Regulatory Open Forum

I recently took the RAPS CMC course, which I found extremely informative.  However, I'm still looking for clarification on the stability requirements for placebo in the CMC section of an IND. 

The RAPS course states that, while requirements will differ depending on the area, to "provide information regarding the manufacture and controls for the placebo to the same level of detail as that provided for the drug product." My question is whether this recommendation extends to stability studies. I do know:

1.  The EMA clearly states for the IMPDs that, "Stability studies are only required in cases where there is reason to suspect that the placebo product will undergo changes in its physical characteristics or degradation... In all other cases, a short justification of the assigned shelf-life will suffice."

2.  However, the non-requirement for placebo stability studies is not clearly stated for INDs, as far as I can find. The FDA Guidance for Industry: Content and Format of INDs for Phase 1 Studies simply states a requirement for "A brief general description of the composition, manufacture, and control of any placebo to be used in the proposed clinical trial(s)". 

3.  The FDA Guidance for Industry: INDs for Phase 2 and Phase 3 studies states "A brief, general description of the composition, manufacture and control of the placebo... should be updated or provided... This information and any updates to this information should be provided in an information amendment. When placebos are used in clinical trials, the placebo clinical study materials should be tested to demonstrate the absence of the drug substance.  The results from the placebo testing should be submitted in an annual report."

Does anyone have experience with placebo stability studies and their reporting in INDs?

As a sidenote, the ICH definition of investigational product appears to include both drug product and placebo: "A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial..."  While FDA uses the term "drug product," could this mean the ICH intends requirements for drug products be extended to placebo?

Thank you for reading my lengthy question!

Thank you so much for sharing your experience, Tom! 

Hi Tom,

I am wondering how you come up with 5 Year shelf-life for placebo? 

A safer way to do it, because it includes a stronger justification, is to piggyback on your stability studies from your active. As your placebo does not contain API it will be likely be at least as stable as the active.

Thanks Tom