••••••

Legislation/Quality Standards

Management of
deviations in a
ICH Q9/Q10 environment
R. CANADELLHEREDIA., E. GARCÍAVIDAL, S. HERREROSAS, J.
LLAJAVILLENA, L. NOGUERASALVANS, A. PIÑASLLAGOSTERA, D.
KNIFE FISH, E. LATE PÉREZ NOW. TÉBAR PÉREZ
(Working group "Management of Quality Risks ICH Q9" of the Commission of
Quality Guarantee of the Catalan Section of AEFI

This article collects In theAEFI monograph "Management of I have some application issues.
the quality risks ICH Q9" furthermore in the pharmaceutical industry such as:
one of the cases to gather the general principles of Tendency to overload of des-
practical included in Risk Management developed in deviations because "everything is reported-
this Guideline has been carried out a This can trigger a poor
the monograph 'Management' eminently practical approach investigation of the root cause and a poor
of quality risks for the pharmaceutical industry. By effectiveness analysis of the implemented CAPA
Here are examples of applications mentioned.
ICH Q9 developed selection of the different tools •A thorough treatment for
by the work group of risk analysis including its all deviations can exhaust the
definition, application, objectives, ope- available resources and cause a
from the Commission of ratification and advantages and disadvantages in a really important problem is not
Quality Guarantee each use. This item is part of conveniently treated. Since the
of one of the application examples the business viewpoint is interesting
of AEFI, formed of the risk analysis tools direct resources based on the im-
by professionals gos FMEA (Failure Mode and Effects) importance of incidents/deviations.
Analysis) •The individualized assessment of
and consultants of the the criticality of the deviations as well
pharmaceutical industry Management Issues consume important resources. If pre-
of Deviations the points are obviously not defined
about the contents of Generally, a deviation is critics of the process and the attributes of ca-
the ICH Q9 Guideline: Quality the non-compliance with a standard critical product liability, each new
established. In Part II of the GMPs the deviation that is generated is a new one
Risk Management. it is established that any deviation research.
of the requirements and procedures Difficulty in conducting an evalua-
approved must be documented and ex- quantitative assessment of the effectiveness of the
applied. effective corrective/preventive actions
The concept of deviation is so am- you, as well as its communication to
more than the management of pre-deviations rest of the organization.

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 Legislation/Quality Standards

Risk Management in Management mental and scientific and, at the same time, offers with-
of Deviations The application of Risk confidence in making a decision
ICH Q9 proposes to apply the process before the regulatory bodies.
Management in the
of risk management as both pro- The following proposes two
productive centers similar to the processes management of deviations examples of application of tools
of the quality management system. The provide a structure risk management for classification
deviation management is one of these consistent for taking and the treatment of deviations:
last and can be seen optimized to apply- Flowchart to decide whether to-
based decisions on
when the management tools of see the criticality of the deviations.
risks in two fundamental aspects: a documentary record and FMEA that introduces the probability-
•Prioritization: The tool scientific dad of non-detection of a problem.
uses to manage to classify the events From the multiple tools des-
unwanted coughs based on some written in ICH Q9, the Modal Analysis
pre-established criteria. The objective is of Failures and Effects FMEA, it is a tool
adapt the treatment of the deviation regulated and used in a related sector
based on the risk it poses to what is the industry of products
the quality of the product. This is a phase sanitary (Medical Devices)
preview of "sieving" that allows simplification It is taken for granted in the examples
but the subsequent treatment of those events are not valued in an isolated manner that the process in which it has occurred
irrelevant events. but rather its gravity and probability the deviation is associated with its aná-
Decisionmaking:Thetool- They are already parameterized in the history. risk analysis corresponding to the
mienta is used to study the im- The new entries update the ma- which are known:
deviation pact in quality of risk matrix of the process facilitating The history of failures (deviations)
product and to justify the actions the "Risk review". with the evaluation criteria of the gra-
preventive and corrective measures that are derived The application of Risk Management associated truths.
Come. This is actually the analysis of in the management of deviations it provides a The probability data of occurrence
risks of the process in which it has been pro- consistent structure for decision making occurrence of the failures (deviations) more
reduced the deviation. In this way the decisions based on a record docu- frequent.

