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Autoclave cold spot, any advice!

Hi Guys,

Could I please get some input from the following question:

During heat distribution study of autoclave

It has been observed that there is cold spot .
What should be the course of action to deal with it?
Much appreciated if you could share practical wisdom.

Regards

[quote=gokeeffe]Hi Guys,

Could I please get some input from the following question:

During heat distribution study of autoclave

It has been observed that there is cold spot .
What should be the course of action to deal with it?
Much appreciated if you could share practical wisdom.

Regards[/quote]

During empty mapping studies, cold spot would be observed. This cold spot should be reproduced during all runs. Place thermocouple and Biological indicator at the cold spot and examine the SAL 6 log reduction. Calculate F subo value at the cold spot to get the lethality factor at coolest place. If the require value is achieve along with 6 log reduction then the cold spot doesn’t make any impact and in case not then using the temperature / pressure tool to achieve the required f subo and SAL.

I would also look into the pre conditioning of the chamber. Trapped air can also cause a cold spot. Also, how cold is this cold spot? Are you passing your other tests? Bowie-Dick? Could be a faulty chamber that isn’t insulated properly or the jacket has an issue. I don’t think you can write off a cold spot and get GMP certified. Your chamber has to demonstrate uniformity.

I have mentioned in my earlier post that if the cold spot is reproduced then it shows that it is a coldest place in the chamber temperature distribution not due to malfunctioning of autoclave because generally coolest point occur due to trapped air or any other malfunctioning reason, it always produce in different positions in different runs.

Hi guys

An effective Autoclave must contain dry saturated
steam to achive the uniform distributon of heat eliminating any cold spot. In order to achieve this ,air must be removed from both
the load and the chamber; this can be accomplished in a number
of ways. Air removal from high mass low load items (i.e.
comprising mainly solid areas that contain little or no air pockets
such as bottled media) will need little air removal and this can be
facilitated by automatic air purging. Here air is allowed to leave
the chamber through a vent as steam enters the chamber either
from an integral source (upward displacement) or an external
supply (downward displacement); this vent only closes when all of
the air is removed from the chamber. This method can be further
advanced by ‘Freesteaming’ when the vent is allowed to stay
open for a set length of time. The turbulent steam then passes
through the vent forcing any trapped air out of the autoclave. For
more stubborn loads that contain a number of air pockets such
as wrapped instruments or fabrics, a more effective method of air
removal is essential. By far the most effective way of air removal
is a vacuum system, whereby a vacuum is achieved in the
chamber before any introduction of steam, removing most of the
air before freesteaming and/or vacuum pulsing.
Once all of the air is removed from the load and chamber the
temperature within the vessel will rise along with the pressure until
the pre-selected temperature is reached and hence like that cold spot can be eliminated.

As Mr Shahnawaz commented that “If the require value is achieve along with 6 log reduction then the cold spot doesn’t make any impact and in case not then using the temperature / pressure tool to achieve the required f subo and SAL” . The main objective is to achive SAL of 6 log reduction from each and every cubic centimeters in an autoclave and Shahnwaz gave nice post.

Thanks Guys,

I have a better understanding now.

Best Regards

I do not think the original question has been answered. There are steams sterilizers around that do have cold spots. All the companies I know that had them - junked them some years ago. To try and prove to a regulator that you have the correct bacterial reduction, without having sterilizing temperature - would be quite silly. I would ask these people that claim they have cold spots, but maintain it does not affect the performance - if they would be quite happy working with a violent pathogen, while relying on such a machine for their own safety.
Cold spots are caused by bad design and usually occur around the drain, where the mass of metal in piping, casing and jacket occurs. This mass conducts heat away and often prevents killing conditions being attained.
Remedies;
First and best option get rid of the machine - second option, one I have had to use (many years ago) - define the low temperature area - manufacture a stainless steel cage, that will prevent product ever occupying this area. Make sure the cage is fixed and cannot be remove accidentally. Re-validate sterilizer paying particular attention to the temperatures in the area surrounding the caged. Lastly ensure that your quality steam system is validated.
Alex

Thanks Alex very insightful

[quote=alexkennedy]I do not think the original question has been answered. There are steams sterilizers around that do have cold spots. All the companies I know that had them - junked them some years ago. To try and prove to a regulator that you have the correct bacterial reduction, without having sterilizing temperature - would be quite silly. I would ask these people that claim they have cold spots, but maintain it does not affect the performance - if they would be quite happy working with a violent pathogen, while relying on such a machine for their own safety.
Cold spots are caused by bad design and usually occur around the drain, where the mass of metal in piping, casing and jacket occurs. This mass conducts heat away and often prevents killing conditions being attained.
Remedies;
First and best option get rid of the machine - second option, one I have had to use (many years ago) - define the low temperature area - manufacture a stainless steel cage, that will prevent product ever occupying this area. Make sure the cage is fixed and cannot be remove accidentally. Re-validate sterilizer paying particular attention to the temperatures in the area surrounding the caged. Lastly ensure that your quality steam system is validated.
Alex[/quote]

