Entries by Andrew Sonderfan

Experience (good, bad) with “Soluplus” vehicle excipient?

Dear RTC -

Has anyone encountered the apparently newish BASF-produced excipient, Soluplus (polyvinyl caprolactam - polyvinyl acetate - polyethylene glycol graft copolymer), designed for immediate-release formulations of poorly water-soluble drugs? ...Presently awaiting some literature requested from BASF.

I've seen some results suggesting acceptable tolerability (specifically, in dogs) and I understand Soluplus is included in one or more marketed formulations in Europe (and elsewhere, but not yet USA). Conversely, I heard anecdotally about "dog pseudo-allergic reactions" (though not described further, nor doses that were well- or poorly-tolerated provided).

Would love to hear more - at this stage both bad news and good news are welcome (though it would be great if Soluplus would improve plasma concentrations for this challenging small molecule to be administered orally).

Thanks; best wishes,
Andy

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

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Client always pays, but always late. Suggestions?

Dear RTC experts-

Reviewing the recent Survey responses, I felt fortunate that, in my first year of consulting, I haven't encountered any real problems with very late payments. However I do have one client who - month after month - never pays on time (net 30 days), but instead pays 45-60 days after invoicing. So every month (after other payments have been received) I send a follow-up message, get the usual apology and promise of payment, and a couplefew weeks later, get paid (it's a bank transfer, it's not like they're hunting down somebody to sign a check).

I wonder if you all have included penalty terms in any (or all) consulting agreements. It's something I'm thinking about as this client's agreement comes up for renewal. What terms, agreed by clients, have you proposed? I'd appreciate some concrete suggestions.

Thanks!
Andy

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

 

TalkList challenges – please read

Dear RTC Colleagues -

Recently there have been several New Posts to TalkList that were not emailed to subscribers. There doesn't seem to be rhyme or reason - sometimes a new post is sent; sometimes not. (Example: I created two New Posts within the space of a couple of weeks - one of these circulated, and the other never did.)

Our website's designer is aware of the issue and is investigating.

Until this is addressed satisfactorily, I suggest that members concerned with following the TalkList (or monitoring comments to their own posting) log into the website and view the TalkList directly.

Meanwhile, I apologize - it's disappointing that this isn't working as members expect it should.

All the best,
Andy Sonderfan
RTC IT

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

...

 

Client suggested using Slack; bad idea?

Hi RTC experts - I imagine someone will have crossed this bridge (or decided not to cross it) before me.

A smaller client has "invited" me to join a shared Slack channel for the program we're collaborating on. I think of Slack (perhaps naively - correct me please) as an always-on instant messenger service.

People who are employees in my client company are using Slack. But, here's the thing, they're EMPLOYEES: Pretty much whatever they're doing at their computer during the day is company-focused (and if it's not....here's looking at you Amazon Prime....maybe a pop-up reminder isn't a bad idea).

I'm happy to keep current with all clients' communications (by checking email between tasks or meetings, time permitting, and responding to [rare] urgent texts), and this has worked well to date. So I'm not sure - on a day that might include teleconferences with a couple of different clients and will absolutely include project work (protocols, reports) for a couple of different clients, not sure that I want to have something pop up in the middle of other work "ANDY IS THE RAT STUDY STARTING NEXT WEEK OR THE WEEK AFTER THAT? THANKS." (This is a smaller client, remember.)

OK, you get it.

Have you been asked to join a Slack channel, and (if so and you agreed) how has it worked for you?

I'm thinking of politely declining, and saying (1) I'm unsure this will increase my ability to meet (client) expectations, and (2) I don't wish to seem unresponsive if I'm on a teleconference with another client for 2 hours.

I read this in an article on Inc., "There's a different expectation of immediacy with real-time communication, so it's crucial your employees and your customers understand how quickly you have committed to respond. And then do it. "Unless you're really committing to responding to every channel within a very short period of time, or you're able to set specific ground rules about when people are going to be available on the channel and stick to them, you're not really able to keep that customer's experience high,"

What do RTCers advise? Thanks!
Andy

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

 

Help a Montana State University student? “Supply chain needs – human hepatocytes”

Dear RTC colleagues -

Are you feeling helpful? Got 10 minutes?

Montana State University student Olivia Smith wrote the following note on the RTC website's "Contact" page -

"Hello, my name is Olivia Smith, I am going into my senior year at Montana State University. I’m reaching out today to ask if you will participate in my summer research project studying the supply chain needs of human hepatocyte cells.

