Shaky Ground: Is It Still Good for 2 Years?

Our plant in Timbuktu manufacturing Phase 3 clinical material proposed a 2-year shelf-life for the product based on historical Phase 1 data generated nearly 4 years ago. At that time, four years ago, we had a smaller drug substance production scale and since then, some important process changes (new drying process, for example). Still, the fact is, the chromatographic impurity profiles are similar between our Phase 1 and Phase 3 product—it is the same formulation—and forced degradation studies also confirm comparability. But, does that comparability justify applying the same shelf-life?

Instead of generating current real-time data, we would like to avoid the 12-month delay and costly stability product runs prior to assigning the 2-year shelf-life. Timbuktu regulatory personnel recommend that we proceed with the 2-year dating and simply place portions of the first three Phase 3 batches on stability concurrent with the ongoing trials—just like post-approval studies. Quality personnel in Montezuma, on the other hand, are raising alarms as to the potential risks, especially pointing out that the Phase 1 material wasn’t extremely robust—it met specifications at 2 years but failed to meet them at 3 years.

What do you recommend as a path forward—we’d much prefer to use Phase 1 dating, so how could we accomplish that goal safely and quickly?

Some possible solutions include:

- Take a chance and move forward without further study

- Add simultaneous studies to show due diligence

- Bite the bullet and wait for new data on which to base a shelf life