[COLOR=“RoyalBlue”][COLOR=“Navy”]Dear Alex before going to the debate one must grasp in his mind what is cold Spot? It is the one which represent the point with least temperature obtained. It doesnt sound a cold temperature or a spot having cold temperature. This is actually the place (worst case scenario) where SAL levels are challanged. This is the point where minimum F° is calculated. and this calculated f° gives the real sense to achieve SAL level and Cold spot is covered by increasing holding time, and by getting satisfactory SAL level, not by installing a steel cage. which makes no sense.Its so silly to just through out the equipment, without knowing the concept of cold spot.
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Thanks

Well before this cold spot becomes a cold war let me clear it. All in all what shahnawaz said thats ok to me, Infact in Autoclave qualification we majorly play with temperature and holding time, and calculate F° for cold spot taking it as a worse case scenario. The idea of Steel cage is out of the question.

Dear Mr Alex

Cold spots means the least temperature in the chamber with respect to the other spots and it does not means that it has a temperature lower than the sterilization temperature.First we should find out the location of cold spot(if any) which is normally due to the trapped air or at the drain point due to the condensation of steam, ensure that all the air has been removed from the chamber and vacuum is made inside and then introduces the dry saturated steam and must ensure the sterilization temperature at the pre located cold spot and hold for the calculated time.

you have kept using the stainless steel cage in the chamber which does not look a professional way of working . What about your way of working for dry heat sterilizers? is there again a cage is being used by you in that?

Thanks

Ahsan Khan

I have heard of the cage method in controlled temperature rooms and even hot air ovens, never heard of it in an autoclave. I guess if you have a reproduceable cold spot, I could see the logic. I don’t think you could ever use an autoclave for sterilization where the Fo somewhere in the chamber is non-conforming. I guess you could increase the cycle time to achieve your kill. This really only applies to non-heat liable goods. IMHO - this type of sterilizer should only be used for decontamination runs, I am pretty certain there are chamber uniformity regulations/guidelines for sterilization. I just don’t have them memorized.

I think Graham , you need to define by what you mean as a cold spot. Somehow from an overall validation point of view, Alex’s solution makes perfect sense to me wihout getting too much involved in the theory . In the end its about protecting lives.

Dear All,

FYI,

Determination of specific “cold spots” in an overkill load is an exercise
which provides information of limited value. In the event the load size is expected to vary, minimum and maximum loads should be identified. (Ref “INDUSTRIAL MOIST HEAT STERILIZATION IN AUTOCLAVES” PDA Technical Monograph No. 1 - 2002 Revision).

When validating the ability to sterile the equipment, heat distribution studies in autoclaves must be done to determine the cold spot.(Ref “Validation of Active Pharmaceutical Ingredients” By Ira R. Berry, Denial Harpez).

Thanks

Several Thoughts (Although it has been awhile since I have done Autoclave work).

There needs to be a clear interpretation as to what is meant by a cold spot. By definition there will ALWAYS be a cold spot. The question is does it reside within an acceptable temperature distribution? There is a huge difference between having a cold spot of 121.4 C and one of 117.4 C.

Furthermore is this a distribution cold spot or a penetration cold spot?

The distribution cold spot is a OQ based activity in my opinion and is reflective of the performance of that machine. I know most publications/standards/guidances such as PDA/USP/EN give a proper range of temperatures in the Empty Chamber.

If its not something that a repair fixes and is truly reflective of the capability of the machine then the question needs to be asked how well was the build of the machine controlled from a specification standpoint.

Certainly if this is a a legacy equipment then it needs to be considered if it’s fit for purpose and what procedural controls are in place for this machine. Furthermore you will have an uphill battle with regulators to say why you chose to ignore guidance documents.

On the penetration side there can be cold spots but that is a different scenario. Quantitative data such as FO and BI results can be used to determine truly if you are acheiving appropriate SALs. Beware of the European Regulation (not sure if it still exists) where they look for Penetration Uniformity within a quick amount of time during exposure.

Lastly Following what has been previously identified is your approach a bioburden based one or is it an overkill approach? Certainly you require precise control for a bioburden approach.