quality risk management - dcvmn · management of risk process 9 ich q9 quality risk management...

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Quality Risk Management

DCVMN regional Workshop Sao Paulo,November 24-28th

Dr. Sandra Olga Rumianowww.sandrarumiano.com

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Agenda

ICH Q9 and ICH Q10 : what is expected?Tools in risk analysisBuilding a probability, severity, detectability

tablePractical ExercisesQuestions open session.

www.sandrarumiano.com

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ICH Q9 and ICH Q10


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PQMS : Medicines supply chain management

(MSCM) and Pharmaceutical Quality System

Demand:ask for

accomplishment ofPQS

SuppliersRequest

accomplishwith PQS ofcustomers

Manufacturing

CenterPQS

Storage &distributio

nCenter

QS(GSP/GD

P)

HealthCenters

(GSP/GDPin

accordanceto QS

requirements)

Second stepfor

Storage &distribution

CenterQS -

(GSP/GDP)

Health AuthorityRegulations & Control

Demand pointof use:

Patient: ask foraccomplishment of

PQS among theMedicines Supply

Chain

Health Authority Regulations & Control

Materials & Medicines flow

Information flow

Medicines reverse flow: complaints, recall

Market Information flow: demand feed backAs a resultSupply chain connectsPharmaceutical QualitySystemsWith QS that Includessuppliers,Third parties centers,storage and distributioncenters.

An integrated PQS troughthe Medicines Supply Chainguarantee that medicines areSupplied in accordance toestablished quality guidelinesto prevent complaints, recalls,returned or salvaged products,and defective productsentering/circulating in theMarket.

Addressing Uncertainties andChallenges Related to Crucial

Quality Check Pointsamong the Quality System


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Quality risk management is asystematic process for the

assessment, control,communication and reviewof risks to the quality of thedrug (medicinal) product

across the product lifecycle.


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Managementof risk process


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ICH Q9

Quality risk management supports ascientific and practical approach todecision making.

It provides documented, transparent,and reproducible methods to accomplishsteps of the quality risk managementprocess based on current knowledgeabout assessing the probability, severity,and, sometimes, detectability of the risk.


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Steps

Define ScopeEvaluateReduce uncertainty“risk under control”“monitoring situations or critical

elements that could lead to a risk”


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How can be defined the criticalprocesses to work on?

The ones that allows to run the businessincluding social responsibilityThe ones that has indirect or direct impact in:Public HealthVaccines shortages

EnvironmentPrivate and Public economy


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Examples of Critical processes in thePharmaceutical Quality System among the Supply

chain management in vaccines

Organization & responsibilitiesPremises layout including materials & personnel

flow:cleaning

Process stepsDocumentationQualifications & ValidationsAudits & CAPA PlanSanitary vigilance


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Quality SystemFundamentals

and main documents


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Key steps in Pharmaceutical QualitySystem

1. Implementation based on risk assessment andknowledge management

2. Maintenance: Status of Control:1. CAPA follow up2. KPIs

3. Improvement: PDCA cycle


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Conclusion:Quality Management is aculture in the company

supported in thePhilosophy of Good

Practicesapplication


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Tools in risk analysis


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Risk or Hazard?


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Risk ISO 14971:2000Combination of the probability of occurrence

of harm and the severity that this implies.

Canadian Standards Association,2002Possibility of damage or loss defined as a

measure of the probability of occurrence andseverity of adverse effects produced on thehealth, property, environment, organization,or other values.image


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Risk characteristics

UncertaintySubjectivityWhat we mean by

shareholdersControls on the riskwww.sandrarumiano.com

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Hazard

Actual or potential conditionthat can cause injury, illness ordeath to persons, damage orloss in systems, equipment, orother public or private property,or environmental damage(Lamarca, 2000)


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Hazard II: characteristics

It is an intrinsic part of a substance, situation,processThere may be more of a hazard associated with

them

Evidential effects not immediately be observed

It can generate a cascade effect

It affects shareholders / Society in different wayswww.sandrarumiano.com

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23 “The investigation of risksis at once

a scientific activity andan expression of culture”

Kasperson, Renn, Slovic etal. (1988)

Reduce uncertainty:

TOOLS FOR RISKANALYSIS


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Classification

InductiveDeductiveQualitativeQuantitative


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Origen in Medical Device and EngineeringFault Tree Analysis (FTA)Failure Mode and Effect Analysis (FMEA)Failure Mode and Effect Criticality Analysis

(FMECA)Origen in Food, Medicines & Pharmaceutical

ProcessRA (Risk analysis)Hazard Analysis and Critical Control Point

(HACCP)


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Risk classes:patientoperationfinancialregulatoryothers

Risk undertanding as integral part of theprocess

What does it mean “To have the risk undercontrol”?www.sandrarumiano.com

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Big severity

Severity is medium

Severity is low

Low

Med

ium

Hig

h

Probability of risk occurrence

Ris

k ty

oeSystemic evaluation

Qua

lity

impa

ct

Some concepts to take into account

Equipment, Systems, Process

Qualified personnel

Process described: FlowchartSpecifications: Acceptance criteriaProcess variability

Change control system

Validated status to be kept: APR


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FTA (fault tree analysis)


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Fault Tree Analysis (FTA)

Deductive, top-down approach

First it is assumed that there exists a failure

Then identify the events that lead directly orindirectly to the failure

The methodology can be applied to theinvestigation of deviations, complaints, findingsfor continuous improvement.


