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stability schedule 30 days or 1 month?

  • 1.  stability schedule 30 days or 1 month?

    Posted 21-Jun-2022 08:28
    Hello, community,

    How should we determine the pulling date for stability studies?
    1) Should one month be 30 days or a calendar month? Similarly, should six months be 180 days or six calendar months?

    2) How to determine the range? 
    For long-term / accelerated studies for biologics, does something like the below make sense?

    1 month +/- 1 day
    >= 3 months +/- 7 days
    >= 1 year +/- 10 days

    Thank you.


    ------------------------------
    Hua Jin
    Woodridge IL
    United States
    ------------------------------


  • 2.  RE: stability schedule 30 days or 1 month?

    Posted 21-Jun-2022 08:33
    Use days.

    The change in the product doesn't know about calendar months, years, etc.

    Also, if you do any data analysis, such as Excel, it will be easier with days not months.

    ------------------------------
    Dan O'Leary CQA, CQE
    Swanzey NH
    United States
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    Original Message


  • 3.  RE: stability schedule 30 days or 1 month?

    Posted 21-Jun-2022 08:42
    Thank you Dan for your quick reply! How about the ranges? 
    Does the following make sense?
    1 month: +/- 1 day
    >= 3 months +/- 7 days
    >= 1 year +/- 10 days

    Thank you!

    ------------------------------
    Hua Jin
    Woodridge IL
    United States
    ------------------------------

    Original Message


  • 4.  RE: stability schedule 30 days or 1 month?

    Posted 22-Jun-2022 07:54
    I don't understand what you would do with the ranges. It appears you want to convert days into months and years, but I don't know why.

    Are you trying to describe an expiration date? If so, a better approach is to be conservative and set the expiration date shorter than the value you determine.

    ------------------------------
    Dan O'Leary CQA, CQE
    Swanzey NH
    United States
    ------------------------------

    Original Message


  • 5.  RE: stability schedule 30 days or 1 month?

    Posted 22-Jun-2022 09:27
    Hello Dan,

    I did not make it clear. I try to put a range on the actual pulling date. 

    For 1 M samples: Duration 30 days
    Allowed Actual Pulling date: Expected pulling date +/- 1 day
    For example, if the expected pull date for 1M sample is 6/29/22, the actual pulling date can be any day between 6/28/22-6/30/22.

    For >=3 M samples:
    Allowed Actual Pulling date: Expected pulling date +/- 7 days.

    For >=12 M samples:
    Allowed Actual Pulling date: Expected pulling date +/- 10 days.

    I hope I have made it clear now. Does the abovementioned range make sense for biologics stability testing?
    Thank you again for answering my questions.

    ------------------------------
    Hua Jin
    Woodridge IL
    United States
    ------------------------------

    Original Message


  • 6.  RE: stability schedule 30 days or 1 month?

    Posted 23-Jun-2022 08:21

    First, I work in devices, so this may color my answer.

    Your approach does not make sense to me.

    I infer that the "pulling date" means the expiration date, and is the date to pull the product from inventory.

    To use your example, the expiration date is 6/29/22, but you would allow use up to 6/30/22. The problem is that you don't have data to support the 6/30/22 date. The problem is event worse in the 12-month case, in which you would allow an extra 10 days with no support.

    You should calculate the expiration date to the day based on the data you have. Then, the product expires on that date.

    If I were conducting an audit and found material in inventory for use without stability support, I would write a nonconformance.

    If it were an FDA Inspection, you should expect a 483.



    ------------------------------
    Dan O'Leary CQA, CQE
    Swanzey NH
    United States
    ------------------------------

    Original Message


  • 7.  RE: stability schedule 30 days or 1 month?

    Posted 23-Jun-2022 09:40

    Having read some of the other responses, I realize that I didn't understand the question. It is about early termination of the stability test not shelf-life of a finished product.

    My answer stays the same. If you want 365 days of data, then you need to run the test for at least 365 days. If you have only 355 days, then you would need to extrapolate to get 365 days; this is not a good practice.

    Again, I think you should do the analysis in days, not months or years. You will have more than one item on test so you will want to calculate the regression line, for example, which is easier in days. Also you will want to determine the mean and standard deviation of the samples before the test and after the test. Presumably the mean is statistically different, and the standard deviation is statistically the same. Calculating the rate of change in days, just makes it easier.

    If the convention is to report results in months, then the conversion from days to months is easy, but is not easy to go the other way.



    ------------------------------
    Dan O'Leary CQA, CQE
    Swanzey NH
    United States
    ------------------------------

    Original Message


  • 8.  RE: stability schedule 30 days or 1 month?

    Posted 23-Jun-2022 08:36
    Hi Hua,

    I don't have experience with the biologics side, but I can assure you that the Office of Generic Drugs is very strict with the time samples are in the chamber.  I have seen them reject a stability study and require it to be redone because the 6 month sample was pulled at 178 days instead of 180 days (SOP stated Pull date +/- 2 days").  To be safe, always set you pull-date ranges to be "pull-date + x days".  At least for OGD, never pull early.  Even if your SOP allows it, OGD will reject it.

    Lisa

    ------------------------------
    Lisa Apolis, RAC
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    Original Message


  • 9.  RE: stability schedule 30 days or 1 month?

    Posted 23-Jun-2022 08:43
    Dear Hua,
    the "tolerance ranges" you are proposing for pulling dates are sensible and in line with common practice for small molecules. Also, "months" are more typically utilized in stability protocols, as opposed to days, at least in case of long-term and accelerated conditions you would rely on to claim stability of your material (hence a retest period, for APIs, or a shelf life, for drug product).
    All these details concerning your stability protocol should be clearly spelled out in an SOP authored by subject matter experts in the analytical development function.
    Hope this helps,
    Maurizio

    ------------------------------
    Maurizio Franzini
    Regulatory Affairs CMC, Director
    San Francisco CA
    United States
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    Original Message


  • 10.  RE: stability schedule 30 days or 1 month?

    Posted 23-Jun-2022 15:39
    Thank you very much to all of you who took the time to answer my question.

    ------------------------------
    Hua Jin
    Woodridge IL
    United States
    ------------------------------

    Original Message


  • 11.  RE: stability schedule 30 days or 1 month?

    Posted 24-Jun-2022 12:58
    I'm a little late responding (I was on vacation for 2wks), but from the biologics perspective, we also use months, not days. I don't know what tolerance ranges my company uses for pulling the samples, but I know that at my previous company we would footnote if the testing was performed more than a month from the stated timepoint for later timepoints (eg, 12M, 18M, 24M). I don't recall the timing for earlier timepoints, but I don't remember it every being as tight as +/- 1 day, even at 1- or 2M. This was for non-viral vaccines. Note that, AFAIK, we always did the testing even if we were outside the allowed pull date; it would just be recorded as a deviation. Some data is better than no data. We never had an issue with this approach. This of course assumes that this only happens once in a while and assumes that you have data generated with no timing issues as well. 

    It probably also depends on the type of product and how the data is used - it's probably important to be more precise when you're doing calculations (eg, Arrhenius equation) to extrapolate your data, which is not the case for biologics.

    ------------------------------
    Rachel Thornton
    Associate Director
    Smyrna GA
    United States
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    Original Message


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