STANDARD OPERATING PROCEDURE

DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
TITLE :
HANDLING OUT OF SPECIFICATION
1.0 PURPOSE
To describe procedure for Handling Out Of Specification (OOS).
2.0 SCOPE
This SOP shall be applicable to all OOS test results of Raw and Packaging Materials, n
Process Materials, !inished Products and Stabilit" Sa#ples at P$%&S'S, (hongir.
3.0 RESPONSIBILITIES
3.1 Origin!ing D"#r!$"n! %&'' (" r"%#)n%i('" *)r:
).*.* +erif" the OOS results for accurac" and error.
).*., Report -uestionable results to ./ depart#ent.
).*.) nitiating the OOS in0estigation and docu#entation and reporting to ./
depart#ent.
).*.1 /arr"ing out re2testing as per OOS in0estigation flowchart, where0er
applicable after appro0al of retest b" ./ depart#ent.
).*.3 &rchi0ing the OOS in0estigation reports.
STANDARD OPERATING PROCEDURE
I%%+" D!":,0-.0..201/ DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
SOP N).
P(4SOP4.&546),466
E**"0!i1" D!"
6*.67.,6*1 TITLE :
HANDLING OUT OF SPECIFICATION
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3.2 H"2 , Origin!ing D"#r!$"n! S&'' (" r"%#)n%i('" *)r:
).,.* Pro0iding training to the personnel of originating depart#ent.
).,., nitiating the actions reco##ended in in0estigation report.
).,.) Monitor and confir# co#pliance to actions reco##ended in the
in0estigation report.
).,.1 !inal disposal of #aterial, if an".
3.3 H"2 , Q+'i!4 A%%+rn0" %&'' (" r"%#)n%i('" *)r:
).).* Re0iew and appro0al of final OOS in0estigation report.
/.0 LIST OF ATTACHMENTS
&nne<ure 2 *= !or#at for OOS >ogbook
!4P(4.&546),4,1
&nne<ure 2 ,= 5epart#ent code for OOS 8&
&nne<ure 2 )= !or#at for record and obser0ation of OOS Results (Phase 2 )
!4P(4.&546),4,3

&nne<ure 2 1= !or#at for /hecklist for n0estigation of OOS
!4P(4.&546),4,;
&nne<ure 2 3= !lowchart for OOS n0estigation (Phase 2 ) 8&
&nne<ure 2 ;= !lowchart for OOS n0estigation (Phase 2 ) 8&
&nne<ure 2 := !or#at for n0estigation Report for Phase ?
!4P(4.&546),4,:
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STANDARD OPERATING PROCEDURE
I%%+" D!":,0-.0..201/ DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
SOP N).
P(4SOP4.&546),466
E**"0!i1" D!"
6*.67.,6*1 TITLE :
HANDLING OUT OF SPECIFICATION
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-.0 PROCEDURE
-.1 Fr":+"n04:
##ediatel" on being aware of OOS results or within * or #a<i#u# , da"s after
co#pleting anal"tical test (&fter being checked, audited and re0iewed b" i##ediate
super0isor).
-.2 In!r)2+0!i)n:
OOS results obtained in the laborator" fall into three general categories=
3.,.* >aborator" error
3.,., 8on2process2related or operator error
3.,.) Process2related or #anufacturing error.
9hen an indi0idual test result does not #eet the specifications, it need not
necessaril" indicate that the batch has failed. The cause of the OOS result should be
in0estigated ade-uatel" and thoroughl" and in ti#e. The results of such an
in0estigation should be docu#ented. /orrecti0e and pre0enti0e actions #ust be taken
and should be re0iewed during batch release.
Phase 2 #eans the >aborator" OOS in0estigation and Phase 2 #eans the !ull
scale OOS in0estigation.
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STANDARD OPERATING PROCEDURE
I%%+" D!":,0-.0..201/ DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
SOP N).
P(4SOP4.&546),466
E**"0!i1" D!"
6*.67.,6*1 TITLE :
HANDLING OUT OF SPECIFICATION
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-.3 A0!i)n !) (" !;"n (4 An'4%!:
3.).* 9hen an" OOS test result is obtained, log the OOS entr" in the OOS log
book as per Ann"<+r" , 1.
