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7/23/2019 Introduction of Validation and Qualification
http://slidepdf.com/reader/full/introduction-of-validation-and-qualification 1/24
Introduction of Validation and
Qualification
Prese ted by Group 7:
Muhamad Bima Muria (144414!
"iri (1444!
#lle (1444!
$herly (1444!
Apothecary Profession Program of ISTN Jakarta
7/23/2019 Introduction of Validation and Qualification
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What is Validation?
Validation is establishing of documented evidence
which provides a high degree of assurance that a
planned process will consistently performaccording to the intended specified outcomes
(WHO, 1997!
Validation is an essential part of GMP, and an element of
QA . The term of validation is normally used for processes
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What "ypes of Validation#
$rocess Validation%
& $rospective Validation & 'oncurrent Validation
& etrospective Validation
'leaning Validation
)nalytical *ethod Validation
+ualification (+,-+, O+ . $+
e Validation/ e +ualification
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Why Validation Should be Implemented?
0eeded to prove control of the critical aspects%
acilities 23% HV)', Water, 4team, 5uilding, etc!
26uipment
23% "ablet $ress, )utoclave, luid 5ed ryer, etc!
$rocess 23% *anufacturing $rocess, 4terile illing, 4teriliation, etc!
Which may affect the 6uality of product, should be validated!
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Cont’…
*anufacturers should plan validation to ensure%
- regulatory compliance and
- product quality, safety and consistency
0eed for confidence that the product will consistently meet
predetermined specifications and attributes!
)n 6uantitative approach is needed to prove 6uality,
functionality, and performance of a pharmaceuticalmanufacturing process!
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Planning For Validation (Validation Master Plan)
)ll validation activities should be planned! "he 8ey elements of a
validation program should be clearly defined and documented in a
Validation *aster $lan (V*$!
"he V*$ should contain data on at least the following% Validation policy
4tructure organiation of validation activities
4ummary of facilities, systems, e6uipment and process to be
validated! ocumentation format (protocol and report format, planning and
scheduling
'hange control
eference to e3isting documents
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o!umentation (Validation Proto!ol)
escribe the study to be performed and include as a minimum%
"he obectives of the study
"he site of the study
"he responsible of personnel
escription of 4O$s to be followed 26uipment to be used
4tandards and criteria for the products and processes
"he type of validation
$rotocol contents%
"he processes and/or parameters
4ampling, testing and monitoring re6uirements
$redetermined acceptance criteria for drawing conclusions
Validation protocol should e estalished to specify and define the validation activity
that !ill e performed. "t revie!ed and approved y the head of Quality Assurance
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o!umentation (Validation "eport)
) validation report should refer to validation protocol%
4ummariing the result obtained,
'ommenting on any deviations observed escribing the necessary conclusions
ecommending changes necessary to correct
deficiencies!
)ny changes defined from protocol should be
reported and documented with appropriate ustification
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$rocess Validation
$rocess validation is defined as the collection and evaluation of
data, from the process design stage throughout production, which
establishes scientific evidence that a process is capable of
consistently delivering 6uality products!
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Critical
control
point
Measure humidity with
humidity meter XIII
I!"
cali#ration
$eigh granulate % #alanceXI& I!"cali#ration
instrument
operation'
cleaning' care
and maintenance
Training
records for
technician
X& Sie(e )!
*sie(e with sie(e type +
X&I ,lend
)!*
granulatemi-er .speed +' + minute/
X&I ,lend 0
with )!*
granulate
mi-er .speed +' )1
seconds/
I!"!P
Cleaning
(alidation
Cleaning' and ,lend
uniformity re2uired to #e
esta#lished during (alidation
X&III $eigh granulateCritical
control
point
3ecision as to whether to
compress or not #ased on
e-pected yield and actual yield
Process step "peration I!"!P re2uirements
'ritical $rocess 4teps 4hould be Validated
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Prospe!ti#e Validation
$rospective validation should be performed and completed
before the pharmaceutical product will be sale and
distributed! ) minimum of three batches of product is
re6uired!$rospective validation should include%
4hort description of the process
4ummary of the critical processing steps to be investigated
:ist of the e6uipments/ facilities to be used (completed with-+,O+ . $+ document and it;s calibration status
inished product specification for release
:ist of analytical method
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Prospe!ti#e Validation
$roposed in&process controls with the acceptance criteria
)dditional testing to be carried out, with acceptance criteria
4ampling plan (location and fre6uency
*ethod for recording and evaluating method
unctions and responsibilities
$roposed and timetable
5atch sie made for process validation ($rospective, 'oncurrent
. etrospective should be the same as the industrial scale batch!
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'oncurrent Validation
-n e3ceptional circumstance it may be acceptable not to
complete a validation program before routine production
starts!
-t can be performed during routine operation/production wherethe product had been sale!
