Bioequivalence and Bioavailability Forum

Hi Hötzi and all,

this isn't so much about whistleblowing. It is about defining a type of deviations that require expedited reporting (analogous to SAE's) and defining who is supposed to do what and when.

It is already giving rise to some confusion. If we forget about fraud and cheating and misrepresentation, then there are certain types of situations that occur regularly and which could perhaps be considered to fall under these paragraphs. Examples include:

1. Someone forgot to activate the audit trail on an LC-MS/MS system. Needs reporting?
   
2. Someone used pippettes (e.g. for QC production) whose calibration interval had expired. 5 days ago, 5 weeks ago, 5 months ago. It happened 4x the past 15 months and went unnoticed by monitors. Needs reporting?
   
3. An injectable IMP arrives without a temperature logger, storage condition is "store in a cool dry place", the box was shipped 3 days ago from Ankara and has been sitting 44 hours at Dubai airport at unknown conditions in August. CRO asks the sponsor if there is a problem, the sponsor responds back there isn't without argumentation. Needs reporting? If yes, by whom?

IMP example 4 in the guideline draft is quite hopeless, by the way: "The IMP was stable" - and how exactly would a CRO or Sponsor know about that in any real-life situation in a way that would be defensible in case of regulatory questions? There is often a reason why an IMP is assigned an expiry of X months and not X+Y months. "Yes, we did study the IMP stability for 24 months, but we are only asking for 12 months on the SPC.", explained Arthur J. Scrotum from Goof Pharma to the regulator and added "and believe I saw Elvis yesterday."
Just imagine an anaphylactic reaction occuring in such a study after the IMP was taken - on investigation it is concluded that it may or may not have occured due to impurity A or whatever. Regulators would surely murder the CRO for using the IMP in such cases, due to hindsight.