The nu#bering s"ste# for OOS shall be as follow=
P( 4 OOS 4 @@@ 4 AA 4 888
P( indicates &rea code allotted b" .&5 to Pegasus, (hongir.
OOS indicates Out Of Specification.
@@@ indicates initiating 5epart#ent
Bas per SOP on SOP =2 P(4SOP4.&5466*46*C.
AA indicates two digits "ear code.
888 indicates three digits nu#erical OOS allocated in an incre#ental
#anner starting fro# 66* fro# each calendar "ear.
i.e. P(4OOS4@@@4./54*)466*
indicates that this is the first OOS raised b" the ./ depart#ent of the
Pegasus, (hongir.
3.)., 9hen instru#ents ha0e been used, check whether the" ha0e been calibrated
and were suitable at the ti#e of use.
3.).) n0estigate for the #iscalculations, weighing error, transcription errors,
inco#plete transfer of #aterial, and incorrect settings of instru#ents
para#eters.
3.).1 Retain all test preparations and check the raw data for an" clear #istakes
such as incorrect preparation, dilution, inDection or storage, inappropriate
en0iron#ental conditions. &lso check if the containers of sa#ple are
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STANDARD OPERATING PROCEDURE
I%%+" D!":,0-.0..201/ DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
SOP N).
P(4SOP4.&546),466
E**"0!i1" D!"
6*.67.,6*1 TITLE :
HANDLING OUT OF SPECIFICATION
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incorrectl" closed, i#properl" sa#pled and i#properl" stored and use of
e<pired working4reference standard #icrobial culture, air bubble in
spectrophoto#eter cell or HP>/ s"ste# or specified conditions not
#aintained in dissolution #ediu#.
3.).3 /heck whether an" de0iations had been noted during the ti#e of &nal"sis
and whether the" were recorded in the worksheets.
3.).; Record the obser0ations in the Ann"<+r" , 3 and hand o0er to the
i##ediate super0isor with all the original data. 5o not repeat the testing.
3.).: Protocol 4 9orksheet should be attached to OOS in0estigation for# and new
Protocol 4 9orksheet is issued b" ./ depart#ent.
-./ P&%" , I 7L()r!)r4 OOS In1"%!ig!i)n8
In1"%!ig!i)n (4 Q+'i!4 0)n!r)' )r i$$"2i!" %+#"r1i%)r:
3.1.* /arr" out the assess#ent of the OOS result as soon as the result is
reported.
3.1., 5iscuss the test #ethod with the anal"st to confir# that the anal"st had
perfor#ed the test procedure correctl".
3.1.) $<a#ine the test data sheet and acco#pan"ing attach#ents in order to find
out whether the results can be attributed to laborator" error.
3.1.1 &rrange for the re2e<a#ination of actual test preparations used b" the
anal"st and to the e<tent possible, the glassware used in the original testing.
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STANDARD OPERATING PROCEDURE
I%%+" D!":,0-.0..201/ DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
SOP N).
P(4SOP4.&546),466
E**"0!i1" D!"
6*.67.,6*1 TITLE :
HANDLING OUT OF SPECIFICATION
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3.1.3 /onfir# the perfor#ance of the instru#ents and ascertain whether the
instru#ent was within the period of 0alidit" of calibration at the ti#e of use.
3.1.; 5eter#ine that appropriate reference standards, sol0ents, reagents and other
solutions were used and that the" #eet -ualit" control re-uire#ents.
3.1.: $0aluate the perfor#ance of the testing #ethod to ensure that it is
perfor#ing according to the authoriEed docu#ents (Specification 4 STP).
3.1.7 Record all the obser0ations of the in0estigation using checklist for
in0estigation of OOS as per Ann"<+r" , /. The checklist has to be filled b"
other i##ediate super0isor.
3.1.F Suspected error #ust be in0estigated b" ./ personnel and if the error found
is genuine then the OOS result #ust be i##ediatel" in0alidated and
disregarded after appropriate recording and filing.
3.1.*6 &nal"st and ./ personnel both shall re0iew for co#pleteness of entire
procedure using the a0ailable checklist.
-.- A0!i)n !) (" !;"n (4 i$$"2i!" %+#"r1i%)r = In,C&rg" QC Si!+!i)n% I:
7C)n0'+%i1" "rr)r r"!"%!8:
3.3.* f clear error has occurred, arrange for the retesting of the second ali-uot of
the sa#e sa#ple solution or ali-uot prepared fro# the sa#e portion of the
original sa#ple b" the sa#e anal"st in triplicate.
