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Introduction of Validation and Qualification

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Page 1: Introduction of Validation and Qualification

7/23/2019 Introduction of Validation and Qualification

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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

Page 2: 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!

!