Human Hepatocyte cells are in limited supply and the quality of the cells can vary from donor to donor, which can create unforeseen problems within research. This project has three objectives; review how consumers are receiving their human hepatocyte cells, the forms consumers prefer, and how to better supply this field with human hepatocyte cells to better progress their own research. Ultimately, the data collected from this project will create a better understanding of the needs associated with human hepatocyte cells.

The survey should take approximately 10 minutes, and someone within toxicology would be best. Anything you can fill out is appreciated."

Here is the link to Ms. Smith's survey: https://montana.qualtrics.com/jfe/form/SV_5msQRFUtZTwQNbT
And here is her email address: olivia.smith1@student.montana.edu

I don't have any information other than what I've shared. If you'd like to help, please do. If not, just ignore this!

Cheers,
Andy
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In vitro micronucleus = positive – next steps

Hi RTC colleagues -

Just received results from a client's in vitro micronucleus test (one of the 2 large genetox providers), and the compound was clearly positive.

The SD raised the possibility of some follow-on, mechanistic work that might clarify whether the compound is an aneugen or clastogen. (While the mechanism interests me, I'm not sure - for a compound heading for development nomination - it would be any less "positive".)

I'm thinking of a different next step: As it happens, the circulating plasma levels of this compound will be very, very low when administered clinically (or in tox studies using the clinical administration route). Hence I suspect, were I to conduct an in vivo micronucleus test and obtain negative results, we could argue that the concentrations achieved in vitro are not relevant to pharmacologic administration.

I did this once before: obtained negative in vivo results after positive in vitro results, and the compound progressed.

As a new RTC member (!), I wanted to see if more-experienced folks suggest other elements I should be considering.

Thanks,
Andy

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

 

Excipient/ formulation question for clinical-stage, inhaled small molecule drug

Dear RTCers –

A friend and former colleague approached me with an issue and a question. Since inhaled products are outside my area of expertise, I’d rather connect him with a Real Expert Opinion.

Is this something you could assist with? Or whom would you recommend?

Here’s how he summarized this nonconfidentially –

1. Inhaled anti-infective intended to treat a target population of ~10,000 patients in the US. Novel compound in a known class.

2. Drug (not the formulation) is designed to penetrate the lung, and only be bioavailable in the lung to avoid systemic toxicity known for the class. In animals, the lung to serum concentration ratio is ~7,000 to 1 (ranging from 5,000-15,000).

3. Formulated as an aqueous suspension which includes 2 detergent-like excipients, let's call them A and B. In the US, A and B have been approved as excipients separately in intranasal formulations. In the EU A and B are part of an approved inhalation product since 1998.

4. Laryngeal toxicity observed in the 14-day rat study, across dose groups, including vehicle, with no difference in intensity/nature in any group, and therefore attributed to vehicle.

a. This toxicity not observed in the 14-day dog or 13-week dog, with the same formulation.

b. This toxicity not observed in the 13-week rat with a modified vehicle without excipients A or B.

5. A formulation with 1/20th the concentrations of both A and B was used in a Phase 1 study, with no observations, and dosing up to 7 days. No observations have been seen after dosing 8 patients in a compassionate use study, including some for more than 6 months.

This formulation will be used for planned Phase 3 study in the USA, and for longer-term tox studies in the rat and dog.

Is there a need, prior to a US filing, for nonclinical study work to demonstrate the safety of the product+excipients in the current formulation?

Thanks for your consideration. Happy to facilitate the introduction.
Andy

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

 

RTCers recommendations – free Web (and audio) conference service?

Hi all -

So far, whenever I've participated on a web-based audio and/ or video conference, I've used the client's selected platform. Recently I've been on Skype, RingCentral, Zoom, Microsoft Teams, WebEx, and Google Hangouts. They all seem to work well enough; I guess I appreciate that there are a couple of the services (RingCentral comes to mind) where I can remain muted and use the space bar as a "push to talk".

I wanted to ask the group - have folks had particularly good or bad experiences with one or another service, and is there a platform you'd recommend that's free me to host audio and video (toll landline for audio OK), and can connect a handful of participants?

I can Google (and I will), but I suspect others in RTC may have good learnings to share for the specific needs of a scientific-consulting small business.

Thanks in advance; stay well, friends,
Andy

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

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