Time Zero testing in med device aging studies

[Sam Lazzara]

What is the relevance of "Time Zero" testing for medical devices from the standpoint of meeting regulatory requirements to defend your labeled shelf life?

In my research, I have found no requirements or mention of this issue in any medical device regulations or standards or FDA guidance. In the past several years, I have seen letters written to my clients where FDA is recommending Time Zero testing in addition to accelerated and real-time aging.

My argument is that while Time Zero test results may be intellectually interesting, in comparison to the aging timepoints, to show changes/trends, they do not support the labeled shelf life (Use By date) and are therefore not necessary. And I have (almost) never come across a situation where polymeric device performance improves due to aging.

What is the legal, regulatory basis for performing Time Zero testing?

 

[shimonv]

Hi Sam,
A very interesting question. I agree that "time zero" testing does not support the labelled shelf life but it does provide a reference point for subsequent tests.
I have seen examples of acceptance cretieria for package integrity (burst, peel) where they compared the results from subsequent years to T=0.

Also, being a reference point, you can expect that the results from T=1,2,3.. should not exceed T=0. Polymers are not like wine

To be frank, the whole concept of shelf life is far from being "least burdensome approach". I suppose that if you can build a shelf life validation protocol that does not relay on T=0 you have a valid case and you save time and money for clients.

Cheers,
Shimon

 

[planB]

Sam,

adding to what Shimon said: To my knowledge, there is no legal or regulatory requirement to have T=0. But it provides you an additional reference point to detect any aging trends over time.

I have also used (comparative) T=0 results in change management activities for building/supporting rationales why you do not need to fully repeat your existing stability studies, e.g. when you introduce 2nd-source suppliers for your SBS packaging materials, modify your terminal sterilization process to some extent etc. To my experience, these rationales have then been accepted world-wide.

HTH, Gerhard

 

[v9991]

My argument is that while Time Zero test results may be intellectually interesting, in comparison to the aging timepoints, to show changes/trends, they do not support the labeled shelf life (Use By date) and are therefore not necessary. And I have (almost) never come across a situation where polymeric device performance improves due to aging.
What is the legal, regulatory basis for performing Time Zero testing?

Your point must be considering, when the data is available for complete shelf-life which is being claimed, then ; however,its relevance is in following instances.
1. when comparing the trend/data of different representative-batches , this gains more important, as we set only representative batch on stability in a year; and it is important to ascertain the initial state of the results through zero time point.
2. where the device/batch is not placed on stability (time lag for any reason) immediately after assembly/manufacturing,
3. any scenario of extrapolation,

What is the relevance of "Time Zero" testing for medical devices from the standpoint of meeting regulatory requirements to defend your labeled shelf life?

In my research, I have found no requirements or mention of this issue in any medical device regulations or standards or FDA guidance. In the past several years, I have seen letters written to my clients where FDA is recommending Time Zero testing in addition to accelerated and real-time aging.

https://www.fda.gov/downloads/Medic...onandGuidance/GuidanceDocuments/UCM081366.pdf

ICH Q1 standard is relevant and widely accepted practice especially for drug substance and drug products;
from ANDA perspective, its often evaluated and where-feasible data is extrapolated from the submission batches which serves as an basis for putting the shelf life on the product.
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm366082.pdf

https://www.ich.org/fileadmin/Publi...uidelines/Quality/Q1E/Step4/Q1E_Guideline.pdf