Won’t be renewing my membership

Hi, Wanted to let folks know I won't be renewing my membership for this coming year as I recently accepted a position (part time) with Esker Therapeutics. I joined a management team I was familiar with as many of them had formerly been with Principia Biopharma a company I had consulted with for the past 10 years. It has certainly beed a pleasure being part of the RTC, and hoping to refresh my membership before too long! All the best in the New Year, Mike



How long are CITES permits taking to acquire?

How long are CITES permits taking, particularly for moving NHP tissues out of the USA? I haven't done a permit since before the pandemic and a new client is 5 mo out and no sign of a permit. They are about to get to the end of stability so it looks like those tissues are lost. The next study has started so I have indicated that they should apply for the next permits now, while the study is in vivo. I have always submitted my permits early and just indicated in the permit about 10% more samples than I expect from the study. Then I always add in saline or empty tubes to the shipment so that the permit sample count actually matches what is on the permit. I'm presuming this trick will still work.



Toxicology Consultant needed for Orthogon Therapeutics

Please reach out to me if anyone has the bandwidth/interest in a toxicology consulting opportunity for Orthogon Therapeutics-
Orthogon is a small, early-stage biotech in the anti-viral, antibiotic arena in the Boston area, I do not have the bandwidth to help them out, but hoping someone on the RTC will be able to. Current focus is on progression of an antiviral candidate. Please reach out to me directly at kim.stickland@gmail.com if there is any interest., or if you can recommend someone for this consulting opportunity.
Best, Kim


Signed Pathology Report Supporting ADR submission for FIH IND

I heard from CRL that if one submits an ADR (audited draft report) with an IND that they are requiring a signed pathology report. This is news to me but then it's been a while since I've submitted draft reports for INDs. Is this the current standard expectation?

Along this line, is it necessary to submit an ADR as opposed to an unaudited draft?

Thanks, Bill...


Plasma analysis for Aluminum

Does anyone know of a lab that can do elemental analysis of plasma for Al? This may also be needed for Zn and Ti. Thanks in advance...


Drug-eluting patches – FDA expectations for total patched days for 9-mo study

For those who are doing drug-eluting patches, do you know if the FDA has an expectation of the mean percentage of days that the minipigs need to be covered with patches over a 9-mo study to prove systemic safety? Comments from anyone else who has had problems with patch holidays and how the FDA responded to you would also be appreciated.

The FDA has indicated that they will not accept a 9-mo study in minipigs using a drug-eluting patch system due to the number of patch holidays. They will accept the study as proof of local safety for the drug and the patch excipients, but they specifically will not accept for systemic safety as there were patch holidays due to skin irritation in the areas of the patch adhesives (this is not a drug-related finding and the patch excipients themselves appear safe). The number of patch holidays varied by group with no dose response. There was a lot of intragroup variability but we did have individuals in all groups who had few to no patch-free days. The group at the clinical dose/schedule was the best group with 96% of days with patches. The placebo patches had the most holidays, with 63% days with patches (these placebo patches were known to be stickier). Groups with fewer and more patches, or extended patch application than the clinical dose/schedule had 69% (fewer patches on clinical schedule), 73% (patches left on longer than clinical expectation), and 81% (more than clinical patches but on schedule) of total days patched.

The FDA dissatisfaction is focused on the safety of the patch adhesive/solid/semi-solid excipients. They would not provide a specific percentage to us, but it appeared that they were OK with the two groups (clinical and above clinical number of patches) that tolerated patches for >80% of the days. We think that the patch holidays were due to the the need to remove and apply patches multiple times each day that resulted in skin damage and irritation ("tape stripping" trauma and repeated cleaning that probably caused drying). This type of study does not have the option to rotate the dosing sites, so once skin damage/irritation starts it is hard to control without patch-free days. When we first started to see skin problems that required patch holidays, we contacted the FDA about the need for dosing holidays and our revision to cleaning procedures (which did help reduce the patch holidays), but the FDA did not respond for 8 months and after the study was completed.



screening for retinal toxicity

Anyone with experience with useful/translatable models for retinal tox for early screening of molecules?
working with MAPK inhibitors (retinopathy --retinal vein occlusion-- known for some MAPKis in clinic)> Client is looking for an early screening opportunity for this toxicity amongst a number of candidates -- Outside of a standard in vivo tox assessment, any thoughts or comments?
Best, Kim


GI toxicity models for screening of molecules

Anyone with experience with useful/translatable in vitro/ex Vivo models for GI tox for early screening of molecules?
working with MAPK inhibitors (dose limiting diarrhea known for some in clinic) and
client is familiar with MatTek 3D Human Small Intestinal Tissue Model (EpiInestinalTM) --to Assess Drug Permeation& Inflammation- they are considering using it to screen through molecules for early selection to try to avoid this clinical toxicity- I am concerned that this might be a waste of resources based on potential for translatability,-- and instead go directly to in vivo assessment
any comments appreciated!
Best, Kim


40 Cyno Monkeys available now – in house and post quarantine – IMMEDIATE STUDY START

Hi, I have 40 cyno monkeys available for study start right now. Client backed out after animal arrival and after quarantine.
These are ready to go. I would like to move these to another sponsor. Please contact me directly. 206.842.1004 or 206.473.2913 or korytko@preclinicalgps.com
thanks, Peter ...


Wistars vs Sprague Dawleys – the quest for a perfect strain – new recommendations?

Hi, This week, I spoke with Barry L about the symposium at ACT regarding the use of Wistar rats instead of Sprague Dawleys for new programs. Barry outlined to me that survival is better in Wistars for longer studies. That is good.
Are there any other key info from that symposium that would convince you to use Wistar Hans instead of Sprague Dawleys?
This seems like a great topic for RTC discussion.
Thanks, Peter K. ...