3.3., f all the three results of retesting are within the specification, a0erage it,
and substitute the a0erage result for the initial test result (ensure that the
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STANDARD OPERATING PROCEDURE
I%%+" D!":,0-.0..201/ DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
SOP N).
P(4SOP4.&546),466
E**"0!i1" D!"
6*.67.,6*1 TITLE :
HANDLING OUT OF SPECIFICATION
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a0eraged results are within the pro0en and acceptable range) and record it
along with an e<planation for the initial anal"sis failure (%enuine lab error 2
re0ersible error). n0alidate and disregard the pre0ious results on knowing
the probable cause of error, (Record and file the obser0ations with
signature) Retain all the data together.
S!!i%!i0' 00"#!n0" 0ri!"ri:
The percentage RS5 of ) replicate deter#inations should not e<ceed the established
precision for the test.
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3.3.) f the result of retesting is outside the specification and there is no clear
error, arrange for the pro#pt retesting in replicates b" a ,
nd
anal"st (with
higher e<perience of testing) using the additional portion of the original
sa#ple. n0ol0e .ualit" &ssurance4Production to look at -ualit" trend of
other batches for the sa#e test to ha0e an idea whether the results of the
earlier batches are within the pro0en and established range.
3.3.1 f the results of retesting () replicates) b" the ,
nd
anal"st are indi0iduall"
within the specification, substitute a0erage of these results for the initial test
results of the *
st
anal"st (ensure that the a0erage results are within the
pro0en and acceptable range) and consider the# for an" decision on batch
release, after in0estigating the cause of the failure of initial results, (%enuine
lab error 2 Re0ersible error). n0alidate and disregard the pre0ious results on
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STANDARD OPERATING PROCEDURE
I%%+" D!":,0-.0..201/ DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
SOP N).
P(4SOP4.&546),466
E**"0!i1" D!"
6*.67.,6*1 TITLE :
HANDLING OUT OF SPECIFICATION
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ascertaining the cause of error (sa#ple integrit" being biased)G docu#ent the
in0estigation with the signature.
3.3.3 f the result of retesting () replicates) b" the ,
nd
anal"st are outside the
specification, report all the results in the worksheet. t #a" still be possible
that the sa#ple is biased and has laid to the failing results. Retain all the
data together.
S!!i%!i0' 00"#!n0" 0ri!"ri:
The percentage RS5 of ) replicate deter#inations should not e<ceed the established
precision for the test.
Si!+!i)n III: 7In1"%!ig!i)n )* %$#'ing #r)0"2+r" n2 %$#'" in!"gri!4
&)$)g"n"i!4 n2 r"#r"%"n!!i1" #)r!i)n8:
3.3.; 9hen the initial test and retest on the sa#e sa#ple produces the
OOS
results, deter#ine whether it is possible that the original Sa#ple was non2
representati0e of the whole lot and re-uires re2sa#pling.
3.3.: (efore re2sa#pling acti0it", it should be conclusi0el" pro0ed that the
original sa#ple was non2representati0e and also the sa#pling procedure
should be thoroughl" re0iewed. Re2sa#pling is not per#itted for unifor#it"
of content and dissolution testing failure.
3.3.7 Re2sa#pling is perfor#ed under the authorit" of Head2.& if the
in0estigation re0eals that the integrit" of sa#ple is affectedG in such
situation a portion of fresh sa#ple fro# warehouse 4 #anufacturing
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STANDARD OPERATING PROCEDURE
I%%+" D!":,0-.0..201/ DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
SOP N).
P(4SOP4.&546),466
E**"0!i1" D!"
6*.67.,6*1 TITLE :
HANDLING OUT OF SPECIFICATION
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depart#ent is subDected to reanal"sis b" an e<perienced anal"st in
triplicates. f the results () replicates) are in confor#ance to the
specification indi0iduall", the batch #a" be released (ensure that the
a0erage results are within the pro0en and acceptable range). n0estigation
into sa#pling error is to be docu#ented. Retain all the data on retesting and
re2sa#pling together.
Situation is not applicable to content unifor#it" and dissolution test.
