QUALITY RISK MANAGEMENT

MANAJEMEN RISIKO MUTU

(QRM/MRM)
 Quality Risk Management
• QRM is a systematic process for the assessment, control and
review of risk to the quality of pharmaceutical product. It can
be applied both proactively and retrospectively.
• The QRM should ensure that :
a. the evaluation of the risk quality is based on scientific
knowledge, experience with the process and ultimately links
to the protection of the patients;
b. the level of effort, formality and documentation of QRM
process is commensurate with the level of risk.
 Quality Risk Management
• Risk is usually related with possibility of bad result or
occurrence that causes loss, such as accident, burn, failure,
etc.
• There is no guarantee that one hundred percent yield will
always be achieved, some bad (unexpected) result is
unavoidable.
• Risk is also related with uncertainty, that is a risk is due to
uncertainty
 Quality Risk Management
• Risk management is efforts to identify, and to
control risk in each activities of a company to
obtain higher effectiveness and efficacy.
 Quality Risk Management
• An effective quality risk management approach can ensure
the high quality of drug product to the patient by providing a
proactive means to identify control potential quality issues
during development and manufacturing.
• Use of quality risk management can improve the decision
making if a quality problem arises.
Risk is usually related with possibility of loss or
unexpected result.
Risk is commonly defined as combination of the
probability of occurrence of harm and severity of that
harm
 Risk Management
Risk management has close relation with other
company’s function, such as finance , safety, production,
personnel, engineering and maintenance, etc.
Protection of the patient by managing the risk to quality
should be considered of prime importance.
Manufacturing and use of drug product , including its
component , necessarily entail some degree of risk.
 Principles of QRM
2 Main principles of QRM :
• RISK Evaluation for Quality must be based on scientific
knowledge and related with protection to the patient as final
target ; and
• Level of efforts, formality and process documentation of
QRM studies should equal with risk level.
(CPOB 2012 aneks 14)
Probabilitas = Occurence
Keparahan (kegawatan) = Severity
 ICH Q9 Link back to patient risk
Opportunities to impact
risk using quality risk
Design management

Process

Materials Manufacturing

Facilities
Distribution

Patient

G.- Claycamp, FDA, June 2006

Quality Risk Management Process
(ICH Q9)

Process
Development

Control Strategy
Development

Continual
Improvement
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CPOB 2012
 FMEA (Failure Mode Effect Analysis)
• FMEA merupakan teknik evaluasi tingkat keandalan
dari sebuah sistem untuk menentukan efek dari
kegagalan dari sistem tersebut.
• Kegagalan digolongkan berdasarkan dampak yang
diberikan terhadap kesuksesan suatu misi dari
sebuah sistem.
 Istilah-istilah dalam FMEA
• Kesalahan (failure) adalah kegagalah proses atau produk
• Keparahan/kegawatan (severity) adalah dampak yang timbul
apabila suatu kesalahan (failure) terjadi
• Kejadian (occurence) adalah kemungkinan atau probabilitas
atau frekuensi terjadinya kesalahan
• Deteksi (detection) adalah kemungkinan untuk mendeteksi
suatu kesalahan akan terjadi atau sebelum dampak kesalahan
tersebut terjadi
• Tingkat prioritas risiko (Risk Priority Number-RPN) adalah hasil
perkalian dari masing-masing tingkat kegawatan kejadian dan
deteksi.
 Responsibilities

Usually undertaken by interdisciplinary teams.

Includes experts from appropriate areas , e.g. : Quality
unit, Business development, Engineering, Regulatory
affairs , production operations , sales and marketing,
legal, statistics, clinical),
Individuals who are knowledgeable about QRM
processes.
 Decision Makers

• Should
♠ Take responsibilities for coordinating QRM across
various function and departments of their organization,
♠ Ensure that QRM process is defined, deployed, and
reviewed and that adequate resource are available
 The desired state driven by ICH Q9
• Manage risk to patient, based on science:
– Understand the product, process and facility
– Robustness of Quality System
– Define areas of risk
– Relevant controls to assess & reduce risk
– Internal governance
• Level of oversight required commensurate with the level
of risk to patients
– Marketing authorization applications
– Post-approval change review
– GMP inspections
 When should we use it ?
I. Proactive Risk Management :
√ Design and implement effective systems
√ Monitor for risks / changing environment
√ QRM integrated into the Quality System
• Not a stand alone, isolated activity or group
• Self-inspection planning
• Vendor classification – supplier management
√ Used in making science and risk-based decisions
• Change management
• Product release
 When should we use it ?(cont.)

