wienui
★    

Germany, Oman,
2019-04-14 11:51
(edited by wienui on 2019-04-14 12:09)

Posting: # 20157
Views: 259
 

 Expiration of Reference drug during Bioanalysis [Bioanalytics]

Dear All,

I face a situation in the evaluation of a Bio-equivalence study which was conducted by a reference drug that was given to the subjects at the last month of it's shelf-life while the bio-analysis for the parent and it's active metabolites of this reference drug was happened after two months of expiration date of the reference drug.

Please enlighten me if this case of Bio-analysis can be accepted.

Best regards,
Osama
Helmut
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Homepage
Vienna, Austria,
2019-04-14 12:56

@ wienui
Posting: # 20158
Views: 237
 

 Expiration of Reference drug during Bioanalysis

Dear Osama,

» […] a Bio-equivalence study which was conducted by a reference drug that was given to the subjects at the last month of it's shelf-life …

Not optimal but still OK.

» … while the bio-analysis for the parent and it's active metabolites of this reference drug was happened after two months of expiration date of the reference drug.
»
» Please enlighten me if this case of Bio-analysis can be accepted.

IMHO, yes (of course, if the long term stability of samples was validated).
  • The reference was within its spec’s when it was administered.
  • Once you deal with samples (parent / metabolites) only BMV is important. The fact that the drug expired in the meantime is not relevant.
A similar question was raised in discussing BMV. Say, stock solution stability was validated and the reference standard expired during the course of the study. Can CCs and QCs still be prepared from the stock solution? The answer was yes.
Only if a new stock solution has to be prepared, either a new reference standard should be obtained or the identity/purity of the old reference standard re-established.

Cheers,
Helmut Schütz
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jag009
★★★

NJ,
2019-04-15 06:51

@ wienui
Posting: # 20160
Views: 185
 

 Expiration of Reference drug during Bioanalysis

Hi,

» I face a situation in the evaluation of a Bio-equivalence study which was conducted by a reference drug that was given to the subjects at the last month of it's shelf-life...

I had the issue 2 times before w FDA studies. As long as dosing is done there shouldn't be any issues. My studies completed dosing a week before the RLD expiry date.

J
wienui
★    

Germany, Oman,
2019-04-15 20:58

@ wienui
Posting: # 20170
Views: 151
 

 Expiration of Reference drug during Bioanalysis

Hi Helmut & John,

Thank you for the reply. is there any guidance which I can refer to in this point?
Best regards,
Osama
Helmut
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Vienna, Austria,
2019-04-16 13:20

@ wienui
Posting: # 20173
Views: 109
 

 Expiration of Reference drug during Bioanalysis

Hi Osama,

» is there any guidance which I can refer to in this point?

For your specific case, none I’m aware of. But:
  • It is acceptable to give a drug on the very last day of its shelf life to patients. Hence, the same is applicable in a BE study.
  • Once the drug is in the circulation only the stability in matrix is relevant. The parent/metabolite(s) don’t “know” whats happening to the formulation. ;-)
  • For my analogy of expired reference standards see the FDA’s drafted BMV guidance Section III.B.1.a.
    That’s similar: If the stability of a stock solution is validated you can still use it, although the reference might have expired in the meantime.
    Logic behind: When you weighed the standard in, it was within its shelf life and therefore, the concentration of the stock solution correct. The drug in the stock solution doesn’t “care” that the standard expired.

Cheers,
Helmut Schütz
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The quality of responses received is directly proportional to the quality of the question asked. ☼
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wienui
★    

Germany, Oman,
2019-04-18 10:04

@ Helmut
Posting: # 20187
Views: 44
 

 Expiration of Reference drug during Bioanalysis

Hi Helmut,

» Logic behind: When you weighed the standard in, it was within its shelf life and therefore, the concentration of the stock solution correct. The drug in the stock solution doesn’t “care” that the standard expired.

Thank you for this logic explanation. I think as a regulatory person you must have a very vast academic scientific background in different fields beside to check every morning this forum otherwise you will lose.

Have a nice day,
Osama
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