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
Pharmaceutical Development
Parents
Technology Transfer
Commercial Manufacturing
Product 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 company’s 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
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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
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SEVERITY Level 5
High
4
↓
3
Medium
2
↓
1
Low
People
Compliance
Membahayakan jiwa Customer/Employee atau menyebabkan cacat permanen Menyebabkan cacat sementara pada employee/pasien menderita namun masih dapat disembuhkan
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 variationnotifikasi
Menyebabkan penurunan fungsi tubuh pasien/employee Berefek terhadap ketidaknyamanan pasien/karyawan Tidak ada resiko kepada Customer/Employee
Tidak ada resiko perizinan
PROBABILITY
Level
Kemungkinan Frekuensi Kegagalan
5
High
≥ 1 kejadian dari 2 cycle
4
↓
Sering terjadi
3
Mediu m
Terjadi beberapa kali
2
↓
Terjadi kadang-kadang
1
Low
Jarang sekali terjadi
f > 1/10
1/10 ≤ f > 1/100 1/100 ≤ f >1/10.000 1/10.000 ≤ f > 1/100.000 ≤ 1/1.000.000
DETECTABILITY
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
RISK EVALUATION –EXAMPLE A
S e v e r i t y
5 4 3
Risk Control
2
Accept w/ Risk Control
Accept w/ Risk Control based on Priority
1 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 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
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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
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Implementation Approach
Existing internal Documentation System
Quality Risk Management (QRM) 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
Rules & Procedures
Records & Reports
(internal regulations)
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
INTEGRATE RISK MANAGEMENT 1
Deviation
Originator All Process
Melaporkan penyimpangan
FR-C4.0554, PT-C4.0093 2
Process Owner Follow up laporan & Identifikasi penyimpangan
DRF, PT-C4.0093
I2.07
Compliance Specialist
C4.03
Risk Management
Register dan review penyimpangan
Product Released & Post Production Monitoring
RMF
DRF, Database, PT-I2.0007
DRF
Apakah kategori penyimpangan major atau kritikal?
Ya
Process Owner Tentukan akar masalah yg menjadi penyebab ketidaksesuaian yg terjadi
PT-I2.0007, PT-C4.0200
20
01
Tidak
3
1
Deviation
01
3
6
I2.07
Process Owner
I2.04
Risk Management
Tentukan tindakan perbaikan yang akan dilakukan
Corrective & Preventive Action
RMF
DRF, PT-I2.0007, PT-I2.0010
CAPA Form 4
5
Compliance Mgr Menganalisa kebutuhan untuk melakukan extended
Compliance Mgr/QM Review penyimpangan &
investigation
correction plan serta approval Deviation Form
DRF, PT-I2.0007, PT-I2.0010
DRF, PT-I2.0007, PT-I2.0010
02
Process Owner
C4.09
Implementasi correction
Change Control
DRF, Dokumen Pendukung
CC Form 7
Compliance Mgr/QM All Process
Verifikasi hasil implementasi
1
DRF, Dokumen Pendukung, Database
03
21
Compliance Mgr
I2.04
Melakukan trending secara periodik
Corrective & Preventive Action
PT-C4.0156, FR-C4.0415, Database
CAPA Form
2
CLASSIFICATION IN DEVIATION
RECORD
CRITICAL
INCIDENT DEVIATION CLASSIFICAT ION
MAJOR
22
MINOR
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)
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.
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
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 Score :
RISK EVALUATION-STAGE 2 5
4
3
stability calibration result
extended calibration period
4th 1 Level
2
3
4
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
calibration pass
2 period calibration
3rd calibration pass
1 period calibration
5
RESULT Man Hour 6800 6700 6600 6500 6400 6300 6200 6100 6000 5900
6685.5
6183.5
w/o RA
with RA
Reduce 6% man hour/year
HOW’S RISK MANAGEMENT GIVE VALUE IN TRAINING MANAGEMENT
Kategori Materi High Medium Low
Evaluation 1 tahun 2 tahun 3 tahun
Training 2 tahun NA NA
Operator N o
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
Petugas Kemas N o
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
Thank You