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The garments at clean room entry were found with no identification ofsterilization and last date to be used

Differential pressure between grade B and C was found yesterday at7Pa and today at 12 Pa. Yesterday an aspetic filling of a vaccine wasdone.

The documentation from Site A it is not completed: vaccines storagedata is not included and when you ask for having the docuemntcomplete, they said they have no idea you`re speaking about.

Large pools of frozen venoms, collected from many individuals, areallowed to thaw at 0 °C, to avoid proteolytic degradation of venomcomponents and, after being thoroughly mixed, aliquots of liquidvenoms are prepared. These aliquots are then freeze-dried and storedin the dark at a low temperature (either -20 °C or 4 °C). Aliquots offreeze-dried venoms should be adequately labelled as perspecification. The storage conditions of the venoms you used ask for(2-8)ªC. Once serum manufacturing process is running you detected inthe documentation preparation and review that the temperature ofvenoms was not reported, you asked it to the WH and the temperaturecontrol shows you data of 3 days at 7ªC and then 3 days at 9ªC.www.sandrarumiano.com

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Pre RA(Pre- risk analysis)


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Pre RA:Based on what if questions

Requires knowledge of the processApply from brainstorming processFlowchartInterdisciplinary TeamQualitativeIdentifies event possibilities and describes the

probability of occurrence


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Pre- RA : steps

Process descriptionRisk scenarios ListRisk prevention meassures

identificationTo evaluate the results and establish

that risks will be “remove" and / orcontrol in a given processDocument the analysis processwww.sandrarumiano.com

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Typical design formColumns were extracted study only.Header orresponds to the system under analysis, date, in chargestaff, and at the foot firms/date must be included.


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I


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Step Potential risk Justification of therisk, how tomanage the risk

Pondera-tion(L;M;H)(1, 2,3)

Follow upyes or not

II


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Step Test to bedone

Responsible/dtae

AC Resultfound

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Failure Mode and Effect Analysis(FMEA)


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Failure Mode and Effect Analysis(FMEA)

Systematic and analyticalmethodology that can preventfailures

Preventive non reactive


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Form example


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SYSTEM DESCRIPTION: BioreactorPW DATE: 20 . June,2012REFERENCES: USP XXIXCOMPILED BY: MS REVIEWED BY: MEA

step

cond

ition

s

pote

ntia

l fau

lt

leve

l afe

cted

pote

ntia

l cau

ses

of ri

sk

cont

rols

that

are

in fo

rce

hist

ory

seve

rity

and

jsut

ifica

tion

(H;M

;L)

poss

ibili

ty o

f det

ectio

n of

the

failu

re

prio

rity

in ri

sk a

naly

sis

(enu

mer

ate)

sampling qualifiedstaff

microbialcontamination

stopoperation

OOS OOS/APR H H late 1

L early

Failure Mode and Effect Analysis (FMEA)

training

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FMECA–failure mode effects and

critically analysis-


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To be used when?

Design building / support systemsNew processesTo Evaluate performance of

servicesAfter Other toolswww.sandrarumiano.com

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How to use it…

Define the universe of study

Identify potential fault models and its effects Setthe RPN

Risk management monitoring

Control and monitoring

Document


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Building probability,severity and detectability

tables in vaccinesmanufacturing

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Risk analysisvs. Risk assessment

Risk assessment is a step in a risk management procedure.Risk assessment is the determination

of quantitative or qualitative value of risk related to aconcrete situation and a recognized threat (also called

hazard).

Quantitative risk assessment requires calculations of twocomponents of risk (R):, the magnitude of the potential

loss (L) named as severity (S) and the probability (p) thatthe loss will occur. In addition the availability of detect it

must be considered (D).


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Form example


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SYSTEM DESCRIPTION: BioreactorPW DATE: 20 . June,2012REFERENCES: USP XXIXCOMPILED BY: MS REVIEWED BY: MEA

step

cond

ition

s

pote

ntia

l fau

lt

leve

l afe

cted

pote

ntia

l cau

ses

of ri

sk

cont

rols

that

are

in fo

rce

Prob

abili

ty

seve

rity

poss

ibili

ty o

f det

ectio

n of

the

failu

re

RPN

sampling qualifiedstaff

microbialcontamination

stopoperation

OOS 2 3 3 late 18

2 3 1 early 6

FMECA

training

WFI loop modification: from a change control for a

new point of use related a CIP SIP (new installation)

CT Protocol modification was approved by HA, as a

result additional samples of blood should be collected

every 3 days instead of once/week. Your sites should

be instructed and documentation follow up is

required.


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HACCP-hazard analysis andcritical control points-


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7 principles of HACCP

1. Perform risk analysis on the process flow2. Determine critical points (critical control

points (CCPs)3. Set limits for these critical points4. Establish monitoring systems thereof5. Establish corrective actions6. Establish verification procedures7. Set the document support


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HACCP main formsafter flowchart is done


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Exercise: HACCP

Aseptic filling of OPVFD process for BCG

Bulk mixer cleaning process with CIP SIP in vaccinesMedia fill interventions planning

CT protocol release and communication to sites


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Final discussion


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Why and where we fault?


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Exercise: HACCPMedia fill risk assessment


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Questions: open session.


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Thank you!

Dr. Sandra O. Rumiano



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quality risk management - dcvmn · management of risk process 9 ich q9 quality risk management...

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