Entries by Andrew Sonderfan

Reminder – 2020 RTC Business Practices Survey

RTCers -

Many of you have already completed the 2020 RTC Survey - great! If not, please take a few moments to provide your input: your experiences and opinions help your fellow Members.

Log in and follow this link for more info (or look for the email you received on May 10):
https://www.toxconsultants.com/newsletter/2020-survey/

Thanks!
Andy Sonderfan
For the EC...

 

Monkey muscle histopathology expertise

Dear colleagues -

I'd appreciate hearing of one or more pathologists with experience evaluating muscle histopathologic changes, particularly in cynos.

Thanks; best wishes,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138

...

 

Pathologist with rodent (esp. kidney) experience?

Dear RTC Colleagues -

A friend who's not (yet!) a client asked if I could facilitate connection with a pathologist that has rodent histopath expertise, especially knowledge of kidney pathology. I know a few pathologists whom I've enjoyed working with for peer reviews, but I'm thinking one or more folks here might know a kidney expert. Can you assist?

Thanks; cheers,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138
...

 

Vendor Qualification?

Dear RTCers -

How often (and under what circumstances) have you or your client formally conducted qualifications as part of selecting a CRO to conduct key GLP nonclinical studies? I had a program manager at a client company ask about this in passing (they're a small company owned by a Very Large pharma company).....and for sure, the parent company has formal procedures in place for qualifying clinical as well as nonclinical CROs.

Thanks to all,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138

...

 

Design strategy for a 13-week combination tox in rats – your thoughts?

Dear RTCers -

I have a client who plans to conduct a 13-week combination study in rats. The study will evaluate the combination of a marketed small molecule with the client's new small molecule: the two compounds are planned to be administered, sequentially, once-daily in planned clinical trials.

The plan is to evaluate a vehicle (innovator vehicle followed immediately by marketed-cpd vehicle); low-, mid-, and high-dose combo, and a single-agent group for each of the two compounds (total 6 groups).

Here's the question: Because the clinical safety (indeed, nonclinical safety too) of the marketed compound is well-established, we're considering keeping the dose of the marketed compound the same ("Standard; Std") while varying the dose of the new compound. So the design would be -

Option 1
========================
Vehicle, vehicle
Low(new), StdDose (marketed)
Med(new), StdDose (marketed)
High(new), StdDose(marketed)
High(new)
StdDose(marketed)

Another possibility is to vary the dose of both the new and marketed compound, so -

Option 2
====================
Vehicle, vehicle
Low(new), Low(marketed)
Med(new), Med(marketed)
High(new), High(marketed)
High(new)
High(marketed)

To me, Option 1 seems the better design (minimizes variables; allows more complete characterization of dose-response for new compound.

Have you had experience with design and conduct, and regulatory review, of either or both of these designs? What do you recommend?

Thanks; best wishes,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138

...

 

Following up: Number of animals for chronic tox studies

Hi RTC colleagues –

I wanted to follow up on Barry's November posting about numbers of animals on chronic tox studies. ...I wish that adding a comment would "bump" the thread to the top of the TalkList so folks would see when there are new comments. Something to consider....

I’ve got a couple of longer-term studies for a non-oncology indication, and preliminary feedback suggests the CRO IACUC is unhappy with numbers (will learn details soon….holidays).

For the rat study (6 months total dosing) I have an interim necropsy at 3 months with 10 rats/ sex in each group, then 20 additional going to 6 months: 15 for terminal necropsy and 5 for recovery.

For the dog study (9 months total dosing) I have an interim necropsy at 3 months with 3 dogs/ sex in each group, then 6 additional dogs going to 9 months: 4 for terminal necropsy and 2 for recovery.

Does this seem appropriate to folks? In my experience (admittedly limited) animal numbers at 30 days are similar to 28 days (i.e., subchronic) and, though numbers at terminal necropsy for the chronics are higher, recovery from a chronic necropsy is the same size as subchronic recovery.

Thanks!
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138...

 

Screening discovery leads for hematologic toxicity

Dear RTC colleagues –

A new client is developing a small-molecule oncology compound. Although first in its chemical class, the client is expecting (based on pharmacology of other compounds sharing the mechanism) to encounter hematologic toxicity (thrombocytopenia, etc.).

This is a little more toward discovery than I’ve typically been involved. I’m wondering if anyone has had experiences with predictive screening platforms for to evaluate discovery leads for heme and/ or GI tox. What’s worked for you/ clients, and what hasn’t? …One company I’ve heard of is ReachBio; any experiences?

Thanks; all the best,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138
...

 

Published nonclinical safety studies supporting a 505(b)(2) IND

Dear RTC Colleagues -

A new client has obtained, via pre-IND response from FDA, concurrence that published-literature reports of nonclinical safety will suffice to initiate clinical trials for a compound proposed to be developed using the 505(b)(2) regulatory pathway.

It seems an obvious point, but - in contrast to nonclinical studies a client would sponsor or conduct themselves [indeed, additional nonclinical studies may well be conducted post-IND to support continued clinical development and/ or registration] - studies in the published literature are likely not amenable to preparation and submission of SEND datasets.

Is there a regulation that exempts literature-published nonclinical studies from the requirement to submit data electronically in support of an IND or NDA? It seems like “common sense”, but that doesn’t mean I wouldn’t welcome seeing this in writing, or hearing “I’ve done this several times; no need for SEND”.

Thanks for your help!
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138

...

 

China’s Medicilon – experiences to share?

Hi all -

Shanghai's Medicilon is another China CRO my client is considering for some IND-enabling non-GLP and GLP studies - I would be grateful if RTCers could share good or bad experiences and impressions.

My China experiences have been limited to WuXi (non-GLP and GLP; studies have gone well) and Pharmaron (non-GLP; generally good [though poor report quality]). I did some non-GLP study work with Medicilon a number of years ago (when it was MPI-Medicilon) but have had no experience since then.

Any information would be useful - thanks!
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138

...

 

Checking back – recent experiences (good or bad) with China’s Joinn?

Hi all –

I've reviewed RTCers TalkList reports and comments about Joinn, but there doesn't seem to me much since 2018. Wondering if folks’ experiences (good or bad) with Joinn have been the same or different over the last couple of years.

Sounds like Joinn has prepared numerous successful INDs in China and the US; I don’t (yet) know their inspection history (but if programs have not approached marketing, perhaps they haven’t been audited, or audited more than once).

I have a client considering Joinn China for IND-enabling (USA or China IND, not yet decided). After reading this and another thread, I surely would have counseled “walk away” in mid-2018: have things improved, stayed the same, declined?

And, separately (but not really) – sorry if it’s a newbie question, but is there a useful digest of SFDA nonclinical safety requirements for China IND (any notable differences in requirements from those in USA)?

Thanks all,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138...