Time Window for Stability Samples

[Sunjay]

Dear All,

I would like to know the time window used for the analysis of stability samples after withdrawl from the chambers?

What is industry standard for this? It will help me in drafting our in house SOP for the same.

If there is any regulatory referance then please share it.

Regards

[shaun78]

It really depends on how long you wish to drag the protocol out.

Generally, nice round numbers are used, such as:

1. 30, 60, 90, 180, etc. days

2. 15, 30, 45, 90, etc days

3. 1, 2, 4, 8, 12, etc weeks

It all really depends upon how fast you think your sample is going to degrade. If you have a sample that will fail specs after 30 days, then there would be no point writing a stability protocol with time points suggested in #1.

Generally, one starts off with small increments and gets larger at time goes on, as I have shown above. Once a year is reached, people generally move out to testing every 6 mo to year.

Hope this helps....

Shaun

[DR]

As it is generally considered to be in the interest of the manufacturer to test their samples in a timely fashion, and there are few, if any known instances of samples improving after withdrawl from chambers, I don't think anyone has gone to the trouble of setting analysis windows aside from internal SOPs, and even doing so internally would be counterproductive (just another length of rope by which you may be hung).

[Bruce Hamilton]

This is a very good question. I don't have the answer, as it's not my field. I went looking for information about this several years ago, and couldn't get a definitive answer from the quality people then.

However, I would point out that removing samples from the storage conditions presumably becomes an "excursion", and the ICH protocols require a description of the excursion, and discussion of the effects, of any excursion longer than 24 hours.

The problem arises when sample testing has to be performed off site, and samples are being shipped to overseas laboratories for specialist testing. You want to ensure that any "rules" you impose will cover all contingencies.

I'd just ask analysts to document the excursion conditions, and let
the quality people earn their keep.

I'm going to be interested in other responses.

Bruce Hamilton

[danko]

If you have documented that storing the samples in a freezer (-20 degrees f. ex. or – 80?) inhibits any degradation of your drug or whatever you’re testing. Then I can’t see any reason for hurrying so much.
Actually if this is the case, then you can collect and store all samples (for instance after 1, 2, 3 months) and then analyse them in one and the same analytical sequence, thus avoiding any intermediate variation due to other factors than stability challenging conditions.

Anyway you should find “the golden ratioâ€

[Alfred88]

Dear Sunjay:
I believe that you intended to ask, “how long the testing can be legally delayed?â€

[Sunjay]

Dear All,

Thanks for your response and Mr. Hamilton for appreciating the question.

As mentioned by Alfred i also disagree with Mr. Denko, that we can pool the samples of different time points. This may not be acceptable to regulatory agencies. Moreover in such case, if you store the product in referigerator condition after withdrawl you have to demonstrate that the sample is actually stable at 2-8°C. This temp may be critical for certain formulations especially liquid formulation.

This is also a good argument that even if we take some time for analysis, the sample degradation will worsen only.

In our internal SOP we hav mentioned the following time window:

10 working days for < 3 Months sample,
15 working days for 3-6 Months sample,
21 working days for >6-24 Months sample,
30 working days for >24 Months sample,

Moreover, we are in R & D and not doing the stability for the commercial batches.

After withdrawl from chambers, we are keeping the samples at room temperature generally between 20-25°C.

It is interesting to read this in USFDA warning letter "Failure to follow (SOP)-007-15 "Acceptable Testing Time Intends", which states stability samples are to be tested within 60 days of their scheduled pull date", this means that even 60 days time window is acceptable to USFDA.

We would like other people to share thier practices about this. This will help us to know the industry standards, as there is guidance available on this from regulatory bodies like FDA etc.

Warm Regards

[danko]

I think, some of the posters missed an important point.
Reading FDA observations is all very well, but technical insight and substantiated rationales - is better yet.

I mentioned something about preserving conditions (e.g. – 20 degrees or lower yet temperature) under which no degradation or other compound modifications occur. Then I can not see any reason for not storing samples until analysis.
By the way storing samples at plus 20 - 25 degrees is something that will attract FDA’s or whoever’s attention more than anything else mentioned above. So it all depends on the storing conditions. I, for instance, will not be comfortable with storing even water at 20 – 25 degrees for more than a day.

If in doubt how to address the issue, one could look at the reference material one uses for quantification of the samples. If there’s no identified and documented preserving conditions for the reference material (standard) then how could one defend the generated results for the stability samples or any other samples?

Bureaucracy is what science fears most

Best Regards

[danko]

I think, some of the posters missed an important point.
Reading FDA observations is all very well, but technical insight and substantiated rationales - is better yet.

I mentioned something about preserving conditions (e.g. – 20 degrees or lower yet temperature) under which no degradation or other compound modifications occur. Then I can not see any reason for not storing samples until analysis.
By the way storing samples at plus 20 - 25 degrees is something that will attract FDA’s or whoever’s attention more than anything else mentioned above. So it all depends on the storing conditions. I, for instance, will not be comfortable with storing even water at 20 – 25 degrees for more than a day.

If in doubt how to address the issue, one could look at the reference material one uses for quantification of the samples. If there’s no identified and documented preserving conditions for the reference material (standard) then how could one defend the generated results for the stability samples or any other samples?

Bureaucracy is what science fears most

Best Regards

[danko]

I think, some of the posters missed an important point.
Reading FDA observations is all very well, but technical insight and substantiated rationales - is better yet.

I mentioned something about preserving conditions (e.g. – 20 degrees or lower yet temperature) under which no degradation or other compound modifications occur. Then I can not see any reason for not storing samples until analysis.
By the way storing samples at plus 20 - 25 degrees is something that will attract FDA’s or whoever’s attention more than anything else mentioned above. So it all depends on the storing conditions. I, for instance, will not be comfortable with storing even water at 20 – 25 degrees for more than a day.

If in doubt how to address the issue, one could look at the reference material one uses for quantification of the samples. If there’s no identified and documented preserving conditions for the reference material (standard) then how could one defend the generated results for the stability samples or any other samples?

Bureaucracy is what science fears most

Best Regards

[danko]

Hi guys,
Something happened and my post got submitted several times. Please don’t take it as way to underline my point

Sorry for the error – if it was my fault.

Best Regards

[shaun78]

Knowing now that you mean window in which stability samples can be tested (sorry for my misunderstanding) ....

I have personally never seen anything less/more than 10-15 working days, no matter how long the product has been on stability.

I know that sliding scales as you have mentioned are acceptable, but companies in which I have worked always held the opinion that anything over 15 working days to get a stability sample tested is simply being delinquent.

Just my 0.02.

Shaun

[Consumer Products Guy]

Our internal SOPs state 10 working days, with extended time for Christmas-New Years. We're R&D also.

[LC_labrat]

For R&D purposes I've always gone with recording the date the sample is removed from the chamber, and complete testing with 10 days. It's a more conservative option to leave the samples in the chamber. A 25C sample in the chamber or on the bench really doesn't change much, except you now have varying temperature/humidity conditions. I think when the FDA is concerned you are better off taking the road of more degradation by leaving them in the chamber, than less by taking them out and storing at a lesser condition. I doubt they will find fault for increasing your chances of a failing result. I have been told in a stability training course I took that 2 weeks is acceptable for acclerated conditions. But in the end whatever you put in your SOP is what the FDA will hold you to, if they disagree with your time you may not end up with a 483 but a warning instead.