Category Archives: Advice Provided

Clean Room Grade for change room in Sterile Area

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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?

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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.

Disinfection of active air-samplers

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The Question posed on LinkedIn.

Avoiding cross-contamination when using microbiological air-samplers is a key activity. But how effective is the procedure? To evaluate this, Tim Sandle and Ravikrishna Satyada have written a paper based on test data…link to Disinfection of active-air samplers.

My comment:

For filling rooms, I’d always use a double wrapped autoclaved sampling head. For ancillary rooms where the risk to the product was lower, IPA was used rather than a new head.

With internal sanitation of air samplers, when I’ve validated units like the Merck MAS100 and Biomeriux RSC+, spraying with IPA was shown to be sufficient.

With regards of HEPA filtering the output airflow, smoke pencil studies showed laminar flow would take the air to the floor. Correct placement of the air samplers within the filling space and ensuring only samplers assigned to critical filling areas were used in critical filling areas would reduce the risk of cross contamination.

Good that you data showed effective sanitation and a lack (or low) cross contamination risk.

Approaches to trend analysis of micro monitoring during aseptic processing?

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The Question posed on LinkedIn.

“Companies are expected to perform trending of their monitoring data. Detecting adverse trends should help to prevent exceedings of regulatory limits, as defined e.g. in Annex 1 to the EU or PIC/S GMP Guide for aseptic operations.

As you all know, microbial counts do not follow a normal Gaussian but a logarithmic distribution, such that the classical way of calculating and defining thresholds for alert (often +/- 2s) and action (+/- 3s) cannot be applied.

Hence, what alternative approaches to setting alert and action limits for microbio monitoring data (environment, staff, water, …) do you apply?”

My advice:

You need to have defined what your alert and action levels are and how many times in a row a site can be in alert before this 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.

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 process and documents will be dependant on which regulatory bodies have oversight at your facility.

The FDA, PDA, PIC(S), ICH and good resources like the PMF are valuable when developing your internal processes.

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

Patties Foods Frozen Berries

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I reply to a post on LinkedIn.

“The Patties Foods frozen berries scandal is a warning for directors about managing risks – what lessons could you learn? ”

My comment:

There’s lots of testing for bacterial contamination in such products as it’s regulated at Government level. Testing for viruses is not a routine requirement (it is not regulated). There’s been discussions on changing this as reportedly, about 20% of food contamination is caused by viruses and it might be a good idea to start testing.

How do we deal with strange theories?

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The Question posed on LinkedIn.

“I’ve been seeing a lot of this study the past couple days, there are a couple things bothering me in the coverage. First, I realize the point of the study was to show that most of the fat being burned is exhaled. However, this is somewhat a simplification and sort of gives the impression that the body is a bomb calorimeter (which is one aspect of many fitness/nutrition articles that bothers me anyway). I guess I would’ve personally addressed that in the explanation had I been the one to write it. Second, and more troubling to me, an unintended consequence of the way that this is covered means that many people are taking this to mean that hyperventilating or taking more oxygen in means that they will exhale more carbon dioxide and therefore lose weight without activity or diet changes. The second point is one I would have never thought to address in writing the article, so it’s made me wonder how far we have to go to address ‘strange unscientific theories’ that will pop up as a consequence of explaining research to those who aren’t as scientifically literate.”

My comment/advice:

Unscientific? Strange? The biochem knowledge seems stable (I learned the same thing in the early ’90’s with regards to carbon dioxide and water). Nothing strange about the metabolic pathways.

The paragraph about hyperventilation said do not do it and in no way advocates it. If the conclusion was to breathe more and pass out causing you to not eat as much, that would have been poor advice and potentially unscientific (passing out vs metabolic rate changes and so forth).

What makes science newsworthy?

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The Question posed on LinkedIn.

“What makes science newsworthy?”

My comment:

For specialists: a new discovery or confirmed hypothesis. Eg inflation marker, fine details of element 117.

For the couch scientist & inquiring minds: anything written well enough to be interesting.
Eg practical uses of graphene, quantum mechanics, “Cosmos”, Neanderthals vs Cromags.

For the non scientist: discoveries and developments that have the potential to affect them directly. Eg faster car, climate change, room temp super conductors, fusion power.

Career Advice

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The Question sent via LinkedIn.

” I am a Microbiologist with 3 years overseas experience. I have completed Bachelor degree in Microbiology and a Post-Graduate Degree in Medical Microbiology. I am finding it difficult to be considered for an interview since I have only overseas experience. I have recently undertaken a Post graduate Single course in Medical Microbiology from RMIT University, Melbourne to update my skills in this area and is currently looking for a job opportunity / work experience in Microbiology and would like to know if you could provide any support / advise in this regard.”

My advice:

I can only provide advice at present as I’m an unemployed microbiologist at present also. With regards to micro roles, you could see if the job agencies can help (in my experience they cannot). You could determine who has the sort of micro positions you are interested in and send the an old fashioned canvassing letter. My first micro job came from one of those and once your foot is in the door, things get easer. When applying for roles, relate your skills and experience to the roles you are applying for.

Do SVP glass containers need depyrogenation

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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.