygiene Basic GMP 4 2 3 High
2 Granulasi Specific Operation 4 2 3 High
3 Serah Terima & Rekonsiliasi General Operation 3 1 2 Low
RM/PM
4 Pengenalan Alur Proses Solida General Operation 3 1 3 Medium
Petugas Kemas
N Competency Matrix Type S P D Risk Level
o
1 5R, Sanitation & Hygiene Basic GMP 4 2 3 High
2 Packing Specific Operation 4 2 3 High
3 Serah Terima & Rekonsiliasi General Operation 3 1 3 Medium
RM/PM
4 Pengenalan Alur Proses Solida General Operation 3 1 2 Low
Thank You