Drawing from over 20 years of industry experience, gain valuable insights and expert perspectives from a trusted microbiology quality assurance leader and internal auditor.
Last year I attended an interview for a technical writer role. Nothing came of it. As part of the application process, I was tasked with taking a provided “document” and rewriting it into something suitable for a scientific environment. I retain the copyright to this rewritten instruction.
Here is the before version: Continue reading
A specified organism is one that according to the pharmacopeia, cannot be present in a sample (usually 10g). These microbes are specified either as they may be an indicator organism (a microbe where its presence may indicate a pathogenic microbe could be present) or they may actually pose product safety concerns (whether by reducing the efficacy or posing a risk to the end user). Continue reading
Updated 18 June 2020
This article is intended to give you an understanding of the following:
“If It Was not Documented, It Was Not Done”
Reviewed and updated July 2020.
At one time there were three monkeys locked in a room. This room also contained a banana, suspended by a cord from the ceiling in the centre of the room. Whenever one of the monkeys grabbed the banana, all the monkeys were subjected to an icy cold shower. After several repetitions of this shower, no monkey in the room would touch the banana. Continue reading
The Question posed on LinkedIn.
“We have all been working with the rationale that glass containers need to be depyrogenated. Depyrogenation meaning a measurable three log reduction of an initial concentration of Endotoxin.
We are now hearing about the impact of excess temperatures on the inner ‘skin’ of a vial and how some ‘hydration’ is lost when blasted with high temperatures and then we hear that after product filling, there could potentially be a ‘re-hydration’ of this ‘skin’. And finally all this dehydration and re-hydration potentially causing glass lamellae formation. (I am not a glass technologist, I’m groping around the dark here, feel free to correct any misconceptions!)
With all this concern about particulates, does it make sense to scale down glass vial heat treatments in SVP to sterilization temperatures rather than depyrogenation temperatures?
A vial which has been washed with a final rinse in hot WFI is not expected to have any significant level of endotoxin in it. Considering the volume adminstered, doesn’t it make sense to move to concentrating on sterilization rather than depyrogenation of an unrealistically large quantity of endotoxin load?”
My advice:
Yes. You must depyrogenate your containers where the product is being injected into the customer and regardless of rinsing or dry heat, you have to show you can remove pyrogens from your containers.
It would be UNWISE to use a sterilization protocol in an attempt to dehydrogenate your glassware if that if what you are suggesting. Pyrogens from when G- bacteria are destroyed. You need to physically remove them or “char them to death” for want of a better term. Using a sterilization to remove pyrogens will ultimately lead to dead customers and your company being severely affected.
You could scale back your temperatures when using a DHO as there is a range of temperatures allowed. Lower temperature equals longer exposure time. If your company is happy with the increased time it takes to make batches, then you could validate your new process and take it from there. If it is an amendment to your current process, then if it is a big enough one, you’d need to alter your product registration.
Regarding temperature effects on your vials. I’d examine where you heard the information and determine if they are a reputable source, determine what other companies are doing (and if the regulatory bodies have said that that’s an acceptable standard practice) and either enlist the services of an expert or conduct your own experiments.
The Question posed on LinkedIn.
“Dehydrated Culture Media used in “Media Fill”. Does the powder specification need to be sterile (irradiated) or it can be sterilized by filtration (0.22µm) just after browth preparation in tank?”
My advice:
Your starting dehydrated media should meet your existing limits for raw materials with regards to microbial load.
If your standard procedure is to formulate your product in an ancillary room and sterile filter it on the way to the filling heads, then I would include this in your sterile media fill trials as it simulates your normal batch process.
A batch simulation with no interventions should demonstrate your filtration sterilises your “product”. Once that’s done, you can then incorporate interventions into your sterile media fill trials.
I was flicking channels last night and came across an episode of Landline on the ABC. Being broadcast at the time was an article entitled “Smell The Roses”.
Of most concern to me were the following words I heard shortly after tuning in “…we actually freeze dry the rose petals, they’re taken down to minus 20 to minus 40 degrees, which means it kills off all potential bacteria, diseases…”
As a microbiologist with over 15 years experience within the pharmaceutical industry, I happen to know a thing or two about preservation processes and the above statement is incorrect.
One of the aseptic manufacturing lines where I worked included a freeze drying chamber. Once the product was filled, it passed into this chamber where all the water would be removed at a negative air pressure and at reduced temperature. This turned liquid drugs into a powder which could be stored theoretically forever before use. To make the powder ready for injection, all the administering doctor or nurse needs to do is add water. The process is explained in the diagram below. I apologize for it being a quick and nasty sketch that is not to polished and to scale. Continue reading
The Question posed on LinkedIn.
Many say storytelling in science is a great way to describe complex material in an understandable way for the masses. In this post, I will try to use an analogy to illustrate the complexity of a typical motile bacterial cell. Link to referenced article.
My advice:
Perhaps, as the blog suggested – write an abstract for Joe Public. As well as the article submitted to a journal, perhaps a press release or one page summary in very general terms as to what the study set out to do and what the conclusions were along with possible applications of the new knowledge (unless the study disproved something or was confirming another study).
The Question posed on LinkedIn.
“Somebody asked me why we continued placing the TOC, List of Figures, and List of Tables at the beginning of a document and not having one these at the beginning of each section/chapter.
Several years ago I released technical manuals using section-based TOCs and other lists. However, that was because Word 97 in my PC (Win 98) could not work with large documents. Once I had a powerful enough PC/Word combination, I never did it again.
I mostly update the TOC and the other lists doing Ctrl-A + F9, which brings up the “Update XXX” dialog box for each table. Since I use appendixes, this methods also generates dialog boxes for them as well. I realize that using TOCs and lists at the beginning of each section would make the updating process longer, as more dialog boxes would pop-up.
However, I now ask myself whether it would be advantageous to do such thing, and why. ”
My advice:
At the beginning of the document as it is easy to find. A sub TOC at the start or each chapter could be a bit more informative.
Word is very bad for formatting and tables, but it seems “everyone” besides the graphic design industry uses it or something similarly bad.
The Question posed on LinkedIn.
“does tga have any guidance on “studies of antioxidant”? ”
My advice:
If the antioxidant is used as a preservative, then you would need to look at the EP 5.1.3.