PMFLIST Archives

June 2020

PMFLIST@LISTS.MICROBIOLOGYNETWORK.COM

Options: Use Monospaced Font
Show Text Part by Default
Show All Mail Headers

Message: [<< First] [< Prev] [Next >] [Last >>]
Topic: [<< First] [< Prev] [Next >] [Last >>]
Author: [<< First] [< Prev] [Next >] [Last >>]

Print Reply
Subject:
From:
Rick Jakober <[log in to unmask]>
Reply To:
The Pharmaceutical Microbiology Forum Email List <[log in to unmask]>
Date:
Fri, 12 Jun 2020 15:02:39 +0000
Content-Type:
text/plain
Parts/Attachments:
text/plain (92 lines)
Hi Mike,

Some comments about your points:

1. No. Method suitability recovery rates should be all you need with a caveat. I have seen acceptable recovery rates in platings with distinctly inhibited colonies (especially with A. brasiliensis). For example, the 1:10 dilution may show a recovery rate of 89% and the 1:100 dilution has a recovery  82% for an organism. However the colonies on the 1:10 plating are obviously inhibited in growth (smaller/no spore formation/obvious morphological changes from the + control). I would still enumerate them with a note describing the inhibitory characteristics and use the 1:100 dilution.
2. USP <1227>, notes this:
"Recovery on Agar Medium
In the tests under 〈51〉 and 〈61〉, ▲▲ (USP 1-Dec-2019) the number of viable challenge microorganisms in the product is estimated ▲▲ (USP 1-Dec-2019) by calculating the concentration of cfu per milliliter by the plate count method. A design for validating neutralization would incorporate the treatment groups as described under Validation of Neutralization Methods—Recovery Comparisons. At least three independent replicates of the experiment should be performed, and each should demonstrate ▲a mean count of any of the test organisms not differing by a factor greater than 2, i.e., 50%–200% recovery, from the value of the control in the absence of product. If it is necessary to solubilize the test ▲sample,▲ (ERR 1-Dec-2019) the effects of the solubilization method on viable microorganisms must be determined. This situation can occur when testing ointments, suspensions, or other articles.▲ (USP 1-Dec-2019)"
Chapter <51> is silent on this however. Three seems to be the most appropriate.
3. "Semi-officially", B. cepacia seems to be the most requested additional microorganism, however, if you have had a product failure with any microorganism, I would absolutely add that bug to the list. I also see some common environmental isolates added occasionally (be careful of adding Gram + rod sporeformers however). These would typically be objectionable microorganisms. USP <51> notes this:
"Challenge organisms are generally based on likely contaminants to a drug product while considering its physical attributes, formulation, and intended use. The standard battery of challenge organisms described in this test need not prevent the inclusion of other species of microorganisms if deemed useful to measure the biological activity of the preservative system for a specific product. These supplemental challenge organisms are not within the scope of this chapter, but may be added in addition to the described test organisms."
4. Negative controls are a great idea, especially in view of number 5 and also if the product has a lot of undissolved material in it.
5. Since these products are non-sterile, it is to be expected that there will be the occasional isolate that is not the inoculated microorganism. I would not count those. A good example would be having a recovery of bacteria as <1 log10 recovery at Day 14 (0, 0 cfu counts at 1:10 dilution) and a 1 log10 recovery at Day 28 (0,1 cfu count at 1:10 dilution of a microorganism that was not inoculated). This would fail for all 4 categories.

Hope this helps


Rick Jakober
Perritt Laboratories, Inc.
609-529-1010 mobile

-----Original Message-----
From: The Pharmaceutical Microbiology Forum Email List <[log in to unmask]> On Behalf Of Michael Barton
Sent: Friday, June 12, 2020 4:03 AM
To: [log in to unmask]
Subject: [PMFLIST] Performing AET

Hi All, i have some questions that may have differing opinions on expectaions as i cant see these activities mentioned within the chapter but should you be applying the principles within other microbiology chapters.

Questions.

  1.
Appart from proving neutralisation and acceptable recovery rates what other type of method suitability is needed before being satisfied that the method works?
  2.
do you need to prove suitability on 3 differnet batches?
  3.
do you need to use additional organisms from those 5 listed?
  4.
do you need to run a negative control at the same time? (either during suitability or in routine) e.g product neutralisation,dilution,plating without being spiked?
  5.  what do you do if you isolate some colonies that are not the expectation from what you inoculated? do you count and investigate or not?

Thanks Mike


------------------
The PMFList is supported by our sponsors as a service to the scientific community.

ease take a second to visit our sponsors' web sites and say thank you for their support of this service.
If your company would be interested in sponsoring this community, please contact [log in to unmask]



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.

------------------
The PMFList is supported by our sponsors as a service to the scientific community.

Please take a second to visit our sponsors' web sites and say thank you for their support of this service.
If your company would be interested in sponsoring this community, please contact [log in to unmask]



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.

ATOM RSS1 RSS2