# or e3ample% when a process is being transferred to a third
party contract manufacturer/assembler!
ocumentation re6uirements same as specified forprospective validation
"he completed protocols and reports should be reviewed and
approved before product is released for sale or supply
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etrospective Validation
etrospective validation is only acceptable for well established
processes and will be inappropriate where there have been
recent changes in the composition of the product, operating
procedures or e6uipment!
4ource of data should include% 5atch processing an pac8aging records
$rocess control chart
*aintenance log boo8 ecords of personnel change
$rocess capability
inished product data
4tability result
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etrospective Validation
or etrospective validation, generally data from ten (1<
to thirty (=< consecutive batches should be e3amines
and to assess process consistency!
"he steps involved in this type of validation still re6uire
the preparation of a protocol, the reporting of the results
of the data review, leading to a conclusion andrecommendation
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Cleaning Validation
'leaning validation should be performed in order to confirm
the effectiveness of a cleaning procedure!
"he obectives of 'leaning Validation include prevention of
possible contamination and cross&contamination!'ontamination by a variety of substances%
'ontaminants >e!g! microbes, previous products (both )$- and
e3cipient residues, residues of cleaning agents, airborne
materials (e!g! dust and particulate matter, lubricants andancillary material, such as disinfectants?!
)lso decomposition residues from product or detergents
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Cleaning Validation
"he aspect to be e3amined% Visual inspection of the e6uipment / machinery cleanliness etermination of residues of active ingredient (along with
degradation when necessary and cleaning solutions 23amination of microbiological contamination -nspection last rinse solution for parameters% "O', pH and
conductivity, to ensure that no residual cleaning materials left
behind!
Validated analytical methods having sensitivity to detect residues
or contaminants should be used!
'leaning of contact surfaces (machine or e6uipment to be
validated, with consideration to @non&contactA parts! 'ritical areas
should be identified!
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Cleaning Validation
"he cleaning validation protocol should include% Obectives and responsible of personnel
escription of the e6uipment or machine including model, serial
number, etc!
"ime intervals and cleaning proceduresB 26uipment used for routine monitoring (e!g! conductivity meters,
pH meters and total organic carbon analyerB
0umber of cleaning cyclesB sampling procedures (e!g! direct
sampling, rinse sampling, in process monitoring and sampling
location!
ata on recovery studies (efficiency of the recovery of the
sampling techni6ue should be establishedB
)nalytical methods
)cceptance criteria
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Cleaning Validation
"wo methods of sampling% $irect surface sampling %s!a&
'inse samples
(ote) c ombination of the two & most desirable
"he three most commonly used criteria are%
Visually clean (o residue visile on equipment after cleaning.*pi+ing studies to determine the concentration at !hich mostactive ingredients are visile. %May not e suitale for high
potency, lo!-dosage drugs.& No more than 10 ppm of one product !ill appear in another
product %asis for heavy metals in starting materials&.
No more than 0.1% of the normal therapeutic dose of one product !ill appear in the maimum daily dose of a susequent
product.
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Analytical Method &alidation
"he obective of analytical method validation ()*V is to
demonstrate an analytical procedure suitable for its intended
purpose!
"he most common type of )*V% -dentification test% intended to ensure the identity of analyte in a
sample, by comparing of sample property (e!g! spectrum,
chromatographic behavior, chemical reactivity, etc to a reference
standard! +uantitative and limit test for impurities content% both of tests is
intended to accurately reflect the purity in a sample +uantitative test of )$-, medicinal product or other selected
components in the medicinal product!
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Analytical Method &alidation
)nalytical *ethod Validation 'haracteristics%
)ccuracy $recision
epeatability -ntermediate precision 4pecificity etection limit (:O
+uantitative limit (:O+ :inearity ange
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Analytical Method &alidation
)ccuracy of an analytical method is the closeness of test results
obtained by that method to the true value!
$recision of an analytical method is the degree of agreement among
individual test results when the method is applied repeatedly to multiplesamplings of a homogenous sample!
epeatability% a measurement is repeatable if the original e3perimenter
repeats the investigation using same method and e6uipment and
obtains the same results!
-ntermediate precision% a measure of within&laboratory variations(different days, different analysts, different e6uipment!
4pecificity% "he ability to measure accurately and specifically the
analyte in the presence of components that may be e3pected to be
present in the matri3
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Analytical Method &alidation
:imit of detection% "he lowest concentration of an analyte in a sample
that can be detected, not 6uantified!
:imit of 6uantitative% "he lowest concentration of analyte in a sample
that can be determined with acceptable precision and accuracy understated operational conditions
noise
Peak A
LOD
Peak B
LOQ
Baseline
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Analytical Method &alidation
:inearity% "he ability of the method to obtain test results that are directly
proportional to concentration within a given range!
$recision% -nterval between upper and lower levels of analyte demonstrated
by the method!
!