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u o
Specication
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Latar Belakang
• Laboratory testing diperlukan untuk memastikanbahwa komponen, kemasan, in-process material,dan bahan jadi sesuai dengan spesikasi ataustandart yang ditetapkan.
• OOS results adalah seluruh hasil test yang telahdilakukan dimana tidak sesuai dengan spesikasiatau acceptance criteria yang ditetapkan dalamdrug applications, drug master es (!"s#,O$cial compendia atau dari manufaktur itu
sendiri.
• %n&estigasi mengenai ketidak sesuaian batch ataucontent dengan spesikasi yang telah ditetapkan,haruslah dilakukan secara menyeluruh baik untuk
produk yang telah maupun belum terdistribusikan.
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Defnitions
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DefnitionsSpecifcation
spesikasi mencankup daftar pengujian yangdilakukan, prosedur analisis analisis, dan kriteriapenerimaan dimana terdapat batasan yang jelas darihasil analisis atau pengujian yang dilakukan. 'sesuaispesikasi artinya bahan obat atau produk jadi yang
telah diuji sesuai dengan prosedur yang terdaftar(tercatat# telah memenuhi kriteria penerimaan yangdigunakan.
Regulatory Approved Specifcation
)eraturan yang mengatur tentang standar atauspesikasi dari suatu produk yang dapat direlease.
Acceptance Criteria
merupakan batasan (berupa angka maupun range#untuk menyimpulkan bahwa prosedur dan hasil analisisbahan obat maupun produk jadi pada setiap tahap
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Defnitions
Assignable Cause
*n identied reason for obtaining an OOS oraberrant + anomalous result.
No Assignable Cause
hen no reason could be identied.
Invalidated test* test is considered in&alid when the in&estigation
has determined the assignable cause.
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Laboratory *nalysisSatisfactor
y OOS -esult
)hase %a%n&estigation
)hase %b%n&estigation
)hase %%%n&estigation
)hase %%%%n&estigation
Batch ispotition
!anufacturing%n&estigation
)roduct %mpact*ssessment
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Laboratory *nalysis%n&estigasi Out of specication/ harus sudah dilakukan
ketika0 1esting batch release dan testing bahan baku
%)2 testing, selama %)2 berlangsung ketika terdapat OOS harussegera diin&estigasi
Studi stabilitas produk jadi atau *)%
%n&estigasi OOS juga dilakukan pada batch yang telah direlease sebelumnya untuk menjadikan hasil tersebut sebagaisampel pembanding dalam in&estigasi OOS selanjutnya
Batch yang akan digunakan untuk uji klinis
*ll solutions and reagents must be retained until all
data has been second person &eried as being withinthe dened acceptance criteria.
1he OOS process is not applicable for %n3process testingwhile trying to achie&e a manufacturing process end3point
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)hase %a%n&estigation
4o 5rrorfound
%nitiate )hase %bLaboratory
%n&estigation
Ob&ious5rror
ocument and2orrect %n&alld
-esult
4o "urther%n&estigation
-e6uired
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)hase %a %n&estigation
Defnition:
7ntuk menentukan apakah telah terjadikesalahan yang jelas karena keadaan eksternalseperti gangguan listrik maupun kesalahan yang
telah secara jelas diketahui oleh analis (sampelatau reagen tumpah#.
"or microbiological analysis this may be after theanalysis has been completed and re&iewed duringreading of the samples.
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I ti ti b A l t d
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Investigation by Analyst andSupervisor
)ada in&estigasi fase ;b analis dan super&isor melakukanlaboratory %n&estigation 2hecklist.
alam analisis mikrobiologi dimana seluruh alat danbahan yang dapat mengakibatkan kesalahan mulai dariplate, hasil pengenceran, &ial, data temperatur, pipet,
reagen dan media pertumbuhan, tidak boleh dicuci ataudihilangkan bagitu juga untuk seluruh hasil plate yangtelah digunakan.
1he *nalyst and Super&isor in&estigation should be
restricted to data + e6uipment + analysis re&iew only.
