change control who

7/23/2019 Change Control WHO

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Change Control

Luisa Stoppa

Manufacture of sterile medicines Advanced workshop for SFDA GMP inspectors

Naning! the People"s #epu$lic of China %&'() Novem$er ())*


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Nanin!" the People#s $epu%lic of &hina" '()2* Novem%er 2**+

Programme

To introduce the general elements on change control

To train ou in the guidelines !WH"#$%&' &()*S

guidelines' +,#$%&-

To become confident with S"&' forms and records of)hange )ontrol Sstem

To de.elop our inspection plan on change control


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Principles of change control

/efore a medicinal product can be released' we need:

the manufacture and qualit control procedure should be

documented in the form of instructions0

The materials to be used must be specified0

The basic conditions required for a reproducible qualit'

efficac and safet must be defined !i1e1 suitable rooms'

qualified facilities' trained personnel' .alidatedprocedures' established specifications-


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/efore the requirements can be implemented' the suitabilit ofequipments*facilities and procedures must be pro.en withqualification * .alidation

This principle is not onl .alid the first time a medicinal product ismanufactured or the first time a facilit is used or a procedure

comes into effect

The principle applies to the whole histor of a medicinal product' aprocedure or a facilit and it is to be guaranteed

2s each requirement is stated in a document' it is clear that eachchange control for the requirements must also alwas in.ol.e adocumentation control


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+ach change to pre.iousl appro.ed requirementsrequires a re.iew and authori3ation to keep the sstem inits original state of pro.en suitabilit

4ormal change control guarantees that all changes aree.aluated for their effect on product qualit or .alidation

status

)hange control minimi3es the risk that changes can ha.eon the qualit or process characteristics

)hange control programs ha.e become recogni3ed asessential element of the pharmaceutical qualit assurancesstem

,he task

of

change

control


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(n the WH"#$%& guideline glossar there is definition ofthe term change control

Howe.er' the $%& guideline basicall contains onl fewnotes about the handling of changes


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(n the 2merican )ode of 4ederal 5egulation )45' the responsibilitfor the .erification and authori3ation of changes is task of the

qualit control unit

(n the +, regulations' the responsibilit is assigned to 6ualit ,nit

2s the change control is considered an essential element of the

pharmaceutical qualit assurance sstem' it is logical the personresponsible is qualit assurance !62 representati.e' 62 head-


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)hange control is not department#specific' rather the taskof the whole compan

The change control monitors all tpes of changes which

can influence the process or product qualit and states

the measures necessar for implementing the change ordecides that a change should not be implemented


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Change control programs

%an tpes of changes affect se.eral areas at the sametime:

GMP re-uirements #egulator. re-uirements

Process securit. /validation0

Product -ualit. /specifications! approval0

1ffectiveness 2 safet. /approval0

Suita$le rooms and e-uipment /-ualification0

Suita$le personnel /training! e3perience0


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2 central processing of change procedures' coordinatedb the qualit assurance department' has se.eral

ad.antages:

8 there is a common understanding of what a change represents0

8 the classification schemes used b the staff in.ol.ed to ratechanges are congruent0

8 the risk connected with the change can be e.aluated in a multi#

disciplinar manner0

8 there is uniform documentation and authori3ation procedure



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The tpe and scope of a change control program mustcompl with the requirements:

91 (n the classical $%rele.ant areas the change control

helpsto maintain the .alidated and established status1

alidated processes' qualified facilities' material

specifications can be influenced b changes and

medicinal products no longer compl with specifications



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;1 Holder of marketing authori3ation must guarantee thatnecessar regulator pre#requisites are met1 )ontract

manufacturers that do not ha.e their own authori3ation

must guarantee that the contract gi.er is informed of

internal changes that could ha.e an influenceon theirapplication documentation !this requires that the contract

gi.er is included in the change control program of the

contract manufacturer-



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%an companies rate the changes requiring control

14'GMP


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"therclassifications are

possible


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(t is not decisi.e which and how man change#classes a compan has rated' but how it is

guaranteed that changes requiring control are

recogni3ed as such and implemented according

to a defined procedure



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=ot all changes require a re.alidation


56+'GMP


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(n the &()*S document &( >> !chapter 1@1A- there is a list ofchanges that ma require a re#.alidation:



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2lso in the WH"#$%& guidelines there is a list of changes thatma require a re#.alidation



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WH"#$%& guidelines



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&()*S document &(>>



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The so called trials cause a problem in change control program1

Trials are preliminar' temporar changes which can permanentl

established or re.oked after a trial period

With trials' there is a risk that these intended temporar changes

graduall become permanent changes without a formal change

control procedure being carried out

How long a trial is retained and whether it is withdrawn after a trial

phase or be introduce permanentl' should be included in the

same procedure change control as all other changes



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Be.iations should not be treated as changes' not e.enwhen de.iations become changes after a failure hasbeen clarified

Be.iation is an unplanned and undesirable de.iation

from a requirement0 it occurs spontaneousl

Be.iations should be dealt with according a procedureabout handling de.iations

2ll .ariations implemented in emergenc !no planned' nocontrolled' no permanent- are included in de.iations



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Changes/planned changes0

Deviations/unplanned changes0

Su$mission of re-uest

'description of change

'rationale1valuation

'effect on validation status

'definition of revalidation measures

Approval

7mplementation of change

Closing

Notification

'description of deviation

1valuation

'effect on product -ualit.

