[Carla Oliva]

Reply To: Supplies with Short Expiry in LATAM

Truthfully, your strategy is probably best discussed with your (contracted) local CRO partners; these folks are “boots on the ground” and much more familiar with the most opportune ways to get drug into the country, even above and beyond your label/pack vendors who are usually working with third party depots, and certainly better than an ex-country based project manager working for any vendor (including the CRO). They are also usually the folks who are applying for the IL on behalf of the sponsor organization as part of the CTA process, and who may also be acting as the IOR. If your company hasn’t signed a CRO contract yet, make sure they bring someone from LatAm into the bid defense meetings and ask them about all of the things I’ve mentioned below.

Given standard DP manufacturing, label/pack lead times, release, shipping, and receipt at regional depots before getting it to a site, I don’t see how you do all that and still get this drug into a person with 6 months shelf life using standard methodology. You don’t mention where this is for dosing in clinic, or if it’s take home, but you also need to keep in mind the duration of dosing in your lead times.

I would absolutely create a separate label group just for the LatAm countries, to also reduce your risk of having to manage multiple different expiries based on feedback you may get from EMA based countries who don’t really love non-real time data based expiry, particularly in the earlier part of your formulation life cycle (I’m looking at you, Italy, Germany and Czech Republic!).

I tried looking into having LatAm sites do labeling (in my case, overlabeling for expiry extension) and the issue I ran into was that it’s considered a manufacturing activity in many LatAm countries, which meant that the hospital would need a manufacturing license to perform the work. Not surprisingly, none of them had this in hand. This was 2019, though, and pre-Covid life was different in a lot of ways. It’s worth checking on this now with your local (LatAm) CRO partner to see if anything has changed, and to understand your options.

I don’t think anything less than 9 months shelf life gives you a viable strategy without packaging it locally, and that’s if you ship it right from your DP vendor into each respective country depot, post release. Keep in mind too that LatAm has several religious and governmental holidays/shutdowns that you have to work around from a calendar perspective; you’d need to line this all up really carefully with your shelf life extension strategy.

Given regulatory approval lead times globally, I would be shocked if LatAm was out front, unless that’s the only place you are running your study. If that’s the case, I would look at my stability pull dates, figure out when I might reasonably get my next best data set, and label in the US at risk with that new shelf life. Queue up your DP and QA folks to do a planned exception and get your shipping warehouse to do as much of the paperwork up front as possible and then hit the green light the second you get that expiry extension signed.

LatAm is so complex that I try to keep 6 months worth of inventory in each regional depot (shipping quarterly and adjusting quantities based on actual enrollment) so that I don’t get caught with missed doses due to import issues. You don’t mention if quantity of available supplies is also a constraint, but I encourage you to consider being more generous with your allocation to LatAm (based on projected enrollment) and keeping more supply locally there than you would in an EU or US depot, which are comparatively easier to resupply. Given that your IL also has a life cycle management component, you will need to have this plan configured before the planned submission and then actively monitor against that with each import, to ensure that there aren’t any gaps.

I found Peru to be pretty quick and probably the least complicated of the LatAm countries (including with their speed to approval); Brazil probably has the most horror stories and worst lead times, for a lot of reasons.

Hope this is helpful to you; looking forward to seeing what other folks come up with as well!