Rakhmat Budi Yuwono (Pharmacist)

06 September 2017

Pekan Ilmiah Tahunan (PIT) IAI 2017

KNOWLEDGE SHARING

MANAJEMEN RESIKO MUTU

QUALITY RISK MANAGEMENT

AN IMPLEMENTATION

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

• 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

In various words

Regulatory Requirements

Product Life Cycle – Risk - Patient

Pharmaceutical

Development

Technology

Transfer

Commercial

Manufacturing

Product

Discontinuation

Patients

US

Friends

Parents Brother

Sister

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 company’s ability to deal with potential

risks

Introduction…..(1)

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.

Introduction…..(2)

7 | Q-Risk

Management | April

24 | Business Use

Only

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

Harm:

Damage to health, including the damage

that can occur from loss of product

quality or availability (ICH Q9).

Risk:

The combination of the probability of

occurrence of harm and the severity of

that harm (ISO/IEC Guide 51).

What is RISK ?

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.

What is (QUALITY) RISK MANAGEMENT ?

10 | Q-Risk

Management | April

24 | Business Use

Only

Quality Risk Management -

General

Level People Compliance

5 High

Membahayakan jiwa Customer/Employee atau menyebabkan cacat permanen

Menyebabkan Recall & izin edar dicabut/perizinan perusahaan dicabut

4 ↓

Menyebabkan cacat sementara pada employee/pasien menderita namun masih dapat disembuhkan

Menyebabkan Recall namun masih memiliki izin edar/major variation

3 Medium Menyebabkan penurunan fungsi tubuh pasien/employee

Menyebabkan produk tidak dapat digunakan/minor variation-prior approval

2 ↓

Berefek terhadap ketidaknyamanan pasien/karyawan

Menyebabkan Complaint dari Customer/minor variation-notifikasi

1 Low Tidak ada resiko kepada Customer/Employee

Tidak ada resiko perizinan

SEVERITY

Level Kemungkinan Frekuensi Kegagalan

5 High ≥ 1 kejadian dari 2

cycle

f > 1/10

4 ↓ Sering terjadi 1/10 ≤ f > 1/100

3 Mediu

m Terjadi beberapa kali

1/100 ≤ f >1/10.000

2 ↓ Terjadi kadang-kadang 1/10.000 ≤ f > 1/100.000

1 Low Jarang sekali terjadi ≤ 1/1.000.000

PROBABILITY

Level Kemungkinan Terdeteksinya Kegagalan

5 High Tidak dapat dideteksi melalui sistem/visual

4 ↓ Berisiko tidak terdeteksi melalui sistem/visual

3 Medium Dapat dideteksi melalui sistem/visual setelah

terjadi

2 ↓ Selalu terdeteksi pada saat terjadi

1 Low Selalu terdeteksi sebelum terjadi

DETECTABILITY

5

4

3

2

1

1 2 3 4 5 6 7 8 9 10

Occurrence : Probability + Detectability

S

e

v

e

r

i

t

y

Risk Control

Accept w/ Risk Control

Accept w/ Risk Control based on Priority

RISK EVALUATION –EXAMPLE A

RISK EVALUATION –EXAMPLE B

16 | Q-Risk

Management | April

24 | Business Use

Only

Not a means of removing industry’s 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

BE AWARE OF ….(1)

17 | Q-Risk

Management | April

24 | Business Use

Only

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

BE AWARE OF ….(2)

Existing internal Documentation System

Where to be in future?

(Mission, Policy)

What to do? (e.g. Directives)

How to do? (e.g. Guidelines)

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

Quality Risk Management

(QRM)

Rules & Procedures (internal regulations)

Records & Reports

Implementation Approach

HOW’S 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

20

3

2

All Process

1

Product Released & Post Production Monitoring

C4.03

DRF

Melaporkan penyimpangan

Originator

FR-C4.0554, PT-C4.0093

01

Follow up laporan & Identifikasi penyimpangan

Process Owner

DRF, PT-C4.0093

Register dan review penyimpangan

Compliance Specialist

DRF, Database, PT-I2.0007

Risk Management

I2.07

RMF

Tentukan akar masalah yg menjadi penyebab

ketidaksesuaian yg terjadi

Process Owner

PT-I2.0007, PT-C4.0200

Deviation

Apakah kategori

penyimpangan major atau

kritikal?