'definition of corrective actions

'effect on validation status

'definition of revalidation measures

7mplementation of deviation

Closing



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P7C2S guideline


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2 problem is the issue of which changes the changecontrol team should dealt with

(t is ob.ious that this team cannot deal with all changes

in the compan

2s matter of fact' onl changes requiring control should

be processed b this team



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4irstl' these are changes rele.ant for the regulatorstatus

Secondl' the are changes which could ha.e an

influences on the attributes of a $%rele.ant sstem'

facilit' equipment' material*product' procedure*process

The team should also deal with all changes whose grade

or implementation is unclear or questionable



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How the team members communicate with each other?

=ot all changes require a meeting

(n cases which are eas to make a decision about' it can

be useful traditional paper#based circulation procedures'e#mail agreement or access to (ntranet#based forms



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When a change control program has been introduced'the effecti.eness of the sstem can be re.iewed using

data which is eas to determine

Total number of changes request /year

Number of completed change requests / year

Change type / department involved

Duration of procedure: from application to closing

Number of deviations/year

Number of internal or external complaints /year

Number of OOS /year



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14'GMP


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)hange control requires a written procedureto establish at leastthe following steps:

hat type of changes does change control ta!e into account"

hat are the requirements for urgent changes"

#or $hich areas does this operating procedure apply"

ho can suggest changes"

%o$ are changes requested &forms' method of communication("

%o$ are changes graded and $ho is responsible for the rating"

%o$ are the measures for carrying out the change established"

ho is responsible for the implementation and monitoring of all measures"

ho is included in the change control team"

hat are the duties of the change control team"

%o$ is the change documented &format' content' storage("

ho is responsible to authori)e changes"

Documentation


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Documentation

)hange control requires a written procedure to establish at leastthe following steps:


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Documentation

)hange control requires a written procedure to establish at leastthe following steps:


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2ll qualit#rele.ant changes should be documented

2ll actions to be taken' including the need for and e7tent

of qualification or .alidation' should be described

The records can be archi.ed in paper form orelectronicall

When storing documents' raw data and other rele.ant

documents for change should be kept accessible

Documentation


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)hanges requiring control are generall documented inthe form of a change request in which the applicant for

the change proposes the tpe of change' suggests the

timeframes and measures for carring out the change

The change control team authori3es or not the change

The documentation for the change procedure should

show that the change was e.aluated !risk analsis-

Documentation


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Documentation

56+'GMP


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)hange controlprocedure

!e7ample 9-

Documentation


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)hange control procedure !e7ample ;' 9*;-

Documentation


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)hange control procedure includes flow chartof thechange control process and the change request form

!or change form-

)hange request formrecords a request for change so

that each change is documented before it is appro.ed

The change request form includes the description of

the change' the benefits' costs' urgenc of the

change' change impact

Documentation


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)hange control procedure: flow chart !e7ample 9-

Documentation


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Documentation

)hange control procedure: flow chart !e7ample ;-

Change Request

Submission

Evaluation of

Change Impact

ValidationChangeRequest

Moreinformation

required

ChangeActivities

Change Closed

Approval

ActivitiesCompletion

ChangeActivities

Approval

ActivitiesCompletion


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Documentation

)hange control procedure: flow chart !e7ample


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)hange controlprocedure: flow

chart !e7ample A-

Documentation

CC8 9 change control $oard


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Documentation

)hange controlprocedure: flow

chart for change

master documents

!e7ample 9-


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)hange requestform !e7ample 9'

9*;-

Documentation


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)hange requestform !e7ample 9'

;*;-

Documentation


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)hange requestform !e7ample ;'

9*;-

Documentation


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)hange requestform !e7ample ;'

;*;-

Documentation


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)hange requestform !e7ample


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Documentation

)hange database:electronic cop


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Documentation

)hange control logbook

Change control logboo! &year:********(

Nb+ ,equestdate

,equester /department

-tem Description .pprovaldate

.ctions andtime limit

Closingdate

age:** of::::

0. 1anager signature ********* Date:::::::

f


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13amples of changes

)hanges to the cleaning procedure# use of a new cleaning agent

# change in concentration * .olumes of cleaning agent

# change in .olumes of rinsing water

# change of cleaning process parameters

)hanges to the production equipment

# changes to the )(& equipment

# changes to * replacement of equipment parts !difficult to give

detailed examples as these changes are too diverse-# change of process parameters

1 l f h


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13amples of changes

)hanges to the product# changes to composition !reformulation with different e7cipients-

# changes to the manufacturing process !i1e1 transfer of a product-

)hanges to H2) sstem * unidirectional flow

)hanges in la#out !i1e1 implementation of a pass#bo7-

7 ti l


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7nspection plan

To ask for the )hange )ontrol standard operatingprocedure

To check that all rele.ant steps for change control

implementation are detailed

To choose some applications !from the list in the logbook-

To .erif the applications and all requested documents

!change request form' in.estigation' request and closing

date-

C l i


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Conclusion

The old adage sas: the onl thing constant is changeC

# f d t


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#eference documents

WH" $%& guidelines 8 Technical 5eport series n1 D


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1orkshop on 13 pre4 alification re4 irements for reprod cti e health medicines

l;stoppa

change control who

Documents