INSIGHT - Comments
Vol. 4 No. 5 - Do You Really Know What is in Your Freeze-Dryer?
Dear Thomas
Thank you for the last issue of Insight. In response to your article we have found that the bottom of our shelves, overtime, becomes lightly coated with a layer of silicon. This silicon comes off the bungs when the vials are stoppered at the end of the freeze drying process, this can cause problems with sealing and breaking vials as the stoppered vials stick to the bottom of the shelf above and then fall off. The bungs are siliconised which
allows them to flow during the filling stage on the filling machine -filling would not be possible without siliconisation. This build up is removed by wiping with alcohol wipes.
We are operating to cGMP standards, practising aseptic techniques in an area that is class A over the product processing area, and a background Class B.
Anonymous - May 2001
Response by T. A. Jennings, Ph.D.
Thank you for sharing your experience with the sticking of the "bungs" (closures) to the upper shelf. Certainly the breaking of the vials allows not only dried product to enter the dryer but could, depending on the nature of the product, represent a hazard for handling of the vial with dust on the outside of vial surface. The broken vials also become a source of glass particles and care must be taken that they are removed.
Can you share with us what alcohol you are using to remove the excess silicone and how do you determine when the upper surface of the shelf is clean?
You also raise another question and that is does the silicone penetrate the bung and is it released during the compression exerted by the stoppering mechanism?
Response by Anonymous
We understand and appreciate first hand the problem/hazard of glass breaking and product being released into the freeze dryer and possibly into the clean room once the door to the freeze dryer is opened, it is especially contentious as we are working in a clean room. Thankfully it is not an everyday occurrence.
The bungs are siliconised by the supplier, and the grade is pharmaceutical and it is validated to be compliant with the product concerned. Currently there are 2 methods for cleaning the shelves if it is thought that there is a build up of silicon (remember we are talking about a very thin film) either using clean room wipes that are impregnated with IPA or using a sterile filtered solution of acetone. The surface of the shelf is deemed clean by a simple visual test, as Silicon is an extremely inert substance so difficult to test for.
I guess there is the definite possibility of Silicon getting into the product from the bung, but as the bung is deemed product contact this is validated during product development/compatibility studies.
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Dr. Jennings,
First, I would like to extend an invitation for you to visit the BOC Edwards Pharmaceutical Systems manufacturing facility in Tonawanda, NY. If you should happen to find yourself near or passing through our area (Buffalo) we would be delighted to arrange a tour.
You are absolutely correct that there is a lot of opportunity for contamination in any industrial manufacturing environment. Our factory floor is quite clean and tidy for a work shop environment and we take precautions such as wearing disposable booties if entering the chamber. Despite the best efforts to maintain a clean work environment it is still necessary to thoroughly clean and passivate the complete freeze dryer prior to shipment.
In the case of a large industrial dryer that must be disassembled for shipment and reassembled at the customer site, additional precautions must be taken. Any open ports on the dryer must be capped as well as the ends of any piping that has been removed. Since the hydraulic piston must often times be removed, it is necessary to stabilize the shelves with packing materials thus introducing foreign materials.
The environment during installation is often far dirtier than anything that could be imagined at the factory. It is not unusual to be installing the new freeze dryer in the middle of a construction site. There are periods when the environment is completely uncontrolled and the customer will necessarily have to fabricate new utility piping to the dryer. Very often foreign material is introduced into the dryer through newly fabricated utility lines. For these reasons it is generally advisable to thoroughly clean and re-passivate the freeze dryer after installation.
Regards,
Mike Stella - May 2001
Manager, Process Training
BOC Edwards Pharmaceutical Systems
Tel 716 695 6354 ext. 1082
Mobile 716 316 4957
Response by T.A. Jennings, Ph.D.
Thank you for the invitation and I certainly will stop in a see your facilities should I be in the area. I am glad to learn that your company is making extra efforts to produce a clean dryer. Your point about the client site being a source of contamination is well taken and perhaps companies should heed the warning and start to take extra care on their part during installation.