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• MANAGEMENT OF DEVIATIONS IN AN ICH Q9/Q10 ENVIRONMENT

FIGURE 1 event classification in one of the si-

following categories:
–––––––––––––––––––––––––––––––––––––––––––––– Incident.
Non-Critical Deviation.
Critical Deviation.
3. Treatment Phase: Based on
the category with which the event is defined
the following actions will be taken:
3.1. Incidence. If the event is classified-
noted as 'Incidence', action will be taken to
its closure, since they are described
the actions to be taken for its resolution.
3.2. Non-Critical Deviation. It is with-
sulta the database of the deviations
of process and the number is checked
of times this has occurred. If not
exceeds the stipulated number as repe-
maximum permissible limit will be maintained
category of 'Non-Critical Deviation'
the event. The following are applied the
timely corrective measures and pro-
I give in to closing the deviation as a fact
punctual. Subsequently, this is introduced.
event in the deviations database
of the process for it to update and feed
the general FMEA of the process.
3.3. Critical deviation. It acquires such
category, that event where:
3.3.1. The responses of the tree of
decisions lead to the definition of
Critical Deviation.
3.3.2. That initially cla-
classified as "Non-critique", but that
exceeds the number of repetitions
maximum allowable limits.
In the face of a critical deviation, one has
to carry out an evaluation process
complete with its impact on quality
of the product, with the tool that
let's have established for the analysis of
general risks of the process.
It is worth noting that to determine
of the root cause of any type of
deviation can use other he-
tools such as Fault
Tree Analysis (FTA). Once known
•The critical points and/or stages in one of the established pre- categories the cause, the co-measures are established
techniques of the process. obviously. It works through a 'tree rectors and timely preventive measures and
The definition of the attributes of of decision" based on a series of pre- they recalculate the risk levels. Final-
product quality critics. dichotomous questions (yes or no type), cu- the final report is being drafted and
In both examples, we work with the your answers lead, directly, to the proceed to close the event.
same methodology: definition of the event category: This information will be used to act-
Analysis phase (which is differentiated P1: Are the corrective actions to be taken... update and feed back the risk analysis
for the tool used in each case). lizards are described in a pro- general of the process when applicable
Classification phase. procedure? Risk review
Tr e a t m e n t p h a s e . Does the deviation affect attributes
critical quality? In the flowchart of Figure 1
Deviation Management through P3: Does the deviation affect stages or the management of an event is schematized
flowchart critical process parameters? described above.
To classify and define the treatment P4: Does the deviation affect the caliber-
of events (potential deviations) is tion of instruments that measure attributed EXAMPLE 1:
you can establish a systematic approach such as quality thresholds or critical parameters of Event description: Contaminate-
the one defined below: process? creation of a work surface in the
1. Analysis Phase: The purpose of 2. Classification Phase: Once injectable dosing room. It
this phase is to frame the event that occurred the strategy developed, the they exceed the limits of action.

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 Legislation/Quality Standards

Notes to highlight:
Class B dosing room (ISO 7). Table 1
A product is dosed that is so-
subject to terminal sterilization with a ci- 5= The deviation affects a critical attribute or parameter
clooverkill (without incidents). for quality
The bioburden of the product is controlled.
SEVERITY The deviation affects an attribute or parameter
to lot a lot.
We e k l y r o o m m o n i t o r i n g . no critical for quality
Other work surfaces in the The deviation does not affect the quality of the product.
same room are within the limits of but it must be documented
control.
Identified microorganism
golden thread PROBABILITY 5= No controls implemented
This is the first occasion in which it is given.
OF NO 3= Final control only when the product is already made
tecta.
Once the description is available DETECTION 1= Control in process
full completion of the event is proceeded to
his analysis:
1. Analysis and classification phase
P1: Do the corrective actions to rea- FIGURE 2
lizards are described in a pro- ––––––––––––––––––––––––––––––––––––––––––––––
procedure?
No, they are not procedural.
actions.
P2: Does the deviation affect taxes?
of critical quality?
Contamination is not considered
of a surface a critical attribute of
product.
P3: Does the deviation affect stages or
critical process parameters?
It is not considered to affect a
critical stage as the process concludes
with terminal sterilization.
P4: Does the deviation affect the calibration?
measurement instruments that measure attribu-
quality tos or critical parameters of the
process?
It does not affect the calibration.
Through the questions posed
in the previous decision tree along with no detection to determine the level of
the premise that this is the first time that risk. It is possible to achieve
detects this contamination, the event Based on the level of risk, it is cla- an effective treatment
it is classified as a non-critical deviation. critical deviation, the events mean,
2. Treatment phase no criticism or incident and the ac-
of the deviations
When it comes to a non-critical deviation corresponding actions. decreasing the
a type in which the number is not exceeded The analysis is carried out taking into account resources and monetizing
stipulated as maximum repetition reference the rating scales (Ta- the information obtained
admissible (n), it only applies bla 1).
I would take a corrective measure such as by With the criteria shown in the Ta-
an example would be to do some cleaning bla 1 builds the risk matrix of
extraordinary in the area. Furthermore, the Figure 2.
deviation should be included within the The events valued with the matrix
deviation database for its they obtain a level score of
count. risks that are grouped into three categories: risk value obtained is taken into account
Risk level >9 (red zone): actions described above. This phase
Deviation Management Critical deviation: it must be investigated. it would be identical to the one described in the example
through FMEA fund, root cause, and impact assessment. previous
In this example, the use of is proposed Risk level >3 (orange zone) The entire process is outlined in the
a risk analysis tool non-critical deviation: research next flowchart (Figure 3).
based on FMEA for classification and proportional to the risk.
treatment of deviations. Risk level≤3 (zone in ver- EXAMPLE 2:
1. Analysis and Classification Phase incident: registration and closing. Descripción del evento: Detección,
The severity of the consequences is evaluated. 2. Treatment Phase during the control process, of com-
consequences of the event and the probability of Depending on the score of the 'ni- peeled shrimps.

