Presentation on Harmonized Microbial Enumeration Methods

8/19/2019 Presentation on Harmonized Microbial Enumeration Methods

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Newly Harmonized USP Chapters

, and


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Offiial USP !iro"ial #imitsChapters

Microbial Limits Tests

Microbiological Attributes ofNonsterile Pharmaceutical Products


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USP !iro"ial #imits Chaptersoffiial from 1$%$&'

Microbiological Examination OfNonsterile Products: Microbial EnumerationTests

Microbiological Examination Of

Nonsterile Products: Tests for SpecifiedMicroorganisms

Microbiological Qualit ofNonsterile Pharmaceutical Products


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Microbiological Examination OfNonsterile Products

Microbial Enumeration Tests: (otal aero"i miro"ial o)nt *(+!C (otal om"ined yeasts and molds o)nt *(-!C

(ests for speified miroor.anisms: Salmonella Pseudomonas aeruginosa Stap!lococcus aureus Escericia coli "lostridia /ile0(olerant ram0Ne.atie /ateria "andida albicans

N "l 3iff / C


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Nota"le 3ifferenes /etween C)rrentChapter and Harmonized4ersion

4alidation 5 Or.anisms for (S+

!SP old : Staphlococcus aureus"Escherichia coli" Pseudomonas aeruginosa"Salmonella

New version:Staphlococcus aureus ATCC 6538 (NCIMB 9518,CIP 4.83, NBC 132!6"

Pseudomonas aeruginosa ATCC 9#2! (NCIMB8626, CIP 82.118, NBC 132!5"

#acillus subtilis ATCC 6633 (NCIMB 8#54, CIP5262, NBC 3134"

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http://biology.clc.uc.edu/fankhauser/Labs/Microbiology/Yeast_Plate_Count/Jeanette_spreads_P1010003.jpg


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Nota"le 3ifferenes /etweenC)rrent Chapter andHarmonized 4ersion

4alidation 5 Or.anisms for S3+

!SP old : No$ %en$ione&

New version:

$andida albicans ATCC 1#231 (NCP' 31!9,IP 48.!2, NBC 1594"

Aspergillus niger ATCC 164#4 (IMI 149##!,IP 1431.83, NBC 9455"

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!edia rowth Promotion 5 !ethodolo.y

!SP old : No$ &e$i)e&

New version: *se )ess $+n 1## C'* er%e&i. Co-n$s %-s$ e wi$+in 5#/ o0on$ro).

'or in+ii$or %iroornis%s in se)e$ive%e&i -se %ore $+n 1## C'* er %e&i.No row$+ %-s$ e 0$er %i%)in-$ion erio&.

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!ethodolo.y 5 !em"rane iltration

!SP old : No$ is$e&

New version: Trns0er v)i&$e& %o-n$ $o $wo 0i)$ers. s+

e+ 0i)$er v)i&$e& %e$+o&.

To$) Aeroi Miroi) Co-n$ (TAMC" 0i)$er is)e& on T7A, in-$e& $ 3#35oC 0or 3 $o 5

&s. To$) es$ n& Mo)& Co-n$ (TMC" 0i)$er is )e&

on 7A, in-$e& $ 2#25oC 0or 5 $o ! &s.


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+eptane riterion

+en n e$ne ri$erion 0or%iroio)oi) ;-)i$ is resrie& i$ isin$erre$e& s 0o))ows:

1#1 C'*: %. e$)e o-n$ 2#= 1#2 C'*: %. e$)e o-n$ 2##=

1#3 C'*: %. e$)e o-n$ 2###,n& so 0or$+.

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7nterpretation of res)lts and retests8

!SP old : M-s$ %ee$ ses. e$es$))owe& -sin 25 r% s%)e.

New version: M-s$ e wi$+in $wo0o)& o0sei0i$ion 0or ro&-$. No re$es$))owe&.

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(est for Pseudomonas aeruginosa

!SP old : Brin sei%en - $o 1## % wi$+T7B. In-$e. I0 row$+, s$re on Ce$ri%i&eAr Me&i-%. Co%re o)onies 0or +r$eris$is

iven ? i0 sen$, %ee$s sei0i$ion. I0 s-se$o)onies resen$, s$re o)onies on$o Pse-&o%onsAr Me&i-% 0or $+e e$e$ion o0 l)oresein andPse)domonas +.ar for the 3etetion ofPyoyanin9 Compare olonies forharateristis .ien on these additional

a.ars5 if a"sent, meets speifiation9 Confirms)spet olonies with o:idase test9 !)st "eo:idase ne.atie to meet speifiations9

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(est for Pseudomonas aeruginosa*ontin)ed

New version:

Ino-)$e s-i$)e %o-n$ o0 T7B wi$+ 1 o0 s%)e. In-$e $ 3#35oC 0or 18 $o 24+o-rs.