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!edia atau reagen disiapkan sesuai dengan proseduryang ditetapkan
ata kriteria penerimaan terpenuhi
ata acceptance criteria met.*nalis telah ditraining
%nter&iew analis untuk menilai pengetahuannya tentangprosedur yang benar
)emeriksaan data mentah bukan data olahan!engecek setiap masalah yang sebelumnya terjadi
mengenai analisis tersebut
!engecek potensi lainnya yang dapat mengganggupengujian
!engecek kondisi lingkungan dalam proses analisis
!eri&iew hasil dari batch sebelumnya dimanamenggunakan proses yang sama
!enilai proses dan hasil &alidasi yang dilakukan
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*dditional considerations for microbiological analysis0
*re the isolates located as e=pected > on glo&e dabmarks, S*S dimples/, lter membrane etc.
as the sample media integral > i.e. no cracks in plates.
as there contamination present in other tests (orrelated tests# performed at the same time, includingen&ironmental controls.
ere negati&e and positi&e controls satisfactory. ere the correct media+reagents used.
ere the samples integral (not leaking#.
ere the samples stored correctly (refrigerated#.
ere the samples held for the correct time before beingtested.
as the media+reagent stored correctly before use.
ere the incubation conditions satisfactory.
1ake photographs to document the samples at time ofreading (include plates, gram stains and any thing else
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)hase %%%n&estigation
2onduct
Laboratory"ailure
%n&estigation
4o*ssignable
2ause%dentied
*ssignable
2ause
!anufacturing
%n&estigation
-aisee&iation+
"ailure
%n&estigation
ispositi
on Batch
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)hase %% 2onducting"ailure %n&estigation
"ollow *ppro&ed )rotocol 5=ecute%n&estiogation (:ypothesis
1esting#
-eport-etest-esult
-eport *ll -esults4o "urther
-etest
4o *ssignable2ause
*ssignable2ause
OOS -esultsObtained 2onrm
OOS
)hase %%%%n&estigation
Batch
isposition
%mpact
*ssessment+ispositionBatch
%n&alidate
Original-esults
8enerate2*)*
7 k 2
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7nknown 2ause4o *ssignable
2ause
-e 3sampling
Stability
!icrobiology
:ypothesis 1esting
Outliertest
*&erage
-e 3 test
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)hase %% %n&estigation2onducted when the phase % in&estigations did not
re&eal an assignable laboratory error.%t is important when considering performing additional
testing that it is performed using a predenedretesting plan to include retests performed by an
analyst other than the one who performed the originaltest. * second analyst performing a retest should be atleast as e=perienced and 6ualied in the method asthe original analyst.
%f the in&estigation determines analyst error all
analysis using the same techni6ue performed by theconcerned analyst should be re&iewed.
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)hase %%% %n&estigation
%f the batch is rejected there still needs to be anin&estigation.
1o determine0
if other batches or products are a?ected.
identication and implementation of correcti&e and
pre&entati&e action.
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)hase %%% %n&estigation 1he phase @ in&estigation should re&iew the completed
manufacturing in&estigation and combined laboratory in&estigationinto the suspect analytical results, and+or method &alidation forpossible causes into the results obtained.
1o conclude the in&estigation all of the results must be e&aluated.
1he in&estigation report should contain a summary of thein&estigations performedA and a detailed conclusion.
1he batch 6uality must be determined and disposition decision taken.'nce a batc$ $as been re(ected t$ere is no liit to !urt$er
testing to deterine t$e cause o! !ailure# so t$at correctiveaction can be ta%en.
"$e decision to re(ect cannot be reversed as a result o!
!urt$er testing&"$e ipact o! ''S result on ot$er batc$es# on going stability
studies# validated processes and testing procedures s$ouldbe deterined by )uality Control and )uality Assurance andbe docuented in t$e conclusion# along wit$ appropriatecorrective and preventive actions&
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*atc$ Disposition%n those cases where the in&estigation indicates an
OOS result is caused by a factor a?ecting the batch6uality (i.e., an OOS result is conrmed#, the resultshould be used in e&aluating the 6uality of the batch orlot. * conrmed OOS result indicates that the batchdoes not meet established standards or specications
and should result in the batchs rejection and properdisposition. Other lots should be re&iewed to assessimpact.
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"or inconclusi&e in&estigations C in cases where anin&estigation03
(;# does not re&eal a cause for the OOS test result
and(D# does not conrm the OOS result
"$e ''S result s$ould be given !ullconsideration +ost probable causedeterined, in t$e batc$ or lot dispositiondecision by t$e certi!ying )P and t$e potential!or a batc$ specifc variation also needsconsidering&
*ny decision to release a batch, in spite of an initial
OOS result that has not been in&alidated, shouldcome only after a full in&estigation has shown thatthe OOS result does not reEect the 6uality of thebatch. %n making such a decision, 9uality*ssurance+9) should always err on the side of
caution.
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Corrective And Preventive Action+CAPA,
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"eri
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