January–February 2008 Pharmaceutical Industry 75

• MANAGEMENT OF DEVIATIONS IN AN ICH Q9/Q10 ENVIRONMENT

FIGURE 3 adequate and thus prevent the phenomenon of

exfoliation of the tablets.
–––––––––––––––––––––––––––––––––––––––––––––– The deviation, its assessment, and the m-
risk mitigation measures were introduced
they lead in the risk matrix of the process
for the review of the effectiveness 'risk re-
view the established intervals.

Conclusions
This article has presented the app-
selection of two analysis tools
of different risks for management of
deviations in the field of production
pharmaceutical action.
The use of a diagram of

Definitions
Corrective ActionAction to eliminate
to state the cause of a non-conformity from-
protected or another undesirable situation.
Preventive ActionAction to eliminate
to the cause of a nonconformity po-
potential or another undesirable situation.
Risk Analysis:
Systematic utilization of information
available to assess the risks.
CauseDeficiency origin of a
non-compliance (Failure Mode in
FMEA).
DetectabilityAbility to discount
to open or detect the presence of a pe-
slang.
FlowchartGraphical representation
it is from the sequence of actions or operates
actions carried out in a process.
Risk Management for Quality
(Quality Risk Management)Process
systematic for the assessment, control,
communication and review of risks
for the quality of a product during
its entire useful life.
Fault ModeThe way in which a
Notes to highlight: classification of 15, so it is classified as parte o proceso puede fallar frente a sus
A worker detects the event du- critical deviation specifications (generally associated
control over the packaging process 2. Treatment Phase to a defect or to a non-conformity.
(5 blisters are unwrapped every 30 minutes) Once it has been determined that it is about ProbabilityPossibility of it being
nutos). a critical deviation is analyzed cause harm.
It is a very difficult event. you are the root cause. SeverityIt is the measurement of
detect both through a telecamera In this example, it is determined, after the the possible consequence of a danger.
like through the dynamic balance. review of the Batch Record and the analysis This concept is also referred to as the
1. Analysis and Classification Phase of process risks, which is due to a name of Gravity (G).
According to the description of the event before- excessive compressive strength reflected Risk Assessment:
From this, the following score is obtained: in some individual hardness values Systematic process of organizing the infor-
Severity: 5 (as it may imply highs close to the tolerance limit information to support the decision about the
a decrease in the active ingredient dosage perior. risk to be treated within a process
active). As a measure to reduce the risk, it risk management. This process with-
Probability of non-detection: 3 proposes to study the influence of the force It focuses on hazard identification and the
(since it is not detected either by the scale or for compression and the obtained values analysis and evaluation of associated risks
by the telecamera). in the hardness control process due to the exposure to these dangers.
Result: A score is obtained to determine control limits

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 Legislation/Quality Standards

decision to classify the deviations in to keep updated knowledge of Bibliography

function of its impact on quality of same regarding: ICH Q9 'Quality Risk Management'. Step
product and based on definitions of the The critical points: redefinition 5, November 2005.
ICH Q7A or part II of the GMPs is of the limits of control. Part II GMP 'Basic Requirements for Ac-'
one of them. The critical quality attributes of Active Substances used as Starting Materials
The second option is the application product and its relationship with parameters ICH Q10 "ICH Q10 "Pharmaceutical
from a tool based on FMEA of process. Quality Systems” Step 3 Note for Guidan-
that takes into account the probability of Process capacity data. this (EMEA/CHMP/ICH/214732/2007)
no failure detection to determine The effectiveness of the actions of May 2007
the degree of risk associated with the dis- CAPA system. Reflection paper on a proposed solution for
aviation. In this way, a tr- is achieved dealing with minor deviations from the detail
In either case, effective treatment of deviations, described in the Marketing Authorisation for
manage to prioritize the deviations and decreasing the necessary resources Human and Veterinary Medicinal products
adjust their treatment based on the by eliminating the irreconcilable incidents (including biological products) Doc. Ref.
risks that threaten quality. raising and capitalizing on the information EMEA/INS/GMP/71188/2006. March
If the information finally generates- tion obtained from the deviations 2006
to be integrated with risk analysis criticism in greater knowledge of - AEFI monograph 'Risk Management'
the general process is achieved process. ICH Q9 quality guidelines.

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