I0 row$+, s$re on$o Ce$ri%i&e Ar n&in-$e $ 3#35oC 0or 18!2 +o-rs.

@%ine o)onies 0or &is$in$ive%or+o)o. Confirm identity of .rownolonies9

Nota"le 3iffe enes /et een


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(est for Salmonella spp

!SP old : Brin sei%en - $o 1## % wi$+ ')-i&$ose Me&i-%. In-$e. I0 row$+, ie$ 1 % in$o 1#%: ')-i& 7e)eni$e Me&i-%, ')-i& Te$r$+ion$e Me&i-%.In-$e 1224 +o-rs. 7$re row$+ o0 o$+ ')-i& 7e)eni$en& ')-i& Te$r$+ion$e on$o: Bri))in$ reen Ar, )osesineeo+o)$e Ar, Bis%-$+ 7-)0i$e Ar. In-$e

0or row$+ ? e%ine o)onies 0or +r$eris$i %or+o)o.I0 o)onies wi$+ +r$eris$i %or+o)o seen, r% s$inn& e%ine 0or r%ne$ive ro&s. 7$7$re o)onieswi$+ r%ne$ive ro&s in$o -$$s)n$ o0 Tri)e 7-rIronAr. In-$e $+e s)n$s n& e%ine 0or re& s)n$swi$+ e))ow -$$s. I0 seen, ro&-$ 0i)s sei0i$ion.

Nota"le 3ifferenes /etween


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(est for Salmonella spp *ontin)ed

New version: Ino-)$e s-i$)e %o-n$o0 T7B wi$+ 1 o0 s%)e. In-$e $ 3#

35oC 0or 18 $o 24 +o-rs. I0 row$+,$rns0er 1 % $o 1# % ;appaport4assiliadis Salmonella nrihment/roth. In-$e $ 3#35oC 0or 1824+o-rs. I0 row$+, s$re on$o =ylose0

#ysine03eo:yholate +.ar. @%ineo)onies 0or &is$in$ive %or+o)o.Con0ir% i&en$i$ o0 rown o)onies.



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(est for /ile0tolerant ram0ne.atie/ateria

!SP old : None rovi&e&

New version: 7%)e rer$ion, $es$ 0orsene n& ;-n$i$$ive $es$ re rovi&e&



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(est for Clostridia


New version: 7ei0i $es$s 0or $+eresene o0 C)os$ri&i rovi&e&



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(est for "andida albicans


New version: In-$e T7B $ 2#25oC 0or5! &s. I0 row$+, s$re on$o 7AIn-$e $ 2#25oC 0or 2 &s. @%ineo)onies 0or &is$in$ive %or+o)o.Con0ir% i&en$i$ o0 s-se$ o)onies. I0 no

row$+, or i0 on0ir%$or $es$s s+owsene o0 $% albicans, ro&-$ sses.



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T+e new version )so on$ins $wo $)es:

T)e 1: Cri$eri 0or %iroio)oi) ;-)i$o0 nonsterile dosa.e forms

@n$ries 0or $o$) eroi %iroi) o-n$s(TAMC"

@n$ries 0or $o$) o%ine& es$s%o)&so-n$ (TMC"

@n$ries 0or sei0ie& %iroornis%s



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T)e 2: Cri$eri 0or %iroio)oi) ;-)i$o0 nonsterile s)"stanes forpharmae)tial )se

@n$ries 0or $o$) eroi %iroi) o-n$s(TAMC"

@n$ries 0or $o$) o%ine& es$s%o)&so-n$ (TMC"



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Route ofadministration

TAMC

(CFU/g orCFU/ml)

TYMC

(CFU/g orCFU/ml)

Specified micro-organisms

Non-aqueouspreparations for oraluse

103 102 Absence of Escherichia coli (1 g or 1 ml)

Aqueous preparationsfor oral use

102 101 Absence of Escherichia coli (1 g or 1 ml)

Rectal use 103 102 -

Oromucosal use

Gingival use

utaneous use

Nasal use Auricular use

102

101

Absence of

Staphylococcus aureus (1 g or 1 ml)

Absence of Pseudomonasaeruginosa (1 g or 1 ml)



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!aginal use

102

101


Absence ofStaphylococcus aureus (1 g or 1 ml)