Ya

1Tidak

INTEGRATE RISK MANAGEMENT

21

4

7

5

6

All Process

3

Tentukan tindakan perbaikan yang akan dilakukan

Process Owner

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

01

Risk Management

I2.07

RMF

Corrective & Preventive Action

I2.04

CAPA Form

Review penyimpangan & correction plan serta approval

Deviation Form

Compliance Mgr/QM

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

Menganalisa kebutuhan untuk melakukan extended

investigation

Compliance Mgr

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

Change Control

C4.09

CC Form

Implementasi correction

Process Owner

DRF, Dokumen Pendukung

Verifikasi hasil implementasi

Compliance Mgr/QM

DRF, Dokumen Pendukung, Database

Melakukan trending secara periodik

Compliance Mgr

PT-C4.0156, FR-C4.0415, Database

Corrective & Preventive Action

I2.04

CAPA Form

02

2

1

03

Deviation

22

CLASSIFICATION IN DEVIATION

DEVIATION CLASSIFICAT

ION

RECORD

INCIDENT

MINOR MAJOR

CRITICAL

23

24 Risk Evaluation

PROACTIVE RISK MANAGEMENT

25 Risk Control

Risk Reduction

26 Risk Control

Risk Acceptance

27 Risk Review

• 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)

HOW’S RISK MANAGEMENT GIVE

MEANING IN CALIBRATION

All measuring devices

calibrated withouth

risk assessment

Interval of calibration

have defined

normative

No procedure to

determine either

measuring devices

needs to be calibrated

or not by reviewing

criticality measuring

device based on the

influence of measuring

device performance on

product quality

Increase the amount

of measuring device

must be calibrated

continuously

Increase calibration

activities, lead to

improper in calibration

management system

risk prioritizing,

calibration schedule

calibration procedure

accuracy result

Risk to patient safety

and regulatory

compliance.

0

500

1000

1500

2000

2500

2014 2015 2016

Measuring Devices

Calibration Activities

DEVICES AND CALIBRATION ACTIVITIES

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.

BACKGROUND AND PURPOSE

5 4 4 4 5 5

4 3 3 4 4 5

3 2 3 3 4 4

2 1 2 3 3 3

1 1 1 2 3 3

1 2 3 4 5

Risk Evaluation Score :

3 : Low

4 : Medium

5 : High

Needs to be calibrated

No needs to be calibrated but verification, include

in Preventive Maintenance

No needs to calibrated

RISK EVALUATION-STAGE 1

5

4

3

1 2 3 4 5

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

stability calibration result extended calibration

period

4th calibration pass 2 period calibration

3rd calibration pass 1 period calibration

RISK EVALUATION-STAGE 2

6685.5

6183.5

5900600061006200630064006500660067006800

w/o RA with RA

Man Hour

Reduce 6%

man hour/year

RESULT

Kategori Materi Evaluation Training

High 1 tahun 2 tahun

Medium 2 tahun NA

Low 3 tahun NA

HOW’S RISK MANAGEMENT GIVE

VALUE IN TRAINING MANAGEMENT

No

Competency Matrix Type S P D Risk Level

1 5R, Sanitation & Hygiene Basic GMP 4 2 3 High

2 Granulasi Specific Operation 4 2 3 High

3 Serah Terima & Rekonsiliasi RM/PM

General Operation 3 1 2 Low

4 Pengenalan Alur Proses Solida General Operation 3 1 3 Medium

Operator

No

Competency Matrix Type S P D Risk Level

1 5R, Sanitation & Hygiene Basic GMP 4 2 3 High

2 Packing Specific Operation 4 2 3 High

3 Serah Terima & Rekonsiliasi RM/PM

General Operation 3 1 3 Medium

4 Pengenalan Alur Proses Solida General Operation 3 1 2 Low

Petugas Kemas

Thank You