How to Quantify Significant Change for a Shelf Life Stability Test

[coolbreeze]

Hello everyone , this is my first post to a forum that I have utilized as a resource for many years. I am glad that I found this site when I did and appreciate all of the people that make this site what it is. Enough of the praise and onto the questions.

I am working on a Shelf Life Stability study for a new pouch that is is used to package terminally sterilized medical devices. I am wondering how to quantify a significant change in material and seal properties? The vendor supplying the pouches has stated that the change in material or seal properties would have to be higher than 25% to be considered significant. Their acceptance criteria statement reads "Historical data and industry references would suggest that a change of more than approximately 25% is a guideline for the determination of a relevant change in the properties of the material."

Does anybody know where I could find these industry references?
Also, how is your company quantifying this significant change?

I have never seen anything like this in any standard or other reference material that I have read and any suggestions would be greatly appreciated.

Thanks,

Coolbreeze

[Stijloor]

A Quick Bump!

Can someone help?

Thank you very much!!

[Ronen E]

Hello and welcome to posting on the Cove!

A clarification question: Are you relating to an intended change by the pouch manufacturer, or to a deterioration in the pouch over time (=lack of stability)? I'm asking because to me it sounds more like a policy which the manufacturer chose to follow when introducing changes (=to make decisions whether or not they have to notify their clients), and they've done their little research so they can justify it when asked "how did you form this policy?".

Either way, 25% sounds a bit dodgy to me. My gut feeling says anything beyond 10%, or even 5%, is notifiable.

Cheers,
Ronen.

[Pads38]

It might be worth comparing your process and changes with those that have been conducted by Dupont, the manufacturers of Tyvek. (trademark plus disclosure - I have no connection).

Last year Dupont announced they were changing the manufacturing method for some of their Tyvek products. They instituted a programme of tests and consultation with many regulatory bodies in what they called the Transition Project. Details here:-

http://www2.dupont.com/Medical_Packa...n_landing.html

Our EU notified body sent a position statement that suggested that device manufacturers of class I, IIa, and IIb could handle the change (of Tyvek) within their own QC systems whilst class III manufacturers would be expected to inform their notified body of a significant change.

[Bev D]

in medical industry (as well as most others such as aerospace) the 'significance' of the change is based on it's potential effect to the end use product and not on the amount of change to the material, component or sub-assembly.

Most suppliers try this type thing to 'get out of' validation testing - this response is not based on truth, physics, generally accepted practices or any regulatory standard or guideline. Your supplier may as well have said that Bigfoot told him what to do.

[coolbreeze]

Thanks for the responses. For clarification, I am performing a shelf life stability test to prove that our seals and the manufacturer's pouch seals remain stable for 5 years.

I came across this statement when reviewing the manufacturer's data, so I am not really sure what the intentions of the statement was. Therefore, it may have been to justify notification to customers or anything for that matter. I also thought that 25% seemed a bit large, although when performing some of our previous aging tests we have seen periodic changes in seal strength that were this large.

Historically, my company has an subjective and open ended statement for significant change which does not provide a definition of what constitutes a "significant change". I was hoping to get some guidance for an objective acceptance criteria or a defensible definition for "significant change" that can be used to measure and quantify the amount of change that occurs during testing. If there happens to be some reference document or standard that states this, all the better.

Thanks again.

[Bev D]

Typically a substantive change is one that is diagnostically significant or would negatively affect your label claims or other published claims. The size of this change is therefore situationally dependent.

[Ronen E]

In Reply to Parent Post by coolbreeze

Thanks for the responses. For clarification, I am performing a shelf life stability test to prove that our seals and the manufacturer's pouch seals remain stable for 5 years.

I came across this statement when reviewing the manufacturer's data, so I am not really sure what the intentions of the statement was. Therefore, it may have been to justify notification to customers or anything for that matter. I also thought that 25% seemed a bit large, although when performing some of our previous aging tests we have seen periodic changes in seal strength that were this large.

Historically, my company has an subjective and open ended statement for significant change which does not provide a definition of what constitutes a "significant change". I was hoping to get some guidance for an objective acceptance criteria or a defensible definition for "significant change" that can be used to measure and quantify the amount of change that occurs during testing. If there happens to be some reference document or standard that states this, all the better.

Thanks again.

Hello again and thanks for clarifying.

In the context of sterile pouches seal stability - IMO the "significant change" clause is irrelevant. Even seal strength is not too relevant, though it's quite easy to measure and process, and thus tempting Of course seal strength has to be above an acceptable minimum, but much more important is the seal barrier (sealing) quality. The best way to demonstrate that is via biological challenge (sterility testing) but since it's a bit expensive and complicated, many start off with mechanical tests such as pressure testing (inflating and looking for pressure drops) and dye testing - each has their pros and cons. I am not aware of 1 comprehensive published standard covering this subject in a very good way - what I've seen is a combination of scattered published test methods, in-house developed test methods, and some (creative?) justifications. You could, though, make some good use of ISO 11607 (probably already are).

Cheers,
Ronen.