Microbiological Trending of Environmental Monitoring Data

Microbiological trending of environmental monitoring data serves multiple purposes:

  • Trending helps to define and hone your limits
  • Trending helps to determine if control of your processes has been lost (or is heading that way)
  • Trending helps to identify the effectiveness CAPA and process ‘improvements’

In order to produce relevant trends, you need to have defined what your alert and action levels are and how many times in a row an alert constitutes an action. You also need to define how many below alert results may indicate an adverse trend. Basically you want to get what is heading out of control under control.

Data to trend includes all data collected from your viable environmental monitoring program.  Showing these trends in graphs allows for easy identification of trends.  As part of your trending, you should identify your top 10 microbe species detected within your production facility.

You need to have a defined trending and reporting period and reports need to be signed off both by the microbiologist and QA manager.

Your internal processes and documents will be dependent on which regulatory bodies have oversight at your facility.

A more detailed, though old post regarding trending can be read here.

Some resources:
http://www.fda.gov/Food/FoodScienceResearch/LaboratoryMethods/ucm124900.htm

http://www.microbiologyforum.org/content/file/PMFNews.17.03.1103.pdf

https://www.pda.org/docs/default-source/website-document-library/chapters/presentations/midwest/making-sense-of-your-environmental-monitoring-data.pdf?sfvrsn=4

Does anyone use Evernote as an ELN (electronic laboratory notebook)?

The Question posed on LinkedIn:

Does anyone use Evernote as an ELN (electronic laboratory notebook)?

Evernote seems to be a powerful, extensible cloud based application. I am curious if anyone in the group uses it in their lab and how do they use it, for what purpose and how well does it work for your needs?/

My reply to this was:

I’d not advise it. Besides a vendor audit to ensure availability of the system and backups you’d need to ensure Evernote data cannot be obscured or changed, make sure time, date and user stamps are in place and the data integrity is maintained for the duration of the retention period.

 

Using MS Excel or MS Access for Tracking

The Question posed on LinkedIn:

“Quality Assurance of Excel-Tables or Access-Databases used for tracking Change Control Procedures , Deviations, or Complaint handling

While larger companies nowadays use validated systems such as Trackwise, SAP modules and the like for following-up on their CCPs, deviations, CAPAs etc., in GMP inspections of smaller companies I usually encounter some sort of electronic Access- or Excel-based lists that are used (typically by QA) for this purpose, i.e. entering cases, assigning event ID’s, and supervising the progress of investigations / implementation measures until approval / close-out.

These lists a quite critical, especially when many events have to be dealt with, a.o. because of the risk that certain events might get ‘forgotten’.

Nevertheless, I see quite often that little is done to ensure that entries in these lists are correct and uptodate. Another issue is controlled handling of hardcopies of these lists which often, not astonishingly, are outdated as soon as they come out of the printer.
Any ideas what it makes challenging to deal with these lists? What are proven good practices worthwhile to share?”

My reply to this was:

Just like for word, Excel has a revision tracking feature.

There are ways to log changes to tables data in Access, but none are particularly robust.

It all boils down to using the right tool for the job. Is Excel or Access a suitably regulatory compliant solution or do you need to use something else?

The last line of the my comment sums things up nicely.

TGA Inspection Trends

My reply to a post on LinkedIn.

Current TGA Inspection trends: This presentation will focus on the common types of deficiencies found by the TGA’s GMP Inspectors as well as some data on the number of inspections performed both locally and overseas and compliance rating outcomes for the inspections performed.

Comment 1 stated “…there are patterns that seem to repeat year after year. Poor QMS, inadequate investigations, lack of training.”

My reply to this was:

“The PIC’S guide to GMP stresses the need for a robust QMS and repeats over and over again the need for documentation, solid investigations and adequate training and retraining. It is a wonder why citations regarding a lack of these keep being given.” Continue reading

GMP Manual

The Question posed on LinkedIn.

“Dear experts..
Is there any links to get the chapters of the GMP manual ?”

My advice:

The ICH link is good as you’ll be able to download the documents various GMP guidance such as PIC/s recommendations and regulatory guide lines such as the Aust Code of GMP (as an example) are based on.

You can then find valuable information on recommendations from sources such as the FDA, eg http://www.fda.gov/downloads/Drugs/…/Guidances/ucm073517.pdf

So we might provide a less general answer, what specifically are you looking for?

Environmental monitoring: viable particles

The Question posed on LinkedIn.

“Hi all, I would like to ask you about how to perform cleanroom microbiological environmental monitoring. Is it clearly defined in guides?
TSA and Sab at different temperatures or only TSA? If only one TSA plate, do you incubate at 20-25ºC and then at 30-35ºC, or only at one temperature?
Do you performe growth promotion test in same conditions?
Thank you for your comments!”

My advice:

USP <791> Environmental Monitoring Program Design and Application

USP <1116> Microbiological Control and Monitoring of Aseptic Processing Environments states “….time & incubation temps is made once…media have been selected. Typically…22.5 ± 2.5 and 32.5 ± 2.5…incubation time of 72 & 48 hrs, respectively. Sterilization processes used to prepare growth media for the environmental program should be validated &…media should be examined for sterility & for growth promotion as indicated under Sterility Tests 71. In addition, for the Growth Promotion test, representative microflora isolated from the controlled environment or ATCC strain preparations of these isolates may also be used to test media. Media must be able to support growth when inoculated with less than 100 colony-forming units (cfu) of the challenge organisms.”

So, pick your media. Test it. After that, validate your sampling recovery methods.

Air Shower Qualification

The Question posed on LinkedIn.

“Can any body guide me how to perform the air shower qualification in potent drugs manufacturing? Is there any guidance for the same? Which test needs to be covered during qualification? ”

My advice:

Having worked in sterile production facilities, I’d consider an air shower a bad idea (increased particulates, impact on pressure differentials, ineffective removal of static particles (even creation of static particles) etc risk of forcing particles through PPE onto operator, cross contamination of surrounding de-gowning area/airlock).

I’ve found an old (2002) article that might help you with any URS and subsequent validation activities you develop:
https://www.alnmag.com/article/2002/12/how-do-air-showers-fit-contamination-reduction-plan

There are also two old (1999 and 2002) references at the end of the (linked) article.

Clean Room Grade for change room in Sterile Area

The Question posed on LinkedIn.

“Please let me guide or give recommendations, what will be grade of change room just opening in Aseptic filling area. Please mention reference also.”

My advice:

PE 009-12 (Annexes) 2015.

Annex 1 states:
“Changing rooms should be designed as airlocks and used to provide physical separation of the different stages of changing and so minimise microbial and particulate contamination of protective clothing. They should be flushed effectively with filtered air. The final stage of the changing room should, in the at-rest state, be the same grade as the area into which it leads.”

So, what Grade is the filling facility? That is the grade you should validate your changing room/airlock to be.

A google search will find you the relevant PIC/S PDF.

Followup comment

You can download all the PIC/S documentation here: http://www.picscheme.org/publication.php

Are Terminal Sterile Filters in Water Systems permissible?

The Question posed on LinkedIn.

Post by a consulting company, “Are Terminal Sterile Filters in Water Systems permissible?”

My comment

Without reading the linked article, my gut feeling was no as viable monitoring would not be able to detect any contamination issues in the water lines. Additionally, a filter failure in a contaminated system could be a tad disastrous. I’d rather assure the quality of a system through monitoring, rather than a slap on filter.

Reading the article, I’d forgotten about endotoxin risk.