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Subject:
From:
Donald English <[log in to unmask]>
Reply To:
The Pharmaceutical Microbiology Forum Email List <[log in to unmask]>
Date:
Tue, 21 Jul 2020 21:28:17 -0400
Content-Type:
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Dear Tony,

I'm in agreement with your statement that tablets should not be tested for
the presence of Burkholderia cepacia complex.

For most aqueous non-sterile product formulations that have the presence of
Burkholderia cepacia complex, the water that is used to manufacture the
product is the likely source of the contamination.

In your posting, you had stated that the expert committee was aware that
companies may use the test for water
monitoring and added the caution suggesting dilution of the
enrichment broth may be necessary to recover Bcc. No endorsement of this
monitoring should be implied.

I would have not included the statement in the chapter as an option and
just leave it for non-sterile aqueous and inhalation product formulations.
If the USP expert committee has a concern about Burkholderia cepacia
complex in the water that is used for aqueous non-sterile product
formulations  it would have been more appropriate for the USP expert
committee to develop an actual microbial test chapter for purified water
instead that is not a guidance chapter.  Most of the microbial test methods
that are used for the microbial analysis of water comes from Standard
Methods for the Examination of Water and Wastewater.  In this book, there
is no enrichment test method for detecting the presence of Burkholderia
cepacia complex in water samples.

Before this chapter had been issued, I would think that it was not a common
practice to conduct enrichment testing on purified water samples.  If
identification is done, it is performed on microbial colonies that are
present on the pour or membrane filtration recovery plate.  Furthermore, I
would tend to believe that most people did not test their purified water
samples for the presence of Burkholderia cepacia complex by
conducting identification on recovered isolates unless the microbial counts
were above the alert and action levels for a water system.

If the USP expert committee has a concern about the presence of
Burkholderia cepacia complex in purified water system for non-sterile
aqueous products which is justified from my perspective, make it a
requirement that speciation be conducted on representative colonies from
recovery plates in a purified water microbial testing chapter instead of
placing this vague statement in the chapter for detecting the presence of
Burkholderia cepacia complex in aqueous finished products that it is
optional for pharmaceutical grade water.  In addition, this purified
water microbial testing chapter should not be a guidance chapter because
the information in it is not requirement.  If such a requirement was put in
place for identification of all recovered colonies on all purified water
samples no matter what was the count, it might cut down the number of
product recalls due to Burkholderia cepacia complex contamination.

I also wonder whether Burkholderia multivorans and Burkholderia cenocepacia
would actually be detected in a purified water sample by conducting
enrichment.  In a purified water system, the microbial population is not a
monoculture environment.  Several different species can be present within a
purified water system at the same time due to the microbial variability of
the source water.  In addition, water borne organisms that have a faster
growth rate may inhibit the detection of Burkholderia cenocepacia and
Burkholderia multivorans by using TSB enrichment of USP Chapter 60 due to
their slower growth rates.

In regards to my statements on this subject, I believe that some people
will agree with me and others would like to burn me at the stake by
providing the wood because I question the expertise of the USP Microbiology
Committee.  However, I believe that the purpose of this forum is
educational by having the free exchange of different viewpoints on a
subject.  This is what makes Microbiology fun.  We all learn in the end.

Regards,
Don

Donald J. English Microbiological Quality Consulting LLC
Florham Park, New Jersey



Don





On Tue, Jul 21, 2020 at 6:30 PM Stephen Langille <[log in to unmask]>
wrote:

> Don and Alison,
>
> I can't speak for all regulatory authorities but the FDA almost never
> requires speciation of WFI isolates due to the significant downstream
> sterilization controls that are implemented to neutralize the bulk drug
> product bioburden.  Speciation could be requested to investigate a
> catastrophic sterility assurance failure but it's rare.  The choice not to
> speciate WFI organisms is supported by a risk assessment showing that the
> levels of microbial contamination in the raw materials (including water)
> and pre-filtration bioburden cannot withstand the sterilization process and
> are not of a sufficient population to affect the purity, strength, potency
> or quality of the finished drug product.  The same risk assessment process
> can be used to determine if testing for B. cepacia complex in
> pharmaceutical water systems used for the manufacture of non-sterile drug
> products is necessary.  Usually it is not, but there are instances where
> testing water systems for B. cepacia complex may be b!
>  eneficial due to factors such as manufacturing/product history, weak
> downstream controls, or the unique nature/intended patient population of
> the drug product.
>
> Best,
>
> Steve
>
> -----Original Message-----
> From: The Pharmaceutical Microbiology Forum Email List <
> [log in to unmask]> On Behalf Of Donald English
> Sent: Sunday, July 19, 2020 8:06 PM
> To: [log in to unmask]
> Subject: Re: [PMFLIST] Chapter <60>
>
> Hi Allison,
>
> I see that no one had responded back to your posting about using USP
> Chapter 60 in a sterile manufacturing facility.
>
> In the introduction of USP Chapter 60, it is stated as follows:
>
> The tests are designed to determine whether a substance or preparation
> complies with an established specification for microbiological quality
> and/or to evaluate whether products—especially those for inhalation use or
> aqueous preparations for oral, oromucosal, cutaneous, or nasal use—contain
> members of the Bcc.
>
> In reality, there is no reason for using USP Chapter 60 because the
> chapter is for non-sterile aqueous and inhalation products based upon the
> introduction of the chapter.  However, it is stated in the testing product
> section that it may be used for the testing of pharmaceutical waters.  It
> would be interesting to see if regulatory authorities would require
> Water-for-Injection that is used for making sterile product formulations be
> tested for the presence of Burkholderia cepacia complex by using the
> methodology of this chapter by having this particular sentence in the
> chapter.
>
> By having this sentence present in the chapter, I would suspect that you
> would be required to conduct Burkholderia cepacia complex of collected
> Water-for-Injection samples because it is kind of vague of what is meant as
> pharmaceutical water in the chapter.  From my perspective, the presence of
> any Gram-negative bacterial species in Water-for-Injection samples would be
> objectionable.
>
> Regards,
> Don
>
> Donald J. English Microbiological Quality Consulting LLC Florham Park, New
> Jersey 07932
>
>
>
>
>
>
>
> On Fri, Jul 17, 2020 at 7:35 AM Berman, Alison <[log in to unmask]
> >
> wrote:
>
> > Hello,
> >
> > Is anyone performing chapter <60> testing at a sterile injectable
> > manufacturing company, at any stage of manufacturing?
> > Is there any reason one may do so and if yes, on what would the test
> > be performed?
> >
> >
> > Thanks
> >
> >
> >
> > Alison Berman, MFS
> > Supervisor
> > Quality Control - Microbiology
> >
> > [AMR_Logo_for Email Signatures_19DEC]
> >
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> Steris - http://www.sterislifesciences.com/
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> Charles River Laboratories -
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>
> Veltek Associates, Inc - http://www.sterile.com
>
> Microbiologics, Inc. - http://www.microbiologics.com
>
> BD Industrial Media - http://www.bd.com/ds/
>
> Associates of Cape Cod, Inc. - http://www.acciusa.com/
>
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> The nature of this service is to provide a medium for communication.  The
> specific statements and endorsements of individuals participating in the
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> Steris - http://www.sterislifesciences.com/
>
> Charles River Laboratories -
> https://www2.criver.com/l/60962/2020-03-27/h6jqv6
>
> Veltek Associates, Inc - http://www.sterile.com
>
> Microbiologics, Inc. - http://www.microbiologics.com
>
> BD Industrial Media - http://www.bd.com/ds/
>
> Associates of Cape Cod, Inc. - http://www.acciusa.com/
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Please take a second to visit our sponsors' web sites and say thank you for their support of this service.
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Steris - http://www.sterislifesciences.com/

Charles River Laboratories - https://www2.criver.com/l/60962/2020-03-27/h6jqv6

Veltek Associates, Inc - http://www.sterile.com

Microbiologics, Inc. - http://www.microbiologics.com

BD Industrial Media - http://www.bd.com/ds/

Associates of Cape Cod, Inc. - http://www.acciusa.com/


=================================
The nature of this service is to provide a medium for communication.  The specific statements and endorsements of individuals participating in the discussions are not necessarily those of the PMF or the sponsors of the list.

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