√ Facilities, equipment and processes

• Design, Qualification, Validation (incl. for analytical
methods)
• Equipment, instrument & utility classification
• Critical Parameter identification
II. Reactive Risk Management :
√ CAPA -Complaints, Deviations, Recalls etc.
 Quality Risk Management
• Integration of quality risk management into pharmaceutical
industry can be implemented as part of :
1.Quality management,
2. Product development,
3. Facility,
4.Equipment and utilities,
5. Materials management,
6. Production,
7.Quality control,
8.Stability testing,
9.Packaging and labeling,
10.Self inspection etc.
 QRM for Facilities, Equipment and Utilities
Design of facility / equipment

1. To determine appropriate zones when designing buildings and facilities, e.g.:

•flow of material and personnel;

•minimize contamination;
•pest control measures;
•prevention of mix-ups;
•open versus closed equipment;
•clean rooms versus isolator technologies;
•dedicated or segregated facilities / equipment.
•To determine appropriate product contact materials for equipment and containers (e.g.,
selection of stainless steel grade, gaskets, lubricants);
•To determine appropriate utilities (e.g., steam, gases, power source, compressed air, heating,
ventilation and air conditioning (HVAC), water);
•To determine appropriate preventive maintenance for associated equipment (e.g., inventory
of necessary spare parts).
 QRM for Facilities, Equipment and Utilities
Design of facility / equipment (2)

2. Hygiene aspects in facilities

• To protect the product from environmental hazards,
including chemical, microbiological, and physical hazards
(e.g., determining appropriate clothing and gowning,
hygiene concerns);
• To protect the environment (e.g., personnel, potential for
cross-contamination) from hazards related to the product
being manufactured.
 QRM for Facilities, Equipment and Utilities
Design of facility / equipment (3)
3. Qualification of facility/equipment/utilities
• To determine the scope and extent of qualification of
facilities, buildings, and production equipment and/or
laboratory instruments (including proper calibration
methods).
 QRM for Facilities, Equipment and Utilities
Design of facility / equipment (4)

4. Cleaning of equipment and environmental control

• To differentiate efforts and decisions based on the
intended use (e.g., multi- versus single-purpose,
batch versus continuous production);
• To determine acceptable (specified) cleaning
validation limits.
5. Calibration/preventive maintenance
• To set appropriate calibration and maintenance
schedules.
 QRM for Facilities, Equipment and Utilities
Design of facility / equipment (5)
6. Computer systems and computer controlled equipment
• To select the design of computer hardware and software
(e.g., modular, structured, fault tolerance);
• To determine the extent of validation, e.g.,
1.Identification of critical performance parameters;
2. Selection of the requirements and design;
3. Code review;
4. The extent of testing and test methods;
5. Reliability of electronic records and signatures.#
 Output / Hasil proses QRM ?

• When you decide, through a risk management process, that a

certain residual risk is acceptable, you can close your QRM
process for that particular risk You should communicate the
outcomes on that QRM process, as appropriate, to stakeholders

• However, quality risk management process is continuous and the

outputs/results may or may not need to be reviewed frequently
during the life cycle.
• The need to review or not should be decided based upon the
level of accepted risk and other cumulative factors (e.g. process
changes, events) #
 CPOB 2012 aneks 14

• Manajemen Risiko Mutu hendaklah

diintegrasikan ke dalam kegiatan yang
dilakukan sekarang dan didokumentasikan
secara tepat.
Contoh
PROBABILITY & SEVERITY
 Penilaian P dan S
Probabilitas (P) Keparahan (S)

LEVEL NILAI LEVEL NILAI

Tinggi Parah

Sedang
Cukup Parah
Rendah

Kecil Tidak Parah

 Prioritas Tindakan Perbaikan/Pencegahan
• RPN : Rate Priority Number
• Risiko (RPN) = Kejadian (occurence/probability) x Keparahan
(severity) X Kemampuan Deteksi (detectability)
• Prioritas perbaikan berdasarkan RPN :

Risiko RPN Prioritas perbaikan

Minor ≤ 4 Rendah
Major 5-19 Sedang
Critical ≥ 20 Tinggi
CONTOH APLIKASI EVALUASI RISIKO MUTU

36
 Pustaka
• CPOB (2012)
• POPP-CPOB 2102 (2013)
• Hamid Mollah ,A;Long,M;Baseman,Harold S, Risk Management Application in
Pharmaceutical and Biopharmaceutical Manufacturing. Wiley (2013)