Absence of Candidaalbicans (1 g or 1 ml)

"rans#ermal patc$es(limits for one patc$inclu#ing a#$esive la%eran# bac&ing)

102 101

Absence ofStaphylococcus aureus (1patc$)

Absence of Pseudomonasaeruginosa (1 patc$)

'n$alation use (specialrequirements appl% toliqui# preparations fornebulisation)

102

101

Absence of

Staphylococcus aureus (1 g or 1 ml)


Absence of bile-tolerantgram-negative bacteria (1 gor 1 ml)



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In &&i$ion $o $+e %iroornis%s )is$e& in T)e 1,$+e sini0ine o0 o$+er %iroornis%s reovere&is ev)-$e& in $er%s o0: -se o0 $+e ro&-$: +Dr& vries or&in $o

$+e ro-$e o0 &%inis$r$ion (ee, nose,resir$or $r$"=

n$-re o0 $+e ro&-$: i$s i)i$ $o s-or$row$+, $+e resene o0 &e;-$e n$i%iroi)reserv$ion=

%e$+o& o0 )i$ion= in$en&e& reiien$: ris % &i00er 0or neon$es,

in0n$s, $+e &ei)i$$e&= -se o0 i%%-nos-ressive en$s,

or$ios$eroi&s= resene o0 &isese, wo-n&s, orn &%e.

+ Seletion of Nota"le 3ifferenes


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+ Seletion of Nota"le 3ifferenes/etween C)rrent Chapter and Harmonized 4ersion

Table 2. Acceptance criteria for microbiological quality of non-

sterile substances for pharmaceutical use

(+!C

*CU$. or

*CU$m#

(-!C

*CU$. or

*CU$m#

7ubstances forp$armaceutical use

1& 1&2


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;eisions to Harmonized !iro"ial#imits (ests ,

Chan.es to Ne$ive on$ro) ever $i%e $+$ $+e ro&-$ is

$es$e&

Chan.es to

Ne$ive on$ro) ever $i%e $+$ $+e ro&-$ is$es$e&

e)e$e in&i$ive roer$ $es$in o0 r [email protected])i

C)ri0i$ion $o C)os$ri&i-% Tes$in

Chan.es effetie !ay 1, 2&&'


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7n)"ators

C-rren$ C+$er

2# ? 25 EC

3# ? 35 EC 35 ? 3! EC

41 ? 43 EC

43 ? 45 EC

Fr%oniDe& Gersion

2# ? 25 EC

3# ? 35 EC 42 ? 44 EC


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(he implementation shed)les

In $+e *ni$e& 7$$es, $+e $es$s wereoriin)) s+e&-)e& $o eo%e

e00e$ive A-. 1, 2##!, -$ $+ei%)e%en$$ion &$e +s eenos$one& $o M 1, 2##9 on $+esis o0 o%%en$s reeive& *7P.


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(he implementation shed)les

7n )rope, implementation has three different shed)lesdependin. )pon the sit)ation8

19 S)"stanes oered "y a mono.raph speifiation8)se the methods of the )ropean Pharmaopoeia *+)ntil the mono.raph is reised and implemented*pro?eted date8 @an)ary 2&&'9

29 S)"stanes not oered "y a mono.raph speifiation8)se either the methods of the )ropean Pharmaopoeia*+ or the harmonised methods */ )ntil @an)ary 2&1&9rom @an)ary 2&1&8 )se harmonised methods */9

9 Preparations8 )se either method of the )ropean

Pharmaopoeia *+ or the harmonised method */ ofhapter %919A )ntil @an)ary 2&1&9 or new preparations,)se of harmonised method */ is adisa"le9 rom@an)ary 2&1&8 Use harmonised method */ of hapter%919A *B9


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hat do we need D

eve)o%en$ n& v)i&$ion ro- 3 )o$s o0 $es$e& %$eri) 0or s-i$i)i$ $es$

T+e )is$ o0 %e$+o&s s+o-)& e +ee& 0or re)evne

T+e %e$+o& rov) $+e A %-s$ no$ e &e)e&

A ree%en$ n& sin$-re 0or rev)i&$ion (H" )o) or )o) o)i 0or en&e& sei0i$ion in

&r- ro&-$s

reser+er %-s$ in0or% -s o-$ $+e in$en&e&reiien$s

In se o0 &isren: w+i+ sei0i$ion s+o-)& e-se&: ven&ors or +r%ooei)H


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Thank

Presentation on Harmonized Microbial Enumeration Methods

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