3.3.F f in a situation where re2sa#pling does not #eet specification it is not
re0ersible classification. Retesting for OOS stops here which has to go for
full scale in0estigation into #anufacturing or processing through .ualit"
&ssurance.
S!!i%!i0' 00"#!n0" 0ri!"ri:
The percentage RS5 of ) replicates deter#ination should not e<ceed the established
precision for the test.
3.3.*6 C)rr"0!i1" $"%+r"% = 0!i)n% !) (" !;"n (4 QA=QC:
3.3.*6.* Training to the *
st
anal"st to perfor# the test, if a laborator" error has
occurred and the sa#e should be docu#ented.
3.3.*6., f the testing procedure4sa#pling procedure needs updation, it
should be done pro#ptl" with due anal"tical #ethod 0alidation and
all concerned should be infor#ed.
3.3.** f the OOS is not sorted at laborator" stage i.e. Phase 2 , then !ull scale
OOS in0estigation of production process re0iew is re-uired i.e. Phase 2 .
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STANDARD OPERATING PROCEDURE
I%%+" D!":,0-.0..201/ DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
SOP N).
P(4SOP4.&546),466
E**"0!i1" D!"
6*.67.,6*1 TITLE :
HANDLING OUT OF SPECIFICATION
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-.> P&%" II: F+'' S0'" OOS In1"%!ig!i)n:
3.;.* 9hen the initial assess#ent does not deter#ine that laborator" error caused
the OOS result and testing results appear to be accurate, a full2scale OOS
in0estigation is re-uired. This in0estigation #a" consist of a production
process re0iew and4or additional laborator" work. The obDecti0e of such an
in0estigation should be to identif" the root cause of the OOS result and take
appropriate correcti0e and pre0entati0e action. & full2scale in0estigation
should include a re0iew of production. Such in0estigations should be gi0en
the highest priorit".
3.;., !ull scale OOS in0estigation should be carried out when a product does not
#eet the appro0ed specification or an" unusual obser0ations are #ade
during the process of storage, handling, #anufacturing or testing of the
product and 4or initiated b" an" of the following conditions.
3.;.,.* OOS in0estigation (not due to anal"tical error)
3.;.,., Market co#plaint.
3.;.,.) Product recall.
3.;.) 9hene0er a failure is identified in product or process or s"ste# the sa#e
should be i##ediatel" brought to the notice of Head .&.
3.;.1 The .ualit" &ssurance depart#ent under instruction of Head .& shall
initiate failure in0estigation.
3.;.3 n0estigation should be e<tended to all the batches4products, which could
ha0e possibl" been affected b" the failure.
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STANDARD OPERATING PROCEDURE
I%%+" D!":,0-.0..201/ DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
SOP N).
P(4SOP4.&546),466
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6*.67.,6*1 TITLE :
HANDLING OUT OF SPECIFICATION
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3.;.; Head .& shall hold the release of the batch during in0estigation of the
subDected batch. Such batch should be -uarantine and should not be released
for dispatch, till in0estigation is co#plete and a decision is #ade.
3.;.: f re-uired, Head .& shall decide the cause of action to be taken after
consultation with Head2/.& to recall those which #ight ha0e been affected
b" the subDected failure.
3.;.7 &n in0estigation report shall be prepared as per gi0en for#at in Ann"<+r"
? .
3.;.F The !low chart for OOS in0estigation (Phase 2 ) gi0en in Ann"<+r" , -
and !low chart for OOS in0estigation (Phase 2 ) gi0en in Ann"<+r" , >
shall be followed in case of an in0estigation of out of specification 4 failure.
-.. C)rr"0!i1" A0!i)n%
3.:.* (ased on the outco#e of the in0estigation one or #an" of the following
appropriate acti0it" should be initiated b" .& 4 Production.
3.:.*.* /hange in the process
3.:.*., nstru#ent ser0icing
3.:., 9hene0er assignable cause is identified and is attributed to i#proper
interpretation of #ethod, the concerned anal"st should be pro0ided
appropriate training in order to a0oid such OOS in the future.
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STANDARD OPERATING PROCEDURE
I%%+" D!":,0-.0..201/ DEPARTMENT:
QUALITY ASSURANCE DEPARTMENT
SOP N).
P(4SOP4.&546),466
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6*.67.,6*1 TITLE :
HANDLING OUT OF SPECIFICATION
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>.0 RE@ISION HISTORY:
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